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pmc-6487142-1 | A 77-year-old woman with prediabetes presented to her primary care doctor for a routine preventative care visit with a new presentation of left-sided axillary lymphadenopathy. She had a screening mammogram performed and a breast ultrasound that showed a 5 mm left breast nodule and left axillary adenopathy up to 3.2 cm. Given concern for breast cancer, she underwent a core needle biopsy of the left axillary node and was diagnosed with classical Hodgkin's lymphoma (cHL) with immunostaining showing large atypical cells that were CD30+, CD15+ (subset), CD20+ (strong), and PAX5+. No flow cytometric analysis was performed. The local pathologist read the specimen as most likely representing a cHL, although the pathologist considered alternatively that the specimen could represent non-Hodgkin lymphoma (NHL) of the diffuse large B-cell lymphoma (DLBCL) subtype.
She was referred to a medical oncologist with no B symptoms and an unremarkable physical exam except for diminished hearing in the left ear and left axillary adenopathy. Her labs were notable for hemoglobin 11.9 g/dL, leukocytes 7,600/μL, absolute neutrophil count 5,400/μL, absolute lymphocyte count 1,500/μL, platelets 261,000/μL, albumin 4.6 g/dL, and LDH 198 U/L (upper limit of normal 243 U/L). She underwent staging with a PET/CT scan and bone marrow biopsy of the right posterior superior iliac crest. The bone marrow morphology showed normocellular marrow (30%) with maturing trilineage hematopoiesis and no evidence of cHL. The flow cytometric analysis also showed no evidence of a B- or T-cell lymphoproliferative disorder. The PET/CT scan from the skull base to the midthigh revealed hypermetabolic adenopathy within the neck, chest, abdomen, and pelvis with the largest area of bulky adenopathy in the left axilla (largest measuring 3.3 × 1.7 cm with SUV 14.5) and a left subpectoral adenopathy (measuring 2.9 × 1.0 cm with SUV 12.3). There was no focal hypermetabolic activity within the liver or spleen. However, there was involvement of a few left paraaortic retroperitoneal lymph nodes and inguinal lymph nodes below the diaphragm. She was therefore staged as stage IIIA.
The patient was sent for a second opinion at a tertiary care referral center to confirm the diagnosis and advised on treatment options. The second opinion oncologist recommended excisional biopsy of the left axillary node for diagnostic clarity. This lymph node biopsy was read by the local pathologist as cHL against a background of extensive nonnecrotizing granulomatous inflammation. The H&E sections demonstrated a lymph node with effaced architecture and nonnecrotizing granulomatous inflammation and scattered large atypical binucleated cells with prominent central nuclei, reminiscent of Reed-Sternberg cells seen in cHL. The background was lymphoplasmacytic with histiocytic infiltrate. On the immunohistochemical studies, the large atypical cells were CD15+, CD30+, CD20+ (bright), PAX5+, MUM1+ and CD3-, CD10-, CD45-, and BCL2-. The flow cytometric analysis showed no immunophenotypic evidence of a B-cell or T-cell lymphoproliferative disorder.
However, a second opinion by the pathology group at the tertiary care referral center rendered a diagnosis of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and cHL, also referred to as grey zone lymphoma (GZL) []. While the morphology of the atypical lymphocytes and presence of CD30+ expression were suggestive of cHL, the strong expression of multiple B-cell markers (CD20+, PAX5+, and OCT2+) was not typical (). Furthermore, in situ hybridization EBV mRNA (EBER-ISH) was positive in many large cells. This case was discussed at an interdisciplinary conference at the tertiary referral care center, and a final diagnosis of GZL was made. Prior to beginning an anthracycline-based treatment regimen, she underwent cardiac echocardiography which revealed a normal ejection fraction of 60-65% with no valvular disease.
She remained at the referral center for treatment of her stage IIIA CD20+/CD30+ GZL and underwent 6 cycles of R-BV-CHP (rituximab, brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone) therapy not as part of a clinical trial, with restaging PET scan after cycle 3 which showed complete response (CR). After completing the total course of 6 cycles of R-BV-CHP, she underwent an end-of-treatment PET scan consistent with CR. She had no significant side effects from her treatment. Since June 2018, the patient remains in complete remission and retains an excellent performance status. |
pmc-6487149-1 | A 70-year-old man was admitted to our hospital with a two-week history of diplopia and right ptosis. He had a history of hypertension and dyslipidemia. Five months before admission, he had been diagnosed with SLE, according to the 1997 American College of Rheumatology classification criteria []. Because his arthritis and bicytopenia were mild, treatment with glucocorticoid had been withheld.
Physical examinations revealed ptosis of the right eye. The position of the right eye was laterally deviated. The adduction and upward and downward movements were reduced. Other significant features were mild drooping of the right angle of the mouth, incomplete closure of his right eye, and asymmetrical crease of the forehead. His hearing was normal, and there was no rash on the ear. Consciousness was clear, and the muscle strength of the extremities was normal.
Laboratory findings were as follows: white blood cell count, 2,200/μL (neutrophils 900/μL and lymphocytes 600/μL); red blood cell count, 373 × 104/μL; hemoglobin, 10.9 g/dL; platelet count, 9.5 × 104/μL; and activated partial thromboplastin time, 32.4 sec. The blood glucose level was 99 mg/dL and HbA1c was 6.4%. C-reactive protein was 0.69 mg/dL, serum IgG was 4,450 mg/dL, and complement components C3 and C4 were 25 and 1 mg/dL, respectively. Serologic markers for hepatitis B and C were negative. Cryoglobulin was not detected. Rheumatoid factor was 18.1 IU/mL (normal <15), and antinuclear antibody was 1 : 2,560 with a homogeneous pattern. Anti-dsDNA antibody was 311.7 U/mL (normal <12), and anti-SS-A antibody was positive at a titer of 1 : 4. Anti-cardiolipin antibody (IgG) was positive at 23.8 U/mL (normal <10). Anti-U1-RNP, anti-Sm, anti-SS-B, anti-cardiolipin (IgM), and anti-β2 glycoprotein I antibodies and lupus anticoagulant were all negative. Urinalysis was normal. Cerebrospinal fluid showed no elevation of cell count or protein. Gadolinium-enhanced magnetic resonance imaging of the brain revealed no increased signal intensity on diffusion-weighted images, and there was no abnormal enhancement of cranial nerves or soft tissue mass around the nerves.
The patient had also noticed a dry mouth. A chewing gum test and salivary gland scintigraphy revealed decreased salivary secretion. Schirmer's test was only positive in his left eye. A labial minor salivary gland biopsy demonstrated focal lymphocytic infiltrations, which was consistent with the finding of SS. The patient was also diagnosed with SS according to the Japanese diagnostic criteria [].
Because the patient was elderly, and had a history of hypertension and dyslipidemia, we first considered several common causes of cranial neuropathies including stroke, diabetes, and infections like varicella-zoster virus. However, these conditions did not explain the cranial nerve palsies. Hence, we considered that the cranial nerve palsies were caused by autoimmune mechanisms. The patient was treated with prednisolone 70 mg/day (1 mg/kg), aspirin, and intravenous cyclophosphamide pulse therapy. Thereafter, both the oculomotor and the facial nerve palsies began to improve in a few days. Both palsies recovered almost completely after two weeks of treatment. |
pmc-6487162-1 | A 74-year-old male, with a history of type II diabetes and previous ischemic heart disease, was admitted on September 2014 to the emergency room of the hospital complaining severe asthenia and nasal bleeding. There was no previous history of hematological disorders. Blood cell count disclosed Hb 6.4 gr/dL (12.0–16.0 g/dL), Plts 35 × 109/L (150–450 × 109/L), a WBC of 62 × 109 (4.30–10.80 × 109/L), basophils <2% (0–1.5%), and with 50% of blasts. The coagulation profile showed INR 1.5 (0.8–1.2), fibrinogen 69 mg/dL (200–400 mg/dL), ATIII 77% (75–128%), and D-dimer 10757 ng/mL (0–500 ng/mL), suggesting a disseminated intravascular coagulopathy (DIC). Bone marrow aspirate showed infiltration by 89% of hypergranular leukemic blasts (Figures and ).
Immunophenotyping of the leukemic population showed positivity for CD45, CD33, CD117, and MPO and negativity for CD34, HLA-DR, CD13, and CD56, compatible with a diagnosis of AML. Clinical examination showed mild splenomegaly (14 cm) and multiple thick and erythematous skin lesions localized on the back. A biopsy of one such lesion followed by histologic examination was consistent with extramedullary localization of AML.
Conventional karyotyping () and FISH () showed the presence of a three-way translocation t(9;12;22)(q34;q13;q11) on 15/15 metaphases.
The p210 BCR-ABL fusion transcript was detected by standard RT-PCR, which allowed to identify both b3a2 and b2a2 transcript isoforms []. Nowadays, no data are available regarding prognostic value of these transcripts in AML; however, studies regarding CML have shown that in some cases transcript, b2a2 has slower molecular and inferior response rates to TKI and a poorer long-term outcome []. In addition, molecular screening allowed to detect the presence of a type A mutation in the NPM1 gene [] and the absence of BCR/ABL p190, RUNX1/RUNXT1, CBFbeta/MYH11, DEK/CAN, FLT3-ITD, and PML/RARalpha rearrangements. Quantitative RQ-PCR showed IS 36% of BCR-ABL, with a copy number of BCR-ABL p210 of 7,152 · 104/ABL [] and NPM1 copies of 101,160 · 104/ABL [].
The CT scan showed hepatic lesions suggestive for extramedullary involvement and disseminated venous thrombosis localized in the sovrahepatic veins and the right frontal sinus. Lumbar puncture showed no central nervous system involvement. The patient was started on initial cytoreductive treatment with hydroxyurea for ten days and was subsequently treated with second-generation tyrosine kinase inhibitor (TKI) dasatinib 140 mg PO daily. Dasatinib was preferred over imatinib, a first generation TKI, due to high risk of the central nervous system involvement, extramedullary localization [, ] and, as proven for CML, it gives deeper and longer molecular responses [].
In December 2014, due to trilineage pancytopenia, research for point mutations in BCR/ABL fusion gene was detected and showed, unfortunately after patient died, T315I mutation.
In January 2015, three months after the start of dasatinib, he was hospitalized for neutropenic fever and was diagnosed with pneumonia. He died of sepsis few days later. |
pmc-6487166-1 | A 16-year-old previously healthy male presented to the emergency department with chills, abdominal pain, worsening nausea, and shortness of breath. He was noted to have increased work of breathing. Abdominal examination revealed mild tenderness in the periumbilical area, but no rebound guarding. His oral temperature was 38.6°C, heart rate 123 beats/min, blood pressure 121/69, and respiratory rate 20 breaths per minute. He was noted to have poor perfusion with capillary refill of 4 seconds, which improved after fluid resuscitation. Complete blood count showed a white blood cell count at 18,300 mm3, platelet count at 78,000/mm3, and hemoglobin of 14.3 g/dL (14-17 g/dL). Blood chemistry demonstrated high blood urea nitrogen at 27 mg/dL, high creatinine at 2.3 mg/dL, high alanine aminotransferase at 442 IU/L, high aspartate aminotransferase at 343 IU/L, and high total bilirubin at 2.8 mg/dL. The patient received one dose of ceftriaxone in the emergency department. He was placed on vancomycin and piperacillin/tazobactam.
The patient was admitted to pediatric intensive care where he underwent abdominal ultrasound to investigate the acute renal and liver injury. Ultrasound revealed a complex 9.3 x 9.2 cm heterogeneous-appearing mixed soft tissue and cystic lesion within the dome of the right hepatic lobe (). After discussion with surgical and infectious disease teams, a CT-guided 10 French pigtail percutaneous drainage catheter (PD) was placed in the abscess and drained purulent brown fluid.
The drained fluid grew Streptococcus anginosus, which was penicillin susceptible, and antibiotic regimen was changed from piperacillin/tazobactam and vancomycin to ampicillin monotherapy. Metronidazole was added later in his hospital course. Following drainage of the abscess, he became hypotensive, necessitating norepinephrine infusion. He developed respiratory failure requiring noninvasive positive pressure ventilation. Minimal fluid was drained from PD in the first 3 days. Follow-up ultrasound two days after the PD placement demonstrated abscess enlargement (18.4 × 117 cm) (). After multispecialty discussion, open surgical drainage was deferred. Instead, tissue plasminogen activator (tPA) was instilled into the PD. Four milligrams tPA was diluted in 50 mL saline, capped for one hour, and then drained to gravity. This was performed every 6 hours for total of five doses. Following instillation of tPA, catheter drainage significantly increased, and the patient's respiratory status and fever curve improved significantly (). Follow-up ultrasound after 5 doses of tPA therapy demonstrated a decrease in abscess size to 11.3 × 6.2cm (). The patient was discharged home on amoxicillin/clavulanate and metronidazole, with the drain in place, after 14 days of hospitalization. Ultrasound performed eleven days after hospital discharge demonstrated further decrease in size of abscess to 7 × 4.9 cm. The PD was removed 34 days after initial placement. |
pmc-6487170-1 | A 69-year-old Caucasian male was referred to our hospital with 3 weeks of abdominal distension and worsening right lower quadrant pain. He was diagnosed with IgG kappa multiple myeloma four years prior to presentation. He was initially treated with bortezomib/dexamethasone with monthly zolendronic acid with good response initially; however, a year after diagnosis, he was found to have disease progression which manifested as a right radius fracture. His regimen was switched to lenalidomide with dexamethasone with good response and clinically depressed levels of paraproteins. After completion of 9 months of therapy, he underwent autologous stem cell transplant with high-dose melphalan. 7 months after bone marrow transplant, his disease progressed with involvement of pericardial fluid. Salvage therapy was initiated with pomalidomide, bortezomib, and dexamethasone which was discontinued a year later due to peripheral neuropathy; however, at the end of treatment, there was no evidence of ongoing disease.
When the patient presented to our hospital, he had an acute abdomen. Initial blood work revealed a normocytic anemia with hemoglobin of 8.4 g/dl and elevated ESR of 44. He also had acute kidney injury with creatinine of 3 mg/dl (baseline of 1.9 mg/dl). CT scan of the abdomen and pelvis revealed extensive stranding seen throughout the abdomen within the peritoneal space with edema in the mesentery ().
He underwent an exploratory laparotomy which revealed induration of the entire base of the mesentery and retroperitoneum. He had an IgG level of 4407 units with predominantly kappa light chains whose level was 4833 units (kappa to lambda ratio 540). Pathology revealed extensive mesenteric infiltration by kappa restricted plasma cells positive for CD138 on immunohistochemistry, without evidence of amyloidosis. Bone marrow biopsy revealed a 30% involvement by plasma cells (Figures –). Cytogenetics showed 1q22 duplication, trisomy 7 and 15, and gain of 8q24.1. The skeletal survey revealed lytic lesions in the left femur and skull (Figures and ).
He was started on carfilzomib and dexamethasone therapy for relapsed multiple myeloma. Unfortunately, he died within one day of start of the chemotherapy from surgical complications of bowel obstruction. |
pmc-6487361-1 | An 80-year old Hispanic American female patient presented for the evaluation of recurrent abdominal pain, and excessive bloating after every meal, without any significant past history of weight loss and change in bowel habits. At initial presentation, her vital signs were within normal range. CT abdomen was insignificant. At this point, she was scheduled for the esophagogastroduodenoscopy (EGD), which showed no significant abnormality. However, her symptoms persisted, and one week later she was scheduled for colonoscopy by a senior gastroenterologist for the evaluation of lower gastrointestinal tract. She was vitally stable, and colonoscopy was passed through the anal canal under the direct visualization. Shortly after the introduction of the scope, significant diverticulosis and kinking were seen the level of the sigmoid colon. Every effort was made to pass, the scope safely beyond that level, but it was not successful; the procedure caused significant discomfort requiring higher dose of propofol and midazolam and the decision made not to proceed further. The scope was withdrawn, and the patient returned to the recovery room. Two hours following colonoscopy, the patient complained of severe LLQ abdominal pain, but she was vitally stable. Additionally, her abdomen was soft; however, significant tenderness in the LLQ of abdomen and subcutaneous crepitus in the right upper thigh was noticed. She was immediately rushed for CT abdomen which revealed massive pneumoperitoneum, pneumo-retroperitoneum, and subcutaneous emphysema (, , ).
At this point, the decision was made to take her back to the operating room (OR). She received proper preoperative intravenous fluids and broad-spectrum antibiotics. Distal sigmoid colon perforation with feculent peritonitis was seen, and laparoscopic Hartman procedure was performed. The postoperative period was uneventful, and her condition improved gradually. Her stoma was functioning very well, and diet advanced gradually. She was discharged home with home health care and scheduled for postoperative follow up in the clinic. |
pmc-6487369-1 | The authors report the case of a 77-year-old caucasian man that presented to the emergency department with sudden onset of dyspnoea, chest retrosternal pain and epigastric pain. Complains were preceded by vigorous vomit. Patient had previous medical history of diabetes, dyslipidaemia and benign prostatic hyperplasia. Upon admission the patient was tachycardic but with normal arterial pressure and no fever. On physical examination breath sounds were diminished on the left side and there was pain in the upper abdomen. All laboratory data were within normal limits but arterial blood analysis revealed PaO2 47 torr, SatO2 78% and hyperlactacidaemia (2.7 mmol/L) on FiO2 of 32%. Chest x-ray showed a large left pleural effusion (A). A CT scan was performed and revealed pneumomediastinum, left collapsed lung and loculated pleural effusion (B). A left intercostal chest tube (32 Fr) was inserted with residue food drainage (C). Hence, Boerhaave’s syndrome was suspected and, as the patient’s general condition was progressively deteriorating, an emergent surgery was undertaken. Patient was intubated with a double-lumen tube (direct visualization laryngoscopy). The patient was positioned in right-lateral decubitus and a left thoracotomy was performed. Intraoperatively a collapsed left lung was found with large amounts of food material (A) and a 2.5 cm longitudinal tear on the left-lower oesophagus was identified. The patient rapidly became more unstable, with need of vasopressor support. So, the authors decided to aggressively debride and irrigate the chest cavity. A T-tube was positioned and sutured to the oesophageal perforation (B) in order to create a controlled fistula. Two chest tubes were inserted and the chest wall was closed. The patient was then admitted to the Intensive Care Unit (UCI) with need for ventilatory support and vasopressor therapy. Intravenous broad-spectrum piperaciline/tazobactam antibiotherapy was initiated. Forty-eighth hours later, a second look thoracotomy was undertaken with further lavage and a definitive oesophageal repair – 3/0 monofilament interrupted sutures reinforced by using a pleural patch (). The remaining ICU stay was complicated by right side pneumonia, but with no prolonged ventilatory support needed. He was transferred to the general surgery ward on the 8th postoperative day. During the hospital stay the patient suffered a fall with blunt head force trauma and head CT scan showed a stroke. Antiplatelet drugs were initiated and physiotherapy was done. He was discharged home on the 38th postoperative day. On 3 months follow-up consultation, the patient is well with no impairments (). |
pmc-6487516-1 | A 51-year-old woman presented with a 2-year history of numbness and left arm pain, with negative spine imaging and peripheral neuropathy workup. Due to new paresthesia of the left hip, MR imaging (MRI) of the brain was performed, which showed T2 hyperintensity in the right insula, associated with edema and mild contrast enhancement. Microscopic examination of the resected tumor showed hypercellular brain parenchyma infiltrated by small round monomorphic cells with perinuclear clearing resembling oligodendroglioma, microcalcifications and perivascular pseudorosettes. Mitotic activity was inconspicuous, and computer-assisted quantitation yielded a Ki67 proliferation index of 7.6% (Fig. ). A diagnosis of oligodendroglioma, NOS, WHO grade II, was rendered following guidelines from the 2007 WHO classification system for tumors of the central nervous system (CNS), which was in force at the time of diagnosis. Fluorescence in situ hybridization (FISH) analysis for chromosomal arms 1p and 19q was negative for codeletion. The patient was treated with intensity-modulated radiation therapy (IMRT) to a total dose of 50.4Gy in 28 fractions, together with 12 cycles of temozolomide chemotherapy.
The patient was placed on surveillance imaging every 3 months and was stable until ~ 3 years after presentation when a new area of contrast enhancement was identified adjacent to the resection cavity. Resection of the recurrent lesion was performed. Microscopic examination showed a compact, densely cellular glioma with morphologic features associated with the recently-described FGFR3-TACC3 fusion glioma [, , ]. The characteristic features evident in this case include a population of glioma cells with monomorphous ovoid nuclei, nuclear palisading and enfilading, thin parallel cytoplasmic processes, endocrinoid capillary network, microcalcifications and desmoplasia (Fig. ) []. The tumor from the second resection showed foci of vascular proliferation, correlating with the presence of contrast enhancement on the preoperative MRI. In contrast to the low proliferation index of the initial tumor, the recurrent tumor showed a Ki67 index of 30.3%. GFAP was expressed in perivascular cell processes of the tumor cells, EMA was negative, and expression of the ATRX protein was retained.
Next generation sequencing analysis (NGS) for mutations (134 genes), copy number variations (47 genes), and fusions (51 genes), was performed on the recurrent tumor. The results showed FGFR3p.K650 T, NF1p.F443C and TERTc.-124C > T mutations, as well as the FGFR3-TACC3 (COSF1353) fusion. These findings prompted analysis of the initial tumor. NGS analysis revealed only the presence of FGFR3p.K650 T mutation; NF1 and TERT mutations were not identified in the tumor from the first surgery (Table ). Conventional RT-PCR with FGFR3 and TACC3 specific primers (5′-AGGAGCTCTTCAAGCTGCTG-3′ and 5′-GGGGGTCGAACTTGAGGTAT-3′) generated a product of the expected size (225 bp) and confirmed the FGFR3-TACC3 fusion in the original tumor. |
pmc-6487516-2 | A 75-year-old female presented to our institution for evaluation of treatment options after a diagnosis of malignant glioma. H&E-stained sections from the biopsy showed a high-grade glial tumor with microcalcifications, perivascular pseudorosettes, elevated mitotic activity, vascular proliferation and necrosis with pseudopalisading (Fig. ). The tumor cells expressed GFAP, punctate EMA staining was present in several areas, and automated quantitation yielded a Ki67 proliferation index of ~ 50%. The final diagnosis was glioblastoma, IDH-wildtype, WHO grade IV, based on the 2016 WHO classification of CNS tumors. Subsequent NGS analysis (same assay as described above) showed the presence of FGFR3p.K650 T and TERTc.-146C > T mutations, and an FGFR3-TACC3 fusion (COSF1348). The patient was treated with concurrent radiation and temozolomide.
These cases illustrate the morphologic and molecular alterations of FGFR3-TACC3 fusion glioma. The molecular alterations emphasize several important points. (1) The strong association between FGFR3-TACC3 fusion and TERT promoter mutations. (2) The novel concurrent association between the FGFR3p.K650 T point mutation and the FGFR3-TACC3 fusion. This association has clinical importance because analysis for gene mutations is more commonly done than fusion analysis. The presence of FGFR3p.K650 T should alert the physician to the possibility of an FGFR3-TACC3 fusion. Previous studies of FGFR3-TACC3 fusion gliomas have focused on fusion detection, with minimal simultaneous mutation analysis. It is therefore unclear if FGFR3p.K650 T is uniformly associated with the FGFR3-TACC3 fusion, although these examples suggest that may be the case. Given the existence of FGFR inhibitors, some which are being evaluated for the treatment of glioblastoma, recognition of the association between these two molecular alterations is important []. (3) The case data presented here supports a potential pathway to progression in FGFR3-TACC3 fusion glioma, from low-grade to high-grade, through acquisition of a TERT promoter mutation.
FGFR3 alterations are common in bladder cancers (~ 35% of cases) but extremely rare in brain tumors. FGFR3 codon 650 is 1 of 3 somatic mutation hotspots in this gene, although it is the least commonly affected (COSMIC). In COSMIC, there are ~ 200 reports of mutations at FGFR3p.650; in total there are 3 high-grade astrocytomas with an FGFR3 p.K650 T mutation. The FGFR3 p.K650 T mutation is reported as a pathogenic mutation in Clinvar and GeneReviews. Also, the FATHMM in silico method gives this mutation a pathogenic score of 0.98; scores of > 0.7 are considered pathogenic and are reported as such in COSMIC. We were unable to find reports with functional data on the FGFR3 p.K650 T mutation. However, FGFR3 p.K650E has been associated with constitutive activation of the receptor [].
There is a noteworthy similarity between the histology of PLNTY and FGFR3-TACC3 fusion glioma. There are also similarities in their genetic alterations, given that the FGFR3-TACC3 fusion has been described in both entities. However, there is a significant difference in the mean age at diagnosis between PLNTY and FGFR3-TACC3 fusion glioma, being 17.6 years (4–32) vs. 67 (35–87) years, respectively. Also, TERT promoter mutations and CDNK2A loss frequently occur in FGFR3-TACC3 fusion gliomas, whereas these alterations have not been reported in PLNTY.
Suspicion for the FGFR3-TACC3 fusion in the two present cases began with microscopic examination of H&E-stained sections, which elicited fusion testing. Recognition of the characteristic histologic feature set of FGFR3-TACC3 fusion glioma (and PLNTY) prompted molecular testing in both cases. In an era in which stratification and treatment of brain tumors is increasingly being guided by molecular information, recognizing the possibility of an FGFR3-TACC3 fusion in an infiltrating astrocytoma is critical, and may result in significant therapeutic impact. |
pmc-6487517-1 | Our patient is a 21-year-old Mexican mestizo woman with a family history of SLE (her father had the diagnosis), who at age 4 developed malar rash, fever, anemia, fatigue, and malaise. She was hospitalized, received a SLE diagnosis, and began taking corticosteroids and immunosuppressive agents, with constant disease flares throughout her early years. At 6 years of age, she developed an episode of septic monoarthritis in her right knee, requiring surgical drainage and antibiotics. Speech and attention problems were noted at this age, along with irritability, apathy, and lack of concentration at school. At 8 years of age, she began experiencing seizures that consisted of a visceral aura (butterflies in the stomach, as referred by the patient), fixed gaze, altered consciousness, oral and buccal automatisms, somnolence, and amnesia of the event at the postictal phase. These seizures occurred once a week approximately and were diagnosed as focal impaired awareness seizures, originating from the left medial temporal lobe. Anticonvulsants provided good control of the seizures until age 15 when these seizures became treatment-resistant.
At age 19 she was received in our hospital with a 3-week evolution symptomatology of generalized fatigue, localized pain, hyperthermia, pruritus, and hyperemia of her right lower extremity. Deep vein thrombosis was diagnosed with Doppler ultrasound, from the right popliteal vein through the right femoral vein, and laboratory tests revealed hemoglobin (Hb) of 4.83 g/dL, mean corpuscular volume (MCV) of 54.6 fL, mean corpuscular Hb (MCH) of 15.1 pg, and reticulocyte count of 5.6%. A lupus anticoagulant test was positive and she was diagnosed as having secondary APS and microcytic hypochromic anemia, requiring anticoagulants and blood transfusions for her treatment. She was prescribed hydroxychloroquine, prednisone, azathioprine, warfarin, calcium, and vitamin D supplements at discharge. The neurological treatment of her seizures consisted of levetiracetam, lamotrigine, magnesium valproate, and phenobarbital.
She then developed a severe major depressive episode as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) []; characterized by anhedonia, abulia, mixed insomnia, depressed mood, and suicidal thoughts; behavioral disturbances were noted including mainly impulsiveness and irritability. During this period, she performed two suicide attempts, the second and more severe occurred 5 months after APS diagnosis, when she ingested lamotrigine and magnesium valproate in an unknown quantity. She was admitted to the emergency room of our hospital with altered consciousness, nausea, dizziness, and weakness. She presented seizures 36 hours after stabilization with the same semiology as mentioned above; despite treatment, the seizures worsened and developed into status epilepticus, and she had to be transferred to our intensive care unit for mechanical intubation and sedation. Electroencephalogram studies showed interictal activity of focal seizures arising from the left frontotemporal region, with secondary generalization. At discharge, rheumatologic and neurologic follow-up was scheduled, and she was referred to the psychiatry department. She had not had a psychiatric or cognitive evaluation before.
During assessment at our clinic, she denied a history of alcohol or drug abuse, but presented with labile affect and emotional dysregulation, symptoms like abulia, mixed insomnia, impulsiveness, suicidal thoughts, and irritability were noted as the most disabling. Psychotic or manic symptoms were not present at the time of evaluation, so these diagnostic spectrums were ruled out. At physical examination, she had normal vital signs: blood pressure 90/60 mmHg, heart rate 87 beats per minute, respiratory rate 14 per minute, and temperature 36.8 °C. She had a normal height and weight of 1.46 m and 47.5 kg respectively, with a body mass index (BMI) of 22.30. A neurologic examination showed normal motor and sensitive findings; a cranial nerve examination was normal too. She did not present paresis of any extremities. Isolated hyperreflexia of lower extremities was noted (+++), glabellar and right palmomental reflex were present, and there were no other signs or symptoms of upper/lower motor neuron disease. Seizure symptomatology was still active, but with a better response than previously in her treatment course (one seizure every 2/3 weeks, approximately).
Magnetic resonance imaging (MRI) was performed and revealed neuroanatomical structural changes most noticeable in the left cerebral hemisphere, including generalized cortical atrophy with skull thickening and ipsilateral widening of sulci, ventricles, and cisternal spaces; hypotrophy of the hippocampus and medial temporal lobe structures was also noted (Figs. a–d and ). She was cognitively evaluated, scoring 15/30 points in the Montreal Cognitive Assessment (MoCA) test and 20/30 points in the Mini-Mental State Examination (MMSE). In the Wechsler Adult Intelligence Scale-IV (WAIS-IV) she received a total intelligence quotient of 65 (extremely low scoring range), which together with her academic history and current coping abilities indicated a moderate intellectual disability according to DSM-5 criteria []. In subscale analysis, she had a Processing Speed Index (PSI) of 77, Verbal Comprehension Index (VCI) of 70, and the most affected areas of the test were Perceptual Reasoning Index (PRI) with a score of 66, and Working Memory Index (WMI) with a score of 55, both of them in an extremely low score range (Table ).
Because of residual depressive symptoms at the time of evaluation, she was prescribed citalopram 20 mg per day, and behavioral interventions to improve conduct symptoms. She had mild improvement in her psychiatric symptomatology with these measures, but depressive symptoms did not evolve into a full recurrent major depressive episode, irritability and impulsiveness were controlled, and her adherence to treatment improved in all her psychiatric, neurologic, and rheumatologic treatments and follow-up visits. The last pharmacological regimen included citalopram, lamotrigine, and topiramate (for depressive symptoms and seizure control) and hydroxychloroquine, azathioprine, warfarin, prednisone, and vitamin D (for SLE and APS), with partial treatment response to these medications as shown by persistent hematologic manifestations. Despite the absence of gastrointestinal bleeding as evidenced by repeated negative fecal immunochemical tests results, she has suffered several episodes of microcytic hypochromic anemia. |
pmc-6487519-1 | A 58-year-old Caucasian woman with hip osteoarthritis was examined by an anesthesiologist for a surgical procedure of total hip arthroplasty. She had a history of SCA, which started when she was 55-years old with motor dysfunction. Her clinical condition had slowly worsened with appearance of dysarthria, horizontal saccadic eye movements, and lower extremities hypertonia. An MRI of her brain showed olivopontocerebellar atrophy; a mild motor and sensory ataxic polyneuropathy was highlighted by electromyography. Recent neuropsychological examinations identified a dis-executive deficit. Her family history is negative for SCA and she denied any history of cardiovascular, respiratory, or gastrointestinal diseases. Prior to the diagnosis of SCA, she was in good health and did not regularly take drugs. She denied smoking tobacco or drinking alcohol. At the time of the examination, she was taking benzodiazepines (triazolam 0.25 mg once daily) for anxious depressive syndrome, baclofen 25 mg three times a day for spasticity, and anti-cyclooxygenase type 2 (COX-2) for pain treatment (etoricoxib 60 mg once daily). Preoperative blood tests, electrocardiogram, and thoracic X-ray were negative. On physical examination, it was possible to appreciate that she was tall, 168 cm, and weighed 63 kg. A cardiopulmonary examination was unremarkable. Her vital signs were normal with blood pressure of 135/90 mmHg and heart rate of 90 beats per minute. On neuropsychological examination, she presented a mild reduction in performance on the Rey–Osterrieth Complex Figure Test, a limited ability to inhibit cognitive interference (Stroop Test), inability during the Multiple Features Targets Cancellation task, and a Spatial Span Score lower than normal; these were proofs of her dis-executive deficit. After discussing the case with a neurologist, general anesthesia was planned. In fact, our patient’s anxiety and spasticity would have made regional anesthesia difficult to practice. Preoperatively, no medications were administered. General anesthesia was induced with propofol 2 mg/kg intravenously and fentanyl 2 mcg/kg intravenously. Tracheal intubation was facilitated with rocuronium 0.6 mg/kg intravenously. Anesthesia maintenance was performed with sevoflurane (in an oxygen/air mixture) and fentanyl. The minimum alveolar concentration of sevoflurane was set to achieve a Bi-spectral Index (BIS) value between 40 and 60. Mechanical ventilation was set with a tidal volume of 7 ml/kg, a positive end-expiratory pressure (PEEP) of 5 cmH2O, and an inspiration/expiration rate of 1:2. These parameters remained stable during the surgical procedure. The respiration rate was adjusted to obtain an end-tidal carbon dioxide (etCO2) between 38 and 45 mmHg. The surgery was uneventful with no significant blood loss and no transfusion was needed. The procedure lasted 2 hours. Upon awakening, she appeared calm and parameters were stable. In the post anesthesia care unit (PACU), she was warmed up and oxygen supplementation was administered. Thirty minutes after awakening, she developed an acute hyperactive delirium. She experienced episodes of confusion, logorrhea, and disorientation. She also exhibited reduced awareness of the environment and hallucinations with aggressive behavior. During this episode, her vital signs remained stable and her oxygen saturation was normal. An arterial blood test revealed no hypercapnia or hypoxia or electrolyte disorders. Haloperidol 5 mg was intravenously administered slowly over 5 minutes, but her behavior did not change. To avoid uncontrolled pain, a single shot fascia iliaca block was performed with 25 ml of ropivacaine 0.375% but she continued to have intermittent episodes of delirium. After 10 minutes, chlorpromazine 25 mg was infused intravenously. This drug seemed to have the same efficacy as haloperidol with a subsequent mild sedation. She was transferred to our intensive care unit (ICU) where chlorpromazine 25 mg was given again during the night for another crisis. She was discharged from ICU the next day under normal neurological conditions.
After 1 month, she was readmitted for the development of an acute periprosthetic hip infection sustained by Staphylococcus epidermidis and Staphylococcus haemolyticus without signs of systemic sepsis. On examination, her temperature was 36.7°C, blood pressure was 128/95 mmHg, and heart rate was 75 beats per minute. Only the wound swab was positive for infection; hemocultures and urine cultures were negative. Preoperative blood tests showed: hemoglobin 10.4 g/dL; platelets 233 × 109/L; neutrophils 4.26 × 10 9/L; erythrocyte sedimentation rate (ESR) 47 mm/hour, and C-reactive protein (CRP) 27.2 mg/L. Renal and hepatic function indices were within normal limits. Debridement, antibiotics, and implant retention (DAIR) was performed under general anesthesia with the same modalities []. During surgery and after taking new periprosthetic tissue for microbiological examination, teicoplanin was administered intravenously at a loading dose of 400 mg. For the second time, our patient developed POD treated with chlorpromazine 25 mg intravenously with immediate sedation. Within 24 hours, the delirium resolved with no consequences. During the following days, 200 mg of teicoplanin was administered daily and 1 gr of cefazolin every 12 hours intravenously until discharge.
One month after discharge, she returned for follow-up. She was taking her habitual medications and, at the time of the examination, she exhibited no evidence of new disorders or joint infection. She looked well and denied any symptoms of confusion, disorientation, or hallucinations. The hip infection healed without any complication. She was re-evaluated at 3 and 6 months after surgery. Her ESR, CRP, and other biochemical values were within normal limits and her neurological status was stable. |
pmc-6487522-1 | A 45-year-old housewife who lived with her husband and two children who was diagnosed as having breast cancer (Stage II) and received a surgical resection. After surgery, she was told that she would need adjuvant chemotherapy. She became anxious about the possible recurrence of her breast cancer and side effects of chemotherapy such as hair loss and nausea. Consequently, she could not go out and stayed home all day long. She gradually became depressive, so she visited the psycho-oncology division of our hospital. She was diagnosed as having an MDD and prescribed antidepressant. However, she was unable to continue the medication because of nausea and fatigue. Though another antidepressant was proposed, she did not agree to use it because of concerns about the side effects. Therefore, she participated in the BAT program. At the beginning of the program, her depression was considered to be moderately severe by HRSD. However, she achieved remission of depression by the end of the program, without antidepressants, and began to live an active life. |
pmc-6487522-2 | A 66-year-old housewife who lived with her husband was found during a biannual medical checkup to have endometrial cancer (Stage III). She was so shocked that she became seriously depressed. She repeatedly thought, “why do I have cancer despite a biannual medical checkup”“I should have had more medical checkups, if I had, I might have no cancer.” She became very nervous and anxious about the possible recurrence of her cancer and its development into a serious physical disease. Her psychiatrist prescribed an antidepressant. She subsequently began participating in the BAT program. However, she was absent-minded during much of every session, and her compliance with the assigned daily homework was poor. Although antidepressant was increased, her depression did not improve much. |
pmc-6487522-3 | A 62-year-old man who lived with her wife and had his own business was diagnosed as having laryngeal cancer recurrence and had an operation 2 years previously. He was only given followed up care and had no symptoms. However, he became nervous about the possible recurrence of his cancer. He repeatedly thought, “cancer may spread to other parts of my body”, “if so, I may die” and he kept to his room all day long. He gradually became depressive, so he visited the psycho-oncology division of our hospital. He was diagnosed as having an MDD and prescribed antidepressant. He subsequently began participating in the BAT program. After taking part in the program, increased business activity, on which he placed great value, gradually allowed him to live his life actively without concerns. |
pmc-6487532-1 | A 61-year-old man from the Peruvian Amazon presented to the Emergency Department with a 1-week history of progressive shortness of breath, fever, and cough. His medical background was significant for essential hypertension and asthma. His home medications included lisinopril, fluticasone/salmeterol, ipratropium, and low-dose prednisone. He worked as a farmer in the Peruvian rainforest and had no known environmental exposure to pollutants or toxins. He did not smoke tobacco but he was a former alcohol user who quit drinking alcohol 5 years before presentation. He had a family history of hypertension. On evaluation, he was ill-appearing and in respiratory distress. His vital signs were: temperature (T) 38.2 °C, blood pressure 110/70 mmHg, heart rate 105 beats per minute (bpm), and respiratory rate 28 respirations/minute with saturation of oxygen (SO2) 87% on room air. Chest auscultation revealed diffuse wheezing and bilateral crackles. His cardiovascular examination showed tachycardia without gallops or murmurs. Furthermore, his neurological examination was negative for focal deficits or meningeal signs. The rest of the physical examination was unremarkable.
Initial laboratory results showed a white blood cell count of 34 × 109/L (bands 5%, lymphocytes 1.7%, eosinophils 0.3%). Biochemical analysis revealed hyponatremia, mild elevation of hepatic enzymes, and severe hypoalbuminemia. His arterial blood gases revealed: pH 7.28, partial pressure of carbon dioxide (pCO2) 55 mmHg, and partial pressure of oxygen (pO2) 59 mmHg. A chest X-ray showed bilateral base-predominant interstitial infiltrates concerning for community-acquired pneumonia (Fig. ). He was administered ceftriaxone and azithromycin, albuterol nebulization, and biphasic positive airway pressure support. In addition, a dose of prednisone (1 mg/kg) was administered orally for severe obstructive airway disease. He exhibited partial clinical improvement over the following 48 hours, but due to worsening oxygen requirements and persistent fever, his antibiotic therapy was switched to meropenem and vancomycin. Figure shows a computed tomography (CT) scan with bilateral consolidations, predominantly on the lower lobe of his left lung.
On hospital day 5, he presented hemodynamic instability and acute encephalopathy, which prompted intubation and vasopressor support. Arterial blood gases showed: pH 6.9, pCO2 70.8 mmHg, and pO2 51 mmHg. His lactic acid level was 10.7 mmol/L. A repeat chest CT scan revealed extensive bilateral infiltrates and ground-glass opacities (Fig. ). Empiric therapy with micafungin was initiated. Bronchoalveolar lavage (BAL) was negative for conventional bacteria, fungi, or acid-fast bacilli. An extensive work-up was unremarkable including investigations for HIV and Human T-cell lymphotropic virus (HTLV-1), which were non-reactive. Considering the patient epidemiological background and his rapid deterioration despite broad-spectrum antibiotics, a new BAL was conducted to test for soil-transmitted helminths (STH). Fecal samples were collected as well. Finally, larvae of S. stercoralis were found in both BAL (Fig. ) and stool specimens (Fig. ). Corticosteroid therapy was discontinued and anti-parasitic treatment was started with ivermectin 200 μg/kg per day orally for 2 days. Therapy was repeated 2 weeks later to ensure adequate parasite eradication. Stool and bronchial specimens were negative thereafter. The patient experienced progressive recovery over the next 4 weeks. Unfortunately, he was lost to follow-up afterward. |
pmc-6487583-1 | A 37-year-old Japanese man was admitted to our hospital due to multiple brain metastases. He was aware of coughing 6 months previously and had a headache 3 weeks ago, so he visited our hospital. Brain magnetic resonance imaging (MRI) revealed multiple brain tumors in the bilateral cerebellum and cerebrum (Fig. ). Chest computed tomography (CT) showed a 15-mm nodular shadow in the middle lobe of his left lung, and he was referred to our Department of Respiratory Medicine (Fig. a). He was admitted for further examination because he was suspected of having lung cancer with brain metastases. There was no special mention in his medical history; there was no alcohol drinking or tobacco smoking history. On physical examination, his body temperature was 36.7 °C, his blood pressure was 122/78 mmHg, his pulse was 56 beats per minute, and his respiratory rate was 12 breaths per minute. His oxygen saturation was 98% in room air. Lung and bronchial sounds were normal. Head, eyes, and nose examinations were unremarkable. His neck had no lymphadenopathy. An examination of his heart, abdomen, and extremities showed no abnormalities. Blood test findings revealed elevation of tumor markers such as carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC). On day 4 after admission, bronchoscopy was performed. The histology at bronchoscopy for the middle lobe of his left lung is shown in Fig. . Adenocarcinoma cells exhibiting a papillary pattern were found, and he was diagnosed as having papillary adenocarcinoma of the left lung according to the World Health Organization (WHO) classification, 4th edition. His adenocarcinoma was positive for ALK according to immunohistochemistry and fluorescence in situ hybridization (FISH) method (Fig. ). Based on this observation, he was diagnosed as having ALK-positive lung cancer with cerebral metastases, and administration of alectinib 600 mg/day was started from day 23 after admission. Adverse events such as allergic reactions, interstitial pneumonia, and gastrointestinal symptoms were not observed. Pulmonary lesion reduction was confirmed at chest CT on day 37, and he was discharged on day 40 (Fig. b). He continued to take orally administered alectinib every day on an out-patient basis. On chest CT at 90 days after initiation of alectinib treatment, continued reduction of the lung lesion and hilar lymph node was confirmed (Fig. c). Regarding the brain metastatic lesions, whole brain irradiation (total 30 Gy/15 fractions) was performed from day 9 after admission, and tumor reduction was found on MRI on day 60 after start of alectinib treatment.
Approximately 96 days after start of treatment, he was aware of headaches and nausea, and he visited our emergency department on day 103 of administration. Contrast MRI confirmed the findings of meningeal carcinomatosis. He was re-hospitalized for systemic management, including pain care. Dexamethasone infusion was started for increased intracranial pressure due to meningeal carcinomatosis. His Eastern Cooperative Oncology Group (ECOG) performance status at the time of his second admission was three, which was markedly lower than that at the onset of alectinib administration. He also experienced severe headache pain, so orally administered oxycodone was started. A few days after start of oxycodone administration, it became difficult for him to take orally administered medications, and palliative treatment was started using morphine hydrochloride infusion. Administration of alectinib was discontinued 108 days after start of treatment. Subsequently, it became difficult for him to sit up, his state of consciousness worsened, and his general condition worsened. He died 124 days after the first administration of alectinib.
After his death, we performed pathologic dissection with the consent of his family. Pathological autopsy showed severe cerebral edema and compression of the brain stem. As a result, respiratory arrest due to brain stem compression was considered to be the direct cause of death. In addition, the primary lesion in the left lung was re-evaluated histopathologically, and approximately 20% of the lesion manifested several characteristics of squamous cell carcinoma as determined by the presence of intercellular bridges and cytokeratin (CK) 5/6 positivity, indicating an adenosquamous carcinoma (Fig. a, b). Histological findings of leptomeningeal carcinomatous lesions also pointed to adenosquamous carcinoma, and the proportion of the squamous cell carcinoma component was higher than that of the left lung. |
pmc-6487607-1 | A 1-year-old girl diagnosed with pneumonia was under mechanical ventilation in PICU ().
She suffered from acute respiratory failure and her ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (P/F ratio) was 135 under mechanical ventilation (moderate acute respiratory distress syndrome). Her CXR images revealed pneumonia and atelectasis. However, LUS showed coalescent B-lines and no another abnormalities. CCT revealed only interstitial pneumonia. |
pmc-6487607-2 | A 4-year-old girl who was on antibiotic treatment and mechanical ventilation was deteriorating on her oxygenation (). Her CXR showed pulmonary opacities and she was diagnosed with pneumonia. One day her oxygenation deteriorated, with unstable oxygen saturation level, and P/F ratio reduced to 135. CXR did not show the source of origin of her worsening hypoxia, thus, the attending doctors decided to conduct CCT. LUS and CCT showed substantial dorsal consolidation, pleural effusion and no other abnormalities. She was prescribed physical therapy including the prone position. After proper therapy, her oxygenation improved, and she was extubated the following day. |
pmc-6487609-1 | A 79-year-old male with a history of chronic obstructive pulmonary disease, type 2 diabetes, chronic kidney disease, and persistent atrial fibrillation was brought to hospital after being successfully resuscitated following a brief pulseless electrical activity (PEA) cardiac arrest. During his convalescence, he had a second PEA arrest, from which he was again successfully resuscitated. Telemetry revealed atrial flutter with atrioventricular conduction that slowed markedly to ventricular rates as low as 34 beats per minute. A balloon-tipped temporary pacing catheter was floated in via left internal jugular vein until adequate ventricular capture was observed. Fluoroscopy was not used during insertion. A follow-up chest X-ray confirmed appropriate placement of the lead, which revealed the lead in the right ventricle with redundant lead slack forming a loop ().
The patient subsequently had a PPM implanted. The PPM was implanted without complication using a standard left cephalic vein access. The lead was advanced under fluoroscopic guidance. Implantation of the PPM lead was carried out without difficulty with active fixation to the right ventricular septal wall. The lead pin was attached to a pacemaker pulse generator which was then placed in a pocket located in the prepectoral plane below the left subclavicular fossa.
The TVP was then removed under fluoroscopic guidance. The large loop of redundant wire was noted, but it exited the cardiac silhouette without any resistance or interaction with the newly implanted PPM lead. However, significant resistance was noted when attempting to pull the tip of the TVP lead out through the introducer sheath. This resistance was only encountered when the TVP lead tip was at the level of the skin; fluoroscopy was not performed at this stage to determine the cause of resistance. The resistance was overcome and the TVP lead was successfully removed. It quickly became evident that the reason for the resistance was that the TVP lead had looped and formed a knot around the RV PPM lead at the junction of the left subclavian and left internal jugular vein. Continued traction had thus dislodged the RV lead tip from the endocardium, resulting in inadvertent removal of the RV lead through the left internal jugular vein (). No dislodgement of the PPM lead had been apparent fluorocopically during removal of the TVP wire from the cardiac silhouette as the ensnarement occurred at the level of the thoracic inlet when fluoroscopy was no longer being employed, and no loss of capture was noted as the patient was in their intrinsic rhythm. The patient remained hemodynamically stable.
In order to place a new RV PPM lead, left axillary venous access was obtained and a new lead was successfully placed, which was connected to the original pulse generator. The ensnared RV lead was cut within the pocket, and the lead pin was removed from the pulse generator directly. The external portion of the RV lead () was then removed without complication from the left internal jugular vein. The new PPM assembly functioned well, and the procedure was completed without any further complication. |
pmc-6487613-1 | A 32-year-old male patient presented in emergency department with the history of ingestion of two celphos tablets 7 hours ago. On examination, blood pressure was 76/54 mm of Hg; pulse rate was 114/minute and respiratory rate was 24/minute. SaO2 was 86% in ambient air which improved after oxygenation at the rate of 4-5 L/minute. GCS was 15/15 and without any focal neurological signs. Review of other systems was normal. Investigations were within normal limits except there was lactic acidosis on his arterial blood gas analysis. Patient was shifted to intensive care unit for management which included central venous pressure guided intravenous fluids, ionotropes and magnesium sulfate injections. On day two of admission, he was complaining of shortness of breath and passing of cola coloured urine. On examination, he was found to be pale. Icterus was present. All the investigations were repeated which showed a fall in the hemoglobin level from the initial baseline level with unconjugated hyperbilirubinemia. In view of unconjugated hyperbilirubinemia and rapid fall in hemoglibin level diagnosis of hemolysis was considered. History was reviewed for hemolytic anemia and it found unremarkable. He denied ingestion of any other drug. Patient was worked up for hemolytic anemia. Peripheral blood film revealed macrocytosis and anisopoikilocytosis. No schistocytes or red blood cells fragments were found. Reticulocyte production index was 2.9. G6PD activity levels were normal. Serum lactate dehydrgenase was 1900 U/L (normal: 250U/L), haptoglobin was 11mg / dL (normal 30-200mg/ dL). Direct Coomb's test was negative. Partial thromboplastin time and prothrombin time were normal. Urine showed presence of hemosiderin. Urine microscopy was normal. Ultrasonography abdomen was normal. Serial hemogram and biochemistry during hospitalisation and follow-up are shown in . During the hospitalisation no drugs were administered which may cause hemolysis. The patient remained afebrile. Patient took a discharge on request on fifth day of admission and reported back on day 10 of ingestion for follow up. He was refered for psychiatry evaluation. |
pmc-6487623-1 | This document reports a 59-year-old gentleman diagnosed with moderately differentiated squamous cell carcinoma (SCC) of left lung with multiple metastasis in liver, brain, bone, subcutaneous tissue in chest and back, left adrenal gland, lymph nodes including right pulmonary hilar, mediastinal, bilateral axillary and right cardiophrenic angle. Tumour marker cytokeratin (CK)7 was found to be positive. He was admitted in ward with complains of loss of appetite and generalized weakness for 3-4 days. Patient was planned for palliative external beam radiotherapy (EBRT) to address painful bony metastasis followed by systemic chemotherapy. Blood was transfused (1 unit packed red blood cells) on the day of admission in view of low hemoglobin (7 gm/dL). Patient also had complaints of urinary retention, but due to resistance during Foley's catheterisation attempts failed and therefore cystostomy had to be done. On 3rd day of admission, patient was shifted to medical intensive care unit (ICU) due to low Glasgow Coma Scale (GCS). Central venous line (CVP) insertion was done on the same day. Investigations revealed high TLC, thrombocytopenia, dyselectrolytemia including hypernatremia, hypokalemia, deranged Kidney function test (KFT). After admission to ICU, blood and urine samples were sent for culture. Both blood and urine cultures showed growth of multidrug resistant (MDR)E. coli. Patient was receiving injection cefepime-tazobactum for 10 days; injection polymyxin B for 6 days.
After one week of stay in the ICU, repeat paired aerobic blood (right femoral line and central venous line) samples were taken in Becton Dickinson (BD) blood culture bottles and sent for culture. Repeat urine sample showed no growth. Paired set of aerobic blood culture samples were processed with the Bactec 1090 (Becton Dickinson, USA). Bacterial growth was detected within 48 hr in both bottles of the samples. Gram stain of positive blood culture bottle showed Gram-negative bacilli. Sub-cultures were done on routine Sheep Blood agar and MacConkey agar. After 24 hr of incubation, smooth, circular, yellow-pigmented colonies were grown on sheep blood agar. On addition of 1 drop of 10% KOH solution, the color of the colonies was changed from yellow to red which indicates presence of flexirubin pigment. The isolate was catalase and oxidase positive, indole weakly positive and urease negative. Oxidation fermentation test results revealed oxidation positive/fermentation negative, mannitol positive non- motile organism. Final identification and sensitivity of the organism was done by Vitek 2 Compact system (BioMerieux). Chryseobacterium indolegenes was isolated from both the blood culture bottles. Antimicrobial susceptibility pattern of both the isolates from blood culture showed same sensitivity pattern with minimum inhibitory concentration (MIC) levels ( and ).
Patient's antibiotics were modified as per culture report and sensitivity patterns. Levofloxacin and minocycline were added and Polymyxin B discontinued. Levofloxacin was continued for 11 days while minocycline for 9 days.
On 20th day of admission in ICU, there was further deterioration of patients' general condition including sensorium and Glassgow coma scale (GCS). In view of advance nature of the disease, sepsis refractory to antibiotics, dyselectrolytemia and aspiration, the patient was put on non-invasive ventilation with informed consent from the primary responsible attendant of the patient. However, the patient had an episode of bradycardia which was followed by cardiopulmonary arrest. |
pmc-6487627-1 | A 53-year old female was admitted to the Intensive Care Unit of Kingston General Hospital in Kingston, Ontario, Canada with diabetic ketoacidosis (DKA). She had a past medical history of type 1 diabetes with recurrent DKA and end stage renal disease secondary to diabetic nephropathy on intermittent hemodialysis. Prior to admission, she was being dialyzed through a left arm arteriovenous fistula.
Shortly after admission, her left arm fistula thrombosed, and a right internal jugular (IJ) tunneled double-lumen catheter was inserted for dialysis along with a peripherally inserted central catheter (PICC) via right basilic vein for intravenous access. The patient had a previous failed right arm AV fistula so the left arm was avoided in hopes of future recovery of the left AV fistula.
Two weeks later during the course of her admission, she continued to have episodes of DKA, and inadvertently her PICC line was dislodged, requiring removal. The patient had poor peripheral intravenous (IV) access and multiple attempts to insert peripheral IVs under ultrasound guidance were unsuccessful. Ultrasound examination of the patient's left internal jugular showed significant narrowing. The patient declined an attempt femoral venous access because she had previous lower extremity venous grafting for her AV fistula and she was told to avoid cannulization of any of those vessels. A 7 French, 16cm triple-lumen CVC was placed into the right internal jugular vein with sonographic guidance without difficulty. The puncture site for the CVC insertion was significantly distal to the tunneled dialysis catheter. Post-procedure, all three lumens were able to draw blood and flush saline. A chest X-ray confirmed placement of the catheter adjacent to the tunneled dialysis catheter () close to the cavoatrial junction. The patient did not have any immediate complaints or discomfort. Approximately six hours later, the on-call resident was called by nursing staff to assess the patient for new neck discomfort and jaw pain which had begun two hours prior.
At the time of assessment, the patient's heart rate was 95 beats per minute and regular. Her blood pressure was 188/84, respiratory rate was 18 and oxygen saturation was 99% on room air. She was afebrile. On examination, the patient had distended neck veins, pronounced facial edema and plethora (). She also had bilateral upper-extremity edema primarily manifesting in her digits. The rest of her cardiorespiratory examination was unremarkable.
All three lumens of the CVC were withdrawing blood and flushing without difficulty.
Point of care ultrasound of the right internal jugular vein revealed no thrombus at the site of CVC entry or distal to it. The SVC was not visualized directly. The CVC was removed promptly. There was no visible clot on the catheter, and no clot was pulled along with the catheter. Within an hour, the patient's facial swelling and plethora began to resolve, and her neck pain began to improve. The next morning, pain and swelling had resolved completely ().
A retrospective chart review revealed a fistulogram performed months prior that showed significant stenosis at the left subclavian vein and mild narrowing at the junction where the two brachiocephalic veins merge to form the SVC (). At that time, angiography was attempted to alleviate the stenosis. However, the patient did not tolerate this, and the procedure did not lead to a significant change in the degree of stenosis.
The events surrounding the SVC syndrome and the previously identified SVC stenosis were disclosed to the patient. In order to prevent a similar event from occurring in the future, a note was made in the chart that would be more visible should the need for further CVCs arise. |
pmc-6488282-1 | On 15 Aug, 2017, a 57-year-old woman with ulcerative colitis, steroid-induced diabetes mellitus, deep vein thrombosis in the lower part of the left thigh, ecchymotic skin lesions, swelling in the left nose, ptosis (i.e., inability to move eyelids), and facial nerve palsy, was admitted to Shafa Hospital in Sari, north of Iran. She was afflicted with intestinal bleeding after Islamic fasting periods (i.e., Ramadan month).
Ulcerative colitis had been confirmed by clinical manifestations and colon biopsy and was managed with the administration of azathioprine (50 mg/day) and high-dose prednisolone (60 mg/day) for 2 months, prior to hospital admission. Due to prednisolone-induced hyperglycemia, the patient was on treatment with insulin for a month before admission to the hospital. She was also on anticoagulant drugs for the treatment of deep vein thrombosis.
One day after hospitalization, the patient developed progressive periorbital ecchymosis, extensive edema of the nasal area, and nasal ulcer (). The eye examination revealed proptosis with 4+ light reaction, evidence of afferent pupillary defect (i.e., Marcus Gunn pupil), no light perception, absolute blindness, ophthalmoplegia, and neurological defects of the cranial nerves 2, 3, 4, and 6.
The results of the laboratory tests and vital signs included a fast blood sugar of 302 mg/dL, white blood cell count of 9460/µl, red blood cell count of 3.53×106/µl, platelets of 60×103/µl, hemoglobin of 8.9 g/dl, blood urea nitrogen of 35 mg/dL, serum creatinine of 2.3 mg/dl, potassium of 2.1 mg/dL, body temperature of 38°C, blood pressure of 120/70 mm/Hg, pulse rate of 80/min, and respiratory rate of 14/min, and glomerular filtration rate of 32. Blood culture and urine culture tests were negative.
On August 18, with regard to the deterioration of the patient's clinical condition and given the high level of suspicion for mucormycosis, the patient was prescribed amphotericin B deoxycholate with a dosage adjustment (0.7 mg/kg/day; 50 mg/day total dosage) coupled with broad-spectrum antibiotics (piperacillin-tazobactam). She was immediately subjected to surgery in which the nasal necrotic tissues were completely removed. The debrided tissues and mucous membranes were immediately sent to the Medical Mycology Laboratory.
The direct examination of the necrotic tissue revealed broad aseptate hyphae with right angle branching compatible to Mucorales (). The cultures grew gray-brown colonies with cottony texture in which Rhizopus species was identified by means of microscopic and macroscopic characteristics. DNA was extracted from the tissue of fresh nasal samples with QIAamp DNA Mini Kit (Qiagen, Hilden, Germany) in accordance with the manufacturer’s instruction.
The diagnosis was confirmed by polymerase chain reaction (PCR) assay using two universal primers, namely ITS1 and ITS4, to amplify the internal transcribed spacer 1 (ITS1) and ITS2 regions and the 5.8S ribosomal DNA (rDNA) region of the fungi as described previously [9]. The amplicons were sequenced and compared with the GenBank database using the Basic Local Alignment Search Tool, and comparative analysis revealed Rhizopus oryzae. The obtained sequences were submitted to GenBank and received the accession number MG946811.
The brain magnetic resonance imaging scan revealed the involvement of the maxillary sinus, ethmoid bone, and left sphenoid sinus with no mass effect. The brain computed tomography scan also demonstrated the involvement of the left maxillary, ethmoid sinuses, and nasopharynx, as well as the destruction of the bone of the medial wall of the left maxillary and ethmoid sinuses ().
Given the rapid progression of the disease and the spread of infection to the eyes and brain, the eye removal was recommended. However, the patient’s family refused the enucleation. Consequently, the infection progressed to the eye, and the patient lost her vision. At the same time, severe oral ulcers appeared. Patient’s respiratory and hemodynamic conditions were stable. The dosage of amphotericin B deoxycolate (75 mg/day) increased, and broad-spectrum antibiotics were continued. Eventually, despite antifungal treatment and special care, the patient expired in September 6 due to the rapid progression of the infection to the brain as a result of the refusal of the patient's family regarding enucleation surgery.
The study protocol was approved by the Ethics Committee of Mazandaran University of Medical Sciences, Sari, Iran (IR.MAZUMS.REC.95.1560). Informed consent was obtained from the patient’s next of kin for each procedure. |
pmc-6488283-1 | Our case was a 4-month-old male infant with neuroblastoma undergoing chemotherapy referred to the Oncology Department of Amirkola Children’s Hospital, Mazandaran, Iran, with fever and neutropenia, without any obvious source of infection. The patient had undergone surgery for neuroblastoma 2 months prior. Laboratory examinations showed the C-reactive protein level of 76 mg/L, white blood cell count of 1.8×103/ μl (i.e., leukopenia), neutrophil count of <500 cell/μl, hemoglobin level of 6.5 g/dl, and platelet count of 134×103/ μl. The blood samples were collected aseptically by arterial puncture in BD BACTEC Plus Aerobic/F culture bottles (Becton Dickinson and Company Spark, MD 21152, Shannon, County Clare, Ireland) and incubated in a BACTEC culture system (Becton Dickinson Microbiology Systems).
The patient was prescribed ciprofloxacin prophylaxis due to mucositis; in addition, empirical therapy with ceftazidime and vancomycin was instituted for up to 7 days; however, his condition deteriorated rapidly. Initial blood cultures were negative for bacteria, whereas two consecutive blood cultures were positive for yeast-like fungi. Positive blood cultures were subcultured on CHROMagar Candida (bioMe´rieux) and resulted in the emergence of smooth colonies with white to cream colors after 24 h in dark. Candida species were initially identified based on conventional assays.
Voucher strains were deposited into the reference culture collection under the accession number IFRC2085. In addition, identification at the species level was performed by using DNA sequencing. Genomic DNA was extracted from 2 to 3-day-old Sabouraud dextrose agar cultures with an UltraClean Microbial DNA Isolation Kit (Mo Bio Laboratories) according to the manufacturer’s protocol, and then stored at -20°C prior to use. The internal transcribed spacer (ITS) was amplified and sequenced using primers ITS5 and ITS4 as previously described [].
Briefly, the amplification of ITS rDNA was performed using a cycle of 5 min at 94°C for primary denaturation, followed by 40 cycles at 94°C for 30 sec, 52°C for 30 sec, and 72°C for 80 sec and a final 7-min extension step at 72°C. The sequence data were adjusted using Lasergene SeqMan software (version 9.0.4, DNASTAR) and compared with the data of GenBank through local BLAST with a molecular database maintained for research purposes at the CBS-KNAW Fungal Biodiversity Centre, Utrecht, Netherlands. The DNA sequence of the ITS rDNA region matched that of C. guilliermondii (MH714912) by showing 99.9% similarity with the ex-type strain.
In vitro antifungal susceptibility test was also performed according to the documents M27-A3 and M27-S4 of the Clinical and Laboratories Standards Institute. For the preparation of the microdilution trays, amphotericin B (Sigma, St. Louis, MO, USA), fluconazole (Pfizer, Groton, CT, USA), itraconazole (Janssen research foundation, Beerse, Belgium), voriconazole (Pfizer), and caspofungin (Merck, Whitehouse Station, NJ, USA) were obtained from their respective manufacturers as reagent-grade powders. The minimum inhibitory concentrations for amphotericin B, fluconazole, itraconazole, voriconazole, and caspofungin were obtained as 0.063, 4, 2, 0.25, and 0.5 µg/ml, respectively.
The patient was empirically treated with 0.75 mg/kg/day amphotericin B deoxycholate intravenously, which is a regimen frequently used as standard therapy for candidaemia in Iran. After treatment with amphotericin B for a week, two sequential blood cultures remained negative. The patient was successfully treated and showed no relapse during the two-week follow-up. This report was approved by the Ethics Committee of Mazandaran University of Medical Sciences, Mazandaran, Iran. In line with the principles of research ethics, written informed consent was obtained from the parents of the patient. |
pmc-6488287-1 | A 35-year-old man with refractory AML was admitted to a tertiary hospital in Tehran, Iran. He was a candidate for EMA regimen, including mitoxantrone, etoposide, and cytarabine. The patient was subjected to central venous catheter and chemotherapy. Four days after chemotherapy, he became feverish due to catheter-related infection with an oral temperature of 38.3°C and an absolute neutrophil count of less than 100 cell/μl.
Laboratory evaluation also revealed anemia and thrombocytopenia with a hemoglobin level of 9.5 g/dl and platelet count of 20,000 per microliter. The results of urinalysis were normal, and meropenem and teicoplanin were prescribed. Ultrasonography revealed acute thrombosis in the jugular vein. Furthermore, Staphylococcus epidermidis was detected in the blood cultures of the central line and peripheral vein. Antibiotic lock therapy was started simultaneously with systemic antibiotics. The patient became afebrile after 3 days.
Ten days later, the patient had another episode of fever and neutropenia. However, other vital signs were stable. Paranasal sinuses computed tomography (CT) scan showed sinusitis generally at the maxillary and ethmoid sinuses with hyperdense opacification (). Liposomal amphotericin B (LAMB) with a dosage of 5 mg/kg was initiated, and he was subjected to sinus endoscopy and functional endoscopic sinus surgery.
Simultaneously, multiple painful erythematous macular and papular lesions with a necrotic center resembling ecthyma gangrenosum were detected on the lower extremities, upper limbs, and trunk, which were then distributed to the head and neck (). Therefore, he was subjected to skin lesion biopsy. Furthermore, the patient complained of the loss of vision in his left eye, and fundoscopic examination revealed endophthalmitis. As a result, intravitreal AMB was added to the systemic antifungal therapy.
While fever and neutropenia were still persisting, 10 ml of venous blood sample was aseptically obtained from the patient via venipuncture according to a standard technique by using a sterile syringe after skin disinfection. Subsequently, the inoculated culture bottles were placed into the BacT/ALERT Microbial Detection System (BacT/ALERT FA Plus, bioMerieux SA, France).
The BACTEC bottle that showed a sign of fungal growth was subcultured on the plates with the brain heart infusion agar (Merck, Germany) and Sabouraud dextrose agar (SDA) (Merck, Germany) separately, and then incubated at 37C and 30C sequentially. After 72 h, the results of blood culture on the brain heart infusion agar demonstrated a colony of fungi, microscopically seen in methylene blue (). The results of culture on SDA media showed the production of hyaline, banana-shaped multicellular macroconidia with foot cell at the base.
DNA was extracted from the fresh and pure culture colonies using the method described by Makimura et al. with some modifications []. Briefly, small amount (approximately 5 mm3) of the fresh colony was allocated in 100 μL lysis buffer (100 mM Tris-HCl, pH=7.5, 30 mM EDTA, 0.5% w/v SDS) and crushed with a conical grinder (Micro Multi Mixer, IEDA Co. Ltd., Tokyo, Japan) for 1 min. Subsequently, it was incubated for 15 min at 100°C, mixed with 100 μL of 2.5 M sodium acetate, kept at -20°C for 60 min, and finally centrifuged at 12,000 g for 5 min.
After the removal of supernatants, DNA was precipitated with an equal volume of isopropanol, and then kept at -20°C for 30 min and centrifuged at 8,000 g for 15 min. Then, the pellet was washed with 300 μL of 100% and 70% ethanol and air dried. Finally, the DNA was resuspended in 50 μL of ultrapure water and kept at -20°C until being used as template for polymerase chain reaction (PCR). The ITS1 and ITS4 universal primers were used for PCR.
In the next stage, DNA sequencing was performed for the accurate identification of the isolate (Bioneer Company, South Korea). For the confirmation of species identity, the obtained sequences were compared with similar sequences in the open access NCBI database (http://blast.ncbi.nlm.nih.gov/Blast.cgi). Alignment of the obtained sequence in BLAST revealed a 99% identicality with the type strain of Fusarium chlamydosporum, indicated with sequence ID: KX783374.1.
The sequences were in GenBank under the accession number ‘‘MK212931.’’ Microdilution testing was performed according to the CLSI document M38-A2 []. The antifungal agents administered were AMB (Sigma-Aldrich, USA), voriconazole (VOR; Pfizer Central Research, UK), and caspofungin (Merck, USA). The endpoint was the antifungal concentration that produced complete inhibition of visual growth during 48 h. The minimum inhibitory concentration (MIC) endpoint for the VOR and AMB was defined as the lowest concentration that produced complete growth inhibition.
On the other hand, the minimum effective concentration (MEC) endpoint for caspofungin was defined based on the previous research [, ]. The MEC is the lowest concentration of drug that leads to the growth of small, rounded, compact hyphal forms as compared to the hyphal growth seen in the growth control well. Fusarium species was susceptible to AMB, VOR, and caspofungin.
After the removal of the catheter, VOR 6 mg/kg (twice a day) was administered for the first day, and then 4 mg/kg (twice a day) was prescribed, in addition to LAMB. Serum galactomannan test results were found to be positive twice consecutively. Histopathological analysis of the skin lesion on the lower extremity revealed deep-sited supportive granulomatous inflammatory dermal reaction, containing mycelial fungal element, which was consistent with deep mycosis.
The smear revealed hyphae that were compatible with Fusarium species (). Sinus biopsy revealed sinonasal mucosa with fragmental elements compatible with mold infection. Furthermore, the sinus biopsy culture demonstrated hyaline septate hyphae, which were suspected as Fusarium species according to the phenotypic criteria (i.e., microscopic and macroscopic characteristics; ). Eight days after the initiation of antifungal combination therapy, the patient’s general condition worsened, and he developed respiratory distress. Therefore, the patient was transferred to the Intensive Care Unit; however, he passed away. |
pmc-6488337-1 | A 69-year-old female was referred to our visual electrophysiology clinic. The referring optometrist was concerned that the nature of her visual field defects, specifically a bilateral altitudinal hemianopsia with macular involvement, suggested a malingering disorder (Figures -). The visual field changes were first noted 10 years prior, and magnetic resonance imaging (MRI) at the time revealed a pituitary microadenoma not affecting the optic chiasm. Yearly MRI examinations of the brain along with her visual fields remained stable without evidence of growth of the pituitary lesion. Her medical history was also significant for hyperlipidemia, hypertension, mitral valve prolapse, hypothyroidism treated with levothyroxine, and a 20-year history of migraine headaches without visual aura, treated with botulinum toxin injections and oral eletriptan hydrobromide. Her family history was notable for migraines in her mother and sister, the latter also having had a ruptured cerebral aneurysm.
Her physical examination was unremarkable. Ophthalmic examination revealed visual acuity of 20/20 in each eye. The anterior segments were normal. The cup to disc ratios were 0.3 with healthy appearing nerves bilaterally. Dilated funduscopic examination was normal in both eyes except for lattice degeneration in the inferior periphery of the right eye. Confrontational visual fields were absent superior to the midline. Optical coherence tomography testing of the optic nerve head and macula were normal. Color vision testing was normal in both eyes. A mfVEP was performed and confirmed bilateral superior altitudinal visual deficits with macular involvement (Figure ). Repeated MRI and magnetic resonance angiogram (MRA) testing of the brain and orbit revealed a hypoenhancing lesion of the right side of the sella turcica, consistent with a pituitary microadenoma, measuring 7.8 x 3.6 mm. This was slightly smaller than the previous examination one year before. |
pmc-6488340-1 | A 69-year-old male came with a complaint of cutaneous lesions on the right arm associated with redness and itching for 11 months. Other skin lesions and systemic symptoms were notably absent. A physical examination revealed three verrucous plaques on the right elbow and ulcerated papulonodules on the medial aspect of the right elbow (Figures -).
A 4 mm punch biopsy from the medial aspect of the right elbow demonstrated chronic granulomatous inflammation with diffuse dermal mixed infiltrate of neutrophils, histiocytes, and plasma cells and occasional microabscesses (Figures -). Gram stain, acid-fast bacilli (AFB), and periodic acid-Schiff (PAS) stains with appropriate controls for organisms were negative. Cultures obtained were negative for fungus and AFB at six weeks.
A diagnosis of sporotrichosis was made based on the sporortrichoid spread of lesions in a linear pattern up the lymphatics, histopathological findings, and the absence of AFB on special stains and culture. The patient was started on itraconazole.
After a month, the patient came back for a follow-up with a flare-up of the lesions on the right elbow. On probing, the patient admitted to cleaning an aquarium at home before the start of lesions. A biopsy of the lesions was sent for AFB stain, PAS stain, and culture for fungus and AFB. The fungal stain showed no yeast and hyphae. No AFB were found on direct smear. No fungus was isolated at six weeks of culture. At seven weeks of culture, AFB was isolated and identified as Mycobacterium marinum (M. marinum). The patient was started on rifampin, 300 mg twice a day, and ethambutol, 400 mg five times a day. The patient reported considerable improvement with the above treatment. |
pmc-6488342-1 | The patient is a 54-year-old male with no known past medical history who presented to the hospital with sudden onset of sharp, epigastric abdominal pain, weight loss, and nausea. Physical examination was remarkable for epigastric tenderness, scleral icterus, and painless jaundice. He was admitted to the hospital after being stabilized with intravenous saline, antiemetic medication, and analgesics. Liver function tests were elevated, Carcinoembryonic antigen (CEA) level was 652.9 ng/ml, and IgG4 was 464mg/dL. Computed tomography (CT) scan of the abdomen and pelvis revealed diffuse parenchymal enlargement, with surrounding inflammatory changes. Magnetic resonance imaging (MRI) of the abdomen revealed heterogeneous enhancement in the head of the pancreas along with a short segmental stricture of the common bile duct with extrahepatic biliary dilatation (Figures -).
Liver biopsy was performed with hematoxylin and eosin stain showing cuff-like periductal lymphoplasmacytic infiltration and normal surrounding pancreatic parenchyma. Plasma cell-rich mixed infiltrate around bile ducts and periductal fibrosis were noted as well. These biopsy findings along with serum IgG4 levels were consistent with IgG4 AIP. The patient responded well to steroids, and the CEA levels dropped. He followed up in office and steroids were tapered with plans to start azathioprine. Ten months later, he presented to the hospital with obstructive jaundice and right upper quadrant pain. IgG4 at that time was >700 ng/ml. MRI of the abdomen and pelvis showed relapse of AIP with cystic changes at the level of the pancreatic neck, as well as a 1-cm long stricture of the proximal intrapancreatic portion of the common bile duct, wall thickening of the common hepatic duct, and the common bile duct. These findings were indicative of sclerosing cholangitis or IgG4-SC. The patient was again started on steroids and is currently doing well. |
pmc-6488343-1 | A 45-year-old Asian male presented with a history of nasal bleeding from the left nostril, watering of the left eye, and nasal obstruction (on and off); examination revealed a mass in the left nasal cavity. Computed tomography (CT) and magnetic resonance imaging (MRI) scans revealed a heterogeneous soft tissue attenuation mass in the left anterior nasal cavity, causing the erosion of the medial wall of the left maxillary sinus, showing irregular speculated calcification with a small, extra-osseous soft tissue component in the anterior deep subcutaneous tissue of the cheek, causing the blockage of the left osteomeatal complex and the narrowing of the left inferior meatus with resultant soft tissue attenuation (Figures -). Biopsy revealed small cell neuroendocrine carcinoma (SCNEC) strongly positive for cytokeratin (CK) and epithelial membrane antigen (EMA), moderately positive for CD-56 and neuron-specific enolase (NSE) and negative for p-63, CK-5/6, synaptophysin, chromogranin A, desmin, and p-40. The patient had no evidence of distant metastasis and received CCRT with cisplatin and etoposide along with a total radiotherapy (RT) dose of 60 Gy in 30 fractions, delivered by the intensity modulated radiotherapy (IMRT) technique. Target delineation was done after a CT-MRI fusion scan (Figure ) and the target coverage (color wash) was between 95% and 107% of the prescribed dose. The clinical target volume (CTV) high was kept equal to the gross tumor volume (GTV) plus a margin of 7 mm (GTV+7 mm) and the planning target volume (PTV) high was kept equal to the CTV high plus a margin of 5 mm (CTV high+5 mm) (Figure ). The patient also received concurrent cisplatin 75 mg/m2 on Day 1 and etoposide 100 mg/m2 on Days 1 to 3 (every three-weekly cycle). The CT scan revealed an optimal response at Week 5 of RT (Figure ). Presently, the patient is on the adjuvant chemotherapy protocol and is planned for three more cycles of chemotherapy. The patient, at present, is symptomatically better and continues regular follow-up. |
pmc-6488344-1 | A 28-year-old male was admitted after a motor vehicle collision (MVC) with low back pain and orthopedic fractures. The admission CT scan of his lumbar spine was read as a posterior superior endplate fracture at L1 extending to the posterior vertebral body, without posterior element displacement or disc space widening (Figure ). The patient was placed in a thoracolumbosacral orthosis (TLSO). MRI was deferred at the time due to an emergent orthopedic procedure for bilateral open fractures of the lower extremities. The patient remained in the hospital for four weeks with immobilization due to his orthopedic procedures. He was not able to obtain an MRI during this period due to the external orthopedic fixation. He did not complain of any neurologic symptoms, was voiding independently and able to wiggle his toes in the orthopedic fixation. When he was released from fixation and finally mobilized the patient had sudden and severe leg weakness both proximally and distally accompanied by paresthesias. An MRI (Figure ) showed complete ligamentous disruption through the disc space and posterior ligamentous complex (PLC) disruption with subluxation of the vertebral bodies, AO L1/2 type C2, L1 type A3. There was significant edema in the conus that extended up into the thoracic spinal cord concerning for ischemic injury secondary to severe compression. The patient underwent emergent open decompression at L1-2 and pedicle screw fixation at T12-L2 (Figure ). The displaced segment was carefully reduced under fluoroscopic guidance using rod distraction. The patient did not recover the motor function of his legs two months later at his last follow-up. His sensory symptoms improved and he had preserved genitourinary function. |
pmc-6488346-1 | A 45-year-old male with a history of a Wolff-Parkinson-White pattern was admitted to the hospital with complaints of a sudden onset of chest heaviness radiating to left arm, along with profuse sweating, for two hours. His family history was unremarkable. He denied smoking, alcohol, cocaine, and tobacco use. Physical examination revealed a blood pressure of 160/100 mmHg and a regular pulse rate of 100/min. The remainder of the physical examination was unremarkable. EKG on arrival revealed sinus rhythm with a right bundle branch block (RBBB), normal axis, and ST-segment elevation of 2 mm in leads V3-V5 with reciprocal changes in leads I and aVL. A short PR interval with delta waves was also observed in the EKG (Figure ). In light of the patient's symptoms and EKG findings, a diagnosis of acute myocardial infarction (AMI) with a WPW pattern was made. Immediate therapy, including aspirin, clopidogrel, metoprolol, nitroglycerine, and heparin, was administered, and the patient was rushed for an emergent coronary angiogram.
A coronary angiogram revealed a nondominant right coronary artery (RCA), a non-obstructive left circumflex (LCX) artery, and a severe lesion in the mid-segment of the left anterior descending (LAD) artery (Figure ). Primary percutaneous coronary intervention (PPCI) to the LAD was performed, and a drug-eluting stent (DES) was deployed (Figure ). During the procedure, the patient developed narrow complex regular tachycardia with poor hemodynamics, so synchronized electrical cardioversion was performed with 100 joules. Post-percutaneous coronary intervention (PCI), thrombolysis in myocardial infarction (TIMI)-3 flow was achieved successfully (Figure ). Complete resolution of the patient's symptoms and EKG changes were reported after the angioplasty (Figure ).
The laboratory evaluation, including a complete blood count (CBC), serum creatinine (Cr), glycated hemoglobin (HbA1c), and posterior-anterior chest X-ray, was within normal limits pre- and post-procedure. Cardiac troponin-I levels came back elevated with a serially rising trend (0.3 ng/ml, 28 ng/ml, 37ng/ml). The echocardiogram revealed moderate left ventricular systolic dysfunction with apical and septal akinesia and an ejection fraction (EF) of 35% with Grade I left ventricular (LV) diastolic dysfunction. The rest of the hospital course was unremarkable, and the patient was discharged home in stable condition. Follow-up echocardiogram at six weeks revealed improvement in the LV systolic function (left ventricular ejection fraction (LVEF) was 45% with apical akinesia). The patient was followed up for two years after the event, and at the last recent follow-up, there were no reported symptoms or events. |
pmc-6488347-1 | A 34-year-old woman was diagnosed with a non-keratinizing, moderately differentiated, large cell squamous cell carcinoma of the cervix, stage IIIB, in 2015. She underwent concomitant chemotherapy (paclitaxel 90 mg/m2 plus carboplatin 160 mg/m2 for six cycles) plus pelvic radiation therapy (5000 cGy) in 25 fractions of 200 cGy). The rationale for the use of such a chemotherapy regimen was not provided by the referring physician. The treatment was completed in July 2015. The patient did not receive brachytherapy immediately, as she was lost to follow-up.
She was referred to the Instituto Nacional de Cancerologia 11 months after finishing pelvic radiotherapy for consideration of brachytherapy. In the evaluation, without evidence of cancer, the patient exhibited a grade III rectal toxicity (mucoid, watery diarrhea, more than eight episodes a day). Based on the length of time since the completion of prior therapy and the residual toxicity from prior therapy, it was determined not to administer brachytherapy. The patient was followed without any evidence of recurrent disease; however, 21 months after the completion of therapy, she complained of occasional hematuria without any other symptoms. She also reported a painful inter-scapular mass that was progressively growing over the course of the prior three months. Physical examination showed a solid left upper paraspinal mass, firmly attached to the deep planes, with a diameter of 4 cm (Figures -). Pelvic examination showed no evidence of tumor relapse.
An abdominal and pelvic computed tomography (CT) scan showed a solid right renal lesion on the cortex of the middle third and lower pole of the right kidney measuring 4.9x5.1x5.2 cms (Figure ). A CT scan of the chest showed a solid lesion with peripheral uptake in the left paravertebral muscles at the level of T5-T8, measuring 3.8x2.8 cms in diameter (Figure ).
A fine needle aspiration biopsy of the paravertebral mass confirmed metastatic, poorly differentiated large cell carcinoma with necrosis. Immunohistochemistry showed a positive immunophenotype for cytokeratin (CK) 7, CK5/6, p63, and p16, favoring squamous cell carcinoma (Figures -).
Given the fact that the images showed evidence of extensive tissue infiltration by the paraspinal lesion, it was deemed that surgery would not be ideal.
The patient underwent a right total nephrectomy by laparoscopy. The pathology report was consistent with metastatic cervix cancer. The immunohistochemistry profile revealed the following: CK AE1/AE3 (+), CK 7 (+), CK 20 (-), p63 (+), CK 5/6 (+), renal cell carcinoma marker (RCC) (-), cell membrane metallopeptidase 10 (CD10) (-), p16 (+), transcription factor protein 3 (guanine - adenine - thymine) (GATA 3): non-contributory (Figures -).
Because she had a complete resection of the kidney, without residual lesion, pelvic radiation therapy was not considered. Then, it was decided to give radiotherapy to the para-spinal mass and chemotherapy. She received conformal three-dimensional conformal radiotherapy (3DCRT) radiotherapy to the para-spinal mass, using a fractionation of 300 cGy to complete 3000 cGy. She did not accept receiving chemotherapy.
Abdominal and pelvic scans in January 2018 showed the progression of the tumor, disease in the right nephrectomy bed, and a new left renal lesion (Figure ). Magnetic resonance imaging (MRI) showed the persistence of the paraspinal lesion (Figure ). The clinically presented growth of the paraspinal mass was 15x11 cm. The patient declined further therapy and died of the disease in June 2018. |
pmc-6488447-1 | A 14-year-old male presented with medically refractory hiccups and vomitus with a history of a post-radiation medullary cavernoma that acutely enlarged with significant surrounding edema. Originally, he presented at five years of age after a fall, and was incidentally found to have a right temporo-parietal and posterior fossa melanotic primitive neuroectodermal tumor (PNET, Figure ). He underwent gross total resection and was treated with adjuvant chemotherapy and radiation.
The amount of radiation received was 3600 cGy to the entire neuroaxis with a 5580 cGy boost to the tumor field. Approximately seven years after radiation, he presented with intermittent hiccups for two weeks. A brain magnetic resonance imaging (MRI) revealed a 4 mm medullary cavernoma that had minimal mass effect or edema present (Figure ). The hiccups were managed medically for over three years. This included an extensive gastrointestinal workup, thoracic bracing, and behavioral modifications, and several medications.
At the age of 14, he then presented to our emergency department with singultus and vomiting for three days. His singultus was refractory to medical management and hindered his ability for oral intake. This disrupted his normal breathing synchrony as well as sleep pattern. Repeat MRI imaging (Figure ) showed that the cavernoma had acutely enlarged from 6 mm to 10 mm over a six-week period with significant surrounding edema. The persistent hiccups and radiological growth prompted surgical intervention. He underwent a midline suboccipital craniotomy and partial C1 laminectomy.
The lesion was approached using a right lazy hockey stick durotomy and a subtonsillar approach. Arachnoid dissection of the right tonsil allowed elevation off the medulla. Pial representation was seen on the lateral wall of the obex and the right lower mid-medulla. This corridor was opened sharply and circumferential dissection of the cavernoma was performed with motor and somatosensory evoked potential monitoring. The surrounding hemosiderin-stained tissue was left in place. Please refer to Video .
Histopathological examination revealed single layer endothelium-lined channels with intervening glial tissue and immature granulation tissue displaying the growing nature of this lesion (Figure ). Post-operative imaging revealed total resection of the cavernoma and his hiccups ceased immediately. The post-operative course was routine and he was discharged home in two days. |
pmc-6488449-1 | A 33-year-old Caucasian male with no identifiable cardiac risk factors other than a five-pack-year smoking history, presented with fevers, body aches, upper respiratory symptoms, and chest pain. Upper respiratory symptoms, progressively worsening, began a few weeks prior to presentation with sore throat, rhinorrhea, lacrimation, and non-productive cough. Chest pain began 24 hours prior to presentation, which was intermittent and located in the left upper chest, radiating to the back and down his left arm. This pain was exacerbated by lying flat or getting up in a certain position but not with exertion. He denied any recent long-distance travel or driving. In the ER, the patient was noted to have low-grade fevers but was hemodynamically stable. The exam was only remarkable for mild left upper chest tenderness. Workup in the ER revealed leukocytosis of 15000 u/L (normal 3800-10600 u/L) and serum troponin of 15.61 ng/L (normal <0.05 ng/L). Electrocardiogram revealed T-wave inversions in the lateral leads (Figure ). He was admitted with a provisional diagnosis of viral myocarditis. Although less likely, as NSTEMI was not ruled out, he was started on heparin drip per the acute coronary syndrome (ACS) protocol. A transthoracic echocardiogram showed inferior, inferolateral, and inferoseptal wall motion abnormality, with a low-normal left ventricular ejection fraction. The coronary angiogram demonstrated an occluded left circumflex artery and obtuse marginal (Figure ) and critical disease of the right coronary artery with occlusion of the posterior-descending artery and subtotal occlusion of the posterolateral branch (Figure ). It was decided to undergo percutaneous intervention (PCI) on the lesion within the left circumflex (Figure : right image). The patient was brought back later to the catheterization lab for staged PCI with a resolution of symptoms. |
pmc-6488451-1 | A 77-year-old female presented with a left clival mass, which was found incidentally on magnetic resonance imaging (MRI) (Figure ). Neurological examination was normal, except casual headaches. Past medical history includes functional endoscopic sinus surgery (FESS) and septoplasty in 1998, and ongoing chronic sinus issues. A positron emission tomography-computed tomography scan (PET-CT) was performed to exclude primary neoplasm. The patient was admitted for biopsy and resection of left clival mass. The patient underwent a total resection of the mass via transsphenoidal endoscopy; the mass was found to be isolated from the sellar and suprasellar area, with no connection between the mass and the pituitary gland nor stalk, and was found on a different plane in the clivus (Figure ). The patient was discharged three days later with no neurological deficit. The histopathology was submitted as “ectopic pituitary adenoma, null cell type” (Figure ). |
pmc-6488563-1 | A 20-year-old female presented to our center with a telangiectatic osteosarcoma of the humerus. There was no history of malignancies within the family.
MRI examination and open biopsy were performed by the previous physician. At the time the results were thought to be malignant lymphoma. After several diagnostic trials, the patient visited our center to seek advice about her telangiectatic osteosarcoma (A).
We observed a circumferential mass on the distal part of the right arm with a slight deformity of the arm, with marked venous engorgmnt and distal edema. The mass was warm and solid on palpation. Function of the right hand was still preserved. From the laboratory findings, there were marked elevation of the alkaline phosphatase and lactate dehydrogenase. From humerus X-ray, there was mixed lesions along the humerus with pathological fracture on the midshaft (A). T2-weighted MRI showed iso-hyperintense and expansile lesions along the humerus (A). For the metastatic workup, chest X-ray showed no coin lesions or metastatic characteristics. Patient also had a PET scan and the result was unremarkable. From the Clinico Pathological Conference (CPC) forum, it was concluded that the diagnosis was osteosarcoma of the right humerus stage IIB according to the Enneking classification.
Patient took neoadjuvant chemotherapy regimen with Doxorubicin and Cisplatin for three cycles from January to March 2016. At the end of the third cycles, clinical and radiological evaluations were performed. Clinically the mass was not getting bigger compared to before chemotherapy (B). From x-ray, the mixed lesions became more marked compared to the previous x-ray (B). MRI showed that the mass was slightly became larger compared to the previous MRI with no involvement of neurovascular bundle (B).
Six months after the initial complaint, the surgery was performed. We used extensive deltopectoral approach with anterolateral extension through the proximal part and curved backward to complete the posterior distal humerus and elbow approach. This approach was used because of the previous biopsy tract was in the posterior aspect of the distal humerus. The vascularity, rotator cuff tendons, biceps and triceps muscle, and majority of the nerves (musculocutaneous, radial, median, and ulnar nerves) were spared during the total resection of the humerus. Axillary nerve was sacrificed during the tumor resection. To reconstruct the humerus, both long shoulder hemiarthroplasty and total elbow prostheses were used. These two prostheses were joined using two long one-third tubular plate that worked as the long stem augmentation. Extension cerclage wire was used to make the implant as one unit (A). Finally, the stem was augmented with a bone cement from proximal through the distal. Prolene mesh then was sheathed to the bone cement, and then the preserved rotator cuff tendons and biceps and triceps muscle were sutured back with the Ethibond sutures (B). The resected tumor and humerus were then sent to the lab for histopathologic analysis (C).
From the post-operative x-ray, the modified prosthesis sat well on the shoulder and elbow joint (). Function of the hand was excellent post-operatively. Patient also could immediately flex her elbow. Post-operative histopathological examination showed telangiectatic osteosarcoma with HUVOS IV (). After the wound healed without complication, patient underwent adjuvant chemotherapy. Two months after the surgery, patient could start writing with her right hand without marked difficulties. Further follow up of three years post-operatively, patient already came back to work and were able to perform daily activities without difficulties. Patient’s shoulder abduction and elbow flexion was shown on the pictures (). The MSTS functional score for the upper limb scored 83% which was excellent. There were no post-operative complications and the immunohistochemical workup used to rule out lymphoma (CD20, CD15, CD 30, and CK) would be planned. |
pmc-6488680-1 | A 70-year old woman was admitted from a dermatologist to the Department of Plastic and Breast Surgery, Roskilde, Denmark. A biopsy verified well-differentiated full-thickness squamous cell cancer was found at the right side of the lower lip. The tumour had been present for three years. The patient had a history of ischemic heart disease with a percutanous coronary intervention and implantation of a stent in 2002. She was a heavy smoker. No alcohol overconsumption was reported. By clinical examination, a 15 × 15 mm sore, firm, central ulcerating tumour was seen located at the vermillion border (). At the mucosal side of the lip, leukoplakia was observed.
No enlarged lymph nodes in the cervical region was found at the clinical examination.
Surgical intervention would remove approximately 50% of the lower lip. The patient was offered radiotherapy as an alternative to surgery and chose the former. She underwent a series of radiotherapy for a period of two months.
Five weeks after the initial clinical examination at our clinic, the patient was readmitted to our department from the Department of Oncology at Copenhagen University Hospital due to recurrence of the squamous cell cancer located to the lower lip. At this point, the patient presented a monstrous, ulcerating tumour, involving most of the lower lip (). No clinical signs of systemic spread to lymph nodes in area was found by thorough clinical examination and palpation of the head and neck. Furthermore, a 18FDG-PET-CT was performed and ruled out further local or systemic spread.
First, a total excision of the lower lip including the commisures during which free resection borders of 1 cm were confirmed by intraoperative frozen section diagnosis. 8 days after primary excision, histopathology confirmed free resection borders, and reconstruction of the lower lip by bilateral Fujimori technique was performed (, , ). Due to paucity of mucosal tissue between the orifice of the parotid duct and commisures of the mouth besides a relatively narrow labial sulcus, the remaining lack of mucosal lining was reconstructed by use of split skin harvested from the right thigh.
At a clinical follow-up three months after surgery, palpable enlarged, firm lymph node was found located to the lower jaw. Biopsy confirmed the histological diagnosis of metastasis from squamous cell carcinoma. Position Emission Tomography Scan (PET) confirmed the localisation of metastasis from a squamous cell carcinoma on the left side of the jaw, but as well on the right side. No distant metastases were found. Clinical presentation 5 months after surgery is seen in .
5 ½ months after the initial admission to our department, bilateral neck dissection was performed. Several metastases with extensive perinodular growth was found on the right side, and infiltrating underlying musculature on the left side. The patient was referred to the Department of Oncology, Herlev Hospital, Denmark, where radiotherapy was given.
One months after completed radiotherapy, the patient presented in our clinic a very sore, ulcerated tumour at the jaw line on the left side. The tumour was adherent and dripping with what appeared to be saliva. Punch biopsies were not representative. A computer tomography (CT) scan confirmed local recurrence of aggressive squamous cell cancer. The patient was referred for more extensive surgery and further treatment, which is why eventual defatting of the lip was postponed. |
pmc-6488916-1 | A 43-year-old female was admitted to our hospital complaining of numbness in the left limb for one week. Past medical history was notable for the diagnosis of NMO and intracranial hemorrhage. The patient was diagnosed with NMO ten years ago due to repeated episodes of blurred vision and numbness and weakness in the limbs. Brain and spinal magnetic resonance imaging (MRI) at that time indicated lesions in the brain white matter as well as spinal cord involving cervical and thoracic regions. AQP4 antibody test was not performed. Considering the potential diagnosis of demyelinating disease, steroid pulse therapy was initiated and the patient improved after the treatment. After discharge, corticosteroid was gradually tapered and the patient was maintained at a low-dose corticosteroid and azathioprine in the long term. The patient was also diagnosed with left basal ganglia hemorrhage three years ago, presenting as right-sided hemiplegia and confusion. Brain angiography was not performed at that time, and the patient recovered after symptomatic treatment. Family members exhibited no sign of the case pathology. Upon examination, the patient appeared lethargic and sluggish, with normal vital signs. Visual acuity was impaired in the right eye with a score of 20/200 on testing. Pupils were 3 mm bilaterally, round and reactive. Regarding motor function, muscle strength was decreased in the left extremities (Medical Research Council strength score, grade 3). Hypoesthesia of the left side was also observed. Babinski sign was present bilaterally. Further investigations revealed a positive AQP4 antibody in the serum, with an elevated titer of 1:32. An initial diagnosis of NMOSD was made considering her medical history and radiological findings. Other tests including complete blood count, basic metabolic panel, serum glucose, and anti-nuclear antibodies were all normal. Brain MRI after admission indicated lesions with restricted diffusion in the right thalamus and hemosiderin deposition in the left basal ganglia (Figure ). Unexpectedly, brain magnetic resonance angiography revealed severe stenosis of bilateral anterior and middle cerebral arteries, as well as stenosis of the right posterior artery and the intracranial segment of the right internal carotid artery. Radiological findings, as a result, strongly suggested the diagnosis of MMD. Digital subtraction angiography further confirmed this diagnosis with findings of bilateral occlusion of distal internal carotid arteries and rich collaterals near the skull base (Figure ). After antiplatelet and other symptomatic therapies, the patient improved. She refused further treatment with vascular reconstruction surgery and received physical therapy at a local rehabilitation center. |
pmc-6489175-1 | An 81-year-old woman with arterial hypertension and a laparotomic appendectomy when she was 12 years old presents to the emergency department with intermittent acute abdominal pain and vomiting. The last defecation was 2 days ago, and the bowel is closed to gas. Current medications only include valsartan 80 mg daily. The body temperature is 37.5 °C, and all vital parameters are normal. The remainder of the examination demonstrates pain and localized peritonism in the lower right quadrant. Laboratory tests are normal except white blood cells at 14,000 per microliter.
Questions include the following: How should this patient be evaluated and treated? What is the working diagnosis? Options include stump appendicitis, right colon diverticulitis, pelvic inflammatory disease, bowel obstruction, gastroenteritis, right renal colic, right colon cancer, bowel ischemia, or inflammatory bowel disease (Fig. ). |
pmc-6489194-1 | A 68-year-old Caucasian female was admitted to our clinic, with suspected deep venous thrombosis, presenting with pain in her left calf that had lasted for 3 weeks starting after a very painful nocturnal leg cramp, and worsened over the last few days. At the time of admission, she had also experienced 5 days of malaise and loss of appetite and in addition 1 day of headache and lower back pain. The patient had been coughing a lot ever since recovering from a confirmed Influenza B upper airway infection 3 months earlier. The patient received antihypertensive medication but had no other known chronical medical conditions.
At the time of admission, she was fully awake with a Glasgow Coma Scale (GCS) of 15. She was afebrile with a temperature of 36.3 °C (97.3 F) and had no neck stiffness. She presented with a well-defined erythema on her left calf (Fig. ) and any touch or movement of her left knee, ankle or calf was very painful. There were no clinical signs of intra-articular fluid in the knee.
Her blood tests showed a very high level of C-reactive protein (CRP) of 450 mg/L (normal range below 10 mg/L) and D-dimer of 18 FEU/L (normal range below 0.5 FEU/L). Her LRINEC score was 5 points (4 points from CRP 450 mg/L and 1 point from hemoglobin 12.9 g/dL (normal range between 12.1 g/dL – 15.1 g/dL)). Treatment with cefuroxime was initiated due to suspected infection of unknown origin. A CT scan of the abdomen and thorax performed due to suspected lung embolism showed discrete bilateral atelectatic areas of the lungs, but otherwise normal findings.
Four hours after admission the patient had developed an altered mental state with GCS of 9 (Eyes 2, Verbal 2 and Motor 5), neck stiffness and a fever with a temperature of 38.8 °C (102 F). Due to suspected meningitis a spinal tap was performed and empiric treatment against meningitis was initiated with Dexamethasone, Ceftriaxone and Ampicillin. The tests of the cerebrospinal fluid (CSF) showed signs of meningitis with a white blood cell count (WBC) of 50 cells/μL that were 81% granulocytes, very high lactate of 17 mmol/L, very low glucose of 0.3 mmol/L and very high protein level above 6 g/L. Initial microscopy showed Gram-positive diplococci. A CT-scan of the patient’s brain was performed and showed no abnormalities.
Eight hours after admission the patient showed a slight decline in GCS of 8 (Eyes 2, Verbal 2 and Motor 4). However, she still showed a disproportionally strong pain reaction to any touch of the left calf. The erythema had not spread since admission to the hospital, but over the next 2 h a spread of about 5 cm proximally was observed. Due to the progression of the erythema together with the strong pain reaction despite a decline in mental state, a diagnostic incision of the tissue was performed in local analgesia. The subcutis was found to be loose from the fascia and the tissues looked nonvital. Antibiotic treatment was changed to Meropenem, Clindamycin and Ciprofloxacin against NF due to national guidelines. An acute surgical débridement was performed (Fig. ). The patient was transferred to a hospital specialized in the treatment of patients with NF, including specialized surgical care, intensive care, and hyperbaric oxygen treatment. Reinspection of the tissue in the left leg was performed with no findings of necrotic tissue. Inspection of the leg was afterwards performed routinely once daily with normal findings.
Over the next days, S. pneumoniae was cultured both in the CSF and in 4 out of 4 blood cultures from the patient. The serotype of the bacteria was determined as 9 N. No bacteria were found by culturing the tissue from the leg, but 16S-PCR of the tissue was performed, which also showed S. pneumoniae. The 16S-PCR was performed at a department of clinical microbiology at a big university hospital. It was performed from a commercially available MicroSEQ kit with a fragment size of 500 base pairs. The cultured S. pneumoniae were susceptible to all antibiotics that were tested, including benzylpenicillin. No other bacteria were found. Therefore, antibiotic treatment was switched to benzylpenicillin on day 3 after admission.
The patient subsequently underwent reconstructive surgery with a split skin graft (Fig. ) and was discharged after 51 days of hospitalization, including in departments of intensive care, infectious diseases and plastic surgery.
The patient later underwent different tests for immunodeficiency. Immunoglobulins, HIV-test and differential WBC count were all normal. The patient was not vaccinated against S. pneumoniae prior to her admission. However, she has been afterwards and serotype 9 N is included in the vaccine. |
pmc-6489214-1 | A 38-year-old Caucasian woman with a history of TOT surgery 2 years ago presented to our hospital with complaints of urinary incontinence that emerged during coughing, walking, and physical exercises or activities. She had also experienced dysuria and urine leakage during sexual intercourse. Therefore, she had not had regular sexual intercourse for 2 years. Prior to her admission to our hospital, she was diagnosed as having SUI and used duloxetine (80 mg, daily) for 3 months. She took no other medications on a regular basis. She had performed Kegel exercises routinely. However, her symptoms persisted. She was a housewife, with no history of alcohol consumption or tobacco smoking. She had had two deliveries: one vaginal birth and one cesarean delivery. There was no similar history of illness in her family.
On admission, her temperature was 36.6 °C, pulse was 82 beats/minute, and blood pressure was 110/65 mmHg. She was fully conscious and responsive. Psychologically, she was depressed. On systematic physical examination, no abdominal tenderness and no anatomic anomalies were detected. No murmurs or arrhythmia were detected during auscultation of her heart. Respiratory frequency was 14/minute and no wheezing or rales were detected. On neurological examination, her muscle strength and tone were normal. Ulnar, patellar, and Achilles reflexes were all normal (2+). A urogynecological physical examination revealed SUI without any urogenital prolapse. In laboratory analysis, her total white blood cell count was 6.9 × 103/mm3, hemoglobin was 12.1 g/dL, alanine aminotransferase was 38 u/l, aspartate aminotransferase was 35 u/l, C-reactive protein was 1.1 mg/l, creatinine was 0.6 mg/dl, and serological tests were negative: hepatitis B surface antigen (HbsAg), anti-hepatitis C virus (HCV), and anti-HIV. Urine analysis showed microscopic hematuria and urine culture was sterile. Post-void residual volume was insignificant. A diagnostic cystoscopy was performed and sling material which crossed her bladder neck from 3 o’clock to 10 o’clock was identified (Fig. ). The mesh material was cut with an endoscopic internal urethrotomy knife and retrieved by using foreign body grasping forceps. Other mesh parts were excised through a transvaginal midurethral incision. New TOT material was placed and the procedure was terminated. Our patient was discharged on the first postoperative day. First week, 3-month, and 6-month follow-up visits showed complete absence of urinary incontinence and other urinary complaints. |
pmc-6489226-1 | The HXEX-ALL1 cell line was derived from a 6-year-old Chinese boy of Han ancestry with BCP-ALL. The patient was admitted to West China Second University Hospital (Chengdu) in 2016 because of podalgia and hemorrhage under the skin. Physical examination upon admission revealed pale lips and enlarged superficial lymph nodes. Complete blood count revealed a white blood cell count of 22.9 × 109/l with 60% blast cells, hemoglobin level of 105 g/l, and platelet count of 52 × 109/l. BM examination revealed hypercellular marrow with 92% blasts that were negative for peroxidase staining. The primary leukemia cells were positive for CD10, CD19, CD22, cCD79 and HLA-DR, partially positive for CD5, and negative for CD20, sIgM, cIgM, CD2, CD3, CD7, cCD3, CD13, CD33, CD117 and CD34 and were thus categorized as the common B subtype according to the EGIL classification []. G-banding analysis of the BM revealed the karyotype 47, XY, +8, del(9p22), del(17p12). FISH analysis demonstrated negative expression of MLL, BCR-ABL, ETV6-RUNX1 and PDGFRB fusion genes. Multiple real-time polymerase chain reaction (RT-PCR) analyses indicated negativity for the following fusion genes: MLL-AF4, MLL-AF6, MLL-AF10, TEL-AML1, MLL-ENL, BCR-ABL P210, BCR-ABL P190, SIL-TAL, E2A-HLF, CALM-AF10, HOX11, HOX11L2, SET-CAN, TEL-ABL1, TLS-ERG, NPM-ALK and E2A-PBX1. The patient received chemotherapy according to the Chinese Childhood Cancer Group ALL 2015 (CCCG-ALL-2015) protocol. The regimen included dexamethasone (DEX), pegaspargase (Peg-Asp), vincristine (VCR), daunorubicin (DNR), cyclophosphamide (CTX), cytarabine (Ara-c), mercaptopurine (6-MP), and methotrexate (MTX). After 19 days of chemotherapy, the proportion of blasts in the BM was reduced to 1%, demonstrating complete remission (CR) and negative minimal residual disease (MRD) (< 0.01%). The patient was classified into a low-risk group. However, he experienced BM relapse after 4 months, and re-induction of chemotherapy led to another CR 1 month later. The re-induction chemotherapy regimen included DEX, mitoxantrone (MTZ), vindesine (VDS), Peg-Asp, MTX, etoposide (VP-16), and Ara-c. Unfortunately, the patient experienced a second BM relapse in 3 months, and this time, chemotherapy did not lead to a CR. |
pmc-6489233-1 | Our patient was a 48-year-old woman with a history of two previous cervical surgeries, the first one in 1987 and the second in 2003, with placement of titanium plates and screws at C4-C5 and C5-C6. She was seen at the clinic in 2005 with a 2-month history of fatigue, chills, headache, nausea, and asymmetric arthralgia. She also had episodes of malar rash after sun exposure and cutaneous fluctuating rash in the trunk. Physical examination revealed arthritis of the left shoulder and left ankle, livedo reticularis, and erythematous cutaneous rash in the thorax. No infection foci were detected. Laboratory studies revealed thrombocytosis 485,000 cells/mm3 (normal range 130,000–400,000 cells/mm3), elevated C-reactive protein (CRP) 75 mg/dl (normal range 0.1–1.0 mg/dl), and erythrocyte sedimentation rate (ESR) 40 mm/h (normal range 0–20 mm/h). Autoantibodies were negative, and complement levels were within normal range.
From 2005 to 2007, she had no treatment, and her symptoms had a fluctuating course. In 2007, fatigue, rash, and arthralgia appeared again, and she developed edema in her hands and feet. Rheumatology started prednisone and methotrexate without improvement. Six months later, dysphagia, halitosis, and “sputum” production of purulent aspect were added to the patient’s symptoms. She consulted an ear, nose, and throat specialist, who did not find any abnormality.
She continued with elevated CRP, ESR, and thrombocytosis. Labeled leukocyte single-photon emission computed tomography (SPECT) suggested spondylitis in the cervical spine (C4-C6) and revealed an inflammatory process in the nasopharynx, an increase in the prevertebral space of > 2 cm, and free air in this area (Fig. ). An esophagogram with hydrosoluble contrast revealed a posterior pharyngoesophageal diverticulum with a fistula to C6 (Fig. ). The patient’s x-rays of the lateral column after the cervical spine anterior fixation in 2003 showed preserved prevertebral space, and intersomatic C4-C5 box and plate were 5 mm anterior to the vertebral bodies, pressing the esophagus (Fig. ).
The patient was taken to surgery; screws and plates were removed from C4 to C6; surgical debridement was performed; and the fistula and diverticulum were removed with cricopharyngeal myotomy and esophageal repair. Esophagography with water-soluble contrast showed no leak after surgery, but the lumen of the esophagus at C4–C6 was increased in diameter with diminished compliance. Removed plates, screws, and tissue were cultured and grew Streptococcus milleri. The patient was treated with oral amoxicillin 1 g every 8 h and probenecid for 4 months, until a gammagram was negative. Her fatigue, arthralgia, rash, and livedo reticularis as well as dysphagia disappeared. Her acute-phase reactants normalized. |
pmc-6489251-1 | A 78-year-old obese female presented to the emergency room with new onset dyspnea of one day duration, which worsened in the past couple of hours. Her medical history included hypertension and a hemorrhagic stroke two years prior which left her bedbound. She denied any familial history of PE, leg pain, or palpitation. At admission, blood pressure, pulse rate and peripheral oxygen saturation were 116/78 mmHg, 135 beats/min and 88%, respectively. On physical examination, she had tachypnea (30 breaths/minute) and electrocardiography revealed sinus tachycardia. Arterial blood gas analysis on room air yielded pH 7.44, PCO2 33.9 mmHg, and PO2 72.9 mmHg. Routine blood tests demonstrated a normal cardiac troponin I levels and no evidence of electrolyte imbalances, while chest X-ray revealed no signs of heart failure. Nevertheless, D-dimer was highly elevated (> 4000 ng/dL) increasing the suspicion of PE. Computed tomography pulmonary angiogram was sought revealing bilateral PE (Fig. a). Lower limb Doppler was negative for deep vein thrombosis.
Twenty-four hours after diagnosing bilateral PE and stabilizing the patient with anticoagulation and hemodynamic support, the patient developed new onset palpitation, dizziness, and fatigue. Cardiac enzymes were repeated showing a mild elevation. Electrocardiography reveled new onset AF with slow ventricular response of 33 beats/min (Fig. b). She was not on any negative chronotropic drugs and no electrolyte imbalance was detected. Echocardiography revealed normal left ventricular systolic function and dimensions, left ventricular regional wall motion, and both left and right atrium dimensions. However, it highlighted dilated right ventricular dimensions with a basal diameter of 50 mm and evidence of McConnell’s sign (right ventricular free wall hypokinesia) with paradoxical septal wall motion. In addition, it revealed impaired right ventricular systolic function with tricuspid annular plane systolic excursion of around 1.5 cm, flattening of intraventricular septum, and moderate tricuspid regurgitation with pulmonary artery systolic pressure around 50 mmHg. As the patient was developing hemodynamic instability, 48 h later, single chamber pacemaker was implanted in the left pre-pectoral pocket and the basal heart rate was set up to 60 beats per minute (Fig. c and d). After a 2-month follow-up, the patient showed normal vital signs and her electrocardiogram showed a paced rhythm with a heart rate of 60 beats per minute. She developed no further complications or clinical morbidities in spite her poor prognosis. |
pmc-6489272-1 | A 36-year-old Zimbabwean black female who had presented to her General Practitioner with shortness of breath, coughing, wheezing, nasal blockage, sneezing and throat irritation was referred to the Asthma, Allergy and Immune Dysfunction Clinic in Harare, Zimbabwe for evaluation of suspected allergic asthma. At presentation she volunteered a 3-month history of a non-productive diurnal and nocturnal cough, shortness of breath, tightness of the chest, wheezing episodes and dyspnoea. She also reported a sore throat, sneezing and itchiness of both eyes and the palate. The symptoms were worse during working hours, but also occurred during working day nights when she had difficulty breathing and constantly cleared her throat. She had no personal or family history of asthma or rhinitis until diagnosed with asthma in the preceding 3 months. She associated the exacerbation of symptoms with exposure to strong smells and generator exhaust smoke. She was using a prescribed salbutamol inhaler 2–3 times per day and used her inhaled fluticasone daily as prescribed.
The patient was employed as a receptionist at the offices of a banking conglomerate whose offices were located in an affluent residential neighbourhood. She lived in the neighbourhood and had been employed at the same premises for more than 10 years. She kept no pets, never smoked cigarettes and did not drink alcohol. She had no unusual hobbies. There was no family history of atopic diseases including asthma and rhinitis.
The symptoms initially manifested in August 2015, when she was relocated to her new office. Exposure to smoke, dust and strong smells for example the diesel-powered electricity generator at the workplace increasingly aggravated the symptoms. She had twice attended an A&E Department in an “attack” and asthma was diagnosed. There was transient improvement on inhaled fluticasone and salbutamol followed by frequent and often daily exacerbations despite adherence to her prescribed medicines. The past medical history was unremarkable, specifically, she denied any previous history of shortness of breath, wheezing, nocturnal dyspnoea, sneezing, allergy, fevers, productive coughing, haemoptysis, dependent oedema, or weight loss.
On presentation she appeared well-nourished and in no obvious distress. Routine vital signs revealed a normal temperature of 36.5 °C, the blood pressure was 147/87 mmHg, the pulse was 91 beats per minute. She weighed 65 kg, stood at 156 cm giving her a healthy body mass index (BMI) of 26.7. The jugular venous pressure was not elevated. The heart was normo-rhythmic, without murmurs, rubs, or gallops. The respiratory rate was 16 breaths/min and pulmonary auscultation was normal with no wheezing. A radiologist had reported a recent chest X-ray as normal. The abdomen was soft and non-tender with normal bowel sounds. The spleen and kidneys were not enlarged. There was no palpable lymph node enlargement. The hands were pink and warm with no clubbing.
With a presumptive diagnosis of asthma and rhinitis, the first order of investigations was to confirm the diagnosis and to identify potential triggering allergen sources. The Asthma Control Test (ACT™) questionnaire was administered []. Skin prick testing (SPT) with a panel of 14 common environmental aeroallergen was conducted using extracts from Stallergenes SA, Anthony, France. Immunoblotting for allergen specific IgE antibodies was conducted using the Euroline test kit, DP3712-1601E/DP3712-6401E, (Euroimmun Medizinische Labordiagnostika AG, Lubeck, Germany). Pulmonary function testing was performed using the MSA99 Table Top Spirometer (Beijing M&B Electronic Instruments, China). Laboratory tests included a complete blood count, urea, creatinine, electrolytes and T lymphocyte subset enumeration. In view of the respiratory deficit being not bronchodilator reversible, alternate explanations were explored. A 15-parameter panel of rheumatological autoantibodies was analysed to exclude pulmonary compromise associated with connective tissue diseases using the Euroimmun ANA Profile 3 (Euroline DL1590-1601-3G) kit from Euroimmun Medizinische Labordiagnostika AG, Lubeck, Germany. |
pmc-6489290-1 | A 43-year-old white male was seen in our clinic due to recurrent sinusitis, ankle and knee arthritis, painless nodular skin lesions at extremities, and eosinophilia in 2008. His clinical history is marked by long-standing pancytopenia and MDS diagnosed in 1996 at age 30, when he complained of spontaneous rectal bleeding and fatigue, which was diagnosed as haemorrhoidal disease (Fig. ). Six years after the MDS diagnosis, he was admitted to the hospital with hepatosplenomegaly, erythema nodosum, retroperitoneal lymph node enlargement, and bilateral pleural effusion. Laboratory investigations failed to demonstrate any fungal, bacterial, or HIV infection. Chronic granulomatous pleuritis was discovered, and he was treated empirically for tuberculosis with standard doses of isoniazid, rifampicin, and pyrazinamide. Allergy to pyrazinamide developed, and ethambutol was used instead. Circulating blood cells demonstrated pancytopenia with low monocytes (haemoglobin, 7,7 g/dL; white blood cell (WBC) 3000 cells/μL; lymphocytes, 750/μL; monocytes, 60/μL; and platelets, 95,000/μL). One year later, monocytopenia improved slightly, but thrombocytopenia worsened (WBC, 1900 cells/μL; lymphocytes 475/μL; monocytes, 114/μL; and platelets, 33,000/μL). Seven years later (2006), developed respiratory distress and bronchial analysis was negative for bacterial infection. He was then treated with clarithromycin for possible atypical pneumonia. In 2007, a 27% decrease in total body weight loss was observed. The patient had been complaining of night fever, night sweats, Raynaud phenomenon, left thigh superficial thrombophlebitis, and painless perimalleolar ulcers. Skin and bone marrow (BM) biopsies were performed. The ulcer biopsy revealed vasculitis with eosinophils, whereas the BM biopsy showed myelodysplastic features and noncaseating granuloma, and myeloculture was negative. In 2008, he developed hypothyroidism, recurrent sinusitis, ankle and knee swellings and nodular skin lesions (Fig. ). Antineutrophil cytoplasmic antibodies and antinuclear antibodies were within normal limits. He presented WBC 28,610/μL with marked eosinophilia (5440/μL).BM aspirate and biopsy diagnosed MDS without excess blasts. Churg-Strauss syndrome was suspected, and after 3 months of prednisone (50 mg/day), he developed arthritis and sustained night fevers. Blood culture, arthrocentesis and thyroid biopsy were performed. Mycobacterium kansasii, a slow-growing mycobacterium, was identified in the bloodstream and synovial fluid. The thyroid histopathological analysis demonstrated chronic and acute granulomatous inflammation. Rifampicin, isoniazid and ethambutol were restarted in addition to clarithromycin for the next 2 years. Progressive spleen enlargement culminated in splenectomy in 2010. Portal thrombosis developed at the immediate post-operatory period, and oral anticoagulant was administered. The histopathology features displayed granulomatous splenic inflammation, abscesses and central necrosis. In 2012, an increased WBC (39,080/μL) with eosinophilia (20,630/μL) and thrombocytosis (1,099,000/μL) were found. The nitro blue tetrazolium test, which is useful in diagnosing chronic granulomatous diseases, suggested a defect in phagocytosis, as it was positive in 38% of cells, and FIP1L1/PDGFRa rearrangement was negative, excluding hypereosinophilic syndrome. He received hydroxyurea, dexamethasone and anti-NTM therapy containing moxifloxacin until 2015, when MDS refractory anaemia with excess blasts (12%) type II (RAEB II) was diagnosed. The entire GATA2 exons were investigated and a heterozygous germline GATA2 (c.1061 C > T; p.T354 M) mutation was determined by Sanger sequencing of peripheral blood leukocytes (as in Additional file : Table S1). The combination of results led to a final diagnosis of MonoMAC syndrome. The patient was treated with 3 days of idarubicin and 7 days of cytarabine chemotherapy and developed cutaneous and pulmonary filamentous fungal infection. A skin biopsy was performed and identified nonspecific spore and septate hyphae. He was treated with liposomal B amphotericin and voriconazole, received consolidation chemotherapy with high doses of cytarabine and was submitted to haematopoietic stem cell transplant (HSCT) with a myeloablative conditioning regimen from his HLA- identical brother. He died nine months after transplantation in October 2016, in other institution, so we are not sure of the exactly cause of death. GATA2 gene sequencing (exon 5) was performed on his relatives, including his HSCT donor and was positive only in his two healthy sons, aged 21 and 28- year-old (Figs. and ). The hotspot regions for acquired mutations exons 11–12 of ASXL1 sequencing were also performed in the three GATA2 mutant (GATA2mut) subjects but were ASXL1 Wild-Type (ASXL1WT) as in Additional file : Table S1. |
pmc-6489293-1 | A 57-year-old male patient visited the Department of Oral Medicine, Kyungpook National University Dental Hospital with the chief complaint of painful ulcer on the tip of the tongue. The ulcer had developed 3–4 weeks ago without any apparent initiating event such as trauma. He described a pricking sensation and an increased soreness at the tongue tip area upon touching. The patient’s medical history revealed a diagnosis of TB over 40 years ago. He reported that complete recovery was gained at that time.
Intraoral examination revealed a round ulcer measuring approximately 0.7 cm in diameter on the tip of the tongue. The ulcer was characterized by a granulomatous center and a whitish, well-defined border with slight elevation (Fig. ). The base of lesion was firm in consistency on digital palpation. Extraorally, there was no evidence of lymph node involvement. A panoramic radiograph showed no evidence of bone involvement. The laboratory examinations showed that complete blood count (CBC) was within normal limits. Serologic tests for human immunodeficiency virus and hepatitis C also revealed negative findings. Based on the clinical examination, differential diagnosis included major aphthous ulcer, traumatic ulcer, granulomatous diseases, and infections.
Topical mouthwash with a mixture of amoxicillin 1.0 g and prednisolone 30 mg in 500 mL distilled water was used for 7 weeks with careful instruction to avoid possible stimuli, and triamcinolone acetonide 5 mg was also injected into lesion twice for 2 months. Despite subtle improvement after these conservative managements, the ulcer had not completely disappeared. Biopsy was eventually performed to rule out malignancy.
An incisional biopsy of the ulcer was carried out under local anesthesia (2% lidocaine with epinephrine 1:100,000). Histological examination revealed the presence of numerous epithelioid cells and multiple Langhans giant cells and Ziehl–Neelsen staining demonstrated acid-fast bacilli (AFB) (Fig. ). Based on histological findings, the oral ulcer was finally diagnosed as lingual TB.
The patient was immediately referred to a pneumologist for further examination and management. AFB stains of lesion were positive for M. tuberculosis. AFB cultures were positive for M. tuberculosis complex. Polymerase chain reaction (PCR) was conducted on his sputum, and analysis confirmed the presence of M. tuberculosis.. Additional blood biochemistry revealed the increased values of erythrocyte sedimentation rate (ESR) (103 mm/h) and c-reactive protein (CRP) (2.54 mg/dL). An IFN-γ release assay (IGRA) using the QuantiFERON-TB Gold in-tube method was positive. Chest computed tomography (CT) showed destructive findings with consolidation and fibrothorax in right lung and formation of cavitary lesion with clustered centrilobular micronodules in left lung apex (Fig. ).
After about 2 months of drug therapy, the oral ulcer of patient almost disappeared (Fig. ), and after another 2 months, AFB culture showed no growth of M. tuberculosis in 4 weeks. The patient was followed up for 9 months without any complications (Fig. ). |
pmc-6489305-1 | A 30-year-old unmarried Indian male presented with the complaint of difficulty in retracting his foreskin for the past 3 years. The symptoms were insidious in onset and there was no history of trauma to the glans or foreskin. On genital examination, his distal penis was club shaped with a bulbous and swollen tip. Phimosis was present, but the preputial skin texture appeared normal (Fig. a, b). On palpation, a diffuse lump was felt concealed in the foreskin on either side of the glans penis measuring approximately 2–3 cm in size and extending dorsoventrally. It had a smooth outline and was soft in consistency. Further examination of the swelling was not possible because of the phimosis. The differential diagnoses considered at this stage were smegma cyst, preputial cavity fluid collection, and benign cyst.
His general medical status was within normal limits and he was taken up for circumcision under spinal anesthesia. The preputial skin was incised and everted which revealed two cystic swellings on the inner preputial surface (Fig. a). The right one measured 3.5 × 2.5 × 1.5 cm, irregular in shape, almost extending to the dorsal surface. The left one was 2 × 1.5 × 1 cm, smooth, rounded, and extending to the glans (Fig. b). The swellings were excised entirely and circumcision completed (Fig. ). Our patient had a smooth postoperative recovery and at follow-up the wound had healed primarily. Histopathology revealed both swellings as unilocular cysts with lamellated keratin and lined by stratified squamous epithelium suggestive of epidermoid cysts (Fig. ). |
pmc-6489309-1 | In March 2017, a 65-year-old Japanese man, a ship designer, had mild epigastric discomfort and general malaise. An attending doctor thought that he had a digestive tract disease; in upper gastrointestinal endoscopy, however, there was no abnormality. He continued to complain of epigastric comfort and general malaise; he was misdiagnosed as having functional dyspepsia and depressive state, and he started taking medicine for them. He continued the same treatment for approximately 6 months, but the symptoms did not disappear. In September, 2017, he had nausea and vomiting, and finally he could not take any meal. He was then hospitalized in our institution so that we could supply him with nutrition.
His height and body weight were 169 cm and 52.9 kg. Systolic and diastolic blood pressure and heart rate were 119/87 mmHg and 87 beats/minute. Body temperature was increased up to 38.5 °C. In physical examination, there was no special abnormality in his heart, lungs, and abdomen. Table shows the clinical characteristics on admission. His C-reactive protein (CRP) was increased up to 13.36 mg/dL, suggesting the presence of inflammation. An increase of blood urea nitrogen (BUN) and uric acid was observed which we think was probably due to dehydration. Although he had high fever and high CRP, all the infection markers that we examined were negative. In addition, several antibodies which we examined were all negative. Taking into account these data, we thought it unlikely that he had some inflammatory disease and/or autoimmune disorder such as collagen disease. Since his blood glucose level was relatively low and the number of eosinophils was relatively high, we examined the possibility of adrenal deficiency. As shown in Table , ACTH and cortisol levels were low and urinary cortisol level was also low, suggesting the presence of ACTH deficiency and adrenal insufficiency. An increased prolactin level was also observed which we assumed was induced by the side effect of dopamine blockers.
Next, we performed rapid ACTH load test. As shown in Fig. a, his cortisol level was increased to over 5 μg/dL 60 minutes after the load, but the peak of cortisol was not so high (11 μg/dL). In abdominal computed tomography (CT), there was no mass in adrenal tissue (Fig. b); in brain contrast magnetic resonance imaging (MRI), pituitary size was within normal range, and pituitary gland deep dyeing delay and/or deeply stained deficit were not observed (Fig. c). As shown in Fig. a, in a corticotropin-releasing hormone (CRH) load test, the response of ACTH and cortisol was poor after CRH loading, suggesting the presence of ACTH deficiency. In addition, in a growth hormone-releasing peptide 2 (GHRP2) load test, ACTH response was poor although growth hormone (GH) response was preserved (Fig. b). Next, we performed a triple load test: thyrotropin-releasing hormone (TRH), GH-releasing hormone (GHRH), and gonadotropin-releasing hormone (GnRH) load. As shown in Fig. a, in a TRH load test, thyroid-stimulating hormone (TSH) and prolactin levels were increased after TRH loading. In a GHRH load test, GH level was increased after GHRH loading (Fig. b). In a GnRH load test, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were increased after GnRH loading. These data suggest that our patient had isolated ACTH deficiency. Since there was no abnormality in brain MRI and in various markers for autoimmune and/or infection diseases, we diagnosed him as having idiopathic and isolated ACTH deficiency.
After diagnosis of isolated ACTH deficiency, we started hydrocortisone on September 14, 2017. As shown in Fig. a, after starting the treatment with hydrocortisone, his body temperature and CRP were decreased. In addition, his sodium level was gradually increased and eosinophil level was gradually decreased after the treatment (Fig. b). Various symptoms such as nausea, vomiting, appetite loss, and general malaise were mitigated soon after the treatment. |
pmc-6489358-1 | The patient was a 61-year-old man with multiple left rib fractures (1–6 ribs), left pneumothorax, left lung contusion, and left thoracic subcutaneous emphysema due to a fall injury. The examination showed a partial depression in the left front rib and abnormal breathing (see Fig. ).
Admission chest CT examination: 1–6 rib fractures on the left side (of which 3, 4 ribs are long comminuted fractures (see Fig. )); left pneumothorax, left traumatic wet lung; a small amount of liquid pneumothorax on the left side.
Patient was given early chest straps, multiparametric monitoring, analgesia, and oxygen therapy. The chest pain was still severe. The visual analogue scale scored 7–8 points for the pain at rest and 9 points for the cough.
Physical examination revealed that the left chest wall was recessed and abnormally breathed. The CT scan of the rib showed a long comminuted fracture of 3 and 4 ribs. The key to successful operation was the reduction and fixation of these two rib fractures. A preoperative CT scan was performed to reconstruct the 3D model based on the scan results (see Fig. ), and 3D printing technology was used to prepare 3 and 4 rib models (see Fig. ). The three D print models of each fracture segment of the two ribs were adherently reconstructed.
The two rib metal plates were separately shaped according to the reconstruction model (see Figs. and ).
The patient is scheduled to have a open reduction and internal fixation of 3–6 rib fracture. After general anesthesia, right side lying position, small incision about 8 cm was performed under the edge of 4th rib underarm. The skin was sequentially incised and the subcutaneous tissue was freed layer by layer. The front of the latissimus dorsi muscle and the anterior serratus were exposed. The tunnel was established on the 3rd and 4th rib surfaces from the back of the chest and small muscles to the back of the scapula. The special long hooks lifted the scapula and exposed the scapular operation space. With assistance of endoscope, the electrocautery is useful to expose 3 cm outside the outermost fracture lines of the 3 and 4 ribs. The locking plate was molded on the surface of the third rib before operation, and the broken end of the non-fracture at the anterior and posterior portions of the third rib was well fitted. The distance between the two ends of the metal bone plate exceeded the fracture line to 3 nail holes distance. Under the thoracoscope, the metal plate and the ribs were temporarily fixed with long-angled forceps. The MIPO system was used to drill the holes. Two screws were implanted and locked at both ends to firmly fix the metal plate. In turn, each fracture segment was reset and drilled and secured to a metal plate. The fourth rib is fixed in the same way. Intraoperative image (Figs. , and ). 5, 6 rib fractures given to fix the ribs, not the content of this article, not elaborated. Sufficient to stop the bleeding, the wound was given to leave a negative pressure drainage tube. After a routine thoracoscopic probe of the chest cavity, a closed thoracic drainage tube was placed posterior to the 7th intercostal space and the incision was closed layer by layer. After the chest wall is well-shaped. Three days after surgery review the map (Fig. ). |
pmc-6491447-1 | The index patient is a seven-month-old boy born to first cousins parents, presenting with a prolonged history of fever and recurrent infections for 4 months. Parents reported intermittent bleeding episodes from the nose, mouth, and anus that, during patient hospitalization, were unsuccessfully treated with broad-spectrum antibiotics and packed red cells and platelets transfusion. Examination revealed a failure to thrive in the child, with both height and body weight below the 3rd percentile. He had severe pallor, bruises all over the body, and there were bilateral anterior and posterior cervical palpable lymph nodes, which were firm and tender. The liver was also palpable; it was 9 cm in span, soft and non-tender, while a firm spleen was also palpable 3 cm in its longitudinal axis. The previous record had shown bicytopenia and leukocytosis, growth of multiple microorganisms in blood, including Burkholderia cepacia and Staphylococcus aureus, and persistently high inflammatory markers. Extensive investigations done during this admission confirmed the anemia, thrombocytopenia, and leukocytosis. Bone marrow aspiration and trephine biopsy showed cellular marrow. Basic primary immunodeficiency workup showed normal immunoglobulin, while flow cytometry revealed normal CD18 expression. There was strong suspicion of primary immunodeficiency due to the persistent leukocytosis and recurrent infections. |
pmc-6491524-1 | A 13-year-old female patient visited the outpatient oral and maxillofacial department of this hospital due to speech problems. In the intraoral examination, the patient had a short soft palate and bifid uvula. Also, the movement of the soft palate was very limited during speech (Figs. and ). An objective assessment was conducted. The patient showed severe hypernasality, articulation disorder, and low speech intelligibility. She did not show language retardation.
Upon these signs, the patient was diagnosed with a VPI with SMCP, and we decided to provide palatal lift treatment and speech therapy.
Higher nasalance shows higher waveform, and nasalance percentages less than or equal to 20% are considered to represent the absence of nasality and are marked with a green line [].
Sustained phonationSingle vowel: /a/,/i/,/e/,/u/ Double vowel: /ja/,/je/,/wi/ Syllable repetitionBilabial plosive: /papi./, /phaphi/, /p’ap’i/ Alveolar plosive: /tati/, /thathi/, /t’at’i/ Velar plosive: /kaki/, /khakhi/, /k’ak’i/ Aveolopalatal fricative: /cica/, /chicha/, /c’ic’a/ Sentence (nasal consonant ratio, NCR 0%): /wɔljoil ohu patatkae kasɔ cokε sɛulɯl cabko hwajoil sεpjɔke tolaoketta/
An assessment of nasalance prior to treatment showed severe nasalance in high vowels /i/,/wi/, high nasalance in /e/,/o/,/u/,/je/, and mild nasalance in /a/,/ja/, as well as hypernasality in syllable repetition and sentences (Table ).
Her parents did not want surgical treatment. We offered the pilot study of conservative treatment using speech aid/speech therapy without surgery, and they accepted the treatment method. The patient showed the closure failure of the velopharyngeal port due to the short soft palate and insufficient contraction of the palatal muscles. Therefore, a palatal lift which elevates the soft palate superiorly was selected. We educated the patient that the palatal lift should be fitted for all hours except when sleeping. The assessment was scheduled to be performed once a month, and weekly speech therapy was recommended. However, the patient was only able to come in once or twice a month.
Palatal lift was made and applied to the patient (Fig. ). Speech therapy including visual feedback, muscle training, perception training, and speech assessment using nasometer was performed at each visit. |
pmc-6491627-1 | The patient is a now 15-year-old Arab-Qatari male born full term with no complications, the fifth of six children of a non-consanguineous union. At 8 days of life, he developed diffuse cutaneous pustules starting in the groin and then spreading across the body. The lesions failed to improve with topical antibiotics necessitating hospitalization at age 44 days for intravenous (iv) antibiotics and incision and drainage (I&D). He was diagnosed with infantile eczema and a superimposed bacterial infection; wound cultures were positive for Staphylococcus aureus.
At 4 months of age, the patient was again admitted to the hospital with a recurrent abscess requiring I&D and iv antibiotics. Throughout his early childhood he continued to develop recurrent skin and soft tissue infections almost monthly and usually without fevers, including at 4 years of age when he had another I&D of a facial abscess with cultures growing methicillin resistant Staphylococcus aureus. At age 5 he was admitted to the hospital with pneumonia complicated by a parapneumonic effusion and multiple cavitary lung lesions (). He was treated with drainage of the lung nodules and prolonged iv antibiotics.
Given his recurrent infections at an early age of onset requiring repeated hospitalizations and iv treatments, the immunology service was consulted. The patient had several immune evaluations at age 2 and 4 that were normal and included immunoglobulin levels with undetectable IgE and normal lymphocyte subsets, CD11 and CD18 expression, nitroblue tetrazolium testing and myeloperoxidase staining.
At 7 years of age, the patient was admitted to the hospital with superinfection of his eczema lesions and his IgE was then found to be elevated at 4,409 kU/L (normal 0–63 kU/L). Given his history of recurrent staphylococcal infections and elevated IgE, AD-HIES was suspected. A de novo, heterozygous missense mutation in STAT3 (c.1934T>A, p.L645Q) was detected (). This novel mutation is located in the SH2 domain, adjacent to amino acids previously reported to contain STAT3 mutations associated with AD-HIES. It is not reported in publically available databases.
This mutation changes a polar glutamine for a non-polar leucine. Reduction of transcriptional activity of STAT3 p.L645Q to 85% of wild-type was confirmed using a luciferase assay (). The patient also had decreased CD3+CD4+ T cells expressing IL-17 (). Furthermore, STAT3 phosphorylation in patient-derived cells was impaired in response to cytokine stimulation (), which has been reported in patients with AD-HIES and STAT3 mutations in the SH2 domain ().
The patient did not have a history of mucocutaneous candidiasis. He did have eosinophilia (10.7%, 560 cells/μL), a common finding in AD-HIES. His peak serum IgE has been 10,665 kU/L. At 14 years of age, the patient sustained a non-displaced fracture in his ankle following a ground level fall. Bone densitometry showed osteopenia. He did not manifest other non-immunologic features of AD-HIES such as coarse facies, high-arched palate, scoliosis or joint hyper-extensibility, although he was noted to have retained primary upper incisors. He did have two separate and resolving episodes of facial nerve palsy at age 5 and 15 years not clearly associated with a viral infection.
After the diagnosis of AD-HIES, the patient was started on prophylactic cephalexin but continued to struggle with recurrent abscesses. After his response to pneumococcal vaccination was judged insufficient, his prophylactic antibiotic was changed to levofloxacin and he was started on immunoglobulin replacement therapy. He has subsequently experienced a significant decrease in the frequency of his infections and improved quality of life. |
pmc-6491636-1 | The proband (IV-1 in ), a 28-year-old man, was admitted into our department for recurrent dysphonia and asymmetric weakness of four limbs with the right side more severely affected. He had experienced the similar episodes twice when he was 14 and 20 years old. The symptoms lasted 4–6 h and resolved without treatment. He denied any infection, exercises, or other possible inducer before the onsets. This time the symptoms completely disappeared after 5 h. During this episode, physical examination revealed bilateral facial palsy, dysarthria, and bilateral positive Babinski sign, with muscle strength grade 3 in the left limbs and grade 2 in the right limbs. After the episode, the neurologic examination showed normal muscle strength, slight intention tremor and unsteadiness when walking on a straight line as well as in the Romberg test. He also had high-arched feet and areflexia in all extremities.
Comprehensive infectious, metabolic, paraneoplastic, and inflammatory panels of the proband were negative. Serum potassium was normal. However, his free T3 (FT3) and free T4 (FT4) value were increased to 9.56 pmol/L (3.10–6.80 pmol/L) and 39.2 pmol/L (12.0–22.0 pmol/L), respectively. Meanwhile, the value of thyrotropin (TSH) was 0.006 mIU/L, much lower than the limit (0.372–4.94 mIU/L). Further, radioactive iodine uptake scan showed his iodine uptake rates were lower than normal and thyroid-specific autoantibody assays were all negative. Twenty days later, his FT3 and FT4 returned to normal. Five months after the episode, all thyroxine test results, including TSH, were all within the reference range and remained for the following 1 year.
During the episode, his brain MRI () showed bilaterally symmetric abnormal T2 FLAIR hyperintensity in the deep white matter and the splenium of the corpus callosum () and reduced diffusion (). The diffusion reduction disappeared mostly 8 days later (). Five months after the episode, the MRI of his brain were almost normal (). Electroneuromyography (EMG) showed reduced motor and sensory nerve conduction velocities, prolonged distal latency as well as reduced sensory and motor nerve amplitudes, indicating both demyelination and axon loss (). Specifically, his right/left median motor nerve conduction velocity is 33.6/37.7 m/s, comforming to the intermediate CMT (). Brainstem auditory evoked potentials were normal.
This family is Chinese Muslim living in Jilin province. Pedigree analysis indicates an X-linked dominant inheritance (). The proband is the only individual in the family who experienced “stroke-like” episodes. EMG was carried out to determine the affected in the pedigree. The common findings among affected males included difficulty running, distal weakness, pescavus, absent tendon reflexes, and atrophy of distal muscles with older affected more severely. III-8 presented typically with all the features above (). Manifestations in female carriers were less severe and varied greatly. Some exhibited weakness and atrophy of hand muscles while some had lower limbs involved. However, a number of female carriers didn't show any symptom at all. The mother of the proband (III-1) was asymptomatic. However, examination displayed that she had high-arched feet and unsteadiness when walking on a straight line. EMG showed that she has demyelinating neuropathy with prominent axonal degeneration ().
All exons of GJB1 of the proband were sequenced by Sanger sequencing. A novel hemizygous variant c.-170T>G was found (). It is located in the nerve-specific promoter P2 region of GJB1, neighboring c.-171G>C (designated as c.-146-25 G>C in the earlier edition of HGMD, ), which has been shown reducing the expression of Cx32 (). c.-170T>G cosegragated with the disease in this pedigree (, ) and was not present in 100 control DNA samples. |
pmc-6491668-1 | We identified a 14-year-old Caucasian male, who at age 4 years presented with treatment-refractory immune thrombocytopenia (ITP) requiring several months of treatment with corticosteroids and high dose intravenous immunoglobulin (IVIG). He also had a history of recurrent otitis requiring tympanostomy tube placement and adenoidectomy. Laboratory studies identified low serum immunoglobulin (Ig) levels and vaccine titers with normal B and T cell numbers. Anti-platelet antibodies were not detected. Bone marrow examination showed increased number of megakaryocytes without other abnormalities. At that time, he was given a diagnosis of common variable immunodeficiency (CVID). Over the next decade, thrombocytopenia (ranging 28,000–114,000/mm3) and dysgammaglobulinemia persisted but he was clinically asymptomatic and without major infections. Laboratory data at age 14 years showed normal total B and T cell numbers but low NK cells, class-switched B cells, and CD4/CD8 ratio ().
The patient's mother had severe ITP diagnosed at age 21 and required several treatments including splenectomy at age 24. Her ITP resolved and never recurred. At age 42, she developed a small ischemic stroke in the cerebellum and was found to have thrombosis of a vertebral artery. There was no evidence of coagulopathy. She had low levels of IgA, IgM, total B cells, switched memory B cells, and naïve CD4 T cells (). Despite the measurable immune dysfunction, she never had severe or recurrent infections.
An in-house next generation sequencing (NGS) panel of 180 primary immunodeficiency-associated genes identified a variant in IKZF1 in the patient. In both the index case and his mother, genetic evaluation by Sanger sequencing verified novel heterozygous missense variant in the DNA-binding zinc finger (ZF) 3 domain of IKZF1 (c.584A>G, p.His195Arg) (). The same mutation was detected in the unaffected maternal grandfather, who, at age 75, was healthy and had no history of recurrent infections or thrombocytopenia. The grandfather had low levels of IgA, total B cells, and naïve CD4 T cells (). Interestingly, CD4/CD8 ratio and class switched memory B cells were markedly low in all three family members. |
pmc-6491679-1 | We here present a 44 year-old male with a history of CMC treated since early childhood with azole antifungal agents. The patient is the second of three children from non-consanguineous parents. He has developed resistance to antifungal drugs including nystatin, fluconazole, and partially to voriconazole to which he had an allergic drug reaction of troublesome and persistent photodermatitis. He is currently controlled on posaconazole and amphotericin lozenges.
The CMC has been associated with the development of esophageal strictures requiring repeated dilation. At the age of 39 years this procedure was complicated by esophageal rupture and mediastinitis requiring a prolonged ICU admission. The esophageal rupture was treated surgically but subsequent investigations for recurrent stenosis led to diagnosis of esophageal cancer at age 40. He underwent esophageal resection a year later with clear surgical margins, followed by adjuvant chemotherapy which was truncated because of severe mucositis. Radiotherapy was commenced for this cancer due to poor prognosis in young age.
Shortly after diagnosis with esophageal cancer, the patient was started on G-CSF therapy (2 times 300 μg per week) for almost 2 years (Dec 2014–July 2016). As the patient reported increased discomfort following discontinuation, G-CSF therapy was re-started a year later at age 43 years and is still current.
During early adulthood, the patient developed progressive hypogammaglobulinemia () with poor vaccine responses and commenced IVIG replacement at age 35. In spite of adequate trough IgG with monthly IVIG, he continues to suffer from recurrent lower respiratory tract infections requiring antibiotics and has been hospitalized on at least 4 occasions with bacterial infections, including salmonella gastroenteritis. He has required periodic courses of IV caspafungin for candida partially resistant to azoles.
Given the severity of the CMC and the antibody deficiency, more detailed immunological work-up was performed in the context of a research study. Detailed flowcytometric immunophenotyping of the patient's B- and T-cells revealed a severe reduction in CD27+ memory B cells and low circulating numbers of Th17 cells at age 42 years following discontinuation of G-CSF therapy (). As the patient did not have typical clinical associations of APS-1, a STAT1 GOF mutation was considered and genetic analysis of STAT1 exons 7-14 was performed on DNA of the patient. Sanger sequencing revealed a heterozygous variant in exon 7 (c.504T>A) resulting in a missense mutation in the coiled-coil domain (p.D168E) (). The same mutation has been previously described in a 5 year old female patient, but was not functionally addressed (). To examine the effects of the mutation, we studied phosphorylation of STAT1 in EBV-immortalized B-lymphocytes of the patient. Thirty minutes after stimulation with either IFNα or IFNγ, the patient's cells showed increased levels of pSTAT1 confirming a GOF phenotype as a result of the D168E missense mutation ().
Given that the patient reported beneficial effects of G-CSF treatment, we retrospectively analyzed immune cells prior-to and during the treatment period. Extensive follow-up of total leukocyte and neutrophil count showed a general increase in numbers during therapy (). Three stored PBMC samples were available for detailed T-cell immunophenotyping, and reporting of relative frequencies of Th17 and Tfh cells. Th17 cell frequencies were within the normal range on only 1 occasion under G-CSF therapy, whereas Tfh cell frequencies were not below the normal range (). Hence, G-CSF therapy was associated with normalization of Th17 cells on at least one occasion.
To gain more insight into the nature of the hypogammaglobulinemia and reduced memory B cells in the patient, we first quantified SHM in IgG transcripts from blood B cells. Overall, SHM levels were normal. However, IgG3 transcripts of the patient contained negligible SHM, in contrast to IgG1 and IgG2 (). Further analysis of the IgG transcripts demonstrated a predominant usage of IgG3 compared to IgG2 ().
T-cell dependent B-cell responses critically depend on IL-21R signaling via STAT3. As STAT1 GOF mutations can inhibit STAT3 activity, we here questioned whether the patient's B cells had intrinsically impaired STAT3 responsiveness. Indeed, in EBV-immortalized B cells from the patient, IL-21 stimulation normally induced STAT3 phosphorylation (). Moreover, nuclear localization studies with imaging flowcytometry revealed normal nuclear localization of pSTAT3 after IL-21 stimulation as well (). Therefore, we next evaluated functional STAT3 signaling by evaluation of expression of CD25, the IL2Rα chain, which is a direct target of STAT3 in B cells (). Following 24 h incubation with IL-21, EBV-LCL from a healthy control upregulated CD25 surface expression (). In contrast, EBV-LCL from the patient had lower levels of CD25 expression. These findings are consistent with previous finding that STAT3 activity was inhibited by STAT1 GOF at the target gene activation level, but not upstream of that (). |
pmc-6491702-1 | A 60-year-old post-menopause female, from Baoji City of the Shaanxi province in China, went to a local hospital complaining of abnormal uterine bleeding for 2 months. No high risk factor for endometrial cancer was observed, such as genetic factors, obesity, diabetes, a history of tamoxifen use and so on. Curettage was performed with a histopathological diagnosis of complex hyperplasia endometrium. No medicine or therapeutic curettage was effective for her with a continued bleeding. Her type B ultrasound in Shaanxi Provincial People's hospital showed a 0.8 cm-thick endometrium. Then, she turned to the First Affiliated Hospital of Xi'an Jiaotong University for further treatment. After written informed consent, she volunteered to get cytological endometrial samplings by Li Brush (Xi'an Meijiajia Bio-Technologies Co. Ltd., China, 20152660054) for cytological examination before D&C. Her histopathological report revealed that papillary epithelial hyperplasia was found, and cancer was a concern according to the structure of tissue but could not be diagnosis due to insufficient tissue (). Meanwhile, the cytopathological report revealed that some malignant cells were found (). Her serum markers showed high serum carbohydrate antigen 19-9 (CA19-9, 42.08 U/ml) and squamous cell carcinoma antigen (SCC, 6.10 ng/ml). A diagnostic laparoscopic hystero-salpingo-oophorectomy was performed and the patient was converted to a laparotomy when intraoperative frozen section examination revealed an endometrial serous carcinoma with ovarian metastasis. Omentum resection, pelvic lymphadenectomy and para-aortic nodes dissection were performed. She was finally diagnosed with stage IIIc endometrial serous carcinoma. |
pmc-6491804-1 | A 25-year-old man who worked in a shrimp farm in Yingkou (Liaoning province, China) presented mild watery diarrhea on Aug-24, 2018. The patient presented with a previous history of raw consumption of mollusc, which was taken from the sediment in Yingkou. After 8 h of the consumption of mollusc, the patient presented with a single episode of watery diarrhea, dizziness, and vomiting. No immune-compromising disease or alcohol abuse was reported.
Over the following 2 days, he complained of abdominal pain and was treated with ciprofloxacin (500 mg every 12 h) orally. The symptom of watery diarrhea was disappeared after 3 days of antibiotic treatment. Biochemical tests revealed a high white blood cell count (14 × 109/L). Stool culture was spread onto Thiosulfate-citrate-bile salts-sucrose (TCBS) and MacConkey agar plates, which gave suspected positive results for V. cholerae. The pure culture was obtained by a serial of sub-culture on TCBS. The suspected bacterium, namely YK-VC11 was identified as V. cholerae by means of VITEK-2 bacterial identifier system (BioMerieux, France) and the sequencing of the amplicon of the 16S rDNA genes (). Agglutination with O1 and O139 antisera showed that this strain was a non-O1/O139 V. cholerae.
PCR was conducted for the major virulence factors of V. cholerae including ompU (outer membrane protein); zot (zonula occludens toxin); tcpI and tcpA (TCP expression); hlyA (El Tor-like haemolysin); hapA (haemagglutinin/protease), rtxA (repeat in toxin) and toxR (central regulatory protein) as described by Ceccarelli et al. (). Results showed that this strain was only positive for the toxR and rtxA gene.
Afterward, we conducted WGS for this clinical strain. Genomic DNA was extracted from overnight cultures grown on TSA and fragmented and tagged for multiplexing with Nextera XT DNA Sample Preparation Kits (Illumina). The tagged DNAs were sequenced using the Illumina HiSeq 2500 at Beijing Novogene Bioinformatics Technology Co, Ltd. The raw sequencing data were submitted to GenBank (NCBI) under the BioProject No. . Contigs were de novo assembled using SPAdes version 3.0.8 ().
Piror to this finding we conducted a 6-month microbiological investigation of three sampling sites along the Liaohe River and identified 102 pathogenic strains from January to June 2018 (), including two V. mimicus and three V. cholerae strains (). The identification of clinical V. cholerae strain promoted us to check whether this clinical case was epidemiologically associated with other environmental stains. To this end, we further selected one V. mimicus strain VM70 and three V. cholerae strains YK-VC7, HC-VC50, and AS-VC37 for WGS to confirm their epidemiological links.
We first applied MLST to have a bird view of the evolutionary relationship of isolated V. cholerae strains. In silico MLST typing of 320 V. cholerae () was performed by MLST 1.8 server from the Center for Genomic Epidemiology () (). Results showed that YK-VC11, YK-VC7, HC-VC50, and AS-VC37 all belonged to a new ST that is not assigned. This ST phylogenetically clustered with another unknown ST strain BJG-01, which was identified in USA (). However, VM70 and strain 532-80 both belonged to outgroups which were distantly related to other V. cholerae strains.
To delineate whether four sequenced V. cholerae strains belonged to the same clone, first of all, 270 genomes of non-O1/O139 V. cholerae retrieved from GenBank (excluded strain 532-80 located in outgroup and ST69 strains) together with four sequenced strains were used for the identification of the core genome content by a method described in our previously work (). The assembled genomes were aligned to the reference V. cholerae strain N16961 using progressiveMauve version 2.3.1 (). Mobile genes, repetitive elements as well as intergenic region between core genes were excluded from the core genome. Results showed that the non-O1/O139 V. cholerae core genome consists of 2,683 genes (), with 2,147 genes on chromosome I and 616 genes on chromosome II.
Afterward, we combined all of the publicly available non-O1/O139 V. cholerae genomes with four sequenced strains and performed a phylogenomic analysis based on the non-O1/O139 V. cholerae core-genome SNPs. A stringent SNP calling was performed by a custom pipeline as described previously to guarantee that only genuine SNPs were included in the analysis (). The Maximum likelihood phylogenetic trees were inferred using RAxML 7.2.8 (). The phylogenetic relationship of closely related strains was constructed using the Maximum Parsimony algorithms in PAUP 4.0 ().
The SNPs alignment of analyzed genomes consists of 149,253 SNPs. The phylogenetic analysis of 277 genomes of V. cholerae and V. mimicus divided them into six clades (). Four V. cholerae strains were all located within Clade III which clustered with strain BJG-01, while three genomes formed Clade VI. Notably, strain 532-80 was identified as V. cholerae in Genbank, but was clustered with V. mimicus strain VM70 and the reference V. mimicus genome ATCC33654. This should be corrected. Interestingly, many STs, such as ST73 and ST515 each formed a clonal cluster in Clade I and Clade VI, respectively. Strains belonged to ST73 were identified in Indonesia, Bangladesh, India, Vietnam and Kenya, while ST515 strains were circulated around Tanzania and Uganda, suggesting that some of non-O1/O139 V. cholerae lineages spread over the countries.
SNP analysis of four sequenced V. cholerae strains revealed that they were genomically related within 9 SNP differences at most, which represented an independent branch, differing strain BJG-01 by 290 SNPs (). Strain AS-VC37 was clustered with HC-VC50 having 2 strain-specific SNPs, while YK-VC7 and clinical strain YK-VC11 formed another cluster with 2 SNP differences, indicating all sequenced V. cholerae strains belonged to the same clone.
Genomic analysis showed that all V. cholerae isolates found in this study were positive for toxR gene, but negative for zot, ctxA, hlyA, tcpA, tcpI, and ompU genes. Antibiotic susceptibility test was performed on Muller-Hinton agar (BD, USA) by disk diffusion method. Breakpoints of the antibiotics were defined according to Clinical and Laboratory Standards Institute guidelines for Enterobacteriaceae () and V. cholerae (). Escherichia coli reference strain ATCC 25922 was used as a quality control strain. All strains were tested for resistance to ampicillin (10 μg), cephalexin (10 μg), cefradine (10 μg), ciprofloxacin (5 μg), chloramphenicol (30 μg), erythromycin (15 μg), florfenicol (30 μg), kanamycin (30 μg), neomycin (30 μg), penicillin (10 μg), rifampicin (30 μg), streptomycin (10 μg), sulfamethoxazole-trimethoprim (SXT) (23.75 and 1.25 μg, respectively), and tetracycline (30 μg). All of V. cholerae isolates were resistant to penicillin, cephalexin, cefradine, and ampicillin. However, V. mimicus strain conferred additional resistance to enrofloxacin, florfenicol, kanamycin, and tetracycline (). |
pmc-6491953-1 | Patient 1 (20–25 years old) presented with agitation. He was threatening, screaming, scratching, and spitting, and refused a conversation. He looked well-groomed (clothing, hair, dental status, cleanliness of skin and nails). The team, consisting of two nurses, a resident and a consultant psychiatrist, had the impression that the aggression of patient 1 was somehow undirected, i.e., not directed against certain persons and irrespective of the context. The perceived subjective and clinical aspects led to the assumption that patient 1 could suffer from an acute and potentially first manifestation of a mental disorder. He expressly refused to undergo medical examination and all offered treatments. The team tried many times to establish contact with the patient by calmly addressing him or offering him to sit down and talk, to drink something, or to retreat in a quiet room and rest. All of these attempts to de-escalate the situation didn’t have any effect. The patient was still agitated, threw himself against the ward door, thus bruising himself, or screamed at the staff. The team members thoroughly discussed the next steps to solve the acute situation.The involved staff members agreed that, in this situation, the legal conditions allowing the use of compulsory treatment and mechanical restraint were fulfilled and that, most importantly, every alternative had been exhausted. The team thus decided that, in order to prevent further harm to himself and others, compulsory treatment was the only available possibility. Because of the acute and dangerous character of the situation, the patient was then, according to the Mental Health Law, mechanically restraint, a blood analysis and an ECG were performed, and he received an i.v. medication. Legal procedures regarding the pursuit of the involuntary hospitalization and compulsory treatments including external medical review and a decision by a judge were initiated. The results of the analysis showed that the symptoms of patient 1 were caused by a severe overdose of L-thyroxine and an electrolyte imbalance due to anorexia nervosa. After a few days of intensive care treatment, patient l switched to outpatient treatment on another ward. |
pmc-6491953-2 | Patient 2 (40–45 years old) presented with severe agitation. He was threatening, screaming, scratching, and spitting, and refused a conversation. He thus showed a similar clinical picture as patient 1 but also appeared to experience auditory hallucinations and to actively talk to them. Patient 2 was in a state of poor hygiene. Taking into consideration his manner of response, one could assume that patient 2 has experienced psychiatric treatment in the past. When the nurse asked him if he had any experience with psychiatric medication, he yelled at her and clarified his wish to refuse haloperidol. He seemed to feel especially threatened by the police and the psychiatric staff, not only due to psychotic symptoms but also due to previous aversive experiences with psychiatric treatment. Once again, the staff members involved in the situation discussed the clinical case in a multiprofessional setting and weighed out every possible option. The team suspected that patient 2 suffered from an acute exacerbation of a disorder that persisted for a longer period of time or a psychotic relapse. In this case, the team decided that patient 2—due to his previous aversive experiences—would have extraordinarily suffered from compulsory treatment, which may exacerbate previous traumatic experiences. Also, he calmed down a bit when given a space to withdraw and did not immediately endanger himself or others; however, he remained tense for several days and threw objects whenever members of staff tried to engage him in a conversation or offered oral medication. When left alone, he did not appear aggressive or present improper handling, showed a regular food intake, and welcomed the possibility to smoke. Somewhat later, he was seeking a medical consultation and expressed the need for a low-dosage medication. To this day, 6 years later, he regularly receives outpatient care and short-term crisis intervention treatment on a psychiatric ward, although he has felt threatened and deprived of his identity by the state and the psychiatric system of another city for more than 25 years. |
pmc-6492172-1 | A 48-year-old man had 2 generalized tonic–clonic seizures within 1 month. At age 11 years, a choroid plexus papilloma was treated by posterior fossa resection and a cadaveric dural patch (1980) but no radiotherapy. There was no family history of brain hemorrhage or cognitive impairment. Clinical examination revealed longstanding right arm mild pyramidal weakness and ataxia, and slightly unsteady gait. Brain magnetic resonance imaging (MRI) showed patchy T2 hyperintensities bilaterally throughout the cerebral white matter, and 5 punctate foci of restricted diffusion at the gray–white matter interface. Electroencephalography demonstrated intermittent left anterior centrotemporal theta/delta activity enhanced by drowsiness and hyperventilation, with occasional sharp slow waves; he commenced levetiracetam. Carotid duplex, craniocervical computed tomography (CT)-angiography, bubble-contrast echocardiography, and 24-hour electrocardiogram were normal. Two months later, he developed confusion, disorientation, and verbal slowing; brain MRI (Fig A–C) showed multifocal abnormal cortical signal and swelling (with adjacent sulcal high signal) on T2-weighted sequences, most conspicuously in the left frontal region (where there was associated leptomeningeal enhancement and recent subarachnoid hemorrhage) and several new punctate foci of restricted diffusion. Gradient-recalled T2*-weighted sequences showed left parietal superficial siderosis and several peripheral microbleeds. A lumbar puncture (performed prior to any clinically manifest intracerebral hemorrhage) showed 680 red blood cells and elevated protein (0.99 g/l). The patient received intravenous methylprednisolone 500 mg daily for 5 days followed by oral prednisolone (50 mg) for a presumed diagnosis of primary central nervous system vasculitis, without clinical response. Three months later, the patient had an acute left frontal intracerebral hemorrhage causing sudden aphasia. Brain biopsy demonstrated leptomeningeal and cortical CAA with scattered leptomeningeal hemosiderin deposits and widespread diffuse parenchymal Aβ deposits, but no perivascular inflammation, vasculitis, or fibrinoid degeneration (Fig A, A1, A2); there was no tau pathology or abnormal prion protein (PrP) deposition. APP, PSEN1, and PSEN2 gene testing was negative for mutations causing Alzheimer disease or CAA. APOE genotype was ε3/ε3. Follow-up MRI 6 months later showed partial resolution of the left frontal swelling and meningeal enhancement, new parenchymal hemorrhage in the posterior left inferior frontal gyrus, multifocal superficial siderosis, and numerous strictly lobar cerebral microbleeds (see Fig D). |
pmc-6492172-2 | A 39-year-old man presented with multiple intracerebral hemorrhages. His past medical history included partial resection of a left parotid cavernous hemangioma at age 2 years followed by external carotid embolization using lyophilized cadaveric dura and “gelfoam” emboli (1981). A procedural ischemic stroke, likely secondary to internal carotid embolism, caused right arm weakness. At age 6 years, the patient had further embolization and parotidectomy. He remained well until age 27 years, when he had 3 generalized tonic–clonic seizures associated with a left frontal intracerebral hemorrhage. After treatment with carbamazepine, he remained seizure-free for 4 years but then had a left frontal lobe intracerebral hemorrhage causing disorientation. He subsequently experienced persistent memory impairment and intermittent confusion with further intracerebral hemorrhages at age 33 years (right parietal) and 35 years (left occipital and right frontal). There was no relevant previous medical or family history. Clinical examination revealed longstanding right hemiatrophy and mild right arm pyramidal weakness. Brain MRI revealed chronic and recent lobar hematomas, patchy superficial siderosis, and innumerable lobar microbleeds (see Fig E, F). 18F-Florbetapir amyloid positron emission tomography (PET) showed widespread moderate cortical amyloid deposition (see Fig G, H). Cerebrospinal fluid (CSF) examination, performed>1 year after the last symptomatic intracerebral hemorrhage (although contemporaneous MRI showed evidence of clinically silent macrohemorrhage), showed low Aβ1-42 (261 pg/ml, normal range = 627–1,322 pg/ml) and normal total tau, tau/Aβ ratio, 14-3-3 protein, and S100β. Next generation sequencing for mutations in genes associated with dementia (including APP, CHMP2B, CSF1R, FUS, GRN, HTRA1, ITM2B, MAPT, NOTCH3, PRNP, PSEN1, PSEN2, TARDBP, TREM2, TYROBP, and VCP)
was negative. APOE genotype was ε2/ε3. After 2 further intracerebral hemorrhages, brain biopsy confirmed widespread severe leptomeningeal and cortical CAA with parenchymal capillary CAA (see Fig B, B1), several cortical microvascular lesions, superficial cortical siderosis, and perivascular hemosiderin-laden macrophages (see Fig 2B2) but no perivascular lymphocytic inflammation. There were moderate diffuse parenchymal Aβ deposits and occasional core plaques but no tau pathology or abnormal PrP deposition. |
pmc-6492172-3 | A 34-year-old woman presented with severe generalized headache and right-sided visual field loss. Head CT showed acute left parieto-occipital intracerebral hemorrhage. Two months later she developed generalized tonic–clonic seizures, treated with levetiracetam. Examination revealed mild ideomotor apraxia only. The patient had a significant head injury causing a left parietal skull fracture at age 4 weeks; post-traumatic focal epilepsy was treated with phenobarbitone and later carbamazepine. At age 3 months, a growing fracture was treated by left parietal craniectomy and cadaveric dural repair (1982).
Brain MRI performed a few weeks after her intracerebral hemorrhage showed several left temporal lobar microbleeds. Digital subtraction angiography (DSA) revealed subtle nonspecific vascular abnormalities around the craniectomy. Imaging 3 months later showed an acute left superior parietal hemorrhage. Repeat DSA showed no new vascular abnormalities. MRI performed 15 months later showed regression of the left temporal hematoma, and mild gyral swelling in the temporal and parietal parenchyma with abnormal sulcal fluid-attenuated inversion recovery signal, local leptomeningeal enhancement, and additional microbleeds (see Fig I–K). 18F-Florbetapir amyloid PET demonstrated widespread cortical amyloid deposition (see Fig L). CSF analyses (performed >1 year after the patient's symptomatic hemorrhage) showed low Aβ1-42 (251 pg/ml, normal range = 627–1,322 pg/ml), low total tau (81 pg/ml, normal range = 146–595 pg/ml) and phospho-tau (13 pg/ml, normal range = 24 to 68 pg/ml), but normal 14-3-3 and S100β. Next generation sequencing for mutations in genes associated with dementia (including APP, CHMP2B, CSF1R, FUS, GRN, HTRA1, ITM2B, MAPT, NOTCH3, PRNP, PSEN1, PSEN2, TARDBP, TREM2, TYROBP, and VCP)
was negative. APOE genotype was ε3/ε3. Repeat MRI, performed 20 months after initial presentation, showed further accumulation of microbleeds. |
pmc-6492330-1 | A term female was born to a 25-year-old gravida-2 para-1 at 39 + 1 weeks gestation. The mother had a history of gestational hypertension in the previous pregnancy, but blood pressures were within normal limits during this gestation. After an uneventful pregnancy, the patient was born via repeat caesarean section with vacuum extraction. The birth weight was 2.66 kg and APGARs were 8 and 9 at 1 and 5 min, respectively. In the postnatal period, the baby had mild respiratory distress, resolved with blow-by oxygen. Physiologic jaundice was treated with phototherapy and the patient was discharged on DOL 2.
On DOL 3, the baby presented to the same hospital with poor feeding and lethargy. Initial laboratory tests indicated severe metabolic acidosis with an arterial blood gas (ABG) pH 6.9/ pCO2 48/pO2 50/HCO3− 10.8/Base Deficit − 21. The patient was given sodium bicarbonate to resolve the acidosis and intubated prior to transfer. The patient was then transferred to a Level III NICU at our institution.
Upon admission, the differential diagnosis was inborn error of metabolism, shock due to sepsis and hypovolemia or cardiogenic etiology. Patient was kept nil my mouth (NPO), given intraveous fluids with dextrose10% water, and placed on mechanical ventilation. An high umbilical arterial catheter and umbilical venous catheter were placed in order to accurately monitor arterial and venous pressures, and obtain blood gases. Initial labs demonstrated white blood cells: 20.6 × 103/mcL, hemoglobin: 14.8 g/dL, platelet 288 × 103/mcL, neutrophils of 70% and lymphocytes of 18%, serum sodium:134 mmol/L, serum potassium: 6 mmol/L, serum bicarbonate: 15 mmol/L, serum blood urea nitrogen: 13 mg/dL, serum creatinine: 0.8 mg/dL, urine specific gravity: 1.004, serum lactic acid level: 7.4 mmol/L, which later worsened to 9.4 mmol/L and ammonia: 74mcmol/L. The patient’s blood pressure on admission was 119/70 mm of Hg in the right arm and 94/59 mm of Hg in the left arm. Empiric antibiotics (Acyclovir 20 mg/kg/dose q8H, Ampicillin 100 mg/kg/dose q8H, Meropenem 20 mg/kg/dose q8H) for suspected sepsis were initiated. However, cerebrospinal fluid studies, urinalysis, and blood cultures were later found to be negative, ruling out an infectious etiology.
The patient had intermittently high blood pressures during the hospital stay with systolic pressures in the 100’s mmHg, and diastolic pressures in the 70’s. An echocardiogram demonstrated mitral regurgitation, tricuspid regurgitation, and severely depressed left ventricular function with an ejection fraction of 33%. It also ruled out other structural cardiac anomalies, including coarctation of the aorta. The low ejection fraction and constellation of symptoms were consistent with the diagnosis of acute heart failure, so treatment with milrinone (1 mcg/kg/min) was initiated and the ejection fraction improved to 44%. The patient showed signs of improvement by DOL 5 with an ABG of 7.48/33.8/60/25/2 and was weaned off of mechanical ventilation. Trophic feeds were initiated; however this resulted in the patient becoming slightly acidotic with a pH of 7.32, so she was again made (NPO).
The patient was transferred to a Level IV NICU with a metabolic specialist, where complete work up demonstrated no inborn errors of metabolism. A CT scan showed right kidney hypoplasia with reduced perfusion, and further labs demonstrated an elevated renin of 194 ng/ml/hr. (Ref 2.0–35) and aldosterone of 1476 ng/dL (Ref 6.0–179.0). This suggested a renovascular etiology of hypertension causing the initial presentation of acute heart failure. After discharge, upon follow-up with the primary care physician (PCP), she was again found to have elevated blood pressures (data not available). The patient was admitted to another hospital and started on enalapril (1 mg/mL) and clonidine (0.1 mg/mL) for blood pressure control. The patient was discharged on this regimen with a home blood pressure monitoring system. She continued to have uncontrolled blood pressures (data not available) and was admitted again to our institution where amlodipine 0.1 mg/kg BID was added to her regimen, and adequate control was achieved. Repeat work up for pheochromocytoma with Urine 24 h vanillylmandelic acid was 0.5 mg/24 h, Urine 24 h normetanephrines 127 mcg/24 h, Urine 24 h metanephrine 12 mcg/24 h, were with in normal for age. Renal ultrasound: mild left renal pelviectasis. Otherwise, normal echogenicity of bilateral kidneys, Rt kidney was 3.9 × 2.3 × 2.7 cm and Left Kidney 5.1 × 2.5 × 2.9 cm (Fig. ). Renal artery duplex ultrasound: No evidence of hemodynamically significant disease bilaterally. At subsequent follow-up appointments, the clonidine was discontinued, and adequate blood pressures were maintained. At 5 months of life, patient was still on enalapril and amlodipine as well as home blood pressure monitoring. Follow-up renal ultrasound: The right kidney is small 4.47 × 1.81 × 1.27 cm and left was 6.25 × 3.04 × 3.49 cm (Fig. ). There is no renal collecting system obstruction identified. Her blood pressures are moderately controlled, and her growth and development were appropriate for post-conceptual age. |
pmc-6492342-1 | A 23-year-old pregnant woman without any history of hypertension or migraine suddenly developed a thunderclap headache, dizziness, and eye pain at 35 + 2 weeks of gestation. She did not take these symptoms seriously and also experienced one episode of vomiting without fever and syncope. By the afternoon of the same day, her symptoms worsened, and she was admitted to the emergency department with a complaint of mistiness of vision in both eyes. At the time of admission, her blood pressure was 170/110 mmHg. Neurological examination revealed no abnormal signs such as hemiparesis and seizures. Serological laboratory tests showed no autoimmune conditions or infectious pathogens such as bacteria and viruses. Brain MRI performed on the same day revealed symmetric lesions in the posterior circulation territories, including the bilateral parietooccipital lobes, left basal ganglia, and corona radiata. These lesions showed hyperintensity on T2-weighted imaging and fluid-attenuated inversion recovery (FLAIR) imaging (Fig. a). DWI (Fig. b) and ADC mapping (Fig. c) revealed mild hyperintensity in the lesions, which indicated vasogenic cerebral edema. The patient was diagnosed with eclampsia-associated PRES and received intravenous infusion of mannitol (125 ml; q8h × 8 days) for the management of intracranial hypertension. On the same day, cesarean section was successfully performed, and her blood pressure decreased to 154/103 mmHg one hour after surgery. However, she complained of headache and bilateral blindness. On the day after surgery, her headache ameliorated, vision improved, and blood pressure decreased to 140/85 mmHg. Ten days later, i.e., one day after the withdrawal of mannitol, FLAIR imaging, DWI, and ADC mapping showed that the hyperintense lesions (vasogenic edema) had disappeared. However, an isolated lesion with restricted diffusion that showed a high signal in DWI and a low ADC value (cytotoxic edema) was observed in SCC; these findings indicated RESLES type I) []. Five days after the discontinuation of mannitol, she showed no abnormal symptoms and was discharged from our hospital. Follow-up brain MRI performed 29 days the clinical onset of symptoms showed no abnormalities (Fig. g–i). |
pmc-6492387-1 | A 36-year-old gravida 2, para 1 Caucasian woman presented at 9 weeks of gestation with headaches. She was normotensive and had no visual changes, chest pain, dyspnea, or other neurological symptoms. Her previous in vitro fertilization pregnancy was complicated by preeclampsia at 27 weeks of gestation. A growth-restricted fetus was delivered by cesarean section at 36 weeks, weighing 1900 g Additional file . Other past history was significant for infrarenal aortic stenosis diagnosed on the basis of a computed tomographic angiogram obtained to investigate persistent hypertension and intermittent claudication postpartum, which showed 75% stenosis of the infrarenal aorta with hypertrophied internal mammary and epigastric arteries (Fig. ). The remaining aortic branches were largely spared. Her regular medications were aspirin 100 mg and calcium 1.2 g daily. Her family history was significant for paternal ischemic heart disease and maternal hypertension.
Laboratory investigations for preeclampsia during her pregnancy revealed low-grade proteinuria (urine protein/creatinine ratio 40 mg/mmol) and normal renal and liver function. A vasculitic screen revealed a normal C-reactive protein (3.8 mg/L); mildly elevated erythrocyte sedimentation rate (ESR) (16 mm/h); and absence of antinuclear antibodies, antineutrophilic cytoplasmic antibodies, anti-double-stranded DNA antibodies, and antiphospholipid antibodies. The estimated fetal weight at a 34-week ultrasound was in the 94th percentile, and placental vascular resistance was normal.
The differential diagnoses for the major finding of significant infrarenal aortic stenosis included congenital abdominal coarctation, Takayasu’s arteritis, fibromuscular dysplasia, aortic neurofibromatosis, aortic tuberculosis, and radiation aortitis [, , ]. The presence of a well-developed collateral vasculature suggested a chronic aortopathy. In the absence of a clinical history or signs of neurofibromatosis, tuberculosis, or radiation exposure, as well as little evidence of active inflammation, the diagnosis of chronic abdominal aortopathy from congenital abdominal aortic coarctation, fibromuscular dysplasia, or inactive Takayasu’s arteritis was made.
The woman received aspirin and calcium as preeclampsia prophylaxis until 36 weeks of gestation, as well as insulin for gestational diabetes. She remained normotensive throughout pregnancy without requiring antihypertensive medications and delivered a healthy female infant weighing 3185 g by cesarean section at 37 weeks without complications. No regular medications were continued during the postpartum period. |
pmc-6492400-1 | A 76-year-old man with a history of left nephrectomy for renal cancer not otherwise specified (NOS) 36 years earlier and radical cystectomy with creation of a right cutaneous ureterostomy for invasive urothelial carcinoma of the bladder 4 years earlier was incidentally found to have a pancreatic tumor and a liver tumor on regular follow-up computed tomography (CT) after radical surgery for bladder cancer. On dynamic CT, the pancreatic tumor was located in the head of the pancreas, ventral to the portal vein, with a size of 10 mm, and it showed clear, strong enhancement in the arterial phase (Fig. a, b). The liver tumor was located in Couinaud’s liver segment 7, with a size of 22 mm, and it showed enhancement in the arterial phase and wash-out in the portal phase (Fig. c, d). No abnormal accumulation was detected in the systemic organs on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). FDG-PET was negative for the pancreatic and liver tumors. To identify tumor features, endoscopic ultrasound-guided fine-needle aspiration (EUS-FUA) for the pancreatic tumor and percutaneous ultrasound-guided biopsy for the liver tumor were performed. Histologically, the pancreatic tumor was diagnosed as metastasis of clear cell RCC, with positive staining for CD10 and vimentin and negative staining for CK7, CK20, alpha-fetoprotein, and neuroendocrine markers on immunohistochemical analysis. The liver tumor was diagnosed as moderately differentiated hepatocellular carcinoma (HCC). Preoperative CT imaging also showed type 3A PAP, in which the MPD ran ventral to the portal vein, and the aberrant parenchyma was located cranial to the confluence of the PV and SPV (Fig. a–c). The pancreatic tumor contacted the MPD, and partial pancreatectomy was avoided to prevent injury to the MPD (Fig. a, b). CP with additional stapler resection and closure of the aberrant parenchyma, needing a total of three pancreatic transections (Fig. d), was planned.
After the adhesiotomy and partial liver resection, the superior mesenteric vein (SMV), SPV, common hepatic artery (CHA), and gastroduodenal artery (GDA) were well mobilized from the head of the pancreas. Then, tunneling of the pancreatic neck over the PV was completed, and the neck and body of the pancreas were well mobilized from the PV and SPV (Fig. a). Intraoperative ultrasound showed the tumor in the head of the pancreas and the MPD clearly, allowing precise determination of the safe surgical margins (Fig. c). The margin of the pancreatic tail side was first cut using a cold scalpel, and the MPD was identified in the cut surface. Intraoperative findings were consistent with type 3A PAP (Fig. b). The safe margin on the pancreatic head side was also determined by ultrasound and compressed by a bowel clamp for 5 min before 10-min stapler resection and closure (Fig. d, e). Finally, the specimen (Fig. f) was removed from the pancreas by two ultrasound-guided pancreatic transections, avoiding the additional resection of the aberrant parenchyma (Fig. e). Negative surgical margins were confirmed by intraoperative pathological frozen section diagnosis. The distal pancreas was reconstructed by the pancreatojejunostomy (PJ) applying a type of Blumgart method []. The operative time including adhesiotomy and partial liver resection was 522 min, and blood loss was 270 mL.
The final pathological diagnosis was identical to the preoperative diagnosis. Histologically, the pancreatic metastasis of clear cell RCC that contacted the MPD formed a fibrous capsule and showed capsular invasion (Fig. ). The proximal cephalic margin without the stapler was 5 mm, and the distal tail-side margin was 9 mm from the tumor. The patient was treated postoperatively for an ISGPS Grade B pancreatic fistula [] from the stapler-closed cephalic stump (Fig. e). No specific treatment other than drainage was needed for the POPF, and the patient was discharged 38 days after the operation. Close follow-up without adjuvant treatment was continued due to repeated pyelonephritis. Although a histologically proven new HCC lesion developed distant from the initial site 8 months after the operation, the patient continued the treatment for HCC and showed no signs and symptoms of the recurrent RCC or abnormal pancreatic function for 2 years after the operation. Genetic analysis was not performed at the patient’s request. |
pmc-6492413-1 | Our patient was a 33-year-old White woman with BRCA2 gene mutation status. She presented to her primary care doctor for abdominal and back pain after bilateral prophylactic mastectomy. She had a strong family history of BRCA2-positive breast cancer in two of her aunts and one cousin. Her physical examination revealed that her vital signs were normal, and her abdominal examination was unremarkable except for mild nonspecific lower abdominal tenderness. For evaluation of lower abdominal pain and back pain, she underwent computed tomography (CT) of the abdomen and pelvis, which showed nonobstructing bilateral renal calculi and incidentally showed right infrahilar adenopathy. She underwent further CT of the chest with contrast enhancement, which revealed a right hilar mass measuring 3 × 2.2 cm and suspicious for malignancy (Fig. ). Routine laboratory blood work was within normal limits and unremarkable, and possible infectious etiology was also ruled out (Table ).
A pulmonologist was consulted for further evaluation of the infrahilar mass. On further inquiry, the patient reported occasional nonproductive cough with expiratory wheezing. She underwent electromagnetic navigational bronchoscopy for biopsy of her 2-cm mass in the right hilum. Biopsy confirmed a carcinoid tumor of the right lung. Atypical cells were positive for Cam5.2, thyroid transcription factor 1, synaptophysin, chromogranin, and CD56. The patient was then evaluated by a thoracic surgeon for possible surgical excision of the mass. She underwent right video-assisted thoracic surgery (VATS) with right thoracotomy, right middle and lower lobectomy, and lymph node resection.
The pathology report of the lung nodule confirmed it to be a typical carcinoid tumor with metastasis to one subcarinal lymph node (Fig. ). A histopathological section of the lung nodule showed a neoplastic proliferation arranged in a nested and organoid pattern. The cells had monomorphic nuclei with “salt–and-pepper” chromatin and scant eosinophilic cytoplasm. Mitotic activity was low, and there was no necrosis. The patient’s tumor, node, metastasis staging is T2aN2M0.
As per discussion with the patient and according to National Comprehensive Cancer Network (NCCN) guidelines, the patient would not receive any chemotherapy currently and would be closely followed by an oncologist.
The patient has had two follow-up appointments with her oncologist since the VATS procedure. After discussion with the patient and according to NCCN guidelines, the patient did not receive any adjuvant chemotherapy. The plan moving forward would be close surveillance with serial CT scans (3–6-month intervals) and chromogranin A measurements. |
pmc-6492432-1 | In October 2012, a 46-year-old woman was referred to our center for the presence of a large mass (50 × 70 mm) in the superior lobe of the left lung with homolateral pleural effusion. The patient was never smoker, without family history of cancer and without comorbidity. The cytological diagnosis was made using a CT-guided fine needle aspiration of the primary tumor and revealed an adenocarcinoma of the lung (TTF1+, CK7+) with the EGFR ex19del mutation. A PET-CT demonstrated the presence of liver and bone metastases and a nodule in the right breast, confirmed as a metastasis by fine needle aspiration. The patient received zoledronic acid 4 mg every 28 days and gefitinib 250 mg daily since November 2012 obtaining a partial response (PR). In August 2013, a disease progression (PD) was documented, with an increase in size of the primary tumor and size and number of liver metastases. A brain MRI revealed the presence of two cortical nodules, which were treated with stereotactic radiotherapy. The patient was enrolled in the IMPRESS trial and received 6 cycles of cisplatin and pemetrexed plus gefitinib obtaining again a PR that lasted until June 2014. Thereafter, a new lung metastasis appeared in the superior lobe of the left lung and the mammary nodule increased in dimensions. From June 2014 to December 2014 the patient received erlotinib 150 mg daily obtaining an initial stabilization of the disease (SD); however, within 6 months, she experienced again a PD with the increase of the mammary nodule and the appearance of a new bone metastasis in the sacrum. In December 2014, EGFR ex19del and T790M mutations were detectable in a new needle biopsy of the primary tumor; only at this time a digital PCR-based method was available for the analysis of circulating tumor DNA (ctDNA). Briefly, the method was optimized in order to recover a suitable amount of ctDNA for molecular analysis from 3 ml of plasma using the QIAmp Circulating Nucleic Acid Kit (Qiagen®, Valencia, CA). ctDNA was examined using the Prime PCR Probe Assay on a QX100™ Droplet Digital™ PCR System (BioRad®, Hercules, CA) for EGFR mutations (ex19del, T790M, and C797S) []. The ctDNA sample was considered as EGFR mutant when at least one droplet was above the fluorescence intensity threshold of 3000 and results were reported as copies/ml. The first plasma specimen was obtained in December 2014 and confirmed the presence of ex19del and T790M mutations (480 and 260 copies/ml, respectively; Fig. ). The patient was treated with atezolizumab from March to May 2015 and received stereotactic radiotherapy on the lung primary tumor and on metastases of the left superior lobe, breast and bone (sacrum and D10). Due to PD, the patient was given afatinib 40 mg daily from June 2015 to September 2015, but she experienced a further PD with an increase in size of the primary tumor and lung nodules, the appearance of new multiple bilateral lung metastases, lymphangitic infiltration and liver metastases. At this time, the presence of ex19del and T790 M was again demonstrated in a biopsy of a liver metastasis. Since osimertinib was available, the patient was enrolled in the ASTRIS trial and given 80 mg daily starting from October 2015 with an immediate clinical benefit. At the first evaluation a PR was documented with disappearance of most of the lung nodules and lymphangitic infiltration, reduction of the primary tumor and of liver metastases as well. A disappearance of ex19del or T790M was demonstrated in ctDNA in a blood sample obtained in October 2016. However, in April 2017, ex19del appeared again (400 copies/ml) and in July 2017 it increased to 1000 copies/ml, while T790M was also detectable (330 copies/ml, Fig. ). Then, ex19del and T790 M continued to increase to, respectively, 1600 and 510 copies/ml in October 2017, 2100 and 550 copies/ml in November 2017, and 6900 and 1900 copies/ml in December 2017.
A radiological progression was demonstrated with increase in size and number of liver metastases in December 2017. The patient underwent a new liver biopsy that confirmed the PD and the presence of ex19del and T790M, whereas the ctDNA showed also the appearance of C797S mutation (170 copies/ml), in addition to ex19del and T790M. The patient started chemotherapy with carboplatin and pemetrexed and in February 2018 she obtained an SD associated with a drop of ex19del (800 copies/ml), T790 M (380 copies/ml), and C797S (90 copies/ml) and then a PR in May 2018, with disappearance of C797S and reduction of ex19del (760 copies/ml) and T790M (90 copies/ml). In July 2018, however, ex19del strongly increased to 2200 copies/ml, even though T790M and C797S were undetectable. Finally, in October 2018, when a PD was documented, ex19del increased to 5100 copies/ml, while T790M and C797S appeared again in plasma with 600 and 180 copies/ml, respectively (Fig. ). At this time a NextSeq 550 NGS platform (Illumina®, San Diego, CA) was available to analyse ctDNA by the AVENIO ctDNA Expanded Kit (Roche®, Pleasanton, CA). A plasma sample collected in December 2018 and analysed by NGS confirmed the presence of the ex19del, T790M and C797S and found, in addition, EGFR and c-MET amplifications, which were not present in tissue in the last re-biopsy of December 2017. |
pmc-6492817-1 | A 2-year-old male was referred for investigation of recurrent lower respiratory tract infections. On history, he was a term baby who was admitted to the special care nursery at birth for 12 days for suspected sepsis. His mother had gestational diabetes under good control. He had a complex medical background with dysmorphic features (low set ears, clinodactyly, micrognathia, and multiple ear creases), multiple midline malformations (cleft soft palate, penoscrotal abnormality, multi-cystic right testicle, Atrial Septal Defect (ASD) and Ventricular Septal Defect (VSD), everted eyelids), feeding difficulty, abnormal cry, hearing impairment and speech delay. Renal and cranial ultrasounds were normal. Neonatal screening was negative for cystic fibrosis. Neurological assessment at birth and subsequently was normal.
In the first 12 months of life, he had recurrent upper respiratory tract infections, and some of the episodes were associated with wheeze. He also had protracted episodes of wet cough with or without viral or febrile illness. There was no history suggestive of upper airway obstruction, but his cry was noted to be soft. He had feeding difficulty and failure to thrive with weight below the third centile. Feeding difficulty was attributed to the cleft palate. Both VSD and ASD had spontaneous closure in the first year of life. Cleft palate was repaired at 10 months of age without any major complications. Despite the repair, the child continued to have recurrent lower respiratory tract infections and chronic wet cough with bilateral crackles, even during periods of wellness. A chest X-ray at the time of referral showed prominent bronchovascular markings with airspace change in the right middle lobe and left lower lobe. The wet cough persisted despite prolonged courses of oral antibiotics. He was thus further investigated for the cause of this chronic wet cough with a computed tomography (CT) chest, flexible bronchoscopy and immunological investigations.
Immunological and aero-allergen screening tests all demonstrated normal limits. Flexible bronchoscopy indicated the absence of an epiglottis. The appearance was consistent with agenesis or aplasia of epiglottis (Figs. , and , Supporting Information). Other findings included widespread bronchitis, mucous plugging of right middle lobe, and branching anomalies. Vocal cord function was normal. Bronchoalveolar lavage fluid (BALF) showed neutrophilia (92% cells neutrophils) and cultured Pseudomonas aeruginosa, Hemophilus influenzae and Streptococcus pneumoniae in significant amounts. CT chest showed atelectasis in the right middle lobe with mild multi-lobar bronchiectasis, most prominent in the lower lobes bilaterally. He was treated with intravenous anti-Pseudomonal antibiotics and was started on oral azithromycin for 12 weeks. He was also started on airway clearance therapy with chest percussions. Video fluoroscopic swallow studies (VFSS) were performed where the child demonstrated prompt swallow triggers and adequate airway protection and was thus not recommended for a modified diet.
Currently, at 4 years of age, he is progressing well with resolution of his wet cough. He is maintained on prophylactic macrolides and chest physiotherapy and remains free of chronic cough and is regularly assessed by speech therapists and respiratory physicians. He continues to have mild speech delay but is fully orally fed and is otherwise neurologically normal. He has a small deficiency in the posterior part of the soft palate resulting in intermittent nasal regurgitation. He is observed to have early digital clubbing. |
pmc-6493931-1 | A 43-year-old Tibetan man from the pastoral area in Qinghai, China, with a history of close contact with dogs and sheep, presented with diminished vision of the left eye, especially when chewing, which had persisted for over 1 month without any concomitant symptoms. The patient had been diagnosed with hepatic CE in 2010 but had not received any treatment at the time. Magnetic resonance imaging (MRI) and computed tomography (CT) of the paranasal sinus revealed a 47 × 44-mm cystic mass in the left infratemporal fossa, which was determined as type CE2 according to the WHO classification. Some lesions infiltrated into the intracranial and orbital areas, and the upper maxillary sinus cavity was compressed, as evidenced by contrast-enhanced MRI (). A transthoracic echocardiogram showed a rounded cyst measuring 16 × 20 mm with a clear boundary, regular shape, and homogenous hypoecho in the left ventricle myocardium. Left ventricle systolic function was normal (left ventricular ejection fraction of 66%). Contrast-enhanced chest CT revealed a low-density mass measuring approximately 33.05 × 12.27 mm within the left ventricle (). An upper abdominal CT scan revealed two round, low-density, echogenic, cystic lesions involving segment seven of the liver, with the largest lesions measuring approximately 28.09 × 27.32 mm; multiple small vesicular structures were also visible within the lesions and were determined to be WHO type CE2. Small lesions were also visible beside the large one (). We also detected multiple purely unilocular cystic low-attenuation masses in the abdomen, with the largest lesions being type CE1 and measuring approximately 60.44 × 54.40 mm, and a low-attenuation multiseptated mass of type CE2 in the pancreatic tail measuring approximately 44.96 × 51.43 mm (). A pelvic CT scan showed uneven distribution of intracystic density and the presence of WHO type CE3B daughter cysts measuring 92.02 × 37.21 mm in diameter located in the pelvic cavity, as well as a large, multiseptated cystic mass of type CE2 measuring 62.32 × 62.51 mm in the left kidney. In addition, the patient was positive for the presence of IgG antibodies against E. granulosus cyst fluid antigen, which was detected using a commercial kit (Haitai Biological Pharmaceuticals Co., Zhuhai, China).
The patient was treated with preoperative albendazole for 2 weeks (15 mg/kg/day). In light of the patient’s obvious eye symptoms, we decided to proceed with surgery for CE of the infratemporal fossa. Under general anesthesia, the cyst was identified and exposed in the lateral wall of the maxillary sinus () and was aspirated with a large bore needle to remove the hydatid fluid before injection of a concentrated iodine solution for 10 minutes. The large cyst and its daughter cysts were completely eliminated. The cyst wall was then dissected from the adjacent tissue using both blunt and sharp dissection techniques. Pathological examination of the specimen revealed irregular laminated layers and protoscoleces ().
After the operation, the patient recovered good eyesight and the lower nasal passage was unobstructed. Dynamic endoscopy showed that the mucosa in the cavity was smooth and without abnormalities 2 weeks after the operation. To treat echinococcosis cysts in the other organs and prevent a relapse requiring operation, the patient continued to take albendazole (15 mg/kg/day, 3-week treatments separated by 1-week intervals). After 16 months of follow-up, head, chest, abdominal, and pelvic CT scans showed no evidence of relapse and the left maxillary sinus structure had returned to normal. Surprisingly, the cysts in the abdomen and pelvic cavity had disappeared. The lesions in the left ventricle, liver, tail of the pancreas, and left kidney had decreased in size; intracystic tension was diminished; and the density was higher, with CT values of 26–40 HU, 27–49 HU, 26–51 HU, and 19–49 HU, respectively. Multiseptated cysts had disappeared completely or were almost undetectable in the liver and tail of the pancreas and left kidney () as compared with pretreatment (). We recommended that oral albendazole be continued, with regular follow-ups. The postoperative course was satisfactory, and no recurrence or abnormalities occurred at the surgical site. |
pmc-6494219-1 | A 43-year-old male patient presented to hospital, complaining of volume growth of the tongue with numbness for the past 1 month before consultation. The patient reported a long-term smoking and drinking habit.
This study was conducted with the approval of Medical Ethics Committee of Chongqing Cancer Hospital, and was performed in accordance with the ethical standards of the Helsinki Declaration. Written informed consents for his data and images to be used for our study and publication were obtained from patient before operation.
On intraoral clinical examination and palpation, an obvious smooth firm mass of about 2 cm in diameter on the mobile tongue with the same color as that of the surrounding mucosa was observed without other oral lesions. The cervical lymph nodes were not swollen on palpation. A biopsy was carried out and histopathological analysis demonstrated tissues formed by adenoid cystic carcinoma. Computed tomography (CT) of the head and neck enhanced scanning revealed an ill-defined measuring 23 mm × 19 mm high density mass with altered enhanced signal entities involving the anterior 2/3rd of the tongue. There was no obvious abnormality in the adjacent mandibular bone. No obvious enlarged lymph nodes were seen in both sides of the neck (Fig. ). The doppler ultrasound indicated that the submental and bilateral submandibular lymph nodes were all reactive.
The patient was positioned supine and then general anesthesia was given through nasal intubation. Incision was placed over the anteriorly till 2/3rd of tongue after emptying cervical lymph nodes at levels I–III ipsilateral to the tumor, and then the anterolateral femoral free flap (ALFT) was used to repair the defect of tongue and preserve the swallowing and speech function. During the intervention, a preventive tracheotomy was carried out to ensure breathing (Fig. ).
A histopathological examination defined ACC with a cribriform pattern. As is typically observed in ACC, the present case was positive for CD117(C-kit), CK8, epithelial membrane antigen (EMA), Ki-67(10%), and P63, while negative for carcinoembryonic antigen (CEA) and S-100 (Fig. ). There is only one regional lymph nodes metastasis that was found in the dissected lymph nodes located in submandibular region at levels I. Because of regional lymph nodes metastasis, postsurgical adjuvant radiotherapy was performed. We used the dose of radiation to tumor bed and lymphatic drainage area to 50 Gy.
The patient is currently under a postsurgical 29-month regular follow-up, showing good health without any clinically metastasis evidence. Despite the large resections these patients underwent, swallowing and speaking function were preserved at their most recent follow up appointment (Fig. ). We also provided the video in supplement data to show the recovery of language function 6 months after surgery. |
pmc-6494259-1 | A 31-year-old man complained of a chronic slight bilateral headache for more than 10 years. He was admitted to hospital because the symptom had been progressive within 1 year. He denied any occurrences of fever, nausea, vomiting, altered consciousness, sensory or movement disorder, visual disturbances, facial palsy, aphasia, incontinence, or convulsion.
Vital signs were stable and neurologic examinations were normal. Results of laboratory examinations were unremarkable. Magnetic resonance imaging (MRI) demonstrated a dilated posterior horn of the right lateral ventricle filled with a well-delineated oval mass, measuring 1.3 × 1.2 × 1.0 cm (Fig. ). The lesion appeared hypointense on T1-weight images (T1WI, Fig. A), including some hyperintense spots, and hyperintense on T2-weight (T2WI, Fig. B) as well as fluid-attenuated inversion recovery (FLAIR) images (Fig. C). Following contrast administration, it did not show obvious enhancement (Fig. D–F).
After excluding all contraindications, a neurosurgery was performed on the patient. To minimize normal tissue destruction, we innovatively treated the patient through a stereotactic neuronavigator-guided ventriculoscopic procedure. The entrance point was carefully determined according to the best trajectory obtained from preoperative MRI. After general anesthesia and successful intubation, the patient was posed supinely with his head turned to the left side and fixed in a head holder (Fig. A). The patient's right scalp was prepared by 2% iodine together with 75% ethanol. Then a 3-cm incision (Fig. A) and a small burr hole (Fig. B) were made according to the surgical plan. The working sheath of the ventriculoscopy guided by a stereotactic navigation guidance system approached to the target point accurately and safely (Fig. C, D). After arriving at the target, clear structures of right lateral ventricle could be seen through the endoscopic vision, with a dark red, smooth-surfaced entity attached to the choroid plexus (Fig. E). The lesion was removed after bipolar coagulation, using microscissors, grasping forceps, and gentle aspiration. There was no bleeding in the surgical field and the trajectory under close inspection (Fig. F). The procedure was satisfactory, with approximate 50 mL blood loss.
Postoperative MRI confirmed a gross total resection of the tumor (Fig. ). The patient recovered uneventfully and was discharged on the 7th postoperative day. He reported a slight but much better headache at the 1-month follow-up visit.
Microscopically, the surgical specimen was mainly composed of cholesterol crystals or clefts and granulomas, infiltrated by lymphocytes, plasma cells, and eosinophils. In some areas, there were several thick- or thin-walled blood vessels with hyalinization and calcification, as well as numerous psammoma bodies. Choroid plexus epithelium and focal areas of fibrous connective tissue were seen in the lesions. On immunohistochemistry, CD68 was positive in histiocytic cells and CD31 was positive in vessels. Glial fibrillary acidic protein was not detected. Ki-67 index was low, <1% (Fig. ).
The final histopathologic diagnosis was a XG of choroid plexus. |
pmc-6494395-1 | A 42-year-old man who lived in a rural area worked as a bricklayer 3 days prior to the onset of disease symptoms. He was admitted into the emergency department, on 04/04/2016 with a medical history of non-productive cough, dyspnea, myalgia, diffuse abdominal pain, and enterorrhagia for 10 days. He was a smoker and alcoholic patient. The physical examination indicated the conditions including a toxemic appearance, emaciation, consciousness, disoriented behavior, icterus (3+/4+), dehydration, and fever. His respiratory rate and cardiac frequency was 40 breaths/min and 140 beats/min, respectively. Pulmonary auscultation revealed a vesicular murmur, snoring sounds, and the presence of basal crackling rales in the left hemithorax. The abdomen was distended and painful owing to hepatomegaly and lower limb edema was observed.
The results of laboratory examinations indicated the levels of hemoglobin (9.8 g/dL), hematocrit (26.5%), leukocyte count (39.640 per mm3), stab neutrophils (5%), neutrophils (84%), platelets (2.46 million per μL), creatinine (3.7 mg/dL), urea (235 mg/dL), K+ (3.6 mEq/L), Na+ (124 mEq/L), amylase (38 UI/L), lipase (238 UI/L), aspartate aminotransferase (128 U/L), alanine aminotransferase (52 U/L), total bilirubin (6.45 mg/dL), direct bilirubin (5.76 mg/dL), indirect bilirubin (0.69 mg/dL), gamma-glutamyl transpeptidase (1512 U/L), alkaline phosphatase (558 U/L), prothrombin time (1.28 INR), albumin (1.5 g/dL), and globulin 4.0 (g/dL). The arterial gasometry results indicated respiratory alkalosis with hypoxemia.
Initially, several hypotheses such as community–acquired pneumonia (CAP), abdominal sepsis, leptospirosis, secondary infections of visceral leishmaniasis, and severe dengue were proposed regarding the pathogenesis.
The results of serological tests were negative for human immunodeficiency and human T-lymphotropic viral infections, hepatitis A, B, and C, leptospirosis, visceral leishmaniasis and dengue.
The patient was admitted into intensive care units during several respiratory failures. Initially, the patient was treated using the intravenous (IV) administration of ceftriaxone (1 g) twice a day. After 48 hours, meropenem (1 g) treatment 3 times a day was initiated owing to clinical worsening. On the third day of hospitalization, B pseudomallei was identified in 2 blood cultures using Vitek 2 System (bioMérieux). We assessed the minimal inhibitory concentration (MIC) of specific drugs to which B pseudomallei was susceptible and the results were as follows: meropenem (MIC: 1), ceftazidime (MIC: 1), sulfamethoxazole (MIC: 0.5), and levofloxacin (MIC: 2).
On the sixth day after initial clinical stabilization, the patient developed a severe hypoxemia, fever (39.4°C), and hemodynamic instability. Therefore, he was subjected to endotracheal intubation.
Computed tomography of the chest (Fig. ) revealed multiple pulmonary nodules in all the lung fields. Each of these nodules was up to approximately 1.6 cm in diameter. Moreover, CCT indicated partial consolidation in the right bottom of lung, air bronchogram, bilateral pleural effusion that was moderate in the right and bulky in the left regions along with thoracic drainage. No complications were observed on the computed tomography of the abdomen.
The clinical condition of patient alternated for several times between the episodes of worsening and improvement. Therefore, administration of a combination treatment comprising trimethoprim/sulfamethoxazole (TMP-SMZ, 20 mg/kg body weight per day) and meropenem (1 g 3 times a day) stabilized the clinical condition of the patient.
We identified B pseudomallei using the cultures of pleural fluid, tracheal aspirate, and urine samples through Vitek 2 system. The cell isolates were subjected to 16S rRNA gene sequencing to confirm the bacterial species.[
The patient was subjected to tracheostomy and ventilatory weaning. He exhibited persistent fever for several days. As progressive clinical improvement was observed, the tracheal tube and chest drain were removed. He was referred to our outpatient clinic for treatment of the infection. TMP-SMZ was prescribed to him and he was monthly monitored up to 1 year. The antibiotic was suspended owing to the remission of disease and he is currently under annual monitoring.
Informed written consent was obtained from the patient for the purpose of publication. |
pmc-6494927-1 | A 71-year-old female obstetrician with no medical history, except hysterectomy and knee surgery, presented to the emergency department (ED) after 1½ days of worsening fatigue, fever, chills, headache, generalized weakness, difficulty walking, and maculopapular rash in both legs. Her neurological status declined while in the ED and she was treated with broad spectrum antibiotics and acyclovir and admitted to the progressive care unit for close monitoring. Initial neurologic examination revealed an elderly febrile woman with a temperature of 102.7°F and nuchal rigidity who was confused, disoriented, following commands poorly, and non-verbal, with eyes open but “glazed.” She had prominent generalized weakness (Medical Research Council 2/5 in proximal muscles and 3/5 in distal muscles) with decreased spontaneous movement in all limbs. The neurologist concluded: “Patient is critically ill with fulminant neurological deterioration with potential for further deterioration and possibly death.” A CT scan and MRI of the brain were normal and spinal tap performed the day of admission showed CSF pleocytosis with white cell count of 720 mm (neutrophils 88%, lymphocytes 7%), protein 174 g/dL, and glucose 65 mg/dL. Meningoencephalitis and arbovirus panels were ordered, including serum and CSF WNV antibody tests (ELISA). The patient's neurological status continued to decline and she developed severe dysphagia and became stuporous, requiring stimulation to remain awake. Given her worsening mental status and inability to clear secretions she was transiently intubated to protect her airways and transferred to the neurosciences intensive care unit. After nasogastric tube insertion, she was extubated because of the low risk of aspiration and the constant supervision from family members. The WNV IgM antibody tests were reported positive on about hospital day 5 (WNV CSF IgM 10.87, normal ≤ 0.89 IV; WNV CSF IgG 0.10, normal ≤ 1.29 IV; WNV serum IgM 4.52, normal < 0.80 ratio). IgM and IgG results for St. Louis encephalitis, California encephalitis, Eastern equine, and Western equine viruses were negative. For a total of 9 days she remained largely obtunded with a depressed level of consciousness, often requiring non-invasive tactile stimulation (e.g., monofilament tickle to inside of nostril) for temporary arousal. Cranial nerve examination revealed dysconjugate gaze, left ptosis, decreased gag reflex, poor tongue protrusion, bilateral hand tremor, involuntary myoclonic-like jerks in right shoulder muscles (mainly trapezius), and equivocal Babinski signs. An EEG showed diffuse 4-7 Hz theta activity consistent with diffuse cerebral dysfunction, but no epileptiform activity. With prognosis still uncertain, a trial of high dose intravenous methylprednisolone (1 gram every morning × 5 days) was initiated. By the end of day 1 infusion, the patient's voluntary movements and spontaneous eye-openings increased; by the end of day 2 infusion, the patient was awake and responding to commands. Improved mentation persisted and following completion of the steroid infusions, she was transferred to a regular care bed. A serum cytokine panel (interleukin (IL)-2, IL-2 receptor CD25 soluble, IL-12, interferon-gamma, IL-4, IL-5, IL-10, IL-13, IL-17, IL-1 beta, IL-6, IL-8, and tumor necrosis factor alpha) drawn the day after completing the 5-day course of methylprednisolone was normal except for a borderline S100B protein (90 ng/L, normal 0–96). |
pmc-6494960-1 | We present the case of a 22-year-old German male high school graduate with a complex psychiatric syndrome including obsessive–compulsive, schizophreniform, and derealization phenotypes. In May 2016, at age 19, there was a sudden exacerbation of these syndromes. At age 14, he first experienced obsessive–compulsive symptoms (i.e., obsessive aggressive thoughts and compulsive avoidance acts). However, he recognized that the obsessional thoughts were a product of his own mind, and these symptoms were well compensated for at the time, enabling him to live a mostly normal life. After his final examinations at school, he consumed cannabis five times. He then experienced an exacerbation of his obsessive–compulsive symptoms and suffered from more severe obsessional thoughts, including the idea that he could injure other people and himself. Furthermore, he experienced involuntary obscene thoughts. At the time, he fought such thoughts and continued to recognize that the obsessional thoughts and impulses were a product of his own mind. He also suffered from hallucinatory symptoms, such as auditory hallucinations (i.e., hearing voices) and optical distortions (i.e., the shape of leaves on the ground appearing distorted). He developed diffuse anxiety and agitation and described extreme dizziness, as if he had drunk “five beers.” Because of his depressed mood and obsessive–compulsive symptoms, he experienced suicidal ideation and complained of difficulty falling asleep and reduced energy levels, especially in the morning.
Due to the severity of these symptoms, he was first hospitalized at age 19. He received pharmacological treatment with selective serotonin reuptake inhibitors for the obsessive–compulsive symptoms (citalopram up to 40 mg/day), neuroleptics for the schizophreniform symptoms (olanzapine up to 20 mg/day, risperidone up to 5 mg/day, and aripiprazole up to 7.5 mg/day; higher doses led to an increase in inner restlessness), carbamazepine for neuronal network stabilization up to 500 mg/day, and an anticholinergic agent because of extrapyramidal side effects (biperiden up to 4 mg/day) over a period of 7 months without significant improvement. Lorazepam (up to 2 mg/day) led to a transient reduction in anxiety. Seven months after symptom onset (December 2016, under treatment with aripiprazole 7.5 mg/day and carbamazepine 500 mg/day), his mental state still revealed obsessive thoughts, depressed mood, and diffuse anxiety. Moreover, he suffered from attention and concentration deficits (, t0), inner restlessness, signs of derealization (with altered, slowed, and delayed perception of his environment), and severe dizziness (still comparable with having drunk five beers). The obsessive–compulsive thoughts were still present and very difficult to manage.
There were no in utero or birth complications, febrile convulsions, seizures, inflammatory brain diseases, or cerebral contusions in the patient’s history. When entering primary school, he showed subsyndromal symptoms of inattention and motor hyperactivity. Nevertheless, he finished high school successfully and his further somatic history was unremarkable. He occasionally consumed alcohol and illegal drugs (nitrous oxide three times and cannabis five times), but there was no history of severe substance abuse. The family history showed that his grandmother suffered from depression, and his mother was diagnosed with insulin-dependent diabetes mellitus. There were no known rheumatic diseases in the family history.
The neurological examination was normal throughout the course of the disease. Initially, the CSF analyses (3 months after exacerbation, August 2016) showed positive CSF-specific OCBs. Five months after the first steroid pulse treatment (December 2016), the patient’s state deteriorated (May 2017). At that time, CSF analysis showed a mild pleocytosis (white blood cell count = 14/µl; reference <5/µl). The initial immunological screening 6 months after exacerbation in November 2016 revealed only a weak positive ANA in the indirect immunofluorescence assay. Another 6 months later (1 year after exacerbation, May 2017), we found clearly increased ANA titers in both serum and CSF (serum: titer = 800 IU; CSF: titer <100 IU) with anti-nucleosome specificity, which was also detectable in serum and CSF. At that time, we also detected decreased levels of complement component C4 and slightly increased C3d serum concentrations as indicators for increased complement activation.
Testing for rheumatoid factors, antiphospholipid abs, lupus anticoagulant, antineutrophil cytoplasmic abs, and a broad set of antineuronal and anti-thyroid abs was negative. In the cMRI, multiple diffuse periventricular white matter lesions were apparent in repeated examinations throughout the course (). The lesions were stable. Furthermore, there was a slightly enlarged adenohypophysis not yet affecting the chiasma opticum. The hormone screening did not detect any pathological hormone activity. The fluorodeoxyglucose positron emission tomography was normal. Repeated EEGs exhibited intermittent slowing (). The neuropsychological test of attentional performances showed severe deficits in alertness, divided attention, set shifting, and working memory (, t0). There were no further clinical, systemic SLE signs such as skin or inner organ involvement.
Focusing on the symptoms our patient developed during his youth, a diagnosis of obsessive–compulsive disorder with obsessive thoughts could be considered. The fact that disease symptoms exacerbated shortly after the consumption of cannabis could point to an acute episode of drug-induced psychosis. If the auditory and optical hallucinations together with signs of derealization persisted over time, paranoid hallucinatory schizophrenia could be a plausible classification, though only if all organic signs were considered pathogenetically irrelevant. The initial organic findings (positive CSF-specific OCBs, disseminated white matter lesions, no antineuronal abs, unspecific rheumatological findings) were interpreted as post-inflammatory changes. Finally, the increased ANAs with anti-nucleosome specificity in CSF and serum, serum complement activation, CSF pleocytosis, OCBs, and cognitive and psychiatric disturbances cumulated to the final diagnosis of NPSLE. Although the patient did not completely fulfill the ACR criteria for SLE, the diagnosis was established. Other supporting biomarkers, such as anti-ribosomal P protein and anti-C1q abs, as well as the direct Coombs test, were unremarkable. Autoimmune encephalitis would also be conceivable for differential diagnosis (). However, the established antineuronal abs were negative in serum and CSF.
Following initial assessment and based on the therapy resistance and inflammatory CSF changes with CSF-specific OCBs, we performed a high-dose corticosteroid pulse therapy with a daily dose of 1,000 mg methylprednisolone administered intravenously for five consecutive days in the context of continued treatment with aripiprazole and carbamazepine in December 2016, which was 7 months after symptom exacerbation. Following the steroid treatment, the patient’s mood, cognitive deficits, motivation, and dizziness improved. Moreover, his obsessive–compulsive symptoms were reduced. Methylprednisolone was subsequently continued orally and tapered over approximately 5 weeks (37 days). Except for steroid acne, no relevant adverse events became evident. After this immunosuppressive treatment, the patient was able to begin a volunteer social year, and treatment with aripiprazole and carbamazepine was continued. However, he still had obsessive–compulsive symptoms and cognitive deficits and felt dizzy (comparable with having drunk two or three beers). Clinically, we did not believe that these symptoms were side effects of carbamazepine because the symptoms were already reported prior to the treatment with carbamazepine, and blood concentrations were within the reference level. Neuropsychological testing showed no relevant improvement (, t1). Over the next 4 months, his mental condition worsened again.
In May 2017, 1 year after his initial symptoms exacerbated, we repeated the diagnostic workup. The patient showed mild pleocytosis in the CSF and laboratory findings compatible with SLE (). We performed a second steroid pulse therapy with 500 mg/day methylprednisolone for five consecutive days with oral tapering over 8 weeks. At the same time, carbamazepine was stopped, and aripiprazole was reduced to 5 mg/day. As maintenance treatment, the patient received methotrexate (up to 17.5 mg/week) orally in combination with folic acid. Due to the threat of azoospermia, cyclophosphamide, which normally shows good results for NPSLE, was not initially used. The CSF white blood cell count normalized, and the cMRI showed that the multiple diffuse periventricular to subcortical white matter lesions remained stable. Neuropsychological testing revealed an improvement in alertness, mental flexibility, and working memory [, t2 (before) versus t3 (after) the second steroid pulse treatment]. Two months later (August 2017, 15 months after his symptoms first exacerbated), we added the antimalarial drug hydroxychloroquine (200 mg/day). The maintenance therapy consisting of methotrexate (17.5 mg/week), hydroxychloroquine (200 mg/day), and aripiprazole (5 mg/day) resulted in a slow but substantial improvement of inner restlessness, cognitive deficits, derealization symptoms, and dizziness. Obsessive–compulsive symptoms disappeared completely. Over several months, he still felt dizzy, like “having drunk one beer.” Sixteen months later (December 2018), the patient was with without dizziness (“zero beers”), aripiprazole treatment was stopped in the meantime, and he enrolled in a vocational training program. Here, he was able to attend vocational school, but on long working days, he cognitively reached his limits. |
pmc-6495004-1 | A 44-year-old man was referred to our interdisciplinary center for vertigo and balance disorders at the University Hospital Zurich (tertiary referral center) with recurrent spontaneous attacks of spinning vertigo, which started several months prior to his first visit. The attacks usually lasted for 3–12 h and were accompanied by fluctuating hearing loss and tinnitus in the right ear.
According to the patient's medical history, he had suffered a left-sided longitudinal TB fracture caused by a car accident at 10 years of age (the original neuroradiology report but not the CT images were available for this study). Pure-tone audiometry (PTA) 4 months after the accident showed a pronounced high-frequency shift in bone conduction thresholds at 6 kHz on the left side (PTA not shown here), consistent with acoustic trauma and probably caused by the impact noise in the car. No further accident-related injuries or audiovestibular symptoms occurred, according to the available clinical records from that time. A synopsis of relevant events in the patient's medical history is given in .
In the initial neurotological work-up at age 44, vestibular-evoked myogenic potentials (VEMPs) indicated left-sided saccular dysfunction (absent cervical VEMPs). Other vestibular test results (ocular VEMPs, subjective visual vertical, video-oculography with caloric stimulation, and video head impulse test) were within the normal range (data not shown). PTA showed that the left ear had mixed, predominantly sensorineural, downward-sloping hearing loss (HL) up to 100 dB HL at 6 kHz (), while the right ear had moderate to severe presbyacusis (). Speech discrimination scores were 35 % on the left side and 100 % on the right side, and stapedial reflex responses were normal on both sides (data not shown).
Two months later, the patient presented in our emergency department immediately after an acute, hours-long vertigo attack accompanied by nausea and emesis. The HL and tinnitus in the left ear temporally worsened. Clinical examination showed a spontaneous nystagmus to the right side, a positive head impulse test to the left, and a positive Romberg test with a tendency to fall to the left side. Finally, a diagnosis of left-sided Meniere's syndrome (, ) was made, and a possible traumatic etiology was considered based on the patient's history.
The patient subsequently received repeated intratympanic dexamethasone (6.6 mg)/hyaluronate (2 mg/ml) injections over the course of several days, and in the following years, he undertook sequential trials of different vestibular suppressants [cinnageron, 75 mg, two times daily for 8 weeks, betahistine, 24 mg, two times daily for 16 weeks; prior to publication of ()]. Although the vertigo episodes continued with an average frequency of two attacks per month, the patient was coping well with the symptoms, and no vestibular ablative treatment was considered. In the 4 years following the onset of MD symptoms, hearing function in the left ear fluctuated in the low and middle frequencies and progressively declined to a level of 50–80 dB HL (). Finally, the patient was fitted with a contralateral routing of signals (CROS) hearing aid. He was then lost to further follow-up.
During initial neurotological evaluation (age 44), high-resolution CT (HRCT) imaging of the TBs was performed to rule out retrocochlear pathologies (e.g., vestibular schwannoma), posttraumatic inclusion cholesteatoma, and otosclerosis. HRCT imaging showed no evidence for the previously mentioned pathologies but demonstrated an old fracture sign in the posterior wall of the external ear canal. Four years later (age 48), gadolinium-enhanced MRI (Gd-MRI) of the inner ear fluid spaces with a 4-h delayed 3D inversion recovery (3D IR) sequence (, ) detected moderate [grade I, ()] vestibular and moderate-to-severe [grade I-II, ()] cochlear hydrops in the left inner ear, consistent with the previously assigned clinical diagnosis. No radiological (Gd-MRI) signs of endolymphatic hydrops were found in the right inner ear.
In the present study, we reassessed the available imaging data with regard to potential pathologies of the VA and ES on the clinically affected left side. On HRCT imaging, the left VA appeared to be almost completely obliterated by bone along its course between the isthmus and the operculum (). In contrast, the right VA exhibited a patent lumen throughout its entire course (). Correspondingly, on Gd-MRI (3D IR sequence), a segment of total T2 signal loss was observed in the partially obliterated left VA () but not in the right VA (). In the left VA, a delineated T2 signal was seen distal (posterior) to the segment with total signal loss (, blue arrows). Fusion of HRCT and Gd-MRI (color-coded) data in the focal plane of the operculum clearly localized this T2 signal distal (posterior) to the operculum (). Therefore, the signal most likely originated from the eES, as proposed previously (). In summary, the HRCT and Gd-MRI data indicated that the left eES was structurally preserved but anatomically separated from the labyrinth due to bony obliteration of the VA. Upon reassessment of the imaging data for the present study, no radiological signs for bony labyrinthine dehiscence, nor for cerebellopontine angle tumors were found that could account for the fluctuating otological symptoms. |
pmc-6495084-1 | A 54-year-old Caucasian female proceeded to our institution with epigastric pain, nausea and vomiting along with pain located around the lumbar area lasting for one week. No previous surgical history or commorbidities existed. Clinical examination did not reveal any palpable abdominal masses or abdominal tenderness and the patient’s vital signs were within the normal spectrum. Blood test detected hypercalcemia (serum calcium: 10.2 mg/dL) and parathyroid hormone level of 111.8 pg/mL. All the findings in conjunction with the clinical presentation lead to the assumption that the patient had primary hyperparathyroidism (PHPT).
Then, an ultrasound was performed but it was negative for any thyroid or parathyroid abnormalities. Subsequently, the thoracic and abdominal CT revealed a soft tissue in the anterior mediastinum 7 × 1 cm. Additional Tc-99m-MIBI scintigraphy followed, which detected an ectopic adenoma located in the lower anterior mediastinum, on the left of the median line (). Following these, a mid-sternal thoracotomy was finally scheduled.
During the operation, after the thoracotomy, surgeons attempted to detect deep into the mediastinum the parathyroid adenoma according to the preoparative localization. Indeed, the mediastinal mass was detected on the left of the median line, at the anterior mediastinum, in front of the anterior surface of the pericardium and close to the left pericardiophrenic vessels and the left phrenic nerve (). The adenoma was covered by a thin fibrous capsule. When surgeons removed the capsule, a dark red mass of 7 × 2.8 × 1 cm was finally revealed (Figs. and 4 ). The detailful preoperative localization of the present mediastinal adenoma which was in close relation with various anatomical structures of the thorax, reduced effectively the difficulty of the mass excision and the potentiality of accidental surgical injuries which may lead to thoracic bleeding and subsequent obstructive symptoms.
Then, the operation continued in the usual fashion and a drainage was placed into the left side of the thoracic cavity. The patient was discharged the 5th postoperative day with instructions, when the drainage was finally removed.
Histology of the mass confirmed the diagnosis of ectopic parathyroid adenoma that was composed predominantly of oxyphil cells arranged in an acinar pattern. Serum calcium level was 2.60 mmol/L and iPTH 17.6 pg/mL 12 h after the operation. Serum calcium and iPTH remained normal after 6 months’ follow-up. |
pmc-6495086-1 | An 89-day old female infant, presented to our clinic with absent nasal columella since birth (). The patient was a product of a normal vaginal delivery (NVD) of a preterm (27 weeks) pregnancy, with birth weight of 1.1 kg. The patient was admitted to the NICU for prematurity and respiratory distress, and was discharged after 70 days. Currently, she has no difficulty in breathing nor feeding. The patient has family history of congenital heart disease of her uncle who is currently 10 years old and is doing well and both of her elder brother and sister are medically free. Moreover, the mother denied radiation exposure or utilization of any medications during pregnancy or breast feeding. The patient has no previous history of trauma, malignancies or infections, and there was no consanguinity between the parents.
The physical examination revealed that her growth chart (weight, height, and head circumference) is at the 30th percentile according to the CDC growth chart for females below 36 months. A total absence of the nasal columella from the nasal tip down to the root of the philtrum, involving the medial crura of the ala cartilage. Surrounding structures such as the septum, nose, and upper lip are normal. The rest of her physical examination was entirely normal.
The laboratory investigations, chest x-ray, echocardiogram, and ultrasound of the abdomen were all unremarkable. After discussing the treatment options with the patient’s parents, they preferred the option of having the newly introduced 2-stage reconstruction of the columella described by Pan et al. [] after the age of one year. The first stage will involve bilateral nasal sill flaps that will be elevated and mobilized medially to create the new columella, and in the second stage we will insert an auricular composite graft to provide support where a portion of the caudal septum was missing, and to complete the new columellar reconstruction []. |
pmc-6495497-1 | A 70-year-old Sri Lankan man with well-controlled diabetes mellitus and hypertension over 6 years developed acute onset, high-grade, intermittent fever associated with headache, arthralgia, myalgia, and nausea with no apparent focus of infection. On day 2 since onset of fever, he developed drooping of his eyelids and dysarthria. On day 3, he developed dysphagia and difficulty in walking because of unsteadiness. He did not experience any alteration of consciousness, seizures, sphincter dysfunction, limb weakness, or paresthesia. He was admitted to hospital on the third day of his illness. A timeline of the events starting from onset of fever is summarized in Table . There was no history of recent respiratory or gastrointestinal infection, or immunization. He had not had any neurological diseases in the past. His current medications included losartan for hypertension and metformin for diabetes mellitus.
On examination, his body temperature was 38.5 °C while general examination and respiratory, cardiovascular, and abdominal examinations were normal. His heart rate was 76 beats per minute and his blood pressure was 140/90 mmHg. On neurological examination, he was noted to be conscious, alert, and oriented. He had bilateral asymmetric ptosis more on right side, mid-dilated pupils with sluggish reaction to light, and complete bilateral external ophthalmoplegia but without diplopia; optic fundi, visual fields, and acuity were normal. He had bilateral palatal weakness and tongue deviation to right side; the rest of his cranial nerves were normal. He had a broad-based ataxic gait, dysdiadochokinesia, and dysmetria; all tendon reflexes were absent; the rest of the neurological examination of limbs, including sensation, was normal.
Investigations revealed thrombocytopenia with a platelet count of 106 × 109/l on day 3, which dropped further to 17 × 109/l on day 6. His platelet count then gradually increased to 164 × 109/l by day 13. His white cell count reduced to 4200 × 109/l on day 5 and then gradually increased to 7100 × 109/l on day 13. Hematocrit was 40% and stable throughout the course of the illness. His creatinine was 99 μmol/l; serum sodium 132 mmol/l; and potassium 3.6 mmol/l. Serum aspartate aminotransferase (AST) showed a rise from 115 U/l on day 3 to 243 U/l on day 5 and normalized to 43 U/l by day 10. Alanine aminotransferase (ALT) was 55 U/l on day 3, increased to 127 U/l on day 5, and normalized to 37 U/l by day 10. Other liver functions were normal. His erythrocyte sedimentation rate was 18 in the first hour and C-reactive protein was 32 mg/l. Urine analysis and an ultrasound scan of his abdomen were normal.
A dengue non-structural protein 1 (NS-1) antigen test by rapid diagnostic test and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) done on the third day of illness and dengue IgM antibodies by enzyme-linked immunosorbent assay (ELISA) tested on the seventh day of illness were positive. Serum IgM antibodies to West Nile virus and Japanese encephalitis virus by ELISA were negative on day 7. Nerve conduction studies showed evidence of mild axonal polyneuropathy. Repetitive nerve stimulation did not show decrement. Computed tomography (CT) and magnetic resonance imaging (MRI) scans of his brain were normal. Cerebrospinal fluid (CSF) analysis performed on the 12th day of illness after recovery of thrombocytopenia was normal with no albuminocytologic dissociation. PCR for dengue virus and dengue IgM antibodies in CSF were negative. Antibodies (IgG, IgM, and IgA) against a panel of gangliosides including GQ1b and GT1a were negative.
DF was treated with fluid replacement at 100 ml/hour while monitoring for plasma leakage clinically and ultrasonically. His fever subsided after 5 days from onset and all hematological parameters returned to normal subsequently. He was treated with intravenously administered immunoglobulin 0.4 g/kg for 5 days starting from the fourth day of his illness. He required nasogastric feeding because of dysphagia. He was treated with swallowing and speech therapy, and gait and balance training.
From around the sixth day of illness, his ptosis and ophthalmoplegia began to improve gradually. His ataxia improved enabling him to walk without support from the eighth day onward. He was discharged from hospital on the 13th day of illness and continued nasogastric feeding, physiotherapy, and speech therapy at home. At review 1 week later, he had made a complete neurological recovery with normal swallowing, complete eye movements, normal gait, and re-emerged deep tendon reflexes. |
pmc-6495498-1 | A 72-year-old right handed male diagnosed with poorly-differentiated, stage IIIB neuroendocrine carcinoma of the colon s/p hemicolectomy, small bowel resection and carboplatin-etoposide × 3 cycles presented to the emergency department with acute altered mental status and right facial droop.
Four months prior, he presented with constipation and anemia. Colonoscopy revealed a large raised flat lesion in the transverse colon and CT abdomen demonstrated RLQ mesenteric lymphadenopathy. He underwent right hemicolectomy and small bowel resection weeks later. Pathology was significant for poorly-differentiated grade 3, neuroendocrine carcinoma with focal lymphovascular invasion and tumor invasion through the muscularis propria into the subserosa. Margins were negative, no perineural invasion and 1/33 lymph nodes were positive for carcinoma. There was an absence of non-neuroendocrine component. Immunohistochemical stains were positive for: AE1/AE3, CD56, chromogranin, and synaptophysin; Ki-67 of 60% proliferative index. He was staged as pathologic T3N1a, stage IIIB.
In the emergency department, head CT was negative for an acute hemorrhagic process and did not demonstrate any suspicious lesions. Within one day of admission, the facial droop resolved. Further imaging, CT chest abdomen pelvis, revealed stable enlarged mediastinal lymphadenopathy and a subcentimeter retroperitoneal lymph node but no progression was evident. Two days into the hospital stay, the patient developed fever and subsequently neck stiffness. His chest x-ray and urinalysis were non-diagnostic; EEG showed diffuse slowing but no seizure activity. A lumbar puncture was performed with cytopathology of the CSF suggesting metastatic disease to the central nervous system (Fig. ), along with lymphocytic pleocytosis, normal glucose, and significantly elevated protein and lactic acid. Cytologic analysis showed tumor cells with characteristically-high nuclear to cytoplasmic ratio, relatively round nuclei with stippled “salt and pepper” nuclear chromatin and minimal cytoplasm, features consistent with metastatic neuroendocrine carcinoma (Fig. a). Immunohistochemistry showed the tumor cells were strongly positive for synaptophysin (Fig. b) and Cytokeratin AE1/AE3 (Fig. c) with a typical perinuclear dot pattern.
Medical oncology and radiation oncology were consulted. No further chemotherapy was recommended as he had progressed after completing 3 of 6 cycles of carboplatin-etoposide. Enrollment in an erlotinib trial was discussed vs palliative therapy. While radiation was considered to be potentially palliative for his symptoms, radiation oncology deemed it would be unlikely to change his overall survival. He was started on palliative high-dose steroids and ultimately transferred to inpatient hospice care. The patient passed away within a week of entering hospice. |
pmc-6495508-1 | A woman aged 52 years with no prior trauma presented with severe pain, swelling and increased local heat in the proximal area of the right knee. The patient’s symptoms developed 3 weeks prior to her arrival at our hospital. She initially presented with pain in both knees at the local clinic and was treated with physical therapy and hyaluronic acid injections. The left knee pain resolved following treatment. However, the right knee pain persisted, and the patient reported that the pain and increased local heat had extended to the more proximal area. Furthermore, the patient developed a high fever of over 39 °C 2 weeks after first treatment. She was referred to our hospital with a suspected distal femur bony malignancy.
The patient had no past medical history of diabetes mellitus, hypertension, hepatitis, or systemic infection. The patient’s Human Immunodeficiency Virus (HIV) test, and liver and kidney function tests were normal. Notably, she had a salphingectomy 15 years prior, and a single tooth extracted approximately 4 months prior to presentation. She received prophylactic antibiotics before the tooth extraction.
On the physical examination, an increased local heat in the proximal area of the right knee without an external wound, or draining sinus was confirmed. Body temperature was 38.8 °C. Laboratory test results showed the following: leukocytes 7260/μL (neutrophil 79.1%), absolute neutrophil count 4050, C-reactive protein (CRP) 21.26 mg/L, and erythrocyte sedimentation rate (ESR) 72 mm/h. We conducted synovial fluid analysis on the fluid extracted from the right knee joint. Synovial fluid analysis revealed a white blood cell count of 870/mm3, a polymorphonuclear leukocyte of 45%, and no crystals were found. Anteroposterior and lateral radiography of the right knee revealed multifocal osteolytic changes in the distal metaphysis area of the right femur. The lesion had an irregular margin but no sclerotic rim (Lodwick classification type 1B). There was no definite destruction of cortical bone. However, a subtle cortical thickening lesion suggesting solid type of periosteal reaction was found at superior aspect of lateral femoral condyle (arrow head, a) (Fig. ). The axial (a), coronal (b), and sagittal (c) T2-weighted magnetic resonance imaging (MRI) of the right knee, which were previously performed at another hospital (with lacking information of T1 weighted and enhanced image), are shown in Fig. . Multifocal intraosseous lesions (6.1 × 2 × 2 cm) at metaphysis and diaphysis of the distal femur were observed with no destruction of cortical bone. However, double-contour periosteal line, which suggesting periosteal reaction (arrow head, A and B) at lateral aspect, and marrow edema were found in the adjacent tissues (asterisk, B). Considering the patient’s age, location of the lesion, margin, and absence of cortical destruction, we suspected osteomyelitis rather than a bony malignancy.
Still considering the possibility of malignancy, we made a 5 cm longitudinal incision in the anterolateral aspect of the distal femur. We split the vastus lateralis muscle and made an oval-shaped bony window in the lateral aspect of the femur. We evacuated yellowish pus-like intramedullary abscess, and the tissues were sent for Gram staining, routine culture, acid-fast bacillus (AFB) culture, fungus culture, and pathology test. Tissues were collected from various sites, and frozen pathology test was performed to exclude the possibility of malignancy. The emergency frozen pathology examination showed an absence of malignant cells. Continuous, massive marginal debridement and irrigation were performed. We inserted a negative-pressure drain into the intramedullary canal through the distal femur bony window. Intravenous first-generation cephalosporin (Cefazolin, 2 g/q8hr) was empirically used to target methicillin-susceptible Staphylococcus aureus, which is still the most common cause of osteomyelitis. The tissue culture, fungus culture, AFB culture, AFB smear, and tuberculosis (Tb) polymerase chain reaction (PCR) tests were negative.
Six days post-surgery, pathologic examination of a bone biopsy specimen revealed acute and chronic osteomyelitis. Furthermore, colonies of filamentous bacteria that were rimmed by neutrophils with sulfur granules, which are indicative of actinomycotic colonies, were present. (Fig. ) However, we were unable to confirm the exact species of Actinomyces. As a result, the treatment plan was altered, and intravenous penicillin G potassium (400 million IU/q6hr) was administered to target the actinomycotic osteomyelitis. The patient received repeated curettage and debridement on postoperative days 13, 27, 41, and 54 because of continuous pus- like discharge through the suction drain and abnormal ESR and CRP results. The specimens obtained on days 13, 27, and 41 were still positive for sulfur granules on pathologic examination. However, the culture tests remained negative. The specimen obtained on day 54 was normal on following pathologic examination. At postoperative day 60, the yellow pus-like discharge decreased in volume, and the ESR and CRP results were normal. The drain was removed, and the wound was closed. Penicillin G potassium was Intravenously administered for 8 weeks followed by amoxicillin-clavulanate taken orally at a dosage of 625 mg every 6 h for 6 weeks. CRP and ESR were tested at 2-week intervals. After confirming the CRP and ESR values were normal for 3 consecutive intervals and that there were no signs of recurrence (local heating, pain, swelling, or painful range of motion), we discontinued the oral antibiotics. Antibiotics were discontinued after total 14 weeks of treatment.
Follow-up was performed at 6 months, 1 year, 3 years and 5 years after surgery. At the follow-up, X-rays showed that the bony window was not fully recovered, but there was no evidence of recurrence or pathological fracture (Fig. ). During the 5-year follow-up period, CRP and ESR levels remained normal, and there were no symptoms of recurrence, such as local heating, swelling, and pain. In addition, the patient had full range of motion in the affected knee. The patient is satisfied with the result of treatment and enjoy daily life with no discomfort. |
pmc-6495538-1 | The case was a 5-year-old-girl, who was admitted to the hospital with a 2-year history of intermittent convulsions. She was born to healthy, unrelated parents. Her mother had slight vaginal bleeding for one week at the three months pregnancy without any therapy. She appeared normal at birth at 40 + 1 weeks of gestation and had normal Apgar scores. Birth weight, length, and head circumference were within normal ranges. Family history was unremarkable for neurologic diseases. Her psychomotor development was delayed. Her parents reported that she sat at eight months, and walked with support until 18 months. She suffered from bruxism and characteristic stereotyped hand movements such as clapping and tapping started at the age of 2 years. At the age of 3 years, she developed seizures characterized by staring eyes, hands rubbing and hypokinesis of the head (10 times per day), severely associated with lip and face cyanosis (1 time per day). Her parents reported that her EEG in a specific hospital showed abnormality at three years of age, and the seizures were not adequately controlled after one year of Chinese medicine therapy. Thus, they gave up drug therapy. In the last year, another abnormal behavior was observed. She regularly tapped her lips using the right hand, and bed using the left hand in awake and stopped until sleep. In the last month, the frequency of seizure increased significantly, and seizure symptoms developed more serious. So her parents took her to our hospital for comprehensive examination. She was diagnosed with RTT from her history and clinical findings. A cerebral magnetic resonance image was normal. Mutational analysis of MECP2 revealed a mutation in this affected girl. Twenty-four-hour video-EEG recordings revealed a slowing advantage rhythm (5-6 Hz) of occipital region and extensive slow wave activity in the background activity. Besides, multifocal discharges were noted during awake, especially in the Rolandic region, significantly aggravated to evolution toward electrical status epilepticus during sleep (ESES). Several partial seizures and constantly-tapping her lips using right hand were recorded during EEG recordings, which was the same as that described by the parents. To our surprise, tapping- lips in light and slow rhythm could trigger extensive low amplitude fast wave rhythm (Fig. ), and relatively stronger and quicker rhythm could result in multifocal bilateral discharges (Fig. ). Corresponding discharges were disappeared when the movement was intervened by parents. The patient chose left hand to rhythmically tap lips when the right hand was restricted, but there were no synchronic discharges accompanied by the action. Moreover, the synchronous phenomenon of action and discharge was not observed when the right hand was tapping cheek or abdomen. More interestingly, the discharges were not precipitated by tapping- lips using observer’s hand at the certain tempo and intensity. The coexistence phenomenon persisted in different EEG caps, instruments, and rooms, which ruled out the possibility of an artifact. By the phone call following-up, the total frequency of epilepsy seizures was markedly less after one year of treatment with valproate, but hand stereotypies did not respond to the antiepileptic drug. |
pmc-6495541-1 | A 5-year-old female child was admitted for intracranial tumor on 29th March 2018. Her chief complaint was polydipsia and polyuria for 3 years. The MRI image of December 2015 in local hospital showed tumor on sellar region, with characteristics of T1 hypointensity, T2 hyperintensity and homogenous enhancement. Recent 2 months, she presented with symptoms of intermittent body seizure and unconsciousness. The reexamination MRI in March 2018 revealed the tumor was bigger (Fig. ). Her height was 95 cm and weight 32 kg, the body mass index was 35.5. Her previous history was negative. Physical examination indicated no obvious signs except obesity and short neck. Although without results of polysomnography test, apnea did take place during sleep, so we inferred there was possibility of obstructive sleep apnea (OSA). We evaluated her with ASA II and Mallampati III. Results of blood routine, coagulation function and D-dimer tests were normal. But the blood electrolytic, such as serum Na+ (154.8 mmol/L) and Cl− (119 mmol/L) were significantly higher than the reference. Meanwhile some blood hormone results were also abnormal. For example, free T4 (0.56 ng/ml) and total T4 (3.27μg/ml) were slightly lower than the reference, but cortisol (1.41μg/dl) and adrenocorticotropin (< 5.0 pg/ml) were significantly reduced. These changes of hormone demonstrated pituitary dysfunction and might cause the electrolytic and distribution of body fluids abnormal. Electrocardiogram and echocardiogram tests were normal, but serious fatty liver was detected by abdominal ultrasound. Thus, for exact diagnosis and treatment in progress, the operation with general anesthesia would be done to draw the tumor tissue for pathological examination.
After admission, sodium valproate 0.5 g/bid and levothyroxine 25μg/qn were administered. Blood electrolytic was monitored and regulated daily. The result of chest computer tomography (CT) on 30th March was negative, and her preoperative chest examination was normal (Fig. ). Na+ 146.6 mmol/L and Cl− 111.6 mmol/L, which re-examined on 3rd April, closed to normal range. Routine cortisol supplement was delayed due to results of cortisol and adrenocorticotropin reported not in time.
On 4th April, this girl was sent to the operating-room by stretcher. It was difficult to establish venous access because she was obese and incompatible, so the sevoflurane inhalation induction was given with 3%~ 8% sevoflurane and O2 6L/min. At the beginning of induction, she struggled for few seconds. The monitor showed SpO2 was 92%~ 96%. Although she was keeping spontaneous breathe, the tidal volume was very low, just 70~100 ml. Meanwhile, her breathe movement was not as same as normal, because there was very mild collapse of suprasternal fossa on inhalation stage, albeit it was not apparent. At the same time, another anesthesiologist was called for more assistance because of difficult jaw-thrust. By squeezing breather bag, support ventilation following her spontaneous breathe was tried, but the situation could not be improved and jaw-thrust was still difficult.
Twenty minutes later, venous access was established. Thus propofol 50 mg, sulfentanil 15μg and rocuronium 40 mg were administered. Endotracheal intubation with 4.5-intensive-tube was successful with routine laryngoscope, because exposing and visualizing her larynx and glottis was easily. No secretion was found in her mouth. And her tonsilla and vocal cords were normal. During the induction phase, although her heart rate and blood pressure waved normally, low tidal volume, low SpO2 and mild airway blocking sustained, the SpO2 was only 91%~ 95% with FiO2 100%.
After endotracheal intubation, mechanical ventilation setting was as follows: tidal volume 200 ml, I:E = 1:2, f 20, FiO2 100%. The monitor showed seriously high peak pressure sustaining at 36~39cmH2O. In the meanwhile the SpO2 was only 90%~ 92% and EtCO2 more than 55 mmHg. Although no wheezing rale and stridor, obvious blistering sound and coarse crackles presented in both lung fields by chest auscultation. Thus airway was aspirated immediately, only little secretion in the tracheal. But the ventilation was not ameliorated. After changing volume controlling model into pressure controlling model, ventilation situation was still bad. Then general anesthesia was enhanced by increasing concentration of sevoflurane and administering sulfentanil 10μg and rocuronim 20 mg. At the same time, methylprednisolone 40 mg and furosemide 10 mg were administered. Unfortunately, ventilation situation was not improved, such as seriously high airway peak pressure and low SpO2. Then the operation had to be cancelled, and she was sent to ICU after taking chest CT scan (Fig. ). Surprisingly, chest CT showed bilateral pulmonary consolidation accompanied by air bronchogram and the ground-glass opacity lesions, but echocardiography demonstrated a preserved left ventricular ejection fraction 65%.
In ICU, positive pressure mechanical ventilation was initiated. Methylprednisolone 40 mg and levothyroxine 25μg for one dose were administered. Although there was no bacterial organisms in sputum culture, meropenem was administered for anti-infection. Several hours later, breathe sound was obviously better except the bottoms of bilateral lung with tiny rale. After 48 h of supportive care in ICU, the pulmonary edema resolved rapidly, reexamined chest CT demonstrated the most of lung field was clean except bilateral lower lobe alveolar infiltrates and consolidation (Fig. ). |
pmc-6495557-1 | A 54-year old man presenting with progressive cognitive impairment was admitted to the memory clinic at the Department of Psychiatry and Psychotherapy. His Mini-Mental State Examination score showed a cognitive impairment (24 out of 30 points). Furthermore, he had mild orofacial dyskinesia, which was suggested to be a side-effect of his medication with melperone. The patient received this treatment because of a sleep disorder and restlessness. After clinical examination he was referred to the Department of Nuclear Medicine with the suspected diagnosis of Alzheimer’s disease for an 18F-FDG PET/CT study. Family history was empty showing no neurodegenerative or psychiatric diseases in first degree relatives. The patient’s father had suffered from a stroke with persisting disability and died at the age of 66 years.
While CT and MRI showed no pathologic findings, the 18F-FDG PET/CT (Philips Gemini TF16, Best, Netherlands) of the brain revealed a severe bilaterally decreased uptake in the striatum (Fig. ). Additionally, we performed two different voxel-based intersubject statistical analyses to a reference database. First, using NEUROSTAT [] we performed 3D standard surface projections (3D-SSP) from patient’s 18F-FDG-PET and compared them to an age-matched 3D-SSP database in order to detect dementia-related hypometabolism in the cortical areas (Fig. ). In a second step, focusing on subcortical regions, we used SPM 12 (Wellcome Trust Centre for Neuroimaging at UCL, London) implemented in Matlab 9.0 (MathWork, Sherborn, Mass.) and performed a voxel-by-voxel single subject analysis of the whole brain. We then compared our patient to an age-matched healthy group used in NEUROSTAT []. Concordant to the visual findings we found a significant reduced bilateral uptake in the striatum (Fig. ).
Following imaging Huntington’s disease (HD) was being favored as underlying cause for the patient’s cognitive impairment. Subsequently, a molecular genetic testing was initiated, which confirmed the diagnosis of HD. One allele showed an abnormal CAG repeat of the Huntingtin gene (HTT) in chromosome 4p16.3 of 41 ± 1, while the other allele was normal (CAG repeat of 20 ± 1). |
pmc-6497185-1 | A 53-year-old African-American woman with ESRD was transferred from dialysis clinic to the emergency room (ER) for evaluation of non-radiating and dull epigastric pain for two weeks associated with fever and chills during hemodialysis (HD). Three months ago, she was hospitalized and treated for Streptococcus pneumoniae and Enterobacter cloacae bacteremia. A year ago she was treated for S. maltophilia bacteremia secondary to an infected dialysis catheter. Past medical history was also significant for hypertension, atherosclerotic vascular disease pending elective coronary artery bypass graft (CABG) surgery, and sudden cardiac arrest followed by ICD placement. With the current presentation, both blood and catheter cultures obtained at the dialysis clinic were positive for S. maltophilia, prompting her subsequent arrival to the emergency room. She presented with a continuation of fever and chills, as well as tachycardia and episodic hypotension. She was noted to have mild epigastric tenderness. There was no surrounding erythema, discharge, or tenderness noted around the tunneled dialysis catheter on the right anterior chest. Initial workup showed elevated troponin and procalcitonin. Chest X-ray findings were suggestive for left lower lobe pneumonia. Within the ER, the patient's hypotension resolved with fluid resuscitation and intravenous levofloxacin therapy was started with blood cultures drawn.
Cardiology was consulted for persistent elevation of troponins and it was presumed secondary to impaired clearance in ESRD. Transthoracic echocardiography (TTE) was done to evaluate for endocarditis given the presentation of bacteremia and fevers. TTE revealed artifact noted on an abandoned ICD lead in the right heart concerning for possible vegetation. Repeat blood cultures were positive for S. maltophilia and the patient was continued on levofloxacin. Infectious Diseases was consulted and as per their recommendation the infected tunneled dialysis catheter was removed on the 2nd day of the hospitalization (DOH). The patient continued to be febrile despite levofloxacin therapy and a transesophageal echocardiogram (TEE) was performed to look for a cardiac source. Subsequent blood cultures were negative at this time but the patient continued to be symptomatic. The TEE was done on the 4th DOH and showed a 1 x 0.5 cm echodensity attached to an abandoned right ventricular (RV) ICD lead in the superior vena cava (SVC) as it entered into the right atrium (RA). The echodensity was concerning for a vegetation due to IE. ID consultation recommended removal of the abandoned lead with culture of the probable vegetation that may have served as a nidus for recurrent bacteremia. Levofloxacin therapy was continued and a new dialysis catheter was placed on the 5th DOH with HD restarted. At this time, the patient became afebrile and reported symptomatic improvement. Despite a strong suspicion for IE by Duke criteria, fluorodeoxyglucose positron emission tomography (FDG PET) on the 6th DOH was non-diagnostic for differentiating infective etiology from thrombotic. Cardiothoracic surgery was consulted for removal of the abandoned lead for culture and planned to do so in coordination with her pending elective CABG procedure. In the interim, repeat blood cultures remained negative on the 7th DOH and the patient was stable and discharged on the 12th DOH with instructions to transition to oral levofloxacin until her CABG procedure, scheduled 18 days from discharge.
Unfortunately, the patient expired due to complications from cardiac arrest secondary to severe hypokalemia in the postoperative period after removal of the infected ICD lead and successful CABG. No vegetation could be appreciated on gross inspection of the removed ICD-lead and subsequent culture was negative for any growth, indicating a resolution of the IE over the one-month course of levofloxacin treatment since presentation. |
pmc-6497187-1 | A 35-year-old man with a medical history of splenectomy due to splenic artery rupture presented to the hospital with diffuse abdominal pain of one-day duration associated with nausea and two episodes of non-bilious, non-bloody emesis. Patient denied any significant aggravating or relieving factors of the pain, no association with food intake or recent antibiotic exposure, and no fever, chills, rigors or diarrhea. He was not taking proton pump inhibitor. On examination, the patient was afebrile, tachycardic with a blood pressure of 85/61 mm Hg. Abdominal examination revealed diffuse mild tenderness without guarding or rigidity and bowel sounds were present. Lab work up was pertinent for leucocyte count of 32 x 109 cells/L (normal range: 3.7-11 x 109 cells/L) with predominant neutrophils 87% and elevated serum lactate 4 mmol/L (normal range: 0.5-1.0 mmol/L) with no end-organ damage. Urine, blood cultures, and chest X-ray did not reveal any source of infection. Computed tomography (CT) of the abdomen and pelvis with intravenous (IV) contrast showed mild-moderate prominence of adjacent proximal and mid jejunum without bowel obstruction or evidence of colitis, most likely representing enteritis (Figure ). The patient was started on broad-spectrum antibiotics with IV pipercillin-tazobactam and vancomycin due to concern for severe sepsis of unclear etiology. As patient signs and symptoms did not improve with broad-spectrum antibiotics, stool studies were obtained and C.difficile was confirmed on stool polymerase chain reaction (PCR). The patient was started on oral vancomycin 125 mg every six hours and IV antibiotics were discontinued. The patient’s signs and symptoms improved after oral vancomycin, and he was discharged home to complete a 14-day course of oral vancomycin. |
pmc-6497188-1 | A 77-year-old, obese, Caucasian male presented to the emergency department (ED) with a sudden onset of lower chest and epigastric pain and sudden collapse after lifting a heavy object while working on his ranch. Per his wife, the patient was a previously healthy and active individual who had lost 50 pounds over the prior year on a diet and exercise regimen. The patient had a past medical history of gastroesophageal reflux disease, hyperlipidemia, diabetes, and hypertension. He was a former smoker from about age 15 to 60. The patient also had a history of daily alcohol use, which ended in his mid-forties.
Upon arrival to the ED, the initial vital signs revealed a blood pressure of 94/72 millimeters of mercury (mmHg), heart rate of 89 beats per minute (bpm), respiratory rate of 16 breaths per minute (BPM), and oxygen saturation of 100% on room air. On physical exam, the patient was somnolent but easily aroused, pale, and in severe distress. The cardiovascular exam revealed that the heart had regular rate and rhythm without murmurs. His lungs were clear and without wheezes, rhonchi, or rales. His abdominal exam was notable for a soft, distended, moderately tender epigastric region but without rebound or guarding. A pulsatile mass was not palpated and there were no abdominal bruits.
His initial complete blood count demonstrated a white count of 24.0 ×109/L, hemoglobin of 11,000 grams per liter, platelet count of 198 ×109/L, with 93% neutrophils. The comprehensive metabolic panel was unremarkable. The creatine phosphokinase and troponin were normal. Amylase and lipase were normal. An electrocardiogram (ECG) showed a sinus rhythm with no acute ST changes and a right bundle branch block, which was seen on a previous ECG.
The patient underwent a computed tomography (CT) angiogram of the chest and abdomen which showed 8.0 centimeter (cm) × 6.0 cm × 6.5 cm aneurysm in the expected location of the celiac artery and splenic artery with extensive stranding of the surrounding fat, representing active hemorrhage as seen on the sagittal abdominal CT ( and ).
Within 30 minutes of arrival to our ED, the patient was in hypovolemic shock with hypotension (59/34 mmHg), tachycardia (142 bpm), and tachypnea (rate 26 BPM). The vascular surgeon was notified immediately and the patient was taken to the operating room within 45 minutes of arrival to undergo a ligation of the neck of the aneurysm. Upon arrival to the intensive care unit, the patient lost his pulses. He was unfortunately pronounced dead after unsuccessful heroic efforts. |
pmc-6497189-1 | A 74-year-old female with a history of diabetes mellitus, hypertension, atrial fibrillation (on warfarin, diltiazem and metoprolol) presented with chest and back pain. A 12-lead electrocardiogram (ECG) was ordered at triage demonstrating possible aberrant pacemaker activity (). |
pmc-6497190-1 | A seven-year-old boy presented to an outside facility after sustaining a hip injury while playing organized football. He reported that he was struggling at the bottom of a pile when he developed severe hip pain. At the outside hospital, he was diagnosed with a posterolateral hip dislocation. No attempt at reduction was made at the referring hospital. After consultation with a local orthopedist, the patient was transferred to our tertiary care facility via helicopter, and he arrived approximately 5.5 hours after initial injury. Prior to his arrival, preparations were made by ED staff for a rapid, comprehensive trauma evaluation and emergent sedation and reduction measures.
The patient complained of right leg pain and tingling upon arrival, with no reported pain elsewhere. Physical exam revealed that he was moderately distressed from pain and slightly tachycardic. The right lower extremity was internally rotated with flexion at the knee. He had normal distal pulses, good capillary refill, and was able to move his toes. Pelvic radiograph confirmed posterolateral right femoral head dislocation without evidence of fracture, as seen in . Point-of-care focused assessment with sonography for trauma exam and chest radiograph were also completed and both were negative.
A complete trauma evaluation confirmed an isolated right hip dislocation with no contraindications to procedural sedation to facilitate dislocation reduction. Given his stable hemodynamics, he was sedated with intravenous propofol. Once sedated, the pelvis was stabilized by providing posteriorly directed countertraction to the pelvic girdle preparing for reduction via Allis technique. The emergency physician (EP) stood on the bed, flexed the hip and knee to 90 degrees, placing the patient’s right leg into a simulated seated position, and provided steady anterior traction by pulling from behind the knee and slightly internally rotating. The right hip was easily reduced without complication and the patient remained hemodynamically stable. Post-reduction, radiographs were performed showing complete reduction of the femoral head, as seen in . The patient’s pain was improved and his paresthesias were resolved.
Pediatric orthopedics was subsequently consulted, recommending a pelvic computed tomography (CT), which was negative for fracture. The patient was placed in a knee immobilizer and admitted for observation. He was discharged the next day with a walker, restricted to toe-touch weight-bearing of the right lower extremity with no hip flexion past 90 degrees or adduction past midline. He did well in follow-up, returning to full weight-bearing activity and exercise two months post-injury. |
pmc-6497191-1 | A 19-year-old primigravida female presented with three weeks of intermittent suprapubic and left lower quadrant (LLQ) abdominal pain, worsening in the prior 24 hours, associated with nausea and vomiting at the time of presentation. Her last normal menstrual period was approximately 17 weeks prior to presentation, but she reported some vaginal spotting nine weeks ago. Abdominal exam revealed diffuse tenderness to palpation, worse in the LLQ, without peritoneal signs. A point-of-care ultrasound (POCUS) showed an intrauterine pregnancy (IUP). However, the patient’s persistent unilateral pain was concerning. Therefore, a formal pelvic ultrasound was performed, which revealed an IUP at seven weeks gestation, including an anechoic region with free fluid in the pelvis (), and a left adnexal complex mass suspicious for extrauterine pregnancy (). She subsequently underwent a laparoscopic left salpingectomy for a ruptured ectopic pregnancy. The IUP was unaffected. |
pmc-6497192-1 | A 67-year-old female with history of chronic tobacco use, chronic obstructive pulmonary disease, hypertension, and hyperlipidemia, presented to the ED with symptoms of TIA. The patient described the acute onset of left-sided facial weakness that waxed and waned, recurring several times throughout the day, and lasting 2–3 minutes at a time. The left facial weakness was also associated with mild, left-arm weakness and “clumsiness” involving fine motor function of her left hand. She noted lightheadedness but denied leg weakness, headache, visual changes, chest pain or shortness of breath. She also noted that symptoms were brought on by use of her upper extremities and when she changed her body position from lying to sitting. She denied any similar symptoms previously or stroke history. Of note, she noticed a rapid improvement in her symptoms to resolution just prior to ED presentation.
On examination, her blood pressure (BP) was 183/86 millimeters of mercury (mmHg). She was awake, alert, oriented, and able to describe a detailed history. Her cranial nerves were intact, motor strength was 5/5 bilaterally, and fine motor movements in both her hands were normal. There was no ataxia, extraocular muscle dysfunction, or indication of posterior circulation involvement.
Just after her initial asymptomatic presentation to the ED, her symptoms recurred when her systolic BP dropped by 20 mmHg upon standing from a supine position. Emergent computed tomography angiogram (CTA) of the head and neck demonstrated a severe flow-limiting lesion of the innominate artery (). Further investigation with magnetic resonance imaging demonstrated decreased signal intensity within the right internal carotid artery at the cavernous sinus and petrous segments, a finding that potentially represented slow flow ().
The patient subsequently underwent emergent cerebral angiogram, which demonstrated occlusion of the proximal innominate artery () at the aortic arch with resultant left to right vertebral artery steal phenomenon supplying the right subclavian artery (). The distal brachiocephalic artery flow was reconstituted via the subclavian artery and secondary steal phenomenon occurred into the right common carotid artery, causing delayed flow to the right cerebral hemisphere ().
The patient was maintained on a norepinephrine bitartrate infusion to increase BP, and her symptoms subsequently resolved. The symptoms recurred when she was positioned supine, but upon being placed in the Trendelenburg position her symptoms again resolved. The patient was therefore maintained with systolic BP goals between 160 and 210 mmHg. She remained asymptomatic during this period of elevated BP management. For definitive care, she underwent elective left carotid to right carotid “necklace” bypass surgery with complete and permanent resolution of her symptoms. |
pmc-6497193-1 | A 72-year-old female with a past medical history of hypertension presented to the emergency department (ED) with one day of generalized weakness, headache and rash. Review of her medical history revealed that she presented to her primary care physician with complaints of vaginal discharge two weeks prior to her presentation to the ED. Despite treatment with metronidazole, symptoms persisted prompting a speculum exam and vaginal cultures obtained by primary care physician five days prior to her ED encounter. These returned positive for N. meningitidis. At the time of presentation, she had not followed up for those results and therefore had no further treatment. The patient had been in her normal state of health until the previous evening when she described general malaise and fell asleep early. Her husband stated that she also slept much later than usual and when he tried to wake her, she seemed lethargic. Review of systems was otherwise negative.
Initial vital signs revealed a temperature of 101.7 degrees Fahrenheit, a pulse of 120 beats per minute, respiratory rate of 24 breaths per minute, and a blood pressure of 107/49 millimeters of mercury. The patient was found to be ill-appearing and obtunded. She had nuchal rigidity and a diffuse, non-blanching, purpuric rash. Other than atrial fibrillation with a rapid ventricular response, the remaining physical exam was unremarkable.
Immediate concern for meningococcemia prompted empiric vancomycin (20 milligrams per kilogram, intravenous [mg/kg, IV]), ceftriaxone (2 grams [g], IV), ampicillin (2 g IV), dexamethasone (10 mg IV), and an initial 2-liter (L) normal saline bolus. After an unremarkable non-contrast computed tomography of her head, a lumbar puncture was performed revealing turbid cerebral spinal fluid with a white blood cell count of 262 cells per millimeter cubed (mm3) (0–5 cells/mm3), glucose of 28 mg per deciliter (dL) (40–70 mg/dL), and a protein of 155 mg/dL (15–45mg/dL). Gram stain showed many gram-negative diplococci. Her initial serum white blood cell count was 7.4 thousand cells/mL3 (4.0–10.0 cells/mL3) and the initial lactic acid was 8.1 millimoles per liter (mmol/L) (0.5–1.6 mmol/L). Despite aggressive fluid resuscitation, the patient rapidly decompensated requiring central line placement, intubation, and norepinephrine infusion.
The patient was admitted to the intensive care unit where she had persistent septic shock that required corticosteroid administration and cardiovascular support with norepinephrine, epinephrine, and vasopressin. Her hospital stay was further complicated by disseminated intravascular coagulopathy and ischemic hepatitis. Cultures from blood and cerebral spinal fluid grew N. meningitidis, which was sensitive to ceftriaxone. She received a seven-day course upon recommendation of infectious disease specialists. On hospital day 10, she was discharged to a long-term acute care facility with ischemic necrosis of the digits of her hands and feet bilaterally, which would later require operative intervention. |
pmc-6497194-1 | An eight-year-old African-American male was brought to the emergency department (ED) by ambulance after a first-time, witnessed seizure at home. The patient arrived approximately 15 minutes after the seizure and was somnolent but arousable and confused, consistent with a postictal state. The remainder of the history was taken from the patient’s mother, who was at his bedside. She stated that the patient had been feeling unwell for the past two to three days. He had been complaining of upper respiratory infection symptoms, including cough and nasal congestion. The mother stated she heard a “thud” upstairs and ran up to find her son on the floor shaking and incontinent of his bladder and bowels. The shaking lasted about one to two minutes. She reported that her son had a decreased appetite recently, but even when well he was a very picky eater with a very limited diet. He had only eaten French fries since becoming sick. The patient’s mother had been encouraging oral hydration with Gatorade and Pedialyte.
The patient had no significant past medical history. He had never had surgery or other hospitalizations. He had an allergy to amoxicillin which resulted in hives. He saw a pediatrician regularly and was up to date on vaccines. He did not take medications on a daily basis. There was a family history of hypertension but no family history of seizure disorders. They lived in a home, and mother stated they felt safe at home. No one else in the home had been ill.
Vital signs included an oral temperature of 38° Celsius, a heart rate of 108 beats per minute, blood pressure of 111/70 millimeters of mercury, breathing at a rate of 26 breaths per minute, and oxygenating 97% on room air. On initial physical exam, patient appeared drowsy, but overall was well developed, with a body mass index of 19 kg/m2, and in no acute distress. His head was normocepahlic and atraumatic. Extraocular movements were intact, pupils were three millimeters and equal, round, and reactive to light. His tympanic membranes were normal and nose was normal. He had dry mucous membranes and his oropharynx was clear without exudate or erythema. His neck was supple and without lymphadenopathy. His lungs were clear to auscultation bilaterally, with good air movement. There were no wheezes, rales, or rhonchi. Auscultation of the patient’s heart revealed a normal rate and regular rhythm without murmurs, rubs, or gallops. Abdomen was soft, non-tender, and non-distended with normal bowel sounds. The extremities had no edema, 2+ distal pulses, no tenderness, and no deformity with normal range of motion. Neurological exam revealed that he was easily arousable without cranial nerve deficits, normal strength, normal sensation, normal coordination, and normal gait. His skin was warm and dry, without rashes, pallor, or jaundice. He had a capillary refill of three to five seconds in all extremities.
After approximately 30 minutes in the ED, the patient’s mother reported that her son seemed to be more alert, interactive, and conversive, and was back to his baseline mentation.
Labs, electrocardiogram (ECG), and chest radiograph were obtained in the ED. Laboratory results are shown in the . ECG and chest radiograph can be seen in and , respectively.
While in the ED, a test was ordered, and a diagnosis was made. |
pmc-6497195-1 | A previously healthy 26-year-old male presented with three days of right upper quadrant (RUQ) pain, worsened with food. Physical exam demonstrated a focal RUQ peritonitis, or positive Murphy’s sign, with no rebound or guarding. Vital signs were stable, and labs showed no leukocytosis or metabolic derangements. Point-of-care ultrasound (POCUS) demonstrated a stone in the gallbladder neck, 4.6 millimeters anterior wall thickness, but no pericholecystic fluid (). Surgery was consulted and the patient was offered outpatient follow-up for biliary colic with adenomyomatosis. He returned to the emergency department (ED) the following day with persistent pain and underwent cholecystectomy for cholecystitis. |
pmc-6497196-1 | A 44-year-old African-American male with a history of chronic low back pain presented to the emergency department (ED) having difficulty walking and trouble urinating. He reported no classic TB risk factors and denied history of international travel or exposure to high-risk populations. He also denied a history of intravenous (IV) drug use. Nor did he report typical preceding symptoms of night sweats, fever, weight loss, cough, or hemoptysis. Initial vital signs included blood pressure 123/85 millimeters of mercury (mmHg), pulse 127 beats per minute (bpm), respirations 28 per minute, oxygen saturation 99% on room air, and afebrile at 98.1° Fahrenheit (F). Due to concern for possible cauda equina syndrome, emergent magnetic resonance imaging (MRI) of the lumbar spine was done (). The patient was diagnosed with discitis, osteomyelitis and ventral epidural abscess at lumbar vertebrae 3 and 4 (L3, L4). Labs revealed leukocyte count 8.6 x109 per liter (L), hemoglobin 12.4 grams per deciliter (g/dL), platelets 319 x109/L, C-reactive protein (CRP) 1.15 milligrams (mg)/dL, erythrocyte sedimentation rate 56 millimeters per hour and lactic acid 0.8 millimoles/L. Urine drug screen, hepatitis panel, human immunodeficiency virus screen and rapid plasmin reagin test all returned negative.
He was promptly transferred to a hospital with neurosurgical capabilities and taken to the operating room for L3 laminectomy with partial facetectomy and evacuation of the ventral epidural abscess. Successful decompression of the L3 and L4 nerve roots was achieved, and abscess fluid was sent for culture. The patient was admitted and started on broad-spectrum IV antibiotics. Culture results from the epidural abscess returned Propionibacterium acnes, while the pathology report was negative for fungal elements. The acid-fast bacilli (AFB) stain was also negative. Antibiotic coverage was narrowed to ceftriaxone only. After eight days in the hospital, the patient improved significantly, ambulating without difficulty, tolerating physical and occupational therapy. A peripherally inserted central line was placed before discharge to home, and arrangements were made for weekly lab monitoring and home IV ceftriaxone therapy. A prednisone taper was also prescribed for lingering radicular pain.
Ten days after discharge the patient presented once again to the ED for progressively worsening lumbar and thoracic back pain, lower extremity weakness and inability to pass a bowel movement. Initial vital signs were blood pressure 127/90 mmHg, pulse 102 bpm, respirations 21 per minute, oxygen saturation 98% on room air, and afebrile at 97.9° F. A second MRI was emergently ordered ( and ), which demonstrated interval progression of infectious changes involving L3 and L4 with associated epidural and retroperitoneal spread of infection. Given the report of upper back pain on this second ED visit the MRI also imaged the thoracic spine, which identified extensive, abnormal epidural enhancement throughout the thoracic spinal canal suggestive of diffuse infection, with focal epidural thoracic spine abscess formation identified at vertebral levels 4–7.
Chart review revealed a positive QuantiFERON®-TB Gold serum test, as well as a culture positive for Mycobacterium tuberculosis from the initial lumbar epidural abscess drained during decompressive neurosurgery. Vital signs were unremarkable with blood pressure 119/72 mmHg, pulse 94 bpm, respirations 18 per minute, oxygen saturation 98% on room air, and afebrile at 97.9° F. Physical examination was significant only for 4/5 strength to bilateral lower extremities. Significant lab abnormalities included critically low potassium 2.7 milliequivalents/L, leukocyte count 10.8 x109/L, platelets 370 x109/L and CRP 10.36 mg/dL. The patient was admitted to a negative-pressure isolation bed and started on rifampin, isoniazid, pyridoxine, pyrazinamide and ethambutol for TB. The original neurosurgery team evaluated the patient again on the second hospital admission and determined no further operative intervention was necessary. The Department of Health was notified of the positive TB result and the patient was discharged home on hospital day eight on a monitored four-drug antibiotic regimen with a diagnosis of retroperitoneal abscess due to extension of Pott’s disease of the spine. |
pmc-6497197-1 | A 76-year-old female with a past medical history of nephrolithiasis, thyroid disease, and osteopenia presented to the ED for right lower quadrant abdominal pain for the prior four days. She stated that she had experienced pain after lifting several flowerpots. On the day of presentation the patient noticed a mass in the right lower quadrant. She went to her primary care physician for evaluation; an attempt to reduce the hernia in the office was unsuccessful, so the patient was transferred to the ED for concern of an incarcerated hernia.
In the ED, laboratory evaluation revealed an elevated white blood cell count at 13.02 millimeters (mm)3 (range 4.8–10.8 mm3), normal serum lactate of 0.57 millimoles per liter (mmol/L) (range 0.5–1.6 mmol/L), and a normal metabolic panel. A second attempt to reduce the mass after intravenous administration of hydromorphone was unsuccessful. Subsequent POCUS showed a blind-ended, non-compressible, dilated loop of bowel one centimeter in diameter within the right lower quadrant mass, concerning for acute appendicitis within the incarcerated hernia sac (, and ). Sonographic criteria for the diagnosis of acute appendicitis include a non-compressible, blind-ended loop of bowel that is greater than 6 mm in diameter without peristalsis.
Given the concern for acute appendicitis within the hernia sac, no further attempts at reduction were made and surgery was consulted. A computed tomography (CT) of the abdomen and pelvis performed per surgery’s request confirmed the diagnosis of a right-sided femoral hernia containing an inflamed appendix, consistent with a de Garengeot hernia with acute appendicitis (). The patient went to the operating room for appendectomy and hernia repair. |
pmc-6497198-1 | A 61-year-old male with history of alcohol abuse and presumed cirrhosis presented to the emergency department with generalized weakness and right facial droop. He was found to be profoundly hypotensive and hypothermic with subsequent rapid decompensation requiring intubation and continuous norepinephrine infusion. Given the presence of ascites, we performed a diagnostic paracentesis that showed 9,787 nucleated cells per microliter with abundant intra- and extra-cellular bacteria. Intravenous vancomycin and piperacillin-tazobactam was started, but he was too hemodynamically unstable to travel to computed tomography to evaluate for perforation. A point-of-care ultrasound revealed air bubbles and debris actively bubbling (“aquarium sign”) through ascites and intraperitoneal A-lines indicative of pneumoperitoneum (). Portable abdominal radiograph was suspicious for free air, and eventually the patient was taken to the operating room where surgeons found a ruptured gastric ulcer and distal ileum and cecum ischemia without frank necrosis. |
pmc-6497199-1 | A 5-year-old female who fell ill after eating dessert at a party presented to our ED via ambulance. The parents reported that the child had two large servings of cake and subsequently developed vomiting, loose stools, and syncope. They noted her to be “blue” (); 911 was called, and she was brought by ambulance to the hospital. During our encounter, the patient was very quiet and did not report any complaints. Vital signs upon arrival to the ED showed blood pressure 75/47 millimeters of mercury (mmHg), pulse oximetry 77% on 12 liters non-rebreather mask, respiratory rate 30 breaths per minute, and heart rate of 117 beats per minute. Her physical exam was significant for cyanosis, clear lungs to auscultation, and tachycardia on cardiovascular examination. The diagnosis of methemoglobinemia was quickly suspected given the clinical presentation of sudden onset cyanosis not improving with oxygen administration as well as low pulse oximetry.
Methemoglobinemia workup was initiated; upon collection, blood appeared very dark in the laboratory tubes. Co-oximetry confirmed an elevated methemoglobin level at 52%, venous blood gas showed a partial pressure of oxygen (pO2) of 178 mmHg, and lactic acid was 3.3 millimoles per liter (mmol/L). Blood pressure improved after two 20 milliliters per kilogram (mL/kg) boluses of normal saline, but patient continued to have tachycardia and cyanosis. We administered one milligram per kilogram (mg/kg) of methylene blue intravenously over five minutes. When we re-checked her methemoglobin level at 30 minutes after methylene infusion, it was 38.6%; pulse oximetry remained in the 70%-80% range. The patient continued to appear cyanotic despite administration of the first dose of methylene blue; therefore, we administered the second dose of one mg/kg of methylene blue. While the patient had some improvement, she continued to be cyanotic throughout her course in the ED.
Due to a persistently elevated methemoglobin level, continued cyanosis, tachycardia, and signs of hypoxia (), despite the second dose of methylene blue, the decision was made to admit the child to a tertiary care center. She was transferred to the facility 60 minutes away by the tertiary care center’s critical care ground transport team, which included a pediatric intensive care nurse and pediatric respiratory therapist, as well as two paramedics. Upon arrival, her methemoglobin level was 6.7% and lactate level was normal; supplemental oxygen was removed and remained off overnight. She tolerated oral intake and was discharged home the next day. No additional methemoglobin level was obtained. |
pmc-6497199-2 | A 33-year-old female with no significant past medical history presented to our ED from the same party after ingesting the same dessert. She reported feeling short of breath and had vomiting, loose stool, and a near-syncope event. She had no chronic conditions, took no medications on a daily basis, and had no allergies. Upon arrival, she appeared in mild distress and slightly anxious. Vital signs in the ED showed blood pressure 99/75 mmHg, pulse oximetry 81% on six liters nasal cannula, a respiratory rate of 16 breaths per minute, and heart rate of 87 beats per minute. Except for cyanosis on physical exam, the patient appeared in no acute distress. She had clear lungs, normal cardiovascular exam and an unremarkable abdominal exam. She had a methemoglobin level of 17.2%. After she was treated with one mg/kg methylene blue, vital signs normalized, and repeat methemoglobin level three hours after methylene blue infusion was 1.2%. She was discharged from the hospital after several hours of observation. |
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.