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pmc-6465601-2 | A 28-year-old male painter suffered from behavioral changes for 1 week after flu prior to hospitalization to the ICU of the local hospital. Head MRI showed long T1 and long T2 signal intensities in the left temporal lobe, and enhanced MRI showed irregular light enhancement (). The anti-NMDAR antibodies in CSF and serum were negative. With the diagnosis of viral encephalitis, the patient received antiviral therapy for 35 days, together with methylprednisolone (1,000 mg, 3 days + 500 mg, 3 days) and prednisolone (35–60 mg, 30 days). Then, he left the hospital. Unfortunately, he was admitted to our hospital 2 days after his discharge due to aggressive behaviors, injuring other people, irritability, and severe delusion of persecution. He was given acyclovir and olanzapine (10–20 mg/day), but the symptoms deteriorated with severe violent behavior and declined cognition function after 7 days of treatment. The CSF pressure was 200 cmH2O. Total cell count was 58 × 106/L, and leukocyte count was 38 × 106/L. The anti-NMDAR antibodies in CSF and serum were both 1:10 (), and the antibodies against AMPA1, AMPA2, LGI1, CASPR2, and GABAb were negative (). The chest and abdomen were detected with B-ultrasound and CT to exclude tumor. After treatment with IVIG (30 g/day, 5 days), methylprednisolone (1,000 mg, 3 days + 500 mg, 3 days), and prednisolone (0–60 mg, 12 weeks), the psychiatric symptoms became worse; even olanzapine (10–20 mg/day, 15 days), quetiapine (25–400 mg/day, 15 days), diazepam (5–10 mg/day, 15 days), and clonazepam (2–6 mg/day, 15 days) did not work. PANSS total score () was 103. Finally, the patient was given clozapine (25–300 mg/day), with 90.6 ng/ml plasma concentration (; ), and all the psychiatric symptoms disappeared completely 3 months later. The patient was discharged. Followed up for 6 months, all the clinical symptoms disappeared. The anti-NMDAR antibodies in CSF and serum were negative, but no obvious changes could be observed in enhanced head MRI. PANSS total score was 21. |
pmc-6465601-3 | A 23-year-old male student was admitted to the local hospital due to headache, babbing, and aggressive behaviors for 1 week. After 7 days of treatment with penicillin and acyclovir, the symptoms were not relieved and then he was transferred to our hospital. No abnormality was found in enhanced head MRI. The CSF pressure was 100 cmH2O. Total cell count and leukocyte count were normal. The protein concentration was 0.46 g/L. The anti-NMDAR antibodies in CSF and serum were 1:1 and 1:10, respectively (), and the antibodies against AMPA1, AMPA2, LGI1, CASPR2, and GABAb were negative (). The chest and abdomen were detected with B-ultrasound and CT to exclude tumor. PANSS total score () was 97. After treatment with IVIG (25 g/day, 5 days), methylprednisolone (1,000 mg, 3 days + 500 mg, 3 days), and prednisolone (0–60 mg, 12 weeks), followed by antipsychotic therapy with olanzapine (10–20 mg/day, 15 days), quetiapine (25–400 mg/day, 15 days), and clonazepam (2–4 mg/day, 30 days), the patient still showed visual hallucination and aggressive behaviors. Then, he was given clozapine (50–100 mg/day), with 65.3 ng/ml plasma concentration (; ). The psychiatric symptoms disappeared after 2 months of treatment. Followed up for 6 months, he was able to live and work normally. The anti-NMDAR antibodies in CSF and serum were negative. PANSS total score was 18. |
pmc-6465652-1 | A 54-year-old man presenting with leukocytosis was referred to our hospital. Blood examination revealed eosinophilia—WBC 15.7 × 109/L (neutrophils 28%, eosinophils 55%, basophils 1%, monocytes 3%, and lymphocytes 13%), Hb 13.0 g/dl, platelet count 339 × 109/L, and LDH 232 U/L (normal range: 100–220). Liver and renal functions were normal. Since no clinical symptom or organ damage was identified, a regular monthly follow-up was advised. After 4 months, he developed respiratory symptoms including cough and dyspnea. Chest X-ray and computed tomography (CT) scanning revealed bilateral lung infiltrates (Figure a). Bronchoalveolar lavage fluid obtained by bronchoscopy revealed increased probability of eosinophils (20.5% eosinophils, 78.0% macrophages, 1.0% lymphocytes, and 0.5% neutrophils). He was diagnosed with acute eosinophilic pneumonia and was given prednisone at a dose of 0.5 mg kg−1 day−1. The clinical course of the patient is shown in Figure . Although treatment with prednisone improved the shadow of infiltrates on the X-ray and the respiratory symptoms, it did not reduce the increased number of eosinophils in circulation. Therefore, bone marrow examination was carried out and it revealed normocellularity with elevated eosinophils (22.1% of nuclear cells) without blastoid cell proliferation (0%) (Figure b). Cytogenetic analysis of the bone marrow showed 46, XY, t(2;5)(q37;q31) [16/20]/46, XY [4/20] (Figure c). FISH analysis in the peripheral blood leukocytes revealed the presence of a split signal at PDGFRB (Figure d). In addition, WT1 mRNA was positively expressed (1,200 copies/μg RNA) in the peripheral blood.
After the detection of PDGFRB rearrangement, imatinib was given at a dose of 400 mg/day, since previous studies have reported a positive outcome from this dose in patients with hematologic neoplasms with PDGFRB rearrangement (Cheah et al., ; Jawhar et al., ). Imatinib treatment was effective, with rapid regression of eosinophils in the peripheral blood and the pneumonia shadow on lung X-rays. The eosinophil number was back to normal after a week of imatinib therapy and the pneumonia shadow disappeared in 6 weeks. Translocation analysis by FISH also revealed the absence of PDGFRB rearrangement in the peripheral blood leukocytes after a month of imatinib treatment. The disappearance of t(2;5)(q37;q31) and a normal eosinophil count in the bone marrow were confirmed after 3 months. WT1 mRNA expression was negative (<50 copies/μgRNA) in the peripheral blood at that time. The dose of imatinib was reduced to 200 mg/day after 12 months of treatment. No recurrence was observed under imatinib therapy for over 4 years. No severe adverse effects were recorded—a grade 1 liver dysfunction, increased CPK level, anemia, renal dysfunction, and edema according to the Common Terminology Criteria for Adverse Events ver.4.0 were the only adverse events that developed during the observation period. This study was approved by the research ethics board of Nihon University School of Medicine in accordance with the Declaration of Helsinki (identifier 150–0) and written informed consent was obtained from the patient before sample analysis. |
pmc-6465669-1 | Case 1 was an 8-year and 2-month-old boy. The patient was born at 40 weeks gestation by cesarean section, with a birth weight of 3,200 g (−0.3 SD) and a body length of 50 cm (−0.2 SD). His parents were healthy and nonconsanguineous. His developmental milestones were delayed, with head control at 10 months, sitting at 12 months, standing at 24 months, walking at 38 months, putting two words together at 24 months. The patient exhibited hypotonia, amblyopia, astigmatism, teeth hypoplasia, and dysmorphic features including hypertelorism, a broad forehead, long philtrum, upslanting palpebral fissures, hypoplastic columella and ala nasi thin upper lip, high-arched palate, epicanthic fold, and micrognathia. He had brachydactyly and a simian crease on his right hand (Figure ). Electroencephalogram was abnormal, showing sharp waves and sharp slow complex waves on bilateral forehead and central region. The boy presented to our Endocrinology clinic at the age of 6 years and 2 months with a height of 102 cm (−3.6 SD) and a weight of 16.8 kg (−2.2 SD) (Z-scores were calculated based on the China's 2009 urban 0 to 18-year-old male height and weight growth reference standards; Li, Ji, Zong, & Zhang, ). Urine and plasma amino acid testing revealed hyperlactatemia. Other laboratory test results including thyroid function, serum insulin-like growth factor I level, Insulin-like growth factor-binding protein 3 level, serum glucose, routine urine analysis, routine blood test, renal function test, liver function test, and levels of electrolytes were all within normal ranges. Growth hormone provocative tests revealed that the peak growth hormone levels responding to two provocative tests (clonidine 5 µg/kg, orally, and arginine 0.5 g/kg, intravenously) were 5.60 ng/ml (Table ). Peak growth hormone levels between 5 and 10 ng/ml on provocative testing are defined as partial growth hormone deficiency according to current guidelines (Grimberg et al., ).
Brain magnetic resonance imaging (MRI) scan showed widened sulci and lateral ventricles and reduced volume of white matter. No signs of hypoplastic corpus callosum, delayed myelination, or simplified gyral pattern (Figure ). Bone age was delayed and was compatible with that of a 3-year-old boy.
Due to the partial growth hormone deficiency and short stature, growth hormone replacement therapy at a dose of 0.12–0.15 IU kg−1 day−1 was initiated. After 2 years of treatment, at the age of 8 years and 2 months, his height was 121.0 cm (−1.9 SD) and weight 19.8 kg (−2.4 SD). The growth hormone therapy markedly improved the linear growth of the patient with a growth velocity of 9.5 cm/year during the 2 years. Growth hormone doses and growth chart in case 1 are shown in Figure . The serum levels of IGF1 increased to 304 ng/ml during the treatment. |
pmc-6465669-2 | Case 2 was a 4-year-old boy. He was the only child of a consanguineous parents. Pregnancy and delivery were uneventful. He was born with a birth weight of 2,900 g (−1 SD) and a birth length of 50 cm (−0.2 SD). He held head at 7 months, sat at 13 months, stood at 18 months, walked at 24 months, put two words together at 20 months, spoke in full sentences at 3 years. He exhibited hypotonia. His dysmorphic features include a broad forehead, hypertelorism, upslanting palpebral fissures, hypoplastic columella and ala nasi, flat nasal bridge, long philtrum, upturned earlobes, high-arched palate, micrognathia. He had brachydactyly and simian crease in both palms (Figure ). The boy was presented to our Endocrinology clinic at the age of 3 years and 6 months. At that time, his height was 90 cm (−2.9 SD), and weight 15.5 kg (−0.1 SD). Laboratory test results including the thyroid function, serum glucose, routine urine analysis, routine blood test, renal function test, liver function test, and the levels of electrolytes were within normal ranges. Growth hormone provocative test also revealed a partial growth hormone deficiency (7.11 ng/ml). The serum insulin-like growth factor I level was low (48.7 ng/ml) and insulin-like growth factor-binding protein 3 was low (2.41ug/mL) (Table ). Brain magnetic resonance imaging (MRI) showed an enlarged cerebellomedullary cistern and arachnoidal cyst. (Figure ). Bone age was delayed and was compatible with that of a 1.5 years old boy.
The patient also underwent growth hormone replacement therapy at a dose of 0.13–0.15 IU kg−1 day−1. After being treated for 9 months, at the age of 4 years and 3 months, his height was 99.3 cm (−1.7 SD) and weight 16.6 kg (−0.4 SD). The growth velocity during 9 months is 12.4 cm/year. Growth hormone doses and growth chart in case 2 are shown in Figure . The serum levels of IGF1 increased to 209 ng/ml during the treatment. |
pmc-6465728-1 | A 30-year-old Chinese man was admitted with complaints of progressive motor deficits in the right lower limb for 1 year and dysarthria for 2 months. The patient's motor symptoms had developed 1 year earlier, along with an unsteady gait. Subsequently, he had gradually developed weakness and numbness of the right limbs, rigidity and aphasia, with occasional dysphagia and dysarthria. The patient had a 6-year history of drug abuse and had taken methamphetamine on ten occasions in the previous 6 months. His symptoms were considered to be encephalopathia toxica in a local hospital and were treated with 500 mg of methylprednisolone per day followed by 30 mg prednisone per day. No improvement was observed. There was no family history of cerebellar symptoms.
Neurological examination revealed normal mental status and normal cranial nerve functions. The strength of the right lower limb was 4/5 with brisk tendon reflexes, bilateral ankle clonus, and bilateral Rossolimo and Chaddock signs. The patient also showed spastic gait and positive Romberg's sign, with slight decrease in pinprick sensation in the lower extremities. The patient was unable to perform the finger-nose tests and rapid alternating movements.
Laboratory evaluation showed normal routine studies. Examination of the cerebrospinal fluid revealed 507.7 mg/dl protein (normal range 15–45 mg/dl) and normal IgG index. Autoimmune, infectious, endocrinologic, neoplastic, and paraneoplastic screenings were unremarkable. However, serum levels of alanine aminotransferase and lactic acid (instant state, resting state, 1 min, and 10 min) were all increased. Brain magnetic resonance imaging (MRI) showed abnormal signals in the bilateral periventricular white matter, the posterior part of the corpus callosum and symmetrically along the corticospinal tract without gadolinium enhancement. In addition, a thin posterior corpus callosum, enlarged lateral ventricle, and widened bilateral parietal sulcus were demonstrated. The diffusion-weighted image (DWI) shows patchy areas of restricted diffusion in the abnormal white matter, confirmed by low signal of the corresponding areas on the apparent diffusion coefficient (ADC) map. The restricted diffusion areas exist for more than 1 year. PET-MRI showed hypometabolism in the posterior part of the cerebral white matter (Figure a). A typical RRF was identified in muscle biopsy for the first time (Figure a).
Targeted gene sequencing of AARS2 identified two variations: c.179C>A and c.1703_1704del (Figure b). These two mutations have not been previously described, and they were not found in the ExAC database (). The patient was compound heterozygote for these pathogenic mutations, which were transmitted maternally and paternally, respectively (Figure b).
The treatment was generally supportive. After the application of intravenous coenzyme complex 200 U one time per day for 10 days, the patient showed gradual improvement in motor function. He could walk 1,000 m alone and remained stable on six-month follow-up. However, the patient showed rapidly deterioration of cerebellar ataxia and motor deficits in 1 year. |
pmc-6465730-1 | The 43-year-old female patient was initially referred to our university hospital because of progressive psychomotor decline during a period of about 1 year. Since the initial magnetic resonance imaging (MRI) of the brain revealed symmetric atrophy pronounced in the frontal lobes and periventricular with matter lesions a neurological examination was initiated (Figure a). The complex clinical presentation including progressive spastic-ataxic gait, spastic hemiparesis, apraxia, hand tremor, saccadic eye movements, speech production disorder, and brisk tendon reflexes was topologically correlated with the brain MRI alterations. For further differential diagnostics of an assumed inherited microangiopathy, the patient was referred to our genetic department at age of 44 years. No dysmorphological features suggesting a recognizable syndrome were detected. The pedigree analysis over three generations revealed several affected relatives with neurological disorders, indicating an autosomal dominant mode of inheritance (Figure ). The patient herself had no children. As far as known, the patient's mother had passed away at age of 45 years because of cerebral infarction leading to rapid neurological decline with aphasia and paralysis. A maternal aunt of the patient had died after several years of tentative diagnosis of Parkinson´s disease. Two maternal uncles of the patient were also supposed to have cerebral infarctions, one of them already deceased. The maternal grandmother is said to have died by renal insufficiency and polyneuropathy in association with diabetes mellitus. On several cousins, no information on their health conditions was available.
Differential diagnoses including CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts, and leukoencephalopathy), Fabry disease, Alzheimer's as well as Parkinson's disease, and frontotemporal dementia were considered clinically. However, using OMIM database search and the program Phenomizer (Kohler et al., , ), we found the best congruence with the clinical synopsis of HDLS and initiated targeted gene analysis of CSF1R which allowed us to confirm the diagnosis of HDLS in our patient.
During follow-up care, our patient was thoroughly examined by a neuropsychologist and a patholinguist at age of 46 years. In accordance with the literature (Freeman et al., ; Kohler, Curiel, & Vanderver, ), testing revealed rather unspecific cognitive deficits with a score of 28 of 30 points in the Mini Mental State Examination (MMSE). Impairment was proven in selective and divided attention, executive functions, and delayed recall in memory. The speech therapeutic diagnostics revealed hypokinetic dysarthria rather than aphasia as the patient was not able to speak, because phonation and word production were so difficult for her. Her understanding was actually quite well. In written form, she was able to produce grammatically correct sentences with orthographically challenging wording. The neuropsychiatric inventory (Schroeter et al., ) revealed apathy and depressive symptoms, the latter especially when she was confronted with her disease. In the neurological follow-up examination, 1 month later, the patient showed further progressive psychomotor decline with severe gait bradykinesia, postural instability, and spastic tetraparesis. The speech therapy had led to slight improvement of the hypokinetic dysarthria. However, severely impeded communication skills and labile affect were still present.
Follow-up MRI scans 30–34 months after the initial MRI imaging revealed a drastic progression of leukodystrophy with patchy and confluent bilateral white matter hyperintensities predominantly in the frontal and prefrontal white matter (Figure b,c; Figure ). Slightly less intense white matter changes with heterogeneous pattern were also seen in the bilateral parietal white matter. The configuration of some of the changes were tract-shaped and along the corticospinal tract bilaterally. We observed an asymmetry with right-sided accentuation of the bilateral ventricular dilatation as a sign of subcortical atrophy. Focal diffusion restrictions were seen in the bilateral precentral white matter as a correlate of the active inflammatory and degenerative processes as described characteristic for HDLS (Bender et al., ). A pronounced thinning of the corpus callosum and a diffuse cortical atrophy was observed. |
pmc-6466552-1 | We report a 74-year-old male with end stage liver disease who received an orthotopic liver transplant in March 2018 with improvement of his hepatic encephalopathy and synthetic function. He suffered from acute kidney injury shortly before the transplant due to suspected hepatorenal syndrome, and became dialysis dependent prior to his transplantation. He had been stably maintained on an outpatient regimen of dialysis every Monday, Wednesday, and Friday. He was listed for a renal transplant and was receiving hemodialysis through a tunneled central venous catheter rather than through arteriovenous access.
The patient presented in October 2018 with weakness and chills and was found to be bacteremic with ESBL Klebesiella oxytoca. He was treated in August 2018 for a polymicrobial bacteremia, due to a catheter related infection. The blood cultures in August grew Citrobacter, Stenotrophomonas ESBL, and ESBL Klebesiella oxytoca. The ertapenem was dosed for hemodialysis and was to be administered with dialysis rather than daily.
One week into therapy, the patient noted a tremor in his voice, weakness, confusion, forgetfulness, and his wife noted a change in his personality. Upon interview with his nephrologist, it was clear this once lucid patient had a profound change in his mentation and personality. Suspecting an interaction between the carbapenem and the prescribed calcineurin inhibitor (tacrolimus), he was sent back to Ronald Reagan Medical Center, UCLA for hospitalization workup and emergent measurement of tacrolimus levels. It was verified that the hepatic cytochrome 450 enzymatic system should not be affected by ertapenem []. The tacrolimus level was 5.3 ng/mL, which is within normal limits and at goal for the patient’s liver transplant.
After the diagnosis of ertapenem neurotoxicity was suspected on clinical grounds, the drug was discontinued with ongoing hemodialysis on the regular Monday, Wednesday, Friday schedule. The patient returned to his baseline mental status rapidly after drug discontinuation. His blood cultures remained clear and he was able to continue use of his tunneled central venous dialysis catheter while awaiting renal transplantation. The patient is now amenable to placement of a permanent arteriovenous access since renal transplantation maybe delayed further due to catheter related infections and frailty. |
pmc-6466781-1 | A 59-year-old Han Chinese male was diagnosed with systemic MCL in February 2014. He received three cycles of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab chemotherapy, one cycle of rituximab mega-CHOP chemotherapy, and two cycles of dexamethasone, cytarabine, cisplatin (DHAP) and rituximab chemotherapy, followed by BCNU, etoposide, cytarabine and melphalan (BEAM) chemotherapy and autologous stem cell transplantation (ASCT) in August 2015, which result in complete disease remission with negative restaging positron emission tomography (PET) scan obtained in November 2015.
In March 2016, the patient complained of redness, pain and blurred vision in the left eye. Ocular examination revealed elevated intraocular pressure (IOP, 24 mmHg), diffuse conjunctival injection and anterior chamber reaction (flare 1+, cell 1+) in the left eye, and cortical cataracts in both eyes. The best corrected visual acuity (BCVA) was 20/50 and 20/60 in his right and left eye respectively. He was diagnosed as “anterior uveitis” and was given 1% prednisone acetate eye drops 8 times daily with tapering, along with topical tropicamide and 2% cartelol eye drops. However, the condition of his left eye continued to deteriorate which presented as “pseudohypopyon” and anterior protrusion of the peripheral iris 2 months later (Fig. a), and his left BCVA dropped to hand motion. Ultrasound biomicroscopy (UBM) revealed confluent ciliary body masses with almost 360°involvement in both eyes (Fig. b,c), while ultrasound B-scan demonstrated a clear vitreous cavity and the absence of retino-choroidal anomalies. Contrast-enhanced magnetic resonance imaging (MRI) revealed no significant findings in the orbit.
Diagnostic paracentesis of the left anterior chamber was performed on April 29th 2016. Liquid-based cytology revealed small malignant cells in the aqueous humor (Fig. ), which were then confirmed to be B-cell in origin by gene rearrangement studies. Given his past medical history, intraocular MCL was diagnosed. A PET examination was re-performed in May 2016 and no signs of systemic recurrence was identified.
Then he was scheduled for 40 Gy external beam irradiation delivered evenly in twenty fractions over a period of 1 month. The pseudohypopyon disappeared 2 weeks after the commencement of irradiation and the symptoms resolved completely after the patient received full irradiation dosage (Fig. a). UBM re-examination disclosed complete regression of ciliary tumor in the right eye (Fig. b) and reduction of tumor size in the left eye (Fig. c). Additionally, his left eye received a series of 400μg/0.1 ml methotrexate (MTX) intravitreal injections, weekly for the first month, every 2 weeks for the second month, and monthly for 10 months [], which resulted in complete regression of ciliary tumor (Fig. d). In January 2017, he underwent cataract surgery in the left eye with insertion of an AcrySof IQ intraocular lens, and the BCVA improved to 20/200.
Unfortunately, the patient suffered peripheral lymph node MCL recurrence in October 2018, which followed by rapid deterioration. In November 2018, he died of the side effects of intensive chemotherapy. |
pmc-6466795-1 | A 13-year-old intact male spaniel was presented for the evaluation of a 4 × 4 cm, ulcerated, and hemorrhagic mass, since 3 months, in the right perianal region (Fig. a). The mass was flat and hard 2 months ago, but had increased in size since then. Two days before the visit to the hospital, it had ruptured and shown hemorrhage.
A CBC test revealed regenerative, mild microcytic normochromic anemia (RBC: 5.09 M/μl, RI: 5.6–8.8; HCT: 30.7%, RI: 37.3–61.7; MCV: 60.3 fL, RI: 61–73.5; reticulocyte: 1.6%, RI: 0–1.2). A serum biochemistry profile showed increased ALT and GGT concentration (ALT: 193 U/L, RI: 10–130; GGT: 10 U/L, RI: 0–7). In the abdominal radiograph, the presence of fecal stasis in the descending colon was observed, and the presence of feces in the anus could not be verified because of the mass. A fine-needle aspirate of the perianal mass was performed and stained with Diff-quick stain for cytologic evaluation (Fig. b–f).
A large number of erythrocytes as hemorrhagic manifestation with many microfilaria were observed throughout the slide. Erythrophagia and inflammatory cells such as neutrophils, eosinophils, monocytes and macrophages were also observed. In some of the fields, cell populations derived from mesenchymal origin with high-grade malignancy were seen (increased nucleus to cytoplasm ratio, macrokaryosis, anisokaryosis, anisonucleoliosis, and distinct multiple nucleoli). Low cellularity, eosinophilic materials outside cells, and cytoplasmic appearance suggested that the cells were derived from mesenchymal origins. Thus, malignant mesenchymal tumor with inflammation and heart worm infection was the diagnosis.
Based on the results of cytologic evaluation, punch biopsy of 3-mm size was conducted at three sites under locoregional anesthesia with lidocaine spray and bupivacaine intralesional injection (< 2 mg/kg) and the biopsy samples were submitted for histopathologic evaluation (IDEXX Laboratories, Inc., Lenexa, KS, USA). Deep dermal and subcutaneous hemangiosarcoma (3 mitotic figures/10 high power field (HPF, 400×)) was diagnosed and histopathological findings were as follows: the specimen was characterized by a poorly demarcated and non-encapsulated proliferation of atypical vascular endothelium (Fig. a and b). These cells proliferated as tortuous sinusoids or capillary like structures within the dermal connective tissue. There was an invasion up to the level of the deep dermis and subcutaneous tissue. Individual cells were characterized by scanty amphophilic to eosinophilic cytoplasm and mild to moderate pleomorphic, euchromatic nuclei with variably sized nucleoli. Immunohistochemistry results revealed strong cytoplasmic staining for cluster of differentiation 31 (CD31) and moderately strong cytoplasmic staining for factor VIII-related antigen in the neoplastic cells (Fig. c and d). |
pmc-6466797-1 | A 15-year-old boy presented to Fujian Medical University with giant scrotal elephantiasis and swelling of both lower extremities. The penoscrotal edema began fifteen years earlier, soon after his birth, and it resulted in bilateral lower extremity edema with the penis becoming buried by the scrotum. His scrotal size was massive, and for the past 5 years, the glans penis was not visible nor palpable (Fig. a–c). He had undergone circumcision 13 year earlier and had no history of travel in filariasis-endemic areas. There was also no family history of scrotal elephantiasis or known genetic disorders.
Upon examination, the patient had a massively enlarged scrotum, with a volume of approximately 16 cm × 13 cm × 7 cm. The anatomical structures and urethral orifice were visible as a deep depression on the scrotum. Both lower extremities exhibited generalized swelling, which was especially noticeable on his ankles. His thigh circumference was 52 cm on the left and 56 cm on the right.
Tissue biopsy of the lower extremities was performed 13 years earlier and revealed lymphangioma and connective tissue hyperplasia. A urinary system ultrasound examination was performed 14 months prior to presentation at our hospital, which confirmed diseased subcutaneous scrotal soft tissues with no abnormalities in the bilateral testicular morphology and blood supply. The results of lower limb lymphoscintigraphy demonstrated that the lymphatic drainage of the lower extremities was obviously tardy. The development of bilateral inguinal and iliac lymph nodes was obviously tardy (Fig. ). The lower limbs and anterior pelvic position was imaged after injecting with the tracer (99mTc-SC) subcutaneously between the first and second toes. The images demonstrated that the lymphatic drainage in both lower extremities were unclear. In the early stage, the images showed that the bilateral inguinal and iliac lymph nodes were blurred, which was obvious on the left side. The concentration of imaging agent (99mTc-SC) in the bilateral inguinal and iliac lymph nodes was gradually increased within 6 h after imaging. There was no significant concentration of imaging agent (99mTc-SC) on the skin of the scrotum during the entire process (Additional files , , , and ). Results of laboratory testing, including human immunodeficiency virus and routine blood evaluation, including a full biochemical profile, were all within the normal ranges.
Surgery was performed on September 18th, 2017. The affected skin and subcutaneous tissues were excised and the flaps was cut in the middle in Y shape to cover the penis and scrotum. The primary goal of surgery was to completely remove the affected tissues. The incision began at the side of the groin outside the outer ring then ran underneath the scrotum and sagittally forward and downward, then back towards the rear of the scrotum, where it then ran around the back of the scrotum. The incision was on the midline, with the contralateral incision rendezvous point in front of the incision from the top to the top of the extension, which was at the midline near the root of the penis and the join with the contralateral incision (Fig. d). The skin was freed on both sides of the flap to the scrotum on the outside, the thickened scrotal wall was transected, and the scrotal lesions were removed (Fig. e and f). Bilateral testicular hydroceles were found intraoperatively that measured approximately 6.0 cm × 6.0 cm × 5.0 cm. Therefore, the testicular sheath was incised, which released thick brown fluid; the cavity of the tunica vaginalis had no connection with the abdominal cavity (Fig. a). We then sutured the flaps with a “Y” suture on both sides to reconstruct the scrotum, placing a drain distally (Fig. b). To address the swollen extremities, we adopted conservative treatment, such as raising both lower limbs and wearing elastic stockings to improve lymphatic reflux.
The excised scrotal tissue weighed 5.2 kg (Fig. c and d). Histopathological examination did not reveal the presence of microorganism or parasites, and confirmed lymphangia with fibroblast proliferation and previous hemorrhage (Fig. e). Three months postoperatively, his scrotal appearance and penile function had improved (Fig. f), with evident wound integrity and patient satisfaction with the outcome (Fig. b).
Important technical points in this surgical treatment include the complete dissection of all involved tissue, and using scrotal advancement flaps from areas with normal, non-edematous skin. Other skin parts may be of use like posterior scrotal flaps, superiorly based flap of the pubic area for testicular coverage, and split-skin graft to the penis. This case shows that surgical therapy can provide good functional and cosmetic results in scrotal elephantiasis. |
pmc-6466879-1 | A 19-year-old right handed woman was referred to our hospital with complaints of persistent fever and headache from 3 days before. At the time of initial symptoms, her family members reported strange behavior as the patient had repeatedly asked the same questions. On admission, she still retained consciousness and could recognize her family members, but was disorientated to time and place. Magnetic resonance imaging (MRI) on admission demonstrated no signal abnormalities in the brain, including the medial temporal areas. Cerebrospinal fluid (CSF) examination on admission revealed lymphocyte dominant pleocytosis (lymphocytes 168/mm3, polymorphonuclear cells 13/mm3) with a protein level of 46 mg/dL (normal 15–40 mg/dL) and a sugar level of 61 mg/dL (normal 50–70 mg/dL). A clinical diagnosis of encephalitis was made and an intravenous administration of acyclovir, fosphenytoin sodium hydrate, and glycerol was initiated. On the second day of admission, she developed repeated generalized tonic-clonic convulsions leading to a convulsive status. She required supportive therapy involving intubation, mechanical ventilation, and sedation. A test for herpes simplex virus (HSV)-PCR of the CSF was negative. Antibodies against GluN1/GluN2 heteromers of the NMDA receptor were detected in serum at two different times (). From this evidence, a diagnosis of anti-NMDA receptor encephalitis was made. Two months after admission, fluid-attenuated inversion recovery (FLAIR) images of brain MRI showed areas of slightly high intensity in the bilateral occipital cortices and subcortical white matter, which were somewhat prominent on the right side, as well as small subcortical high intensities in the right frontal lobe (). Over the following several months, orofacial dyskinesia and bibrachial spasm occurred frequently despite immunotherapy with high-dose methylprednisolone (1000 mg/day for 3 days) twice and intravenous immunoglobulin (400 mg/kg/day for 5 days) once. She was weaned off the ventilator 6 months after admission, though she was still unconscious.
Abdominal computed tomography (CT) and MRI for the purpose of detecting ovarian tumor were both negative on initial examinations. However, a repeated abdominal CT after 8 months of admission revealed a small ovarian calcified cystic mass on the right side (). The patient had the tumor removed, which was diagnosed as a mature cystic ovarian tumor on pathological examination. After the removal of the tumor, she received high-dose methylprednisolone and intravenous immunoglobulin therapy again. Three months after these treatments (12 months after admission), the patient's consciousness improved gradually and she was slowly able to respond to verbal commands.
At this time, she stated that she could not see anything. Ophthalmological examination revealed that pupillary reaction and extraocular movements were normal. In addition, there were no abnormalities in the anterior and posterior components of the eyes, including the lens, retina, and optic fundi. The patient's exact visual acuity was difficult to estimate because she complained of fatigue and often refused to continue the test. Regarding color perception, she could differentiate a red cup from a blue cup; however, she could not distinguish a blue cup from a green cup. On behavioral observations, she behaved like a blind person; although she could walk while holding hands with a caregiver, she frequently collided with doors. When she attempted to pick up her comb or toothbrush from a table, she explored these objects by palpating with her hand across the table. She could not recognize stationary objects by visual inspection alone, but she could identify them by tactility or hearing the sounds that they made. Around this time, it was incidentally noticed that she could successfully respond to the examiner's motions. For example, when the examiner waved their hand, she waved back. On a different occasion, when the examiner swayed their body, the patient immediately imitated the movements. These observations suggested the patient was able to see moving objects better than stationary objects, despite her serious visual impairment.
Subsequently, we further examined her visual abilities in detail. First, the patient was asked to detect stationary visual stimuli presented on a computer screen placed 30 cm from her eyes. We prepared two different stimuli, a black dot with 1 cm in diameter (approximately 2 degrees in visual angle) and another with 0.4 cm in diameter. They were presented randomly for three seconds on each of the five points, comprised of four corners and the center of the screen. She was able to identify the larger stimuli perfectly (10/10: correct/total) indicating that she had no obvious hemianopsia or quadrantanopsia of the cortical type, although she often missed the smaller ones (2/10: correct/total). Second, the patient was tested for her ability to detect the motion of a visual stimulus. A small black dot 0.4 cm in diameter was presented in the center of the screen for 3 seconds with no motion (stationary condition), or with rightward lateral motion with a velocity of 2 cm/sec (moving condition) (). She was able to detect the moving stimuli better (8/10: correct/total) than stationary ones (1/10: correct/total). Third, the patient was tested to see if the motion of a figure influenced her ability to identify the shape of the figure. Four different figures in black: a circle, a star, a triangle, and a square, were inscribed in a circle with a diameter of 1 cm. Each figure was presented in the center of the screen with no motion for 4 seconds (stationary condition) or with a clockwise rotational movement from the center tracing on a circle of a 4 cm diameter with a velocity of 2 cm/sec for 4 seconds (moving condition) (). She showed a tendency to recognize the shape of moving figures better (7/18: correct/total) than stationary ones (3/18: correct/total) (). The test results suggested that the patient retained some capacity of form-from-motion perception: i.e., an ability to recognize the shape of an object under motion.
The patient's visual symptoms and general cognitive function gradually improved. Fifteen months after admission, she was able to recognize stationary objects as well as moving ones in everyday life. She also was able to pick up an object with appropriate preshaping of her fingers. At this time, the patient scored 28/30 on the revised Hasegawa dementia scale (normal >21/30). Further, we administered Visual Perception Test for Agnosia (VPTA) to her. On VPTA, a mistake or failure in performance is each scored 1 or 2 points according to the criteria. Thus, greater score indicates more severe visual disability. The patient showed a partial impairment in her basic visual perception (VPTA score 6/24), yet she was able to read kana and kanji characters. Notably, we observed severe impairment in perceiving famous faces (VPTA score 10/10). She could not tell if a photograph of a person was young or old, or man or a woman, but was able to identify if two faces presented were identical or not. The patient also demonstrated difficulties in identifying family members by visual inspection alone, stating “I can recognize my family members when I hear their voice but cannot by sight alone because their faces look dark and ambiguous.” On the other hand, her color perception had recovered to near normal levels (VPTA score 2/30).
She was discharged 18 months after admission, and had become able to identify family members and medical staff on sight, with no complaints of any visual symptoms. Brain MRI performed on discharge showed no signal abnormalities except for subcortical small high intensities in the occipital lobes. |
pmc-6466880-1 | The patient is a 57-year-old nulligravid female who presented to clinic with symptoms of urinary urgency incontinence. She had a past medical history of endometriosis, autoimmune hepatitis, cirrhosis, and denied any pertinent mental/psychological history or trauma. Her initial symptoms included urgency, voiding up to 5 times an hour, and nocturia up to five times per night. She had no previous vaginal surgeries. Baseline sexual function evaluation was completed at intake with the Female Sexual Function Index (FSFI) questionnaire where the arousal domain equaled 0.9 (range 0-6, with 6 indicating maximal arousal) (). Pelvic examination was significant for vaginal atrophy but no notable clitoral or labial abnormalities were visualized. There were no signs of prolapse or pelvic floor musculature hypertonicity. She was asked to keep a voiding diary and then advised to attempt timed voiding upon its completion. She was also started on vaginal estrogen and a generic anticholinergic agent (oxybutynin 10 XL daily). After 4 weeks of treatment, she experienced significant worsening of anticholinergic side-effects and stopped the medication on her own. She was then started on a beta sympathomimetic (mirabegron 25mg daily). After 6 weeks of this therapy, she did not have any subjective improvement in her symptoms. The dose was increased to 50 mg daily and continued for an additional 4 weeks. Again, she did not have an adequate reduction in symptoms and was counseled on third tier treatment options. Ultimately the decision was made to proceed with SNM.
The sacral neuromodulator was implanted per manufacturer instructions after undergoing a peripheral nerve evaluation with >50% improvement in her urgency symptoms. At one-week follow-up, her incisional pain was minimal. She did not require oral analgesics and had reported marked improvement in urinary symptoms consistent with the test phase.
However, near the six-month follow-up appointment, she expressed concerns about persistent arousal symptoms in the vaginal area overall with new onset hypersensitivity localized to the clitoris. She did not have these symptoms prior to or immediately postimplant, but she reported gradual development of arousal symptoms postoperatively over the six-month period. She had not initiated the use of any new medications or therapies during the same time period.
Pelvic examination did not demonstrate engorgement of the clitoris, change from the intake examination, or evidence of hypertonic pelvic floor muscle dysfunction based on digital assessment. To manage her arousal, the four programs that were programmed into the system were alternated with cycling activated. Behavioral modifications were suggested including loose clothing. Upon no change in symptoms, device deactivation was performed. This resulted in no notable improvement of the manifest arousal symptoms. However, her urgency symptoms immediately recurred upon the deactivation. At this point, the plan was to trial a new set of programs to see if her arousal symptoms could be eliminated using different settings. The patient agreed to trial all four new programs, each over at least a 10-day period and assess which one was associated with fewer arousal symptoms. The programming was done at sensory levels. Alternation of pulse width and frequency was performed as well. The patient was instructed to complete a 4-week diary indicating arousal and bladder activity. At follow-up, she had trialed each program and continued to experience sexual arousal symptoms. Her symptoms were present even when the device was turned off and intensified when the machine was on. The symptoms were also present without any clitoral contact by undergarments. It was becoming so bothersome that it was difficult for her to stay asleep at night and creating anxiety. Complete testing of the neuromodulator unit was reperformed with normal values noted for impedance. Reprogramming of the unit with a new set of programs was performed again with subsensory levels used at this point. Additionally, she was offered sexual counseling but it was declined.
One year after placement, she elected for removal of the generator and lead. The generator and lead, intact with tip, were successfully removed with no complications. At the 6-week follow-up after explant, she had recurrence of urinary urgency symptoms with persistence of hyper-arousability. One year later, she continues to be sexually active with mild discomfort due to vaginal atrophy (as noted on the pain domain in the FSFI). She reports that the clitoris remains hypersensitive with persistence of the arousal symptoms, although moderately improved from prior to SNM. At the follow-up visits, no changes in medications or new medical diagnoses were reported when compared to prior visits. Furthermore, she denied any new stressors or change in her personal life regarding the relationship with her husband. |
pmc-6466884-1 | A 39-year-old Asian male, with a recent diagnosis of severe hyperthyroidism and family history of coronary artery disease but no other cardiovascular risk factors, presented with intermittent angina-type chest pain of 8-month duration. He also reported heat intolerance, recurrent palpitation, sweating, watery diarrhea, and weight loss of 10 kg over a 3-month duration. Methimazole and propranolol were initiated two days before the actual presentation. On examination, he had normal heart sounds, no gallop, murmur, or rub tachycardia but with regular and synchronous heart rate, and no clinical signs of heart failure. Neck exam revealed diffuse mild thyroid enlargement and general exam showed fine hand tremors. Electrocardiography on presentation showed biphasic T waves in V1 and V2 (). Three sets of cardiac enzymes were negative; TSH was <0.005 mIU/L (0.45-4.5) and T4 was 48.3 pmol/L (9-20) reference and units. Transthoracic echocardiography was normal with good left ventricular function (ejection fraction (EF): 70%) and no regional wall motion abnormalities. As the patient did not tolerate exercise treadmill stress test, he underwent a dobutamine stress echo. Dobutamine was infused at 3-minute intervals, starting with 10 μg/kg and increasing to 20 μg/kg, 30 μg/kg, and 40 μg/kg in addition to 0.5 mg atropine IV until a target heart rate of 153 bpm accounting for 95% of his maximal predicted heart rate. The patient developed severe chest pain and systemic hypotension with a blood pressure of 80/50 mmHg. ST elevation in the anterolateral leads, new RBBB, and short runs of nonsustained ventricular tachycardia (VT) on continuous ECG monitoring were noted ().
Echocardiography showed new regional wall motion abnormalities in the form of akinesia of the apical, mid anteroseptal, and mid anterior walls and hypokinesia of the mid anterolateral and mid posterolateral walls with a drop of EF to 30%. The patient was transferred to the intensive care unit, and resuscitation with IV fluids led to improvement in his blood pressure and propranolol was uptitrated till heart rate became controlled. Chest pain and ST elevation normalized spontaneously resolved. Cardiac troponin T reached a peak of 1900 ng/L but serial troponins showed progressive improvement. Global longitudinal strain measures () were abnormal in the left anterior descending (LAD) territory (). Dual antiplatelets, heparin infusion along with propranolol and statin, started and kept on IV hydrocortisone 100 mg three times daily for 3 days to decrease the possibility of thyroid storm with coronary angiography (CAG). CAG was done 3 days later and showed 40% LAD stenosis proximal to D1 with no evidence of thrombus, myocardial bridging, or coronary vasospasm. Left circumflex artery (LCX) and right coronary artery (RCA) were normal. No provocation test was done and the patient was discharged home in a stable condition on full medications.
The patient showed dramatic improvement of symptoms over the next few days with improvement of the hyperthyroid state and was discharged successfully with minimal symptoms. |
pmc-6466908-1 | The patient is an 18-year-old female with Graves' disease and history of medication nonadherence who presented to the emergency room with fevers, chest pain, palpitations, and diarrhea. She had been diagnosed with Graves' disease two months earlier with an initial presentation of unintentional weight loss, palpitations, tremors, and diarrhea, but no compressive symptoms. She was prescribed methimazole which she intermittently took. Her family history was significant for a cousin with thyroid cancer, mother with uterine cancer, half-brother with skin cancer, and two relatives with breast cancer.
In the emergency room, she had tachycardia (heart rate 155 beats/minute) and orthostatic hypotension. She was afebrile. Her exam was notable for a diffusely enlarged thyroid with no palpable nodules. An electrocardiogram showed sinus tachycardia, and a chest X-ray was negative.
She was admitted due to concern for impending thyroid storm and was started on atenolol and restarted on methimazole. Her symptoms improved gradually after initiation of these medications. During the hospitalization, she had a thyroid ultrasound which showed an enlarged hyperemic thyroid gland consistent with Graves' disease and an indeterminate focal area (1.3 × 1.7 × 1.1 cm) in the right lobe containing abnormal linear echogenicities (). She was discharged home on methimazole with outpatient follow-up. At her follow-up visit two weeks later, the patient had a repeat ultrasound which showed a similar 1.7 cm nodule with indistinct margins containing linear and punctate echogenicities, concerning for microcalcifications. A fine-needle biopsy of the nodule was performed, and it showed a benign cluster of reactive follicular cells and lymphocytes (Bethesda II). Despite the cytology results, there was a continued concern for malignancy given the sonographic features of the nodule in the first two ultrasounds, so repeat imaging was performed four months later, which showed minimal change in the nodule size and features.
Given the poorly defined thyroid nodule and the patient's desire for definitive therapy for the hyperthyroidism, she underwent a total thyroidectomy. The surgery was complicated by postoperative hypoparathyroidism for which she received intravenous and oral calcium and oral calcitriol. Surgical pathology identified benign thyroid tissue with papillary hyperplasia and a benign nodule of ITT with foci of Hassall's corpuscles with calcifications (). At follow-up visits, she was started on levothyroxine for postoperative hypothyroidism. Her calcium levels improved such that calcitriol was discontinued and oral calcium dosing was decreased. |
pmc-6466910-1 | Patient 1 was an 84-year-old woman who had undergone thoracic endovascular aortic repair (TEVAR) for an aortic dissected aneurysm () and was hospitalized for thrombocytopenia and abnormal coagulation. Her laboratory data showed hemoglobin (Hb) 7.9 (reference; 11–16) g/dl, platelet count 79,000 (reference; 150,000–360,000)/μl, fibrinogen degradation product (FDP) of 101.5 (reference; <5) μg/ml, D-dimer of 49.8 (reference; <1.0) μg/ml, fibrinogen 98 (reference; 200–400) mg/dl, thrombin-antithrombin complex (TAT) 40.5 (reference; <3) ng/ml, and plasmin-α2 plasmin inhibitor complex (PIC) 12.7 (reference; <0.8) μg/ml. Prior to admission, she had been treated with warfarin. Our vascular surgeons regarded her aneurysm condition after TEVAR as inoperable. She was started on a continuous intravenous infusion of 10,000 units/day heparin and 250 mg twice daily intravenous tranexamic acid. This combination treatment was effective as her plasma FDP and D-dimer concentrations decreased while her fibrinogen level and platelet count increased (). To facilitate her discharge, she was switched from intravenous to oral tranexamic acid (750 mg/day) and from intravenous to subcutaneous administration of heparin calcium (5,000 units twice daily), and warfarin was stopped. Although this combination was effective, the patient was intolerant of subcutaneous heparin calcium because of pain, and she was transitioned to oral rivaroxaban 15 mg/day for discharge from hospital. |
pmc-6466910-2 | Patient 2 was an 87-year-old man who had undergone TEVAR for a Stanford type B aortic dissection 7 months earlier (). Thereafter, he was sent to a rehabilitation center, where his plasma FDP and D-dimer increased gradually, while fibrinogen and platelet count decreased, and anemia progressed. He received transfusions of packed red blood cell (PRBC) and platelet concentrate (PC) several times (precise units unknown), although the cause of his abnormal coagulopathy was not adequately assessed. Following persistent gingival bleeding for 2 weeks, he was transferred to our hospital for evaluation. His laboratory data showed Hb 7.9 g/dl, platelet count 73,000/μl, FDP 96.8 μg/ml, D-dimer 24 μg/ml, fibrinogen 73 mg/dl, TAT 58 ng/ml, and PIC 17.6 μg/ml. Following PRBC (4 units) infusion, he was treated with subcutaneous heparin calcium (5,000 units twice daily) and oral tranexamic acid (1,500 mg/day). After 1 week, his laboratory data improved, with Hb 9.1 g/dl, platelet count 146,000/μl, FDP 10.9 μg/ml, D-dimer 6.3 μg/ml, and fibrinogen 186 mg/dl. Later, he was successfully switched to oral rivaroxaban (15 mg/day) as maintenance treatment at the outpatient clinic (). |
pmc-6466910-3 | Patient 3 was a 91-year-old woman, who was hospitalized for gingival bleeding. Her laboratory data showed Hb 8.4 g/dl, platelet count 100,000/μl, FDP 109 μg/ml, D-dimer 51.4 μg/ml, and fibrinogen 72 mg/dl. Enhanced CT revealed bilateral iliac aneurysms, with the right and left aneurysms having maximum diameters of 60.5 mm and 43.7 mm, respectively (). She was initially treated with PRBC (6 units) and fresh frozen plasma (FFP; 10 units), followed by intravenous tranexamic acid (250 mg four times daily) for 3 days. However, because these aneurysms were thought to be responsible for her coagulopathy and the patient was regarded eligible for surgery, EVAR operation was performed, after which her DIC resolved. |
pmc-6466910-4 | Patient 4 was an 83-year-old woman, who was hospitalized with gastrointestinal (GI) bleeding and dyspnea due to persistent chronic obstructive pulmonary disease. Her laboratory data showed Hb 3.0 g/dl, platelet count 62,000/μl, mean corpuscular volume 82.9 (reference; 83–100) fl, serum blood urea nitrogen 98.0 (reference; 7.8–18.9) mg/dl, and creatinine 1.41 (reference; 0.45–0.82) mg/dl. Upper GI endoscopy showed bleeding in the duodenum which continued after admission, and it was found to be DIC-related. Her plasma FDP was 177 µg/ml, D-dimer 81.7 µg/ml, TAT 69.2 ng/ml, and PIC 12.6 µg/ml. Eventually, she was identified with an aortic aneurysm (), and hemostasis laboratory abnormalities were attributed to be related to her aortic aneurysm. Surgical treatment of her aortic aneurysm was discussed; however, her general condition was poor, and because of repeat GI bleedings, she required upper GI endoscopy 13 times over 23 days for emergency hemostasis and with incomplete and persistent DIC. During the period, she received PRBC (36 units), FFP (70 units), and PC (50 units) transfusions. On day 38, she was started on systemic treatment for DIC, consisting of intravenous heparin (12,000 U/day) and intravenous tranexamic acid (250 mg twice daily), which resulted in rapid improvement of laboratory data. Unfortunately, the patient died of aspiration pneumonia 2 days later. |
pmc-6466915-1 | A 7-year-old healthy Caucasian boy was referred by the orthodontist to investigate the edentulous space between the first and second primary upper left molars, together with an unusual swelling in the same region. After an interview with the parents, a noncontributory medical history was confirmed.
The intraoral clinical examination revealed mixed dentition with no decayed teeth. A 6 mm edentulous space between the two primary upper left molars was observed. In addition, expansion of the cortical bone was present on the vestibular aspect of the right hemi-maxilla. The bony hard swelling was firm and asymptomatic. The overlying mucosa was normal and nontender on palpation. Second-level radiological investigation was performed by means of the cone-beam computed tomography (CBCT) scan, which confirmed the presence of an irregular radiopaque mass located by the roots of the primary molars ().
In more detail, the well-corticated lesion was characterized by multiple radiopaque structures encapsulated within a radiolucent cavity. Moreover, the lesion progressed in a vestibular direction so that the permanent second premolar germ resulted dislocated palatally. As a matter of fact, the germ could be palpated on the palatal aspect of the edentulous ridge. The clinical and radiographic presentations led to an initial diagnostic hypothesis of compound odontoma. The suggested treatment plan consisted of surgical removal of the lesion under oral sedation of the patient on an outpatient basis. After discussing the aforesaid surgical procedure, an informed consent signed by the parents was obtained.
Before the surgery, the following vital parameters were recorded: arterial blood pressure (systolic/diastolic pressure ratio: 85/50 mmHg), peripheral capillary oxygen saturation (SpO2: 99%), and heart rate (84 bpm). The weight and height of the patient were also registered (26 kg and 126 cm, respectively). At this point, the anxiolysis protocol used in the department in the case of pediatric patients was adopted ().
In this specific case, premedication consisted of oral administration of 15 drops of diazepam [] 3 mg/ml (Valium®, Roche Pharmaceuticals, Monza, Italy) and topical application of 15% lidocaine spray (OGNA Pharmaceuticals, Muggiò, Italy). A fingertip pulse oximeter was used during the entire procedure to monitor the oxygen saturation of the patient.
Local anesthesia was induced with infiltrations of mepivacaine hydrochloride 3% (Optocain® 30 mg/ml, Molteni Dental Srl, Milan, Italy). Crestal incision with vertical releasing incisions located at the mesial and distal aspects of the first and second primary molars, respectively, was performed to raise a trapezoidal mucoperiosteal flap. The odontoma was accessed by removing the thin overlying cortical layer with a round bur mounted on a straight surgical handpiece under copious irrigation of sterile saline ().
The denticles were subsequently exposed and removed in a total of 14 pieces ().
All harvested samples were sent for histopathological analysis. The surgical site was debrided and irrigated to remove any remnants, and the integrity of the maxillary sinus walls was checked. First intention sealing of the surgical wound was finally achieved with a 4/0 resorbable suture (Polysorb™, Covidien, Dublin, Ireland).
The time elapsed between the premedication and the end of the surgical procedure was 90 minutes. The vital parameters recorded immediately after the surgery were as follows: arterial blood pressure (systolic/diastolic pressure ratio: 80/50 mmHg), peripheral capillary oxygen saturation (SpO2: 100%), and heart rate (82 bpm).
The patient was prescribed antibiotic therapy consisting of 7.5 ml amoxicillin clavulanate pediatric suspension (Augmentin® pediatric suspension, GlaxoSmithKline, Verona, Italy) 3 times daily for 6 days and analgesics according to the patient needs. The rationale for antibiotic administration was to reduce the risk of infection of the blood clot during the immediate postoperative period in view of the considerable size of the lesion.
Postoperative care instructions included soft warm diet for 48 hours, 0.2% chlorhexidine mouthwash 2 times daily up to suture removal, topical application of ice, and refrainment from mechanical plaque removal of the primary molars for 7 days. The patient was discharged in stable conditions 90 minutes after the end of the surgical procedure. The healing proceeded uneventfully, and sutures were removed after 7 days. The histopathological report provided by the Department of Anatomic Pathology confirmed the diagnosis of compound odontoma (). |
pmc-6466927-1 | A previously healthy 41-year-old Caucasian woman was admitted to the Emergency Department at the Regional Hospital of Horsens with a three-day history of severe headache, nausea, and dizziness. The physical examination was unremarkable with no evidence of impaired vision. Regular medication only included oral contraceptives (75 microgram desogestrel). Initial blood screen tests revealed moderate hyponatremia (126 mmol/l) and borderline low levels of iodothyronines (T3 and T4) and thyroid-stimulating hormone (TSH, ). An acute cerebral computed tomography (CT) did not show haemorrhage or infarction, and no mass lesion in the sellar region. Lumbar puncture showed no signs of infection or bleeding. Additional blood tests showed normal anterior pituitary function () except moderate hyperprolactinemia. During the first two days of admission, plasma sodium concentrations dropped to a nadir level of 111 mmol/l (). On the third day, a magnetic resonance imaging [MRI] of the brain showed recent bleeding into a cystic process (10x10x8 mm) in the sellar region in close proximity to the optic chiasm with displacement of the pituitary gland to the right (). Urine and blood examination at day two () were consistent with SIADH according to standard criteria []. The patient was treated with fluid restriction (day two to day five) and an intravenous bolus of hypertonic saline 3% (day two only), which induced a gradual increase in plasma sodium concentrations (). During the following weeks, the patient developed polyuria, polydipsia, and persistent hypernatremia. She was diagnosed with central diabetes insipidus (CDI) and successfully treated with desmopressin (dose 0.1 mg daily).
A MRI follow-up after three and ten months showed no change in the size of the cystic adenoma and automated perimetry showed a normal visual field. Anterior pituitary function remained intact, whereas the patient's CDI is considered permanent. |
pmc-6466957-1 | In 2000, a 34-year-old woman without disease was referred due to epigastric discomfort. A physical examination revealed no abnormal findings. Endoscopic examination showed normal findings. An electrocardiogram (ECG) showed regular sinus rhythm with a normal PR interval (160 ms) and no LVH by the Sokolow-Lyon index (28 mm) (). The Sokolow-Lyon index for LVH defined as S in V1+R in V5 or V6 (whichever is larger) ≥ 35 mm [].
The patient was repeatedly admitted to our hospital from 2003 to 2010 ().
In 2014, the patient was referred to our hospital with dyspnea and chest pain. An ECG showed a shorter PR interval (100 ms) and more severe LVH (50 mm) by the Sokolow-Lyon index than the previous examinations (). Laboratory testing revealed a normal creatine phosphokinase (CPK) level (132 U/L; normal range 60-190 U/L), an elevated creatine kinase- (CK-) MB isoenzyme level of 15.44 ng/mL (normal range 0.1-6.7 ng/mL), and a slightly elevated lactate dehydrogenase (LDH) level of 302 U/L (normal range 140-271 U/L). TTE revealed LVH and partially decreased LV global longitudinal strain rates (Figures and ).
In 2016, the patient was again hospitalized with chest discomfort. The blood pressure was normal. An ECG showed a short PR interval (100 ms) and severe LVH (63 mm) by the Sokolow-Lyon index (). Laboratory testing revealed elevated CK-MB (15.21 ng/mL; normal range 0.1-6.7 ng/mL), LDH (494 U/L; normal range 140-271 U/L), and brain natriuretic peptide (pro-BNP) levels (2223 pg/mL; normal range < 115 pg/mL) with a normal CPK level of 151 U/L (normal range 60-190 U/L). Creatinine was normal and the 24-hour creatinine clearance ratio (Ccr) was 101.1 mL/min/1.73m2. TTE showed a thicker LV wall than the previous results. In addition, TTE revealed marked decreased LV longitudinal strain rates (Figures and ). Magnetic resonance imaging findings showed a delayed enhancement at the basal segment of LV lateral wall and LVH, and thus, FD was suspected (Figures and ). Ophthalmic examination showed cornea verticillata (). We measured α-GLA in patient's blood plasma using a fluorometric enzyme assay. Leukocyte α-GLA was significantly reduced to 10.6 nmol/h/mg protein (normal range > 35 nmol/h/mg protein). We identified one hemizygous mutation in exon 6 of GLA, c.969delC (p.Leu324 Trpfs∗24). Therefore, this patient was diagnosed with classic FD.
In 2017, the patient was admitted to cardiology for enzyme replacement therapy (ERT). Before ERT, an ECG still showed a short PR interval (100 ms) and extreme LVH (67 mm) by the Sokolow-Lyon index (). Laboratory testing revealed elevated CK-MB/CPK (38.91 ng/mL; normal range 0.1-6.7 ng/mL/272 U/L; normal range 60-190 U/L), LDH (289 U/L; normal range 140-271 U/L), and pro-BNP level (2853 pg/mL; normal range < 115 pg/mL). Eight months after ERT, ECG still showed a short PR interval and extreme LVH. TTE still showed LVH but a marked improvement of LV longitudinal strain rates (Figures and ). The patient's family members also underwent genetic testing, and the patient's two sons were diagnosed with classic FD (). We summarized the organ involvement and changes of Gb3 and lysoGb3 biomarkers of the affected family member in Tables and . |
pmc-6466958-1 | A 66-year-old African-American female with no significant past medical history presented to the emergency department (ED) with a four-week history of worsening abdominal discomfort. It was associated with the feeling of an urge to defecate without having an actual bowel movement, decreased appetite, and about six-pound weight loss over two months. She had not seen a physician for over ten years and never had a screening mammography, colonoscopy, or Pap smear. She reported chronic nonsteroidal anti-inflammatory agent (NSAID) use. Physical exam revealed stable vitals, abdominal distension, diffuse abdominal hardening, and positive shifting dullness.
The initial labs were significant for normocytic anemia with hemoglobin (Hb) of 9.6, normal white blood cells, and creatinine of 2.57 mg/dL. The electrolytes such as potassium, phosphorous, and calcium were normal. As there was no baseline creatinine available, it was unclear if the patient has chronic kidney disease (CKD) or acute kidney injury (AKI) or AKI on CKD. Fractional Sodium Excretion (FeNa) was less than 1 indicative of prerenal cause of acute renal failure. Urine eosinophil was negative which ruled out interstitial nephritis. A computed tomogram (CT) scan of the abdomen and pelvis without contrast (Figures and ) showed a 6.3 cm hyper dense focus adjacent to the right lobe of the liver, the large ascites, and the findings suggestive of peritoneal carcinomatosis along with diffuse body wall mass, large ascites, and grossly enlarged uterus containing multiple large partially calcified fibroids. CT chest without contrast showed a moderate left-sided pleural effusion as well as mediastinal lymph nodes measuring less than 1 cm in diameter.
She underwent paracentesis and biopsy of the mass adjacent to the right liver lobe. The peritoneal fluid analysis showed red cell count (RBC) of 673,333, absolute neutrophil count of less than 250/mm3, unsuggestive of spontaneous bacterial peritonitis. Serum ascites albumin gradient (SAAG) was less than 1.1, indicating that the fluid was an exudate.
During the hospitalization, her clinical condition started deteriorating with dropping Hb. She was transfused with two units of PRBC to keep Hb above 7 g/dL. Esophageogastroduodenoscopy (EGD) showed chronic active gastritis with intestinal metaplasia and positive H. pylori but no carcinoma. She did not receive any chemotherapy or radiation therapy.
Her kidney function also continued to worsen with poor urine output (less than 200 cc per day). On day 6 of hospitalization, creatinine rose to 5.22 mg/dL. She developed metabolic acidosis with bicarbonate of 18, while the other labs showing uric acid of 14.1 mg/dL, phosphorous of 6.2, calcium of 8.7, potassium of 5, and lactate dehydrogenase (LDH) level of 1449 IU/L (above six times the upper limit of normal). The electrocardiogram showed normal sinus rhythm. She met both laboratory and clinical tumor lysis syndrome criteria with worsening creatinine and elevated uric acid and phosphorous levels.
She was given one dose of rasburicase 3 mg intravenously (IV) and started on IV hydration and renal dose-adjusted oral allopurinol. Due to her poor response to the above measures, she was started on hemodialysis after which uric acid and phosphorous levels trended down. Lactate dehydrogenase (LDH) remained persistently elevated. The progressive creatinine, uric acid, electrolyte, and LDH values were shown in .
The peritoneal fluid cytology showed atypical cells with hyperchromatic nuclei in a bloody background. The pathology of the tumor mass biopsy revealed neuroendocrine tumor, consistent with small-cell carcinoma. The hematoxylin and eosin (H&E) stain and immunohistochemical (IHC) stain patterns did not point to a specific primary site (IHC showed strongly positive synaptophysin and CD56, negative cytokeratin AE1/AE3, CD 45, chromogranin, TTF1, calcitonin, and S100, with no diastase resistant material on PAS with diastase). shows H&E staining, and shows synaptophysin staining of tumor tissue. FoundationOne study identified genomic PIK3CA amplification showing potential clinical benefit if treated with everolimus and temsirolimus. Owing to the progressive clinical deterioration and multiple embolic strokes which were diagnosed later, the patient was deemed a poor candidate for chemotherapy and she opted for comfort care. She was made hospice and passed away after. |
pmc-6466965-1 | A 25-year-old male patient with a C6 fracture and dislocation (AO classification C1.2.4) was treated with skull traction following an unsuccessful manual reduction on the day of the accident (). After six-day preoperative preparation and traction, he had cervical spinal surgery for a C6 corpectomy, a C4/5-C6/T1 discectomy, and fusion of the C-spine using a titanium mesh cage. Radiographs indicated that the mesh cage was not well positioned postoperatively (). The patient was thus taken for secondary surgery to revise the plate and mesh cage (). A white purulent discharge from the surgical site was observed 30 days after the first operation. An oesophageal fistula at the level of C6 was confirmed by a gastrografin swallow test and laryngoscopy (). The patient was immediately taken for a thorough wound debridement; subsequently, continuous extensive irrigation was performed, intravenous vancomycin was started, and gastric decompression was done using continuous nasogastric tube drainage. Four weeks later, the results of three continuous cultures of bacteria were negative. After eight weeks, an upper GI endoscopy and a repeat gastrografin swallow were performed, and the irrigation and nasogastric tubes were removed. The patient reported no discomfort at three-month follow-up (Figures and ). |
pmc-6467181-1 | A 29-year-old man was transferred to our facility following primary closure of an injury to the left heel sustained via hydraulic boom of a logging truck. This resulted in degloving of the skin overlying the posterior Achilles tendon and heel, creating a distal flap. Extensive debridement was performed for necrosis of the heel pad and skin over the calcaneal tendon (). The resulting defect was reconstructed with a free latissimus dorsi myocutaneous flap (). An external fixator with multiplane placement was employed for 18 days. Two additional rods and 2 connectors were used to create a “kickstand” (). Repeat skin grafting was necessary with subsequent revision. The patient did well postdischarge, and the muscular flap remained viable. |
pmc-6467181-2 | A 25-year-old man sustained a crush injury to the left heel by a bulldozer. Lower extremity fractures were repaired at an outside hospital, and he was transferred to our facility for reconstruction of the resulting soft tissue defect. The wound was repaired with a free latissimus dorsi myocutaneous flap and a split-thickness skin graft. The patient was placed in an external fixation for a total of 6 weeks. The external fixator was modified with additional bars to keep the heel elevated as seen in patient 1. The hospital course was complicated by a methicillin-resistant Staphylococcus aureus (MRSA) infection and hematoma at the injury site requiring evacuation. The patient did well after discharge, and the muscular flap remained viable. |
pmc-6467181-3 | A 69-year-old man sustained third-degree frostbite to both feet. The patient underwent bilateral transmetatarsal amputation and required bilateral latissimus dorsi myocutaneous free flaps to cover the remaining defects. The patient was placed in an external fixator with kickstand modification on each leg as previously shown for 6 weeks. Revisional shortening of the metatarsals of the right foot was necessary secondary to partial flap necrosis. The patient did well after discharge, and the muscular flaps remained viable. |
pmc-6467182-1 | A 63-year-old African American woman presented to the Plastic Surgery clinic from her nursing home with a 2-year history of a painful distal forearm mass. The lesion was initially thought to be a keloid from a stab wound more than 20 years ago; however, she decided to have it evaluated because of a recent increase in size and intermittent bleeding. She denied any numbness, tingling, or weakness of the hand. Her neurovascular examination had normal findings. Clinically, the mass was located on the volar aspect of the mid-forearm, was pink and ulcerated, and 3 × 3 × 4 cm in size (). There was no associated supracondylar or axillary lymphadenopathy.
Because of the unique characteristics of the mass, we further evaluated the lesion with a magnetic resonance image of the right forearm. This image demonstrated a 3.8 × 2.1 × 4.1-cm mass in the subcutaneous tissue without invasion into the fascia or muscle (). The lesion was concerning for malignancy, so she was referred to a surgical oncologist for excisional biopsy. One month later, the mass was excised en bloc with careful dissection of the deep margin to maintain the fascia. We used a 6 × 4-cm elliptical incision, and this defect was closed primarily using suprafascial flaps for a tension-free closure.
On final pathology, the entire specimen was 6 × 4 × 0.8 cm. It was found to be an invasive nodular melanoma with positive, deep, and radial margins. This case was discussed at our multidisciplinary tumor board with plans of positron emission tomographic (PET) scan, reexcision, and sentinel lymph node biopsy.
Before her postoperative follow-up appointment, she underwent a PET scan, which unfortunately demonstrated a hyperactive node in the right axilla as well as a concerning left breast lesion. At her follow-up appointment, we offered a wide local excision with sentinel lymph node biopsy; however, the patient refused to have further surgery. On physical examination, there was a small, red, scaly lesion in the middle of the surgical site concerning for rapid recurrence. We referred her to a breast surgeon for workup of the left breast lesion, which ultimately was found to be ER/PR+ invasive lobular breast cancer. The patient was scheduled for close follow-up in both clinics but had not made her appointments. After reviewing the medical records, the patient refused to have any further surgical procedure at this time. |
pmc-6467352-1 | A 63-year-old male was found to have a polypoid colonic lesion during screening colonoscopy in January 2016. The polyp was biopsied and was found to have involvement by mantle cell lymphoma. Bone marrow aspirate and biopsy showed low-level involvement by mantle cell lymphoma. During the few months prior to diagnosis, the patient had been experiencing fatigue, loss of energy, and subjective fever. After his diagnosis, he began experiencing abdominal bloating and insomnia. The insomnia is believed to be due to anxiety about the diagnosis. He denied night sweats or weight loss. Original laboratory tests showed a normal complete blood count (CBC) with differential, beta-2 microglobulin, lactate dehydrogenase (LDH), and uric acid, and an unremarkable comprehensive metabolic panel (CMP). On computed tomography (CT) of the chest, abdomen, and pelvis, lymphadenopathy was found both above and below the diaphragm, with the largest lymph node being in the left groin, measuring up to 2.5 cm in the short axis. There was no splenomegaly. A positron emission tomography/computed tomography (PET/CT) scan showed metabolically active adenopathy in the supraclavicular, subpectoral, and axillary regions, as well as the middle mediastinum, subcarinal space, superficial and deep inguinal chains, and periaortic region of the lower abdomen (Figure ). Based on the diagnostic testing, the mantle cell lymphoma was classified as stage IV. The patient did not undergo next-generation sequencing, so p53 mutation status was not available. Treatment was started in February 2016.
The patient was referred to a specialty hospital to determine the optimal treatment regimen. The decision was made to proceed with the Nordic protocol, consisting of Maxi-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), high-dose cytarabine, and rituximab. In addition, the patient was given pegfilgrastim on the second day of each chemotherapy cycle. After completing the six cycles of chemotherapy, the patient was found to be in complete remission (Figure ). Shortly after, the patient returned to the specialty hospital where he underwent BEAM conditioning, followed by autologous stem cell transplant. He also received filgrastim and plerixafor during this time. The patient was placed on trimethoprim-sulfamethoxazole and penicillin V for post-transplant prophylaxis. He remained at the specialty hospital for several weeks following the transplant, due to complications, including neutropenic fever, orthostatic hypotension, generalized weakness, and poor engraftment, requiring multiple filgrastim injections.
Approximately two months after autologous stem cell transplant, the patient presented to the emergency department with dyspnea. He was admitted to the hospital and a CT angiography (CTA) was performed. The CTA was negative for pulmonary embolism but did show large bilateral pleural effusions (Figure ). Analysis of the pleural fluid using Light's criteria revealed a transudative effusion. Thoracentesis and bronchoscopy did not show any evidence of infection. Doppler of the abdomen was negative for portal vein thrombosis and hepatic vein thrombosis. Two-dimensional echocardiogram revealed a normal left ventricular ejection fraction of 60%-65%, which was unchanged from the patient's baseline echocardiogram. The patient had a remote history of tobacco use of about one pack of cigarettes per day for four years but had not used any tobacco products in over 40 years. He had no history of lung disease. The patient was given two doses of methylprednisolone 125 mg intravenous (IV) eight hours apart. The next day, he was started on prednisone 1 mg/kg of body weight for 10 days and then tapered by 5 mg every two days. The patient’s symptoms completely resolved following steroid administration (Figure ). The bilateral pleural effusions experienced by the patient are thought to be due to BCNU-related lung toxicity. |
pmc-6467428-1 | A 55-year-old male with a 40 pack-year smoking history, hepatitis C, and extensive IV drug use presented to the emergency department (ED) complaining of hip pain and mild shortness of breath after falling on his side in his home. The patient was admitted and an initial computed tomography (CT) scan revealed a small, left-sided pleural effusion. After appearing stable on medical observation, the patient was discharged after one day with pain medication for his symptoms. Three days later, the patient again presented to the ED with worsening dyspnea, confusion, and continuing left-sided hip pain. Physical examination was positive for confusion and unequal pupils. The patient denied any subjective fevers, but stated that he had experienced sweats prior to admission. Objectively, the patient’s vital signs showed an oxygen saturation of 86% on room air, though his respiratory rate and temperature were within normal limits at the time. A large, loculated, left-sided pleural effusion was revealed on non-contrast CT of the chest (Figure ).
Initial labs revealed no leukocytosis, but they did reveal a mildly elevated serum lactic acid of 2.3 mmol/L (normal: <2.0 mmol/L). Additionally, urine screen was positive for amphetamines, benzodiazepines, and opiates. Later that day, the patient became febrile (39.0 Celsius) and tachypneic (40-50 breaths per minute). He was subsequently transferred to the medical intensive care unit for acute hypoxic respiratory failure and placed on 10-15 liters of high-flow oxygen and empirically treated with levofloxacin and piperacillin/tazobactam. The day after admission, ultrasound-guided thoracentesis was performed revealing bloody fluid containing 20,000 white blood cells (WBC)/microliter (normal: <1,000 cells/microliter) with 95% neutrophils, a pH of 6.91 (normal: 7.60-7.64), and lactate dehydrogenase (LDH) of 7,827 U/L (serum LDH: 559 U/L). Additionally, the patient's serum WBC count was now elevated at 15,000 cells/microliter and blood cultures were positive for methicillin-sensitive Staphylococcus aureus (MSSA), prompting a switch in antibiotics to vancomycin and ampicillin/sulbactam. Four days after admission, the patient underwent bronchoscopy and video-assisted thoracic surgery (VATS) for decortication of the suspected loculated empyema. Status-post VATS, the patient's fever and leukocytosis began to resolve. Empiric antibiotics were discontinued and the patient was started on intravenous (IV) cefazolin.
Four days status-post VATS (eight days status-post admission), the patient began to exhibit subtle right-sided shoulder pain and numbness extending into the right hand. Initial non-contrast CT scan revealed posterior C6-C7 osteophytic spurring, disc bulging, and moderate spinal stenosis. A cervicothoracic magnetic resonance imaging (MRI) scan with contrast was attempted but was not completed due to the patient being agitated and anxious during the imaging process. Eight days status-post VATS, the patient reported increasing weakness and 'cramp-like sensations' in all extremities at rest. Additionally, the patient complained of plantar numbness in the feet, decreased sensation to light touch in bilateral upper extremities, and neck pain radiating to the thoracic and lumbar spine. Neurology was consulted and a focal neurological exam found decreased grip strength and clonus of the knees and ankles. The patient was prescribed gabapentin for symptomatic treatment. Cervical and thoracic MRI with contrast were performed, which revealed fluid collections with circumferential dural thickening and enhancement spanning spinal segments C3 to T2 in the anterior epidural space, prevertebral fluid collection spanning from C4 to T2, retropharyngeal fluid and edema from C1 to T3, discitis and osteitis from C5 to C7, and spinal cord narrowing from C4 to C6 with signal abnormality consistent with compressive myelitis (Figure ). These findings were concerning for SEA given the patient's positive blood cultures for MSSA, IV drug use, and previously diagnosed empyema.
A decompression laminectomy and washout of purulent fluid and thick phlegmon in the epidural space from C1 to T3 was performed by neurosurgery the day after diagnostic MRI. Culture and sensitivity testing of the purulent fluid from the spinal epidural space revealed MSSA.
The day after spinal decompression and laminectomy, the patient's WBC count dropped back into the normal range and remained there for the rest of the hospitalization. However, the patient reported continued extremity weakness and paresthesia that only partially improved with gabapentin. The patient was discharged for physical rehabilitation. Over the next few days, the patient’s arm strength improved and he required minimal assistance with daily activities. The patient continued to improve but had persistent upper extremity pain and weakness and was followed by the internal medicine and infectious disease services throughout the course of his antibiotic treatment with IV cefazolin. |
pmc-6467430-1 | An 80-year-old Caucasian female who was an active smoker with a 40 pack year smoking history and a past medical history of primary hypertension and chronic obstructive pulmonary disease (COPD) presented to our hospital emergency department (ED) in February, 2017 with fatigue, generalized weakness, and shortness of breath for the last two days. She had been noticing progressively worsening shortness of breath on exertion without any fever, chills, cough, chest pain, orthopnea or paroxysmal nocturnal dyspnea. She did not have any sick contacts and had not travelled anywhere recently.
Upon arrival to the hospital, she was noted to have a heart rate of 122 beats per minute, a respiratory rate of 30 breaths per minute with an oxygen saturation of 85% on room air, and a blood pressure of 161/86 mmHg. Further physical examination revealed a thin and cachectic female who appeared to be in mild respiratory distress. She was noted to have normal heart sounds without any murmurs, rubs, or gallops. A pulmonary examination revealed expiratory wheezing bilaterally without any rales or rhonchi. She did not have rashes or peripheral edema. Due to her respiratory distress she was started on non-invasive ventilatory support in the emergency department (ED), which led to improvement in her respiratory status.
Laboratory investigation revealed a hemoglobin count of 15.1 g/dL (reference range [ref], 12.3-15.3), a peripheral white blood cell count of 21,130 cells/mm3 (ref, 4400-11,300) with a relative neutrophil percentage of 80% (ref, 37%-77%), a platelet count of 301,000/mm3 (ref, 145,000-445,000), a sodium level of 134 mmol/L, a serum creatinine level of 0.30 mg/dL (ref, 0.70-1.5), and a blood urea nitrogen of 8 mg/dL (ref, 9-20). Her liver enzymes were within normal limits. Venous blood gas analysis revealed a pH of 7.26 and a CO2 of 83 mmHg (ref, 41-51). Initial serum procalcitonin was 0.07 ng/mL and a chest radiograph was only significant for hyper-inflated lungs (Figure ).
She was admitted to the hospital for management of mild COPD exacerbation and treated with inhaled bronchodilators and systemic steroids. Repeat blood work obtained 12 hours after initial presentation was significant for a serum procalcitonin of 2.07 ng/mL and a peripheral white blood cell count of 35,170 cells/mm3 with a relative neutrophil percentage of 91% and 2% bands. Due to concerns for development of CAP, sputum cultures, two sets of blood cultures via peripheral blood draw and urinary antigens for S. pneumoniae and L. pneumophila were obtained. She was started on intravenous ampicillin-sulbactam 3 grams every six hours and azithromycin 500 milligrams every 24 hours. A computed tomography scan of the chest revealed tree-in-bud opacities along with regions of bronchial wall thickening in the bilateral lower lobes (Figure ).
A sputum Gram stain revealed many Gram-positive rods, rare Gram-positive cocci, less than 10 squamous epithelial cells and greater than 25 white blood cells per low power field. Her blood cultures remained negative and the final sputum culture grew normal respiratory flora. Surprisingly, urinary antigens for both S. pneumoniae and Lp1 returned positive. Antibiotics were then de-escalated to intravenous levofloxacin 500 mg every 24 hours for a total of five days. The patient’s clinical status improved, and she was discharged home in a stable condition after a one-week hospital stay. |
pmc-6467431-1 | A 45-year-old woman with a substantial past medical history of squamous cell cancer (SCC) was treated with laryngectomy and offered tracheostomy. She presented in the emergency department with complaints of shortness of breath (SOB). Her shortness of breath was getting progressively worse starting two days prior to admission. She denied any fevers, chills, sick contacts, nausea, abdominal pain, or diarrhea. She specified that she had actually been drinking a lot more water than regular prior to admission.
On admission, her vital signs revealed a blood pressure of 101/73 mmHg, a heart rate of 91 beats/min, a temperature of 37.4 degree Celsius, and a respiratory rate of 26 breaths/min. Her body mass index (BMI) was 18.6 kg/m2. Physical examination revealed a sick-appearing woman in severe respiratory distress using accessory muscles. She had a dry mucous membrane with poor skin turgor. The rest of the physical examination was unremarkable.
On laboratory assessment, the hemoglobin was 11.9 mg/dl, leukocyte count 3.6/mm3, serum creatinine 0.8 mg/dl, potassium 3.3 mmol/L, chloride 110 mmol/L, sodium 148 mmol/L, and bicarbonate 6 mmol/L. She had high anion gap metabolic acidosis (AGMA), (anion gap (AG) = 22). Her serum albumin on admission was 4.2 g/L, urine analysis revealed 80 mg/dl ketones, and serum lactate was 1.9 mmol/L. Furthermore, her liver enzymes revealed aspartate aminotransferase (AST) = 48 units/l, alanine aminotransferase (ALT) = 82 units/l, and alkaline phosphatase 199 units/l. Additionally, her blood glucose level was 133 mg/dl, salicylates = 6.8 mg/dl, and acetaminophen level was <2.0 ug/ml. Her blood alcohol level was normal and chest X-ray (CXR) on admission did not show any sign of acute cardiopulmonary problems.
Based on the initial evaluation, she received stoma suctioning and was placed on high O2 via a tracheostomy mask. Her history of laryngeal cancer, mild tachycardia and hypoxia raised the suspicion of pulmonary embolism, so a chest computed tomography angiography (CTA) was ordered. The chest CTA was negative for pulmonary embolism but showed mild emphysema.
In addition to that, an arterial blood gas (ABG) test was done, which revealed a high anion gap metabolic acidosis (HAGMA) as presented in Table . The patient continued to hyperventilate to compensate for the acidosis and was subsequently intubated.
Differential diagnoses including carbon monoxide poisoning, aminoglycoside toxicity, methanol, uremia, diabetic ketoacidosis (DKA), alcoholic ketosis, acetaminophen toxicity, iron ingestion, lactic acidosis, ethanol toxicity, salicylate toxicity, and aspirin ingestion were investigated. However, given the patient's normal acetaminophen, salicylate, lactic acid, and ethanol levels, these etiologies were ruled out. Furthermore, serum osmolality was normal and the osmolal gap was less than 10. Our differential diagnosis was further narrowed due to the presence of elevated ketones. Given the patient's malnourished state, the most likely cause of HAGMA in this patient was starvation ketosis. The patient was started on 5% dextrose water and sodium bicarbonate drip, and tube feeds. The ABG level swiftly improved within three days and she was extubated.
After four days of intensive care unit (ICU) course, she was downgraded and later on discharged after detailed counseling from a nutritionist regarding a balanced diet and avoiding fasting. She was followed up after three weeks of discharge with significant improvement on repeat basic metabolic panel with bicarbonate of 25 mmol/L, sodium 138 mmol/L, potassium 3.8 mmol/L, and chloride 102 mmol/L. |
pmc-6467432-1 | A 70-year-old male presented to his primary care physician with jaundice. Bloodwork revealed a bilirubin of >100 µmol/L. A CT scan of the abdomen and pelvis revealed moderate intrahepatic biliary dilatation and a stricture of the common hepatic duct within the head of the pancreas. Soft tissue infiltration around the common hepatic artery and portal vein was suspicious for a cholangiocarcinoma. On subsequent imaging, an ill-defined hypoattenuating mass (5.4 cm x 2.8 cm) was observed adjacent to the hepatobiliary tract extending into the right lobe of the liver consistent with a liver metastasis from the cholangiocarcinoma (Figure ). He underwent endoscopic retrograde cholangio-pancreatography (ERCP) and bile duct brushings revealed adenocarcinoma cells. Functionally, he was well with an Eastern Cooperative Oncology Group (ECOG) performance status of 1.
His previous medical history was remarkable for gout, hypothyroidism, dyslipidemia, benign prostatic hypertrophy, appendectomy, and remote pancreatitis. His medications included levothyroxine, allopurinol, omeprazole, rosuvastatin, and vitamin B12. He had a 30 pack year history of smoking, and quit 19 years ago. At baseline, he consumed two to three alcoholic drinks per day but has abstained from alcohol since the time of his diagnosis.
As part of his initial staging investigations, a CT scan of the chest was performed which revealed a 1.8 cm spiculated right apical pulmonary nodule (Figure ). A transthoracic, image guided biopsy of the pulmonary nodule revealed an adenocarcinoma. Immunohistochemistry (IHC) was positive for cytoketatin 7 (CK7), thyroid transcription factor 1 (TTF-1) and Napsin A, and negative for cytokeratin 20 (CK20), consistent with a primary NSCLC. IHC for anaplastic lymphoma kinase (ALK) was negative and programmed death-ligand 1 (PD-L1) was 1% to 49%. There were insufficient cells in the bile duct brushings to do mismatch repair (MMR) testing or to compare the NSCLC and biliary tract specimens in terms of morphology and IHC profile. However, because the lung tumor was small in size, with no evidence of hilar or mediastinal lymphadenopathy, these were deemed to represent two distinct primary cancers.
After review of his case in both the lung and gastrointestinal provincial tumor boards, he received eight cycles of palliative-intent cisplatin and gemcitabine chemotherapy. He required a dose reduction because of rash and neutropenia. During chemotherapy, the liver metastasis grew slightly to 5.4 cm x 3.6 cm and appeared more conspicuous compared to a prior examination. The lung mass, however, remained stable, as per response evaluation criteria in solid tumors (RECIST criteria) []. Chemotherapy was stopped and the patient continued on observation. On a follow-up CT scan, both the disease in the chest and the abdomen remained stable. As the patient maintained an excellent functional status over one year since the initial diagnosis, the option of SBRT to the lung lesion was considered.
As part of the pre-SBRT assessments a positron emission tomography (PET) scan and CT brain were performed, which confirmed that there were no other sites of distant or nodal metastatic disease consistent with an AJCC 8th ed. [] stage of T1bN0M0 NSCLC. He was then treated with radical SBRT to the right upper lobe NSCLC with a total dose of 48 Gy in four fractions (Figures -). His treatment was planned using a four-dimensional CT simulation scan with fusion of a pre-treatment PET scan to aide with delineation of the primary tumor. His SBRT was delivered using two 240-degree RapidArc™ 6 megavoltage photon arcs using a Varian Edge Linear Accelerator. Daily cone beam CT scans were used for purposes of daily image guidance for his SBRT. He tolerated his SBRT very well and did not suffer any acute severe adverse effects as a result of treatment.
Three months post-completion of SBRT to the NSCLC, he presented to his primary care physician with a jaundiced appearance and mild scleral icterus. Bloodwork revealed transaminases and cholestatic liver enzymes were three to five times the upper limit of normal. Total bilirubin was 79 µmol/L, and direct bilirubin was 61 µmol/L. A CT scan of the chest, abdomen, and pelvis was performed in order to rule out tumor progression as a cause for his change in clinical status. The CT scan of the chest revealed stability of the right upper lobe lung tumor. Within the abdomen, the hepatic metastasis had completely resolved (Figure ). Bloodwork repeated one week later showed that his liver enzymes and bilirubin had completely normalized. The carbohydrate antigen 19-9 (CA 19-9) had decreased from 41 to 14 (upper limit of normal = 34 U/mL). A dedicated MRI of the liver was performed four months post-completion of the SBRT to the NSCLC in order to further assess the status of the liver metastasis. This scan confirmed the complete and spontaneous out-of-field resolution of the hepatic metastasis in keeping with an abscopal event (Figures -).
The median survival of patients with locally advanced or metastatic cholangiocarcinoma treated with palliative gemcitabine/cisplatin chemotherapy is 11.7 months []. This patient is now 21 months removed from his initial diagnosis of unresectable cholangiocarcinoma and he is enjoying a more protracted survival than expected. He remains functionally active, exercising on a daily basis and is able to maintain employment as the proprietor of a construction company. It is unclear why the abscopal effect was limited to a metastasis in this case, however, it is plausible that the primary cholangiocarcinoma tumor may also change with time and further follow-up will be performed to monitor for this possibility. |
pmc-6467610-1 | A 63-year-old nonsmoking woman, with left breast cancer, opted for bilateral autologous breast reconstruction (Fig. ). Intraoperatively, the patient was placed in lithotomy position. Skin paddle fleur-de-PAP patterns were drawn on both thighs with a transverse component along the superior-medial thigh, and a vertical component, posterior to the adductor longus. Flaps were elevated with initial incision made over the gracilis muscle anteriorly and dissection performed in a subfascial plane proceeding posteriorly. The dominant perforators through the adductor magnus was identified and circumferentially dissected (Fig. ). Retrograde dissection was taken to the profunda artery and vein. The vessels were clipped and divided. The superior and posterior incisions were then performed and the flap was harvested, anastomosed to the internal mammary artery and vein. In a similar fashion, the left thigh flap was harvested and taken to the left chest for microvascular anastomosis. The flaps were inset using the transverse portion of the flap to provide superior fullness and the vertical portion of the flap providing an inferior sling along the inframammary fold (IMF). Final flap weights were: right 316 g, left 298 g with each flap measured 22 cm × 7 cm. Perfusion to all components of the skin paddle was confirmed with SPY (Novadaq, Toronto, Ont.) fluorescence imaging.
At follow-up appointments, the only complication was minimal dehiscence at the T-junction of the thigh incisions bilaterally which was treated with silver nitrate applications. She subsequently underwent second-stage esthetic procedures for contouring by excising the skin paddle, fat grafting for volume in the superior pole (140 mL to right breast and 80 mL to the left breast), and nipple tattooing, without complications (Fig. ). |
pmc-6467610-2 | A 42-year-old woman with unilateral breast cancer who was not a candidate for bilateral DIEP flaps secondary to a previous abdominoplasty. She was offered autologous breast. With the patient in the lithotomy position, bilateral fleur-de-PAP flaps were marked and harvested by means of similar technique as patient 1 (Fig. ) with flaps weighing 360 and 380 g. The flaps were transferred to the chest wall for microvascular anastomosis using the internal mammary system. Inset was completed using an inverted T-position, with the lateral limbs folded posteriorly to create a 3-dimensional teardrop with greater projection at the inferior pole of the breast.
Her postoperative course was complicated by a surgical-site infection at the left breast, which responded to antibiotics, local debridement, and wound care. A second-stage procedure was completed 6 months later to finalize the reconstruction. At that time, the patient underwent bilateral fat grafting with 150 mL of fat to each breast and had bilateral nipple reconstruction. |
pmc-6467954-1 | A 40 year-old male presented to an outside hospital with 3 days of persistent dyspnea, non-productive cough, chills and diaphoresis. He denied fever but also noted intermittent, non-radiating, burning chest pain and an unpleasant taste in his mouth. His past medical history was significant for pulmonary embolism upon returning from military deployment in Afghanistan 8 years prior. He was no longer on Warfarin, however had been taking Ibuprofen, 1,600 mg by mouth twice daily for the last 48 h. He was a former smoker who had recently re-started smoking again within the last week after over a year of abstinence. He was previously incarcerated though was released from prison ~1 year prior to admission and now worked as a construction worker. He had not recently traveled and had no pets or sick contacts at home.
On admission, vital signs were significant for a temperature of 38.2°C, heart rate of 123 beats per minute, blood pressure of 123/88 mm of Hg, respiratory rate of 32 breaths per minute, and peripheral capillary oxygen saturation of 94%. He was 186 centimeters tall and weighed 110 kilograms. Physical examination was notable for diminished breath sounds bilaterally, though the patient was not in respiratory distress or wheezing. There was no lymphadenopathy, no calf tenderness and no rash present. The patient was alert and oriented, though anxious appearing. Laboratory values were significant for a white blood cell count of 15.4 × 10∧9/L with 84% segmented neutrophils, 8% lymphocytes, 7% monocytes and 1% eosinophils. Complete metabolic panel and D-dimer were within normal limits. Chest radiography revealed bilateral pulmonary infiltrates () and chest CT revealed widespread mixed groundglass and solid airspace opacities predominantly in the middle lung zones without evidence of pulmonary emboli (). Piperacillin/Tazobactam, Vancomycin, Azithryomycin, Micafungin, and Bactrim were empirically initiated.
Over the course of the next 12 h, the patient began experiencing refractory hypoxemia. He was placed on a non-re-breather mask, then high-flow nasal cannula and then emergently intubated for ongoing hypoxemia. Arterial blood gas following intubation was significant for a pH of 7.20, PCO2 of 54, PO2 of 60 and bicarbonate of 20.8. Ventilator settings at that time included a positive end expiratory pressure of 22 cm H2O, fraction of inhaled oxygen at 100%, peak inspiratory pressure of 44 cm H2O, tidal volume of 860 mL, and respiratory rate of 28 breaths per minute. The PaO2/FiO2 was 65. In the setting of profound hypotension and acute hypoxic respiratory failure, the patient was then transferred to our tertiary care facility for emergent V-V ECMO; cannulation of the right internal jugular vein with a 31 French dual lumen cannula was performed at the bedside. Immediate improvement in pulse oximetry was noted at an ECMO blood flow of 4.6 liters per minute, fraction of membrane lung oxygen at 100%, sweep gas flow of 5 L/minute and 3,800 rotations per minute. The patient was started on stress dose Hydrocortisone, 50 mg IV every 6 h, in the setting of distributive shock secondary to presumed adrenal insufficiency, Norepinepherine at 0.3 micrograms per kilogram per minute, and Vasopressin at 2.4 units per hour. White blood cell count upon transfer was measured to be 38.4 × 10∧9/L, though a cell differential was not drawn at that time.
Bronchoalveolar lavage (BAL) was performed 1 day later and notable for copious amounts of thin, green liquid without evidence of pus, bilaterally. Cellular analysis revealed a total nucleated cell count of 380 cells/mL with marked eosinophilia at 21% eosinophils (absolute cell count, 80 cells/mL), 4% neutrophils (15 cells/mL), 38% lymphocytes (144 cells/mL), 1% basophils (4 cells/mL), 6% macrophages (23 cells/mL), and 30% alveolar pneumocytes and bronchial cells (114 cells/mL). Complete blood count then revealed ongoing leukocytosis (18.6 × 10∧9/L) with evidence of peripheral eosinophilia (12.8%, 238 cells/mL) (see for complete blood cell count trends). IgE levels were also found to be elevated at 1,434 IU/mL. Extensive infectious and autoimmune work-ups were performed and found to be unrevealing; an HIV test was also negative.
While the work-up of this patient's acute hypoxic respiratory failure was ongoing, stress-dose hydrocortisone was continued. His clinical condition began to improve over the next several days; he was weaned from V-V ECMO prior to being weaned from invasive mechanical ventilation, with the fraction of membrane lung oxygen, blood flow, and sweep gas flow on ECMO all decreased gradually. A diagnosis of AEP was reached after the infectious work-up was confirmed to be negative and all other causes of pulmonary eosinophilia were ruled out. Piperacillin/Tazobactam was continued for 10 days empirically; all other antimicrobials were discontinued on day 6 of hospitalization. He was decannulated from V-V ECMO and started on Prednisone, 60 mg by mouth daily on day 7 of hospitalization. Peripheral eosinophil counts continued to downtrend while on corticosteroids (). He underwent tracheostomy on day 4 of hospitalization, was weaned off of vasopressors and mechanical ventilation on days 3 and 8 (respectively), transferred out of the intensive care unit on day 12 (), and eventually discharged home on day 16. He was continued on Prednisone, 40 mg by mouth daily until follow-up with Pulmonology 2 weeks after discharge. |
pmc-6468034-1 | The patient was a 62-year-old man who underwent gastric partial resection for GIST 2 years previously. Six months after the surgery, a single tumor emerged in the hepatic left lobe. Because it was thought that tumor was metastasis of the gastric GIST, he had started on imatinib based on the pathological and genetic evidence of the original lesion. Two months after beginning imatinib, the tumor had enlarged and the imatinib regimen was changed to sunitinib. Eleven months later, the tumor had grown further and he was referred to our hospital for surgery because the tumor was considered to be tolerant to tyrosine kinase inhibitors. His blood tests showed the following: aspartate aminotransferase, 32 U/L (normal range, 5 to 30 U/L); alanine phosphatase, 37 U/L (normal range, 10 to 30 U/L); total bilirubin 1.2 mg/dL, (normal range, 0.2 to 1.2 mg/dL); carcinoembryonic antigen, 3.5 ng/ml (normal range, < 5.0 ng/ml); and carbohydrate antigen 19–9, 8.0 U/ml (normal range, < 15 U/ml). An indocyanine green retention rate of 15 min was 15.1% with Child–Pugh grade A. Abdominal ultrasonography showed a 51-mm-wide tumor in hepatic segment 4 with heterogeneous echo and it didn't present bloodstreem increase. Sonazoid-enhanced ultrasonography with hypervolemic contrasting pattern revealed that the tumor was enhanced in the early phase and washed out in the late phase (Fig. ). Enhanced computed tomography showed a 40-mm-diameter tumor in hepatic segments 3 and 4 (S3 + 4) with an enhanced solid nodule along the wall (Fig. ). On the right side of the tumor, there was an additional 50-mm tumor, which suggested a hemorrhagic cyst (Fig. ). Gadolinium-enhanced magnetic resonance imaging also showed an enhanced S3 + 4 tumor, a hemorrhagic cyst, and small nodules, which represented enhancement defects in the hepatocyte phase in hepatic segments 6 (S6), 7 (S7), and 8 (S8) (Fig. ). 18F-Fluorodeoxyglucose positron-emission tomography showed a high FDG uptake lesion in only the S3 + 4 tumor verge. No evidence of metastasis from other organs was observed (Fig. ). Although the imaging findings which suggested that the tumors were possibly other hepatic malignant tumors such as hepatocellular carcinoma had been considered, we diagnosed the tumors as hepatic metastases of gastric GIST because of the existence of multiple tumors and treatment progress. We performed hepatic left lobectomy and partial resections for three lesions. Intraoperative ultrasonography showed the tumor in hepatic medial segment and hematoma between the tumor and middle hepatic vein. The tumor measuring 73 mm × 65 mm × 36 mm in the resected left lobe showed a 40-mm white solid component, an adjoining 22-mm black nodule, and a cystic lesion with bleeding close to the margin (Fig. ). The histopathological findings showed that the spindle-shaped cells with nuclear atypia and eosinophilic cytoplasm proliferated diffusely in the solid component (Fig. ). Characteristically, the tumor cells were full of pleomorphism. The partially resected specimens did not contain tumor tissues. The S6 nodule was a cyst, while the S7 and S8 specimens represented dilated ducts. Accordingly, those lesions were not considered GIST metastases. Immunohistochemical analysis showed that desmin was positive, α-smooth muscle actin (α-SMA) was slightly positive, and heavy caldesmon and muscle actin (HHF35) were positive in 30% of the tumor tissue (Fig. ). S-100 protein and myogenic differentiation 1 (MyoD1) did not present significant staining (Fig. ), and c-kit and CD34 were negative.
In contrast with these findings, the gastric GIST specimen resected 2 years previously showed that although c-kit was positive and CD34 was weakly positive, the desmin, αSMA, and S-100 protein were negative. Additionally, c-kit gene mutations were not detected in the hepatic tumor tissue, whereas these mutations were positive in gastric GIST (Table ).
According to these findings, we diagnosed the patient with primary hepatic PLMS. The postoperative course was good, and the patient was discharged 9 days after the operation. Because a chemotherapeutic strategy for PLMS has not been established, imatinib was administered as an adjuvant chemotherapy for GIST. Tumor recurrence was detected in the vicinity of the pancreatic head 10 months after the operation, and doxorubicin is now being administered. |
pmc-6468141-1 | A 16 years old male was injured during school basketball when he touched the ground after jumping. He directly feels severe pain in his left knee and fell in terrain, he was admitted at the emergency department, the clinical examination of his left knee detected a flessum, swelling and exquisite pain of anterior tibial tuberosity with the inability to ambulate. X-rays showed a displaced avulsion fracture of tibial tuberosity (). A computerized tomography scan with 3D imaging demonstrated tibial tubercle avulsion fracture () and categorized it Ogden Type III.
Operative intervention was achieved through open reduction and internal fixation via an anterior midline incision. By direct visualization, the tibial tubercle fragment was reduced manually and fixed using 2 cannulated screws with washers. Attention was taken to prevent splitting of tuberosity using small screws 3.5 mm. Post-operative X-rays showed a good reduction. ()
The operated limb was kept in full extension at cylinder cast for 4 weeks. At 4 additional weeks later, he began physiotherapy and prone active-knee flexion limited to 90°, with passive extension.
At 8 weeks, complete knee motion was authorized. At 3 months follow-up appointment, we notice radiographic union, and no clinical pain or limp, without any skeletal anomaly. Successful back to all normal activities including school sports, with a full range of knee mobility was attained at 6 months. At one-year follow-up, the alignment of lower limbs was preserved. |
pmc-6468145-1 | A 57 -year-old female presented with incidental ultrasonic evidence of left upper pole renal mass in Nov. 2001. Further evaluation with abdominal Magnetic Resonance Imaging revealed a mass in the upper pole of the left kidney with radiologic characteristics of renal cell carcinoma (). Left radical nephrectomy was performed sparing the left adrenal gland. The pathology specimen analysis showed a cystic mass 3 × 3 × 5 cm with yellowish friable tissue. Sections showed malignant epithelial cells, arranged in sheets. The picture was consistent with renal cell carcinoma, Grade II Fuhrman nuclear characteristics, confined to the capsule, neither pelvicalyceal nor vascular invasion was found (pT1bN0M0). Postoperatively she did not receive immunotherapy or chemotherapy. Apart from her hypertension which was well controlled with amlodipine and valsartan, subsequent clinical and radiological follow up showed no local or metastatic recurrence till 5 years after the operation then she stopped her visits. On October 2016 an incidental mass was found in the right adrenal gland during a checkup visit for the status of her right solitary kidney. Abdominal and pelvic computed tomography scan was done, revealing a well-defined mass with a smooth outline in the right adrenal gland measuring 54 × 48 × 39 mm with a central necrosis. The density of the solid component was 38 HU. In dynamic study the solid component showed significant enhancement after intravenous contrast administration (). Thorough hematological, biochemical and hormonal investigations were performed; all were within normal range. The results of laboratory examination showed the adrenal mass to be nonfunctional. The condition was well clarified for the patient and consent was taken to do right adrenalectomy. Under general anesthesia, in left lateral position through right transcostal incision, right adrenalectomy was done (). No any perioperative complications were recorded and she was discharged home on 4th post-operative day. Pathological examination revealed morphological and immunohistochemical findings in line with metastatic renal cell carcinoma, including positive staining for AE1/AE3, cytokeratin 7, vimentin, and CD10, and negative staining for CDX-2, inhibin, and synaptophysin (, ). During the last 2 years she has being on regular follow up. Whole body Positron Emission Tomography-Computed Tomography with fluorodeoxyglucose was performed, neither local nor metastatic recurrence was observed in any system. |
pmc-6468153-1 | A 70 year old female came to Out Patient Department of Department of Surgical Gastroenterology, with 1 months history of vague pain abdomen, more localized to right lower abdomen, associated with generalized weakness, nausea and decreased appetite from last 6 months, no history of surgeries in the past. Patient reported mild right iliac fossa tenderness on palpation. She was afebrile. Laboratory investigations showed Leucocytosis with neutrophilia. Abdominal Ultrasonography showed encapsulated cystic lesion in the lower quadrant of the abdomen with a liquid content of variable echogenicity -? Appendicular Abscess /Mucocele Appendix. Abdominal CECT was done which showed Well circumscribed low attenuating tubular mass contiguous with the base of the caecum showing thin curvy linear mural calcifications with few low attenuating areas along the surface of the lesion f/s/o Mucocele of Appendix (, ). Vertical Midline Incision Laparotomy was performed. Intraoperatively a cystic mass of appendix with dimensions 8 cm × 5 cm with broad base and inflamed walls communicating with caecum but without perforation was discovered in right iliac fossa. Multiple significant lymph nodes of mesoappendix and ileocolic region were also found. With suspicion of malignancy and non-availability of frozen section, Extended right hemicolectomy with ileotransverse anastomosis was done (, , ). Histopathological diagnosis of Mucinous Cystadenoma with Mucocele was reported. After 6 months of surgery patient is doing well with no postoperative complications. |
pmc-6468507-1 | A 22-month-old boy with Down syndrome was admitted to our department for elective adenotonsillectomy because of sleep apnea due to adenoidal and tonsillar hypertrophy. Despite conservative treatment for the previous five months with nasal rinsing and intranasal steroid spray, his symptoms had deteriorated and he was indicated for surgery with post-operative observation overnight. Except for the presence of habitual belching, his medical history revealed no other abnormalities.
After a nontraumatic and uneventful orotracheal intubation, guillotine adenotonsillectomy was performed under general anesthesia. Hemostasis was achieved by dry gauze compress on both sides, no bipolar cautery was necessary. Both tonsils were easily removed without remarkable adhesions and there was no excessive bleeding during or after the procedure. Our patient was monitored in the recovery room and discharged to the ward after 40 min.
The next morning during visitation rounds, the patient’s dismissal home was postponed due to inadequate fluid intake. The physical examination and vital signs showed no aberrant findings. In the afternoon the patient was reassessed because of a swelling on the right side of his face. His vital signs were normal and there was no fever or difficulty breathing. Further physical examination showed facial swelling on the right side and crepitus was felt during palpation. There were no signs of cellulitis. Oral examination of the tonsil bed revealed normal wound healing without obvious mucosal tears. Ultrasound confirmed the presence of subcutaneous emphysema.
The progression of the emphysema quickly resulted in signs of an obstructed airway with a saturation of 81% SpO2 and the use of accessory muscles of respiration. The patient was quickly transferred to the pediatric intensive care unit where he was intubated. Shortly after successful intubation, the patient went in cardiac arrest and 2 min of cardiopulmonary resuscitation was performed. Bedside evaluation arrest ruled out pneumothorax, cardiac tamponade, hypoxia or airway obstruction and hypovolemia. Cardiac ultasonography showed a diminished ventricular function.
Blood tests showed white blood cell count of 0.78 × 103e/uL and a C-reactive protein of 142 mg/L. Blood cultures were positive with group A beta-hemolytic streptococci. A computed tomography scan (
) revealed mediastinal infectious infiltration besides subcutaneous emphysema. In retrospect, the cause of the cardiopulmonary arrest turned out to be due to sepsis/mediastinitis.
Our patient was treated with broad spectrum antibiotics, inotropes and intravenous immunoglobulin. The further course was uneventful. The subcutaneous emphysema resolved over the following days and the patient could be extubated 6 days after admission to the PICU. Finally, 15 days after surgery he was discharged home. Fortunately, follow-up consultations showed no neurological residual symptoms. |
pmc-6468526-1 | The first case is about a 74-year-old man, ECOG PS (Eastern Oncology Cooperative Group Performance Status) 1, diagnosed with non-oncogene addicted lung adenocarcinoma with lung, pleural, bone, and adrenal lesions, with PD-L1 expression in 30% of tumor cells. He progressed to the first line chemotherapy with cisplatin and pemetrexed and underwent second line treatment with nivolumab (3 mg/kg every 2 weeks) in June 2017. Immunotherapy was interrupted in August 2017 after 8 cycles due to disease progression with evidence of spinal infiltration in D3–D6, treated with focused radiotherapy until September 2017.
Two weeks later, he presented with diffuse tremors, difficulty in walking, and head bending. Blood tests excluded other causes such as diabetes, B12 or folate deficiency, thyroid-stimulating hormone (TSH) impairment, and HIV infection. Onconeural antibodies were negative. After a clinical neurological evaluation, an electromyography (EMG) documented a serious axonal motor-sensor polyneuropathy, particularly involving the lower limbs. A spinal computed tomography (CT) and brain Magnetic Resonance Imaging (MRI) did not show signs of myelopathy or metastasis; furthermore, the lung cancer lesions appeared to be stable.
The patient’s syndrome was managed with dexamethasone 16 mg daily with an improvement in neurological symptoms in 4 days and a complete remission in 14 days.
A third line chemotherapy with taxanes was administered at the complete recovery of good clinical conditions. |
pmc-6468526-2 | In September 2016 a 64-year-old man, ECOG PS 0, was diagnosed with lung, pleural, bone, and brain relapse of a surgically treated non-oncogene addicted lung adenocarcinoma with PD-L1 expression in 10% of tumor cells. He received a gamma-knife treatment on the right frontal and ipsilateral temporal brain lesions and subsequently started first-line chemotherapy with cisplatin plus pemetrexed (4 cycles), followed by maintenance with pemetrexed.
At disease progression on May 25th 2017, the patient began second line treatment with nivolumab 3 mg/kg every 2 weeks.
Nine days after the second dose of immunotherapy, the patient developed transaminase elevation and a bilateral medial diplopia. After an evaluation by a neurologist and optician ruled out ocular disorders, migraine, and other cranial nerve disorders, an isolated bilateral sixth cranial nerve deficiency was suspected. No signs of trauma or inflammation were visible. In the suspect of irAES we discontinued immunotherapy.
A brain MRI showed a reduction in the size of the right frontal lesion and a significant reduction of the associated edema, without the appearance of new metastasis or any alterations that might explain the patient’s symptoms and signs. The absence of pain enabled us to rule out orbital myositis and ophthalmoplegic migraine.
Following the immunologist and neurologist’s suggestions, we checked the thyroid function and related autoantibodies and the acetylcholine receptor antibodies. The first were normal. The positivity of the acetylcholine receptor antibodies (AChR) test (1.4 nmol/L, with upper limit of 0.5 nmol/L) as well as the neurologist’s opinion supported the hypothesis of nivolumab-related myasthenia gravis (MG), even though 41% of these cases have negative MG autoantibodies [].
We hospitalized our patient and started methylprednisolone 1 mg/kg, with a quick improvement in neurological symptoms and a progressive reduction of transaminase and AChR levels until complete normalization.
A month after the patient recovery, we resumed immunotherapy that is still ongoing with oncological partial response. |
pmc-6468526-3 | In March 2016 a 74-year-old man, ECOG PS 1, known for arterial hypertension and carotid stenosis, was diagnosed with non-oncogene addicted stage IV lung adenocarcinoma with PD-L1 expression in 2% of tumor cells. The patient received 4 cycles of first-line chemotherapy with carboplatin plus pemetrexed, followed by 3 cycles of maintenance treatment with pemetrexed. In April 2017, because of disease progression, the patient started second-line treatment with nivolumab 3 mg/kg every 2 weeks. Exactly thirteen days after the first infusion, he developed grade 3 diarrhea without fever or emesis. Suspecting a nivolumab-related colitis, oral methylprednisolone 1 mg/kg was promptly started obtaining a rapid improvement in symptoms and the second dose was delayed. After a week, he started reducing the dose of steroids and on May 15th he resumed nivolumab.
A few days after the fifth infusion of immunotherapy, while the patient was still tapering the steroid, he developed grade 2 diarrhea and grade 3 asthenia, rapidly followed by mental confusion and dysarthria with evidence of acute isolated left peripheral VII cranial nerve palsy. No electrolyte imbalance, renal function impairment, or signs of dehydration could be detected.
A brain and facial MRI with gadolinium excluded the presence of brain metastasis, ischemic or hemorrhagic lesions and showed no alterations along the VII cranial nerve. The neurologist diagnosed Bell’s palsy.
Considering the recurrence of diarrhea at steroid tapering and its association with Bell’s palsy, we suspected that the cause of both symptoms could be immune-related. The diarrhea disappeared after we interrupted the immunotherapy and increased the dose of oral methylprednisolone, but Bell’s palsy remained unchanged.
In consideration of the patient’s desire to continue treatment, and the good ECOG PS maintained despite neurological toxicity, vinorelbine chemotherapy was started.
He died in summer 2018 due to disease progression. |
pmc-6468526-4 | In February 2017 a 55-year-old woman, ECOG PS 1, with a history of arterial hypertension and lung emphysema, received the diagnosis of a non-oncogene addicted stage IV squamous NSCLC.
In August 2017, when the disease progressed after first line chemotherapy with cisplatin and gemcitabine, she began immunotherapy with pembrolizumab with the schedule of 200 mg every 3 weeks, since PDL-1 was expressed in more than 50% of tumor cells. A few hours after the first dose of immunotherapy, the patient acutely developed mental confusion, drowsiness, and a left brachio-crural motor sparing syndrome. A brain CT scan without contrast excluded acute events and after approximately two hours, neurological symptoms and signs disappeared spontaneously.
In the following days, the same neurological symptoms and signs reappeared intermittently. As suggested by the infectivologist and neurologist, we started empirical treatment with intravenous acyclovir 10 mg/kg every 8 h as in herpetic encephalitis, and an antibiotic treatment with intravenous meropenem 2 gr every 8 h. Further laboratory tests revealed negative IgM and IgG for Herpes Simplex Viruses 1 and 2.
Assuming that the neurological syndrome could be caused by immunotherapy, we started methylprednisolone at the dose of 2 mg/kg.
Three weeks after the first dose of pembrolizumab the patient showed signs of clinical and neurological improvement with normalization of blood calcium levels, a resolution of leukocytosis, a reduction of C-reactive Protein (CRP), and stable apyrexia.
We decided to re-challenge pembrolizumab achieving clinical benefit and a very good partial response in the lung and lymph nodes. |
pmc-6469050-1 | A 76-year-old man with a history of chronic obstructive pulmonary disease (Gold grade 4) and type 2 diabetes was admitted for abdominal pain radiating to the back for 10 days; pain was punctuated by brief episodes of diarrhoea. Nine months before admission, the patient had undergone endovascular treatment of an abdominal aortic aneurysm (abdominal stent graft).
Patient was afebrile, and physical examination was unremarkable apart from diffuse abdominal tenderness without guarding or rebound. Laboratory tests showed mild anaemia (111 g/L), a total white blood cell count of 7.6 × 109/l with a neutrophil count of 5.21 × 109/l; CRP was 233.5 mg/l and procalcitonin 0.09 μg/L. Kidney (creatinine, urea, sodium and potassium dosage) and liver (ALT, SGOT, SGPT, bilirubin, gamma-glutamyltranspeptidase dosage) function tests were within normal ranges.
A contrast-enhanced abdominal computed tomography (CT) scan showed infiltration of the fatty tissues around the aortic endoprosthesis and increase of the aneurysmal sac expansion by 6.0 mm (57 versus 51 mm) compared to a previous CT performed 2 months earlier; no endoleak was observed. No other abnormalities were observed. 18F-FDG PET/CT (Fig. , a-e) showed a hypermetabolic (SUVmax = 8.5) mass with a diameter of 15 mm in contact with the superior antero-medial of the endoprosthesis, suggesting an abscess. CT colonography excluded neoplasia.
Serum immunofixation was normal, without increase in the IgG4 subclass. The interferon-gamma reactivitiy assay was negative. Serologies for Treponema pallidum, Bartonella henselae and Coxiella burnetii were negative, as were Brucella agglutination tests (Rose-Bengal and Wright). Multiple blood cultures showed no growth. Real-Time Quantitative broad-range PCR on blood was negative. Stool PCR testing for Campylobacter jejuni/coli, Shigella spp. and Salmonella spp. was negative.
Multidisciplinary consensus involving interventional radiologists, vascular surgeons, infectious disease specialists, and internists, led to the decision for a surgical revision. During the procedure, an infrarenal peri-aortic abscess was noted, from which samples were performed. In the post-operative period and before culture results were available, patient was started on oral ciprofloxacin (500 mg/12 h) and doxycyclin (100 mg/12 h). Histopathological examination of the intraoperative specimens revealed fibrous tissue with accompanying inflammation rich in histiocytes and cholesterol crystals; no microorganisms were identified on hematoxylin/eosin, Gram or Grocott stains.
Cultures of intraoperative samples (5/5) became positive for L. monocytogenes after 10 days incubation. These results were further confirmed by a broad-range PCR. Susceptibility testing (Kirby-Bauer disk diffusion susceptibility tests (SirScan 200 Automatic, i2A, France) interpreted according to the EUCAST clinical MIC breakpoints) [] showed a pan-susceptible (“wild type”) L. monocytogenes strain with a minimum inhibitory concentration [MIC] for amoxicillin of 0.380 mg/l. Antibiotic treatment was then switched to intravenous amoxicillin ((2 g/6 h) for a duration of 6 weeks. The patient’s clinical course was favourable, and CRP levels became within normal range. At the end of antibiotic course, an abdominal CT scan showed regression of the peri-aortic abscess and collection. At 6 months follow-up the patient was well, without recurrence.
Frozen aortic tissue was cut into small pieces on a disposable Petri dish support using a scalpel. DNA was extracted from 83 mg of shredded sample using the Ultra-Deep Microbiome Prep kit (Molzym, Bremen, Germany) for enrichment of bacteria/fungal DNA, according to the manufacturer’s instructions (Version 2.0) for tissue samples.
The concentration of bacterial and human DNA was determined by qPCR experiments as previously described [], using 16S rRNA and beta-actin reference genes, respectively. The reference curves for bacterial and human DNA quantitation were generated using known concentrations of Escherichia coli DH5α genomic DNA and human genomic DNA from the TaqMan beta-Actin Detection Reagent kit (Applied Biosystems, Framingham, MA), respectively.
Metagenomic libraries were prepared from 1 ng DNA (sum of bacterial and human DNA load determined by qPCR), using Nextera XT DNA Sample Preparation Kit according to Illumina (San Diego, USA) instructions, except that 16 (instead of 12) PCR enrichment cycles were used. The libraries were sequenced for 2 × 250 + 8 cycles on an Illumina MiSeq instrument at Fasteris (Plan-les-Ouates, Switzerland) using the MiSeq Reagent Kit v3 and MiSeq Control Software 2.6.2.1.
The Trimmomatic package was used by the sequencing service provider to remove bases that correspond to the standard Illumina adapters and to trim low-quality ends of reads at the beginning of a 4-base wide sliding window with an average Phred quality < 5 []. We further trimmed the reads with the low-quality base score of Q10 and a mean quality score Q30 over a sliding 20-base window. Any read that, after trimming, had a length < 150 bases was discarded. To filter out putative artificial replicate reads, we used a home-made script which retains only the longest sequence from those with identical first 100 bases in either forward or reverse reads. Unpaired forward or reverse reads were discarded. Remaining reads were classified with Kraken v.0.10.5-beta with the default parameters []. After filtering out the read pairs that matched human genome, the data were deposited to European Nucleotide Archive (ENA) database (accession number PRJEB21816).
The reads classified by Kraken to genus Listeria were retrieved and mapped to complete reference genomic sequences of Listeria strains (downloaded from the NCBI Reference Sequence (RefSeq) prokaryotic genome collection) [] using USEARCH 8.1.11861 [] (−ublast -id 0.98 -cov 0.98 -top_hits_only -strand both -evalue 0.00001). The number of hits was counted for each Listeria strain. The strain with the maximum number of hits was retained as a reference for read mapping using GView []. MetaPhlAn2 taxonomic profiling, based on read mapping against ~ 1 million markers from more than 7500 species was used with default settings [] (Fig. ).
Although culture and broad-range PCR detected L. monocytogenes in the clinical specimen, we performed next-generation sequencing in order to determine the clinical utility of such a technique. We extracted DNA from the aortic tissue using a protocol that improves the bacterial-to-human DNA ratio based on selective lysis of host cells and removal of host DNA before the lysis of bacterial cells [, ]. The concentrations of human and bacterial DNA in purified extracts were 5983 and 214 pg/μL, respectively, as determined by qPCR assays. The whole metagenome shotgun sequencing generated 5,509,950 raw paired reads of which 3,026,609 passed quality control (Fig. a). In line with qPCR results, most reads (97.7%) corresponded to human genome sequence. Of 66,451 read pairs classified by Kraken as bacterial, 65,805 (99%) were assigned to the genus Listeria and 64,035 (96.4%) to L. monocytogenes (Fig. b, c). Most of the remaining bacterial reads corresponded to Propionibacterium (464 reads) and Micrococcus (32 reads), both of which are frequent reagent contaminants. We have previously identified Propionibacterium in negative extraction controls (PRJEB20595) obtained with a DNA extraction kit of the same lot []. Mapping of sequencing reads against clade-specific marker genes using MetaPhlAn2 confirmed the results obtained by Kraken. The MetaPhlAn2 taxonomic profiling showed high abundance of Listeria (99.91%) and L. monocytogenes (96.28%), with a minor presence of Cutibacterium acnes (formerly Propionibacterium acnes) (0.089%). |
pmc-6469077-1 | A 27-year-old Caucasian woman was admitted to the Emergency Department of our Institution because of bloody diarrhoea – up to 10 bowel movements per day – during the last month, 3 weeks after quitting smoking. Physical examination showed no abnormalities but confirmed haematochezia on digital rectal examination. Colonoscopy showed continuous severe colonic inflammation with small ulcers from the anus to the descendent colon, classified as grade 3 in Mayo endoscopic sub-score and 3 points in Ulcerative Colitis Endoscopic Index of Severity (UCEIS); complete examination was not performed because of the risk of perforation. Empirical antibiotic treatment with ciprofloxacin and metronidazole, as well as oral and rectal mesalamine were started and partial symptomatic improvement was achieved. Venous thrombosis prophylaxis with subcutaneous enoxaparin, 40 mg per day, was started. At admittance, haemoglobin, white cell count, platelets, fibrinogen and C reactive protein (CRP) were within the reference range. Stool cultures were negative. Cytomegalovirus (CMV) infection was also ruled out in colonic biopsies (polymerase chain reaction – PCR – and, later, immunohistochemistry). As bloody diarrhoea persisted 48 h later, and histopathological examination of colonic biopsies showed crypt distortion, a mixed inflammatory infiltrate of the lamina propria and crypt abscesses suggesting the diagnosis of UC, intravenous methylprednisolone (1 mg per kg of weight, daily) was started. After 3 days of corticosteroids the patient achieved partial clinical response (6 bowel movements per day, Edinburgh index 2 points, CRP within the normal range); nevertheless, 2 weeks later infliximab therapy (5 mg/kg of weight) was started due to sustained clinical activity, with 10 bloody bowel movements per day and a progressive increase of CRP levels, up to 10 mg/dL. Three days after the first dose of infliximab, the patient presented a massive lower bleeding with haemodynamic instability and severe anaemia; CT scan showed active arterial haemorrhage from ascendant colon; a subsequent arteriography demonstrated active arterial bleeding from a colic branch of the superior mesenteric artery; selective transcatheter embolization with platinum microcoils (MicroNester©, Cook Medical) was performed with immediate technical success; nevertheless, the patient persisted with rectal bleeding 2 days after embolization, requiring laparoscopic subtotal colectomy and ileostomy. Pathological evaluation of the colon confirmed the diagnosis of UC. Eight days after surgery the patient was discharged. |
pmc-6469086-1 | A 52-year-old male patient with initial diagnosis of pulmonary arterial was admitted to the Department of Cardiology for medical assessment and decision on further treatment. The patient had a history of right-sided spontaneous pneumothorax, treated with thoracentesis and vacuum drainage 35 years earlier. The patient felt increasing dyspnea on exertion. He also complained about signs of right ventricle failure and cyanosis. Four years earlier the patient was hospitalized three times for paroxysmal atrial fibrillation that was converted to sinus rhythm by electric cardioversion besides electrocardiographic examination was normal.
In the same year coronary angiography indicated normal coronary arteries. Echocardiography revealed mild pulmonary hypertension with calculated right ventricle systolic pressure of 36 mmHg without right ventricle dilation.
In the following years, progressive heart failure with increasing pulmonary artery pressure in echocardiography has been observed. Angio-CT was performed on two occasions and chronic thromboembolic pulmonary hypertension was excluded each time. High-resolution computed tomography has excluded interstitial pulmonary pathology. Spirometry was normal. Screening for autoimmune diseases and HIV infection was negative (Table ).
At admission to our clinic functional class of patient was assessed as WHO III, In physical examination the second heart sound (S2) was accentuated with widened split S2. Moreover, heart auscultation indicated holosystolic murmur of tricuspid regurgitation. The auscultation of the chest did not show a vascular murmur. Peripheral and central cyanosis was marked. Hepatomegaly, peripheral edema and varicose veins bilaterally were examined.
SaO2 obtained by pulse oximetry method was reduced to 88%. Electrocardiography revealed atrial fibrillation, right axis deviation and negative T wave in precordial leads v1-v3. Additional tests were as follows: NT-proBNP concentration – 3383 pg/ml, six-minute walking test distance - 373 m with 7/10 points in Borg dyspnea score.
Echocardiography showed features of severe pulmonary hypertension: right ventricle enlargement to 44 mm (four chamber view), with depressed function of right ventricle TAPSE 9 mm, right atrium area enlargement to 40 cm2, severe tricuspid valve regurgitation (++++), increased calculated RVSP to 112 mmHg, shortened pulmonary artery acceleration time to 60 ms and mild pericardial effusion. There was no interventricular septum defect. Trans-esophageal echocardiography did not show a defect in the atrial septum too, which was confirmed later by angio-CT (Fig. ).
SaO2 of blood obtained from radial artery was reduced to 87,8%. Right heart catheterization was performed. SaO2 of blood samples obtained during RHC from vena cava superior, vena cava inferior, right atrium, pulmonary trunk, middle lobe artery of the right lung and left pulmonary artery amounted respectively: 64,8%; 77,4%; 73,2%; 70,2%, 69,3%; 71,2% and did not indicate the presence of a left-to-right shunt.
Hemodynamic measurements showed severe precapillary pulmonary hypertension, irreversible in vasoreactivity testing with inhaled nitric oxide (80 ppm) and a combination of oral sildenafil (50 mg) and inhaled nitric oxide (80 ppm) [] (Table ).
Based on the whole clinical data and the results of RHC, a diagnosis of idiopathic irreversible pulmonary hypertension was established.
Treatment with inhaled iloprost (Ventavis) 6 × 5 μg and sildenafil (Revatio) orally 3 × 20 mg was initiated. Moreover, digoxin (0,1 mg daily), warfarin (INR range: 2–3), furosemide (40 mg orally daily) and spironolactone (100 mg daily) were administered.
Noninvasive follow up was performed one month later – the patient reported improved physical capacity, class II WHO, NT-proBNP concentration: 1014 pg/ml. Six-minute walking test distance - 471 m.
Invasive assessment was done five months later. RHC showed higher than in initial measurements values of PAP [75,4/51,8 (59,7) mm Hg] and PVR (13,4 WU) (Table – control RHC).
Oxygen saturation of blood samples obtained during RHC from upper lobe artery of the right lung was elevated and amounted 89.7%.
In the pulmonary angiography reduction of peripheral vascular drawing typical of pulmonary arterial hypertension and the lack of contrast of the right upper lobe artery were detected. Additionally the evidence of retrograde blood flow visible as a negative contrast in right pulmonary artery was found (Fig. a-d). Afterwards, right subclavian artery arteriography was performed and a huge vascular malformation communicating with right upper lobe artery (Fig. e-k) was detected.
Angio-CT of systemic arteries confirmed presence of previously described fistulas and revealed additional presence of bronchial artery fistulas to upper lobe of right lung arteries (Fig. ).
Selective embolisation of fistulas was performed (50% mixture of Lipiodol and monomeric n-butyl-2-cyanoacrylate glue). Embolisation did not bring any clinical change in the patient’s condition. |
pmc-6469106-1 | A 78-year-old man with a medical history of hypertension, hypercholesterolemia, aneurysm of the ascending aorta, and chronic inflammatory pleurisy presented headaches and visual disturbances (left homonymous hemianopia). Brain magnetic resonance imaging (MRI) revealed an occipital extra-axial lesion with surrounding edema (Fig. a). Three weeks later, the patient underwent a total resection, which revealed a malignant meningioma with Ki-67 proliferative index of 40% (Fig. a). Next-generation sequencing (NGS) detected no specific mutation. Immunohistochemical analysis found high expression of pankeratin AE1/AE3, vimentin, INI-1 (clone MRQ-27), and focal expression of epithelial membrane antigen. P53, cytokeratin 7, and cytokeratin 20 were negative. All melanocytic makers (HBM45, SOX10, Melan A) were negative. Moreover, there was no expression of STAT-6 (Fig. a), bcl-2 (Fig. b), and a nonspecific granular cytoplasmic staining of CD99 (Fig. c). Postoperative brain MRI showed hemorrhagic remodeling without any evidence of a residual tumor (Fig. b). According to the actual data of the literature, postoperative surgical bed irradiation with total dose of 68 Gy (34 daily fractions of 2 Gy) was performed. At the end of RT, the patient was in a good health condition without neurologic symptoms. One week after the end of RT, he underwent a total resection of a right shoulder cutaneous lesion. Histopathological analysis revealed a superficial spreading melanoma. Four months after the end of RT, the patient presented dizziness and left arm weakness. A brain MRI revealed a local recurrence and six new brain lesions (Fig. c). In order to distinguish melanoma brain metastases between meningioma brain metastases, the occipital lesion was biopsied. Pathological analysis confirmed WHO grade III meningioma with Ki-67 proliferative index (MIB-1) of 80%. Immunohistochemical analysis revealed a focal expression of progesterone receptor (Fig. b) without any expression of melanocytic markers (SOX10, HMB45, Melan A). Thus, a hypothesis of melanoma brain metastases was excluded. Positron emission tomography with radiolabeled [18F]-fluoro-2-deoxy-D-glucose coupled to a CT-scan (18FDG PET/CT) showed six hypermetabolic cerebral and cerebellar lesions (Fig. a, b, c, d), a focal intense uptake lesion of the fundus (Fig. e, f), and a sigmoidal nodule. The results of the brain MRI, 18FDG PET/CT, and the pathological examination of the brain lesion suggested that the patients developed several distant brain metastases of a malignant meningioma. No specific treatment was initiated. Five weeks after the cerebral biopsy, the patient presented a digestive hemorrhage. Gastroscopy showed many duodenal micro-ulcerations; no biopsy was made. He had a second digestive hemorrhage 5 days later, which required hemostatic surgery. Pathological examination of a gastro-intestinal tract specimen revealed a malignant lesion, which had the same morphological and immunohistochemical features of the right occipital lesion (Fig. c). Again, there was also no specific mutation on NGS. Radiation therapy of the whole brain was performed (30 Gy in 10 fractions of 3 Gy). One month after the end of RT, despite the lack of guidelines, a systemic treatment with bevacizumab (10 mg/kg intravenous every 2 weeks) was administrated. Only one injection was made. The patient died suddenly on the 15th of June. The main hypothesis of the cause of death was a cardiac arrest secondary to a pulmonary embolism. An autopsy was not proposed to the family to understand the cause of death that is why the post-mortem examination was not performed to determine the real cause of death. |
pmc-6469211-1 | A 39-year old male presented with a two-year history of spontaneous, intermittent, non-traumatic left hip pain. Symptoms were worsening at night, with no irradiation to the leg, fever, or other associated signs/symptoms. Pain was initially reported as mild, then it worsened and became unresponsive to non-steroidal anti-inflammatory drugs, especially salicylates. At first outpatient examination, diffuse tenderness of the hip was noted, with pain not changing with movement. No palpable swelling or decrease of muscular tone was observed. Hip range of motion was preserved, with negative flexion, abduction and external rotation (FABER) test. No neurological signs were found and Laségue maneuver was negative on both sides.
The patient underwent pelvis and left hip plain radiography, which was unremarkable. Clinical suspicion of OO was raised and the patient underwent CT examination. It revealed the synchronous presence of an intracortical radiolucent nidus (7 mm) with central hyperdensity and mild sclerosis of the adjacent bone, located in the anterosuperior portion of the left femoral neck. A second lytic lesion (8 mm) with similar features was also seen, surrounded by denser sclerosis, located along the anterior column of the acetabulum. A diagnosis of multicentric OO was made (Fig. ). Thus, the patient was treated using RFA in a single session. He well tolerated the procedure without complications. Biopsy performed before RFA confirmed the radiological diagnosis of OOs. After treatment, hip pain decreased but did not disappear, actually recurring a few months after treatment. Thus, the patient underwent magnetic resonance imaging (MRI), which showed a smaller lesion (5 mm), along the posterior column of the acetabulum, with imaging features consistent with OO (Fig. a-e) and associated to bone marrow oedema. This finding was was overlooked on the previous CT examination (Fig. c). Biopsy yielded a diagnosis of OO, which was treated using RFA with disappearance of symptoms (Fig. f). Thus, based on the occurrence of two OOs in different part of the same bone and in different bones, a diagnosis of multicentric and multifocal OO was reached. Nevertheless, after 18 months, the patient experienced pain recurrence with the same clinical features as before. Thus, he underwent MRI and CT showing OO recurrence on the posterior column of the acetabulum (Fig. ). The lesion was biopsied and successfully re-treated with RFA (Fig. ). Biopsy and pathologic examination yielded again a diagnosis of OO. At present, at 8-month follow-up, the patient is still asymptomatic. |
pmc-6469666-1 | A 28-year-old female was injured by forklift crush that caused skin degloving in the lower left abdomen, as well as the entire thigh and the knee joint. The total damaged area was about 2200 cm2. The wound was contaminated and accompanied by circumferential multi-plane injury. The patient was also suffering traumatic and hemorrhagic shock (Fig. ), with the blood pressure: 76/39 mmgh, p:112 beats/min, HGB:62 g/L, albumin: 23.5 g/L, total protein: 46 g/L, HCT:24.3%, PT:15.3 s. Emergent operation was performed. After wound debridement and hemostasis, the scale of the skin ischemia was decided by puncturing and trimming the skin edge: the fringe of the ischemia lies where there’s no bleeding (Ziv et al. ). Skin flap lack of blood supply was excised. The remaining skin was pulled together by suture to reduce the wound, and the remaining wound was covered by the Vacuum Sealing Drainage (VSD, Waystech, Guangzhou, China).
Medium-thickness skin grafts were harvested from the excised flap with a rolling knife. The skin grafts were rolled up between two layers of gauze. The gauze was then stitched up with a needle and steel wire to form a cylinder. At one end of the cylinder, an appropriate length of the steel wire was reserved, so that the cylinder could be readily pulled out of the liquid nitrogen tank once necessary. The cylinder was first immersed into the antifreeze solution [composed of 20% dimethyl sulfoxide, 6% glycol propylene and Kreb Ringer solution (Zhu et al. )] for 30 min. Then it was immediately transferred into the liquid nitrogen tank for storage.
During and after the operation, blood transfusion and albumin infusion were carried out. Antibiotics were also used to prevent infection. Thirteen days after the injury, the hemoglobin and albumin of the patient returned to normal. PT:14.1 s, and the patient had no fever. After the removal of VSD, fresh granulation tissue could be seen. No infection or active bleeding was observed (Fig. ).
The second operation was carried out. The preserved skin grafts were taken out of liquid nitrogen. They were rapidly thawed in 42–45 °C normal saline for 1 min. The grafts were washed for 3 times, 5 min each time with saline, then immersed in normal saline of the room temperature for 15 min. The preserved skin grafts showed minimal change as to color, wholeness and softness. Skin grafts that had sustained the least damages were chosen for the operation. They were transplanted to the wound, and then covered with VSD. After the operation, the skin grafts preserved were left about 150 cm2. The entire surgery lasted for 5.5 h.
Nine days after the second operation, the VSD was removed. Spotted necrosis was found on the edge of the skin graft. But overall, the survival rate of the skin graft had reached 95%. The survived part showed no difference from the surviving skin in a grafting operation that uses healthy skin tissue (Fig. ). For the next 40 days, the dressing was changed regularly and the wound was kept dry until the healing was complete (Fig. ). One year later, the skin color changed from flushing to normal color and the hip flexion was slightly restricted (Figs. , ). |
pmc-6469666-2 | A 56-year-old female was run down by a car. Her right leg suffered extensive degloving injury from the knee right down to the back of the foot. The total wounded area, which added up to 1200 cm2, was severely contaminated and accompanied by circumferential multi-plane injury, fibula exposure and partial muscle rupture (Fig. ). Blood pressure: 109/61 mmHg, heart rate: 84 beats/min, HGB: 98 g/L, HCT: 30.4%, albumin: 25.8 g/L, total protein: 52 g/L, PT: 12.2 s.
We did roughly the same procedures as with case 1. The only difference was that the skin was harvested with a pair of scissors in the form of full-thickness skin graft. There was no break in the entire graft.
Ten days after the injury, we found that the granulation in the wounded area had been growing relatively slowly and that there were a small amount of residual necrotic tissues. Debridement was carried out, as well as a change of the VSD coverage.
Skin grafting was carried out 16 days after the injury. By that time, fresh granulation tissue had fully covered the wounded area apart from the medial malleolus. There was no infection or active bleeding (Fig. ).
The skin graft preserved in liquid nitrogen was rewarmed using the same method as in case 1. The graft was then replanted to the wounded surface, with the edge of the skin pruned and the entire grafted area covered with VSD. The remaining unused part of the skin graft was fixed with 4% polyformaldehyde, for pathological examination.
The VSD was removed 10 days after the operation. A small area of the anterior of the ankle failed to take hold, while about 96% of the skin graft proved viable (Fig. ).
After 1 years of follow-up, the skin texture and the function was acceptable (Fig. ).
Since one large skin grafts instead of several small skin grafts was preserved and then grafted, there was less scar and the final appearance of the operated area looked remarkably better than it was with case 1. The wound was kept dry and the regular change of dressing was maintained until the wound completely healed 28 days after the third operation. Pathology performed on the remaining skin graft showed that the cells and the tissue structure were complete, but the size of the nucleus increased slightly (Fig. ).
After a 1-year follow-up, no systemic or local complications such as hepatorenal toxicity, tumors, dermatitis and so on were found in the both of the two patients. |
pmc-6470063-1 | A 61-year-old man from Okinawa, Japan, presented at his local hospital complaining of cough and bloody sputum during the preceding week. He was a current smoker with a history of chronic obstructive pulmonary disease (COPD), and rheumatoid arthritis that had been treated with prednisolone 7.5 mg per day and methotrexate 12 mg per day since 2005 by a primary care physician. He was a professional gardener. Chest X-ray demonstrated a thin-walled cavitary lesion in the upper right lobe. He was referred to our hospital for further evaluation. Chest computed tomography (CT) on the first visit showed a large, thin-walled cavitary lesion, pleural wall thickening, trabecular and linear shadows in the upper right lobe, and bronchiectasis in the upper and middle lobe (Fig. A–C). Acid-fast bacilli were found on Ziehl–Neelsen staining of two separate sputum smears, respiratory specimens were cultured with 2% Ogawa agar, and the resulting bacterial colonies were collected for species identification. Polymerase chain reaction for tuberculosis (TB) was negative. The resulting suspension liquid was tested using a DNA–DNA hybridization (DDH) method from a commercially available identification kit (Kyokuto Pharmaceutical Industrial Co. Ltd., Tokyo, Japan). Finally, an NTM was isolated from two separate expectorated sputum samples by DDH, which failed to identify the NTM species. The patient's haemoptysis symptoms improved spontaneously without treatment, and he was discharged from the hospital on his own judgement. Although we encouraged him to attend regular follow-ups at the outpatient centre of our hospital, he declined due to personal reasons.
Two years later, in December 2017, the patient was readmitted to our hospital with a recurrence of bloody sputum. The CT scan showed that the cavity in the upper right lobe had extended and the cavity wall had become thinner compared to the previous lesions. Microbiological work-up again isolated an NTM from two separate expectorated sputum samples, and DDH again failed to identify the bacterial species. The positive cultures were sent to a specialized microbiology laboratory for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and M. shimoidei was finally identified. The activities of antimicrobial agents were examined by a commercially available drug susceptibility kit for NTM (Kyokuto Pharmaceutical Industrial Co. Ltd., Tokyo, Japan), with the breakpoints derived using Mycobacterium kansasii as a reference. M. shimoidei proved susceptible to clarithromycin (CAM), ethambutol (EB), streptomycin, amikacin, and levofloxacin (LVFX); and resistant to rifampicin (RFP). After referring to published literature and the advice of an expert on acid-fast bacteria, the patient was started on a treatment regimen of CAM, EB, and LVFX in January 2018. His haemoptysis decreased gradually and the cavitary lesion improved (Fig. D, E). Six months after treatment, acid-fast culture of sputum was negative. |
pmc-6470431-1 | A 47-year-old previously healthy Sinhala female's right foot was bitten by a snake near the back door of her home in the Kegalle district, Sri Lanka. Within seconds, she felt burning pain ascending along that limb, and there was heavy bleeding from the site of bite. Within a couple of minutes, she felt dizziness, nausea, and numbness of the whole body, had profuse sweating and frothy salivation, and was screaming in pain from the site of bite. On the way to the nearby hospital, she started to clench her jaw tightly and limbs became rigid; she was frothing and was not responding for about 5 minutes, indicating a generalized seizure. She arrived at the hospital within 30 minutes. The doctor at the outpatient department decided to administer ASV and directed the patient to an internal medicine ward for that. Physical examination findings at the ward were a pulse rate of 100/minute and blood pressure of 150/90 mmHg, and lungs were clear to auscultation bilaterally with an arterial oxygen saturation of 95% whilst breathing air with no neurological deficit. By this time, the killed snake was brought in and doctors identified it as a HNV; thus, antisnake venom (ASV) was not administered. Even though there was bleeding at the site of the bite even on admission to the hospital, her 20-minute whole blood clotting time, platelet count, prothrombin time and international normalized ratio, and activated partial thromboplastin time and liver function tests were all normal. Urine sample obtained via the catheter showed 50–55 red cells per high-power field, arterial blood gases indicated a compensated metabolic acidosis, and serum sodium and potassium levels were normal. Her urine output was <100 ml for the first 24 hours and serum creatinine rose from 80 μmol/l to 277 μmol/l. She was transferred to the Teaching Hospital, Kandy, on day 2 for further management.
On day 2, a bulla developed at the site of the bite, and there was an edema and warmth at the right foot. Complete (full) blood count demonstrated neutrophilic leucocytosis, and the CRP level of the following day was 261 mg/l. Intravenous antibiotics was started to cover the wound infection. Serum creatinine was 377 μmol/l with oliguria on day 2. Serum sodium and potassium levels remained within the normal range from day 1–5. On the day 5, creatine kinase was 75.1 U/l. Regular hemodialysis every other day from day 2 to day 24 and fluid management were started. Oral sodium bicarbonate was started, and management of her acute kidney injury with collaboration of nephrology team continued.
On day 3, her blood pressure rose to 160/90 mmHg, and it was controlled by prazosin and nifedipine SR; however, it generally remained on or above 140/90 mmHg until her discharge. She developed bilateral lung crepitations on day 3 that remained for 7 days. She developed bilateral parotid swelling and edema of the right leg on day 3, and it lasted 3 days. Edema below her right knee persisted another 10 days. Her blood picture on day 2 did not show hemolysis and was suggestive of bacterial infection but blood picture on day 5 showed evidence of microangiopathic hemolytic anemia (MAHA), and same changes were there in a blood film taken on day 11, as depicted in .
Her day 2 hemoglobin level of 10.8 g/dl dropped to 8.4 g/dl on day 5. On day 2, her platelet count was 104 × 109/l and that dropped to nadir of 29 × 109/l in day 6 and was <150 × 109/l until day 20. A consultant in transfusion medicine has assessed her, and blood transfusion and plasmapheresis was performed on day 7. Another four cycles of plasmapheresis followed. Local edema at the site of the bite increased with necrosis (); thus, wound debridement was done on day 7 and followed up by regular wound toilets.
We did an electroencephalogram (EEG) on this patient on the earliest available day (day 11) and that was normal. The 2D echocardiogram done on day 17 was also normal.
The offending snake's carcass was taken to the Peradeniya University, and an expert on HNV, Dr. Kalana Maduwage, has confirmed it as a Hypnale hypnale. is a photo of the offending snake.
As her daily urine output improved to >1000 ml, she was discharged on day 30 and asked to come for a review in five days. She defaulted treatment and was on alternative medication. After developing progressive bilateral ankle edema and exertional dyspnea, she came back again on day 46, and hemodialysis and supportive therapy were restarted at the nephrology unit. On day 49, she had an anterolateral non-ST-elevation myocardial infarction (non-STEMI), and she was managed at the cardiology unit. She had progressive impaired vision of the left eye starting from a few days after the snakebite and could not count fingers held 30 cm in front of that eye on the 46th day. She was referred to the eye unit, there was bilateral optic disc edema more on the left, the patient was diagnosed of left anterior ischemic optic neuropathy (AION), and steroid therapy was started. Her erythrocyte sedimentation rate and contrast-enhanced computed tomography (CECT) brain done on day 53 were normal. is a photograph of fundi of this patient.
She had two episodes of seizures on day 76, and we suspected a possible relationship to her envenomation. The opinion of the neurology team regarding three seizures was obtained. Repeated EEG and CECT brain were normal. Despite being on calcium carbonate 500 mg plus 0.25 μg 1-alpha-hydroxycholecalciferol daily from day 46, her serum calcium level was low (1.8 mmol/l). Last two seizures were attributed to hypocalcemia due to chronic kidney disease following HNV envenomation, and daily calcium carbonate dose was increased to 500 mg thrice daily. After three months, she was diagnosed of end-stage renal disease by nephrology team and on hemodialysis once in four days and was searching for a kidney donor at six months. |
pmc-6470434-1 | A 55-year-old male presented to the emergency department with abdominal pain, abdominal distension, nausea, vomiting, and constipation persisting for two days. The patient stated that he had a history of chronic constipation that resolved spontaneously or with laxatives. He had no history of long-term medication, chronic systemic disease, or surgery.
The physical examination revealed abdominal distension, tenderness, and absence of bowel sounds. The rest of the examination was unremarkable. His vital signs were within normal limits, and there was no clinical evidence of peritonitis.
Abdominal X-rays showed multiple air fluid levels with dilated small bowel loops, suggestive of intestinal obstruction. CT images revealed internal herniation, which occupied part of the right abdomen, containing part of the ileum (). The latter appeared distended, likely due to obstruction. The patient also had neutrophilic leukocytosis, and he was taken urgently to theater where an exploratory laparotomy was performed.
Intraoperatively, a fibrotic membrane covering all of the abdominal viscera was found. The small bowel loops were encased and interloop adhesions could be seen (Figures and ). Incisions were made along the thick membrane in order to release the encased small intestine, and extensive adhesiolysis of the small bowel loops was performed, without resection. The histological findings showed peritoneal fibrosis with sites of chronic nonspecific inflammation. There were no complications during the postoperative period, and the patient was discharged on the 10th postoperative day. |
pmc-6470434-2 | A 54-year-old male presented to the emergency department of our hospital with acute cramping abdominal pain and nausea. He had similar episodes during the previous year, with milder symptoms which responded to conservative treatment, without the need for hospitalization. He had no significant past medical or surgical history.
His clinical examination revealed a palpable mass in the right lower paraumbilical area, with sluggish bowel sounds. The radiographic findings were compatible with ileus. Due to the deterioration of his clinical status, a CT scan was performed, which revealed dilatation of the jejunal loops in the left upper abdomen, with fluid collection. Mesentery was thick-walled and amorphous calcifications were also seen (). An exploratory laparotomy was planned.
Intraoperatively, a thick fibrotic membrane encasing the entire small intestine and part of the large intestine was found. Obstruction was due to the pressure applied by the thick membrane on the small bowel loops. During the operation, the fibrotic membrane was excised, followed by adhesiolysis between the intestinal loops (). The histological findings showed peritoneal fibrosis. The postoperative period was uncomplicated, and the patient was discharged on the 8th postoperative day. |
pmc-6470634-1 | A 64-year-old female with a history of hypertension, asthma, pulmonary fibrosis, and hyperthyroidism secondary to multinodular goiter presented with abdominal pain and diarrhea and was admitted for possible colitis. On admission, she was noted to have acute kidney injury (AKI) with serum creatinine (Scr) of 2.8 mg/dL (baseline Scr was 1.2 mg/dL). She denied use of nonsteroidal anti-inflammatory drugs, proton pump inhibitors, or herbal medications; however, she reported having completed a course of clarithromycin for a respiratory infection 2 weeks prior. Her only home medication at the time of presentation was methimazole, which she had been taking for ~ 2.5 years (5 mg/p.o). She denied smoking or the use of illicit drugs, and her social history was otherwise nonrevealing. Subsequently, she developed gross hematuria with worsening AKI.
Laboratory data revealed an elevated serum C-reactive protein, white blood cell (WBC) leukocytosis of 29.1 × 103/µL, blood urea nitrogen was 50 mg/dL, Scr increased to 5.67 mg/dL, and potassium was elevated to 7.2 mg/dL. Serological work-up was positive for antinuclear antibody (ANA, 1:640), perinuclear antineutrophilic cytoplasmic antibodies (p-ANCA, 1:320), and myeloperoxidase antibody (MPO, 109.4), and negative for human immunodeficiency virus, hepatitis B, hepatitis C, rheumatoid factor, ribonucleoprotein antibody, double stranded (ds)-DNA antibody, Sjogren SSA and SSB antibodies, and antiglomerular basement membrane (GBM) antibody. Serum complement levels were within normal limits; C3 = 99 mg/dL (reference range 81 – 157) and C4 = 34 mg/dL (reference range 13 – 39). Serum free light chain ratio was not elevated, and serum immunofixation did not show any monoclonal gammopathy. Urinalysis showed 173 red blood cells, 13 WBCs, and spot urine protein to creatinine ratio was elevated at 1.2. Additionally, a chest X-ray showed bilateral pleural effusions. Kidney ultrasound revealed increased bilateral cortical echogenicity with bilateral hydronephrosis. The patient was started on empirical therapy for Clostridium difficile due to her diarrhea, but the test for C. diff toxin was negative. CT of abdomen was performed that was negative for infectious processes. She also underwent urine culture, stool culture, and blood cultures testing multiple times, however, they were all negative. Stool was also negative for ova, parasites, and protozoa.
Given the negative anti-GBM and ds-DNA antibodies, normal complement levels, and positive ANCA serologic test with anti-MPO specificity in this patient presenting with pulmonary-renal syndrome, ANCA-driven vasculitis and pauci-immune crescentic glomerulonephritis was at the top of our differential diagnosis. Foley catheter was placed, and she was initiated on pulse dose corticosteroids due to clinical suspicion of ANCA)-associated vasculitis (AAV). She subsequently underwent kidney biopsy, which showed severe necrotizing small vessel vasculitis and crescentic glomerulonephritis, consistent with AAV. Methimazole was discontinued. Three days after the kidney biopsy, the patient developed hemoptysis and was initiated on plasmapheresis for concern of pulmonary alveolar hemorrhage. She eventually became oliguric, requiring hemodialysis. Few days later, she underwent change in mental status and eventually coded. cardiopulmonary resuscitation was unsuccessful, and the patient expired. |
pmc-6471807-1 | A Sicilian seventy-year-old man was admitted to the Infectious Diseases Unit of the University Hospital of Palermo (Sicily, Italy) in July 2017 referring progressive asthenia and irregular fever not responsive to antibiotic therapy lasting 2 months. The patient suffered from diabetes mellitus, mild kidney disease, and HCV-related liver cirrhosis (Child-Pugh B7), for which had been treated with sofosbuvir and ledipasvir for 24 weeks until December 2015.
About 3 months later the end of the HCV-treatment, the patient suffered from a marked worsening of thrombocytopenia, not considered related to liver cirrhosis and not responding to steroid therapy for which he had been treated with romiplostim whenever platelet count was under 20,000/mmc.
At admission in our division, the patient had fever (BT 37.8°) with a pulse rate of 78 bpm, blood pressure and respiratory rate were normal. No other symptoms were reported except asthenia. At the physical examination he had no respiratory alterations, systolic heart murmur at apex (grade II/VI), hepatosplenomegaly and grade 1-encephalopathy with bradilalia and minimal flapping tremor.
Laboratory tests revealed pancitopenia (WBC 3100/mmc -neutrophils 46%, lymphocytes 33%-, Hb 8.1 g/dl, platelets 46,000/mmc), an increased C-reactive protein (33 mg/l), D-dimer 6980 UI/l and INR 1.5, eGFR 63 ml/min/1.73m2, AST/ALT 2xN, modest hypoalbuminemia with polyclonal gammopathy.
The abdominal ultrasound exam showed an increase in splenomegaly (17 cm) compared to the previous ultrasonography from 1 month earlier (14.5 cm). Thoracic CT scanning was normal. Trans-thoracic echocardiography excluded vegetations. Blood culture, brucellosis serology, HIV-IgG and HBsAg were negative. Leishmania serology resulted positive in enzyme-linked-immunosorbent-assay (IgG 1:12800), immunofluorescent antibody test (IgG 1:25600) performed as previously described [] (Table ) and Western Blot.
Leishmania infantum DNA was detected in peripheral blood by Real-time Polymerase Chain Reaction (PCR) targeted on a 117 bp fragment in the mini circle kinetoplast DNA (kDNA), carried out as previously described by Vitale et al. [].
A bone marrow aspirate was not performed because of low platelet count. Liposomal amphotericin B was started at the dose of 3 mg/kg from day 1 to 5 and a further dose on day 10 for a total dose of 18 mg/kg.
The blood cells count and the clinical conditions of the patient progressively improved until reaching normal values; L. infantum real-time PCR on peripheral blood at the end of the treatment was negative. |
pmc-6471832-1 | A 63-year-old woman admitted to our hospital with a mass at the sternum and right second to third costochondral cartilage. She had undergone bilateral mastectomy for breast cancer 13 years earlier. Computed tomography (CT) revealed a 40-mm mass in sternum (Fig. a). Positron emission tomography (PET) revealed the maximum of the standardized uptake value of [18f]-fluorodeoxyglucose to be 7.30 at the mass in the sternum, with no other lesions detected (Fig. b). A percutaneous biopsy was performed, and the mass was diagnosed as solitary metastasis due to breast cancer. She received two courses of weekly paclitaxel and bevacizumab, and CT revealed shrinking of the mass in sternum, while the hot uptake on PET disappeared (Fig. a and b). We performed surgical resection with curative intent for a multimodality approach.
First, a latissimus dorsi myocutaneous flap was harvested with the patient in left lateral position (Fig. a). We could not assert that the tumor was not infiltrating the pectoralis major muscle and the subcutaneous layer. Therefore, we decided to remove these muscles. Parasternectomy and removal of the right second and third costochondral cartilage, the pectoralis major muscle, and the subcutaneous layer was performed in the supine position (Fig. b and c). A prosthesis was created to fill the defect by sandwiching molded methylmethacrylate between polypropylene mesh (Fig. a). The prosthesis was fixed to the cut ends of the costochondral cartilage and the residual sternum (Fig. b). Finally, the harvested latissimus dorsi myoctaneous flap was transpositioned to cover the chest midline wound and the prosthesis (Fig. c).
The postoperative course was uneventful, and her respiration was normal without paradoxical movement of the thorax or hypoxemia. A histological examination revealed that viable cells of metastatic breast cancer account for 30% of total cells, and cicatrization of metastatic breast cancer accounts for 70% of total cells in the sternum and the intercostal spaces. Immunohistochemistry revealed positivity for estrogen-receptor (ER) and progesterone-receptor (PR) and negativity for human epidermal growth factor receptor 2 (HER2). Furthermore, negative surgical margins at the stump of the sternum and costochondral cartilages were noted. Therefore, we decided not to do adjuvant therapy.
This patient has shown no complications and no recurrence in the four months since surgery. We planned to take CT every half year. |
pmc-6471850-1 | A 34-year-old caucasian female with past medical history of surgically treated HSCR.
No other significant symptoms were reported. As her son received the diagnosis of CCHS (see the case described above), she underwent to nocturnal polysomnography that was normal. Nevertheless, the sequencing analysis of the PHOX2B gene was carried out and the same mutation (c.255_256delCT) was singularly detected. Even though the same mutation was detected, the phenotype observed in her son was more severe with early onset of symptoms. |
pmc-6471901-1 | A 69-year-old female was diagnosed with TA at the age of 19 years, and steroid therapy controlled the diseases; however, her renal function declined gradually with renovascular hypertension developing as a complication of TA. At the age of 61, PD was initiated because hemodialysis was inappropriate because of severe aortic regurgitation and peripheral arteriosteogenesis that precluded the creation of an arteriovenous fistula.
The patient remained stable on PD for more than 5 years, with well-preserved residual renal function (RRF) and peritoneal function and only one episode of peritonitis, without any cardiocerebrovascular events. However, a gradual decline in RRF was accompanied by a concomitant increase in serum C-reactive protein (CRP) levels. The patient was evaluated for other inflammatory diseases, such as malignancies, infections, and autoimmune diseases including TA reactivation; however, nothing abnormal was detected. She also suffered from fatigue and vomiting; therefore, the increase in CRP indicating inflammation was considered to be due to malnutrition, inflammation, and atherosclerosis (MIA) syndrome resulting from inadequate renal replacement therapy with PD, evident from the RRF decline, leading to the accumulation of uremic solutes. Transition to hemodialysis or combination therapy with hemodialysis and PD were considered to improve her clinical condition; however, hemodialysis was challenging to the limitations associated with TA. Seven and a half years after the initiation of PD, she received a living-related KTx from her husband (Fig. ).
The immunological profile of the KTx was as follows: ABO, incompatible (from B+ to O+); human leukocyte antigen (HLA), six mismatches; complement-dependent cytotoxicity, negative; flow cytometric lymphocyte crossmatch test, negative; and donor-specific antibodies (DSA), positive against HLA-DQ4 with a mean fluorescence intensity of 3683. She had severe arterial calcifications: bilateral external iliac arteries were disrupted, and many corkscrew vessels ran from the internal iliac arteries toward the femurs as compensatory vessels (Fig. ). The internal iliac arteries were comparatively smooth, and living KTx surgery using the left donor kidney was performed in her right iliac fossa by end-to-side anastomosis with the right internal iliac artery. The intermittent claudication in the legs did not worsen after the surgery. The right ankle brachial index declined from 0.40 to 0.31, which was considered negligible, because a change of 0.15 or above is considered significant []. Total ischemic time, warm ischemic time, and onset of diuresis were 1 h 18 min 9 s, 5 min 16 s, and 14 min 53 s, respectively. Immunosuppression was induced with tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab. Rituximab, two sessions of double-filtration plasmapheresis (DFPP), and one session of plasma exchange were also performed as desensitization therapy because of ABO incompatibility and DSA positivity. Her creatinine level was almost stable; however, urinary protein was detectable even 3 months later. The protocol and episode biopsy performed at the time revealed chronic active antibody-mediated rejection (CAAMR), with Banff 2015 [] scores of g2 and cg1b (Fig. ). Peritubular capillaries exhibited focal C4d positivity by immunofluorescence (C4d2). We considered that this histological change was caused by anti-HLA antibodies and was not due to ABO incompatibility because ABO-related AMR tends to occur especially within 2–7 days posttransplant and does not occur more than 1 month posttransplant owing to accommodation [, ], which leads to the excellent outcome in ABO-incompatible recipients in our country []. The patient was treated with pulse methylprednisolone, rituximab, and two sessions of DFPP for CAAMR. Although the urinary protein was still positive for 1 year after KTx, the mean fluorescence intensity of DSA against HLA-DQ4 declined to 2426 and the renal graft function was preserved throughout the follow-up period (Fig. ). |
pmc-6471959-1 | A 90-year-old Hispanic male dairy farmer with a complex medical history notable for a left total hip arthroplasty (THA), bladder carcinoma in situ status-post intravesicular Bacillus Calmette-Guérin (BCG) (a live attenuated strain of Mycobacterium bovis) treatment, and chronic kidney disease who presented with subacute worsening pain of his left thigh. He had a THA placed thirty-one years previously. He had papillary bladder tumor status-post fulguration five years prior to admission with subsequent recurrence of bladder carcinoma in situ diagnosed a year later; he underwent six initial and six maintenance instillations of BCG treatment with remission of his bladder cancer.
Four years after BCG therapy, the patient developed new-onset drainage from the left lateral thigh. This was followed by swelling of his entire left thigh with increasing purulent discharge and pain with movement. He subsequently experienced chills, rigors, and a fever of 101 °F the morning prior to admission. On presentation he was afebrile with normal vital signs. His exam was significant for an open wound on the lateral left thigh with purulent drainage and surrounding erythema. Pain was noted adduction of the left hip. Initial laboratory tests were notable for a white blood cell count of 10,200 cells/mm3, a C-reactive protein of 9.7 mg/dL, and sedimentation rate of 71 mm/hr. Radiograph of the left hip showed “extensive lucencies” around the left THA (Fig. ).
The patient underwent incision and drainage with an antibiotic spacer placed following admission. Wound, hip fluid, and abscess cultures obtained during irrigation and debridement were negative for bacterial pathogens, however given his history of prior BCG therapy the microbiology laboratory was asked to additionally perform mycobacterial cultures and these grew acid-fast bacilli (AFB) concerning for Mycobacterium tuberculosis complex. After a brief course of clindamycin, ceftriaxone, vancomycin, and metronidazole, he was started on isoniazid 300 mg PO daily, rifampin 600 mg PO daily, pyrazinamide 1500 mg daily, ethambutol 1200 mg daily, and Vitamin B6 50 mg PO daily. He was placed in temporary airborne isolation while he had three sputa assessed for active pulmonary tuberculosis, which were negative for Mycobacterium spp. Nucleic Acid Amplification Testing (Cepheid, Sunnyvale, California) detected Mtb complex in his hip fluid culture.
Susceptibility testing for Mtb complex showed monoresistance to pyrazinamide, which was suggestive of M. bovis. As the patient had prior exposure to livestock and BCG therapy the isolate was further evaluated by spacer oligonucleotide typing (spoligotyping) and found by the California State Department of Health to be identical to that of the vaccine strain M. bovis BCG used previously in the treatment of his bladder cancer. The patient completed a 12 month course of rifampin, isoniazid and ethambutol without event and free of symptomatic, or radiographic recurrence. |
pmc-6472004-1 | A 59-year-old man with 3 months history of intermittent melena accompanied by the episodes of abdominal pain in the left upper quadrant and generalized fatigue was admitted to the department. He denied any other change in bowel habits or a history of hemorrhoids and was referred to hospital for evaluation of the GI bleeding. Patient’s medical history did not include any previous diagnoses. He was not taking any medications. At the time he was a non-smoker and did not consume any alcoholic drinks or recreational drugs. The patient also had two repeated episodes of left upper quadrant abdominal pain and dark black tarry feces within the last 3 months prior to admission to our hospital. However, symptoms resolved spontaneously and the patient did not make an appointment to see the doctor.
On examination the patient was pale, the abdomen was tender in the left upper abdominal area with no signs of rebound tenderness, no lump was palpable. Digital rectal examination revealed melena; the rest of the examination was unremarkable. The investigations showed that the patient had a low hemoglobin level, i.e. 10.9 g/dL with hypochromic microcytic anemia pattern seen in complete blood count (MCV 70.2 fl, MCH 21.4 pg). In addition, the patient had low serum iron, i.e. 6.4 μmol/L (normal range 9.5–29.9 μmol/L) and low ferritin levels, i.e. 28.8 μg/L (normal range 20–300 μg/L). The carcinoembryonic antigen level was 1.2 μg/L (normal < 5.00 μg/L). Other routine blood tests including lipase, plain chest and abdominal X rays along with abdominal ultrasound, esophagogastroduodenoscopy and colonoscopy were unremarkable. Thorough conventional evaluation of GI bleeding has failed to reveal a source, therefore, it was rational to proceed with further investigation of the small intestine.
Usually most cases of bleeding in the small intestine are caused by abnormal blood vessels in the wall of bowel - angioectasias, angiodysplasias, or arteriovenous malformations. However, there are many other possible causes of bleeding in the small intestine, including Crohn’s disease, benign and malignant tumors, polyps and ulcers.
Unfortunately, the capsule endoscopy is not reimbursed by Patient Sickness Fund in Lithuania, therefore we performed magnetic resonance (MR) enterography to help visualise possible bleeding site in the small bowel. MR enterography revealed a large pedunculated (attached to the intestinal wall by a 3 cm length pedicle) polyp, measuring approximately 2.5 × 2.3 cm and involving middle third of the ileum (Fig. .). Furthermore, ulceration marks at the top of the polyp were described.
For further investigation, the patient underwent retrograde single-balloon enteroscopy (SBE) to directly visualize pedunculated polyp, described previously on MR enterography. Examination by SBE revealed a polyp with a long pedicle located approximately 1.5 m distal to the terminal ileum (Fig. .). Endoloop-Assisted polypectomy was performed. However, the procedure was complicated with postpolypectomy bleeding from the pedicle. Dilution of adrenaline 20 ml (1/10.000) was injected into the bleeding area and the bleeding was controlled.
Brownish polyp with rugged surface was noted in the gross specimen. Cross-section of the polyp revealed a yellow node sized 1.5x1x1 cm. In addition, histopathological examination was performed. The report stated that the specimen contained ectopic pancreatic tissue involving longitudinal muscle layer of the ileum (Fig. .). Ectopic pancreatic tissue included acinar cells and cystically dilated secretory ducts without islets of Langerhans. Also, there was evidence of mucosal ulceration of the ileum.
The patient recovered after the enteroscopy well and had no further GI symptoms (since discharge until the time of writing). |
pmc-6472080-1 | An 83-year-old woman with epigastric pain was hospitalized for suspected gallstones. The patient’s medical history included diabetes, hypertension, hyperlipidemia, and dementia from stroke. The symptoms of epigastric pain disappeared after admission, but she developed a fever on day 2. Blood examination on day 4 revealed an inflammatory reaction (white blood cells, 12,200/μL; C-reactive protein, 27.39 mg/dL) and increased hepatobiliary enzymes (total bilirubin, 4.4 mg/dL; aspartate transaminase, 31 U/L; alanine transaminase, 54 U/L; lactate dehydrogenase, 217 U/L; alkaline phosphatase, 494 U/L; and gamma glutamyl transferase, 53 U/L). Urinalysis showed bilirubinuria. We considered cholecystitis or cholangitis and performed abdominal ultrasonography, which revealed gallbladder enlargement, biliary sludge, and hyperplasia of the bile duct wall. However, biliary expansion was not evident. Gallstone-related cholecystitis with bile duct inflammation was diagnosed. Antibiotic treatment with SBT/ABPC was initiated on day 4, and PTGBD was performed on day 5. The patient developed hypotension on day 6, and we therefore began noradrenaline administration. The disseminated intravascular coagulation did not merge (platelet count, 10.9 × 104/μL; prothrombin time(PT), 11.4 s; activated partial thromboplastin time(APTT), 31.9 s). The treatment was successful, and the noradrenaline was discontinued on day 8. However, the patient developed bilateral pleural effusion because of hypoalbuminemia. We were unable to discontinue oxygenation. Therefore, we drained the right and left pleural cavities on days 13 and 17 (Fig. ), respectively. The thoracentesis decided a puncture position in an echo, but we did not use the echo at the time of puncture. No signs of vascular injury that may have caused the hypotension were found. There was pleural effusion discharge of 300–400 ml from both drains, and the pleural effusion were transudative pleural effusion. On the morning of day 18, the patient had tachycardia (pulse rate, 130 beats/min) and hypotension (systolic blood pressure, 50 mmHg). We confirmed the presence of severe anemia using a blood test, and hemorrhagic shock was diagnosed. Because bloody fluid was exiting the drain in the right thoracic cavity at the time and we were unable to examine the right lung using chest X-ray, we suspected that the hemorrhagic shock was due to massive hemothorax (Fig. ). A blood test showed extensive coagulation dysfunction (PT, 68.0; APTT, immeasurable), and we considered the presence of vitamin K deficiency because the platelet level was normal. We performed red blood cell and fresh frozen plasma transfusions, and administered vitamin K to improve the anemia and coagulation disorder as quickly as possible (PT, 11.5; APTT, 32.0). On day 19, we performed cystography–computed tomography to identify the bleeding source. Enhancement rose from the 8th to 11th intercostal space during the arterial phase, and we considered this to be the bleeding site (Fig. ). We performed contrast-enhanced examination of the intercostal arteries during urgent interventional radiology. We were unable to clearly identify the bleeding source, but confirmed an abnormality in the path of the intercostal artery (Fig. ). We inferred that the cause of hemothorax in this case was injury to a small vessel, and not truncus due of the abnormality. Because of the likelihood of rebleeding, we performed coil embolization from the seventh to the ninth intercostal artery. Subsequently, because we confirmed vitamin K deficiency-induced coagulation dysfunction, we measured the concentration of PIVKA-II, and it was found to increase with 23,000. The patient’s condition stabilized, and she was awaiting hospital transfer at the time of this writing. |
pmc-6472087-1 | The patient, a boy, was born at term via uncomplicated spontaneous vaginal delivery to an 24-year-old gravida at 38 weeks of gestation. His birth weight was 3.5 kg. Prenatal course had no preeclampsia; neonatal history was benign. Both parents had no history of neurological disease and developmental delays. At ~ 12 months, his parents became concerned for delays in language skills. At 3 yrs., he was given a diagnosis of autism disorder by pediatric evaluation. His past medical history is significant for strabismus, short stature and hand anomalie (Fig. ). He is impulsive, hyperactive and inattentive in terms of behavior, and has severely limited social skills. |
pmc-6472324-1 | A 48-year-old man with ESRD secondary to diabetic nephropathy was admitted for initiation of renal replacement therapy. He had undergone 36 cycles (36 hours of 1 L/h cycle) of acute PD, through a temporary PD catheter inserted through the infra-umbilical approach, at another center 10 days prior and presented to us for maintenance dialysis. After discussing the options, he was started on hemodialysis through a temporary catheter and was planned to start on CAPD. He had a history of diabetic retinopathy and neuropathy. He did not have any history or symptoms suggestive of neurogenic bladder.
The patient underwent 3 sessions of hemodialysis and was planned for CAPD catheter insertion with vancomycin prophylaxis. As per protocol, he was advised to void his bladder completely and to pass stools before insertion. An infraumbilical midline incision was made under local anesthesia and IV sedation, an 18-G introducer needle was inserted through the rectus sheath until it reached the peritoneal cavity, and 1.5 L of peritoneal dialysate was instilled intraperitoneally. After instillation of fluid, a guidewire was passed through the needle, with the tip directed towards the suprapubic region. The needle was removed, the tract was dilated using a 16 Fr dilator followed by insertion of a 16 Fr peel away sheath/dilator. The guidewire was removed followed by the dilator, and Tenckhoff swan-neck double-cuff straight catheter was inserted through the peel away sheath. The sheath was peeled away, and a subcutaneous tunnel was created with the exit site facing down and out towards the left iliac fossa. The deep cuff was positioned over the peritoneum, and the superficial cuff was placed in the tunnel. The incision site was sutured in layers. Postprocedure, the inflow and outflow were found to flow without resistance, and the catheter was brought out through a left-sided tunnel. A 500-mL flush was given, and good inflow and outflow were noted. The outflow was initially blood-mixed, followed by drainage of clear fluid. There were no complications during the immediate postoperative period. With a plain abdominal radiograph, the position of the catheter tip was confirmed to be in pelvis (). Ultrasonography was not used during the procedure due to logistic reasons.
On the 3rd day after insertion, after instillation of 500 mL of PD fluid, the patient complained of urinary urgency with an increase in urinary volume to 700 – 800 mL/day from his baseline of 300 – 400 mL/day. Also, there was decrease in the outflow volume with drainage of only 100 mL following instillation of 500 mL of PD fluid. With the increase in the inflow volume, there was a significant increase in his urine volume. Urine analysis was done to look for glycosuria, which showed a 3(+) on dipstick, from his baseline glycosuria of 1(+). He was asked to void after instilling 500 mL PD fluid through the PD catheter, and urinary creatinine testing was done, which was found to be absent. A possibility of peritoneovesical fistula was considered, and a cystogram was planned. The instilled fluid presumably entered predominantly into the urinary bladder through the side holes and led us to presume that the PD catheter could be in the preperitoneal location. Urine culture and PD fluid cultures were sent, which revealed growth of enterococcus (> 105 colony forming units/mL), and he was treated with vancomycin intraperitoneally (IP) and broad-spectrum antibiotics intravenously.
The cystogram revealed a smooth-walled bladder, with no intraperitoneal leak of the contrast, and the catheter abutting the bladder wall (). A plain abdominal computed tomography (CT) was performed to confirm the position (). The catheter was seen to be piercing the anterior abdominal wall and entering the bladder anteriorly, perforating and coursing through the bladder before exiting through the posterior wall, with the tip in the rectovesical fossa. PD was discontinued, and he was continued on hemodialysis through a temporary femoral access catheter. After discussion with the urologists, it was planned to remove the catheter, followed by reinsertion at a later date, with conservative management for the bladder perforation. With cessation of PD, there was decrease in urine output to ~ 50 – 100 mL/day, and a repeat urine routine performed 3 days later showed reduction in pyuria (from plenty of white blood cells/high power field to 6 – 8 WBC/HPF).
The options were discussed with the patient, and the need for a vascular access was explained. However, due to logistic reasons, an attempt was planned towards catheter salvage. He was planned for catheter repositioning using fluoroscopic guidance under the cover of intravenous and intraperitoneal broad-spectrum antibiotics.
Using fluoroscopy with contrast (urograffin), first the bladder perforation was confirmed. The infraumbilical incision was re-explored under local anesthesia, while leaving the tunnel in situ. The deep cuff was identified, and the PD catheter was pulled back by ~ 6 cm (as measured by the prior abdominal CT image). Contrast was injected through the catheter, and it was confirmed to be intraperitoneal with no filling up of the urinary bladder. Using a guide wire, the catheter was redirected towards the right iliac fossa, and the position confirmed. On subsequent contrast injection through the PD catheter, the intraperitoneal nature and absence of bladder filling was confirmed. The bladder was later filled up with contrast, and there was no presence of any leaks (). The initial bladder perforation could have been an intraperitoneal perforation since pulling back and re-positioning the catheter, without any new entry into the peritoneum, confirmed it to be in the peritoneal cavity.
The patient was continued on IV antibiotics for 5 days, IP ceftazidime for a week, and IP vancomycin for 21 days, and was continued on hemodialysis. IP vancomycin was given in a single dwell (1,000 mL) for 6 hours every day. One week post repositioning, he was started on low-volume CAPD and discharged, and a repeat urine and peritoneal fluid culture were sterile. He was continued on Foley’s catheter for 4 weeks, with a residual urine output of ~ 200 – 300 mL/day. At 9-month follow-up, the patient is comfortable with CAPD 3 exchanges/day with good ultrafiltration (~ 1.4 L/day), and no change in urinary volume, with no further episodes of peritonitis. |
pmc-6472687-1 | We present the case of a 75-year-old man with a history of hyperlipidemia, giant cell arteritis on steroids, and recent urinary tract infection on antibiotics, who presented acutely with a complex aortic arch aneurysm. Ten days prior, he experienced chest pain and voice hoarseness, which persisted. CT angiogram revealed two saccular aortic aneurysms arising from penetrating atherosclerotic ulcers (PAUs). Between the origins of the left common carotid and left subclavian arteries (LSCA), there was a 3.7 × 4.4 × 5.2 cm aneurysm directed towards the left, inferiorly and posteriorly (). A second 4.3 cm saccular aneurysm arose from left lateral wall of the descending thoracic aorta. The presence of peri-aneurysmal fluid, left hemothorax, and hemopericardium as well as his clinical presentation, confirmed relatively acute contained rupture (). The patient was hemodynamically stable, with weak but symmetrical peripheral pulses and a normal neurologic exam except for a hoarse voice. We counselled him about the natural history and possible therapies including medical management, possible enrollment in the Terumo Aortic Relay Plus Dual Branched-graft clinical trial (NCT03214601) or open therapy. Over the following 6 hours, the patient became hypotensive with a drop in his hemoglobin concentration, so with the patient’s consent, we proceeded emergently to the hybrid operating room.
Right axillary cannulation was performed for systemic and later antegrade cerebral perfusion (ACP), by suturing a 10 mm Dacron graft to the right axillary artery. A right femoral arterial sheath was placed through which a soft guidewire was traversed to the descending thoracic aorta under transesophageal echocardiographic (TEE) guidance. Following sternotomy, the patient was placed on cardiopulmonary bypass (CPB) and cooling was started to 28 °C. The aorta was cross-clamped and dissected. On inspection, the ascending aorta had heavy intramural hematoma requiring debridement to the sinotubular junction, which was reconstructed with felt. The aortic valve was structurally normal and was resuspended at the level of the commissures. Upon reaching 28 °C, hypothermic circulatory arrest (HCA) was initiated with ACP through the right axillary artery. Extensive destruction of the distal aortic arch including the os of the LSCA, necessitated debridement to zone 3. The cut end of the proximal DTA was inflamed, atherosclerotic, and friable. Next, a TEVAR (34 × 100 mm Terumo Aortic Relay Plus) was deployed antegrade over the guidewire placed initially through the right femoral artery (). The stent-graft size was based on measurements on the CT scan (oversizing by approximately 10%). Use of the TEVAR as a frozen elephant trunk (FET), allowed reconstruction of this totally destroyed arch tissue, and provided a stable platform on which to construct the proximal arch graft, as well as a landing zone for future TEVAR within the FET. Importantly, when deployed antegrade, the Terumo Aortic graft allows a Dacron end to sew to. The proximal end of the TEVAR stent-graft was allowed to protrude 1.5 cm out of the arch. The cut end of the DTA was approximated to the stent-graft using a running horizontal 4-0 polypropylene suture. The distal anastomosis was constructed between the stent-graft and a 30 × 10 × 8 × 8 mm trifurcated Dacron arch graft (). CPB was resumed and the arch vessels were anastomosed starting with the LSCA, with sequential replacement of the clamp proximal to each completed anastomosis. During this time, the body was perfused with CPB and the brain with ACP for a total of 55 minutes. Finally, the graft to STJ anastomosis was completed (). Cross clamp was removed after 189 minutes. There was significant bleeding at the stent-Dacron graft anastomosis due to the stiff nature of the stent-graft which did not conform well to the Dacron graft to allow for hemostasis. Therefore, a second proximal retrograde TEVAR (Terumo Aortic 36 X 150 mm) was deployed via right femoral artery under fluoroscopic guidance. The proximal landing zone was at the level of the proximal arch just distal to the take-off of the side branches. The patient was weaned from CPB with ease after a total of 258 minutes, hemostasis was achieved and ultrasound examination revealed bilateral carotid flow. The patient’s postoperative recovery was complicated by poor calorie intake requiring the placement of a feeding gastrostomy and a perforated stress gastric ulcer that required emergent exploratory laparotomy and repair. He also required tracheostomy for airway protection due to weakness and vocal cord paralysis. He was subsequently discharged to a rehabilitation facility on post-operative day 14. In follow-up, the patient was clinically well and resumed light activities. Interval CT angiogram re-demonstrated the second saccular aneurysm which had now grown to 2.9 x 3.8 cm, as well as two PAUs (). The patient was offered endovascular repair which we performed 13 weeks after the index procedure. He underwent TEVAR extension with 36 X 200 mm Terumo Aortic Relay Plus endograft with use of a spinal drain. Completion angiogram revealed no endoleak and the final CT shows exclusion of the second aneurysm and PAUs (). The patient was discharged in excellent condition on lifelong suppressive antibiotics for Salmonella UTI in the setting of extensive graft material. No definitive evidence of salmonella aortitis was found. |
pmc-6472714-1 | A 60-year-old male with a remote history of tonsillar squamous cell cancer (SCC) treated with chemoradiation presented with a three-day history of new-onset epigastric pain radiating to his back, which was associated with nausea and vomiting. He had a remote smoking history but no alcohol intake. Three months before this presentation, he was found to have metastatic SCC in the jejunum, which was treated with curative resection.
In addition to his severe pain, the patient noted a 14-pound weight loss over the past three weeks due to his symptoms of anorexia with nausea and vomiting. On clinical examination, vital signs were stable; icterus was present. Abdominal exam was very tender to palpitation in the epigastric region but with normal bowel sounds. He had multiple abnormalities in his liver function panel, including aspartate aminotransferase (AST) - 160 U/L, alanine aminotransferase (ALT) - 218 U/L, alkaline phosphatase - 281 U/L, and total bilirubin - 3.0 mg/dl. Lipase was also markedly elevated at 10304 U/L. Right upper quadrant ultrasound showed biliary sludge. Computed tomography (CT) abdomen with contrast showed gallbladder distention and mild prominence of the intra-and extrahepatic bile duct (Figure ).
Magnetic resonance imaging (MRI) abdomen showed a double duct sign (Figure ).
He underwent esophagogastroduodenoscopy (EGD), which showed infiltrative thickening of the duodenal bulb and the second and third portions of the duodenum (Figure ).
Multiple biopsies were taken, and he underwent endoscopic retrograde cholangiopancreatography (ERCP) with biliary stent and drain placement. His abdominal pain improved significantly and was discharged in a stable condition. Pathology of the biopsied mass was consistent with metastatic squamous cell carcinoma of the tonsil. |
pmc-6472717-1 | A 62-year-old female with no significant past medical history presented to our facility with complaints of palpitations and associated dizziness for three months. Prior work-up of her palpitations with Holter monitoring showed no irregularities. On arrival, she was in no acute distress and her palpitations had subsided. Vitals that were obtained were largely unremarkable except for a blood pressure of 142/77. Her EKG showed no acute irregularity and laboratory testing was within normal limits. On physical, a regular rate was observed, no murmurs, gallops or rubs were auscultated. She did not exhibit jugular venous distention or peripheral edema and other organ systems did not yield and irregularities.
The patient was admitted for further evaluation and a transthoracic echo was performed, revealing a 4.4 x 3.0-cm mass in the left atrium attached at the interatrial septum and aortomitral intervalvular fibrosa. Additional imaging studies including cardiac magnetic resonance imaging (MRI) and transesophageal echocardiography (TEE) were obtained for further confirmation of the mass and its location (Figures , ). Surgical resection was planned, and pre-operative cardiac catheterization was performed which revealed mild prolapse of the mass causing intermittent obstruction of the mitral valve.
The patient underwent full-thickness resection of the mass, resulting in an iatrogenic atrial septal defect which was closed with a Dacron patch. Her postoperative course was complicated by the development of intermittent complete heart block with junctional bradycardia and subsequent atrial fibrillation. She was evaluated by electrophysiology and a permanent pacemaker was implanted without complication. Discharge follow-up several weeks later noted the resolution of her prior symptoms, and repeat imaging showed no evidence of mass recurrence or mitral valve prolapse. |
pmc-6472718-1 | A 75-year-old Caucasian male with a past medical history of essential hypertension, prostate cancer status post prostatectomy, and lifetime nonsmoker presented to his primary care provider with progressive shortness of breath and chest heaviness for one month. He denied systemic symptoms including weight loss, fevers, chills, or appetite loss. He reported ongoing productive cough with clear sputum. He was urgently referred to cardiology, in which an exercise stress test yielded ST-segment depression coinciding with anginal symptoms. Cardiac catheterization was performed and unremarkable for coronary disease. A post-catheterization chest X-ray (CXR) was significant for a right hemithorax with a moderate-to-large pleural effusion (Figure ). He was then sent to pulmonology for a thoracentesis, with three liters of pleural fluid removed. Pleural fluid studies indicated an exudative effusion that was negative for both malignancy and bacterial growth. He initially reported improvement of his dyspnea, however, his symptoms reappeared after a few days. Recurrent accumulation of fluid evident on CXR one week later prompted an additional thoracentesis and further evaluation for secondary causes, including autoimmune-mediated processes.
Serology results included the presence of antinuclear antibodies (ANA), low-titer anti-double stranded DNA (anti-dsDNA) antibodies 15 IU/mL, and rheumatoid factor (RF) 16 IU/mL. Anti-histone antibodies (AHA) were moderately positive at 2.5 Units. Anti-Smith antibodies and anti-cyclic citrullinated peptide (anti-CCP) antibodies were absent. Both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated at 52 mm/h and 32 mg/L, respectively. C3 and C4 complement levels and urinalysis with microscopy were normal. Table includes laboratory results with their normal references ranges.
In the setting of positive ANA, anti-dsDNA, and AHA, the patient was referred to Rheumatology for possible SLE. The patient denied classic systemic symptoms associated with SLE, including arthralgias, joint swelling, skin rash, or Raynaud’s phenomenon. However, it was still believed that his pleural effusion was secondary to an autoimmune etiology. He was started on a trial of oral prednisone 30 mg daily for seven days. A repeat ultrasound one week later demonstrated a decrease in size of the pleural effusion. Further evaluation with a CT scan of the chest revealed multiple pleural masses, including a 7.8 cm x 2.4 cm lobulated pleural mass in the right upper lobe. Additionally, there was nodularity of the right mediastinal and diaphragmatic pleura, suggestive of possible pleural mesothelioma. The presence of enlarged cardiophrenic lymph nodes was indicative of potential metastatic disease (Figures -).
A bronchoscopy with lung biopsy was consistent with epithelioid mesothelioma. A positron emission tomography (PET) scan revealed hypermetabolic activity corresponding with the lesions demonstrated on the CT scan of the chest (Figures -). The patient was then referred to Hematology/Oncology where he underwent treatment for his newly diagnosed malignant mesothelioma. |
pmc-6472869-1 | A 38-year old Caucasian male patient with a history of CD (with hemicolectomy four years ago) was admitted to the emergency room after an acute onset of singultus, dysarthria, and severe left-sided sensory motor hemiparesis (NIHSS 15). A head computed tomography (CT) scan revealed an occlusion of the right middle cerebral artery (MCA, M1-section) with a perfusion deficit of the complete territory and a partial mismatch in this area. The occluded MCA was re-opened by combining intravenous thrombolysis (74 mg rtPA) and local mechanical revascularization 165 min after symptom onset. Twelve hours later, the patient surprisingly presented with only a discrete left-sided hemiparesis without hypesthesia and mild dysarthria. Despite the clinical course, a follow-up CT revealed a large infarction comprising two-thirds of the right MCA territory with a slight 3 mm midline shift. Additional magnetic resonance imaging (MRI) scans (Days 2 and 8), however, were not suggestive of significant cerebral edema (Figure ).
Duplex sonography, 24h-ECG, echocardiography, as well as laboratory and genetic testing for hypercoagulability and vasculitis were unrevealing. There was a history of smoking (18PY). Adalimumab had been started 3Mo prior to admission. The drug concentration in serum on admission was 29.83µg/ml (reference 2.0-33.0µg/ml). Adalimumab therapy was discontinued after the ischemic episode. The patient was discharged with an NIHSS of 1. Three months later the patient showed no motor or sensory deficits and resumed his employment. |
pmc-6472871-1 | A 66-year-old man with alcoholic liver cirrhosis presented for orthotopic liver transplantation with a model for end-stage liver disease (MELD) score 20 on United Network for Organ Sharing (UNOS) waitlist. He had decompensated cirrhosis with hepatic encephalopathy, hypoalbuminemia, hyperbilirubinemia, coagulopathy, thrombocytopenia, portal hypertension, splenomegaly, and ascites requiring frequent paracentesis. He also had secondary restrictive lung disease from a chronic left-sided pleural effusion and pre-existing diabetes mellitus. A pre-transplant esophagogastroduodenoscopy (EGD) showed gastric antral vascular ectasia and Los Angeles Grade B esophagitis.
The patient received a deceased donor liver transplant from a 60-year-old male who died of a cardiac cause. Donor warm time was 26 minutes, cold ischemic time was 373 minutes, and warm ischemic time was 30 minutes. Biopsy of the donor liver showed no significant steatosis, fibrosis, or iron present. The patient remained hemodynamically stable throughout the operation on our typical vasopressor regimen. He was brought intubated to the intensive care unit (ICU) off of vasopressor support.
One hour postoperatively, the patient became hypotensive with mean arterial pressures below 70 mmHg for eight hours requiring escalating doses of vasopressors. After achieving hemodynamic stability, the patient was extubated on POD 0, approximately nine hours after arrival to the ICU. He experienced sustained hyperglycemia requiring an insulin drip for the first 48 hours postoperatively.
The patient’s diet was advanced in standard fashion, and he exhibited no symptoms between POD’s 0 and 10. On POD 10 a suspected bile leak necessitated an endoscopic retrograde cholangiopancreatography (ERCP). Evaluation revealed a black-appearing esophageal mucosa involving the entire length of the organ, ending at the GE junction (Figures -). No biopsies were taken and the bile duct was stented.
The patient remained nil-per-os, maintained on high dose intravenous proton pump inhibitor therapy, and started on empiric antibiotics, antifungals, and antivirals. A repeat EGD done on POD 14 found viable pink friable and oozy middle third of the esophagus (Figure ).
Despite overall clinical improvement, the patient experienced dysphagia. On POD 23 a repeat EGD showed improvement with resolution of necrosis (Figure ). By POD 32 the portion of the esophagus previously shown to have diffuse ischemia healed, with a small distal stricture requiring stent placement and removal four months later. This final endoscopy revealed a normal appearing, healed esophagus (Figure ).
Unfortunately, the patient’s overall health began to deteriorate in his second month of hospitalization. Recurrent pleural effusions necessitated multiple re-intubations and a percutaneous tracheostomy and gastrostomy with repeated bouts of sepsis and shock. Five months after his liver transplantation, the patient expired from sepsis and multi-system organ failure. |
pmc-6472884-1 | Patient 1 is a girl who received BCG vaccine when she was 4 months old, then a lump of finger size began to appear under her left armpit. When they came to the Wuhan jinyintan hospital, the lump had appeared for nearly four months. Blood routine examination displayed the number of leukocytes were increased. The patient was given debridement and treatment with anti-inflammatory drug of cephalosporins as well as isoniazid (INH). Patient 2 is a girl who received BCG vaccine when she was 3 months old. After one month, her parents found a lump about 3.0× 2.0cm in her left armpit. The patient was treated with anti-infection and external application of Chinese Medicine. Patient 3 is a boy, who received BCG vaccine, a big lump in the left armpit were found by his parents when he was 8 months old. The lump’s size like a pigeon egg. Puncture showed tuberculosis in lymph nodes and acid-fast stain is positive in these three patients, the three patients also received other test and were diagnosed with Mendelian susceptibility to mycobacterial disease (MSMD) in Wuhan Jingyintan hospital. Pedigree of the three families were shown in . |
pmc-6473054-1 | A previously healthy 67-year-old man presented with an acute onset of back pain, followed by progressive numbness and weakness of the limbs for 1 week. He could still ambulate with minimal help. On the day he was admitted to our hospital, his condition aggravated suddenly and reached a plateau within 8 h. He developed urinary retention and could barely raise his arms or move his legs. His family members mentioned that he also became irritable and forgetful. The neurological examination revealed severe quadriparesis (Medical Research Council strength score, upper extremities: grade 3; lower extremities: grade 1), a sensory C4 level, tendon hyperreflexia, and Hoffmann and Babinski sign. Physical examination was unremarkable.
Laboratory investigations including full blood counts, thyroid function, liver and renal function, LDH, β2-microglobulin, and tumor markers were normal. HIV antibodies and syphilis antibodies were negative. Antibodies mediating autoimmune encephalitis (anti-NMDAR, -AMPAR, -LG1, -CASPR2, -GABABR) or paraneoplastic syndromes (anti-Yo, -Hu, -Ri, -CV2, -amphiphysin, -PNMA2) in the cerebrospinal fluid (CSF) and serum were negative, so were antibodies against aquaporin-4 (AQP-4), myelin oligodendrocyte glycoprotein (MOG), and myelin basic protein (MBP). CSF analysis revealed normal CSF pressure, a mild pleocytosis (8 cells/ml) without atypical or malignant cells, an elevated protein level (132.9 mg/dl), and normal glucose and chlorine levels. Bacterial and fungal cultures were negative. CSF IgG index was 0.17, and the IgG oligoclonal bands were absent. Brain MRI revealed multifocal periventricular lesions with gadolinium enhancement in the left medial temporal lobe (). Spine MRI revealed longitudinally extensive abnormal signal extending from the cervical to the thoracic cord ().
The patient was suspected to have inflammatory demyelinating disease with a working diagnosis of ADEM or serologically negative NMOSD. He was treated with intravenous methylprednisolone (1 g/d for 5 days), followed by prednisone taper, and his condition markedly improved. The back pain was substantially relieved. Neurological examination revealed improved extremity strength (upper extremities: grade 4+; lower extremities: grade 4), with a sensory level of T12. He was subsequently treated with intravenous immunoglobulin, but without further improvement. The patient was discharged to rehabilitation.
For the following 6 months, the patient's condition remained stable. He could ambulate with minimal help. However, the 6-month follow-up brain MRI revealed an unexpected enhancing temporal mass with extensive perifocal edema (). Repeat spine MRI revealed decreasing lesions without contrast enhancement (). Brain stereotactic biopsy of the right temporal mass was performed. Histopathological findings of the specimen demonstrated DLBCL (). Whole-body positron-emission tomography/computed tomography (PET/CT) imaging was performed to evaluate extra-neural involvement. Abnormal hypermetabolism was found in the left testicle and in multiple abdominal and retroperitoneal lymph nodes (). Subsequent testicle and bone marrow biopsies were consistent with DLBCL (Stage IV disease).
Systemic chemotherapy (Methotrexate + Rituximab + Ara-C) combined with involved field radiotherapy was conducted. Due to severe vomiting, the chemotherapy had to be discontinued after the fourth therapy cycle. Repeat brain MRI showed necrosis of the original mass lesion, no new lesions were observed (). Sixteen months after the initial admission, he could ambulate by himself without any help. |
pmc-6473229-1 | During the rainy season in January 2016, a 39-year-old Indian man from Teluk Intan, Perak (Northwest of Peninsular Malaysia), complained of 10 days of fever, associated with headache, generalized myalgia, and rash over the lower limbs. There was no history of antibiotic therapy before the rash’s onset. He suffered no vomiting, visual complaints, confusion, or neck pain. The patient was a lorry driver, working for an oil-palm plantation and had frequent contact with rats around the oil-palm factories. There was no report of recent travel and involvement in forest or water-based recreational activities. His medical history was otherwise not significant.
Upon physical examination, he was alert and orientated. His vital signs included an oral temperature of 39 °C, blood pressure of 110/77 mmHg with pulse rate of 88 beats per minute, respiratory rate of 18 breaths per minute and oxygen saturation of 98% on room air, with a score of 0 by using the quick sepsis related organ failure assessment (qSOFA) scoring []. Skin examination revealed erythematous macular papular rashes over both lower limbs, which spared to the palms and soles. There were no visible eschars. Eyes were normal and there were no palpable cervical lymph nodes, mouth ulcers, or myositis elicited. Cardio-respiratory examination was unremarkable, and abdominal examination failed to demonstrate organomegaly.
The initial laboratory parameters demonstrated white cell counts of 7.9 × 109 cell/L (reference range 4.0–12.0 × 109 cell/L), mild thrombocytopenia of 126 × 109 cell/L (reference range 150–440 × 109 cell/L), normal serum creatinine level of 99 µmol/L (reference range 62–106 µmol/L), and hyponatremia at 127 mmol/L (reference range 136–145 mmol/L). Both liver enzymes were moderately elevated, with alanine aminotransferase of 131 IU/L (reference range 10–50 IU/L) and aspartate aminotransferase of 156 IU/L (reference range 10–40 IU/L). Normal total bilirubin level was 14.5 µmol/L (reference range ≤ 21 µmol/L) and mild hypoalbuminemia of 33 g/L (reference range 35–52 g/L). C-reactive protein (CRP) and procalcitonin level (PCT) were elevated at 80.23 mg/L (reference range < 5 mg/L) and 0.98 ng/mL (reference range < 0.5 ng/mL), respectively.
In view of the clinical history and demographic considerations, the patient was treated empirically for leptospirosis using intravenous ceftriaxone, (2 g once a day). However, the initial leptospiral microagglutination test (MAT; using three local serovar and 17 serovar recommended by WHO) [], dengue NS1, IgM and IgG (PanBio Dengue Capture ELISA), blood films for malaria and blood culture taken upon admission (BACTEC 9240, Bactec) were all negative. Furthermore, there was persistence in symptoms and worsening septic parameters, despite antibiotic therapy, which prompted the need to reconsider the initial diagnosis, one of which included murine typhus and other rickettsial diseases (). Serological tests using rapid diagnostic kits for both scrub typhus (InBios scrub typhus IgM) and murine typhus (GenBio R. typhi) were both performed and yielded positive results in the later test. Ceftriaxone treatment was ended and oral doxycycline was initiated, with a loading dose of 200 mg followed by 100 mg twice a day for seven days (). Symptom relief was achieved within 24 h of doxycycline administration. ().
Initial sera samples collected on the day of admission (day 10 of illness) were tested by IFA for IgM and IgG against Orientia tsutsugamushi (Karp, Kato, Gilliam and TA716 strains), R. typhi (Wilmington strain), and spotted fever group (R. felis strain) as described previously [,]. This revealed 1:3200 murine typhus IgM and 1:100 IgG in the IFA. Repeat convalescent sera sample collected five days later, revealed further increase of both IgM (1:12800) and IgG (1:800) (). Comparatively, IFAs for scrub typhus IgM and IgG were <1:100 for both samples and spotted fever group rickettsia IFA resulted in 1:100 IgM and IgG <1:100, compared to 1:800 IgM and IgG <1:100 in the convalescent sample. Nucleic acid detection assays targeting the 47 kDa and 56 kDa outer membrane proteins of O. tsutsugamushi for scrub typhus and Lipl32, respectively, as well as the 16s rRNA for leptospirosis, and 17 kDa ompB genes of R. typhi were all negative. The patient completed seven days of doxycycline with blood parameter normalization and was subsequently discharged in a healthy condition ().
This study had been approved by the Malaysian National Medical Research and Ethics Committee (1 September 2015). An informed consent was signed by the patient. |
pmc-6473255-1 | A 46-year old Asian male presented to the emergency department with recurrent hemoptysis. The patient had been diagnosed with dermatomyositis and IgM nephropathy 10 months prior to presentation, and was started on prednisone (50 mg/day; 0.9 mg/kg/day). In an attempt to limit corticosteroid exposure, two weeks after starting prednisone the patient was given azathioprine for two weeks, but he could not tolerate its adverse effects. As a result, he resumed high-dose prednisone (40 mg/day) up to the time of the current hospital admission.
The patient had presented a month prior to the current admission with a cough productive of clear sputum with streaks of bright red blood. A CT scan of the chest at that time showed interstitial thickening and a left lower lobe pulmonary nodule versus atelectasis. Bronchoscopy revealed no endobronchial lesions. Bronchoalveolar lavage fluid grew Candida albicans and usual respiratory flora. Serologic testing for infection with Coccidioides, Histoplasma, Strongyloides (IgG by ELISA, ARUP Laboratories, Salt Lake City, UT, USA), and Cryptococcus was all negative. An interferon-gamma release assay for the diagnosis of latent tuberculosis conducted one month prior to the current admission was indeterminate, and three sputa for acid-fast bacilli were negative by smear and culture. A urine culture grew Klebsiella pneumoniae and Escherichia coli. The hemoptysis resolved and the patient was discharged on ciprofloxacin for the urinary tract infection. The patient then presented with hemoptysis of three days duration, associated with fever and chills. He also noticed a rash on his abdomen two days prior to presentation.
The patient was born in Laos and had spent three years in a refugee camp in Thailand before emigrating to the United States 25 years ago. He had lived primarily in San Antonio, Texas, but had travelled to New York City multiple times to work at a landfill. The patient had a 25 pack-year history of smoking, but no history of incarceration or alcohol or recreational drug use.
On presentation, the patient was lethargic and appeared unwell. Vital signs were: Temperature 38.4 °C, blood pressure 70/40 mm Hg, pulse 125/min, and respiratory rate 20 breaths per minute. On exam, the patient had bilateral coarse crackles, diffuse abdominal tenderness, and a purpuric rash on the anterior trunk extending to the flanks, suprapubic area, groin, and upper thighs (). An electrocardiogram showed atrial fibrillation with rapid ventricular response.
Initial laboratory results were: White cell count 19.5 K/µL (reference range (RR) 3.4–10.4 K/µL) with 51% bands, 38% neutrophils, 3% lymphocytes, 1% eosinophils; hemoglobin 11.8 g/dL (RR 12.8-17.1); platelets 214 K/µL (RR 140-377 K/µL); creatinine 1.2 mg/dL (RR 0.6–1.3 mg/dL), bilirubin 1.2 mg/dL (RR 0.2–1.2 mg/dL); alanine aminotransferase 71 IU/L (RR <46 IU/L); aspartate aminotransferase 47 IU/L (RR <36 IU/L) and alkaline phosphatase 124 IU/L (RR 45–117 IU/L). A CT scan of the chest showed interval development of diffuse ground glass opacities (likely alveolar hemorrhage), interlobular septal thickening, and a single 9 mm right middle lobe cavitary lesion (A,B). The patient was admitted to the medical intensive care unit with septic shock. He was started on cefepime, vancomycin, and metronidazole. The next day he required intubation for hypoxemic respiratory failure. Bronchoscopy showed a normal airway with fresh and old blood present, but without an obvious source of bleeding. The differential diagnosis for the hemoptysis considered at the time was tuberculosis, atypical mycobacterial infection, bacterial pneumonia, vasculitis, and Pneumocystis jiroveci pneumonia. A punch biopsy of the abdominal rash was performed.
Blood cultures from the day of admission grew K. pneumoniae and Enterococcus faecalis. The grossly bloody bronchoalveolar lavage fluid () grew Nocardia asteroides and also revealed the presence of S. stercoralis larvae. Histopathologic exam of the skin biopsy showed multiple intradermal helminths consistent with Strongyloides (). A stool exam conducted on hospital day 13 was also positive for Strongyloides.
Starting on hospital day 3, the patient was treated with ivermectin 200 µg/kg/day and albendazole 400 mg twice daily through a nasogastric tube. The patient received albendazole for 21 days and ivermectin for 32 days. The ivermectin was continued until serial sputum and stool studies were negative for the presence of Strongyloides. The patient also received cefepime and vancomycin for the polymicrobial bacteremia and trimethoprim-sulfamethoxazole for the nocardiosis. The prednisone dose was decreased to 20 mg per day during the hospitalization. Due to altered mental status, the patient was evaluated by an MRI of the brain and a lumbar puncture, but there was no evidence of CNS infection. The patient was extubated after 10 days of mechanical ventilation. The patient gradually improved and was discharged to a rehabilitation facility in stable condition. |
pmc-6473255-2 | The patient is a 36-year old Hispanic man with a history of acute lymphoblastic leukemia that had been diagnosed 14 months prior to the current admission. At that time, he had received induction chemotherapy with cyclophosphamide, vincristine, doxorubicin, dexamethasone, and rituximab (hyper-CVAD-R) and intrathecal chemotherapy, which he finished four months prior to the current admission. He was maintained on monthly 6-mercaptopurine, vincristine, methotrexate, and prednisone (200 mg per day for five days of each month). He had been admitted to the hospital three weeks prior to the current admission for chest pain, malaise, weight loss, and a persistent cough productive of yellow sputum. At that time, he was febrile to 38.4 °C and was initially given vancomycin, piperacillin-tazobactam, and azithromycin. He was found to have diffuse infiltrates on chest X-ray. Sputum culture grew Pseudomonas aeruginosa and the patient was transitioned to ciprofloxacin. A nasopharyngeal respiratory pathogen polymerase chain reaction panel (Biofire, Salt Lake City, UT, USA) was positive for Rhinovirus and Enterovirus. Serologic studies for Histoplasma, Cryptococcus, Strongyloides (IgG by ELISA, ARUP Laboratories) and Coccidioides were negative, as were stains of the sputum for fungal and acid-fast organisms. Given the patient’s immunocompromised condition, the diffuse pulmonary infiltrates raised concern for Pneumocystis infection. Trimethoprim-sulfamethoxazole (TMP-SMX) and corticosteroids were started empirically with rapid improvement, and the patient was discharged to finish 21 days of TMP-SMX and 14 days of tapering prednisone. The patient presented for the current admission with worsening dyspnea, malaise, fever, and hemoptysis four days after completing ciprofloxacin and TMP-SMX.
The patient was born in Honduras and had emigrated to the United States 16 years prior. The patient lived in San Antonio, Texas, and worked as an electrical technician. He had no animal exposure and no history of incarceration, homelessness, or recreational drug or alcohol use.
On exam, the patient was tachypneic; vital signs were: Temperature 37 °C, pulse 112/min, respiratory rate 30 breaths/min, oxygen saturation of 88% on room air, and a blood pressure 80s/30s mm Hg. Pulmonary exam revealed diffuse rales and expiratory wheezes. The remainder of the exam was unremarkable.
Hematologic results were: White cell count 5.3 K/µL with 36% neutrophils, 6% lymphocytes, 18% eosinophils, 20% bands, and 8% metamyelocytes; hemoglobin 9.7 g/dL; and platelets 138 K/µL. Serum chemistry values were: Sodium 120 mmol/L (RR 135-145 mmol/L) and bilirubin 1.6 mg/dL (0.2–1.2 mg/dL); creatinine, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels were all within normal limits. A CT scan of the chest showed interval worsening as compared to three weeks prior, with extensive ground glass and patchy parenchymal opacities throughout the bilateral lungs, suggestive of multi-lobar Pneumocystis pneumonia (see ).
The patient was admitted to the intensive care unit with septic shock. The initial differential diagnosis for the patient’s respiratory distress included viral or bacterial pneumonia, vasculitis, malignancy, and P. jirovecii pneumonia. He was started on cefepime, vancomycin, TMP-SMX, metronidazole, and azithromycin, and received five liters of normal saline and norepinephrine for blood pressure support. Prednisone was held. Sputum cultures again grew P. aeruginosa with the same susceptibility pattern as in previous cultures. A nasopharyngeal swab for viral respiratory pathogens was again positive for Rhinovirus and Enterovirus. Sputum cytology was also obtained to evaluate for malignancy. The patient improved after 24 days and was transferred to the ward.
Sputum cytology revealed helminth larvae consistent with S. stercoralis (). The patient was started on ivermectin (200 µg/kg/d) and continued to improve. Sputum cultures also grew Aspergillus flavus and Candida tropicalis. Bronchoscopy was performed and the lavage fluid grew A. terreus; C. guilliermondii grew from tissue from a transbronchial biopsy, and he was started on voriconazole. He was discharged in stable condition. At clinic three weeks later, the patient reported a constant dull headache and a lumbar puncture showed neutrophilic pleocytosis; a CSF culture grew Aerococcus viridans. He was successfully treated with a 14-day course of vancomycin. He continued ivermectin until two weeks of serial sputum and stool samples were negative for the presence of Strongyloides (64 total days of treatment). |
pmc-6473395-1 | A 19-year-old female kindergarten teacher presented with a 2-month history of repeated occipital headache which aggravates on activities, nausea and vomiting. When she was admitted to our hospital, no obvious neurological abnormalities were found via physical examination. The head magnetic resonance imaging (MRI, Siemens, Munich, Germany) scan showed a mass in the left cerebellar hemisphere (). The patient underwent the left cerebellar hemisphere tumor resection, dural repair, and cranioplasty 1 week later. Hematoxylin and Eosin (H&E) staining was performed (), and positive expression of CD31 and CD34 (Aotang Medical Technology Co., Ltd., Zhongshan, China) were detected using immunohistochemistry (). The postoperative pathological analysis and diagnosis confirmed the diagnosis of HBs. |
pmc-6473395-2 | The girl's father, a 44-year-old peasant, suffered from a headache 6 months later, and the right occipital swelling pain was the main symptom without nausea and vomiting. Physical examination showed no abnormal neurological symptoms. Results of MRI indicated multiple masses in the cerebellum and spinal cord (). Multiple cysts were found on the right kidney with B-mode ultrasound. The patient underwent the multiple cerebellar tumor resections, posterior cranial fossa decompression, and dural expansion plasty 1 week after admission. The detection of H&E staining () and immunohistochemistry () was the same as Case 1. The postoperative pathological analysis and diagnosis confirmed the diagnosis of HBs. |
pmc-6473520-1 | A 36-year-old male was admitted to a general hospital in Gauteng Province in May 2017 for investigation of acute psychosis. Laboratory investigations on admission (day 1): Negative serology for Treponema pallidum, values in the normal range for thyroid-stimulating hormone, full blood cell count and vitamin B12, elevated serum levels of C-reactive protein, alkaline phosphatase and gamma-glutamyl transferase, with low serum albumin levels and hyponatraemia (). Further investigations on day 3 included a lumbar puncture (LP), with normal CSF chemistry, 20 erythrocytes/µL and cell counts of zero for polymorphonucleocytes and lymphocytes. Both CrAg LFA (in duplicate) and India ink staining of the CSF were negative, although on the CSF culture there was heavy growth of C. neoformans. The patient had a CD4 count of 19 cells/µL, which prompted reflex screening for cryptococcal antigenaemia. Again, the CrAg LFA was negative. The CSF specimen and the clinical isolate were referred to NICD for further testing.
At NICD, possible pre-analytical errors (such as specimen collection from the wrong patient, or mislabeling) and analytical errors (such as specimen mix-up, incorrect specimen processing, a haemolysed specimen, incorrect reading time for the CrAg LFA, poor visual acuity of laboratory personnel, incorrect interpretation of CrAg LFA results, transcription errors) were excluded after thorough investigation. The CrAg LFA continued to yield a negative result despite the use of kits from three different lots, and serial dilution testing (titration 1:1280) to exclude ‘hook’ effects. The CrAg EIA yielded an optical density of 0.630/0.778 (positive result) on the CSF specimen. The identification of C. neoformans was confirmed phenotypically with the development of brown-pigmented colonies on Staib’s niger-seed medium, and no colour change (negative) growth on CGB agar. C. neoformans was confirmed by MALDI-TOF. Sequencing of the ITS region and LSU of the ribosomal gene also confirmed that this isolate was C. neoformans, whilst MLST revealed that this isolate had the molecular type VNI (serotype A) and sequence type (ST) 31. Insufficient residual CSF meant that the reference laboratory performed India ink staining on the cultured isolate (cells suspended in saline for staining), but still failed to detect any encapsulated cells. Ultrastructural comparison of the cells of the clinical isolate, with those of the control culture (ATCC 34875) illustrated obvious differences between the two cultures that could be quantified, and which were shown to be statistically significant when compared with the control cells (p = 0.001) ( and ). The extensive and uniformly reticulate nature of the capsule of control cells contrasted markedly with that of the case 1 isolate, which was notable for its variability in texture, appearance and thickness. Case 1 capsule was seen to be reduced in comparison with the control isolate (mean of 192 nm compared with 395 nm in the control; n = 100).
On diagnosis of CM, the patient received amphotericin B deoxycholate-based induction treatment, but continued to deteriorate clinically and subsequently died one week later. |
pmc-6473520-2 | A 51-year-old female was admitted to a hospital in the Eastern Cape Province in June 2017, for investigation of seizures. Laboratory investigations on admission (day 1) revealed a non-reactive rapid plasma reagin test, no hepatitis B virus surface antigen, a CD4 count of 119 cells/µL, hyponatraemia, low serum chloride concentrations, borderline abnormal liver function with elevated serum alkaline phosphatase and gamma-glutamyl transferase (), and peripheral white blood cell counts and haemoglobin within normal ranges (4.5 to 11.0 × 109/L and 12.0 to 15.5 g/dL in women), but with a lowered platelet count (121 × 103 cells/µL; normal range 150–400 × 103 cells/µL). CSF parameters from the initial, and subsequent, lumbar puncture(s) are tabulated (). A CSF CrAg LFA and latex agglutination test, and CSF India ink staining were negative, although on culture of CSF, there was a heavy growth of C. neoformans—an identification confirmed by VITEK mass spectrometry (bioMeriéux, Marcy-l’Étoile, France). Once again, the CSF specimen and clinical isolate were referred to NICD for further testing.
The phenotypic identification of C. neoformans made by the referring laboratory, was confirmed at the NICD by culture (Niger seed agar positive, CGB agar negative), which was supported by Bruker Biotyper MALDI-TOF results, molecular identification (C. neoformans) and genotypic characterisation (molecular type VNI [serotype A] and ST31). However, repeat India ink staining was negative (CSF and cultured cells), as were 4 different kit lots for CrAg LFA, a 1:5 to 1:1280 titration series with CrAg LFA, and a negative CrAg EIA on CSF (optical density −0.034/−0.039). The clinical isolate was also referred for capsule characterisation using TEM, which revealed the presence of a consistently thin capsule (mean of 168 nm; n = 100), with a uniformly fibrous, tomentose appearance, and very much reduced in comparison with that of the ATCC control cells ( and ). Once again, the measured difference between the capsule thickness of control cells and those of the case isolate, were statistically significant (p = 0.0001).
On diagnosis of CM, the patient received standard treatment with amphotericin B deoxycholate + fluconazole (1200 mg daily for two weeks) and completed the induction phase of treatment uneventfully. CSF taken on day 6 proved to have no cryptococcal growth on culture (14 days culture incubation). By day 23, she was clinically well and was discharged.
The patient was readmitted on day 43. Few details are available other than an LP report () and a laboratory test result which was a positive blood culture for extended spectrum beta-lactamase-producing Escherichia coli. The patient died shortly after admission. |
pmc-6473553-1 | A 31-year-old Caucasian male patient with catatonia was admitted to our closed psychiatric ward. In the emergency contact, he was disoriented as to the situation, time, and place; confused; anxious; and mutistic. Besides incoherently expressed psychotic fears of poisoning and other incoherent phrases, he was not open for exploration. Most information was gathered from his accompanying parents. According to them, he had never moved out but had been living his whole adult life in the basement of their house. Usually socially withdrawn and very calm, his behavior had changed rapidly approximately 5 days prior to admission toward agitation, repetitive movements, verbal and physical aggression, and sexual disinhibition. The patient had no prior personal or family psychiatric history and no history of drug abuse. Besides being underweight (Body Mass Index = 18.4 kg/m2), he was in good physical health and had never taken medication.
On the ward, the patient initially refused water, food, and medication. Remaining in bed in a rigid posture, appearing confused and anxious, and avoiding eye contact and any kind of communication, he exhibited classic psycho-motoric symptoms of catatonia such as stupor, waxy flexibility, and mutism. The Positive and Negative Syndrome Scale (PANSS) () on admission added up to 148 points; the Northoff Catatonia Rating Scale (NCRS) () added up to 30 points in total, indicating severe psychosis and catatonia, respectively (see also ). Due to a sudden state of agitation, the patient had to be temporarily restrained. Initial blood tests, clinical examination, and cranial magnetic resonance tomography () were without significant pathological findings. In particular, no gross abnormalities (e.g., tumor, space-occupying cystic lesion greater than 3 mm, signs of bleeding, contusion, infarction, and major gray or white matter lesions) were found. Due to reduced health conditions of the patient (dehydration, fever, and elevated CreatinKinase) on day 3, treatment with intravenous lorazepam and electrolyte solutions was initiated under physical constraints to prevent malignant catatonia. This led to stabilization of the patient’s state with partial remission of catatonic symptoms. Although some level of communication could be achieved, the patient, however, still refused any kind of treatment and demanded discharge. Therefore, his father was installed as legal guardian; the patient was involuntarily committed to treatment according to German law, and coerced antipsychotic medication with olanzapine and lorazepam was legally approved. Administration of oral olanzapine 20 mg daily over the course of 2 weeks and a subsequent intramuscular injection of 300 mg of its depot formulation resulted in further remission () and allowed for a more in-depth exploration and neuropsychiatric testing.
Five weeks after admission, the patient began to leave his room for dinner and ward rounds if requested. However, he never addressed someone actively. He was fully oriented and did not show any positive psychotic symptoms. Psychomotorically, he was calm and slow. He barely showed emotions, his affect was flat, and his voice and body language were monotonous. Any kind of communication, however, evoked apparent unease in the patient, accompanied by vegetative arousal signs such as sweating and tachycardia. In conversations, he never held eye contact. He still insisted on discharge, stressing out his will to return to his usual daily activities undisturbed by others. The patient admitted having been in critical conditions on admission, but rejected disease-related medical explanations. He refused voluntary medication, repeating that all it required to maintain his health was good food and his daily routine, which mostly comprised playing computer games, watching television, and cooking for himself. He reported an inverted circadian cycle of nightly waking and sleeping from early in the morning to late in the afternoon, so—despite living under one roof—he would rarely interact with his parents and younger sister. He would not leave the house for weeks except for short walks. He did not work and relied financially on his parents who also did all the shopping and housework. He reported not having had any friends or social contacts outside the family for 3 to 4 years. He never had a sexual relationship, albeit being sexually aroused by women, e.g., on television. Asked about his future plans, the patient seemed to be fully convinced that his current living situation would continue unchanged for an indefinite amount of time and considered this positive. When aging and potential mortality of his parents were addressed, he seemed not to be able to conceptualize this possibility. When asked about his parents’ and sister’s ages, he missed it by more than a decade (estimating them younger), albeit being fully oriented and exactly knowing his own age and date of birth.
The patient was born in Germany in a middle-class family. According to his parents, he was a healthy, normal-weight infant without any complications during pregnancy or birth (via naturalis). No infections of mother or child were memorable. His motor development was retarded; reportedly, he started to walk at the age of 2. Later, he would have coordinative difficulties to prepare bread or to walk downstairs. The speech development was reportedly unaltered. At the age of 3, he attended kindergarten. After the birth of his younger sister (by 5 years), he would have reacted “properly” and care for her. At the age of 7, he was sent to school. His teacher in the first grade advised the parents to put him in a special school due to his “odd” behavior, but they refused. During kindergarten and school, he was reported to have a hard time finding friends. The patient passed middle school with mediocre grades. According to himself, he did not like a special subject, but was bad at math and reading. He acquired a driver’s license at 18. After school, he finished a full training for a computer technician but did not attend the final exams. According to his parents, this was a breaking point in the patient’s life. He withdrew socially and ceased to adapt to social norms. He was dismissed from an internship at a warehouse due to inability to cope with the social structure at work and disrespect toward supervisors. Until clinical presentation, he had been living in the basement without much contact to the outer world. Interestingly, a stress situation could be described, which might have contributed to the acute psychotic state. The family reported that a renovation took place in the patient’s basement. Therefore, he had to move temporarily upstairs, and his daily routine was disrupted. Asked about this situation, he reported that the inability to withdraw and to follow his routines evoked feelings of anger and fear of change.
We performed a series of neuropsychological tests on the patient. In contrast to the clinical impression and his education, he performed poorly on the Intelligence Structure Test (IST-2000R) IQ test (), reaching an overall IQ of 74 (). However, the patient worked extremely slowly, over-carefully and anxiously, not proceeding adequately, leaving the majority of tasks uncompleted. He showed a substantial lack of motivation and worked only on tasks corresponding to his interests, leaving everything else out. Those items that he completed were solved correctly. Therefore, the results might underrepresent his intelligence. Furthermore, the Marburger Beurteilungsskala zum Asperger Syndrom (MBAS) (), the Structured Clinical Interview for DSM-IV-TR (SCID II) (), and a facial emotion recognition test were carried out. In the MBAS, the patient reached the cutoff for high-functioning ASD (). He could identify all emotions except for anger (). The patient underwent Autism Diagnostic Observation Schedule (ADOS-IV) after the partial remission of psychotic symptoms. This module is used with adolescents and adults with fluent speech (). In this testing, he fulfilled the criteria for ASD and showed deficits mainly in communication and social interaction. The total score of ADOS-IV was 17 points (, A4 = 1; A8 = 2; A9 = 2; A10 = 1; B1 = 2; B2 = 2; B6 = 2; B8 = 2; B9 = 1; B10 = 1; B11 = 1; D1 = 1; D2 = 2; D4 = 1; and D5 = 1) and he reached the cutoff criterion for ASD. Autism Diagnostic Ineterview (ADI-R) was not performed. Still, the patient’s parents were interviewed extensively about his development.
Continued lack of patient’s therapeutic adherence and legal restrictions resulted in an interruption of therapy with olanzapine depot. Within a few weeks after discontinuation, the patient returned to a mutistic state, mostly refused to communicate, to leave his bed, and to participate in any social activities. He re-expressed high levels of anxiety and psychomotor agitation accompanied by vegetative symptoms. Resumption of forced medication with biweekly intramuscular olanzapine depot led once again to rapid remission. To encourage the patient to engage in social activities, we installed a behavioral plan where participation in ward rounds, ergotherapy, and meals was rewarded by computer time. In cooperation with psychologists and social workers, we strongly involved the parents in the therapeutic process. After multiple extensive psychoeducational sessions, the patient started to accept his biweekly medication. He was discharged in good physical and mental condition after 101 days of treatment (Figure 1B). Currently, he biweekly visits our outpatient office for medication and clinical controls and has been in remission for over a year. |
pmc-6473594-1 | A 69-year old woman was referred for possible lung volume reduction. She had a history of COPD with dyspnoea progressively worsening over 6 years. Her medical history included past smoking (stopped 17 years earlier and totalling 40 pack years), thyroidectomy for multinodular goitre, uncomplicated systemic hypertension and type 2 diabetes. At the time of referral, her treatment included inhaled tiotropium and salmeterol/fluticasone, levothyroxine, valsartan, hydrochlorothiazide and metformin.
She complained of dyspnoea grade 2–3 (modified Medical Research Council –mMRC-scale; that is, she stopped for breath after walking 200–300 meters (m) on the level) and acknowledged a sedentary lifestyle. She experienced less than one exacerbation per year. The COPD assessment test (CAT) score was 24/40, suggesting a high impact of COPD on the patient’s health and daily life.
Clinical examination showed severely diminished breath sounds at the lower part of the right hemithorax. Besides overweight (BMI 29.5 kg/m2), it was otherwise unremarkable.
As shown in , pulmonary function tests (PFT) showed severe airway obstruction (GOLD stage 3) with significant lung hyperinflation. Lung diffusion was relatively preserved. She walked 342 m on a 6-min walk test (6MWT) with oxygen saturation measured by pulse oximetry (SpO2) dropping from 97 to 92%. The BODE index was 5/10. According to the 2015 (time of the initial assessment in our centre) GOLD guidelines, she was classified as grade D for risk stratification (Grade B according to the current GOLD guidelines) [].
A chest X-ray showed right lung hyperinflation with a shift to the left of the mediastinum. A high-resolution computed chest tomography (HRCT) (; panels A, C) showed mild paraseptal and centrilobular emphysema in both lungs with emphysematous destruction and severe hyperinflation of the right lower lobe. The latter was associated with contralateral mediastinal shift along with complete middle and partial right upper lobe atelectasis. Review of the chest CT performed 1 and 6 years earlier in another hospital showed that the right lower lobe experienced slowly progressive distension. Visual assessment of the HRCT suggested great fissure completeness.
A transthoracic echocardiography was unremarkable, without significant pulmonary hypertension (systolic pulmonary arterial pressure: 40 mmHg).
The patient was deemed to be a good candidate for EBV lung volume reduction and was first included in a pulmonary rehabilitation program. After 3 months of rehabilitation, dyspnoea was mildly improved (grade 2 mMRC) as was the CAT score (26/40). The 6 MWT was unchanged (340 m). Her chest auscultation and PFT were not significantly improved ().
After exclusion of collateral ventilation with the use of the Chartis Diagnostic System (PulmonX Intl, Neuchatel, Switzerland), as previously described [], 2 one-way EBV (Zephyr; PulmonX Intl, Neuchatel, Switzerland; provided by RMS Medical Devices, Roosdaal, Belgium) were placed in the right lower lobe, under general anaesthesia. The post-procedural course was marked by fever 48 hours after valves placement. A chest X-ray showed ground glass opacities in the inferior part of the right lung while the right hemidiaphragm was shifted upwards. The patient was treated with amoxicillin-clavulanate. She rapidly improved and was discharged home on the 7th day without any change in inhaled therapy.
After one month, the patient reported marked improvement. She was no longer limited in her daily-life activities by dyspnoea (dyspnoea mMRC score 0–1). Her CAT score markedly improved (10/20) as did the 6 MWT (399 m). Chest auscultation still revealed diminished breath sounds on the posterior right side but asymmetry was reduced. HRCT showed a marked reduction in the right lower lobe volume (1233 mL versus 3491 mL before treatment) with accompanying right upper lobe re-expansion and disappearance of the mediastinal shift (; panels B, D).
The improvement in PFT was even more remarkable. Indeed, the patient no longer met the GOLD initiative spirometric criteria for COPD () [].
These improvements were confirmed at 4 months and were maintained at the latest control, nearly 3 years after the procedure. The SpO2 measured at rest were stable in the follow-up and the minimal SpO2 during the walk tests remained above 90%. Inhaled steroids were progressively tapered after treatment.
Despite the PFT and dyspnoea improvements, the patient experienced 5 exacerbations requiring ambulatory antibiotic treatment in the 3-year follow-up. |
pmc-6473657-1 | A 22-year-old African-American man presented to the Emergency Department complaining of bright red blood per rectum, diffuse abdominal pain, dark-colored urine, malaise, and 30-pound weight loss in the last month. Bowel habits were unchanged. There was no hematemesis or dysphagia. He also reported vomiting and subjective fevers, but denied dyspnea, cough, night sweats, arthralgia, dysuria, or prior bleeding events. There were no episodes of recurrent infections. His past medical history was unremarkable and he denied taking any medications. He did not report any substance abuse. His sexual history was significant for unprotected same-sex intercourse, with the last encounter two weeks prior to presentation. He reported no recent travels or sick contacts. On physical exam, the patient appeared emaciated and lethargic. There was no pallor, icterus, adenopathy, or rash. Oral examination revealed gingivitis but no thrush or sores. Abdomen was soft and diffusely tender with no distension or guarding. A large, posterior anal fissure was noted on rectal exam with minimal amount of blood. The remainder of examination was unremarkable. No genital ulcers or urethral discharge was noted.
Laboratory studies revealed normal hemoglobin at presentation, but during the course of his hospital stay, he had a significant drop from 14.7 g/dL to 10.3 g/dL over the course of two days (NR 12.9–16.8 g/dL) despite no further bleeding, reaching as low as 8.4 g/dL after the first week. The elevated lactate dehydrogenase of 2100 u/L (NR 85–210 U/L) and slightly increased bilirubin (1.3 mg/dL, NR 0.2–1.2 mg/dL) was suggestive of hemolysis (performed on Beckman Coulter AU 5800). Haptoglobin was found to be low (<6 mg/dL), with a negative direct Coombs test and no schistocytes on the peripheral blood smear. Glucose-6-phosphate dehydrogenase (G6PD) was significantly decreased at 0.4 units/g Hgb (reference range: 4.6 to 13.5 units/gram of hemoglobin). Reticulocyte production index was inappropriately low at 0.48. Vitamin B12 and folate levels were normal, but ferritin was greater than 7500 ng/mL (performed on Beckman Coulter AU 640, NV 23.90–336.20 ng/mL). Platelets were mildly decreased (114 × 103/μL) and white count was within normal limits. He also developed acute kidney injury with creatinine of 1.9 mg/dL upon admission, which resolved two days after fluid resuscitation. Urinalysis revealed a large amount of blood but just one red blood cell per high power field. Urobilinogen was positive and there was also proteinuria 30 mg/dL. Meanwhile he was also worked-up for his abdominal pain with computed tomography (CT) scan, magnetic resonance imaging (MRI), endoscopy, and colonoscopy, all of which were unrevealing.
The patient consented to testing for human immunodeficiency virus (HIV) testing, which revealed positive fourth-generation screening but negative confirmatory results by the western blot technique. Viral load was above the detection limit of two million copies/mL. CD4 lymphocyte count was 456 cells/μL. He was screened for other sexually-transmitted infections with negative hepatitis panel but positive urethral swab for Chlamydia trachomatis and Neisseria gonorrhoeae, for which he received a single dose of ceftriaxone 250 mg and azithromycin 1g. Further infectious work-up that included quantiferon-TB gold, toxoplasmosis serology, and Histoplasma urine antigen were all negative. Epstein–Barr serum DNA and Cytomegalovirus IgM were both negative. The patient received supportive and symptomatic treatment with no blood transfusions. He was started on antiretroviral therapy with dolutegravir, tenofovir alafenamide, and emtricitabine prior to discharge. His hemoglobin remained stable at 7.7 g/dL and his LDH and indirect bilirubin were down-trending after treatment. |
pmc-6473674-1 | An 84-year-old female patient presented to Tokushima University Hospital with only three anterior residual roots in the maxilla and anterior teeth with a bilateral free end saddle in the mandible. Although the crowns in the lower jaw had poor esthetics, the patient was unwilling to receive a revised prosthesis. A treatment plan was devised that involved fitting of a complete overdenture to the maxilla and a RPD to the mandible. Silicone impressions (Exadenture, GC Corporation, Tokyo, Japan) using individual trays and the interocclusal record were obtained according to conventional methods. After trial application of a wax denture, the final denture was made (). The clasp retainer was made of nonfiller type PEEK as follows. First, we scanned the working model with a dental scanner; then, we designed the clasp retainer with CAD software (Geomagic Freeform, 3D Systems, South Carolina, USA) and used a milling machine (RXP500 DSC, Roeders BmbH, Soltau, Germany) to shape the clasp from a PEEK disk (JUVORA Dental Discs, Lancashire, UK) (). Details of form were modified using technical bars, and polishing was performed with silicone points (Shofu, Kyoto, Japan) and a Robinson bristle brush with polishing paste.
The adhered surface of PEEK embedded in a resin base was treated using sand blasting with Al2O3 50-μm particles (HiBlaster Ovaljet, Shofu, Kyoto, Japan). The denture was then molded using a heat-curing acrylic resin (Acron, GC, Tokyo, Japan) with a conventional flask investment method (). Although the clasp apex was primarily positioned in the far zone of the abutment teeth at the fabrication, it was prepared slightly beyond the central line of the abutment at the denture delivery because of the aesthetic problem.
, and show the PEEK clasps two years after delivery. The patient reported that denture had been rinsed under running water after every meal and immersed into a denture cleanser for the night at bedtime. Few color and texture changes were found macroscopically, and denture plaque adherence around the clasp appeared minimal. However, staining with a plaque-disclosing agent revealed clear denture plaque on both the inside and outside of the clasps.
The rest part and the clasp arm still fitted well without any deformation, and the participant reported no particular problem with occlusal contact.
No specific mobility of the abutment teeth, and no specific inflammation of the gingiva around the abutment teeth were found. The subjective operational opinion of the practitioner about wearing and detaching of the denture was also reported as good. |
pmc-6473675-1 | The patient is a 76-year-old woman with right hip OA. Preoperatively, her hip ROMs were as follows (right (R)/left (L)): hip extension −10°/15°, hip flexion 90°/125°, and hip abduction 25°/45°. Hip muscle strength measured by Manual Muscle Testing preoperatively was as follows (R/L): hip extension 4/5 and hip abduction 4/5. Spinomalleolus distance (R/L) was 69.0/71.5 cm. She had difficulty in gait and in performing activities of daily living (ADL), such as changing socks, bathing, stair use, getting in or out of a car, and shopping, because of pain and stiffness of the right hip. Her gait had features of pelvic rotation and anterior pelvic tilt accompanied with pain and restriction of hip extension during the right stance phase. Therefore, she underwent THA. Conventional rehabilitation programs, such as sitting, standing, and gait training using a walker with a physical therapist, were performed at 1 day after surgery according to the clinical pathway in our hospital.
This study was approved by the Ibaraki Prefectural University of Health Sciences Ethics Committee (approval no. e192). Then, sufficient explanation regarding study procedures was provided to the patient prior to obtaining written consent for study participation. |
pmc-6473779-1 | A 41-year-old woman came under our observation to undergo intensive neurorehabilitation due to ischemic stroke. Her family history was negative for neurological disorders. Her personal history was unremarkable, and neither smoking habits nor alcohol or drug consumption were reported. She denied the use of oral contraceptives or other drugs potentially affecting coagulation. Body mass index was within the normal range (a BMI of 23). She had a personal history of migraine, high blood pressure, and nodular thyroid disease. After one month from a miscarriage with intrauterine death of the fetus (at the 26th week of gestation), she presented a thrombosis of the left popliteal vein with pulmonary embolism. A treatment with dabigatran (150 mg/twice a day) was prescribed. One month later, she suddenly presented with difficulty in moving her right limbs and in articulating words. She was then admitted to a Stroke Unit. Neurological examination showed a right deviation of head and eyes, and a left hemiplegia with homolateral dysesthesias (NIH-Stroke Scale score: 15). She then underwent a computed tomography angiography, detecting a right M2 occlusion, with a consequent mechanical thrombectomy. During admission, she was submitted to several investigations, including (i) chemiluminescent immunoassay (CLIA) for the detection of anticardiolipin antibodies (aCL) and enzyme-linked immunosorbent assay (ELISA) for the IgM/IgG anti-b2 glycoprotein I; (ii) functional clotting time-based assay for the determination of the lupus anticoagulant; (iii) transcranial Doppler with microbubble test; and (iv) trans-esophageal Doppler. The immunological tests were performed using the LIAISON® Cardiolipin IgM/IgG CLIA assay and the ETI-Beta 2 Glycoprotein I IgM/IgG ELISA kit (DiaSorin; Sallugia, Italy). The immunological tests were performed using the LA1 Screening Test and LA2 Confirm test by Sysmex South Africa (Pty) Ltd. (Ferndale, Randburg; South Africa).
Specifically, there were high levels of aCL (IgG 764.1 CU—n.v. < 20; IgM 167.90 CU—n.v. < 20), whereas the IgG/IgM antib2-glycoprotein I and lupus anticoagulant were within the normal range. The transcranial Doppler with microbubble test disclosed a right-to-left shunt with a bubble passage > 25 at rest. Finally, the trans-esophageal Doppler showed a patent foramen ovale (2.5 mm × 5 mm). She was therefore switched from dabigatran to acenocumarole (4 mg/daily). At discharge, she presented amaurosis in the right eye, distal weakness at the left upper limb and a left tendon hyperreflexia, with an NIHSS of 3. At one-year follow-up, after a 3-month-rehabilitation, clinical conditions further improved without any sign/symptom of thromboembolism.
The patient gave written consent for publication of the case. |
pmc-6473795-1 | The subject of the study was a 68-year-old male, left-handed and a native of a rural area in Lugo (Galicia, NW Spain). He was single and used to live with his mother until she passed away; he then lived alone until 2014, when he was admitted to a geriatric center close to his town. He has two brothers, a basic level of education, and his profession was agricultural worker.
The study was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from the participant and the legal responsible.
According to the medical records, the patient presented arterial hypertension, hypertensive heart disease, paroxysmal atrial fibrillation, mild kidney failure, diabetes mellitus—type II, cholecystitis, confusional syndrome, dyslipidemia, anxiety disorder, inguinal hernia, and diffuse Lewy bodies dementia (LBD). The patient did not present toxic habits.
The documentation provided by the family in reference to the development, prior to being admitted into our gerontological center, shows an oscillating clinical course, with crisis and a negative development, with difficulties for a neuropsychiatric differential diagnosis and a clear therapeutic approach. In particular, the medical records from December 2014 show admissions in August and November of the same year in relation to “disorientation and behavioral disturbances evolving during these months”, with a hypothetic diagnose of VD vs. Parkinson disease (PD) and treatment with levodopa/carbidopa. During the same month, he showed extreme agitation and escaped from the geriatric center where he used to live. He was, therefore, examined by the Emergency Service of the Hospital Universitario de Lugo (HULA). The examination upon admission suggests that “he is disoriented in time and space, person oriented, hardly cooperative, he employs circumlocutions with partially incoherent speech, irritable, shaky, anxious and presents visual hallucinations”. Admitted in the Psychiatry Service of the same hospital, the examination shows “amnesia about his stay in the institution and about his hospital admission, incoherent speech. Lack of data about hallucinatory—delirious symptomatology. Sleeping and eating disorders. General sense of wellbeing, he ignores the reason for his admission. Unawareness of the disease”. Regarding the evolution in the hospital, the level of consciousness tends to fluctuate, with episodes of visual hallucinations without emotional response, relating situations and images with a high level of detail during periods of a few short minutes. These symptoms are presented without structured delusional ideation.
Following pharmacological adjustment, there is a gradual improvement of the visual hallucinations, but the patient still shows episodes of isolated irritability related to brief confusional states. The patient’s sleep pattern improves, but the noticeable cognitive impairment and functional dependency persists. Following pharmacological adjustment with quetiapine, 150 mg/day, there is a notable worsening of the symptoms of confusion and treatment is therefore suspended, maintaining olanzapine and tiapride.
The patient remains at the hospital for 24 days and, during that time, he is explored using additional tests. New pharmacological adjustment is done with the aim of decreasing the fluctuations in the level of consciousness, a remission of the visual hallucinations, and a decline in behavior alterations. He is referred to the primary-care center for follow-up, and it is recommended that he be re-admitted to a geriatric center, with a diagnosis of LDB in the presence of a progressive cognitive decline, consciousness fluctuations, visual hallucinations, and parkinsonism. Treatment using olanzapine is suggested, 5 mg/night/24 h, and tiapride, 100 mg/8 h. Lorazepam 1 mg is also prescribed, without signs of anxiety or insomnia. The following medications are kept: omeprazole 20, simvastatin 20, acetylsalicylic acid 100, bisoprolol 2.5, doxazosin 4, and insulin Lantus.
Consultation with the Neurology Service for physical examination, concludes that there are signs of rigid-akinetic parkinsonism and risk of falling. Blood test: dementia screening showed normal parameters in hematimetry and biochemistry. Human immunodeficiency virus (HIV) serology, syphilis, hepatitis B & C are negative. Electroencephalography with frequency analysis shows a “daytime NREM I wakefulness and sleep pattern with well-configured, symmetric, normoreactive, with no appreciable anomalies, neither under resting conditions nor during the activations performed. Signs of drowsiness”. Magnetic resonance imaging (MRI) scan includes “exploration performed in sagittal and axial planes in habitual sequences. There is a small spot of increased signal in T2 and flair in the subcortical white matter compatible with small vessel ischemic pathology. No recent ischemic pathology or other significant findings are evident”.
The patient is institutionalized and followed by external consultations with the Psychiatry Service, making adjustments to pharmacological treatment in accordance with the symptomatology. He visits the HULA emergency department as a result of behavioral changes and aggressive behaviors. At that time, he was treated with lorazepam 1 mg/24 h, olanzapine 15 mg/24 h, and clonazepam 1.5 mg/24 h. Tiapride solution is added in case of agitation.
Re-admitted to the Psychiatry Service due to an episode of agitation and aggression in the institutional environment. At that time, he was treated with rivastigmine 4.6 mg/24 h, clonazepam 4.5 mg/24 h, and clozapine 100 mg/24 h, given the therapeutic failure and the apparent paradoxical response with quetiapine, olanzapine, risperidone, haloperidol, and tiapride, in addition to the treatment for heart diseases and diabetes. During the hospitalization, the patient lacks awareness of the disease. He is restless, requiring physical restrictions and also hypoprosexic. No alterations are detected in the course or content of thought, although his spontaneous speech is not very fluid and is of a repetitive nature.
The pharmacological adjustment with rivastigmine 9.5 mg/24 h and the decrease in clonazepam due to somnolence, associated with clozapine up to 150 mg/24 h, seems to partially improve the BPSD, although the presence of low-grade fever and leukocytosis suggest the progressive withdrawal of clozapine. Gabapentin 400 mg/24 h is introduced in order to mitigate the psychomotor restlessness and behavioral alterations, with an excellent response, leading to a referral to the geriatric center where he remained until his transfer to the current gerontological center. On the day of his referral, the treatment continued with rivastigmine 9.5 mg/24 h, lorazepam 3 mg/24 h, trazodone 100 mg/24 h, clonazepam 1 mg/24 h, and gabapentin 400 mg/24 h.
During the following 6 months, there are oscillations in his cognitive functions and in his CBs, presenting nocturnal agitation, wandering, and disorganized motor behaviors, hostility, insomnia, anxiety, as well as hyperorality, constant verbalization related to food and sexual disinhibition. This symptomatology demands modifications in the pharmacological treatment with variable responses. At the end of November, he is evaluated by the Psychiatry Service, which prescribe rivastigmine 9.5 mg/24 h, trazodone 100 mg/24 h, clonazepam 1 mg/24 h, olanzapine 10 mg/42 h, and quetiapine 100 mg/24 h, withdrawing lorazepam and gabapentin. |
pmc-6473802-1 | A 39-year-old Eritrean male was referred to the Division of Respiratory Medicine and Allergy of the Karolinska University Hospital in Stockholm, Sweden, due to fatigue, fever at nights, loss of weight and appetite, general body pain and interstitial lung abnormalities at the radiology. He had previously suffered from a myocardial infarction in his home country three years before and also had type two diabetes, hypercholesterolemia and hypertension. He was a smoker (15 pack years at the time of referral) and had no specific occupational exposure. The family history of interstitial lung diseases was unknown since the patient had no contact with his family in Africa. He was not aware of any respiratory disease in his family. Physical examination revealed inspiratory and basal crackles. Rheumatoid factor as well as C–reactive protein, hematology laboratory tests and liver function were unremarkable. Computed tomography (CT) showed bilateral, peripheral, reticular changes and ground glass opacities concentrated mostly basally, additionally a five centimeter’s hiatal hernia; the CT-scan was initially identified possible UIP–pattern (A). Pulmonary function tests (PFT) showed a vital capacity (VC) of 74 per cent of the predicted level, forced expiratory volume in one second (FEV1) of 74 per cent of the predicted level and a diffusion capacity of carbon monoxide (DlCO) 72 per cent of the predicted level (). The patient underwent a bronchoscopy with no macroscopic findings; no infection from common or atypical pathogens were found in the cultures from bronchial samples. Bronchioalveolar lavage (BAL), performed according to standard procedures in the middle lobe, showed very few lymphocytes and a CD4/CD8-ratio of two, other results were also unremarkable. A treatment with proton-pump inhibitors was prescribed, due to the presence of reflux, but the patient did not continue with the prescribed drugs. The patient missed the follow–up visits, and was therefore discharged from the outpatient clinic.
He presented again three years later to our service due to general illness and productive cough. Unfortunately, he was still smoking. Physical examination revealed crackles as previously prescribed but also mild clubbing. A new CT-scan showed a basal, subpleural interstitial pattern with honeycombing and traction bronchiectasis but also dominating ground-glass-opacities in the same areas. Progress compared to the pattern three years earlier was seen with, according to the radiologist, a pattern more compatible with an atypical UIP or a non–specific interstitial pneumonia (NSIP) (B). Pulmonary function tests showed an unchanged VC of 79 per cent, FEV1 of 80 per cent but a clearly deteriorated DlCO of 58 per cent of the predicted level (). At this time point, the patient was also screened for autoantibodies (including antinuclear antibodies and anti-neutrophil cytoplasmic antibodies) and HIV, which were all negative. The patient went through another bronchoscopy and BAL, again with, unremarkable findings. The case was discussed at a multidisciplinary team conference (MDC) and a decision to go further with a video-assisted thoracoscopic (VATS) biopsy was made.
Two biopsies, one from the right upper lobe and one from the right lower lobe, showed a pattern of interstitial and fibrotic changes with heterogeneous characteristics (). A new MDC (with the presence of a skilled pathologist) made a diagnosis of atypical idiopathic pulmonary fibrosis (IPF) and the patient was started on an antifibrotic treatment with pirfenidone.
Since the start of this therapy, the disease had a slower progression compared to the period before the diagnosis (). Nevertheless, PFT showed deterioration of lung function over time, with a drop of 19%, 15% and 25% for the VC, FEV1 and DlCO over a time period of seven years. In CT-scan, a clear UIP–pattern developed over time, with traction bronchiectasis, honeycombing and progression of the reticular abnormalities in the lower lobes (C,D). The patient was considered clinically relatively stable at the last follow-up visit in autumn 2018. |
pmc-6474052-1 | Case 1: The patient was a 51-year-old non-smoking woman with a 68-month history of RA. Before tofacitinib was administered, she had been treated with prednisolone (PSL, 10 mg/day) and bucillamine (BUC, 200 mg/day) for 13 months and was then switched to receive the recombinant humanized anti-human IL-6 receptor monoclonal antibody tocilizumab (TCZ, 8 mg/kg, every 4 weeks) intravenously. Under this treatment, her disease activity score in 28 joints using C-reactive protein (DAS28-CRP) was well controlled as follows: from 3.8 (the baseline) to 2.5 (after 4 months of treatment). However, TCZ was discontinued after 4 months due to signs of pneumonia in the right lung. She was then switched to the fully humanized anti-TNF-α monoclonal antibody adalimumab (ADA, 40 mg/2 weeks) subcutaneously, which resulted in a well-controlled DAS28-CRP for 34 months as follows: from 3.9 (the baseline) to 1.4 (after 34 months of treatment). She was then transferred to a local rheumatology clinic and showed a similar RA condition for 8 months with 5 mg/day of PSL and 12 mg/week of methotrexate (MTX). However, she returned to visit to the Niigata Rheumatic Center with joint pain and swelling. Her CRP levels were gradually raised and at the last visit of that clinic, it was 3.45 mg/dL. The clinical and laboratory assessments at our rheumatic center revealed DAS28-CRP 4.32 and global visual analogue scale (gVAS) 28, possibly due to the secondary failure of the response to ADA treatment. Two weeks later, we evaluated her periodontal condition and started the administration of tofacitinib (10 mg/day) according to the European League Against Rheumatism recommendations for the management of RA []. For some reason, her CRP level was decreased to 0.1 mg/dL, but her gVAS was worsened to 51 (Table ). The patient had no complications, such as hypertension or systemic viral infections, at baseline.
The rheumatologic assessments showed a decrease in the simplified disease activity index (SDAI) and gVAS at reassessment after starting tofacitinib therapy (Table ). In addition, the laboratory analyses of blood samples showed that the serum levels of anti-cyclic citrullinated peptide (CCP) immunoglobulin G (IgG), TNF-α, and IL-6 were decreased at reassessment compared to the values at baseline (Table ).
Furthermore, the periodontal assessments indicated that the patient had localized moderate chronic periodontitis at baseline according to the criteria of the Centers for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) [] (Fig. a). Tofacitinib therapy reduced periodontal inflammation as indicated by the mean values of the gingival index (GI), probing depth (PD), and clinical attachment level (CAL), as well as the percentage of sites with bleeding on probing (BOP) and of those with PD and CAL of ≥4 mm at reassessment, although the teeth count and supragingival bacterial plaque level as defined by the plaque control record (PCR) were relatively unchanged after tofacitinib therapy (Fig. b and Table ). |
pmc-6474052-2 | Case 2: The patient was a 43-year-old non-smoking woman with a 39-month history of RA. Before tofacitinib was administered, she had been treated with MTX (4 mg/week) and BUC (100 mg/day), and the DAS28-CRP was well controlled for 29 months as follows: from 2.0 (the baseline) to 1.2 (after 29 months of treatment). However, because of the lack of a response to the treatment with MTX and BUC, the further administration of tofacitinib (10 mg/day) was started. The patient had no complications, such as diabetes mellitus, hypertension, or systemic viral infections, at baseline.
The rheumatologic assessments showed a decrease in the SDAI, DAS28-CRP, tender joint count (TJC), swollen joint count (SJC), and gVAS at reassessment after starting tofacitinib therapy (Table ). The laboratory analyses of blood samples showed that the serum levels of rheumatoid factor (RF), matrix metalloproteinase-3 (MMP-3), and IL-6 were decreased at reassessment compared to the values at baseline (Table ).
Furthermore, the periodontal assessments indicated that the patient had localized moderate chronic periodontitis at baseline according to the criteria of the CDC/AAP []. Tofacitinib therapy reduced periodontal inflammation as indicated by the mean values of the GI, PD, and CAL, as well as the percentage of sites with BOP and of those with PD and CAL of ≥4 mm at reassessment, although the teeth count and supragingival bacterial plaque level as defined by the PCR were relatively unchanged after tofacitinib therapy (Table ). |
pmc-6474053-1 | A 36-year-old man, originally from Latin America, presented at our outpatient department with complaints of abdominal pain that had persisted for 2 months. The patient had first noticed right lateral abdominal pain 2 months prior to the visit, and the pain was gradually worsening. The abdominal pain was localized in an area ranging from the right upper to the right lateral abdomen. The patient had undergone cholecystectomy for acute cholecystitis as a 32-year-old in Latin America and had moved to Japan for work approximately 3 years prior to his initial visit to our hospital. He had returned to Latin America once about 6 to 7 months before presenting at our clinic. When he went back to Japan, his weight had increased from 130 kg to 145 kg. He did not experience abdominal pain immediately after his return to Japan, but, as noted above, he started to gradually feel pain in the right lateral region about 2 months prior to presentation.
He first visited another hospital emergency department 1 month after onset of the pain. Initially, gastrointestinal tract spasm was suspected, and he was treated with tiquizium bromide. Though the medication partially relieved his abdominal pain, most of the pain persisted. The result of a workup by a urologist was negative, even though nephrolithiasis was suspected. His abdominal pain was exacerbated upon changing posture, and thus it was suspected to be of somatic rather than visceral origin. Abdominal pain persisted despite treatment with loxoprofen sodium hydrate, and any cause of abdominal pain was not detected on further evaluations, including hematologic laboratory analysis, urine analysis, gastroscopy, or abdominal computed tomography (CT). Finally, he was referred to our hospital for further examination.
The results of screening for depression were negative, and the patient did not have symptoms such as loss of interest, depressed feelings, or any specific changes of surrounding conditions, such as family or work environment changes. He had no history of sexually transmitted infection, and his vital signs were within normal limits. His physical examination result was positive for Carnett’s test, and a prior surgical scar of approximately 18 cm was apparent at the right subcostal region. The patient experienced strong pain surrounding the surgical scar that was exacerbated by tapping. There were no skin rashes localized surrounding the pain. His pain exacerbated to 8 on a pain scale when he moved, such as during standing up or rolling over simultaneously. When he stopped moving, pain was partially relieved within 1 minute (3 on a pain scale). When he moved again, abdominal pain was again exacerbated. Hence, he was awakened by the abdominal pain when rolling over. No inflammation was detected (leukocyte count was 8580/mm3 and C-reactive protein was 0.10 mg/dl), and other laboratory findings were nonspecific, including liver/kidney function, blood glucose, and electrolytes. Urinary analysis indicated red blood cell count < 1/high-power field, white blood cell count 1–4/high-power field. Additionally, no abnormality was detected for Chlamydia trachomatis IgG/IgA, and no abnormality was apparent on the electrocardiogram. Enhanced CT revealed bilateral renal stones and fatty liver.
We first considered abdominal wall pain due to nerve entrapment because the Carnett’s test result was positive; therefore, we scheduled a trigger point injection at the site of tenderness. About 2 weeks later, the patient visited the emergency department of our hospital, reporting that his prior abdominal pain had decreased but that he was experiencing right inguinal pain. Loxoprofen administration had no effect on the pain. Costovertebral angle pain was apparent on tapping, the result of urine analysis was positive for occult blood, and abdominal CT revealed a urinary stone at the right urinary duct to the bladder. After pentazocine hydrochloride was administered for pain relief, the urinary stone was passed the following day. However, the patient’s right lateral abdominal pain was not relieved.
He felt that lying in the lateral position mostly relieved his pain. He had occasional vomiting. The abdominal pain was exacerbated by movements, such as rolling over, standing up, walking, and coughing. Injection of 1% xylocaine 10 ml at a trigger point of the right lateral region led to about 30% relief in pain. The patient was referred to an anesthesiologist for further evaluation and treatment, who performed transverse abdominal plane block and administered multiple analgesic medications (tramadol hydrochloride, pregabalin, celecoxib, and scopolamine butylbromide). These medications decreased the patient’s pain somewhat, and he reported that scopolamine butylbromide was most effective when the pain worsened. Because the patient’s symptoms were not relieved after trigger point treatment to the abdominal wall, we considered potential causes that might be associated with the location between the abdominal wall and visceral wall or related to other sources, including psychosocial, physiological, and other anatomical factors. We rechecked the abdominal CT scan for a suspected adhesion or abdominal hernia at the region of tenderness due to the prior surgical procedure, and we asked a radiologist to reevaluate the right upper abdomen in more detail. The radiologist confirmed a slight abnormality in the right upper abdomen and suggested the possibility of an adhesion around the surgical scar (Fig. ). We referred the patient to a gastrointestinal surgeon for laparoscopic evaluation and adhesiolysis. The patient underwent additional investigations, including cholecystocholangiography and colonoscopy for suspected postcholecystectomy syndrome, biliary dyskinesia, or colon abnormality. However, no cause of the abdominal pain was identified. On laparoscopic evaluation, a broad adhesion was observed. Adhesiolysis was performed 6 months after the patient first visited our hospital. Figure a shows adhesion between the peritoneum and omentum, liver, and ascending colon; Fig. b shows the condition after adhesiolysis. One month after adhesiolysis, the patient’s right abdomen pain level during movement improved from 8 to 2–3 on a pain scale. Therefore, he was able to move with less pain, and he did not feel pain when rolling over. The result of Carnett’s test was negative. After the patient started walking around his house, he felt abdominal pain about 5 minutes after walking. Hence, he was afraid of recurrence of abdominal pain and felt a little depressed and frustrated because he was unable to return to work early. We recommended a gradual increase in activity. He went on a trip 4 months after the operation without problems due to abdominal pain and then resumed his job 6 months after the operation.
However, his abdominal pain deteriorated within 1 month after he resumed working. He presented with bleeding at the umbilicus, which was the laparoscopic port site, and abdominal incisional hernia was confirmed on the basis of CT. Repair of the abdominal incisional hernias and laparoscopic adhesiolysis were performed 8 months after the first operation. After the second operation, although it took time for some symptoms to improve because of surgical site infection, the patient’s symptoms were ultimately relieved, and he resumed his job again 5 months after undergoing the second operation. Although he reported mild abdominal pain and required analgesic medication, his weight decreased to 133 kg, and he was able to walk normally and work full-time, 2 years after he initially visited our hospital. The timeline of interventions and outcomes is shown in Additional file . |
pmc-6474058-1 | A 74-year-old male retired accountant with a background of asthma, atrial fibrillation, and gout presented to our emergency department with syncope following an insidious 6-month history of systemic symptoms. He had had intermittent fevers, 15-kg weight loss, general malaise, regular diaphoresis that occurred day and night, nausea, vomiting, diarrhea, and a nonproductive cough with sporadic morning hemoptysis. His exercise tolerance had reduced from unlimited walking capacity to breathlessness after roughly 2 km. His medications included rivaroxaban, verapamil, digoxin, and fosinopril. He had received a short course of prednisolone 25 mg daily for a flare of gout 3 weeks prior. He had a 50-pack-year ex-smoking history, having given up smoking 30 years prior. He lived independently with his wife. He had undergone outpatient chest computed tomography (CT) 2 months earlier that showed consolidation in the left lower lobe and a peripheral opacity in the right lung base measuring 14 mm by 12 mm. He had received several courses of oral antibiotics, including amoxicillin for 10 days and doxycycline for 2 weeks for presumed pneumonia. Because of his ongoing cough, he had a repeat CT scan 1 month later that showed resolution of the consolidation but no change in the peripheral opacity. His general practitioner had then referred him to a respiratory specialist, who felt that his illness was in keeping with a pneumonia that was now resolving. He advised withholding fosinopril, cessation of antibiotics, repeat CT scan in 3 months, and follow-up in 3 weeks. Prior to this appointment, he had had the syncopal episode that led to this presentation.
On arrival to the emergency department, he felt washed out, with vital signs that were notable for low-grade fever of 38.3 °C, sinus tachycardia to 130 beats per minute, and fluid-responsive hypotension (82/45 mmHg), and his physical examination was largely unremarkable. Investigations revealed a white blood cell (WBC) count of 10.6 × 109/L (neutrophil count 9.1 × 109/L, lymphocyte count 0.9 × 109/L), C-reactive protein (CRP) 119 mg/L (normal range 0–5 mg/L), Streptococcus mitis on blood cultures (penicillin minimum inhibitory concentration [MIC] 0.030 mg/L [susceptible = MIC < 0.5 mg/L]), and transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) demonstrating a mobile 30 × 25-mm vegetation on the PV that extended into the right ventricular outflow tract (Figs. and ). Complete destruction of the anterior cusp with severe pulmonary regurgitation was seen. Initial management included intravenous benzylpenicillin and gentamicin for a total of 4 and 2 weeks, respectively. A surgical opinion was obtained, but a trial of medical management was advised. The patient felt better, and his inflammatory markers normalized.
Two months after antibiotic cessation, the patient still felt well, with a normal WBC count and CRP of 5.3 mg/L (normal range 0–5 mg/L). Cardiac and chest imaging was performed to check resolution of lesions. TTE showed a reduction in the PV vegetation to 29 × 9 mm. A follow-up chest CT scan, however, showed new nodular lesions thought to be due to embolization (Fig. a), suggesting persistent endocarditis. Repeat blood culture results remained negative.
After 3 months, he again began to feel lethargic with breathlessness on exertion. His examination was unremarkable, but his WBC count was 16.1 × 109/L and CRP was 182 mg/L. Results of five sets of blood cultures were negative, and the vegetation size had improved on TTE to 23 × 10 mm. He was then started on a 2-week course of amoxicillin and clavulanic acid. Again he began to feel well, with improvement in his CRP and WBC count, so he was discharged to home.
Repeat outpatient CT of the chest 1 month later showed new lesions, including a cavitating lesion (Fig. b). In light of the recurrent lung lesions, he underwent surgical PV replacement. His PV had been destroyed with a perforated anterior leaflet that was completely encompassed by a large vegetation. The other leaflets were untouched. After valve and vegetation excision, a 27-mm Carpentier-Edwards PERIMOUNT tissue valve (Edwards Lifesciences, Irvine, CA, USA) was inserted. Histology confirmed IE with expansile inflammatory masses composed of fibrin and neutrophils. Small clusters of degenerate bacterial cocci were noted, but a valve culture revealed no growth. The patient made a good recovery on intravenous benzylpenicillin and oral clindamycin. TTE showed a normal-functioning bioprosthetic PV. Over the following weeks, the patient’s radiographic and inflammatory markers normalized. |
pmc-6474063-1 | A 40-year-old Hispanic woman, with a history of obesity, a body mass index (BMI) of 32, and hypertension, presented to our emergency department (ED) complaining of squeezing bifrontal headache for 3 days. Her headache started gradually, had a progressive course, and was associated with nausea, vomiting, dizziness, transient visual disturbances in her right eye, and a feeling of both her ears being clogged. A day prior to the presentation, she started to feel numbness and weakness of the right side of her face, along with an inability to close her right eye properly. She denied having diplopia, loss of vision, photophobia, tinnitus, or any feeling of weakness, numbness, or tingling in other locations of her body. She had no history of migraine headaches, tick bite, or any recent illness or fever. She was not taking oral contraceptive pills at the time.
On initial evaluation, she was hemodynamically stable and afebrile. On neurological examination, she was fully alert and oriented, and had fluent speech and intact comprehensive abilities. There were no signs of meningeal irritation. CN testing revealed: 3–4 mm pupils that were equal in size and reactive to light and accommodation; intact extraocular movements with no nystagmus, saccadic movement or skew; and full visual fields. No signs of abducens nerve palsy were present. However, there was facial asymmetry evident by right lower facial droop, weaker right eye closure, and limited ability to raise the right eyebrow. Facial sensation, on the other hand, was equal on both sides, with a strong jaw opening and a midline tongue of good power. In addition, shoulder shrug was symmetrical, and hearing was intact. A fundus examination revealed bilateral grade I–II papilledema. The rest of her neurological examination, including motor function, sensation, reflexes, coordination, and gait analysis, was within normal limits.
She underwent a computed tomography (CT) scan of her head that showed some right-sided pontomedullary hypodensity. Brain magnetic resonance imaging (MRI) with magnetic resonance venography (MRV) revealed a stenosis in the lateral aspect of the transverse sinus, a partially empty sella turcica, and a picture of mild papilledema, findings consistent with ICP (Fig. ). A lumbar puncture (LP) produced CSF with an opening pressure of 28 cm, which is above the limit of the reference interval. The cytological and chemical findings of the LP were otherwise within normal limits: white blood cells (WBCs) 2, lymphocytes 100%, protein 24, red blood cells (RBCs) 13, and glucose 58. She was initially treated with intravenously administered 25 mg diphenhydramine and 10 mg metoclopramide along with 500 ml intravenous normal saline 0.9% (IVF) and her headache subsequently subsided. She was also started on prednisone 60 mg daily for 5 days and 500 mg of acetazolamide twice daily. Two days later, she reported a dramatic improvement in both the headache and the facial nerve palsy. A week later, she attended our clinic for a right facial nerve examination, which was completely normal. |
pmc-6474392-1 | An 8-year old boy with DS was referred to the DS outpatient care unit of the Bambino Gesù Children's Hospital for progressively impaired gait and signs of early puberty.
During neurological examination, a slight asymmetrical gait pattern was noted. This anomaly was firstly attributed to the general motor clumsiness typical of DS patients. When evaluating sexual development, a Tanner Stage of P2G2 was observed, with a bilateral testicular volume of 8 ml. To confirm the clinical suspect of early puberty, Gonadotropin-releasing hormone (GnRH) stimulation test was performed. The results showed: basal FSH of 0.7 mIU/mL and after LHRH administration: 3.78 mIU/mL; basal LH was 1.3 mU/mL, and after stimulation: 20.11 mU/mL; Testosterone basal level was 54.5 ng/dL, PRL, beta-HCG, DHEAS and thyroid function were all normal. These results confirmed the suspect of an early puberty of central origin and a brain Magnetic Resonance Imaging (MRI) was then performed. The brain imaging showed diffused pathological tissue, extending from the left diencephalic region and involving the cerebral peduncle caudally, the basal ganglia region cranially (globus pallidus, putamen and posterior arm of the internal capsule), the outer capsule laterally, the temporo-mesial cortex and subcortical white matter, which extended deeply to the anterior portion of the temporal lobe, to the optic chiasm and bilateral retrochiasmatic tract ().
The patient underwent partial resection of the lesion and the histopathological examination was compatible with the diagnosis of WHO grade II Pleomorphic Xanthoastrocytoma. BRAF p.V600E mutation was then assessed by immunohistochemistry () and through Sanger sequencing of the BRAF gene, revealing positive. Based on these results, after the parents of the patient provided formal, informed consent and the therapy was approved by Institutional Review Board, treatment with the BRAF p.V600E inhibitor Vemurafenib was started. Initially, the lower dose proved to be active in adults was administered (i.e., 240 mg/day per os twice a day) and was later increased to 480 mg twice a day. After 32 months the therapy was discontinued, and the disease remained stable 3 months after the stop therapy.
The only side effect reported was a transient follicular truncal rash in the first month of administration with fickle subcutaneous nodules, treated with local topical corticosteroids. No ECG changes or/and suspected skin lesions developed.
A new brain MRI after 6 months of therapy demonstrated an important reduction of the lesion and a substantial reduction of enhancement, the last MRI (30 months after diagnosis) demonstrated a stable disease ().
Clinical response, with gait and movements improvement, was also noted shortly after the beginning of therapy. |
pmc-6474780-1 | A previously healthy 73-year-old man presented to the emergency department after a motor vehicle collision. Computed tomography (CT) of the chest, abdomen, and pelvis demonstrated a 2.0 × 2.4 cm left lower lobe pulmonary nodule with endobronchial extension and a 2.5 × 2.1 cm right-sided kidney mass (Fig. ). He was a life-time non-smoker and reported only occasional alcohol intake. He worked as a mechanic all his life. His only complaint was a cough, productive of yellow sputum without haemoptysis. He denied any fever, dyspnoea, weight loss, or night sweats. Positron emission tomography (PET) scan demonstrated a standardized uptake value (SUV) of 3.5 for the lung nodule and 5.1 for the renal mass.
Flexible bronchoscopy demonstrated a large endobronchial polypoidal mass lesion within the left mainstem bronchus. Forceps biopsies and fine-needle aspirates were non-diagnostic and demonstrated only necrotic tissue. The patient was advised to undergo a repeat bronchoscopy with cryobiopsies under general anaesthesia. However, he declined any additional sampling. He was also evaluated for thoracic surgery and refused resection of the lung mass. He presented 1 year later with worsening of cough and new-onset dyspnoea. Repeat imaging demonstrated significant increase in his left-sided pulmonary nodule (8.5 × 7.5 × 8.5 cm) with stable renal mass (2.0 × 2.0 cm). Our leading diagnosis was metastatic renal cell carcinoma (RCC) given the presence of a kidney mass on imaging. A CT-guided biopsy of his left lower lobe lung mass was performed, and that demonstrated monotonous, densely cellular spindle cells in a vaguely fascicular pattern (Fig. ). It stained strongly positive for BCL-2, vimentin, and transducin-like enhancer of split 1 (TLE1), which is characteristic of synovial sarcoma (Fig. ). Polymerase chain reaction (PCR) demonstrated the presence of an SS18-SSX1 fusion confirming the diagnosis. He underwent a video-assisted thoracoscopic surgery (VATS) sleeve lobectomy with lymph node dissection, which was negative for metastatic disease.
Our patient did well post-lobectomy. He subsequently underwent partial nephrectomy, with pathology demonstrating RCC. Follow-up imaging five months after surgery showed no residual disease in the chest, abdomen, or pelvis. |
pmc-6475104-1 | An 85-year-old Caucasian woman presented to our hospital with right flank pain 10 years ago. She had a past medical history of type 2 diabetes mellitus and essential hypertension. She denied any history of thyroid disease and neck irradiation. She had no family history of any cancer. She was a housewife and had no history of tobacco smoking or consuming alcohol. A physical examination at the time of presentation was not significant except for right costovertebral angle tenderness. Her heart rate was 96 beats per minute and blood pressure was 155/90 mmHg. The findings of laboratory tests, which were complete blood count, liver and renal function tests, and urine analysis, were within normal range and they did not help us find the etiology of her right flank pain. Abdominal screening with computed tomography (CT) revealed a mass on her right kidney, which was considered a primary renal cell carcinoma and she underwent a right nephrectomy. Unexpectedly, PTC metastasis was diagnosed from demonstrative histopathological findings, such as positive immunoperoxidase staining for thyroglobulin (Tg). After further examinations of her thyroid and neck with ultrasonography (USG), a total thyroidectomy was performed. Pathological examination of thyroid tissue revealed a 5 cm tumor with capsular invasion and a strong positive immunoperoxidase staining of cytokeratin-19, HBME-1, and galectin-3. She was diagnosed as having metastatic PTC. Orally administered levothyroxine 75 mcg daily was initiated in addition to the metformin 1000 mg twice daily and amlodipine 10 mg daily treatments she received prior to PTC diagnosis. Postoperative serum Tg was above 300 ng/ml and anti-Tg was negative. Afterward, she was screened with unenhanced thoracic CT and skeletal scintigraphy. They revealed bilateral multiple nodules in her lungs and bone metastasis on T10 vertebra and right sacroiliac joint. Initially, 30 Gy radiotherapy was implemented to her T9–10 vertebrae for 12 days. We also started treating her with L-thyroxine to keep her thyrotropin (TSH) level below 0.1 mIU/L. After 2 months, she was treated with 200 mCi RAI for ablation. A RAI whole body scan (WBS) showed extensive RAI uptake in lungs and bones. A second 200 mCi RAI was applied 8 months after the first treatment. A post-ablative WBS showed progression. Serum Tg was still above 300 ng/ml and 200 mCi RAI administration was applied for the third time. A WBS was still displaying high radioactive activities in multiple areas of her body. Because of the existence of increased uptake, we planned a fourth RAI treatment but our patient was lost to follow-up for 2 years.
When she presented again in 2015, her serum Tg was above 300 ng/ml again and a fourth 200 mCi RAI WBS of our patient was done. Unexpectedly, the WBS revealed diminished RAI uptake compared with the previous ones (Fig. ). However, a neck USG showed two solid thyroid nodules at the previous thyroid area and bilateral lung metastases were identified by thoracic CT. For the next 3 years, she was lost to follow-up, again. Finally, in February 2018, she was referred to our clinic and presented with a huge hemorrhagic draining cervical mass (Fig. ). Of interest, besides this finding, she did not have any other complaints other than a little dyspnea when lying down. Summing up all previous RAI treatments, cumulative 800 mCi RAI was given to her in the past 10 years; however, a physical examination and screening findings were not yet promising at the last follow-up (Fig. ). Eventually, considering her elderly age, harboring multiple metastases, and the absence of severe complaints, we planned radiotherapy to the giant mass on her neck. After applying radiotherapy, she was lost to follow-up again and at the end of the year her sons reported that she was dead. |
pmc-6475105-1 | A 60-year-old Japanese man was referred to our hospital for evaluation of severe bone pain and pathological fracture of the neck of the right femur. He had been receiving treatment for chronic hepatitis B with lamivudine (100 mg/day) and ADV (10 mg/day) since December 2006. In June 2013, he noticed low-back pain and then developed severe pain in the right hip. One month later, he also developed pain of the great toe during walking and was referred to an orthopedic surgeon at our hospital. Fracture of the neck of the right femur was found, despite no history of trauma (Fig. ). In addition, 99mTc-hydroxymethylene diphosphate scintigraphy revealed significantly abnormal uptake in the bilateral ribs, hips, and knees (Fig. ). In August 2013, he was referred to our outpatient clinic for evaluation of multiple pathological fractures.
On examination, his body mass index was 18.0 kg/m2, temperature was 36.7 °C, blood pressure was 151/86 mmHg, and pulse rate was 67 beats/min (regular). He had generalized bone pain and gait disturbance. His past medical history was appendicitis in 1967 and stomach polyps in 2011. In his family medical history, there was pancreatic cancer, but there was no liver disease. His regular medications were adefovir and ursodeoxycholic acid. He had smoked three packs of cigarettes per day for 30 years, but he had quit since 51 years old. He drinks 350 ml/day of beer. Laboratory tests showed marked elevation of alkaline phosphatase (ALP) (1223 U/L), as well as hypophosphatemia (1.9 mg/dl) and mild hypocalcemia (8.5 mg/dl). His serum creatinine was slightly elevated, whereas serum 1α,25(OH)2 vitamin D3 was relatively low at 26.4 pg/ml (reference range, 20.0–60.0 pg/ml) (Table ).
Urinalysis showed glycosuria (2+) and proteinuria (1+). Urinary β2-microglobulin was markedly elevated at 138,885 μg/g creatinine (Cr), and tubular reabsorption of phosphate was significantly decreased to 41.59% (reference range for percentage tubular reabsorption of phosphate, 80–94%) (Table ). On the basis of these results, we diagnosed hypophosphatemic osteomalacia secondary to Fanconi syndrome caused by ADV therapy.
Dual-energy X-ray absorptiometry showed an extremely low bone mineral density with a mean lumbar T-score of − 3.6 SD. Several bone resorption markers were highly elevated (urinary cross-linked N-telopeptide of type I collagen, 216.1 nmol bone collagen equivalents/mmol; urinary deoxypyridinoline, 6.7 nmol/mmol Cr; serum tartrate-resistant acid phosphatase 5b, 781 mU/dl) (Table ). Taken together, these findings suggested that the patient had excessive bone resorption combined with hypophosphatemic osteomalacia.
To treat his condition, we first reduced the dose of ADV from 10 mg daily to 10 mg every other day and administered calcitriol (1.0 μg/day) because he had both hypophosphatemia and mild hypocalcemia. In October 2013, he underwent prosthetic replacement of the head of the right femur. However, his generalized bone pain was not relieved by these measures, and several bone resorption markers remained very high, as did serum ALP despite treatment for osteomalacia. In June 2016, we added denosumab (60 mg subcutaneously), a human monoclonal antibody that inhibits RANKL, to ongoing vitamin D therapy in an attempt to suppress persistently high bone resorption. Two months after initiation of denosumab, his hip and knee pain were relieved, along with a decrease in serum ALP and several bone resorption markers (Figs. and a–c). Urinary β2-microglobulin decreased gradually after addition of denosumab to vitamin D3. After 9 months of denosumab treatment, the patient’s mean lumbar T-score increased from − 2.0 SD to − 1.4 SD (Fig. d). We administered denosumab 60 mg every 6 months, and currently he continues to receive denosumab. |
pmc-6475524-1 | Our patient was a 51-year-old Japanese man who had undergone a left total nephrectomy for RCC 10 years ago. Four years later, he experienced back pain. Apart from sustained ankle clonus bilaterally, results of his physical examination were within normal limits. Magnetic resonance imaging and computed tomography (CT) of the spine revealed spinal metastases involving the T1–T3 vertebrae, with a pathological fracture of T2 causing spinal cord compression. Metastases were also detected in the right adrenal gland, sternum, left clavicle, and sacrum (Fig. ). The pathology results of a CT-guided biopsy specimen of the T2 vertebral lesion were consistent with mRCC. Spinal metastases in this patient were classified as grade III according to Enneking classification, type 6 according to Tomita classification, and zones 4 to 9, layers A to D, according to Weinstein-Boriani-Biagini classification with a Spine Instability Neoplastic Score of 16, which indicated instability. The patient was treated with zoledronic acid 4 mg/month. One month after the diagnosis of spinal metastases, a TES with reconstruction—using a cryo-treated tumor-bearing bone graft—was performed.
TES was performed using a single posterior approach. The first, second, and third ribs were resected on both sides. The lower half of the C7 lamina was removed to expose the superior articular facet of T1. The posterior elements of the T1–T3 vertebrae were removed via pediculotomy using a flexible multifilament thread wire (T-saw; Pro Medical, Kanazawa, Japan). The cut surface of the pedicles was sealed with bone wax for hemostasis and to minimize tumor cell contamination due to the involvement of the T2 pedicles by the tumor. The T2–T3 nerve roots were ligated and cut bilaterally; the T1 nerve roots were preserved. Blunt dissection was performed around the T1–T3 vertebral bodies and C7/T1, T1/T2, T2/T3, and T3/T4 intervertebral discs. Bilateral pedicular screws were inserted and affixed to a rod from C7 to T5. An L-shaped chisel was used to cut through the C7/T1 intervertebral disc, and a T-saw was used to cut through the body of T3. The T1, T2, and upper half of the T3 vertebral bodies were removed en bloc. The tumor and soft tissues such as the ligaments, disc, and cartilage were removed from the excised tumor-bearing bone. The excised tumor-bearing bone was then immersed in liquid nitrogen at − 196 °C for 20 min, cut into small pieces, and packed into a titanium mesh cage. The cage then replaced the removed vertebrae, and, after being fixed to another rod, was slightly compressed by posterior instrumentation.
The pathological findings of the affected vertebrae were consistent with a diagnosis of modified International Society of Urological Pathology grade 2 metastatic clear cell RCC (Fig. ).
Blood samples were collected from the patient before undergoing surgery and 1, 3, 6, and 12 months thereafter. Serum interferon (IFN)-γ and interleukin (IL)-12 concentrations were measured. The preoperative IFN-γ concentration was 133.0 IU/ml, and at 1, 3, 6, and 12 months after surgery, the concentrations were 79.4, 151.0, 145.0, and 42.0 IU/ml, respectively. The preoperative concentration of IL-12 was 60.4 pg/ml, and at 1, 3, 6, and 12 months after surgery, the concentrations were 53.1, 113.0, 107.0, and 62.2 pg/ml, respectively.
Sunitinib was started 3 months after surgery. This was changed to everolimus 2 years later because of a slight increase in size of the right adrenal gland metastasis from 15 mm to 17 mm. One month after TES, sacral radiotherapy was provided, with a total dosage of 45 Gy. Two years after the patient underwent TES, zoledronic acid was substituted with denosumab 120 mg/month because of slight progression of the sternal metastasis. Thereafter, the bone metastases remained stable.
At the follow-up examination 6 months after TES, radiographic union between the bone graft site and the adjacent vertebrae had been achieved. At a recent follow-up appointment, 5.5 years after TES, no evidence of local recurrence at the spondylectomy site was demonstrated by CT (Fig. a, b). Moreover, the metastases in the sternum, left clavicle, and sacrum were stable. A sclerotic rim around the sacral lesion was clearly visualized (Fig. d, e, and f). The right adrenal gland metastasis gradually increased in size (to 24 mm) while the patient was receiving everolimus (Fig. c). |
pmc-6475530-1 | The first case was a 59-year-old African American male with a past medical history notable for schizoaffective disorder, depression, and substance abuse who was brought in to the emergency room for disorganized behavior and agitation in the community. At the time of admission the patient demonstrated disorientation, repetitive motor behavior, and an alternation between agitation and psychomotor retardation. He had poor response to communication and tactile stimuli. A suspicion of altered mental status due to organic causes was suspected with the possibility of catatonic excitement and retardation. He was admitted to the medical floor, with a work-up revealing a positive toxicology screen for cocaine and opioids. The patients CBC and BMP were within normal limits except for his ammonia level which was 80 mg/dl. The patient was initially treated with Chlorpromazine Hcl 50 mg orally daily for his agitated behavior as well as Naltrexone 50 mg orally daily for his opiate intoxication.
The patient exhibited incoherent thought process in addition to mumbled speech that made a significant portion of his assessment evaluation difficult. During evaluation, he displayed abnormal movements of his arms and face, with tremors and restlessness. His affect was flat. He did not display any perceptual disturbances or delusions. An assessment for cognitive impairment was noncontributory during his most recent admission. The patient received Mirtazapine 45 mg orally at bedtime and Olanzapine 10 mg orally daily in his treatment and by day three of admission had shown improvement in his disorganized behavior with supportive care. The patient demonstrated more effort to directly communicate with house staff after treatment began.
The patient reported a past history of psychiatric illness that was late in onset. His first presentation at the age of 51 years was significant for depressed mood, paranoid delusions, and auditory hallucinations for which he was diagnosed with a major mood disorder. His symptoms responded poorly to medications including antidepressants. His disease course involved increasing periods of impulsive behavior and agitation. He became noncompliant with his prescribed medications. He was later admitted to the medical floors at the age of 54 years for “repetitive behavior” during which he was found moving from his bed to the bathroom repeatedly as if he wanted to use the bathroom all the time. He also showed some abnormal rocking movements during this time period. A medical work-up for seizure was negative. He was discharged with a presumptive diagnosis of a psychotic disorder. Thereafter, at the age of 56 years he had an episode of property destruction in the community and it was noted that he had “abnormal body movements” in addition to lability of mood. His diagnosis was revised to schizoaffective disorder and he was treated for mood lability at the time with risperidone.
Given the late onset of his neuropsychiatric symptoms, a computed tomography scan (CT) of his brain was done during his presentation, as seen in . Reviewing his chart, it was noted that the calcifications were apparent in his first head CT taken in January of 2012 with no changes to the current CT in January of 2019. |
Subsets and Splits
Exclude ER emergencies
Retrieves 100 descriptions that do not contain the terms 'ER' or 'emergency', providing a basic filter of the dataset.