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pmc-6296145-3 | A 35-year-old man without systemic disease first attended our clinic in August 2004 for bilateral JOAG. He denied having a family history of glaucoma, but his uncle had been diagnosed with LHON. When he was undergoing therapy with timolol 0.5%, his IOP was approximately 20 mmHg in both eyes. His BCVA gradually decreased from 20/200 in both eyes in 2006 to counting fingers at 25-30 cm in both eyes in 2016. Gonioscopy revealed a normal iridocorneal angle; pachymetric measurements were 561 μm in the right eye and 563 μm in the left eye. Fundoscopic examination revealed paled optic disc with enlarged disc cupping of the optic nerves with sectorial excavation and reduction of the neural rim in both eyes (Fig. ). OCTA disclosed diffuse RNFL thinning and a decreased peripapillary vascularity in both eyes (Fig. ). The VF (30–2 SITA standard) was characterized by progressive central scotoma in both eyes. The ERG was subnormal in both eyes, and the pattern ERG revealed decreased N95 amplitudes in both eyes (Fig. ). The genetic test revealed an ND4 m11778G > A mtDNA mutation, which is pathognomonic for LHON. |
pmc-6296152-1 | A 28 year-old nulliparous woman, previously diagnosed for HWWS, was referred to San Camillo-Forlanini Hospital during her third spontaneous pregnancy. The clinical history of our patient began when at her birth, the ectrodactyly of the right foot (absence of the 2 medial rays), immediately became apparent. The karyotype analysis was normal 46 XX. At age 1, she underwent a surgical correction of this anomaly with consequent partial improvement of a functional deficiency. An upper abdominal ultrasound, performed after a history of recurrent urinary tract infections and pyelonephritis, revealed the absence of the left kidney and the right megaureter. At 12 years, after 2 months from menarche, due to severe acute pelvic pain, a pelvic ultrasound and a magnetic resonance imaging (MRI) were performed. MRI showed a left blind hemivagina with hematocolpos, uterus didelphys with hematometra in the left hemiuterus and ipsilateral hematosalpinx. These imaging findings were later confirmed by the diagnostic laparoscopy which showed normal right uterus, right fallopian tube and both regular ovaries. Consequently, she underwent a surgical reconstruction of the vagina consisting in the drainage of hematocolpos and the removal of the vaginal septum, whereas an abdominal left hemi- hysterectomy and ipsilateral salpingectomy were performed through a Pfannenstiel incision. Her obstetric history was significant for two spontaneous abortion at the age of 26, occurred at 7th and 12th weeks respectively. She had no problem of fertility in anamnesis. The woman came to our observation for the first time at 15 weeks of pregnancy for abortion threats resolved with vaginal progesterone. Singleton fetus was anatomically in the norm. The patient had a moderate protenuria of 1400 mg in 24 hours, so she started a proper diet and a monitor of urine proteins. Close and regular surveillance (clinical, laboratory, and ultrasound) was initiated. The obstetric ultrasound controls revealed adequate growth of a fetus without major malformations, and normal Doppler indices of the fetal, feto-maternal and utero-placental vessels. During the three trimesters, frequent urinary infections occurred that were appropriately treated after urine culture and antibiogram test. At 33 weeks + 5 days of gestational age she was admitted to our hospital for premature spontaneous rupture of membranes (pPROM): she reported light amniotic fluid leak one hour before our observation. The admission assessment detected a reduced amniotic fluid index, a regular fetal growth and posterior placenta in the norm; the umbilical artery Doppler values were in the range, the fetal cardiac monitoring was regular and uterine contractions were present. The vaginal examination revealed a soft cervix, 80% effaced, dilated about 2 cm, and the fetus was in breech at station -3. The ultrasound cervical length was 24 mm. A single course of antenatal corticosteroid therapy for fetal lungs maturity induction and tocolytic drugs were administered. On the second day of hospitalization, an emergency caesarean section was performed because the cervix was modified (dilatation about 4 cm), uterine contractility increased while persisting breech presentation (Fig. ). A female infant was born weighing 2278 gr, with Apgar scores 8/9/9 at 1, 5, and 10 minutes respectively; the umbilical artery ph was 7.35. The placenta weighed 380 grams. The mother and the newborn, made an uncomplicated post-surgical/postnatal course and were discharged on day 3 and 15 respectively. Seventeen days after caesarean section, the woman came back again to our institution for a complaint of asthenia and fever ( > 38°C), resistant to paracetamol for five days. On physical examination, she had abdominal tenderness in the lower quadrants and physiological vaginal lochia. Blood exams showed increased leukocyte and inflammatory markers: white blood cells (WBC) were 14,2 x 103/ml (range 4,0-10,0 x 103/ml); C-reactive protein (CRP) was 19.98 mg/l (range 0,01-1 mg/dl) and procalcitonin was 0.22 ng/ml (negative: <0,05 ng/ml). The pelvic ultrasound and the computerized tomography (CT) demonstrated a pelvic abscess neighboring to the lower anterior wall of the uterus with dimensions of 53 x 47 mm (Fig. ). The treatment started immediately and consisted in intravenous antibiotic therapy with Meropenem 500 mg three times a day and low- molecular weight heparin (LMWH), Enoxaparin 4000 UI subcutaneous daily. Six days after the hospital admission with the right therapy, the inflammatory indices reduced: WBC were 9,8 x 103/ml, PCR was 4.37 mg/l and procalcitonin was 0.12 ng/ml. After discharge, we started a follow-up to assess the clinical conditions of our patient: she was asymptomatic, her blood exams were within normal ranges and the pelvic abscess was significantly decreased. Histopathologic examination of the placenta and umbilical cord obtained after about 40 days, not identified signs of chorioamnionitis and/or funisitis. |
pmc-6296693-1 | In Apr 2008, a 9-yr-old girl with initials A.S. (born in 1999, in Maglaj, Bosnia and Herzegovina) was admitted into the General Hospital Tesanj (Tesanj, Bosnia and Herzegovina) with a severe headache, mental confusion, high fever, and a cough. Neither the patient's own medical history nor that of her family contained details of any specific disorder. Both her birth weight (3850 gr) and her birth length (58 cm) were considered normal. Prior to that admission to the hospital, she manifested no cognitive disabilities. She was diagnosed with having epilepsy with mental disorientation and she was treated with phenobarbitone, sodium valproate, and lamotrigine. Then, in 2010, she started having seizures: they would begin with nausea, impaired vision, and a loss of consciousness. During the seizures, her eyes were tightly closed and she exhibited no twitching of her legs nor her arms. After ten to thirty min, the patient would regain consciousness and would complain of feeling cold at the terminal part of extremities. Additionally, she would feel pain in her ankles, with bruising joints, after which the pain would progress towards her toes, followed by swelling and reddening. Magnetic resonance imaging (MRI) of the patient's head showed no apparent changes in the structure of the patient's brain.
During the third year following the onset of her symptoms and her first seizure, the patient experienced a different type of "seizure" during her sports class: she began to walk aimlessly and insecurely, with tottering, she had a fixed gaze, pale face, and was rambling (calling a friend by her name over and over again). However, she did not lose her balance and did not fall. In addition, she manifested no twitching of extremities. That particular "seizure" lasted for about ten minutes, after which she regained consciousness. However, following that particular seizure the patient failed to re-establish her previous state: she had absent gaze, difficulty using cutlery, she lost her sense in space and time, and she did not recognize her parents and people she previously knew around her. On one occasion, she had a generalized epileptic seizure.
In July 2011, the patient experienced a sudden loss of consciousness, and she lost her balance and fell, her body becoming rigid and cyanotic, without twitching of the extremities, while her eyes were closed. At the time, the patient's pupils were round, symmetrical, with proper response to light. Following recovery from this seizure, the patient had difficulty walking independently; she walked aided and her walk was atactic (suggesting a lack of muscle coordination), with significant deviation to the left. She also had difficulty in performing a walk on heels and toes and could not walk in a straight line. Dystonia of torso and extremities was present. Romberg was unstable, with a deviation to the left. Finger to nose test was abnormal (suggesting dysmetria). Gross motor abilities test was in order. Muscle tendon reflex (MTR) was symmetrical, live. Right, Babinski sign was positive. Lumbar puncture test, as well as findings of ophthalmologists and cardiologists, were without noticeable pathologies. Hormonal status of the patient was within the normal range. An electroencephalogram test (EEG) showed continuously discharging of the high voltage Delta Theta activity with interposed sharp and steep waves of high voltage and paroxysmal high voltage spikes, as well as multiple spike-and-wave discharges. During the stay at the hospital, the EEG registration did not change. The patient was subjected to additional MRI scans which revealed no apparent changes in the brain structure. Seizures were classified as visually partial twitches, eventually becoming myoclonic, and generalized tonic-clonic twitching. At this time, the patient exhibited evident cognitive deterioration. No cranial nerve deficits were present, but rapid irregular myoclonic twitches that were palpable at rest were present and were increased by voluntary movements of the upper limbs. There was no sign of Babinski. The patient was able to cooperate with the doctor during the examination. In addition, the patient was decelerated with a little verbal and motor activity.
Genetic testing was carried out in Genoa, Italy, on Mar 2013, from the DNA that was extracted from leukocytes of peripheral blood. Analysis of exons 1-4 of the EPM2A gene (NM_005670) and the single exon, exon 1, of the NHLRC1 gene (NM_198586), using direct sequencing, was performed. Multiplex Ligation-dependent Probe Amplification (MLPA) method was used to examine the genes and the genomic region that includes the region from exons 1 and 4 of the EPM2A gene and exon 1 of the NHLRC1 gene. The genetic testing identified that the patient is the carrier of the homozygous 1-bp deletion, 990G, within the NHLRC1 gene. Following the result of the genetic testing, clonazepam was included in the patient's therapy.
In July 2015, levetiracetam was added to the therapy. In May 2015, treacheostoma was placed, as well as percutaneous endoscopic gastrostomy. Currently, (Apr 2017), the patient is bedridden, in a continuous horizontal position, with the rapid irregular myoclonic twitches noticeable at rest, and increased by voluntary movements of the upper limbs. Furthermore, the patient also experiences frequent episodes of fever, which is insensitive to antipyretics. |
pmc-6296698-1 | The patient was a 9-yr-old Iranian girl presenting to the Pediatric Emergency Room of Moosavi Hospital, Zanjan, Iran in January 2017, with sudden onset of headache and recurrent vomiting, ataxia and history of 3 consecutive days of fever and malaise. There were left eye ptosis and decrement of left nasolabial fold in patient’s face. The patient had tremor and truncal ataxia. The force of the extremities and deep tendon reflexes were normal in physical examination. Her heart rate was 110 min, blood pressure 90/60 mm Hg and temperature 38.2 °C. The patient’s weight was 21 kg and had 133 cm height and head circumference was 52 cm. The patient had no history of head trauma.
An informed consent was obtained from her parents in order to publish data as a case report without publishing her name. Ethics Committee of the university approved the study.
Diagnostic focus and assessment:
The patient underwent a brain CT scan without contrast in first day of admission preceded by CBC, diff, BUN, Cr, Na, K, Arterial blood gas sampling (ABG) and Urine analysis. On the second day, brain magnetic resonance venography (MRV) and magnetic resonance imaging (MRI) with flair, T1, T2 and DWI sequences and also EEG were ordered, then lumbar puncture with 3 samples was carried out. About 48 h after the MRI the patient became aggressive and had severe headache, nausea and vomiting plus ataxia and delirium, then the patient transferred to PICU and we decided to order the second CT scan and after the results, we asked for urgent neurosurgery consultation and the patient was prepared for brain surgery. The day after surgery the patient underwent brain CT scan without contrast again and laboratory tests were repeated. The patient underwent the last brain CT scan without contrast on thirteenth day and also had an EEG on the same day. We also did a portable echocardiography plus electrocardiography to determine presence of any PFO or ASD or any cardiac problems.
Therapeutic focus and assessment: The patient presented with sudden onset of headache and recurrent vomiting, ataxia, and history of 3 consecutive days of fever and malaise. Our first clinical suspicion was cerebellitis or post infectious ataxia () so we ordered intravenous ceftriaxone, intravenous pantoprazole, and ondansetron for two days. We also ordered acyclovir ampule plus dexamethasone ampule for the patient and after the brain MRI results that were consistent with cerebellar infarction aspirin tablet was prescribed for the patient. On the fourth day (48 h after) because of the patient’s severe headache, intravenous acetaminophen was administered and dexamethasone was held and the patient was transferred to pediatric intensive care unit (PICU) and intravenous phenytoin ampule plus vancomycin ampule were prescribed. After the brain CT, because of obstructive hydrocephaly arising from cytotoxic edema mannitol and dexamethasone ampule were ordered for the patient and the patient became ready for the brain surgery. The next day after the surgery and inserting a drain in the left lateral ventricle, mannitol was discontinued. The day after, phenytoin ampule was held and Diamox tablet (acetazolamide) was ordered. Physiotherapy and occupational therapy of the left extremities begun for the patient and because of constipation lactulose syrup were ordered.
Follow-up and outcomes
The first EEG report was mildly abnormal due to some spike and wave discharges (Figure 2 Left) and in the last EEG report, there were some background attenuations without epileptiform activity (Figure 2 Right). The patient had a lumbar puncture with normal result. The first and the last laboratory data are as follows ()
The urine analysis result was normal. The HPLC Amino Acid profile was normal except lower than normal range of arginine (26.8) and higher than normal range of alanine (148.0). We also obtained an Arterial Blood Gas sample from the patient that was normal (Table 1). The echocardiography and electrocardiography results both were normal. Findings on the first brain CT scan were a dim hypodensity in the left cerebellar hemisphere accompanied by a mild generalized ventriculomegaly ( Left). The MRV’s result was also normal ( Right). In the MRI report, there were abnormal low T1 and high T2 signal intensity in left cerebellar hemisphere involving superior and middle cerebellar peduncles in the same side as well ( Right , Middle), restriction was noted in this region. DWI findings were consistent with cerebellar infarction in this region ( Left). On the second brain CT scan that was 48 h after the MRI, there was an intense hypodensity arising from cytotoxic edema in the left cerebellar hemisphere with concomitant cortical entanglement exerted pressure on fourth ventricle and had resulted in hydrocephaly, severe ventriculomegaly was also seen in the CT scan ( Left) . On the third brain CT which was after the patient’s surgery, there were evidence of craniotomy in occipital bone on the left side and hemispherectomy of the left hemisphere of the cerebellum, the drain in the left lateral ventricle was in its appropriate position ( Middle). The last brain CT scan had no new findings and the drain was extracted from the brain ( Right). Pathology result of surgical biopsy of brain tissue was cerebellar tissue with small foci of hemorrhage accompanied by presence of vascular malformation, most probably venous angioma.
After 5 months the force of the extremities was normal and the ataxia was completely disappeared. The patient now goes to school and has no problems in daily life activities. The patient is now under treatment with an aspirin 80 mg tablet daily. |
pmc-6297053-1 | A 20 years old male presented with history of intermittent right shoulder pain, for last 2 years. There was no history of trauma or fever. On examination he was a young gentleman with average height and built with no obvious deformity of the shoulder joint, range of motion was normal although extremes of movements at right shoulder were painful. Plain radiographs that included shoulder antero-posterior and scapular Y-views showed radio opaque densities in right gleno-humeral cavity, sub acromial space and medial aspect of proximal humerus (, Left side). Provisional diagnosis of synovial chondromatosis was made. His MRI showed presence of multiple chondromatoid bodies and no other pathology. He was planned for arthroscopic removal of loose bodies. Arthroscopy was performed which revealed extensive synovitis and multiple loose chondromatoid bodies. All loose bodies were removed including those which were still attached to synovium but clearly visible or palpable. Post-Operative x-rays shows clearance of most of the loose bodies ( Right side). Clinical picture of the chondromatoid bodies is shown in . Axial, sagittal and coronal images of MRI are shown in …
Post Op full range of motion was allowed. At 2 years follow-up, there were no symptoms and range of motion was normal. |
pmc-6297057-1 | A 43 year-old female was admitted to our hospital with a chief complaint of right upper pain and palpable mass. On physical examination, there was slight tenderness and semimobile mass in the right upper abdomen. Clinical examination did not demonstrate any persistent weak abdominal pain and mass. Her past medical and surgical history was unremarkable. Moreover, Family history and psychosocial history were also not particular.
In abdominal contrast-enhanced computed tomography (CT), 130 × 100 × 90 mm huge cystic mass was demonstrated in right upper peritoneal cavity. The cyst had thickened wall and many enhanced nodules. Many nodules and the thickened wall were slightly enhanced in early phase (A) and gradually enhanced in delayed phase (B). Gadolinium-enhanced magnetic resonance imaging (MRI) showed that intra-cystic fluid was bleeding or mucinous fluid as the intensity was slightly high in T1WI (C), high in T2WI (D), and slightly high in fat suppression T1WI. The thickened wall of the cyst and mural nodules were high intensity in Diffusion-weighted MRI. The findings of connection with pancreatic head suggested a tumor originated from pancreas. The differential diagnoses were MCN, mucinous cystic adenocarcinoma and hemorrhagic cyst. After an extensive discussion in our institute, we planned pancreaticoduodenectomy for this abdominal tumor.
She was taken to the operating room by a surgical oncologist who primarily specialized in pancreatic resections and had been in practice for over 10 years. In surgical findings, this tumor did not attach to gastrointestinal tract and originated from pancreatic head (A). The aspirated fluid was bloody and the cyst had re-increased for short time in operation. In these reasons, we diagnosed the tumor as hemorrhagic cyst and selected partial pancreatectomy because this tumor was resected completely (B). The cystic wall was thickened and elastic soft. No tumoral change found in the surface of cystic wall (C). Post-operative course was good and she was discharged on post-operative day 9. CEA and CA19-9 in intra-cystic fluid were 115,060 ng/ml and 113,373 U/ml.
Final pathology demonstrated that the cystic mass had well-formed cyst wall with an inner mucosal lining, submucosal layer, and muscularis propria as gastrointestinal tract (A–C). As the non-tumoral epithelium in small area was similar to crypt epithelium of the stomach and immunohistochemistry of the non-tumoral mucosa was positive for CK7 (D), negative for CK20 (E), and negative for CDX-2 (F), the pathological finding of non-tumoral tissue was the enteric duplication cyst of gastric type. Adenocarcinoma with moderate to well differentiation invaded to subserosal layer over smooth muscle layer in broad area of the cystic wall (A–C). The invasive cancer cells invaded lymphatic system, venous system, and nervous system. Several lymph nodes resected together besides tumor had no metastasis. The immunohistochemistry of the tumoral mucosa was 50% positive for CK7 (D), positive for CK20 (E), and positive for CDX-2 (F). The final diagnosis was completely isolated advanced enteric duplication cyst cancer because this cyst was not attached to a wall of gastrointestinal tract and adjacent to pancreatic head. Therefore, this cyst was not originated from pancreas head.
During hospital stay in post-operative period, she was counseled that we identified an isolated enteric duplication cyst with advanced cancer. We recommend treatment by S-1 as adjuvant chemotherapy according to the adaptation for criteria of advanced gastric cancer. She had taken S-1 for 1 year without rest of medication and lived for 1.5 year after surgery without any evidence of malignancy. |
pmc-6297111-1 | A 49-year-old Caucasian lady with history of polysubstance use disorder and related complications including, recurrent cutaneous abscesses, spinal diskitis and septic thrombophlebitis presented to the emergency room with complaints of intermittent fevers and right hip pain. A month prior to the presentation, she had left another hospital against medical advice after being diagnosed with Methicillin-resistant Staphylococcus aureus bacteremia and right hip septic arthritis. Post discharge, she was off antibiotics, but continued heroin and methamphetamine and was taking multiple dose of ibuprofen in addition for pain control. On admission, her physical exam was notable for severe tenderness in her right hip, marked bilateral lower extremity edema and multiple deep, circular, punched-out looking atrophic scars involving all extremities at prior skin popping (subcutaneous injection of illicit drugs) sites. Pertinent laboratory data included chronic anemia with a hemoglobin of 9.8 g/dL, WBC count of 10.23 k/uL and a platelet count of 395 k/uL. She had negative HIV, Hepatitis B antibodies and elevated Hepatitis C antibody with undetectable Hepatitis C viral load. Her basic metabolic profile noted a sodium of 140 mmol/L, potassium of 3.5 mmol/L and a creatinine of 2.9 mg/dL (estimated glomerular filtration rate of 17 ml/min) which was a significant rise from the normal creatinine levels a month earlier. Her urine analysis noted >500mg/dL proteinuria with a protein/creatinine ratio of 28.25. She had no monoclonal proteins on serum or urine electrophoresis. CT scan of her right hip noted marked degenerative changes in the right hip, with right acetabular protrusion and cortical disruption of the medial acetabular wall. She was diagnosed with right hip osteomyelitis and was in acute renal failure with evidence of nephrotic range proteinuria. She was placed on antibiotics (daptomycin) and underwent hip arthroscopy with irrigation and debridement along with lavage shortly after admission. Differential diagnoses considered for her renal disease included acute tubular necrosis due to sepsis, post infectious glomerulonephritis, focal segmental glomerulosclerosis associated with heroin use, acute interstitial nephritis from NSAIDs and membranoproliferative glomerulonephritis associated with Hepatitis C. She underwent a renal biopsy which revealed acute tubular necrosis and secondary (AA) amyloidosis with the classic apple green birefringence when stained with Congo red () and positive immunohistochemical stain for serum amyloid A protein (). Two weeks after admission she underwent Girdlestone arthroplasty. During the hospital stay, she developed intermittent hypotension, had evidence of primary adrenal insufficiency attributed to amyloidosis and was initiated on steroids. She was discharged home after completion of prolonged antibiotic therapy with daptomycin and was maintained on oral doxycycline. She was referred to outpatient opioid treatment program. Eight months after her admission, she remained committed to be off all illicit drugs and underwent right total hip replacement. Her creatine levels normalized (estimated GFR of 82 ml/min) but she continued to have proteinuria from renal amyloidosis (protein/creatinine ratio of 28.25) and required diuretic therapy for symptomatic management of her edema. |
pmc-6297190-1 | A 37-year-old male patient presented to the emergency department complaining of three days history of abdominal pain, bleeding per rectum, nausea and recurrent attacks of vomiting. The pain was recurrent for the past three months and increased over the last month. On examination, the patient was malnourished and pale. He was vitally stable. His abdomen was soft, lax, without evidence of peritonitis. No masses could be appreciated. Digital rectal examination revealed blood on the glove with no masses or hemorrhoids. Routine blood tests were within normal ranges.
Abdominal ultrasonography US showed a well-defined oval-shaped hypoechoic lesion in the right lower quadrant area (). Contrast-enhanced abdominal computed tomography CT showed a well-defined cystic lesion within the lumen of cecum with thick septations measuring 4 × 4 cm (). As well, a doughnut shape was seen suspecting ileocecal intussusception. No enlarged or suspicious lymph nodes were detected in CT. As well, no free intraperitoneal fluid was seen. Colonoscopy revealed a cystic swelling in the cecal submucosa occupying half of its circumference. Biopsy from the mass was technically difficult. Advancement of the scope was impossible due to obstruction of the ileocecal valve by the mass.
The patient was kept nil per mouth and on intravenous fluid. He underwent elective diagnostic laparoscopy. He was placed in supine, Trendelenburg position. Closed pneumoperitoneum was created using a Veress needle in Palmer’s point. The scope was inserted through a supra-umbilical incision using an 11-mm Visi-port trocar. Two trocars were inserted five centimeters below the costal margins at right and left midclavicular lines. Diagnostic laparoscopy showed a mass involving the appendix, the ileocecal junction and the cecum with no free fluid in the peritoneal cavity. Devascularization was done starting five centimeters proximal to the ileocecal junction up to the hepatic flexure. Transection of distal ileum and transverse colon distal to hepatic flexure was done using Endo-GIA tristapler. Side-to-side ileo-transverse anastomosis was created using Endo-GIA tristapler. The specimen was retrieved en-bloc using Endo-bag. The patient tolerated the procedure well. He started clear liquid on the third postoperative day. He was discharged home on the sixth postoperative day.
Histopathological examination of the specimen showed mucinous cystadenoma of the appendix with extravasation of mucinous material into the submucosa of the cecum, leading to formation of a pseudocyst. No malignant cells were found in the resected ileocolic lymph nodes. All margins were free from malignant cells. After multidisciplinary meeting with medical oncology, pathology and radiology teams, there was no need for any further surgical intervention nor follow-up imaging. He was followed up regularly in the surgical clinic for two years with no symptoms or signs. |
pmc-6297209-1 | A 34-year-old woman was admitted to our hospital with no relevant past medical history. She first noticed lumbago and pain in her legs 1 month prior to admission. 2 weeks later, she became aware of muscle weakness of the lower limbs. She had been eating a balanced diet and drinking moderately. She had no family history of similar symptoms. Her general physical findings were unremarkable, with no signs of heart failure. Neurological examination disclosed no disturbance of consciousness or cranial nerve abnormalities. No muscle weakness was present in her neck or upper extremities, but mild weakness was evident in the lower limbs. During daily physical activities, she experienced severe pain in the gastrocnemius muscles with tenderness. Deep tendon reflexes in the lower legs were hypoactive without pathological reflexes. Mild distal-dominant hypoesthesia in bilateral legs was also noted.
Blood examination revealed mild hepatic dysfunction. Serum creatine kinase (CK) was not elevated at 39 U/ L (normal, 45–163). Neither myoglobin nor aldolase was elevated at 13.1 ng/ml (normal, < 106.0) and 5.1 U/L (normal, 2.1–6.1), respectively. The serum thiamine level was 12 ng/ml (normal, 24–66). Regarding the low levels of thiamine, we examined its level three times and confirmed to be low in all the three determinations. We conducted investigations including gastrointestinal endoscopy and blood examination to explore the cause of thiamine deficiency such as malabsorption, obstruction, hyperthyroidism, and adrenal insufficiency. However, we could not identify the obvious cause for the low levels of thiamine. Levels of vitamin B2, B12, and folic acid were within normal range. All the autoantibodies tested in the present were negative, including antinuclear antibodies, anti-neutrophil cytoplasmic antibodies, paraneoplastic autoantibodies (Hu, Yo, Ri, Ma1, Ma2, and CV-2, amphiphysin), and anti-cardiolipin antibodies. The cerebrospinal fluid was normal, and the IgG index was 0.59.
On admission, needle electromyography of tibialis anterior and gastrocnemius exhibited a decreased recruitment pattern with mostly normal motor unit potentials in voluntary contraction, although these muscles showed the fibrillation potentials and positive sharp waves as spontaneous activities, suggesting active denervation. Moreover, early recruitment was not observed. The findings of chronic denervation were not observed. These findings in needle electromyography were compatible with acute motor axonopathy. In nerve conduction studies, motor conduction velocities and the compound muscle action potential amplitude (CMAP) were within normal range in the extremities, but mild generalized large fiber sensory axonopathy was revealed. To summarize these findings, neurophysiological investigations indicated sensorimotor axonopathy with active denervation of motor nerves in lower limbs.
Muscle MRI on admission revealed patchy high signal intensities of various degree in her bilateral gastrocnemius muscles, left soleus muscle, left anterior and posterior tibialis muscles, and left extensor digitorum longus muscle on spectral attenuated inversion recovery (SPAIR) T2-weighted images (Figure ), whereas there were no abnormal intensities on T1-weighted images and no gadolinium contrast enhancement (Figures ). Brain and spinal MRI findings were normal.
Under the tentative diagnosis of thiamine deficiency neuropathy, massive intravenous thiamine replacement therapy was initiated at a dose of 300 mg/day. Myalgia and weakness in the lower limbs and gait disturbance markedly improved 2 days after therapy was initiated. MRI findings on SPAIR T2-weighted images improved within 1 month (Figure ). We have measured the serum thiamine level several times after her recovery and confirmed that the serum thiamine levels were normalized. Abnormal needle electromyography findings were completely normalized within 2 months. The patient was discharged from the hospital on day 17 and is currently followed up to 13 months in the outpatient clinic without relapse. |
pmc-6297551-1 | A 68-year-old woman presented features of BPS since 2014. She had undergone hysterectomy in 1993, which was followed by genital prolapse. She subsequently developed perineal pain without urinary symptom, which was attributed to pudendal neuralgia. Surgical decompression of the right pudendal nerve was performed in 2000. However, perineal pain significantly persisted, and gradually acquired neuropathic features. Spinal cord stimulation was initiated in 2005, with good efficacy [mean reduction of perineal pain scores from 8 to 2/10 on a numerical rating scale (NRS) from 0 to 10] and the stimulator is still activated until now with the same efficacy on this type of perineal pain. However, in 2014, the patient developed a totally new painful syndrome, characterized by suprapubic pain (NRS: 8/10) associated with urgency and increased micturition frequency with an average of 25 micturitions per 24 h, including 10 nocturnal micturitions. Such symptoms, in the absence of urinary tract infection or other cause of lower urinary tract dysfunction, defined BPS, although cystoscopy did not show Hunner ulcer lesions. In detail, the pain syndrome presented by the patient included a permanent pain described as a sharp and burning sensation, limited to the suprapubic region, and paroxysms of increasing pain described as a sensation of pressure, more diffuse in the hypogastric region and leading to uncomfortable urge to urinate. The clinical picture was also characterized by mood disorder (HAD, Hospital Anxiety and Depression scale: 24/42), sleep disturbance (NRS: 7/10), and fatigue (NRS: 5/10) with a major impact on activities of daily living. Cystoscopy and bacteriological urine examination excluded urinary tract infection. Bladder hydrodistention was performed but was not beneficial. Treatment with pentosan polysulfate was also ineffective. An rTMS therapy was then proposed to the patient. According to the results obtained in a previous patient with BPS (see above), we performed high-intensity, low-frequency rTMS of the right DLPFC (1 Hz, 1,200 pulses per session, delivered at 110% of the motor threshold, MT). The patient underwent one session per day for five consecutive days, followed by one session per week for 5 weeks, for a total of 10 sessions. The first five sessions were performed during hospitalization in our Pain Center. The permanent component of suprapubic pain was reduced from the second session (NRS: 6/10) and continued to gradually improve, to become well tolerated after the eighth session (NRS: 2/10) (Figure ). The number of micturitions also decreased from the second session and was reduced by one half after the seventh session (between 12 and 13 micturitions per 24 h, including five nocturnal micturitions) (Figure ). However, fatigue and sleep disorders persisted.
To treat depression, rTMS is usually applied either at high frequency (10–20 Hz) on the left DLPFC or at low frequency (1 Hz) on the right DLFPC. However, in one study, showed that rTMS of the left DLPFC, when applied at a high intensity of stimulation (110% of MT, as in our case), was similarly effective to produce long-term antidepressant effects whether it was delivered at low frequency (1 Hz) or high frequency (20 Hz), as usual. This surprising result led us to propose to our patient a series of monthly sessions of 1 Hz rTMS of the left DLPFC (1,200 pulses per session, delivered at 110% of MT) for 6 months. Permanent suprapubic pain, but also paroxysms of hypogastric sensation of pressure and urge to urinate completely vanished. Micturition frequency further decreased with an average of 10 micturitions per day (60% improvement compared to baseline) and two micturitions per night (80% improvement) (Figure ). Sleep and fatigue similarly improved, with NRS scores of 3/10 (57% improvement) and 2/10 (60% improvement), respectively. The percentage of reduction of depression score was lower (30% improved, HAD score: 17/42). At the end of the series of 16 rTMS sessions, the patient was able to resume most of her activities of daily living with an overall satisfaction rate of 80%. It is planned to repeat sessions of 1 Hz rTMS of the left DLPFC two or three times a year in our Pain Center. |
pmc-6297859-1 | A 21-year-old man with acute myelogenous leukemia and horseshoe kidney underwent human leukocyte antigen–matched unrelated donor myeloablative allo-HSCT. He was admitted on post-transplant days 40–44 for flank pain, hematuria, and low-grade fever (). History was negative for sexual activity in the prior 6 months. Work-up was notable for urinalysis showing hemoglobin and leukocyte esterase, urine culture without growth, and negative urine and serum BK virus polymerase chain reaction (PCR). Computed tomography (CT) of the abdomen and pelvis demonstrated a 3-mm nonobstructive stone in the superior pole of the right kidney and dilated right calyx with layering stones without hydronephrosis. Urology considered nephrolithiasis the most likely explanation for the patient’s symptoms, and he was discharged on alpha-1 antagonist treatment.
The patient was readmitted on post-transplant days 53–62 for ongoing dysuria and hematuria (). Labwork was notable for mild acute kidney injury; urinalysis showing hemoglobin, protein, and leukocyte esterase; urine culture without growth; and negative urine and serum BK virus PCRs. Renal ultrasound revealed a dilated right calyx with small stone fragments without hydronephrosis. Ureteroscopy was performed and revealed diffuse bladder inflammation with mild to moderate dilation of the intrarenal collecting system. Placement of a right-sided ureteral stent did not improve the patient’s symptoms, so it was removed 48 hours later. On discharge, the etiology of the patient’s symptoms remained unclear, so a urine gonorrhea/chlamydia nucleic acid amplification test was sent, returning positive for Chlamydia trachomatis. At outpatient follow-up 2 days postdischarge, the patient was started on a 14-day course of doxycycline with resolution of his urinary symptoms.
Plasma NGS was positive for Chlamydia trachomatis 7 days before initial symptoms and 30 days before standard microbiologic diagnosis (post-transplant day 32), as well as a day before discharge from the first admission (post-transplant day 43). |
pmc-6297859-2 | A 69-year-old woman with myelodysplastic syndrome/myeloproliferative neoplasm underwent intermediate-intensity mismatched unrelated donor allo-HSCT. Her post-transplant course was complicated by engraftment failure, Clostridium difficile infection, veno-occlusive disease, renal failure, and respiratory failure, requiring a prolonged course of intensive care ().
On post-transplant day 22, the patient developed methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. After starting intravenous (IV) vancomycin, blood cultures cleared within 1 day (post-transplant day 23), and she received a 2-week course that ended on post-transplant day 39. On post-transplant day 49, blood cultures drawn for worsening hemodynamic instability showed recurrent MRSA bacteremia. Given poor oncologic prognosis, the patient was transitioned to comfort-focused care and died.
Plasma NGS testing was positive for S. aureus the day before initial MRSA bacteremia (post-transplant day 21), throughout the vancomycin course (post-transplant days 27 and 35), after stopping vancomycin (post-transplant day 42), and on the same day as recurrent MRSA bacteremia. |
pmc-6297859-3 | A 56-year-old woman with JAK2 V617F+ postpolycythemia vera myelofibrosis underwent reduced-intensity conditioning unrelated donor allo-HSCT, with her immediate post-transplant course complicated by neutropenic fever and C. difficile colitis (). On post-transplant days 70–82, the patient was readmitted for neutropenic fever and found to have MRSA bacteremia. After starting IV vancomycin, blood cultures cleared within 48 hours. The patient’s Hickman catheter was removed, and transthoracic echocardiogram and magnetic resonance imaging of the spine showed no endocarditis or osteomyelitis/discitis. Due to subtherapeutic serum levels, vancomycin was changed to daptomycin, and the patient completed a 4-week course of antibiotic therapy (through post-transplant day 99).
On post-transplant day 118, the patient presented to clinic reporting a right chest wall mass. On post-transplant day 134, ultrasound showed soft tissue thickening/hyperemia surrounding a 2.6 × 0.7 × 2.7-cm fluid collection, and chest CT demonstrated stranding and soft tissue swelling of the right anterior chest wall. Bacterial culture from same-day ultrasound-guided aspiration preliminarily identified Staphylococcus epidermidis. On post-transplant day 137, speciation was corrected to MRSA, and the patient was started on a 14-day course of oral doxycycline with improvement in chest wall tenderness.
Plasma NGS remained positive for S. aureus after completion of daptomycin for bacteremia (post-transplant day 110) and preceding the clinical and microbiological diagnosis of chest wall abscess (post-transplant day 139), becoming negative after drainage and antibiotics for abscess. |
pmc-6297873-1 | An 83-year-old man was referred from an ENT specialist practitioner to the ENT-department due to a painful process situated in level II-III on the right side of the neck. He had a history of arterial hypertension, low-malignant carcinoma in situ of the bladder for which we had undergone a transurethral resection whereafter he developed postoperative sepsis, and one perioperative episode of arrhythmia with consequent cardiac arrest during hip surgery in 2017. The process had developed over ~3 weeks. The patient had experienced pain and discomfort with right-sided otalgia upon swallowing. He had no signs of dysphonia, was afebrile, had no erythema or calor in relation to the mass, and no neurological abnormalities. Thus, infection was not a provisional diagnosis. Ultrasound showed a hypoechoic, ill-defined tumor mass sheathing ~50 percent of the right CCA. No flow in the mass was detected with Color Doppler Ultrasound. Therefore, UPT was suspected.
Fine needle aspiration was inconclusive twice. Open biopsy and core biopsy was not an option due to the uncertainty of malignancy and potential spreading and bleeding. Therefore, diagnostic imaging was ordered.
Magnetic Resonance Imaging (MRI) and Positron Emission Tomography/Computed Tomography (PET/CT) showed what was concluded to be a tumor suspected of malignancy sheathing the carotid artery, though a slight dilation of ~2.3 cm of the right CCA was detected (Figure ). Furthermore, the PET/CT showed uptake both in the lungs and the colon, thus postponing further ENT-diagnostics due to the search for the primary focus of the tumor. Since malignancy/metastasis was suspected, no initial blood tests for infection were conducted.
Sixteen days after being enrolled in the ENT fast-track program, having undergone a colonoscopy and initial examination at the department of pulmonary medicine, the patient was admitted due to pain and further growth of the process on the neck. The patient was not able to eat or drink sufficiently and was experiencing general fatigue. The patient's family found that the patient's mental condition had deteriorated.
Upon admission, his vital signs were: A temperature of 38.4°C, 172/98 mm Hg blood pressure, a heart rate of 105 beats/min, and an unlabored respiratory rate of 16/min.
Biochemistry showed markedly high inflammatory indices with a c-reactive protein of 266 mg/L, white blood cell count of 26.9 × 109/L, and 24.1 × 109/L neutrophils. A urine sample was sent to the laboratory for cultivation and analysis of sensitivity.
Initially, the patient was prescribed Piperacillin and Tazobactam, treating symptoms as an infection with unknown primary focus. A diagnostic ultrasound was performed, which raised the suspicion of an aneurysm. CT-angiography showed an IA of about 5.4 × 3.9 cm (Figure ). The patient was transferred to the vascular surgery department. Surgery consisted of resection of an 8.0 × 5.0 cm IA. Because of massive inflammation of the area involving both the external and the internal carotid artery and thrombosis of the internal carotid artery, both arteries were ligated and oversewn. Furthermore, due to thrombosis and necrosis, the internal right jugular vein was resected. A culture from the surgical site was positive for E. coli and relevant antibiotics were administered.
The only sequela was dysphonia due to paralysis of the right recurrent nerve.
After the resection of the IA, growth of E. coli with the same resistance pattern as seen in the IA was found in the urine samples from the admission date. This suggested the bladder to be the primary focus of infection. |
pmc-6297948-1 | A 1-month-old Japanese girl, born at 38 weeks gestation with a normal birth weight (2870 g) and no family history of TMA or kidney disease, was examined at a hospital due to a 2-day history of cough. She was admitted 3 days later because B. pertussis was detected in her nasopharyngeal culture. She was treated with oxygen supplementation, antibiotics (piperacillin), and bronchodilators; her bacterial infection was complicated by a respiratory syncytial virus (RSV) superinfection. Fourteen days after admission, her laboratory evaluation revealed anemia, thrombocytopenia, elevated lactate dehydrogenase (LDH) levels (up to 4,428 IU/L), and markedly increased serum ferritin concentrations (up to 26,208 ng/mL) (Fig. ). Hemophagocytic syndrome (HPS) was suspected, and treated with steroids and gamma globulin.
She was transferred to our hospital 17 days after her initial admission, and the HPS diagnosis was excluded following a bone marrow analysis. The patient’s plasma complement levels were low (C3, 59 mg/dL; C4, 11 mg/dL; CH50, 31.0 U/mL) and a urinalysis showed hematuria and proteinuria; her kidney function worsened over the next few days (creatinine, up to 0.58 mg/dL). Her ADAMTS13 level was normal, but her haptoglobin level was significantly below normal and schistocytes were found in a peripheral blood smear. As a result, we diagnosed her with HUS caused by B. pertussis infection.
During our preparation to initiate ECZ treatment, her LDH levels started decreasing. Thereafter, her creatinine level decreased and her condition improved spontaneously. Hence, we did not perform PE/PI or administer ECZ. The C3 level increased to within normal limits (115 mg/dL). She was discharged 46 days after her first hospitalization, without any complications, and remained in remission 3 years later. A genetic workup was performed to examine for potential complement regulator mutations; however, no mutation was found in CFH, CFI, CFB, C3, MCP, THBD, or DGKE. |
pmc-6297952-1 | An 86-year-old woman was admitted from an outside institution to our neurological intensive care unit with fluctuating consciousness after hitting her head during a fall. Four weeks before admission, she was in normal health for her age with a history of arterial hypertension. Because of atrial fibrillation, she was treated with rivaroxaban 20 mg once daily. Two weeks before hospitalization, she experienced pain in her lower abdomen accompanied by a feeling of illness and fatigue which she self-medicated with aspirin. She experienced nose bleeding but continued to take aspirin. She was then admitted to an external clinic after falling. During the first in-hospital night, she fell out of bed and struck her head. Thereafter, consciousness decreased and she was transferred to the neurocritical care unit of our institution. She presented with dysarthria and mild motor aphasia, but language comprehension was fully preserved. In addition, mild right-sided hemiparesis was noted. Most of the time, she was awake but intermittently somnolent. Body temperature was 37.6 °C. Routine laboratory tests revealed prolonged prothrombin time, increased international normalized ratio (INR), increased CRP, leukocytosis and corresponding signs of a urinary tract infection. She was treated with prothrombin complex concentrate and antibiotics.
The initial computed tomography (CT) on day 0 showed contusions in the left frontal and temporal lobes and tSAH. Figure a shows this first CT scan with subarachnoid blood in two sulci of the left frontal cortex. A contre-coup injury was found in the right posterior cranial fossa with an epidural hematoma and corresponding tSAH. In addition, a small intra-parenchymal hemorrhage was observed in the right basal ganglia. Arterial aneurysms or arteriovenous malformation were ruled out using CT angiography (CTA). Blood was also detected in the fourth ventricle, but signs of disturbed cerebrospinal fluid circulation were not seen. Accordingly, the patient did not receive external ventricular drainage. Further CT scans on days 1, 3 and 5 showed neither increase of the epidural hematoma nor development of an occlusive hydrocephalus. They revealed only the progressive decrease of Hounsfield units within the blood-related hyperdensities. Nimodipine was not given because there is currently no recommendation for its use after tSAH [].
The patient was alert and in an improved general condition when she was transferred to the normal ward on day 7. On day 8, however, the patient experienced a secondary deterioration of her neurological status, as characterized by reduced consciousness and global aphasia, with loss of ability to speak or understand. Whereas the CT scan on day 9 was still unremarkable, the MRI scan on day 10 revealed new cortical laminar infarcts adjacent to the sulcal clots (Fig. c and d). The infarcts included both Broca and Wernicke areas. Transcranial Doppler sonography (TCD) on day 10 showed normal mean velocities of the posterior cerebral arteries (right PCA 29 cm/s, left PCA 23 cm/s) and normal pulsatility indices. The bone window was not sufficient to assess velocities of the middle cerebral arteries (MCA). Neither MR angiography (MRA) on day 10 nor CTA on day 14 showed any signs of proximal vasospasm (Fig. e and f). However, the CT scan on day 14 revealed the same infarcts as the MRI scan on day 10 (Fig. b). Over the following week, the patient improved again. She was able to respond to simple commands when she was transferred to clinical rehabilitation. |
pmc-6297984-1 | The proband was a 2-year and six-month-old female patient from healthy unrelated parents at full-term normal delivery and with a birth of weight of 3.2 kg. Her perinatal period was unremarkable. At around 4 months of age, she was admitted to the local hospital due to vomiting. At that time, the laboratory finding showed that she suffered from metabolic acidosis and hypokalemia (Table ). She accepted the supplementary treatment of potassium chloride and sodium bicarbonate for a short time and then therapy was discontinued. At about 2.5 years old, she was hospitalized in our renal unit because of recurrent hypokalemia, hyperchloremic metabolic acidosis and growth retardation. Physical examinations on admission showed height (84.0 cm, <3rd percentile) and weight (10.1 kg, <3rd percentile) were lower than normal. Clinical features and biochemical data revealed that the patient presented hypokalemia (2.7 mmol/l, normal 3.5–5.5 mmol/l),hyperchloremic (115 mmol/l, normal 99-110 mmol/l), metabolic acidosis (pH 7.28, normal7.35–7.45) and paradoxical alkali urine (Urinary pH > 6.0 while CO2CP < 18 mmol/l) (Table ). Thus, the clinical and biochemical features of this patient suggested a diagnosis of dRTA.
To make a definite diagnosis, renal ultrasound and audiological assessment were performed. Renal ultrasound indicated bilateral nephrocalcinosis. Automated auditory brainstem response (AABR) test revealed that bilateral sensorineural hearing loss, with moderately severe (45 dB) on the left ear and severe (80 dB) on the right ear, which was accompanied with EVA on both sides determined by high-resolution computed tomography (HR-CT) (Fig. ).
To identify the pathogenic gene mutation, Genomic DNA was extracted from the peripheral blood of the patient and her parents using Blood genome DNA Extraction kit (TaKaRa, Japan). Both ATP6V1B1 and ATP6V0A4 genes were preferentially screened in this study. If inconclusive (no mutation or only one was identified in either gene) then SLC4A1 gene should be analyzed for further verification. Direct sequencing analysis was employed to screen both of ATP6V1B1 and ATP6V0A4 genes, and two novel mutations were identified in ATP6V1B1. One mutation was a successive 2-nucleotide deletion in exon 2(c.133-134delTG)(Fig. ), which resulted in a frame shift mutation (p.Cys45Glnfs*37) and was expected to produce a truncated protein. The other mutation was a guanine to adenine substitution of the first nucleotide within the intron 8(c.785 + 1 G > A)(Fig. ). No mutation was found in ATP6V0A4 and we did not perform the SLC4A1 gene analysis since the causal mutations have been found.
For the mutation in the first nucleotide of intron 8(c.785 + 1 G > A), which just located in the 5′-splice donor site, splicing prediction programs presumed this mutation cause the disability of donor site and skipping exon 8with the on-line software BDGP (Score decreases from 0.92 to 0), NetGene2 (Confidence decreases from 0.88 to 0) and Spliceview (Score decreases from 85.6 to 0), respectively.
To verify this mutation really led to exon 8 skipping in vivo, the cDNA from the peripheral blood of the patient was amplified by nested PCR with primers spanning exon 7 to exon 9 (Table ). By direct PCR products sequencing, the exon 8-excluded transcript was visualized, while the normal was not (Fig. ). Of note, the absence of RT-PCR product corresponding to the allele harboring c.133-134delTG from this patient might suggest a marked nonsense mediated mRNA decay (NMD). The parents of this patient gave their informed consent. The study protocol was approved by the Ethics Committee of the affiliated hospital of Qingdao University.
A systematic treatment was performed by administration of sodium citrate (0.7 mmol/kg/day), potassium citrate (0.65 mmol/kg/day), and citric acid (0.62 mmol/kg/day) to correct metabolic acidosis and hypokalemia in this patient, and her normal growth was also restored in about 2 years (Fig. ). However, during the follow-up period, from the age of 2.5 to the age of 4.5 years, her hearing decreased gradually with fluctuating exacerbation which was associated with common cold infections. Finally, she had to accept the use of bilateral hearing aids. |
pmc-6298006-1 | A 62-year-old woman had undergone vitrectomy 30 years previously for traumatic vitreous hemorrhage, scleral buckling surgery 15 years previously for rhegmatogenous retinal detachment, and phacoemulsification without intraocular lens implantation 1 year previously for cataract in her left eye. She suffered acute loss of vision in her left eye 4 months before admission to our hospital, with pain, left-sided headache, and nausea, and consulted another hospital. Records show that the visual acuity in her left eye was light perception and the intraocular pressure (IOP) was 50 mmHg, and a slit-lamp examination showed diffuse corneal edema associated with hyphema and vitreous hemorrhage. IOP was 25 mmHg after the administration of glaucoma medications (Azopt® Eye Drops containing brinzolamide; Timolol Eye Drops containing timolol maleate; Alphagan® containing brimonidine tartrate), accompanied by the relief of both headache and nausea. The patient had experienced a relapse, with pain, left-sided headache, and nausea, 4 days before attending our hospital. Upon examination, her left eye showed visual acuity of light perception, diffuse corneal edema, hyphema, and vitreous hemorrhage (Fig. a), and an IOP of 45 mmHg. B-ultrasound showed vitreous opacities, and a high-luminance indentation of the eye wall with an acoustic shadow could be seen in the vitreous cavity on the B-scan (Fig. b). The axial length was 33.70 mm (IOLMaster 500, Zeiss). The patient was diagnosed with secondary glaucoma and treated with lavaging of the anterior chamber and vitreous cavity.
After the vitreous haemorrhage was cleared, a blue suture knot was detected standing out on retinal surface and projecting into the vitreous cavity at 5 o’clock (Fig. a). Using forceps, we found that the knot was loosely connected to the underlying tissue, and we removed it with forceps like any other intraocular foreign body, causing no haemorrhage or other complications (Fig. b). The next day, the visual acuity in the patient’s left eye was hand motion, the IOP was 14.9 mmHg, and her pain was relieved. One week later, her best correct visual acuity was hand motion and her IOP was 13.6 mmHg in the left eye without anti-glaucoma medication. The vitreous was clear, the retina was still attached, and the ring-shaped protrusion was still visible around the equator. Around 5 o’clock, where the suture knot had been located, the choroid and retinal tissue were missing and the silicone buckle had penetrated into the vitreous cavity (Fig.). We opted to treat the patient with steroid eye drops and conservative follow-up (observation), unless retinal redetachment or vitreous haemorrhage occurred.
Microscopy showed the suture as a multifilament of four fibers, each having 11 microfibers of diameter 16 μm (Fig. ). Mass spectrometry revealed that the material was polyethylene terephthalate (PET) (Fig. ), possibly Dacron. |
pmc-6298014-1 | A 56-year-old Caucasian man with severe AS (valve area 0.81 cm2, mean gradient 54 mmHg), high Society of Thoracic Surgeons (STS) score (> 8), moderate chronic obstructive pulmonary disease with forced expiratory volume in 1 second (FEV1) of 1.9 L at 53% of predicted, Crohn’s disease (on immunosuppressive therapy), hypertension, and non-obstructive coronary artery disease presented for a TAVR procedure under monitored anesthesia care. An echocardiogram and subsequent left ventricular hemodynamic study completed as part of the preoperative evaluation showed symmetric, concentric left ventricular hypertrophy with no left ventricular outflow gradient. His early intraoperative course was unremarkable. Following successful deployment of the transcatheter valve and cessation of rapid ventricular pacing at 180 beats per minute, he became hypotensive, tachycardic, and short of breath. Despite escalating doses of phenylephrine, ephedrine, vasopressin, norepinephrine, and epinephrine, he remained profoundly hypotensive and unresponsive. He continued to decompensate and developed acute pulmonary edema, requiring oral suctioning and rapid sequence intubation. Given his deterioration immediately following rapid pacing and valve deployment with poor response to epinephrine, an LVOT obstruction was considered, but other etiologies were included in the differential (Table ). Consequently, inotropic medications were ceased and rate-control and afterload-increasing medications (esmolol, phenylephrine) were prioritized with marked improvement in symptoms. An expedited intraoperative transesophageal echocardiography (TEE) assessment confirmed the presence of hypertrophic cardiomyopathy pathology causing LVOT obstruction with associated mitral valve systolic anterior motion, as shown by the “hockey sticking” of the anterior mitral valve leaflet into the LVOT in Fig. a. The physiologic consequence of this decompensation is clearly represented in Fig. b, showing a near obliteration of flow across the LVOT. The initial peak gradient across the LVOT obstruction reached 70 mmHg, and we considered performing an urgent septal alcohol ablation in the event that the gradient remained refractory to our attempts at medical management. Beta blockade with metoprolol was titrated for rate control, a phenylephrine infusion was started to maintain systemic vascular resistance, and fluid resuscitation to achieve euvolemia was guided by TEE. This resulted in a significant improvement of the LVOT obstruction (peak gradient of 25 mmHg, mean of 13 mmHg) as shown in Fig. a and b. Intubated, paralyzed, and showing stable vital signs, our patient was transported without external pacing to the intensive care unit. Subsequent arterial blood gas was normal with improving respiratory status.
He was mechanically ventilated, sedated, and remained on a phenylephrine infusion until postoperative day (POD) 1 when he became responsive. A transthoracic echocardiogram showed moderate to severe concentric left ventricular hypertrophy, normal left ventricle (LV) systolic function, ejection fraction of 60%, and a normally functioning prosthetic valve with peak gradient of 27 mmHg and mean systolic gradient of 10 mmHg. An overlying LVOT gradient of 40 mmHg that was late peaking was also observed. He was weaned from vasopressor medications and extubated on POD 2. He was ambulatory and able to move to the ward on POD 4, and was discharged on POD 5. Post-discharge, his LVOT gradient gradually increased again and his HOCM was deemed refractory to medical management. Eight months after his TAVR, he received an alcohol ablation which successfully relieved the LVOT obstruction. |
pmc-6298017-1 | The patient was a 63-year-old man who had neither microscopic nor macroscopic hematuria at his previous medical checkup. There was no apparent family history of kidney disease. His leukocyte and platelet counts had begun to decrease 6 years ago, and he was diagnosed with myelodysplastic syndrome (MDS) by bone marrow aspiration. He started treatment for anemia with blood transfusion 2 years ago. He was not on any antiplatelet or anticoagulant medications and his serum creatinine (Cr) level was 0.74 mg/dL 9 months previously. He started taking the oral iron chelator Deferasirox at 125 mg due to post-transfusion iron overload 6 months ago. The dosage was then increased to 1000 mg 3 months ago. When the serum Cr level increased, the Deferasirox dosage was reduced to 500 mg 3 weeks before hospitalization. Although the serum Cr level decreased once, he developed a fever and macroscopic hematuria 1 week before hospitalization. The serum Cr level increased again, and Deferasirox was stopped 4 days before hospitalization. He was admitted urgently to our hospital for the evaluation of acute kidney injury and macroscopic hematuria.
On admission, his body temperature was 36.7 °C, and his heart rate was 81 per minute. His blood pressure was 125/64 mmHg. A physical examination revealed no abnormalities except for anemic palpebral conjunctiva. The laboratory values at the time of hospitalization are shown in Table . Pancytopenia was noted, and the coagulation values were within the respective normal ranges. The blood urea nitrogen and serum Cr levels were 42.0 and 3.97 mg/dL, respectively. The serum ferritin level was high at 14230 ng/mL. A urinalysis showed proteinuria and hematuria, and a urinary sediment analysis revealed more than 100 dysmorphic red blood cells (RBCs) per high-power field with epithelial casts, granular casts, and RBC casts. The urinary protein-to-creatinine ratio was 1.20 g/gCr. Urinary N-acetyl-β-D-glucosaminidase and β2 microglobulin values were 18.4 g/gCr and 2757 μg/L, respectively. The myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA), proteinase-3-ANCA, anti-glomerular basement membrane (GBM) antibody, antinuclear antibody, and anti-streptolysin O were all negative.
After hospitalization, the patient was treated with intravenous administration of 500 mg of methylprednisolone for 3 consecutive days, followed by 30 mg of prednisolone per day orally. Hemodialysis therapy was initiated due to oliguria and discontinued after 10 days because his urine volume recovered. A kidney biopsy was performed on the eighth day of admission.
One of 11 glomeruli was globally sclerotic. None of glomeruli showed crescentic formation or adhesion. Although there were no major abnormalities in the glomeruli (left-upper panel, Fig. a), the leakage of RBCs into the Bowman’s space was observed (inset of left-upper panel, Fig. a). An electron micrograph showed leakage of red blood cells, two of which were dysmorphic, into Bowman’s space (right-upper panel, Fig. a). Interstitial fibrosis with acute tubular necrosis were observed in approximately 40% of the total area (lower panel, Fig. a). Erythrocyte cast formation was observed in the tubular lumen, which was associated with tubular simplification (Fig. b). There were positive blue signals both in glomerular cells and Bowman’s capsular epithelial cells on Berlin blue staining, which was reflected glomerular hemorrhaging (left-upper panel, Fig. a). The positive blue signals were prominent in the tubular cells (right-upper panel, Fig. a). There were no apparent positive blue signals in the normal human kidney sections, which were purchased from Zyagen (HP-901, CA, USA) (lower panels, Fig. a). There was no significant staining for immunoglobulin G (IgG), IgA, IgM, complement 3 (C3), C1q, or fibrinogen.
Since there were no signs of rapidly progressive glomerulonephritis on a kidney biopsy, the amount of prednisolone after the second round of the intravenous administration of 500 mg of methylprednisolone for 3 consecutive days was decreased. Although the macroscopic hematuria disappeared at 2 weeks after admission, the serum Cr level was 1.92 mg/dL at the time of discharge and was unchanged after 2 months. The results of the electron microscopic study revealed thinning of the GBM without any immune complexes (Fig. b). The thickness of the average GBM was 199 ± 47 nm, which was consistent with TBMD. Therefore, a genomic sequence analysis of the COL4A3 and COL4A4 genes was performed by Sanger sequencing method after purifying the polymerase chain reaction products of exons, and five and six missense mutations were found in COL4A3 and COL4A4, respectively (Table ). |
pmc-6298615-1 | A 64-year-old African American male patient with no significant family history and recently diagnosed poorly differentiated invasive ductal carcinoma and ductal carcinoma-in-situ was referred to our institution after a mammogram showed that the breast cancer had increased in size from 2.2 to 2.6 cm and detection of new abnormal axillary lymph nodes. Ultrasound-guided core biopsies of the palpable right axillary lymph nodes showed that the primary breast cancer had metastasized to the nodes (Figure ) and the tissue was positive for antibodies to estrogen receptors or anti-estrogen receptors (ER) and antibodies to progesterone receptors or anti-progesterone receptors (PR), but negative for antibodies to human epidermal growth factor receptor 2 (Her2/neu) receptors.
Genetic testing yielded negative BRCA1/BRCA2, however was positive for heterozygous partner and localizer of BRCA2 (PALB2) c.3027del gene and variants of nibrin (NBN) c.1354A>C and c.511A>G genes. The patient underwent a right modified radical mastectomy with appropriate follow-up.
The patient returned within three months of his mastectomy with symptoms of prostate enlargement which included difficulty urinating and retention and was subsequently found to have an elevated prostate-specific antigen (PSA) >12. The patient underwent a robotic laparoscopic radical prostatectomy with bilateral pelvic node dissection in which biopsies of the prostate and pelvic nodes demonstrated prostatic adenocarcinoma Gleason grade seven with capsular involvement (Figure ). No vascular involvement was detected and surrounding pelvic nodes were negative for carcinoma. Currently, the patient is undergoing chemotherapy with adriamycin which inhibits topoisomerase and cyclophosphamide, an alkylating agent, to be followed by paclitaxol which inhibits microtubule function. |
pmc-6298618-1 | A 64-year-old female presented to our medical center with abdominal pain, nausea, and vomiting for one day. The pain was diffuse, sharp, and it was concentrated in the lower abdomen. Her past medical history was significant for breast carcinoma status post bilateral mastectomy, hysterectomy, Helicobacter pylori infection successfully treated with triple therapy and metastatic squamous cell carcinoma of the esophagus. Four years ago, she underwent an uneventful placement of a fully covered 19 x 100-mm esophageal Wallflex® stent (Boston Scientific, Natick, MA, USA). Her family history was unremarkable and her home medications included iron and vitamin C supplementation. The patient was non-alcoholic, non-smoker and drug-free. On physical examination, she appeared comfortable; well-oriented in time, space and person; well nourished; and there was no acute distress. Cardiac examination was notable for tachycardia. The chest was clear to auscultation with good air entry bilaterally. The abdomen was tender in the hypogastrium and left-lower quadrant, but it was soft and non-distended. Vital sign examination revealed blood pressure 112/68 mm Hg, heart rate 111 beats per minute, temperature 98.5°F and respiratory rate of 18 breaths per minute.
The patient underwent an extensive diagnostic evaluation. The details of her laboratory workup are provided in Table .
Computed tomography abdomen identified the esophageal stent in the left-lower quadrant of the abdomen with the presence of free air in the abdominal cavity, consistent with the gastrointestinal tract perforation (Figure ).
The migrated stent-related perforation of the jejunum with multiple loops of small bowel measuring up to 4.5 cm, bowel-wall edema, and thickening of the loops proximal to the stent were evident (Figure ).
The patient was emergently shifted to an operating room. An uneventful exploratory laparotomy was performed. It showed a moderate collection of a purulent fluid within the abdomen. The esophageal stent was palpated 16 cm into the jejunum in the pelvis, with markedly dilated proximal small bowel. The stent along with the perforated distal jejunum was resected and an end-to-end anastomosis was performed. The post-procedure clinical course of the patient was unremarkable. After she resumed enteral feeds, she was discharged from the hospital in stable condition. On the one-month follow-up, she reported a good recovery without any inadvertent events or recurrence of the gastrointestinal complaints. |
pmc-6298621-1 | A 65-year-old, deconditioned male was referred for the evaluation and treatment of chronic low back pain. He reported a history of back pain that began in 1960 when he was hit in the lower back during a high school football game. Imaging noted fractures of the right L4 and L5 transverse processes and an L4-5 disc herniation, which was treated with rest. He was injured again during a pick-up rugby game in 1963, which resulted in the use of a rigid Boston brace for three months to treat L4-5 instability. He developed increasing episodes where he lost the ability to weight bear on his right lower extremity, resulting in a non-instrumented L4-S1 lumbar fusion in 1972.
He unsuccessfully trialed various pain medications, such as hydromorphone, morphine, oxycodone/acetaminophen, tramadol, gabapentin, lidocaine patches, and capsaicin patches, over many years. He eventually developed severe opioid-induced pruritus, which was treated with diphenhydramine. If the pain was severe, he would take a hydromorphone. He had many prior lumbar epidural steroid injections and local ketorolac and lidocaine injections, sometimes weekly, in the emergency room.
I met the patient in 2009 when he transferred his care to our office. His physical examination was most pertinent for visual analog scale (VAS) 1-10/10 pain in the right buttock that radiated into the right leg with associated numbness and tingling in the right foot. On examination, his strength was 4/5 in the right hip flexors and 5/5 in the remaining lower extremity muscles with intact ankle reflexes bilaterally. His sensation was also intact to light touch throughout the lower extremity dermatomes. Bilateral straight leg raise signs were negative. On palpation, he had very tight bilateral lumbar paraspinal muscles that were diffusely sensitive. His pain was often severe, and on multiple visits to our office, he would very slowly shuffle into the office using a single-point cane under a great deal of distress.
Subsequent lumbar X-rays in 2010 demonstrated no abnormal lumbar motion with flexion and extension and pelvic and right hip X-rays in 2011 were unremarkable. We could not order a magnetic resonance imaging (MRI) study due to his implantable pacemaker. His most recent lumbar computed tomography (CT) scan in 2010 noted an osseous fusion of the facet joints from L4-S1, a mild disc bulge at L5-S1, moderate sacroiliac joint degeneration, and mild T12 and L1 anterior wedging, with no change compared with the 2007 study.
He was not interested in chronic opioid or adjuvant therapy other than for occasional hydromorphone with diphenhydramine for severe exacerbations. We trialed physical therapy, which always exacerbated his pain. In total, during our attempt to manage his pain, he had 10 right L5-S1 epidural steroid injections as well as a caudal epidural injection and over 20 blind and ultrasound-guided right L5-S1 paraspinal trigger point injections with corticosteroids and anesthetic. These procedures only improved his pain for several days, but they were effective enough to allow him to walk normally out of the office after shuffling in. An ultrasound-guided right hip joint corticosteroid injection in 2011 was not helpful. During one of these trigger point injections on January 29, 2014, we noticed a laminar flow of the triamcinolone and 1% lidocaine injectate within the thoracolumbar fascial plane (Figure ). Several days later, he reported an uncharacteristically remarkable improvement, yet it was again temporary.
Although the thoracolumbar fascia is connective tissue that separates the individual erector spinae muscles, an anatomical cavity is not known to exist in this region. On February 6, 2014, we proceeded with an ultrasound-guided right L5-S1 thoracolumbar fascia plane platelet-rich plasma infiltration using a total volume of 8 ml. By March 11, 2014, the patient reported a significant improvement in his pain with eventual resolution. He reported that he could accomplish all activities without pain, including walking unlimited distances and running for the bus with no discomfort. Over time, he also began to engage in heavy yard work, which he had not done for decades and was no longer spending weeks lying in bed. This improvement continued through the last follow-up in 2017. |
pmc-6298624-1 | A 39-year-old male presented to our medical center with acute-onset sharp abdominal pain for four days. The pain was continuous, radiating to the back, and it was associated with nausea. The patient had a past medical history significant for gout, pre-diabetes, and hyperlipidemia. He was not on any medications and was educated to control the metabolic abnormalities only with diet and exercise. He was married and worked as a chef. He denied tobacco, alcohol, or illicit drug use. His family history was negative for metabolic syndromes and lipid abnormalities. On presentation, physical examination was remarkable for epigastric tenderness. He appeared dehydrated and diaphoretic, febrile to 101.2° F, and tachycardic to 114 beats per minute.
Laboratory parameters were remarkable for hypertriglyceridemia, hyperglycemia, and markedly elevated serum lipase levels. The details of his laboratory evaluations are provided (Table ).
Serum electrolytes, liver and renal function tests, coagulation profile, and lactate dehydrogenase were within normal limits. Computed tomography abdomen demonstrated peripancreatic fatty infiltration and moderate edema, suggestive of acute pancreatitis (Figure ).
There was no evidence of gallstones. Therein, the probable causes for patient’s disease were systematically excluded, and he was eventually diagnosed with HTGP based on the detailed clinical history, physical examination, laboratory parameters, and radiological findings.
The patient was admitted to the medical intensive care unit. Conservative treatment was initiated with intravenous hydration utilizing Ringer’s lactate and morphine for pain control. As therapeutic apheresis for hypertriglyceridemia was not available, he was initiated on insulin infusion 0.1 units/kg/hour along with 75 cc/hour intravenous sugar solution (dextrose 5% in water). After one day of insulin treatment, his triglyceride level trended down to 3894 mg/dL (normal, <150 mg/dL). He was continued on insulin infusion and dextrose water with hourly blood glucose monitoring. After 12 days of intensive insulin monotherapy, the triglyceride level decreased to less than 500 mg/dL. The patient recovered well with insulin treatment with diminution of symptoms. After he resumed enteral feeds, he was discharged from the hospital in stable condition on a long-term fenofibrate therapy (TriCor®; AbbVie Inc., North Chicago, IL). Furthermore, he was also referred for genetic testing to rule out genetic disorders associated with his metabolic lipid aberration. At the one-month follow-up, the patient showed complete recovery of the symptoms with normal biochemical profile. |
pmc-6298625-1 | A 34-year-old Chinese female with a previous medical history of interventricular hemorrhages was admitted for refractory migraines and changes in behavior. During the year, the patient’s family noted behavioral changes stating that she seemed depressed for at least three months, with fluctuating mood, decreased appetite, increased somnolence, and bizarre behavior. She also seemed to be less active and was not interested in her regular activities. She was brought to the hospital after she was found unresponsive, and a right temporal intracranial hemorrhage was detected (Figure ).
As shown in Figure , over 12 years ago, the patient was admitted for a left frontal hematoma that required an indirect revascularization of the left hemisphere through encephalo-duro-arterio-myo-synangiosis (EDAMS) to prevent further ischemia. Upon discharge, she was noted to have neurologic deficits, primarily expressive aphasia and right-sided weakness, although she was ambulating independently. Her family history was significant for hemorrhagic strokes on her paternal side of the family. A cerebral angiogram was performed to rule out arteriovenous malformations and aneurysms; however, a right-sided MMD pattern was observed (Figure ).
Genetics was consulted, which led to the patient being found to have an RNF213 gene mutation. Due to the risk of hemorrhagic and ischemic stroke of the right hemisphere, the possibility of revascularization of the right hemisphere was discussed. However, she was not willing to consider treatment at the time. A psychiatric evaluation reported the patient to have expressive aphasia, unclear etiology of the patient’s catatonic state. Her catatonia included selective mutism, rigidity, immobility, fixed gazing, negativism, oppositional paratonia, and refusal for oral intake. Differential diagnoses of the aforementioned symptoms included apathetic delirium, depression, or a neurobiological disorder. She was initially treated with loxapine and mirtazapine, but yielded no improvement. Mild improvement occurred after changing loxapine to risperidone. A trial of 2 mg intravenous (IV) lorazepam (Ativan) briefly helped alleviate symptoms of catatonia, and the patient became less resistant to examination and paid more attention to her surroundings. However, she remained selectively mute. After two weeks with mirtazapine (15 mg), risperidone (1.5 mg), and clonazepam (1 mg bid), the patient showed notable improvement. She was more interactive with her surroundings, less agitated, cooperative to examination, able to follow simple commands, and able to get out of bed but remained non-verbal. Once clonazepam was decreased, she became less drowsy, able to eat independently and continued to show signs of further improvement. She became verbal, however, her speech was non-fluent, nonsensical, disorganized, and showed minimal language comprehension. The patient returned to being mute and refused to eat for the ensuing two weeks requiring nutrition to be maintained by a nasogastric tube. Mirtazapine was increased to 30 mg and risperidone to 2.5 mg. Repeated electroencephalogram (EEG) did not show epileptiform activity but showed slow waves consistent with structural changes. Electroconvulsive therapy (ECT) was briefly considered due to her continuing refusal to eat. Fortunately, the patient showed remarkable improvement. She began to eat, spoke clearly, and interacted with her family. Though she denied any depressive or psychotic features, she was observed smiling spontaneously for the first time since her admission. Major depression with catatonic features, complicated with comorbid medical conditions remained the preferred diagnosis. |
pmc-6298627-1 | A 23-year-old Hispanic male presented to the emergency department, with rash, mouth sores, and subjective fevers that began after eating fish five days prior. His symptoms started with sores in his mouth and on his lips with penile and anal pruritus. After 24 hours, the patient developed a pruritic rash over his upper extremities, neck, upper back, and palms, as well as two non-painful sores on his penis and one blister on his rectum. Despite medicating at home with Benadryl, the patient’s symptoms persisted, which caused the patient to seek care in our emergency department.
At presentation, the patient was alert and calm, without anxiety or an ill appearance. The patient reported having unprotected intercourse with a female two months ago. He denied ever having anal intercourse, a history of sexually transmitted infections, dysuria, or penile discharge. He also denied any past medical problems and did not take any prescription medications or over-the-counter supplements. The patient’s vitals were within reference range. On physical examination, he had heme-crusted polycyclic erosions of vermillion lips, buccal mucosa, and labial mucosa (Figure ). He was also found to have numerous 2-12 mm erythematous, urticarial, targetoid papules and plaques with central hyperpigmented purple/red duskiness over bilateral palms (Figure , Figure ), dorsal hands, upper arms, lateral neck (Figure ), cheeks, nasal tip, and alae. He had several urticarial, targetoid papules with central duskiness over the penile shaft. Cardiovascular, neurologic, respiratory, and abdominal examinations were otherwise unremarkable. Both dermatology and infectious disease were consulted on this patient.
Laboratory work for this patient consisted of complete blood count, comprehensive metabolic panel, sexually transmitted infection testing, bacterial and viral blood cultures and serology, viral direct detection test, and anti-nuclear antibody testing. Of note, the patient had a white blood cell count of 5.4x10^9/L, hemoglobin of 14.7 gm/dL, platelet count of 302x10^9/L, and creatinine of 0.85 mg/dL. The patient was negative for herpes simplex virus (HSV) and human immunodeficiency virus (HIV) while positive for anti-nuclear antibody (ANA). At the time of discharge, the only test the patient was found to be positive for was anti-nuclear antibodies. He was initially treated with acyclovir, but the medication was discontinued after negative laboratory testing. Biopsy of a lesion on the patient’s upper arm exhibited interface dermatitis, consistent with erythema multiform. The patient was treated with “magic mouthwash,” consisting of Benadryl, Maalox, and lidocaine, and instructed to continue with the treatment as symptoms persisted. On the day of discharge, the patient’s rash and sores were improving and he did not have any new lesions. |
pmc-6298902-1 | A 77-year-old Japanese woman with end-stage renal disease due to chronic glomerulonephritis was introduced to our hospital because of a fourth episode of distal end-to-side radial-cephalic autologous AVF in her right forearm, which had been created 29 months previously. Hemodialysis had been initiated approximately 10 years before the current event, and she had undergone operations related to previous AVFs a total of 21 times: the creation of bilateral radiocephalic AVFs two times and percutaneous transluminal angioplasty (PTA) 19 times. A physical examination revealed a weak vascular murmur and thrill in her right forearm. Preoperative ultrasonography of the right forearm demonstrated venous stenosis located 0–4 cm from the site of anastomosis, and affecting 6 cm of the median cubital vein. Additionally, the diameters of both lesions was <2 mm, and the distal and proximal diameters of the lesions were approximately 4–6 mm. PTA was successfully performed as a salvage operation (A–P).
After disinfecting the patient’s right upper limb, we inserted a 5 Fr × 3 cm sheath (Mosquito Sincere Catheter Introducer, including a guidewire [diameter 0.025 inch × length 50 cm], Boston Scientific Japan K. K., Tokyo, Japan) in the cephalic vein around the middle of her right forearm toward the site of anastomosis by the Seldinger technique [] (A).
Retrograde angiography from the vein under avascularization revealed venous stenosis 0–4 cm from the site of anastomosis (B). Kyousha™ NT Peripheral Guidewire (diameter, 0.018 inch; length, 100 cm; Boston Scientific Japan K. K., Tokyo, Japan) and NSE PTA balloon catheter GDM01 (balloon diameter, 4 mm; length, 4 cm; and rated burst pressure, 18 atm; Nipro corporation, Osaka, Japan) could pass through the lesion. After 2000 units of heparin were administered and allowed to circulate for 5 min, we dilated the lesion several times at 4–18 atm for 30 s, and retrograde angiography showed the improvement of stenosis (C,D).
We subsequently decided to treat a lesion downstream from the sheath insertion site. First, we detected the stenosis (length, approximately 6 cm) of the median cubital vein by antegrade angiography (E). A dilator and guidewire were threaded into the sheath (F), and the guidewire was placed in the vein (G). Next, the coaxial dilator/sheath was pulled and gradually stood (H,I), and the tip of the dilator/sheath was slightly inverted toward the downstream side (J). While maintaining this state, the distal end of the guidewire was pulled around the tip of the dilator, inverted toward the downstream side, and navigated (K). The coaxial dilator/sheath was carefully reinserted into the vein over the guidewire and the guidewire and dilator were removed from the sheath (L,M).
We confirmed the stenosis of the median cubital vein by antegrade angiography again (N). The guidewire and balloon catheter could pass through the lesion; we then dilated the lesion several times at 2–10 atm for 30 s (O). As angiography showed the improvement of stenosis (P), we removed the sheath and finished the procedure. A schematic illustration of her AVF in the right forearm is shown in .
The patient was able to receive hemodialysis therapy uneventfully after PTA. |
pmc-6299309-1 | A 71-year-old female with past medical history of hypertension, abdominal and thoracic aortic aneurysm, and chronic obstructive pulmonary disease presented to the hospital complaining of pain and bruising in right thigh of 6 days duration. She denied any history of abnormal bleeding, family history of bleeding disorders, or use of any anticoagulant medications. Physical examination revealed large subcutaneous hematoma on the anterior aspect of the right thigh, extending posteriorly and laterally (). Imaging including ultrasound to rule out deep venous thrombosis was negative, and magnetic resonance imaging showed intramuscular bleeding into the anterior compartment of the right thigh (). Laboratory data () including complete blood count revealed hemoglobin level of 6.8 g/dL that responded appropriately to 1 unit of blood transfusion. Coagulation profile showed prolonged activated partial thromboplastin time (aPTT) 52.5 seconds, normal prothrombin time, and normal international normalized ratio. Mixing study failed to correct aPTT, factor VIII assay was low at 2%, and inhibitor levels were elevated at 16 Bethesda units (BU) suggestive of AHA. Treatment was started with factor VIIa 5 mg multiple times daily, Obizur (porcine-derived recombinant factor VIII) 15 000 units twice daily, and methylprednisone 80 mg daily without any improvement. Due to the lack of any clinical response to the initial therapy, chemotherapy with cyclophosphamide and rituximab was initiated. The patient received 1 cycle of the combination chemotherapy, followed by second cycle of rituximab monotherapy after 1 week. She was transitioned from methylprednisone to prednisone during the same period. After the second cycle of chemotherapy, factor VIII assay was rechecked and improved to >5%. The thigh hematoma reduced in size, and the patient did not experience any further bleeding during the hospitalization. She was later discharged on a prednisone taper and with an outpatient follow-up with hematology to continue rituximab cycles weekly. |
pmc-6299503-1 | A 79-year-old man with mCRPC metastatic to bone and lymph nodes and a history of atrial fibrillation presented with blurred vision and pain and stiffness in the upper back after 8 weeks on a clinical trial with nivolumab (1 mg/kg) and PROSTVAC, both given every 2 weeks. Eye exam was within normal limits, while musculoskeletal exam revealed tenderness in trapezius muscles and decreased motor strength in arms (III/V) and neck (IV/V). The rest of the physical exam was within normal limits, with the exception of an irregular heart rhythm. Laboratory tests were as follows: creatinine kinase (CK) 3200 U/L (normal: 39–308 U/L), CK-MB 65.7 mcg/L (normal: 0–7.6 mcg/L), troponin I 0.209 ng/mL (normal: 0–0.056 ng/mL). Electrocardiogram (ECG) revealed atrial fibrillation with QT prolongation (QTc 514 msec) and left anterior fascicular block, all unchanged from baseline three months before. 2D-echocardiogram showed a left ventricular ejection fraction of 65% with an enlarged left atrium, a dilated right ventricle and increased pulmonary artery pressure (45 mmHg). ProBNP was elevated at 1463 pg/mL and peaked at 3066 pg/mL one day later after hydration. With a presumed diagnosis of autoimmune myositis and possible myocarditis, the patient was admitted and started on methylprednisolone 1 mg/kg/day.
The cardiac MRI findings were consistent with myocarditis involving small areas of the myocardium. Left ventricular size and function were normal (ejection fraction 59%) with normal regional wall motion. Patches of late gadolinium enhancement (LGE) were seen in the basal and mid inferior wall showing an epicardial pattern compatible with myocarditis. Early gadolinium enhancement was abnormal in a similar distribution to the LGE but more extensive. Myocardial T1 was 1411 ms. in the basal inferoseptum and 1231 ms. in the mid inferior wall (normal native T1 < 1350 ms.). Myocardial T2 was normal in all segments except the mid inferior wall where it was at the borderline between normal and mildly elevated. Extra cellular volume fraction (ECV) was more diffusely abnormal in the basal inferior wall 41.1% (normal 25.5, 95% confidence intervals 20.5–30.5%) in the closest region of interest to the area of abnormal LGE but also diffusely mildly elevated (32–33%) in several basal and mid ventricular segments (Fig. ).
The patient was discharged on a multiple week oral prednisone taper after normalization of cardiac enzymes on day 4. Treatment with PROSTVAC continued for three more months; nivolumab was discontinued. Six months later, patient is doing well, with no residual cardiac damage. |
pmc-6299517-1 | A 16-year-old boy was admitted to the Hospital das Clínicas de Porto Alegre, Porto Alegre, Brazil, febrile with abdominal and joint pain. At clinical investigation, he presented with anemia, splenomegaly and leukocytosis (white blood cells count 19.6 × 109 /L) with 72% lymphoblast. Bone marrow (BM) aspiration disclosed lymphoblast cells infiltration (92%). The central nervous system (CNS) was not infiltrated by blast cells. The immunophenotyping was characterized by nTdT, cCD10, CD20, CD22, CD38 and CD45(low) and cCD9, CD19, cCD79, and CD58(interm)-positive cells in 45% of blast cells. Myeloid and T-cell markers were negative. The patient was treated according to the GBTLI-ALL2009 at high-risk arm. He was a prednisone poor responder (at day 8; > 1000 circulating lymphoblasts), minimal residual disease at day 35 was negative, and he was considered in complete remission (CR). Twelve months after CR, he was hospitalized with a CNS infiltration and BM highly infiltrated with lymphoblasts. The laboratorial investigations demonstrated a similar immunophenotype profile and distinct karyotype. Despite undergoing the relapse treatment-rescue, the patient died due to complications from an opportunistic infection.
The diagnosis and characterization of leukemia were established by morphology, immunophenotyping, and molecular-cytogenetic analysis according to the World Health Organization classification [].
Cytogenetic analysis of leukemic BM was performed using GTG-banding standard procedures, and the karyotype was described according to the International System for Human Cytogenetic Nomenclature (ISCN) of 2013 [, ]. The karyotype of the diagnostic sample showed evidence of two concomitant chromosomal translocations (48,XY,t(1;19)(q23;q13.3),del(4)(q27q35),der(9)t(9;17)(p13;q11.2),del(10)(q24q26),del(18)(q21q3,+ 8,+ 22,+marc[20]) (Fig. a). In addition to the two rearrangements observed at diagnosis, the karyotype of the BM at relapse also showed near-triploidy: 73,XX,t(1;19)(q23;p13),+ 1,+ 2,+ 3,+ 5,+ 5,+ 6,+ 7,+ 8,i(9q),+ 9,10,+ 12,+ 12,+ 13,+ 14,+ 14,+ 15,+ 15,+ 17,+ 18,+ 19,+ 20,+ 20,+ 20,+ 21,+ 22,+ 22,+ 22,+ 22,+mar [] (Fig. b). The presence of TCF3-PBX1 was confirmed in both diagnostic and relapse samples by reverse transcription PCR (RT-PCR) followed by sequencing (Fig. c, d).
Additional copy number alterations (CNA) were identified by multiplex ligation-dependent probe amplification (MLPA) using the SALSA MLPA P335-A4/B1 and P202-B1 kits (MRC-Holland, Amsterdam, the Netherlands) as previously described []. MLPA data were analyzed using Coffalyser.Net. The relative copy number was obtained after the normalization of peaks against controls. Values between 0.70 and 1.3 were considered to be within the normal range. Values below 0.70 or above 1.3 indicated deletion or gain, respectively. Values below 0.25 indicated homozygous deletion. Submicroscopic deletions were only identified at relapse moment affecting CDKN2A (exons 2 and 5), CDKN2B (exon 2), IKZF2 (exons 2 and 5) JAK2 (exon 23), and miR31 (exon 1), as well as a partial gain in RB1 (exons 14, 19, 24 and 26) (Fig. a, b).
To investigate the presence of a putative gene fusion derived from the PAX5-r we performed a 3’ Rapid amplification of cDNA ends (3’RACE)-PCR based on Scotto-Lavino’s protocol []. After cDNA synthesis, including an oligonucleotide (dT)-tailed primer (QT), two rounds of PCR were performed to enrich the reaction for fragments containing the 3’end of PAX5 transcripts. The first round of amplification used the forward primer PAX5.E4.F1 (5’-AACCAACCAGTCCCAGCTTC-3′), while the second was performed using the PAX5.E5.F1 primer (5’-TACTCCATCAGCGGCATCC-3′). The results showed a head-to-head fusion between exon 6 of PAX5 and a 17q11.2 region, where intron 3 of SPECC1 is located (Fig. c).
Subsequently, we used SuperScript™ III One-Step RT-PCR System (Invitrogen, Carlsbad, EUA) and sequencing on ABI®3500 Genetic Analyzer (Applied Biosystems, Foster City, EUA) to confirm that PAX5-r was present at both time points diagnosis and relapse (Fig. d). Furthermore, the predicted truncated PAX5 protein consisted of 266 amino acid residues, preserving the paired domain, the octapeptide motif and the homeodomain of PAX5, and a tail of 6 amino acids coded by the contiguous intron 3 sequence of SPECC1, which does not correspond to any predictive functional domain (Fig. e, f). |
pmc-6299518-1 | A 79-year-old Caucasian woman reported for an outpatient consultation, presenting with urgency (12–15 times/day), nocturia (3 times/night), inability to fully empty her bladder, and reoccurring UTIs (three times in the past 3 months). Our patient was declared cardiopulmonary stabile with blood pressure of 130/90 mmHg and a pulse of 67 beats/min. A detailed medical history revealed a multidrug regimen (bisoprolol 5 mg, candesartan cilexetil 16 mg, lercanidipin hydrochlorid 10 mg) controlled her hypertension for 15 years with the use of no diuretics, and the presence of open-angle glaucoma, which contraindicated the use of anticholinergic therapy. She took no other medications on a regular basis. Our patient had had three deliveries, including one vaginal birth and two cesarean deliveries. Previous operations included the following: benign left ovarian cystectomy, right nephrectomy after a vehicle accident, abdominal herniotomy, and anal abscess extirpation. Our patient was married, a retired elementary school teacher, with a history of no regular alcohol or drug consumption or smoking. Any allergy was not known. A blood test revealed normal liver and kidney function, and no sign of generalized infection (glutamic oxaloacetic transaminase [GOT]: 40 U/L, glutamic oxaloacetic transaminase [GPT]: 25 U/L, gamma-glutamyl-transpeptidase [GGT]: 43 U/L, amylase: 56 U/L, alkaline phosphatase: 91 U/L, lactate dehydrogenase [LDH]: 180/U/L, creatinine: 0.93 mg/dL, sodium [NA]: 138 mmol/L, potassium [K]: 4.1 mmol/L, calcium [Ca] 2.52 mmol/L, haemoglobin 13.9 g/dL, leukocytes: 6.6/nL, thrombocytes: 301/nL, erythrocytes: 4.8/pL, C-reactive protein [CRP]: 23. mg/L). On admission, a urine dipstick tested positive for nitrite, leukocyte esterase, and blood, with alkaline pH (8.5). Microbiology revealed ongoing Escherichia coli UTI, which was treated with oral cefuroxim 2 × 250 mg for 7 days. On urogynecological physical examination, we found no signs of urogenital prolapse (pelvic organ prolapse quantification [POP-Q] scores Aa: − 3, Ap: − 3, Ba: −3, Bp: −3, C: −7, GH: 2, Pb: 2, TVL: 9, D: −8), vaginitis, and vaginal or cervical erosion. Pelvic ultrasound confirmed no altered pelvic anatomy, with an atrophic 5.18 × 2.8 × 2.4 cm-sized uterus, with an endometrial thickness of 3 mm, sharp endomyometrial borders, with no sign of adnexal pathology, and no presence of free abdominal fluid. The introitus ultrasound found the urethral length to be 3.66 cm, with a significant visible stenosis at the middle segment of the urethra (0.4 mm). During catheterization, 150 mL post-void residual urine was detected (Fig. ). A neurologic examination included the assessment of the tone, the strength, and the coordinated movements of the lower extremities, especially focusing on the abduction and the spreading of the toes, proving intact S3 innervation. The bulbocavernosus reflex and the anal sphincter reflexes were also found to be normal (intact S2˗S4 innervation). The preoperative urodynamic examination resulted in detrusor pressure at maximum flow ranges of 40 cm H2O with maximum flow rates (Qmax) of less than 10 mL/s. After the informed consent of the patient, we carried out urethral dilation with ascending Hegar sticks ranging from 3 to 13 mm (Ch9 to Ch39) in diameter in general narcosis. Before each dilatator insertion, lidocaine jelly was administered transurethraly (Fig. ). All metallic dilatators were inserted 4 cm deep in the long axis of the urethra, and then gently pulled saggitally downward till they met resistance. Intraoperative cefuroxime 1500 mg, and metronidazole 500 mg antibiotic prophylaxis was given to our patient to avoid postoperative uretrocystitis developing. Before and after the dilatation, cysto-urethroscopy was carried out, to confirm preoperative urethral stenosis, and no urethra or bladder injury postoperatively (Fig. ). Six months after our patient’s surgery, she was reported her to be symptomless, continent, and the post-void residual urine volume was found to be completely eliminated, with no sign of UTI. |
pmc-6299528-1 | A 22-year-old female admitted to THP with a one-day history of fever proceeded by frontal headache of 3 days. On admission, she had arthralgia, myalgia, mild postural dizziness and nausea. She has passed urine normal amount. She was hemodynamically stable with a blood pressure of 96/64 mmHg without a postural drop. Abdomen was soft and non-tender. Clinically, she did not have evidence of plasma leak. Her blood test was positive for dengue NS1 antigen. On 3rd day of fever, ultra sound scan of abdomen detected thin rim of free fluid in the hepato-renal pouch and moderate gall bladder wall oedema with mild pericholycystic fluid. She did not have pleural effusion or ascites. Neither she had postural drop of blood pressure, tachycardia or right hypochondrial tenderness. However, her haematocrit has risen from 33 to 38%. In a flash, within the next 6 h, she developed significant ascites (moderate) and bilateral moderate pleural effusions with a reduction of urine output. She had fluctuation of urine output and blood pressure and required several normal saline boluses and Dextran-40 along with frusemide to maintain vital parameters. Sixty percent of her calculated fluid quota was utilized in the 1st 12 h of tentative critical phase. Her clinical status gradually improved within the next 3 days. But, there was delayed resolution of effusion and ascites. Her serum albumin level dropped during the critical phase and took days reverse. Her recovery was uneventful and discharged on day 6 of the hospital stay. She had erratic rapid leaking of plasma into serous cavities during critical phase. |
pmc-6299528-2 | A previously healthy 39-year-old female, admitted to the THP with a history of fever for 4 days. She had nausea, vomiting, arthralgia, myalgia and headache. She did not have any bleeding manifestations or abdominal pain. On examination, she had mild dehydration with low volume pulse. Blood pressure was 100/80 mmHg in supine position and 90/80 mmHg on standing. Right lung base was stony dull on percussion and had absent breath sounds. Ultrasound scan revealed a right sided plural effusion with free fluid in the abdomen. The patient was managed as critical phase of dengue haemorrhagic fever (DHF) with meticulous titration of fluids according to the haematocrit values. She remained hemodynamically stable with a stable haematocrit values during the critical phase. On day 7 of illness, dengue serology showed positive IgM and IgG titers. After completion of critical phase on 7th day of the illness, she complained of abdominal pain and back pain. Clinical examination found s mild icterus and tense ascites. Laboratory investigations revealed a marked rise in liver enzyme levels (ALT 204 to 1391 u/L and AST 505 to 4519 u/L) with an INR of 1.9. Diagnosis of acute hepatitis leading into acute liver failure was made and viral hepatitis was excluded by doing hepatitis A IgM, hepatitis B surface antigen and hepatitis C IgM which were negative. She denied self-medication with high doses of paracetamol. Further, she was treated with intravenous N acetyl cysteine 150 mg/hour infusion as an empirical treatment. Her low albumin level was corrected with intravenous human albumin administration. Antibiotics including oral metronidazole and intravenous ceftriaxone was administered at the same time to cover bacterial infections. She was given intravenous vitamin K for 3 days to prevent clotting factor depletion whilst monitoring liver transaminases and clotting parameters. Finally she was discharged on 12th day of the illness with near normal liver transaminases and normal clotting profile without residual free fluids in her abdomen. Further follow of after 21 days revealed completely normal liver biochemistry. |
pmc-6299528-3 | A19- year-old male, previously healthy university student admitted to THP having a febrile illness with arthralgia and myalgia for 5 days duration. On the way to the hospital, the patient had postural dizziness and fainting attack causing impact on the forehead. Soon after admission, he developed a generalized tonic-clonic seizure which lasted for 5 min with post ictal drowsiness. On examination, he was not pale but had conjunctival hemorrhages. He had a contusion over the forehead due to fall. He was hemodynamically stable with a blood pressure of 126/90 mmHg and a pulse rate of 92 beats per minute without clinical evidence of plasma leaking. Ultrasound scan revealed a thin rim of free fluid in the abdomen. Dengue NS 1 antigen and Dengue Ig M and IgG both were positive. Serotype of dengue was identified as DEN 2. Diagnosis of DHF entering into critical phase was made and commenced intense monitoring with administration of intravenous and oral fluid according to guidelines, Meanwhile, the patient was found to be drowsy but arousable without having any lateralizing neurological deficits. Both optic fundi were normal. Non-contrast CT brain revealed bilateral frontal lobe hyperdense areas with mild cerebral oedema with minimal midline shift, suggestive of intra-cranial hemorrhages. His clotting parameters were within the normal limits. He was transfused with platelets to keep the platelet count more than 50 × 106/L and managed conservatively with adequate intravenous fluids, intravenous antibiotics and antiepileptic drugs. He was started on intravenous phenytoin sodium and later converted to oral phenytoin. Cerebral oedema was managed with intravenous dexamethasone and intravenous mannitol. He was administered with intravenous tranexamic acid to retard further bleeding. Critical phase was uneventful. His headache and drowsiness improved over the next 5 days and discharged with oral antiepileptics. |
pmc-6299528-4 | A-17-year-old previously healthy female presented to THP with a history of fever for 2 days associated with body aches and nausea. She didn’t have any abdominal pain, bleeding manifestations or postural symptoms. On examination, she was flushed and febrile but was not pale or icteric. She was mildly dehydrated. Blood pressure was 100/70 mmHg, pulse rate 100 beats/min and capillary refilling time (CRFT) was less than 2 s. On abdominal examination, there was no free fluid. Lung fields were clear on respiratory system examination. Other systems examination was normal.
Her NS1 antigen was positive and serotype was identified as DEN1. She was managed as dengue fever with continuous monitoring. On the 3rd day of fever, she complained of retrosternal chest pain and undue tiredness. At that time her cardiovascular system examination was normal and electrocardiogram (ECG) showed acute T wave inversion in V2-V5 leads. Troponin I was negative and 2D echo showed global left ventricular hypokinesia and mild impairment of LV function. Ejection fraction was 40–45%. She was treated as having dengue fever complicated by myocarditis. Intravenous hydrocortisone 200 mg 8 hourly was administered for 2 days to reduce myocardial inflammation. On the 4rd day following admission, she complained of abdominal pain and ultrasound scanning revealed free fluid in hepato-renal pouch. Blood pressure was 100/70 mmHg, pulse rate 70 bpm, and CRFT was less than 2 s. She was taken to High Dependency Unit (HDU) and was managed as having DHF complicated with myocarditis with continuous monitoring and with careful administration of fluid to avoid fluid overload. She was discharged on day 7 of illness after recovering from critical phase of dengue fever. She was advised on limiting physical activities. During the follow up on day 14 of the illness, ECG showed reversal of T inversions. Echocardiogram showed improvement of left ventricular function with an ejection fraction of 55%. |
pmc-6299528-5 | A-22-year old previously healthy male admitted to THP with a history of on and off fever for 10 days associated with 3 bouts of hematemesis and melaena. On examination, his pulse rate was 88 beats/m, blood pressure was 90/60 mmHg and CRFT was less than 2 s and lungs were normal. Abdomen was soft and there was no detectable free fluid. Rest of the examination was unremakable. Serology for dengue IgM and IgG were positive on admission. His liver enzymes were high on admission (AST 840 U/L and ALT 560 U/L) with a high INR value of 2.1. His complete blood count showed 11.5 g/dl of haemoglobin and platelet count of 144 × 109/l. Ultrasound examination of abdomen did not show any evidence of leaking thus, DHF was excluded. Hence, the patient was managed as in primary dengue fever with bleeding manifestations. Intravenous fluids were given along with tranexamic acid and vitamin K to reduce bleeding. Intravenous infusion of omeprazole was continued for 24 h and converted to twice day intravenous boluses. He was started in intravenous N acetyl cysteine infusion as liver transaminases were high. His symptoms resolved within the next few days, with symptomatic management. |
pmc-6299528-6 | A-12-year old previously well female child was transferred to THP from a private hospital due to fever for 5 days associated with melena, haematemesis and haematuria with passage of blood clots. She did not have abdominal pain or any other warning signs of dengue on admission.
On examination, she was ill looking, adequately hydrated and GCS was 15/15. Blood pressure was 125/75 mmHg, pulse rate was 90 beats per minute and capillary refilling time was less than 2 s. On respiratory examination lungs were clear and on abdominal examination the abdomen was soft and non tender. Rest of the clinical examination was normal. Both NS1 and IgM were positive and dengue PCR revealed serotype of DEN 2. Ultrasound examination of abdomen did not show any evidence of plasma leaking. She was managed as having primary dengue fever with bleeding manifestations. Her liver enzymes were only mildly elevated (AST 87 u/L and ALT 56 u/L) with a normal clotting profile. Complete blood count revealed hemoglobin of 7 g/dl and platelet count of 17 × 109/μL. Due to low haemoglobin, she was transfused with 1 pint of blood and 4 units of platelets. Her symptoms resolved within the next few days. |
pmc-6299528-7 | A 14-year-old boy presented to THP with a history of fever for 2 days along with headache, arthralgia and myalgia. He did not complain of abdominal pain and did not have bleeding manifestations or any other warning symptoms. On examination, blood pressure was 110/70 mmHg and pulse rate was 100 beat per minute and capillary refilling time was less than 2 s. The abdomen was soft and non-tender and there was no free fluid. Lung fields were clear on respiratory system examination. Rest of the examination was normal. His NS-1 was positive and the PCR appeared as DEN 2 serotype. The patient was managed as having dengue fever. He continued to have fever spikes for 4 days following admission. On the 5th day following admission, he developed postural dizziness, vomiting and heavy diarrhoea. On examination, he was febrile, dehydrated, flushed and had warm peripheries. Blood pressure was 90/60 mmHg, pulse rate was 130 beats per minute and a capillary refilling time of 2 s. Ultrasound examination of abdomen revealed free fluid in the hepato-renal pouch with increased gall bladder wall thickness. He was clinically diagnosed as having DHF complicated with septic shock and gastroenteritis. He was taken to HDU and critical phase monitoring commenced. His c-reactive protein was high 112 mg/dl. Broad-spectrum intravenous antibiotics (ceftriaxone and metronidazole) were started cover the sepsis after taking blood and urine cultures. Within about 1 h, the patient deteriorated significantly and continued to have vomiting and diarrhoea. Blood pressure dropped to 60/30 mmHg and the pulse rate increased to 120 beats/min. Several fluid boluses were given including normal saline and IV Dextran 40. The haematocrit value dropped from 36 to 30 and patient went into decompensated shock with no urine output. He needed continuous transfusion of whole blood amounting to 9 pints over 20 h to maintain blood pressure and urine output. However, there were no obvious bleeding sites. Further, intravenous noradrenaline infusion supported the blood pressure. Gradually patient improved with fluid, blood, antibiotics and vasopressors. He was given intravenous antibiotics for total of 7 days. Vasopressor was gradually weaned off. He was plethoric during convalescence due to over transfusion and was discharged on day 8 of admission. |
pmc-6299528-8 | A 51-one-year-old previously healthy female admitted with a history a febrile illness with arthralgia and myalgia for 4 days. Her NS1 antigen was positive on admission. She was ill and complained of postural dizziness and abdominal pain. On examination, she was ill looking, dehydrated and had bluish cold peripheries. She had central cyanosis and collapsed superficial veins. Her supine blood pressure was recorded as 90/80 mmHg and standing blood pressure was unable to measure due to severe postural symptoms. Capillary refilling time was prolonged, and her respiratory rate was 24 breaths per minute. Lungs were clear and clinically there was no evidence of free fluid in abdomen and pleura. She did not pass urine for 12 h. She was clinically diagnosed to have dengue haemorrhagic fever with decompensated shock. Then she was admitted to the HDU and critical phase management was started. Ultrasound scan of the abdomen did not show free fluid in peritoneal cavity despite patient was possibly in the peak of plasma leaking. However, 12 h after admission, repeat ultrasound scan showed thin rim of free fluid in the hepatorenal pouch. She was resuscitated with boluses of crystalloids and colloids., She became hemodynamically stable gradually and took about 8 h to gain warm peripheries. Fluid management and monitoring was continued, and her symptoms improved within the next 2 days. Although she went in to decompensated shock due to DHF, she had minimum detectable amount free fluid in the abdomen in the later phase of leaking. |
pmc-6299528-9 | A 34-year-old female presented with a febrile illness with arthralgia and myalgia for 2 days duration. Her Dengue NS1 was positive. Her hemodynamic parameters were stable on admission. She was having continuous fever on day 6 of illness. There was no evidence of hemoconcentration or plasma leak and managed as uncomplicated dengue fever. She was kept on intravenous saline infusion at a slower rate. On 6th day of fever she developed cough and shortness of breath. Auscultation of lungs heard crepitations in bases. Over next 6 h she was not improving despite continuous infusion of normal saline and commencing antibiotics. Later, she became agitated and restless and was confused. She had warm peripheries despite blood pressure of 80/40 mmHg which further dropped to 60/30 mmHg. She had pulse rate of 108 beats/ min. There were widespread coarse crackles in the both lung fields involving all 3 zones. Her oxygen saturation dropped to 85% on room air. Her haematocrit remained within normal range. To counter the shock, she was given more intravenous normal saline, Dextran 40 and 2 units of blood transfusion. Then, she developed pulmonary oedema and required CPAP in the intensive care unit with high flow oxygen and intravenous frusemide. Patient was treated with intravenous meropenum 1 g 8 hourly and metronidazole. She had very high CRP and procalcitonin levels suggestive of severe sepsis. After 6 h of resuscitation her blood pressure got stabilized and she recovered completely over next 5 days. She was diagnosed as dengue fever complicated by septic shock probably originating from lungs even though, dengue shock syndrome (DSS) was contemplated at the outset. |
pmc-6299537-1 | A 41-year-old female was referred to the Michigan State University (MSU) endocrinology clinic in 2008 for elevated 24-h urinary free cortisol which was presumably obtained to evaluate hirsutism and irregular menstrual cycles. She had increased facial hair for more than 20 years, which she had managed cosmetically with intermittent waxing. She attained menarche around age 13, and had regular menstrual cycles till her early 20s, at which time she started to have irregular periods and was told she had polycystic ovarian syndrome. She has two children. The first child was conceived spontaneously and the second pregnancy required clomiphene therapy. Other medical history included hypothyroidism following radioactive iodine treatment for a toxic thyroid nodule and depression.
On physical examination, her blood pressure was (122/80 mmHg) and body mass index (BMI) was 22.6 Kg/m2, both normal. She had mildly increased facial hair on her chin and a palpable thyroid nodule in the right lobe. The remainder of the physical exam was normal, and she did not have any clinical features of Cushing’s syndrome.
On laboratory evaluation, 24-h urinary cortisol levels were 317 mcg (normal 3.5–45 mcg /day). Even though she didn’t have any signs or symptoms of Cushing’s syndrome elevated urinary cortisol levels required further evaluation. Repeated overnight and 48 h dexamethasone suppression tests (DST) failed to suppress cortisol levels and 24-h urine cortisol levels were persistently elevated at multiple times. (Table ).
ACTH levels were inappropriately normal, “too high” for elevated cortisol levels (Table ) suggesting ACTH dependent hypercortisolism. Magnetic resonance imaging (MRI) of the pituitary was obtained, which did not show any abnormalities. (See Fig. a and b).
Total testosterone levels were elevated with a level of 136 ng/dl (< 20–80) dehydroepiandrosterone sulfate (DHEA-S) levels were 278 mcg/dL (normal range 35.0–430.0). She was started on metformin with some improvement in hirsutism. Spironolactone was not given due to prior history of allergy. Pelvic ultrasound showed a simple cyst measuring 1.1 cm in the left ovary likely representing a follicle.
During the subsequent years she continued to have elevated cortisol levels with some nonspecific weight gain. Her blood pressure remained normal. Her hemoglobin A1C levels were normal and no clinical signs of Cushing’s syndrome developed over the next 10 years. She met with another endocrinologist for a second opinion who referred her for an Inferior petrosal sinus sampling. (Table ) The sampling suggested pituitary source of ACTH. However, she was told that no further workup was needed till she developed clinical signs of Cushing’s. MRI of the abdomen was obtained that did not show adrenal mass or enlargement. A Dual-energy X-ray absorptiometry (DXA) obtained in May 2013, revealed osteopenia. A repeat bone mineral density (BMD) in December 2016 did not show any significant deterioration.
To determine if she had glucocorticoid resistance syndrome, genetic testing was performed (courtesy of Dr. Ameilia Sertedaki, Ph.D., Division of Endocrinology, First Department of Pediatrics, University of Athens Medical School, Athens, Greece 1152).
The coding regions of the human glucocorticoid receptor gene (hGR, NR3C1) were sequenced and showed no mutation. Her mother and daughters were tested for plasma cortisol levels, which were normal.
In order to determine if higher doses of dexamethasone will result in cortisol suppression, increasing doses of dexamethasone were administered (2, 4 and 8 mg) at night and plasma cortisol was measured the following morning. Plasma levels of dexamethasone were also obtained to confirm the patient had taken the prescribed doses of dexamethasone. The results are shown in Table .
To date (March 2018), she continues to have hypercortisolism without clinical stigmata of Cushing’s syndrome. |
pmc-6299540-1 | The patient was investigated at our institute when he was 38 years old because of slowly progressive difficulty in walking and climbing stairs presenting since the age of 35 years. No familial occurrence of neuromuscular disorders or consanguinity was referred.
On neurological examination scapular, anterior and posterior thigh muscle atrophy were observed. Assessment of muscle strength using the British Medical Research Council (MRC) scale, showed weakness of shoulder girdle muscles (with arm flexion and abduction possible against gravity until 90°), without scapular winging, inferior trapezius (2/5), arm extensors (2/5), elbow flexors (3/5), hip flexors (3/5), hip extensors (2/5), knee flexors and extensors (4/5), dorsal foot extensors (4/5). No cranial nerve involvement was observed. Joint contractures and skeletal deformities were not detected. The patient presented a waddling gait with an increased lumbar lordosis and was unable to get up from the floor. Functional ability of upper limbs was 3 according to Brooke scale (from 1: normal; to 6: no function for upper extremity) [] and lower limb function was 3 according to Vignos scale (1: able to climb stairs without help; to 10: bedridden for lower limb function) []. CK was only slightly increased (253 UI/l). EMG showed myopathic findings in all tested muscles with fibrillation potentials and positive sharp waves. On muscle CT scan, moderate fatty changes were found in bilateral quadriceps and hamstrings and medial gastrocnemius. Respiratory and cardiac functions were normal. Symptoms progressively worsened in the following years, loosing the ability to climb stairs at the age of 45.
A muscle biopsy from the left quadriceps, taken at age 38, displayed fibre size variability, a few central nuclei, scattered degenerative fibres (Fig. ), few cytochrome oxidase-negative fibres, and ragged red appearing fibres that, although rare (about 1%) were above the expected number in a 38 years old man. Immunostaining for dystrophin, sarcoglycans, caveolin 3, and alpha-dystroglycan, was normal, as well as dysferlin and calpain 3 immunoblotting. Respiratory chain activity and mitochondrial DNA analysis by Southern blot were normal.
By next generation sequencing analysis, a heterozygous G > A transition (c.G2453A) in exon 20 of the TNPO3 gene was found (reported in exon 21 in the original paper) []. The G > A point mutation changes the arginine in position 818 with a glutamine in a highly conserved residue, predicted to be damaging by all the used bioinformatic tools. This mutation is now listed in dbSNP (rs587777431) and it is present in gnomAD (The Genome Aggregation Database) with a population frequency of 0.00004215. This variant was not found in the two healthy sisters.
After publication of the original report [], we extensively reassessed muscle biopsy, clinical features and radiologic findings in the patient and performed transfection studies to characterize the mutation.
On his last visit, at age 54, the patient showed a severe waddling gait and was able to walk only with assistance of the caregiver. The patient needed a wheelchair for longer distances. He also required assistance for dressing, bathing and getting up from the chair. Neurological examination showed mild cranial nerve involvement, including tongue weakness, eyelid ptosis and minimal ophthalmoparesis in the lateral gaze. Bilateral elbow joint laxity and left Achilles’ tendon retraction were observed. Beevor’s sign (upward movement of the umbilicus on flexing the neck in supine position) was present. Assessment of muscle strength showed weakness of neck extensors (3/5) and flexors (4/5), arm flexion and abduction, both possible until 20–30° and without scapular winging, inferior trapezius (1/5), elbow flexors and extensors (2/5), finger flexors and extensors (4/5), hip flexors, adductors, extensors and abductors (1/5), knee extensors (right: 1/5; left: 2/5), dorsal foot extensors, especially tibialis anterior (left: 3/5; right: 4/5). Functional ability of upper and lower limbs according to Brooke and Vignos scales [, ] was 4 and 6, respectively. Lower limb muscle MRI at 54 years revealed an almost complete and symmetrical fatty substitution of thigh muscles, with relative sparing of gracilis and rectus femoris (Fig. ); medial and lateral gastrocnemius and, to a lesser extent, tibialis anterior and soleus, were the most involved muscles in the legs (Fig. ). Pulmonary function tests showed a moderate decline of forced vital capacity (60% of predicted value); nocturnal saturimetry was normal. No cardiac involvement was detected.
Reassessment of morphology on a second muscle biopsy of the right quadriceps, taken at the Ospedale Maggiore Policlinico of Milano at age 40, showed no overall progression of histopathological features compared to the biopsy at age 38 years. These included the presence of ragged red and COX-negative/SDH-positive fibres (Fig. ) (about 1% as in the first biopsy), and of degenerating fibres. Electron microscopy confirmed the presence of non-specific degenerative aspects, and showed small areas of myofibrillar disorganization in a few fibres, cytoplasmic bodies in the subsarcolemmal region of two fibres, mitochondrial abnormalities in several fibres (Fig. ), but no clear rimmed vacuoles or nuclear alterations. Mitochondrial abnormalities consisted of increased number and size of these organelles that appeared often as gigantic and contained densely packed cristae, paracrystalline inclusions or dark homogeneous inclusions (Fig. ).
Western blot analysis of muscle homogenate using antibodies against transportin 3 showed that the band corresponding to the protein was of greatly reduced intensity in the patient compared to a control subject (Fig. ).
A Real Time PCR assay, carried out to quantify transcript levels of TNPO3 in the patient, revealed a reduction of more than 50% in the patient mRNA compared to controls (Fig. ).
By immunohistochemistry, transportin 3 localized normally at the muscle fibre nuclei, and myofibrillar desmin- or myotilin-positive aggregates typical of myofibrillar myopathies, were not observed (Fig. ). Immunohistochemical evaluation of autophagy using antibodies against EEA1 (early endosome antigen), LC3 (microtubule-associated protein 1 light chain 3), LAMP2 (marker of lysosomes and late endosomes), P62 (Sequestosome-1), FK2 (ubiquitinylated proteins), and BAG3 (BCL associated athanogene-3) failed to show autophagy activation (not shown). Transfection of COS7 cells with a mutant TNPO3 cDNA containing the exon 20 G > A transition, or with the wild-type TNPO3 cDNA showed correct localization to the nucleus of both mutant and wild-type transportin 3 (Fig. ). Immunostaining of transfected cells with anti-p62 or anti-LC3 failed to show any difference between wild-type and mutant TNPO3-transfected cells. |
pmc-6299545-1 | A 42-year-old male patient with a 21-year cardiac medical history presented at our emergency department in 2001. His symptoms worsened in the days preceding the surgical intervention. Upon examination, he was heavily dyspneic, with severe palpitations, worsening chest discomfort, coughing and haemoptysis.
Since 1983, on numerous occasions he was advised to undergo cardiac surgery to alleviate his symptoms; however, the patient was unable to decide on surgery.
Transthoracic echocardiography (TTE) revealed a Giant Left Atrium (GLA), dilated cardiomyopathy, prominent right atrial protrusion, and hemodynamically significant mitral and tricuspid regurgitation (Table ). Computed tomography showed mid-oesophageal and bilateral pulmonary compression from the left atrium combined with congenital bilateral bullous emphysema – specific for congenital lung cystic emphysema. Cardiac autotransplantation and surgical remodelling were successful (Table ).
Nevertheless, the patient experienced several respiratory complications related to the underlying congenital disease. Also, he experienced thrombocytopenia and excessive bleeding during the postoperative course.
Severe bacterial pneumonia and recurrent pneumothorax further complicated the clinical condition. The patient required prolonged ventilation support and surgical tracheostomy.
His condition further deteriorated in the following months. Our examinations revealed severe mesenteric ischemia with the involvement of the ileum at day 190; This complication was finale fatal after 202 days. |
pmc-6299545-2 | We hospitalised a 65-years-old man, in 2003, complaining of fatigue, dyspnoea, heart palpitations, hepatomegaly and peripheral oedema. TTE revealed severe mitral and tricuspid regurgitation resulting from myxomatous degeneration of both valves, with significant atrial cardiomegaly (Table ).
The postoperative course was uneventful. Due to progressive rheumatic disease, 4 years after the surgical procedure the patient developed high-grade atrioventricular block for which a single chamber pacemaker was implanted; no other cardiac abnormalities were detected since then.
The patient succumbed to an acute septic shock, as a consequence of a neglected right lateral incarcerated inguinoscrotal hernia, after 10 years and 5 months. |
pmc-6299545-3 | A 65-years-old woman was referred to our hospital, in 2004, with severe mitral valve stenosis that manifested with severe chest pain, fatigue, dyspnoea, hepatomegaly and peripheral oedema. Her symptoms started 8 years before her hospitalisation.
She had an episode of rheumatic fever when she was 10 years old and had undergone a left nephrectomy.
TTE indicated severe mitral stenosis with severely enlarged left atrium (Table ). Mitral valve replacement, reconstruction of the tricuspid valve and surgical remodelling of the left atrium was performed on the explanted heart. The patient recovered swiftly in the absence of postoperative complications.
The patient experienced a symptom-free postoperative course until 2016 when she complained about significant chest pain. Magnetic resonance imaging detected bone metastasis; the patient refused further medical care and passed away, presumably from cancer, mid-2017. |
pmc-6299545-4 | We hospitalised a 64-year-old woman due to palpitations, fatigue, dyspnoea, and giddiness. TTE revealed severe mitral and tricuspid regurgitation (Table ) - due to myxomatous degeneration - with bi-atrial enlargement. X-ray analysis indicated a significantly enlarged left atrium. Subsequent confirmed the case of GLA, indicated by a distorted cardiac silhouette and a cardiothoracic ratio of 0.8 (Fig. a). Given the high degree of right lateral protrusion and LA dimensions, we opted for cardiac autotransplantation (Fig. ) in order to perform mitral valve replacement, tricuspid valvuloplasty and reductive atrioplasty. The Intrahospital postoperative course was uneventful. Several check-ups at our outpatient clinic during the first postoperative year confirmed her improved clinical condition, improving cardiac silhouette, a better cardiothoracic ratio of 0.6 (Fig. ) and a normalised left atrial area of 23 cm2 (Fig. a). We noted only low-grade residual mitral insufficiency and AF that is successfully managed using anti-coagulation medication and conventional medical treatment. |
pmc-6299646-1 | A 63-year-old man visited our hospital’s outpatient clinic on August 1, 2016, reporting a month-long loss of vision in his left eye; he was admitted with the tentative diagnosis of uveitis. He had been treated at another hospital a month earlier with no improvement, and his vision continued to deteriorate. As for the patient’s medical history, he had surgery for esophageal cancer 2 months earlier. The results of the eye examination were as follows: his visual acuity was only light perception in the left eye, respectively. In the left eye, we observed a transparent cornea, mild aqueous flare, partial posterior synechia, nondilating pupil, and pigment deposits on the anterior lens capsule (Fig. a). In addition, the part of lens behind the pupil was highly turbid, and the fundus could not be seen. B-scan ultrasonography showed pronounced vitreous opacities and macular retinal thickening in the left eye (Fig. b). On August 3, 2016, under local anesthesia, the patient underwent cataract surgery (by phacoemulsification) in the left eye combined with 25-gauge vitrectomy and silicone oil tamponade. During the surgery, we noticed vitreous opacities that looked like floccose white balls as well as flocculent vitreous opacities; part of the vitreous was therefore aspirated for bacterial and fungal culture. After the turbid vitreous body was removed, we observed a flat retina and a many beaded or yeast-like white plaques and spots in retina. We also found that the ciliary body was coated with a white film-like substance (Fig. c). So, a pus sample was collected from his vitreous body for routine microbial cultivation. After incubation for 24 h, cream white colonies without hemolytic reaction were detected. Gram staining showed the presence of Gram-positive spore morphology clusters. The strain was identified with YST card by Vitek 2 Compact system (bioMérieux, USA) as Candida albicans. In addition, antibiotic susceptibility tests were determined using the ATB™ fungns 3 kit (bioMérieux, USA), and the strain was found to be susceptible to fluconazole, itraconazole, amphotericin B, voriconazole, and 5-fluorocytosine. At the meantime, we had collected a sample for blood culture; after two days, the patient refused to collect another blood samples for culture again. So it’s very regret that we couldn’t obtained a positive result for blood culture. Subsequently the patient received antifungal treatment via an intravenous infusion comprising 0.1 g of fluconazole once daily for 3 days followed by the oral administration of 100 mg of itraconazole once daily for 1 month. At 3-month follow-up, the unaided visual acuity of left eye was 0.02 and corrected visual acuity was 0.2. The color fundus photograph showed that the vitreous cavity of the left eye was filled with silicone oil, the retina was flat, and there were no white exudates in retina (Fig. d). These results indicated a good recovery. In addition, there was no recurrence of the endophthalmitis within 1 year of the surgery. |
pmc-6299653-1 | A 40-year-old woman, 90 kg, was admitted to the Intensive Care Unit of University of Campania “L. Vanvitelli” from an outlying hospital because of an intubation-related tracheal lesion. The intubation has been necessary for the removal of right vocal cord using direct suspension microlaringoscopy (SDML) with CO2 laser. The patient showed severe subcutaneous emphysema extended from the chest up to the neck and head. She was affected by dyspnea, with 50% inspired oxygen through the Venturi mask. Blood pressure (BP) was 150/95 mmHg, mean arterial pressure (MAP) 113 mmHg, heart rate (HR) was 120 bpm, and peripheral oxygen saturation (SpO2) was 93%. The neck and chest CT (computerized axial tomography) scan showed “a 4-cm length lesion into the right posterolateral wall of the trachea in correspondence with the fourth dorsal vertebra, about 37 mm from carena; pneumomediastinum; diffuse signs of subcutaneous and perimuscular emphysema were visible, from the chest till to the neck to the head; and normal expansion of lung areas.” (Fig. ). The patient was, immediately, carried to the operating theater for a diagnostic bronchoscopy and for the endoscopic suture with fibrin glue. We decided to manage the airway using an LMA positioned in deep sedation. Sedation was induced using propofol 4 mg/kg/h and fentanyl 1 μg/kg. We also administered 0.5 mg/kg of intravenous lidocaine to blunt laryngeal reflexes. We conducted the anesthesia by mean of spontaneous breathing with oxygen supplement throughout manual breathing circuit. The patient was placed in extended neck position. The blood pressure monitoring was executed by left radial artery catheterization and pulse oximetry on the other side. Heart rate and end expiratory CO2 (ETCO2) were also monitored. The flexible bronchoscope was introduced through the LMA (Fig. ). Intraoperative monitoring: the thoracic surgeon first of all confirmed the tracheal lesion and then sutured it with 6 ml of fibrin glue. The procedure lasted about 30 min. During the procedure, all the hemodynamic parameters were stable. At the end, the patient was awakened in the operating room and moved to the Intensive Care Unit spontaneously breathing with 50% inspired oxygen through the Venturi mask. Forty-eight hours after the surgery, a chest and neck CT scan was made. It showed the resolution of pneumomediastinum and subcutaneous emphysema, and so the patient was transferred to the thoracic surgery ward and 72 h after the surgery she was discharged. She came back 15 days after the surgery and for a diagnostic flexible bronchoscopy that showed a complete resolution of the tracheal rupture. |
pmc-6299653-2 | A 53-year-old woman, 125 kg weight, 175 cm tall, body mass index (BMI) 40.8 kg/m2, was admitted to the Intensive Care Unit of University of Campania “L. Vanvitelli” from a nearby hospital because of an iatrogenic intubation-related tracheal lesion. The intubation has been necessary in order to perform anesthesia for a laparoscopic sleeve gastrectomy. The patient was affected also by hypertension and hypercholesterolemia. She arrived with an orotracheal tube (size 7.0 mm reinforced) and in assisted ventilation through manual breathing circuit. She presented a severe subcutaneous emphysema from the chest till to the neck to the head. The hemodynamic parameters were not too stable (BP 180/100 mmHg, MAP 127 mmHg, HR 130 bpm, SpO2 97%). A diagnostic fibrobronchoscopy was immediately performed. It showed a 2-cm lesion of pars membranacea in subglottic region. During fibrobronchoscopy, the orotracheal tube was changed with a 6.0-mm-size tube, positioned distally the lesion and before the carena. A chest radiograph was made, and pneumomediastinum and subcutaneous emphysema were confirmed. The patient was thus carried to the operating room. We decided to anesthetize the patient with propofol 6 mg/kg/h and fentanyl 2 μg/kg. We also administered 0.5 mg/kg of intravenous lidocaine to blunt laryngeal reflexes. The neuromuscular blockage was achieved with rocuronium bromide 0.6 mg/kg. During the procedure, protective mechanical ventilation was set up (tidal volume 6 ml/kg, positive end expiratory pressure (Peep) 5 mmHg, FiO2 50% respiratory rate 15). The patient was placed in extended neck position. The blood pressure monitoring was done by left radial artery catheterization and pulse oximetry on the other side. Heart rate and ETCO2 were also monitored. The flexible bronchoscope was introduced next to the lesion and before the tube cuff. The thoracic surgeon first of all confirmed the tracheal lesion, and then, he sutured it with 5 ml of fibrin glue. At the end of the surgery, the patient was awakened and extubated and then she was carried to the Intensive Care Unit for postoperative monitoring in spontaneous breathing with 50% inspired oxygen through the Venturi mask. Forty-eight hours after the surgery, esophageal X-ray was taken to exclude an esophageal lesion and to check the sleeve gastrectomy and eventually the nasogastric tube was removed. Seventy-two hours after the surgery, there was a notable reduction of subcutaneous emphysema and good hemodynamics. Consequently, the patient was moved to the thoracic surgery ward. |
pmc-6299653-3 | A 63-year-old woman, weighing 60 kg, 165 cm tall, with BMI of 22 kg/m2 was admitted to the Intensive Care Unit of University of Campania “L. Vanvitelli” from a regional hospital because of an iatrogenic tracheal lesion probably due to the removal of a neoplasm that was involving the epiglottis and vocal cords. At the end of the surgery, during the patient’s awakening, hemoptysis showed up with dyspnea and a fibrobronchoscopy had to be made that showed a lesion on the right bronchus. Excluding the right lung, a double-lumen tube (Robertshaw 37F) was positioned in order to reduce the air leak and protect the airway from bleeding and then the patient was carried to the Intensive Care Unit of University of Campania “L. Vanvitelli”. The patient was suffering from hypertension. She was affected by subcutaneous emphysema from the chest to the neck and the head; thus, a right chest drainage was positioned because of pneumothorax. The blood gas analysis showed respiratory acidosis with hypoxia (partial pressure of oxygen (PaO2) 75 mmHg) and hypercapnia (partial pressure of carbon dioxide (PCO2) 60 mmHg). The patient was connected to a mechanical ventilator (FiO2 65%, Peep 5, tidal volume 4 ml/kg, inspiratory/expiratory ratio 1/2.5). A flexible fibrobronchoscopy was taken that showed a lesion of the right bronchus 4 cm distal the carena. A chest X-ray demonstrated emphysema of the chest wall and neck, pneumomediastinum, and bilateral pleural effusion. The patient was transferred to the operating room in order to proceed with the operative bronchoscopy. We decided to manage the airway by removing the double-lumen tube and positioning a small size single lumen tube (5.5) into the left bronchus in anesthesia with propofol 6 mg/kg/h and fentanyl 2 μg/kg. The neuromuscular blockage was achieved by rocuronium bromide 0.6 mg/kg. We also administered 0.5 mg/kg of intravenous lidocaine to blunt laryngeal reflexes. During the procedure, the mechanical ventilation was started (tidal volume 4 ml/kg, Peep 5, FiO2 50%, respiratory rate 18). The flexible bronchoscope was introduced beside the orotracheal tube next to the lesion, and the thoracic surgeon sutured the bronchus lesion with 5 ml of fibrin glue. After the surgery, the patient was carried to the intensive care unit without changing either the tube or the mechanical ventilation (tidal volume 4 ml/kg, Peep 5 mmHg, FiO2 50%, respiratory rate 18). Twelve hours after the surgery, a consultation with an otolaryngologist was asked for and a flexible videolaryngoscopy was taken which both confirmed edema and hyperemia of the larynx, glottis, and subglottic region. The extubation was not considered safe, the single-lung ventilation was no longer acceptable, and the normal double-lung ventilation could be detrimental to the bronchus suture. So we decided to practice a percutaneous tracheostomy (single-dilator percutaneous tracheostomy Ciaglia techniques), and at the end of the procedure, the mechanical ventilatory weaning both in analgosedation with remifentanil and in assisted ventilation (Peep 0, pressure support 8, FiO2 0, 45 tidal volume 500, respiratory rate 16) was carried out. Twenty-four hours after the surgery, the patient was freed from mechanical ventilation and put in spontaneous breathing by tracheostomy with oxygen supplement 5 l/min. Ninety-six hours after the surgery, there was a notable reduction of subcutaneous emphysema and good hemodynamics and so the patient was moved to the thoracic surgery ward. Eighteen days after the surgery, a new consultation with the otolaryngologist and a flexible videolaryngoscopy were carried out that showed the complete resolution of edema; hyperemia of the larynx, glottis, and subglottic region; and normal mobilization of the vocal cords and so the tracheostomy tube was removed, and the day after, the patient was discharged from the hospital. |
pmc-6299987-1 | A 32-year-old female with non-diabetic chronic kidney disease was on regular hemodialysis for 3 years, via a right forearm arteriovenous fistula. The patient was admitted to our department due to involuntary movement for 5 days. Starting 5 days prior to admission, the patient’s shoulder and neck displayed a resting tremor, which became increasingly severe, with the limbs beginning to move uncontrollably. The patient’s vital signs were stable, with no complaints of headache, fever, blurred vision or mental disorder. Myodynamic examination and deep tendon reflexes in both legs were normal, and the Babinski reflexes were suspiciously positive. Significant fluctuation of blood creatinine levels (predominantly due to inadequate dialysis), along with altered hyperthyroidism [intact parathyroid hormone (iPTH) levels of almost 3200 pg/mL], were reported 1 week ago with no accompanying history of hypertension, DM, respiratory tract infection, fever, stoke, liver disease, hypoxia or toxic fume exposure. Brain magnetic resonance imaging (MRI) was performed 5 days after the onset of symptoms in the local hospital, and showed symmetrical T2-weighted imaging (T2WI; Fig. ) and T2/fluid-attenuated inversion recovery (T2FLAIR; Fig. ) hyperintense non-hemorrhagic lesions in bilateral basal ganglia, as well as corona radiata lesions showing mild diffusion restriction. Both T1-weighted imaging (T1WI) and diffusion-weighted images (DWI) were normal.
Blood analysis immediately after admission revealed high levels of uremic toxins (urea nitrogen 25.80 mmol/L, serum creatinine 1206 μmol/L, uric acid 548 μmol/L, phosphorus 1.88 mmol/L, calcium 2.33 mmol/L,anion gap 23.9 mmol/L), and severe hyperthyroidism (iPTH 2487 pg/mL). Bicarbonate, arterial blood gas indices, hemoglobin, albumin, lactic acid, B-vitamins and liver function were all normal.
The patient was diagnosed with UE as a symptom of bilateral basal ganglia lesions. She did not suffer from DM or other diseases such as cerebrovascular events, intoxication or hyperlactacidemia. Thus, UE was possibly due to a combined effect of uremic toxins and hyperthyroidism. The patient was treated with high frequency and high flux dialysis (4 h hemodiafiltration with APS 15 uc dialyzer, 4 times per week), hyperbaric oxygen therapy (1.5 h per day), declining parathyroid hormone (1 μg of calcitriol injection every 2 days), and treatment for symptom relief (2 mg of haloperidol, 2 mg of clonazepam and 2 mg of benzhexol administered orally twice per day). Gradually, the symptoms reduced in frequency, and the amplitude of involuntary movement decreased. Fourteen days after admission, a subsequent brain MRI revealed high signal in the bilateral basal ganglia on T2WI (Fig. ) and T2FLAIR (Fig. ), which were significantly weaker compared to the initial MRI signal.
About 1 month later, the patient achieved complete remission and restoration of normal body movement, and was discharged. Upon discharge, blood test results showed relatively stable uremic toxins (urea nitrogen 10.48 mmol/L, serum creatinine 641.5 μmol/L, uric acid 435 μmol/L, phosphorus 1.43 mmol/L, calcium 2.30 mmol/L,anion gap 15.9 mmol/L), and relieved hyperthyroidism (iPTH 1609 pg/mL). Brain MRI was performed again upon follow-up, with T2WI (Fig. ) and T2FLAIR (Fig. ) showing an almost complete resolution of the lesions with slightly hyperintense signal in the bilateral basal ganglia. |
pmc-6299998-1 | A 34-year-old male presented to the THP on 11th May 2017 with a 3-day history of fever, arthralgia, backache, headache and skin flush. He had no cough, abdominal pain or diarrhoea. On admission, he was ill looking and had postural giddiness and cold peripheries. Blood pressure was 80/50 mmHg and pulse rate was 98 beats/min. Resuscitation was attempted with rapid infusion of 500 ml of normal saline followed by continuation normal saline infusion. His blood pressure (BP) picked up to 100/70 mmHg, but he remained oliguric over the next 12 h. Dextran 40 colloid 500 ml bolus infusion was given to raise the BP and to produce more urine. Twelve hours later, he developed generalized convulsions and needed immediate intubation and assisted ventilation in the Intensive Care Unit (ICU). Chest radiograph showed bilateral lung shadows suggestive of pulmonary oedema. Other investigations are shown in Table . In the ICU, at 3 PM, BP was 130/80 mmHg and pulse rate was 130 beats/min. However, at 3.30 PM, pulse rate was 160 beats /min, and BP dropped to 97/53 mmHg. The patient had central cyanosis, cold peripheries, feeble peripheral pulses and the haematocrit (HCT) rose to 55% requiring more Dextran 40 infusion.
On morning of the fifth day at 5 AM, HCT and haemoglobin dropped to 28% and 9 g/dl respectively without any obvious bleeding. With transfusion of one unit of blood, BP rose to 130/95 mmHg. With further transfusion HCT and urine output improved. Two dimensional echocardiogram showed global left ventricular hypokinesia with an ejection fraction of 40%. Cardiac troponintitre was high. From noon, the BP was falling - 80/50 mmHg and tachycardia persisted that needed continuous inotrope infusion. Despite meticulous management, the patient developed cardiac arrest and resuscitation failed. |
pmc-6299998-2 | A 36-year-old male suffering from type 2 diabetes for 3 years was transferred to the Teaching Hospital, Kandy on the 15th July, 2017 with a 3-day history of fever and arthralgia.On admission he was febrile and BP was 130/80 and pulse rate was 90 beats per min. Lungs were clear and abdomen was soft with no hepatomegaly. Initial investigations revealed WBC of 3 × 109/l, platelets of 63 × 109/l and HCT of 45%. On day 1 of admission, his basic clinical parameters were normal and urine output was adequate throughout the day. On the next day, ultrasound scan examination of abdomen showed evidence of early plasma leaking, thus initiating critical phase monitoring from 9 am on 16th July. At this point his BP was 100/70 mmHg and HCT was 45%. His WBC was 3.7 × 109/l, platelet count was 34 × 109/l. His alanine transaminase (ALT) and aspartate transaminase (AST) were 383 U/l and 463 U/l respectively.
From the onset of the critical phase, the patient had tachycardia which persisted. He had satisfactory urine output initially, but his HCT continued to increase. At about 7 pm, a Dextran-40 colloid 500 ml bolus was given, but at midnight the urine output started dropping to a level of 35 ml/h. Thus, another bolus of 250 ml of dextran-40 was given. Meanwhile, the patient developed melaena, and 500 ml of whole blood was transfused. As the patient developed lactic acidosis, sodium bicarbonate infusion was given.
The patient was transferred to the ICU, Teaching hospital, Peradeniya (THP) at 3 am of 17th July while managing the critical phase into the 18th hour. On admission, blood pressure was 125/91 mmHg which rapidly dropped to 100/80 mmHg and the peripheries were cold to touch. The patient was conscious and rational. The urine output dropped to 20 ml/h. Pulse rate remained at 140 beats/min. Auscultation of the lungs revealed reduced breath sounds with fine crepitations in both lungs. Melaena was present on rectal examination. Arterial blood gasses showed lactic acidosis. Ultrasound examination of abdomen showed a significant amount of ascites. The patient was given two 250 ml boluses of dextran-40. The investigations are shown in Table . By about 7 AM, the patient became anuric with BP of 99/65 mmHg and HCT was 50%. The patient was transfused with 3 units of blood within the next 2 h but he remained anuric. By 9 AM, the patient was confused and disoriented and had cold peripheries with sluggish capillary refilling. He was intubated and ventilated electively. At 1.20 pm the patient developed bradycardia followed by cardiac arrest and resuscitation was unsuccessful. |
pmc-6299998-3 | A 40-year-old female with a history of bronchial asthma for 17 years, presented to the THP with fever of 3 days duration associated with vomiting and postural giddiness on 22nd July 2017. On admission, pulse rate was 108 beats /min and blood pressure was unrecordable. Ultrasound scan of the abdomen showed evidence of fluid leaking. The onset of critical phase was calculated 8 h backward and prompt resuscitation was attempted. Despite fluid resuscitation tachycardia persisted with reduced urine output. On admission her ALT was 1365 U/l and AST was 2999 U/l. Serum albumin was 30.8 mg/dl and serum creatinine was 84 μmol/l. Her INR was 1.38. Serum amylase was 37 U/L.
On the evening of the same day she complained of abdominal pain with tenderness of the right hypochondrium. She passed melaena stools. She had tachypnoea and blood gasses revealed acidosis. A small right sided pleural effusion was also present. She was transfused with one unit of whole blood. By the next morning her abdominal pain and postural symptoms increased and she developed mild icterus. She had tachycardia, but the blood pressure was maintained and urine output was satisfactory. She then developed ascites and bilateral pleural effusions. The next AST was 3661 U/l and ALT was 1579 U/l. By the evening her oxygen saturation dropped despite administering 100% oxygen. Subsequent AST and ALT were 8543 U/l and 2981 U/l respectively. The serum amylase was 48 U/l and serum creatinine was 105 μmol/l.
Towards the latter part of the critical phase the HCT started falling and the urine output declined to 25 ml/h. Several units of blood, FFP, and human albumin were infused to maintain the HCT. The patient rapidly developed difficulty in breathing with bilateral moderate pleural effusions. However, her AST and ALT levels reduced to 3661 U/l and 2685 U/l. On 24th July, the critical phase monitoring was over, but the patient gradually became confused and disoriented. She had high fever and oral bleeding but her other vital parameters and urine output were satisfactory. There were crepitations all over the lung fields and she needed assisted ventilation in the ICU. She died on the 2nd day in the ICU. |
pmc-6300016-1 | A 10-year-old girl was admitted to the orthopaedic surgery department for further assessment of a pain localized in the posterior part of the right hemithorax. According to the physical examination, there was no evidence of a palpable chest wall mass, but the patient reported worsening of symptoms during palpation. Skin and subcutaneous tissue showed no swelling or discoloration. Laboratory values, including serum levels of tumour markers, were all within the normal reference ranges. The initial chest X-ray performed in another institution has been lost. We opted for MRI instead of the CT as the next diagnostic procedure in order to avoid additional exposure of the young patient to ionizing radiation.
Magnetic resonance imaging (MRI) of the thorax revealed a spherical, lobulated tumour, located in the posterior arch of the right fourth rib and the adjacent chest wall, 10 mm from its costovertebral junction. The lesion measured 30 × 50 × 20 mm in all three diameters and showed heterogeneous signal intensity. It was mostly hyperintense relative to the muscle on non-contrast T1-weighted (T1W) fast spin echo (FSE) images (Fig. a), with prominent postcontrast enhancement on T1-weighted (T1W) fast spin echo (FSE) images (Fig. b) and hyperintense on T2W-weighted fat-suppressed (T2W FS) images (Fig. c, d). Compression of the adjacent lung parenchyma and thickening of the adjacent pleura was observed as the tumour showed endogenous growth but without signs of lung parenchyma invasion. Vascularization was observed as two vessel branches, 2.5 mm in diameter, arising from the intercostal blood vessels, while the clarity of another feeding branch from the thoracic aorta was limited and only suspected (Fig. d). In Fig. (a - d), branching feeding vessels are noted in the center of the lesion. This observation was suggestive of an apparently vascular tumour mass with three feeding arteries but can also be interpreted as distended vascular structure. Those structures are optimally presented in contrast-enhanced T1W in the coronal plane, however, contrast-enhanced T1W was in this case performed only in the axial plane.
The patient underwent a surgical biopsy. After an opening of the cortical layer, abnormal bleeding from the rib was seen. Macroscopically, the tumour lesion corresponded to an aneurysmal bone cyst. A specimen was collected, and the material sent for histopathological analysis (Fig. ). Pathohistological analysis of the tumuor has revealed its numerous blood vessels with a thick wall of smooth muscle layers and partially irregular lumina. Atypical or mitotic smooth muscle cells were not detected. Foci of adipose metaplasia were present in between the blood vessels. The smooth muscle antigen (SMA) immunoreactivity was observed for proliferating perivascular smooth muscle cells and the muscular wall of thick blood vessels, whereas endothelial cells were CD34 positive. These observations were sufficient to establish the diagnosis of intraosseous angioleiomyoma – venous type.
Following the histopathologic diagnosis, selective arteriography was performed in order to plan adequate surgical treatment. The right femoral artery was the route and contrast agent was injected into three catheter tip positions: the ascending aorta, brachiocephalic trunk and descending aorta, in order to visualize all the potential feeding vessels. Non-homogeneous tumour enhancement was obtained only after contrast agent application in the ascending aorta. The three feeding arteries were also visualized – two of them were proximal and very thin, less than 1 mm in diameter, while the distal artery was 2.2 mm in diameter (Fig. e). Embolization and surgery were finalized through resection and confirmation on histopathology. |
pmc-6300024-1 | A 16 years old male, who was diagnosed as celiac disease by family screening. Anti TTG levels were 89 Ru/ml (normal: up to 20) with normal total IgA (without any gastrointestinal symptom). Upper endoscopy was done and nodularity in bulb and second part of duodenum was observed (biopsy was obtained). Pathological examination showed marsh 3a. Laboratory tests also showed low levels of 1, 25(OH) D3 < 8, Hb: 12.4 g/dL, AST: 31 U/L, ALT: 15 U/L, ALP: 905 U/L, TSH: 1.9 mIU/L, Anti TPO: 24 IU/Ml, calcium: 10 mg/dl, and phosphore: 6.8. In his genetic study DQ2 was positive and DQ8 was negative. His TTG levels approached to the near normal levels of TTG (27 Ru/ml) after 2 years of gluten free diet (GFD). He started to have a regular diet arbitrarily and anti TTG levels got back to 110 Ru/ml without any symptom of gastrointestinal problem. After one more year of regular diet, he referred with chief complains of weight loss (about 10 kg), polyuria, and polydipsia. Blood sugar was 570 and he admitted to the hospital with an insulin therapy. He started the GFD and regular and long acting insulin to decrease blood sugar. He had no familial history of diabetes. After about 3 months, he had episode of hypoglycemia and we started dose reduction of insulin in 1 month. Finally, his FBS got back to the normal level by low dose of insulin (anti TTG level was 56 Ru/ml). Two months after GFD, we stopping insulin and after 2 months of follow up he still had normal FBS: 99 and HbA1C was 7%, but level of anti-islet cell was 7.3 IU/ml and glutamic acid decarboxylase was 200 IU/ml. He started to have gluten few times a week after about 4 months and TTG raised, and again he got symptomatic T1D. Now he is on insulin for control of FBS even with strict GFD and his Hb A1C is 7.7. |
pmc-6300024-2 | Sister of first case who was 14 years old female, had been referred with chief complains of dyspepsia, anemia, and oral aphtha. Level of anti TTG was 274 RU/ml with a normal total IgA. Endoscopy with duodenal biopsy was also done for this case and there was scalloping and fissuring in bulb and second part of duodenum. Duodenal biopsy was obtained and pathological tests showed marsh 3c. Other laboratory tests also showed Hg: 8.8, SGOT: 18 U/L, SGPT: 15 U/L, ALP: 308 u/l, 1, 25(OH) D3: 4 ng/mL, Ca: 9.8 mg/dl, TPO: 69 IU/ml, and normal TSH level. DQ2 was positive and DQ8 was negative. She had low levels of selenium (80 μg/L) and zinc was normal (899 μg/L). She started a gluten free diet and levels of TTG dropped to 50 Ru/ml. HCT was 35.7% and her symptoms were getting much better without any abdominal pain. After 2 years, she started on regular diet arbitrarily and after 1 year she referred to the clinician by chief complains of weight loss and tremor. In her laboratory tests, anti TTG level was more than 200 Ru/ml, TSH < 0.005, T3: 360 ng/ml, T4: 16.4 mμg/dl. After 4 months of GFD her symptoms got better and TSH get back to normal and methymazol was tapered without any problem. After 1 year she is in GFD and low level of anti TTG and she is still on remission of hyperthyroidism without any treatment. |
pmc-6300031-1 | A 34-year-old woman presented with sudden onset of vertigo and vomiting on the first day of her menstruation. Brain diffusion weighted imaging (DWI) revealed newly occurring multiple infarctions in the right cerebellum and left temporal lobe (Fig. ). Magnetic resonance angiography (MRA) and carotid CT angiography (CTA) did not show any atherosclerotic changes. Transesophageal echocardiography (TEE) did not reveal any evidence of valvular vegetation. No evidence of arrhythmia was found by ambulatory electrocardiography. Transvaginal ultrasonography (TVS) showed adenomyosis (Fig. ). Laboratory investigations revealed elevated D-dimer (1050 μg/L; normal range, < 500 μg/L), CA125 (937.1 U/mL; normal range, < 35 U/mL) and CA19–9 levels (462.5 U/mL; normal range, < 37 U/mL). The hemoglobin level was 134 g/L. The D-dimer, CA125 and CA19–9 levels re-evaluated 1 week later were 440 μg/L, 122.9 U/mL and 38.5 U/mL, respectively. |
pmc-6300031-2 | A 37-year-old woman presented with sudden onset of weakness of her left limbs on the second day of her menstruation. DWI revealed newly occurring infarction in the right basal ganglia (Fig. ). Brain MRA, carotid CTA, TEE, and ambulatory electrocardiography were performed. There was no evidence of arteriosclerosis, cardiac diseases including valvular vegetation and arrhythmia. TVS showed adenomyosis. Laboratory investigations revealed elevated D-dimer (2340 μg/L; normal range, < 500 μg/L), CA125 (735.7 U/mL; normal range, < 35 U/mL) and CA19–9 levels (43.2 U/mL; normal range, < 37 U/mL). The hemoglobin level was 108 g/L. Other laboratory results were normal, including the protein C and protein S activities. Therefore, we re-evaluated the CA125 and CA19–9 levels 1 week later, which were 456.8 U/mL and 50.3 U/mL, respectively. |
pmc-6300031-3 | A 46-year-old woman developed left hemiplegia on the second day of menstruation. Brain DWI revealed multiple fresh infarcts in the right thalamus, occipital lobe, and bilateral frontal and parietal lobes (Fig. ). Brain MRA revealed stenosis of the right posterior cerebral artery (PCA) (Fig. ). The carotid CTA, TEE, and ambulatory electrocardiography findings were normal. Positron emission tomography (PET)/CT showed no malignancies. Pelvic MRI showed an inhomogenenous mass in the uterus (Fig. ), suggesting of adenomyosis. This was comfirmed by histopathological study when hysterectomy was performed five months later. Laboratory investigations revealed elevated D-dimer (12,040 μg/L; normal range, < 500 μg/L), CA125 (546.5 U/mL; normal range, < 35 U/mL) and CA19–9 levels (1076.6 U/mL; normal range, < 37 U/mL). The hemoglobin level was 121 g/L. The levels of D-dimer, CA19–9, and CA125 re-evaluated 1 week later were 2200 μg/L, 213.7 U/mL, and 193.9 U/mL, respectively. After hysterectomy, the levels of D-dimer, CA19–9, and CA125 returned to within normal ranges, and no infarction recurred. |
pmc-6300032-1 | In July 2017, a 54-year-old male was hospitalised for the recent appearance of multiple purpuric spots on the legs associated with gum bleeding. The patient was an HIV-negative man having sex with men, receiving HIV pre-exposure prophylaxis with tenofovir/emtricitabine for over a year. His medical history was significant for a primary syphilis in 2014 and multiple episodes of urethritis in the recent years. He reported frequent unprotected anal sex, with occasional bleeding, insertive and receiving fisting without gloves, and the use of nasal mephedrone during sexual encounters. He was previously diagnosed with an acute genotype 4 HCV infection in 2011 (Versant HCV genotype 2.0 assay (LiPA), Siemens Healthineers, Erlangen, Germany), cured following a 6-month course of pegylated interferon (IFN) and ribavirin. Acute genotype 1a HCV reinfection was diagnosed on 2017, June 26th (NS5A Sanger sequencing), while HCV-RNA was still negative on 2017, April 4th (Abbott RealTime HCV, Abbott, Molecular, Des Plaines, USA). The patient was asymptomatic at that time, platelet count was normal and HCV-RNA surveillance was scheduled, following the recommendations from the European AIDS clinical society [].
Initial physical examination found no other symptoms apart from a petechial purpura of the lower extremities and oral haemorrhagic blister. Blood pressure was 130/97 mmHg, heart rate 60 bpm with no fever, lymphadenopathy, or splenomegaly. There was no evidence of severe haemorrhage. Laboratory data at the admission are resumed in Table . Complete blood count found a severe thrombocytopenia (5 G/L) without any other cytopenia. Thrombocytopenia was confirmed on the peripheral blood smear which exhibited no morphological abnormalities and the absence of schistocytes. No other associated haemostasis abnormality was present (normal fibrinogen and factor V). Serum protein electrophoresis found no clonal gammopathy. Thyroid-stimulating hormone was normal. HIV serology was repeatedly negative and Hepatits B surface antibodies were detectable following a previous vaccination. At that time, mild elevation in aspartate transaminase (AST, 6 times the upper limit of normal (ULN)) and alanine transaminase (ALT, 7 x ULN) was found associated with a detectable HCV viral load of 4.9 log IU/mL (Fig. ). There was no evidence of other replicating viruses including cytomegalovirus, parvovirus B19, human herpes virus type 6 and type 8 (except a slight Epstein-Barr virus replication which was considered insignificant (348 UI/mL). Cryoglobulin investigation was negative. No circulating anti-platelet IgG antibodies were detected. A bone marrow aspiration was performed; normal cellularity with an increased number of megakaryocytes and normal erythropoiesis and myelopoiesis was found, thus confirming the diagnosis of ITP secondary to acute HCV infection.
An initial administration of intravenous immunoglobulin (IVIG; at the dose of 1 g/kg on day 1 and day 3) had clinical benefit (regression of gum bleeding and purpura), but did not have any effect on the platelet count which remained below 10G/L. A second administration of IVIG (1 g/kg daily for 2 days) combined with methylprednisolone (1 mg/kg daily) improved platelet count which reached 40G/L but a normal value was not attained (Fig. ). At which point it was decided after collegial discussion to start treating the infectious trigger. Pegylated IFN and ribavirin combination was contra-indicated because of severe thrombocytopenia, therefore a 12 weeks course of sofosbuvir-ledipasvir was indicated. At initiation of the treatment, the platelet count was 43 G/L and HCV viral load was 6.3 log IU/mL. At day 15 of antiviral treatment, HCV viral load was undetectable (< 12 IU/ml) and the platelet count had increased to 108 G/L allowing rapid tapering and discontinuation of corticosteroids before the end of antiviral therapy. HCV viral load remained undetectable until week 12 post-treatment, confirming HCV cure (Fig. ). Platelet count fully normalised 5 weeks following treatment initiation and remained within normal range thereafter. The patient went through his 12 weeks course of sofosbuvir-ledipasvir with a good tolerance, without any specific adverse event reported. |
pmc-6300093-1 | A 41-year-old man was referred to our hospital with a two-year history of a tumor in his right elbow. Physical examination confirmed a 75 × 51 × 15 cm mass localized on the medial aspect of the right elbow (). The range of motion (ROM) of the elbow was within normal limits. Plain radiographs revealed the shadow of a soft tissue mass, with no abnormal findings in the humerus, radius, and ulna. On T1-weighted magnetic resonance (MR) imaging (T1WI), the lesion showed mainly as an iso intensity. On T2-weighted MR imaging (T2WI) (), the lesion presented as a high intensity. On gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA)-enhanced T1WI, the lesion presented an inhomogeneous contrast enhancement (). Subsequent pathological examination of biopsy tissue confirmed a diagnosis of synovial sarcoma. After three courses of neoadjuvant chemotherapy, a wide tumor excision, with a 2-cm safety margin, defined on the basis of a brightness change of Gd-DTPA-enhanced T1WI, was performed, followed by reconstruction using an autograft treated with liquid nitrogen and a free ALT flap. The tumor was excised en bloc (), with the level of resection determined based on preoperative MR images. The following muscles were included in the resection: pronator teres, wrist and finger flexors, brachialis, anconeus, and part of the triceps brachii. The ulnar nerve was sacrificed out of necessity, but the median nerve was preserved by using ethanol as an adjuvant []. One third of the medial humerus and ulna were also resected using a bone saw. With the exception of the articular capsule attached to the humerus and the tendon of the triceps brachii with its insertion, all other soft tissues and the tumor were dissected from the bone sections (). The resected bone was then frozen in liquid nitrogen for 20 min, thawed in air at room temperature for 15 min and thawed in distilled water for 10 min, according to a previously published protocol (). The bones were then reconstructed in situ using locking plates (LCP Distal Humerus Plate, LCP Metaphyseal Plate 3.5: DePuy Synthes, Zuchwil, Switzerland), a headless compression screw (4.5 mm HCS: DePuy Synthes) and a cannulated cancellous screw (3.0 mm CCS: MEIRA, Japan). The tendon of the triceps brachii was repaired using a triclosan-coated polidioxanone suture (PDS® PLUS: Ethicon Inc., Somerville, NJ) (). An ALT musculocutaneous flap with a vastus lateralis muscle of appropriate size was harvested and the soft tissue defect at the elbow reconstructed. Arterial revascularization was performed end-to-end to the transected ulnar artery. Venous anastomosis was done end-to-end to the cephalic vein. The affected limb was elevated postoperatively and the elbow was immobilized for 14 days to obtain wound healing and to avoid the risk of flap failure. Subsequently, range of motion (ROM) exercise was initiated. Bone union was defined as trabecular bone continuity, which can be seen as filling of the host-graft junction gap []. Filling of the host-graft junction gap was observed 12 months after the operation.
At the 2-year follow-up, elbow ROM was −35° of extension and 130° flexion, and bone union was achieved (), with complete and stable coverage of the defect (). No local recurrence of the tumor was observed. |
pmc-6300093-2 | A 76-year-old woman visited her previous doctor with a six-month history of two tumors in her elbow. An excision biopsy was performed, with a diagnosis of fibrosarcoma confirmed through pathological examination. The patient was referred to our hospital for further assessment and treatment. On physical examination, two masses (2 × 2 cm in size) were identified on the lateral aspect of the right elbow (), with the scar of a previous surgery between the two masses. The ROM of the elbow was within normal limits. No abnormal findings were identified on plain radiographs. On Gd-DTPA-enhanced T1WI, contrast enhancement was observed in the tumors and the fascia and subcutaneous tissue surrounding the lesions, which was considered as residual tumor tissue (). The location of the skin incision and the level of resection were defined in the same manner as in Case 1. The tumor was excised en bloc (). Briefly, the wrist and finger extensor, supinator, anconeus, and triceps brachii were resected. One third of the lateral portion of the distal humerus and radial head were also resected using a bone saw. With the exception of the radial articular capsule attached to the humerus, the fascia of the wrist and finger extensor with its insertion and the tendon of the triceps brachii with its insertion, all other soft tissues and the tumor were dissected from the bone sections. The excised bone portion was frozen in liquid nitrogen in the same manner as in Case 1 () and then reconstructed in situ using a locking plate (LCP Distal Humerus Plate: DePuy Synthes) and headless compression screw (3.5 mm HCS: DePuy Synthes). The triceps brachii, augmented with the Leeds-Keio ligament, was reattached to the olecranon and the radial articular capsule was reattached to the radial notch using a suture anchor (Corkscrew, Mini Corkscrew: Arthrex, Naples, FL). The wrist and finger extensor were repaired by using a polyethylene terephthalate suture (ETHIBOND®: Ethicon Inc.) (). The soft tissue defect was reconstructed with a free, 27 × 18 cm, ALT flap (). Arterial revascularization was performed end-to-end to the deep brachial artery. Venous anastomosis was done end-to-end to the vena comitans of the deep brachial artery and the basilic vein. The affected limb was elevated postoperatively and the elbow was immobilized for 14 days. Subsequently, ROM exercise was initiated in the same manner as in Case 1. Filling of the host-graft junction gap was observed 7 months after the operation. At the 1-year follow-up, elbow ROM was −35° extension and 130° flexion. Bone union was achieved (), and a complete and stable coverage of the defect was obtained (). Local recurrence of the tumor was not detected. |
pmc-6300189-1 | This is a case of a 59-year-old morbidly obese female with situs inversus totalis who presented for a laparoscopic sleeve gastrectomy. Her BMI was 38 (height 4 ft 11.5 inches, weight 188.2 pounds), and she had a lifelong history of morbid obesity and obesity-related comorbidities, including obstructive sleep apnea requiring a continuous positive airway pressure machine, an elevated hemoglobin A1c (5.8) and a fasting blood glucose increasing her risk of developing diabetes mellitus, and degenerative joint disease which significantly impacted her ability to exercise. The main challenges she identified in losing weight involved eating carbohydrate rich foods, overeating during meals and limited activity due to musculoskeletal pain. The patient had made multiple attempts to lose weight through commercial dieting programs but had been unsuccessful. The patient also completed a six-month medically supervised diet through her primary care provider, which also included working closely with a bariatric registered dietician, following a strict diet of about 1800 calories/day and performing modified exercise, about 120 minutes/week. Despite these intense medical weight loss efforts, she was unable to maintain a healthy weight. The patient was motivated to try bariatric surgery after she witnessed the significant weight loss success her daughters had from this intervention. Her greatest hope from the bariatric surgery was to be healthier and to alleviate her obesity-related comorbidities.
The patient’s surgical history included cesarean section and evacuation of an ectopic pregnancy. She was a former smoker, quitting over 25 years ago, and has no other history of substance or alcohol use. Family history is positive for obesity, diabetes, hypertension, coronary artery disease and hypercholesterolemia. She did not take any medications, including supplements, except for Ibuprofen 800 mg 1–3/daily for musculoskeletal pain.
The patient underwent a comprehensive evaluation and treatment plan prior to the surgery including: psychiatric evaluation and clearance, nutritional consultation with a registered dietician, education about bariatric surgery and pre/post op expectations, routine preoperative labs, UGI, esophagogastroduodenoscopy (EGD), pulmonary function analysis, and a cardiovascular exam. Situs inversus totalis was confirmed with abdominal X-ray and CT, and echocardiogram. Pre-procedural evaluation with UGI revealed mild gastroesophageal reflux observed to the level of the distal one-third esophagus and small sliding-type hiatal hernia. EGD revealed normal esophagus and duodenum. Stomach biopsy was obtained for antral gastritis, and no helicobacter organism was identified. Abdominal ultrasound confirmed fatty liver disease. Pulmonary function analysis including spirometry, lung volumes and diffusion was normal. A pre-procedural cardiovascular exam was performed due to dextrocardia to exclude other structural cardiac abnormalities. 2-D echocardiography with M-mode demonstrated a left ventricular ejection fraction of 60%, no structural abnormalities in the aortic, pulmonic, tricuspid and mitral valve, or right and left atrium and ventricles. Color Doppler and continuous and pulse wave Doppler demonstrated mild pulmonic regurgitation and mild tricuspid regurgitation.
The patient discontinued the Ibuprofen more than one month before her surgery and began a low-calorie liquid diet two weeks prior to surgery. On the day of surgery, preoperative antibiotics, Cefazolin, were given within 60 minutes before the first incision. Prior to induction, the patient received 5000 units of heparin subcutaneously and sequential compression device (SCD) boots were placed for deep vein thrombosis (DVT) prophylaxis. No beta-blockers were administered. The patient was placed in the supine position and general anesthesia was induced. A Foley catheter was placed and the patient was supported with positioning devices including: arms on padded arm boards, gel pad under left axilla, footboard with gel pads, hover mat and a bariatric safety belt over patient’s thighs. The abdomen was then prepped and draped in the standard surgical fashion.
A Veress needle was used in the right upper quadrant to access the abdomen and insufflation was created to 15 mmHg. Veress was removed and replaced with a 5 mm trocar and the scope was placed. Additional trocars were placed in the following position: right and left 5 mm lateral trocars, right and left 12 and 15 mm supra-umbilical trocars. The placement of all retractors and graspers was adjusted accordingly to the mirror image anatomy of the intraabdominal organs. The primary surgeon was positioned on the left side of the patient and the assisting surgeon on right side of the patient. Situs inversus totalis was confirmed with the majority of the liver oriented to the patient’s right, spleen on the right, greater curvature of the stomach on the right and gallbladder on the left.
The operating table was placed in the reverse Trendelenburg position. The patient’s right-sided half of the liver was retracted cephalically using a Nathanson retractor to expose the vicinity of the esophageal hiatus. The peritoneum over the cardia was incised using the Ethicon Harmonic scalpel, and the plane between the cardia and the left crus of the diaphragm was opened to expose the right diaphragmatic crus. No hiatal hernia was present. A point 5 cm proximal to the pylorus along the greater curvature of the stomach was marked corresponding to the incisura angularis just proximal to the crow’s foot of Latarjet’s nerve. The vessels along the greater curvature and all the short gastric vessels were sealed and divided using the Ethicon Harmonic scalpel, freeing the greater curvature and the fundus of the stomach. A 42-French bougie was placed and oriented towards the antrum along the lesser curvature (Figure ). The stomach was stapled and divided alongside the tube in a vertical fashion towards the angle of His (Figures -).
An Ethicon Echelon Flex triple staple line power stapler with a total of one black, three green, and one gold staple loads was used. All staple loads were 60 millimeters in length with staple line bio-absorbable reinforcement. Hemostasis at the external staple line was achieved (Figure ). The stomach was removed from the abdomen via the left-sided 15 mm trocar (Figures , ). Intraoperative endoscopy was performed using a 5 mm Olympus Ultrathin gastroscope revealing no areas of stenosis, internal staple line bleeding, nor staple malformation or leak seen. Total operation time was 108 minutes. There were no post-operative complications.
Post-operative care included pain management and DVT prophylaxis with SCD, heparin and early ambulation four hours post-surgery. A UGI was performed on post-op day 2 with normal findings for a post-bariatric surgery evaluation and clear fluids were started. The patient was discharged on post-op day 3 without any complications. Upon discharge, the patient had a treatment plan that was previously discussed that included instructions for diet and medications, including vitamin supplementation and antacids. At her three-month follow-up, the patient was still without complications and very pleased with her weight loss of 46.2 lbs, weighing 142 lbs (BMI 29). |
pmc-6300385-1 | A 77-year-old man on PD for five months transferred his care to our unit in January 2018. He had a history of type 2 diabetes mellitus for 40 years and had been followed for chronic kidney disease presumed to be secondary to diabetic nephropathy since 2009. In November 2015, histological examination of colonic polyps removed during routine colonoscopy revealed the presence of prominent nodular aggregates of atypical small to medium size lymphocytes positive for b-lymphocyte antigen CD20 (CD20), cyclin D1, and B-cell lymphoma 2 (BCL-2), with weak expression of lymphocyte antigen CD5 (CD5) and approximately 20% of the lymphoma cells staining for cellular proliferation marker Ki-67 (Ki-67). The histological diagnosis of mantle cell lymphoma was made. He had no symptoms consistent with lymphoma. Complete blood count revealed modest anemia, and normal white cell and platelet counts. The blood smear did not contain abnormal lymphocytes at that time. Serum lactic dehydrogenase (LDH) level was in the normal range at presentation and throughout the course of his disease. Positron emission tomography-computed tomography (PET-CT) showed scattered metabolically active enlarged lymph nodes in both axillae, mediastinum, and around the upper abdomen around the pancreas. Diffuse metabolic activity was also detected in the spleen, which was enlarged. The patient, who lives at a distance from Albuquerque, New Mexico, chose to be followed by an oncologist closer to his home who suggested postponing the start of antineoplastic treatment until the appearance of signs of disease progression.
Clinical manifestations of lymphoma and signs of disease progression on subsequent surveillance PET-CT studies were absent initially. However, renal function, which was worsening slowly up to that point, worsened rapidly in the second half of 2016, and he was placed on hemodialysis in a dialysis unit close to his home. A percutaneous kidney biopsy performed in December 2016 showed diffuse proliferative (class 4) lupus nephritis, which did not respond to a four-month course of prednisolone and mycophenolate. He had no past medical history of lupus.
In August 2017, he changed his dialysis modality to PD. For the first five months of PD, he was followed in the dialysis unit close to his home. The status of peritoneal transport was investigated by a standard peritoneal equilibration test performed approximately two months after the onset of PD. This test showed a four-hour dialysate-to-plasma ratio for creatinine (four-hour D/P creatinine) of 0.81 which is consistent with high-average transport. Adequacy of azotemic substance removal was tested by standard weekly total (peritoneal plus renal) fractional urea clearance (Kt/V urea) which was 1.81. Kt/V urea values ≥ 1.70 weekly are considered adequate.
On his first visit to our PD unit he had no abdominal symptoms but the spent peritoneal dialysate was cloudy. Dialysate cell count was as follows: red cells 135/mm3, nucleated cells 693/mm3 (neutrophils 5%, lymphocytes 79%, macrophages 15%, mesothelial cells 1%). The lymphocytes had an atypical morphological appearance consistent with the diagnosis of mantle cell lymphoma. At the same time, blood hemoglobin was 13.1 g/dL, hematocrit 38.0%, platelet count 134 × 103/mm3, and white cells 11.8 × 103/mm3 with 26% neutrophils and 69% lymphocytes disclosing atypical features. He was started empirically on intraperitoneal vancomycin with the presumptive diagnosis of peritonitis. Spent dialysate culture, however, was negative. On each subsequent PD clinic visit, spent peritoneal dialysate contained atypical lymphocytes. Atypical lymphocytes were also found repeatedly in his blood samples.
Recent PET-CT scans showed modest enlargement of several metabolically active lymph nodes and spleen. Blood hemoglobin and hematocrit had decreased to 9.9 g/dL and 30.4%, respectively, in mid-July 2018. At the same time, white blood cell count was 18.6 × 103/mm3 with 81% atypical lymphocytes. Fluid retention, manifested by peripheral edema and moderate right pleural effusion, was present in all his visits to the PD clinic, but became symptomatic with respiratory distress in early July 2018 when he was admitted with the presumptive diagnosis of pneumonia. This diagnosis was not confirmed. However, paracentesis of the right pleural effusion revealed cloudy fluid with 12142/mm3 red cells and 3505/mm3 nucleated cells, 9% of which were neutrophils and 74% lymphocytes with atypical appearance. In the same sample, protein concentration was 2.6 g/dL, LDH 723 U/L, and glucose concentration 107 mg/dL while serum glucose was 151 mg/dL.
The following serum laboratory values were obtained recently: albumin 2.4 g/dL, LDH 432 U/L (normal range 300-670 U/L), and antinuclear antibodies negative. Serum light chain analysis showed kappa chains 330.5 mg/L (normal range 3.3-19.4 mg/L), lambda chains 175.3 mg/L (normal range 5.7-26.3 mg/L), and kappa/lambda ratio 1.89 (normal range 0.26-1.65). Weekly total Kt/V urea was 1.63. The decline over the previous value of Kt/V urea of 1.81 was due to loss of residual renal function. A repeated peritoneal equilibration test showed a high transport state with a four-hour D/P creatinine of 0.86 and ultrafiltration volume of 265 mL. The value of the Kt/V urea was not in the adequacy of dialysis range and the high transport status diagnosed by the last peritoneal equilibration test is known to be associated with fluid retention. The prescription of PD was changed with addition of one daily exchange containing icodextrin to the previous five nocturnal exchanges containing dextrose. In the last PD clinic visit of the patient in August 2018, his edema was substantially reduced and he had not had symptoms related to lymphoma. He is currently discussing the potential advantages and disadvantages of chemotherapy with his oncologist.
Figure shows atypical lymphocytes and a few neutrophils in his peritoneal effluent. Figure shows a recent PET-CT image with enlarged and metabolically active lymph nodes and an enlarged and metabolically active spleen. |
pmc-6300387-1 | A 28-year-old female presented with a staghorn calculus (Figures -) and in need of a nephro-ureterostomy stent placement. Using fluoroscopic guidance, a 21-gauge needle was introduced through the skin into an inferior renal calyx and an antegrade pyelogram was performed demonstrating opacification of the collecting system. After demonstrating return of urine, a wire was passed through the needle and a dilator was introduced over the wire. The existing wire was removed and multiple catheters and wires were subsequently used to attempt to gain access to the collecting system. After unsuccessful attempts through the inferior calyx, the superior renal calyx was attempted in the same manner. Due to the obstructive staghorn calculus, this was also unsuccessful (Figure ).
After approximately two hours of procedure time and several unsuccessful attempts to access the central renal pelvis, it was evident the procedure might have to be abandoned. As a final attempt, the decision was made to use a SwiftNINJA® SMC (Merit Medical Systems, South Jordan, UT). This catheter easily circumnavigated around the staghorn calculus through the left renal collecting system and eventually into the proximal ureter (Figures -). This maneuver was completed within one minute.
A Platinum Plus™ guidewire (Boston Scientific, Marlborough, MA) was used to guide the SMC into the bladder (Figure ). The SMC was then exchanged for a 4-French Berenstein catheter, which was then exchanged over a stiff guidewire for an 8.5-French nephro-ureterostomy stent (Cook Medical, Bloomington, IN). The distal loop of the stent was formed in the urinary bladder (Figure ). Due to the space-occupying staghorn calculus, the proximal loop was unable to be formed in the renal pelvis. Contrast was injected through the stent demonstrating flow into the urinary bladder (Figure ). Hemostasis was achieved and the nephro-ureterostomy stent was secured in place with a fixation device and capped. |
pmc-6300388-1 | Our patient is a bed-bound 57-year-old male with a past medical history of Down's syndrome and quadriplegia. He was sent to the emergency department (ED) by his primary care provider (PCP) for being hypotensive and febrile. The patient had multiple episodes of urinary tract infections (UTIs) over the course of several years, but this time he was found to be septic. On admission, he was afebrile with a blood pressure of 97/64 and a heart rate of 89 bpm. On the medicine floors, urine analysis (UA) confirmed moderate blood in the urine along with a positive leukocyte esterase, confirming a urinary tract source. Urine and blood cultures were drawn and turned out positive for Proteus mirabilis in the urine. This complicated his hospital stay as XGP was eventually diagnosed as the outcome of his longstanding bacteriuria. During a routine physical exam by the medicine night team, what appeared to be a pressure ulcer was identified on our patient’s lumbar spine. Non-contrast computed tomography (CT) showed a highly atrophic left kidney with visible inflammation surrounded by a collection of fluid (Figure ). Additionally, a peri-nephric abscess and a 3.5-cm staghorn calculi were readily seen. A contrast CT showed a fistulous tract from the left kidney through the para-spinal muscles of the back and into the lumbar spine (Figures -). Infectious disease and urology consultations recommended intravenous (IV) ampicillin and ciprofloxacin. The patient underwent incision and drainage by interventional radiology and had a Jackson-Pratt (JP) drain inserted. IV fluids were given to return the blood pressure to the baseline. Additionally, a total course of six weeks of antibiotic therapy was recommended by urology to cool down the inflammation until a left nephrectomy would eventually be performed. |
pmc-6300455-1 | A 12-month-old male patient with a predominently protruding premaxilla due to unsymmetrical BCLP was referred. To align the premaxilla, minimal amount (3 mm) of the bone was removed from the vomer, posterior to the VPS. The septo-premaxillary ligament anterior to the VPS was preserved. The repositioned premaxilla was stabilized by interosseous suturing with 2–0 polyglactin 910 (Vicryl®, Ethicon Inc., USA). After orbicularis muscular repair, limited rhinoplasty was performed via reverse U-shaped incision. Postoperatively, his columella was elongated, and nasolabial structures were normalized (Fig. ). |
pmc-6300455-2 | A 10-month-old female patient with a predominently rotating premaxilla due to a complete BCLP was referred. To align the premaxilla, minimal amount of the bone was removed from the vomer, anterior to the VPS. The premaxillary segment was indirectly stabilized with bilateral mucosal bridging over the alveolar gap. For this patient, the lower lateral cartilages of the nose were approximated via nostril rim incision. Two years later, her nasolabial structures were normalized and there were no signs of anterior crossbite (Fig. .) |
pmc-6300455-3 | An 8-year and 1-month-old male patient with protruding premaxilla due to BCLP was referred. To align the premaxilla, 11 mm of the bone was removed from the vomer, posterior to the VPS. The extent of ostectomy was determined by prediction tracing of the lateral cephalogram with consideration of postoperative ideal nasolabial angle. After separating the septal cartilage from the vomer groove, the premaxillay segment was bodily repositioned to its new position (back and up), where rigid fixation was performed using a 1.6-mm, 4-holed titanium plate and screws (M3®, Osteomed Co, U.S.A.) (Fig. ). Labial repair and concomitant rhinoplasty were performed. Preoperative and postoperative three-dimensional CT images are also presented in Fig. . Two years later, his nasolabial structures were normalized, and his upper dental arch was well aligned without anterior crossbite (Fig. ). |
pmc-6300466-1 | A 71-year-old woman presented with a chief complaint of dysarthria and was subsequently diagnosed with ALS. At age 75, her breathing became difficult, and she underwent TIV. At age 78, she was hospitalized due to fever, tachycardia, hypoxia, and drowsiness. She had pyuria and increased white blood cells and C-reactive protein. An ECG showed ST elevation in V1–V5. Echocardiography demonstrated markedly decreased wall motion in the apex, which was incongruent with the coronary artery supply region. The basal motion was normal. She was diagnosed with a urinary tract infection and TTS. Eleven days after admission, the abnormal wall motion and her symptoms completely disappeared. |
pmc-6300466-2 | A 57-year-old man presented with right arm weakness and was diagnosed with ALS. At age 60, he underwent TIV due to progressive dyspnea. At age 67, he was admitted to our hospital due to respiratory discomfort. An ECG showed negative T waves in V1-V6, and echocardiography indicated decreased wall motion over the entire circumference of the apical region. Blood testing showed increased white blood cells, transaminase, gamma-glutamyl transpeptidase, and C-reactive protein. Abdominal CT demonstrated wall thickening of the common bile duct, which was consistent with acute cholangitis. The cholangitis was successfully treated with antibiotics. The wall motion abnormality and his symptoms completely disappeared, and he was discharged from our hospital after 27 days. |
pmc-6300466-3 | A 60-year-old man presented with weakness in the left foot. He subsequently developed dysarthria and swallowing difficulties and was diagnosed with ALS. At age 63, he was admitted to our hospital with fever and exacerbation of swallowing difficulties, and he was diagnosed with aspiration pneumonia. Two days after admission, he reported chest pain. An ECG indicated negative T waves in V3–V6. An echocardiogram indicated severe left ventricular dysfunction with akinesia; however, the basal segments were preserved (Figures , Supplementary Video ). The ejection fraction was 20%. Coronary angiography did not indicate any significant stenosis. Although his chest pain subsided with conservative treatment, he underwent tracheostomy due to difficulties in sputum expectoration. The abnormal wall motion was subsequently resolved (Figures , Supplementary Video ). He was transferred to another hospital and died at 65 years of age. Pathological examination of the heart demonstrated no coronary stenosis (Figures ) and localized patchy fibrosis that occurred toward the endocardium of the left anterior wall (Figures ). The neuropathological findings were consistent with ALS [Brettschneider stage 4 () and Nishihira Type 2 ()] (Figures ). |
pmc-6300466-4 | A 52-year-old woman presented with dysarthria, followed by swallowing difficulties and limb weakness, and she was diagnosed with ALS. At age 55, she developed hypoxia and consciousness disturbance after excreting a large amount of stool induced by an enema. An ECG indicated abnormal Q wave in V3 and ST elevation in V2–V3. Echocardiogram revealed diffuse akinesia in the apex with preserved wall motion in the basal segments. She died of hypoxia on the following day. Pathological examination of the heart demonstrated no apparent occlusion of the coronary artery (Figures ). Patchy myocardial necrosis was observed in the anterior wall of the apex and the intraventricular septum, accompanied by inflammatory cell infiltration that mainly involved neutrophils and lymphocytes (Figures ). Intraventricular hemorrhage was also observed. The neuropathological findings were consistent with ALS (Brettschneider stage 4 and Nishihira Type 1) (Figures ). |
pmc-6300719-1 | An 18-year-old woman with bilateral DDH was referred to our arthroplasty clinic because of bilateral groin pain and increasing difficulty with walking. Radiographs showed bilateral DDH type III Crowe classification (). There was no leg length discrepancy due to bilateral pathology. On preoperative templating, by placing the acetabular component in the true acetabulum, planned limb lengthening was 4 cm.
The THA was performed using a posterior approach. A 42 mm monobloc acetabular cup (Zimmer Maxera; Zimmer Biomet, Warsaw, IN, USA) was placed in the true acetabulum to restore the hip center of rotation. The cup used is a monobloc, uncemented implant with a non-modular ceramic liner (Biolox Delta; CeramTec, Plochingen, Germany). Matching ceramic femoral head size was 32 mm. With medialization, cup coverage was sufficient without the requirement for bone graft. The femoral stem was a straight conical uncemented stem (Zimmer Wagner cone prosthesis).
During the procedure, the surgeon (AR) noted a tight sciatic nerve, but thought it was acceptable and no femoral shortening was performed. Neither electromyographic monitoring nor wake-up tests are commonly used in our practice. On the day following surgery, the patient had paresthesia in the sciatic nerve distribution but motor function was intact. The postoperative radiographs () showed a 5.5 cm leg lengthening which was thought to be the cause of the sciatic nerve paresthesia. As there was no motor palsy, the initial diagnosis was a neurapraxia. Therefore, the patient was monitored to see if there was any recovery of nerve function. During the next 5 weeks, there was no improvement of the symptoms with a persistence of paresthesia when the knee was in full extension. A diagnosis of axonotmesis was made and the decision was taken to perform a femoral osteotomy to reduce the nerve tension and potentially favor nerve recovery. To avoid compromising the stability of the hip reconstruction surgery, a distal femoral osteotomy was seen as a better option.
At 6 weeks after the initial surgery, the distal femoral osteotomy procedure was performed (3 cm shortening). Within the immediate days after the osteotomy, there was a significant reduction in pain and paresthesia. Complete recovery of sciatic nerve function was obtained within 6 weeks. The osteotomy was fully united by 3 -months. At 6-year follow-up, the patient remains asymptomatic with excellent hip function, no pain or dislocation, and normal motion.
2 years after the left THA, the patient requested surgery for her right hip. At the time of surgery on that side, a distal femoral osteotomy was performed in the same setting, immediately prior to the THA (3 cm shortening). The THA was uncomplicated, with importantly no sciatic nerve problems postoperatively (). |
pmc-6300719-2 | A 35-year-old woman suffering from unilateral left DDH was referred to the same surgeon (AR). A THA was performed without using a shortening osteotomy.
In the recovery room during the postoperative examination, a sciatic nerve palsy was diagnosed with a complete motor palsy. An excessive 6 cm lower limb lengthening was diagnosed to be the cause of the injury. The surgeon decided to take the patient back to the operating room the following day. The previously described distal femoral osteotomy technique was performed (shortening of 3 cm). 2 days after the osteotomy, there was complete recovery of the motor and sensory function of the sciatic nerve. At 2 years’ follow-up, there was complete union of the osteotomy and no functional consequences of the transient nerve injury. |
pmc-6300872-1 | A 28-year-old white woman checked herself into an outpatient clinic of psychosomatic medicine and psychotherapy (PSO) for the first time. She reported having a vacuum-assisted child delivery 6 weeks prior, during which significant blood loss led to the surgical removal of her placenta. Since then, she could not bond with her baby and had been experiencing feelings of emptiness as well as a decrease in energy and general happiness. In addition, she had withdrawn from social activities. Later, she began experiencing migraines. During her visit, she was short-spoken, emotionless, and gave conflicting responses to simple questions. When asked about her mood, she indicated that she was feeling very relaxed.
Three days later, the patient was referred to the psychiatric emergency room for ambiguous psychopathology and progressive headaches. Upon arrival, she was not able to explain why she was in treatment at the outpatient clinic for PSO. The patient’s mother added that her daughter had barely spoken or answered questions over the past 2 days. The patient later reported that she had stopped breastfeeding owing to insufficient lactation while also experiencing sharp, bilateral headaches (intensity 7, 0 = no pain, 10 = unimaginable pain) without noticeable triggers. These headaches lasted about 10 minutes, occurred several times per day, and had appeared for the first time 6 days before her second visit. She also described having nausea and flashes of light in her left eye. Painkillers did not relieve the migraines during the day, but she slept comfortably and pain-free at night. She did not take any other drugs, and she had never before had mental disorders or other relevant diseases. Her micturition and defecation were normal. She did not have night sweats, fever, or weight loss. Her social network was supportive. There was nothing of note in her family medical history. A psychopathological assessment demonstrated mild disorientation (date indeterminable, wrong month), a severely impaired capacity to concentrate (not able to solve easy arithmetic problems), deficits in long-term memory, poverty of speech (sparse replies to questions, sometimes delayed or unanswered), a flat affect, and feelings of helplessness. There were no indications of rumination, incoherence, delusions, perceptual disturbances, movement disorders, or aggressive thoughts toward herself, her baby, or others. The targeted physical examination did not show pathologies.
On the basis of the acute onset of these symptoms after a complicated birth and a normal physical examination, she could have been diagnosed with severe postpartum depression. Nevertheless, the sudden onset of severe headaches with flashes of light, disorientation, and long-term memory impairment raised suspicions. Therefore, a neurologist was consulted. Blood analysis results ruled out the possibility of a cerebral venous sinus thrombosis and, although it showed mild anemia and leukocytosis, revealed normal C-reactive protein and D-dimer levels. In response to the recurrent headaches that appeared to be depression-related, recommendations were made for the patient to take a fixed intake of nonsteroidal anti-inflammatory drugs for the next few days.
As a result of the conspicuous psychopathology, the patient was advised to undergo magnetic resonance imaging (MRI), but she ultimately declined. Two days later, the patient was admitted for acute right-sided hemiparesis. A brain MRI scan displayed a contrast-enhanced mass lesion in the left frontal lobe (Fig. ). The patient underwent urgent tumor resection that revealed a GBM harboring an isocitrate dehydrogenase 1 mutation (IDH1). After 10 days, the patient was discharged with a substantially improved psychopathology and without neurological deficits. The subsequent concordant radiochemotherapy, which was initiated 2 weeks after discharge, was tolerated very well. Owing to chemotherapy, the patient was not able to breastfeed her baby. At the last follow-up, almost 3 years after tumor resection, the patient was in excellent mental and physical condition with no evidence of tumor recurrence. |
pmc-6301189-1 | A 54-year-old male who had a left hemisphere ischemic stroke 2 years ago was recruited. The participant had limited voluntary motion in the arm and hand with significant muscle atrophy but had no cognitive impairments. The average ratio of the subject's maximum finger forces between hands was 0.076, and the subject's Chedoke-McMaster Stroke Assessment hand score was 2, both indicating severe impairment. A 35-year-old male participant was also recruited as a neurologically-intact control subject for comparison. This study was carried out in accordance with the recommendations of the Institutional Review Board (IRB) of the University of North Carolina at Chapel Hill with written informed consent from the subject. The subject gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the local IRB. Additional written informed consent was obtained from the subject for the publication of this case report. |
pmc-6301901-1 | A 65-year-old man with no significant past medical history underwent chest radiography at routine medical check-up. This revealed a nodular opacity in the right lung field. He was referred to our department for further examination. He had presented no symptoms such as fever, dyspnea, dysphagia, weight loss, or hemoptysis. He worked in a construction company and had travelled to Taiwan 2 years previously. He had two cats as pets. He had smoked one pack of cigarettes per day for 20 years. His physical findings, tumor markers, and other laboratory tests were unremarkable. Spirometry test showed normal pulmonary function. The first computed tomography (CT) scan showed a nodule of 24 mm in diameter with an irregular and spiculated border in the posterior basal segment of the right lung (Fig. a), and two smaller nodules (8 mm and 6 mm) in the same lobe (Fig. b). One month later, the main tumor had enlarged to 27 mm in size, and the others to 10 and 7 mm. The head magnetic resonance imaging (MRI) showed no intracranial mass. The fluorodeoxyglucose positron emission tomography (FDG-PET) showed abnormal uptake in the main nodule (24 mm) (Fig. c) and the right hilar lymph nodes (Fig. d).
Thus, a diagnosis of primary lung cancer with intralobar metastases and ipsilateral hilar lymph node metastases was made, and he underwent right lower lobectomy with hilar and mediastinal lymph node dissection via thoracotomy. We inserted a chest drainage tube intraoperatively. Ampicillin/sulbactam was administered only on the day of surgery as prophylactic treatment.
At thoracotomy, a hard mass adjacent to the pleura was observed in pulmonary segment 10, but no other specific abnormalities were found.
Histopathological analysis revealed well-circumscribed nodular lesions with noncaseating epithelioid cell granulomas, without features of malignancy. There were numerous small yeast-like fungi stained by Grocott’s methenamine silver procedure in the granulomas. Alcian blue and the Mucicarmine dye failed to show capsules around them. These findings and the forms of the fungi led to the diagnosis of lung histoplasmosis (Fig. ). No fungi were detected in the excised lymph nodes.
The patient was discharged on postoperative day 20. Length of hospital stay was prolonged due to a persistent pleural effusion. The amount of pleural effusion drainage was 410 ml on postoperative day 1. More than 200 ml per day had been drained until on postoperative day 13. The pleural effusion was clear and pale yellow. We removed the chest tube on postoperative day 16. No antifungal drugs were administered after surgery. At 6-month follow-up, he did not show any signs of relapse. |
pmc-6301907-1 | An 80-year-old man was admitted to a nearby hospital for the sudden onset of severe abdominal pain. Plain computed tomography (CT) showed a large left internal iliac aneurysm (IIA). An aneurysmal rupture was suspected, and he was transferred to our hospital for surgical treatment. His past medical history was significant for hypertension and a lack of a history of renal calculus. On physical examination, his blood pressure was 135/75 mmHg; pulse, 90 beats per minute and regular; and temperature, 36.5 °C. His abdomen was distended and tender to palpitation, but was without peritoneal signs. Laboratory data revealed a normal hemogram, with the exception of increased leukocytes (11,400/μL), normal serum electrolytes, blood urea nitrogen level of 20 mmol/L, and serum creatinine level of 1.2 mg/dl. Chest X-ray demonstrated no cardiomegaly or any abnormal findings.
Contrast-enhanced CT revealed a large left IIA (6.5 cm in diameter) (Fig. ). Blood extravasation into the periaortic soft tissue and other CT signs of a ruptured aneurysm were not observed in the arterial phase. Specific CT signs of an inflammatory aneurysm, such as the typical image of soft tissue surrounding the aortic wall enhanced with contrast medium (enhancing periaortic soft tissue, “mantle sign”), were also not observed. However, a left hydroureteronephrosis and leakage of iodinated urine in the left-side retroperitoneum were demonstrated in the delayed phase, indicating a spontaneous ureteral rupture resulting from the direct compression of the ureter by the aneurysm (Fig. ).
To avoid the potential risk of graft infection due to urinary extravasation, a ureteral double-J stent was placed under endoscopic and X-ray fluoroscopic guidance. Endovascular aortic repair (EVAR) was performed under general anesthesia on the same day to avoid aneurysmal rupture. The patient underwent endovascular coil deployment within the left IIA and endovascular stent grafting from the left common iliac artery to the left external iliac artery (GORE® EXCLUDER® AAA Endoprosthesis PLC201000J, W. L. Gore and Associates, Inc., Flagstaff, Arizona, USA) (Fig. ). Final angiography showed full occlusion of the aneurysm and an optimal result.
His postoperative course was uneventful, and he was discharged in good health on postoperative day 20. The progressive reduction of an urinoma was followed by serial CT performed 2 weeks later, which showed its complete resolution. |
pmc-6302270-1 | A 55-year-old man with a history of extensive alcohol and tobacco use presented with a 2-month history of a progressively enlarging, 5-cm ulcerative, and painful midline tongue lesion extending to the floor of mouth resulting in an anterior tongue cleft. This lesion was associated with unintentional weight loss, left otalgia, and submandibular swelling. Bilateral nontender palpable lymphadenopathy in levels I, II, and III were present.
Prior biopsies by an otolaryngologist in private practice did not demonstrate carcinoma but were otherwise inconclusive with reactive inflammatory changes. However, a positron emission tomography scan revealed hypermetabolic lesions of the anterior tongue as well as lymph nodes bilaterally in levels I, II, and III suggestive of malignancy (). The assessment was a likely T3/4N2cM0 tongue squamous cell carcinoma. He underwent a panendoscopy with biopsies and a physical examination under anesthesia for surgical planning. Biopsy results again did not yield carcinoma but showed granulomatous inflammation without organisms present.
A multidisciplinary tumor board recommended a rheumatologic workup and an excisional lymph node biopsy. Lymph node biopsy results demonstrated noncaseating granulomatous inflammation with no malignancy (), while laboratory results demonstrated markedly elevated ACE (angiotensin converting enzyme) levels. These findings suggested an atypical case of sarcoidosis, and the patient was referred for pulmonary consultation. The patient had developed scattered erythematous macules involving the extremities, palms, soles, and trunk. Laboratory evaluation demonstrated T pallidum immunoglobulin G antibodies present with a reflex RPR (rapid plasma reagin) titer of 1:512. The lymph node biopsy sample was then analyzed with immunohistochemistry (IHC) revealing spirochetes (). The patient was diagnosed with tertiary syphilis and started on doxycycline 100 mg twice daily for 30 days because of a severe penicillin allergy. After receiving treatment, the patient came back to our clinic with his tongue lesion healing well but with a persistent anterior tongue cleft (). The patient has not obliged with further laboratory evaluations to recheck a RPR titer after antibiotic therapy. |
pmc-6302271-1 | A 54-year-old Caucasian man was initially diagnosed with central nervous system coccidioidomycosis at age 14 in 1976. He received intrathecal amphotericin B deoxycholate on a declining schedule from age 14 to 29 via cisternal puncture. He suffered auditory, but not vestibular, nerve damage related to intrathecal amphotericin B deoxycholate neurotoxicity.
After fluconazole was approved by the US Food and Drug Administration in early 1991, he was started on fluconazole 400 mg. Mild hydrocephalus was initially detected at this point. The hydrocephalus continued to worsen, and by 1995, at age 31, a ventriculoperitoneal shunt was placed, which required 2 subsequent revisions.
He had persistent cerebrospinal fluid (CSF) cultures of Coccidioides, and therefore, fluconazole was gradually increased up to his current dose of 1200 mg by 2001.
In 2008, at age 45, he developed severe lumbar pain and was found to have lumbar arachnoiditis. Soon thereafter, he developed a neurogenic bladder and suffered from erectile dysfunction. As a result, CSF monitoring was returned to cisternal puncture due to the lumbar pain. He had a hypokalemic paralysis that was suspected to be related to fluconazole therapy in 2011, at age 48. Most recently, in 2017, he had an episode of headache and ataxia secondary to transient ventriculoperitoneal shunt malfunction.
After an episode of unstable angina in 2010, at age 47, he underwent a heart catheterization that demonstrated coronary artery disease leading to a quadruple coronary artery bypass. In January 2016, at age 53, he suffered a non-ST elevation myocardial infarction for which he received multiple drug-eluting stents, and he was started on dual antiplatelet therapy. His current medications are lisinopril, metoprolol, aspirin, clopidogrel, ezetimibe, anti-PCSK9 monoclonal antibody bimonthly injections (evolocumab), and fluconazole 1200 mg daily.
Despite 42 years of therapy, longitudinal CSF studies reveal persistent lymphocytic pleocytosis (), elevated protein (), normalizing glucose (), and persistent complement fixation titers (). The clopidogrel represents a contraindication to cisternal puncture; therefore, there are no recent CSF studies. Last available CSF studies in late 2015 showed white blood cell count of 13 cells/cm2 (89% lymphocytes, 11% monocytes), protein 170.5 mg/dL, glucose 45 mg/dL, and immunoglobulin G (IgG) immunodiffusion reactivity with complement fixation titer of 1:1. The most recent serum IgG immunodiffusion was reactive with complement fixation titer as high as 1:8. Serum fluconazole levels have been routinely collected (). The patient refused to try a newer azole. |
pmc-6302297-1 | A 52-year-old man was admitted to our institute due to a history of chronic cough, dysphagia and an abnormal chest radiographic finding. A chest x-ray and computed tomographic angiography scan (CTA) revealed an ARSA behind the esophagus with about 5.6-cm sized proximal descending aortic aneurysm (Fig. a). The esophagus was clearly compressed by the ARSA (Fig. b), likely causing the dysphagia. Both carotid arteries had a common origin. Because of his progressive symptoms and large fusiform thoracic aneurysm, we planned the hybrid repair for simultaneous relief of ARSA causing dysphagia and thoracic aneurysm. First, an ARSA to the right carotid artery transposition with a proximal ligation of the ARSA along distal to the right vertebral and mammary arteries was performed via the right supraclavicular incision (Fig. c). One hour later, we performed a thoracic endovascular aortic repair (TEVAR), deploying of a thoracic endovascular covered stent graft (Valiant™ thoracic stent graft with the Captivia™ delivery system) in the descending thoracic aorta with the coverage of the origin of the ARSA and the proximal descending thoracic aneurysm. The postoperative recovery was uneventful. The follow-up thoracic CTA revealed no endoleak, no graft migration, and complete exclusion of the ARSA and aneurysm. The right carotid to subclavian artery re-routing was showed to be excellent structural integrity and normal flow patterns with well-preserved right vertebral artery and right upper limb flow (Fig. ). He was asymptomatic with complete resolution of his cough and dysphagia. |
pmc-6302302-1 | A 43-year-old Hungarian man with poor socioeconomic living conditions was found lying on the floor unresponsively by a family member. He was taken to a regional hospital “Szent György” University Teaching Hospital, Székesfehérvár, Hungary. On admission he had low level of consciousness accompanied by stiff neck, constricted pupils and fever (38.6 °C). Alcohol abuse, smoking and epileptic seizures were found in his past medical records. Urgent skull CT scan was performed revealing left side mastoiditis but neither brain abscess nor vascular disorders were described. Blood was drawn for clinical chemistry and for bacterial culture. Relevant parameters of the blood test showed elevated white blood cell (WBC) count 24.1 109/L (87.5% Neutrophils), increased C-reactive protein and procalcitonin levels (211.4 mg/L and 0.46 ng/ml, respectively). Laboratory parameters of blood and liquor are shown in Table . The results of the urine tests were normal.
Lumbar puncture was carried out and the CSF sample was taken to the laboratory immediately. The slightly xanthochromic CSF was cloudy showing increased WBC count (7400 cells/μl), elevated protein level (12.4 g/L), and low glucose level (< 0.6 mmol/L) compared to the elevated serum glucose level (8.1 mmol/L).
After taking blood and CSF specimens for culture Ceftriaxone (2 × 2 g), Vancomycin (2 × 1 g) and Ampicillin (6 × 2 g) were started and completed with supportive treatment.
The patient’s CSF sample was processed routinely in our Microbiology laboratory (SYNLAB Székesfehérvár, Hungary) on arrival. The Pastorex Meningitis agglutination kit (Bio-Rad) testing the CSF sample for the presence of soluble antigens of Streptococcus pneumoniae, Haemophilus influenzae type b, Neisseria meningitidis group A, group B/E.coli K1, group C, group Y/W135, and Streptococcus group B was negative. Microscopic examination showed several neutrophil granulocytes and a very few number of hardly dyed short rods or elongated cocci that seemed to be Gram-negatively stained at first examination. To exclude tuberculous meningitis Ziehl-Neelsen staining was performed, but no acid-fast bacilli were detected. At the 18–24-h and 48 h readings bacterial growth was negative both on the blood and on the chocolate culture media. Only the enrichment broth was slightly cloudy, indicating bacterial growth. On the next day, after 72 h of incubation tiny grey pinhead colonies were found on both blood and chocolate agar plates that were catalase and oxidase negative. Similar colonies were seen on the anaerobic plates. Irregular small Gram-positive bacilli and coccobacilli were observed in the microscope. The bacterium was identified as A. turicensis by VITEK 2 ANC ID Card (Biomerieux) and API Coryne (Biomerieux). The identification was verified by molecular method. PCR was performed with primers that amplified 1343 bp fragment of bacterial 16 s rRNA coding sequence []. PCR thermal profile was as follows: 5 min at 94 °C, 40 cycles of 94 °C for 1 min, 55 °C for 1 min and 72 °C for 1 min and a final extension at 72 °C for 2 min []. PCR amplicons have been purified by Qiagen PCR Purification Kit (Qiagen, GmbH, Hilden, Germany) and have been sequenced (BIOMI Kft., Gödöllő, Hungary). Analysis of nucleic acid sequence was done based on online tools of NCBI GenBank thus, the strain was identified as A. turicensis.
Antibiotic susceptibility of tested strain was performed by E-test after the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations. The isolated strain was susceptible to penicillin, ampicillin, imipenem, meropenem and vancomycin at concentrations ranging from 0.125 to 0. 5 mg/L.
As the patient’s condition did not improve a left side mastoid surgery was performed. During the mastoidectomy intraoperatively removed purulent discharge was sent to our Microbiology laboratory. After two days of incubation colonies grew on the agar plates that were similar to those isolated from the CSF sample. Identification both by biochemical reactions of automated systems and by 16S rRNA PCR and sequencing resulted A. turicensis. Moreover, the strain presented the same antibiotic MIC values as isolate of the CSF sample.
Postoperative bleeding occurred leading to the necessity of reoperation. On the third day of postoperative period severe polyuria was presented with dilated pupils insensible to light. The skull CT scan revealed cerebral herniation, intensifying oedema and sinus thrombosis. (Figures and ). Unfortunately, there was no chance of reoperation because the patient passed away.
After 5 days of aerobic and anaerobic incubation of the blood cultures no bacterial growth was detected. Autopsy was performed that confirmed the clinical diagnosis of cerebral herniation due to the purulent meningitis and the consequent oedema in the CNS. Moreover, a greenish-yellow discharge accumulated at the brain stem and in the lateral ventricules. During histopathology an infiltration of granulocytes at the meninges was seen and suspected signs of actinomycosis was also observed. |
pmc-6302303-1 | A 56-year-old Pacific Islander woman was admitted to our hospital after she presented with hemoptysis, which she quantified as about a handful. She was a lifelong nonsmoker with no history of obstructive or restrictive lung disease and no reported allergies. Her past medical history was significant for chronic myeloid leukemia on imatinib therapy and a previous case of mild hemoptysis 6 years prior to current presentation. At that time, the patient was diagnosed with ILPS; however, her symptoms resolved, and she did not pursue any treatment.
On arrival, the patient was hemodynamically stable (blood pressure 100/60 mmHg, heart rate 54 beats/minute) with mild anemia (hemoglobin 12.0 g/dl). Her physical examination was notable for coarse breath sounds throughout the lower left lung field without dullness to percussion to suggest hemothorax. Her cardiac, abdominal, and neurological examinations were without focal findings. Her airway was patent, and her oral mucosa was moist. Her laboratory work was notable only for the mild anemia noted above; her chemistry panel and coagulation profiles were within normal limits. Her body mass index was 20.8 kg/m2. A chest x-ray showed left lower lobe nodular opacities. Computed tomography of the chest with contrast demonstrated left lower lobe ILPS. The aberrant vessel was traced to its origin at the descending thoracic aorta, where it measured approximately 1 cm (Fig. a, b). Bronchoscopy was not pursued, because this could induce coughing and/or dislodge a clot. Furthermore, with radiographic evidence of the sequestration, another source of bleeding was not clinically suspected.
With PS, the usual treatment is resection of the sequestration. In those patients with the extralobar subtype, this is completed by removal of only the sequestration. The intralobar type is managed by segmental resection or lobectomy []. The patient was evaluated by a cardiothoracic surgeon, who noted that surgical resection would likely require a thoracotomy and lobectomy instead of a less invasive video-assisted thoracoscopic surgery (VATS), given the size and location of the arterial blood supply to the sequestration. When we explained the risks and benefits to the patient, she declined surgery, given her ongoing treatment for chronic myeloid leukemia and her personal desire to avoid surgery.
After review of the case with a multidisciplinary team, the interventional radiology service offered embolization of the lesion as an alternative to surgery. Multiple 6–13-mm coils, including Nester Embolization Coils (Cook Medical, Bloomington, IN, USA), AZUR® CX Peripheral Coil System (Terumo Interventional Systems, Somerset, NJ, USA), and hydrocoils, were used to embolize the sequestration. There was no considerable flow distal to the coils postembolization (Fig. c, d). The patient’s postprocedural course was notable for pleurisy that responded to oral analgesia. No signs or symptoms of infection occurred, and the patient did not require antibiotics. At her 9-month and 1-year follow-up visits, she reported no pulmonary symptoms, cough, or hemoptysis. |
pmc-6302382-1 | Seventeen-year-old woman, nulligravida, presented with a complaint of abdominal pain and was admitted due to infectious colitis. Ultrasonography incidentally revealed a multiseptated cystic mass in the pelvis. Family history and past medical history were unremarkable, and her menstrual cycle was regular. Blood cell counts and blood biochemistry were normal. Serum levels of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA19–9) were all within normal limits, while cancer antigen 125 (CA-125) was elevated at 76.3 U/mL (normal range 0–35.0). Levels of serum hormones including estradiol (76.3 ng/ml; normal range, 22–144 ng/ml), luteinizing hormone (LH; 4.7mIU) /ml and follicle-stimulating hormone (FSH; 2.9 mIU/ml) were normal.
Pelvic magnetic resonance imaging (MRI) showed a 141 × 96 × 127-mm well-demarcated multilocular cystic mass with irregularly thickened septa and solid components originating in the left adnexa. On T2WI, the signal intensities of the cystic components had the same SI as water, and those of the irregularly thickened septa and solid components had intermediate SI, higher than the SI of uterine myometrium (Fig. a). On T1WI, the septa and solid components had slight higher SI than uterine myometrium and showed early strong enhancement on contrast-enhanced T1WI (Fig. b) and slight hyperintensity on DWI (Fig. c). PET-CT showed mild FDG uptake in solid components of the tumor (SUV: 2.11) (Fig. ).
The preoperative imaging diagnosis was SST or granulosa cell tumor, and it was not likely to be associated with a malignant ovarian tumor because of its low FDG uptake.
The patient underwent left oophorectomy and omentectomy. The cystic mass originated in the left ovary and measured 15 cm in diameter. Grossly, some thickened septa were observed in the mass but there were no obvious solid components. The cysts contained clear, straw-colored fluid.
Histological examination revealed that the mass consisted of hypercellular areas with prominent vascular networks separated by hypocellular areas that corresponded to collagenous and edematous areas, or a so-called “pseudolobular appearance”. Coarse collagenous fibers surrounding individual cells formed collagen bundles between cells, leading to heterogeneous cell density even in cellular areas (Fig. a). The hypercellular areas were composed of a dual cell population of collagen-producing bland spindled cells and rounded epithelioid cells. Prominent vascular networks with a hemangiopericytomatous pattern were observed (Fig. b). Immunohistochemically, tumor cells were positive for α–inhibin. Thus, the final histological diagnosis was SST of the ovary.
We searched the PubMed database for previous cases published in English from 1966 to September 2017 with the terms of “sclerosing stromal tumor”, “ovary” and “imaging”.
The results showed only one report describing PET findings for SST and three reports describing imaging findings on DWI for SST, including the above-mentioned report describing PET findings. Imaging findings on PET and DWI are summarized in Table .
According to one report describing PET findings of SST, the tumor showed intense FDG uptake (SUV max: 7.0). Although SST tended to show high SI on DWI, the exact degree of high SI varied between cases. |
pmc-6302396-1 | We present a case of a 49-year-old woman with renal and heart failure following a long-term (lasting from 13 years of age) SLE prepared for kidney transplantation. Due to LN (class III, then IV), starting at childhood, she was treated with steroids, together with cyclophosphamide, replaced later by methotrexate and then azathioprine. Hence, the partial remission of nephrotic syndrome was achieved and from 2002 the patient did not receive any immunosuppressive therapy. She was also HBV and HCV positive. SLE involvement of circulatory system presented with early coronary atherosclerosis, ischemic heart disease, and myocardial infarction at the age of 20. In 2007, because of deterioration of kidney function with a serum creatinine concentration of 2.2 mg/dL and proteinuria of 2 g/day, the kidney biopsy was performed. The biopsy showed active and sclerotic focal proliferative lupus nephritis nevertheless immunosuppressive therapy was not introduced for the reason of active replication of HCV. The kidney function was gradually deteriorating over time. Despite cardiac intervention (PCI RCA), the patient developed severe post-infarction and dilated cardiomyopathy and required ICD implantation in primary prevention in 2009. Later, on lupus and secondary cardiomyopathic background, the patient developed severe MV and TV regurgitation. For this reason, the patient underwent mitral and tricuspid valve repair and left ventricle volume reduction surgery complicated by low cardiac output syndrome with a need for intra-aortic balloon pump use (2014). In the postoperative period, the kidney function deteriorated, requiring the initiation of renal replacement therapy. The patient has been on dialysis for 4 years. While being on active waiting list for kidney transplantation presented remission of laboratory indices of lupus (complement splits within normal limits: C3–0,93 g/l, C4–0,4 g/l, ANA negative) and persisting circulatory insufficiency with markedly reduced stair-climbing capacity (to one flight of stairs) with elevated BNP 619 pg/ml (n. 0–100). In transthoracic echocardiography, performed before renal transplantation, the left ventricle and the left atrium were significantly enlarged and the left ventricular systolic function was significantly reduced with LVEF 26% and GLS -3 (Fig. ). Due to the implantation of the mitral ring, it was not possible to assess the left ventricular diastolic function. The high tricuspid regurgitant flow gradient with widened and poorly respiratory mobile inferior vena cava indicated a high probability of pulmonary hypertension. Furthermore, while preparing the patient for the surgical procedure, it was decided to include cardioprotective therapy with Levosimendan. Due to the time frame associated with the transplantation procedure, the drug infusion was started as soon as possible after cross-match results were known, immediately after the dialysis session. The infusion at a dose of 0.1 μg/kg/min was continued after surgery for a total of 24 h. The patient’s anesthesia for kidney transplantation and perioperative care included the aspect of optimizing transplanted kidney perfusion, avoiding the use of renal toxic drugs and those excreted by properly functioning kidneys, as well as the use of nephroprotective agents. Because of the patient’s cardiological burden, including recurrent episodes of extrasystole proceeding with decompensation of the circulatory system, together with the need of ICD turning off for the transplantation period, the Swan-Ganz catheter for hemodynamic assessment was not used. Anesthesia monitoring was limited the to ECG, central catheter with CVP assessment, direct blood pressure measurement from the cannula inserted into the radial artery, and cardiac ultrasound. In the perioperative period the CVP parameter was used to assess the volatility, and in the postoperative period, a cardiac ultrasound was used along with the assessment of VCI respiratory fill and motility. The therapy was aimed at the standard of fluid therapy called Goal Directed Therapy (GDT) [, ]. During general anesthesia, fentanyl, triacrium, propofol, desflurane, antibiotic therapy, and standard immunosuppressive treatment were used as well as 25 g of mannitol infusion was administered as a nephroprotective treatment and 0.9% NaCl as a fluid therapy []. In the course of postoperative immunosuppression, she received steroids, tacrolimus with mycophenolate mofetil which was stopped due to persistent leukopenia and cytomegalovirus infection. Furthermore delayed graft function was observed with a need for hemodialysis for almost 6 weeks (mostly due to fluid retention). BNP levels raised to 2996 pg/ml and then slowly decreased. The kidney biopsy performed 2 weeks after transplantation revealed acute rejection (AR II B Banff 2015) with ATN. Finally, the patient was discharged from the hospital on the 67th POD with the serum creatinine concentration of 1.4 mg/dL and BNP level of 1794 pg/ml. One month after kidney transplantation, there was a reduction in left ventricular dimensions, improved systolic function in the EF (increase to 30%) and GLS (decrease to − 6) assessment (Fig. ). In addition, there was a decrease in the tricuspid regurgitant flow gradient with normal width and respiratory motility of the IVC, which indicates a low probability of pulmonary hypertension. The improvement of echocardiographic parameters also reflected the simultaneous improvement of exercise capacity in the recipient from NYHA III/IV to NYHA II. In the 5-month observation, further improvement of heart function with a drop of BNP to 1066 pg/ml and normal kidney function were noted. |
pmc-6302415-1 | The male infant was born to a 23 year-old primi-gravida mother. Pregnancy was uneventful, fetal urinary tract appeared normal on ultrasound, the mother’s medical history was negative for any medication as was family history for renal or cardiovascular disease. While amniotic fluid volume seemed normal on routine ultrasound examinations, anhydramnios of unknown origin was observed at 32 weeks of gestation. No signs of tear or leak in the amniotic membrane were detected. Anhydramnios and pathological umbilical blood flow led to Caesarean section at 34 + 0 weeks of gestation. Birthweight was 2515 g (66th percentile), head circumference 31 cm (24th percentile), APGAR scores 9 at 5′ and 10 at 10 min, umbilical cord artery pH 7.35. The anterior fontanelle was wide and the infant showed features of Potter-sequence with contractures of wrist and ankle joints as well as epicanthus. He also presented with distinct general edema.
After good postnatal adaptation, the infant needed mechanical ventilation due to respiratory distress caused by a spontaneous right-sided pneumothorax at the age of 1 h. He quickly stabilized after nasotracheal intubation and placement of a chest tube. Neither signs of pulmonary hypoplasia nor pulmonary hypertension were evident from chest x-ray or echocardiography (see Fig. a and b). Pre- and postductal oxygen saturation monitoring did not show any significant difference, ventilatory support was minimal (SIMV-mode, PIP 13 mbar, FiO2 0,25) and the patient had no signs of surfactant deficiency.
During the first day of life, he developed severe arterial hypotension (mean arterial blood pressure around 30 mmHg, below 10th percentile []) and consecutive renal failure and anuria (no urinary output for 36 h, serum creatinine 1,98 mg/dl, blood urea nitrogen (BUN) 120 mg/dl) which poorly responded to fluid boluses, catecholamine therapy (dobutamine, noradrenaline and epinephrine), furosemide and hydrocortisone therapy. Sepsis, cystic kidney disease and connatal nephrotic syndrome were ruled out. The cortisol level was normal. Echocardiography revealed good biventricular function without signs of pulmonary hypertension.
After 36 h, vasopressin therapy was initiated with excellent response at doses of 0,001 IE/kg/min; blood pressure stabilized with consecutive onset of diuresis almost immediately after starting of vasopressin (see Fig. ). Initially elevated creatinine and blood urea nitrogen normalized with the onset of diuresis. Weaning of vasopressin, however, was difficult due to rapid deterioration of blood pressure and urinary output and could not be discontinued for the next three weeks. Oligohydramnios, refractory arterial hypotension, renal failure with normal renal ultrasound was highly suggestive of renal tubular dysgenesis. On the fourth day of life, the patient suffered from a spontaneous gastric perforation, which was surgically treated without complications (see Fig. ). On the 21st day of life, hyperkalemia needed to be treated with repetitive doses of furosemide. As renal tubular dysgenesis was suspected, endocrinological assessment was performed on day 12. It revealed an excessively high active renin concentration > 330 ng/l (normal 6.3 to 149 ng/l), a low concentration of ACE < 8 U/l (normal 8.3 to 21.4 U/l) and hypoaldosteronism (aldosterone < 37 ng/l, normal 73–425 ng/l). As this is a common finding in RTD, we established a fludrocortisone therapy resulting in stable electrolytes and bicarbonate. The infant required a gastric tube due to poor feeding until the 6th week of life. He was discharged at the age of 7 weeks.
Mutational analysis of the ACE gene showed a novel compound hyterozygous mutation. C.5303 + 1G > A has been described before and impairs splicing of pre-mRNA of ACE []. The other mutation was c.1487G > A and has not been reported before in RTD. Therefore, we present a patient with a novel compound hyterozygous constellation of RTD.
The patient is now 17 months of age and has been re-admitted several times for dehydration due to poor feeding in times of respiratory infection. Whenever fludrocortisone therapy was discontinued due to non-compliance, the patient developed hyperkalemia and rise of creatine levels. Currently he is suffering from stage 2 chronic renal disease with a GFR of 60 ml/min/1,73m2 (normal > 90 ml/min/1,73m2). Renal ultrasound shows increased echogenicity but no enlargement of the kidneys. With reestablished fludrocortisone therapy and sodium bicarbonate substitution electrolytes and blood urea nitrogen are normal, serum creatinine and cystatine C only slightly elevated (Creatinine 0,45 mg/dl, cystatine C 1,43 mg/l). Blood pressure is on the 50th percentile. Cognitive and psychomotor development are age-appropriate. |
pmc-6302428-1 | A 78-year-old female farmer diagnosed with H7N9 infection was referred to our hospital with a 7-day history of fever (39.5 °C), cough and chest tightness. She had a well-controlled 4-year history of hypertension and reported having had contact with a dead chicken. Examination revealed stable vital signs, normal muscle strength, a white blood cell count of 6.9 × 109/l, a CRP of 229 mg/L, a creatine kinase of 83 U/l, a creatine kinase-MB of 10 U/l, a lactate dehydrogenase of 278 U/l, an alanine aminotransferase of 23 U/l, and an aspartate aminotransferase of 35 U/l. A chest CT revealed the upper lobes on both sides, and the lower lobe of the left lung showed high-density and large-scale shadows. (Fig. a and b) She was treated with oral oseltamivir (150 mg twice), piperacillin tazobactam 4.5 g q8 h, methylprednisolone (40 mg once daily), intravenous immunoglobulin, as well as probiotics. Total parenteral nutrition was initiated and continued for 2 days with regular insulin (50 units, microinfusion pump) and was later changed to enteral nutritional suspension (500 ml daily, nasal jejunal feeding tube). By 36 h after admission, her illness rapidly progressed with the development of ARDS. Oxygen therapy and mechanical ventilation were started along with a series of ventilator-associated pneumonia(VAP) prevention strategies, such as elevating the head from the bed by 30 degrees, careful oral care, and removal of subglottic secretions.
This patient fought a severe, mixed bacterial infection throughout the next two months in the hospital and even developed septic shock on day 15. During this period, intravenous peramivir, administered 300 mg once daily, was added to the antiviral treatment on day 18, and a chest CT scan revealed a better result on day 26 (Fig. c and d). Another 2 days later, the tests for H7N9 virus turned negative, use of midazolam and fentanyl were stopped, and withdrawal of mechanical ventilation was attempted. Until this time, a more complicated clinical condition of limbs and respiratory muscle weakness was present, with a physical examination revealing an upper limb proximal muscle strength measurement of level 0/5, distal parts level 1/5, and lower limb muscle strength level 0/5. That of the right foot dropped significantly, and there were weak leg reflexes. Seat balance and standing balance could not be completed, which could not be explained by her improved pulmonary disease. Electrodiagnostic testing showed upper and lower limb peripheral nerve damage, which was managed with long-term neurotrophic drugs, combined with an immune-modulator, as well as physiotherapy. During this period, several attempts to withdraw the mechanical ventilation failed. A chest CT scan taken on day 42 showed that lesions had shrunk (Fig. e and f). Cough and other symptoms also alleviated gradually, and finally, she began absorbing oxygen via venturi mask one month later. The last chest CT scan was token on day 80 (Fig. g and h), and another 10 days later, she was discharged with a slight cough and expectoration and with no significant dry and wet rales heard. Her upper limb proximal muscle strength was measured at level 2/5, distal parts at level 4/5, and lower limb muscle strength at level 2/5. |
pmc-6302428-2 | A 56-year-old female patient was diagnosed with H7N9 infection and was transferred to the Emergency ICU of our hospital. She had a 3-day history fever(40 °C), cough with yellow sputum, chest tightness and shortness of breath. A chest CT scan from the local hospital showed bilateral lung infection and consolidation in part of the right lobe. She had had a resection of a meningioma brain tumour but had been well before admission. She reported having been to a live poultry market during the 2 weeks before disease onset. She had a fever (38.8 °C) and unstable vital signs when admitted. She showed a blood pressure of 79/53 mmHg and an SpO2 of 83% under the application of a macadamized respiring ball charged with mechanical ventilator, morphine 30 mg combined with midazolam and a combination administration of intravenous infusion via micro-pump dobutamine 100 mg, deslanoside 0.4 mg and noradrenalin 10 mg to stable her blood pressure. Another examination revealed a white blood cell count of 1.5 × 109/l, a CRP of 165.90 mg/L, a creatine kinase of 199 U/l, a creatine kinase-MB of 18 U/l, a lactate dehydrogenase of 671 U/l, an alanine aminotransferase of 19 U/l, and an aspartate aminotransferase of 59 U/l. A chest X-ray (Fig. a) showed bilateral large dense shadows and pleural effusion. Oseltamivir (150 mg, twice daily, nasal jejunal feeding tube) and peramivir (300 mg, once daily, intravenously), as well as methylprednisolone (40 mg, once daily, microinfusion pump), piperacillin tazobactam, intravenous immunoglobulin, pinaverium bromid, and probiotics were administered on day 1. In addition, enteral nutritional suspension (500 ml daily, nasal jejunal feeding tube) was applied with regular insulin (50 units, microinfusion pump), as well as methycobal (500 μg daily, microinfusion pump) to nitrite nerves.
However, her condition persistently deteriorated. On day 5, she experienced refractory septic shock. After ineffective management of cardiopulmonary resuscitation and other rescue drugs, extracorporeal membrane oxygenation (ECMO) was initiated in combination with continuous renal replacement therapy because of anuria. Tests turned negative for H7N9 in the blood sample on day 10, then we gradually stopped using anti-viral drugs and decided to remove ECMO. 10 days later, she was found to have muscle weakness when a physical examination revealed an upper limb muscle strength measured at level 3/5 with a lower level of 2/5, which was bilateral. That of the distal parts was better than that of the proximal. When her vital signs became sufficiently stable, she received the first chest CT scan, which still revealed large dense shadows (Fig. b and c). Electrodiagnostic testing showed upper and lower limb peripheral nerve damage. Nasal feeding of vitamins B1 and B2 along with long-term physiotherapy, on the basis of methycobal and an immune-modulator, were initiated, as well as strategies to prevent VAP. The next two months were a long battle against severe bacterial and fungi co-infections. A chest CT scan revealed slight absorption of the lesions at the left lung on day 31(Fig. d and e). At last, she was discharged on day 77 after taking a chest CT scan (Fig. f and g) with an upper limb muscle strength measurement of level 4/5, lower limb distal of level 3/5 minus, and proximal parts of level 2/5. |
pmc-6302445-1 | We present a female born via Caesarean section at 32 weeks gestational age to a 31-year-old gravida 4 para 3 (now para 4) mother. The pregnancy course was uncomplicated, and no prenatal genetic testing was indicated. Delivery was emergent due to fetal heart rate decelerations, and after delivery a nuchal cord was noted. Birth weight was 1304 g (10–25%ile for gestational age). The patient stayed in the neonatal intensive care unit for 2 months, during which her course was complicated by intraventricular hemorrhage of unknown grade.
Paternity testing was obtained a few months after birth due to court regulations involving the patient’s parents. Samples from the patient, mother, and alleged father were analyzed using PowerPlex© 16 and CS7 in accordance with standard laboratory practices. A total of 21 polymorphic loci were genotyped. Initial results appeared to exclude the alleged father from paternity due to genetic inconsistencies at loci F13A01 and D5S818. However, the mother insisted on the alleged father’s paternity, and additional testing was subsequently performed. As part of the process for resolution of this unique case, the lab tested PowerPlex© ESX, PowerPlex© Fusion, and PowerPlex© LC5 test batteries. HLA testing was performed as well. Of note was the finding that the patient was homozygous for maternal alleles for all loci located on chromosome 6 (see Table ). These findings prompted the laboratory to recommend that the patient receive a medical genetics evaluation for possible maternal uniparental disomy. Table summarizes the genetic irregularities associated with chromosome 6 that led to suspicion of the underlying condition.
The patient presented for a medical genetics consultation at 10 months of age following the updated test results. During the visit, her mother reported that the patient appeared to be developing well and reaching milestones appropriately. No concerning symptoms were discovered on review of systems. Upon physical examination, her weight was less than the 3rd percentile (even when corrected for prematurity) and length was less than the 3rd percentile (10th percentile when corrected for prematurity). Head circumference was at the 25th percentile. The exam was otherwise unremarkable except for small preauricular pits. Her family history was notable for a maternal half-brother with attention-deficit/ hyperactivity disorder and grandparents with hypertension.
Due to potential health implications of UPD, chromosomal microarray (CMA) testing was ordered to confirm chromosomal composition. CMA analysis using Agilent 4x180k aCGH+SNP array supported the diagnosis of maternal UPD6 (Fig. ). Of note, after confirming this diagnosis, the additional inconsistency on chromosome 5 was concluded to be an unrelated single inconsistency. A single inconsistency in paternity testing is usually interpreted as an inconsequential mutation, and for the D5S818 locus these single inconsistencies are seen in about 0.17% of paternity cases [].
The patient was next seen at 14 months of age to discuss the results of the CMA. At this time, her weight and length were at the 5th percentile (10–25th percentile when corrected for prematurity). She had continued to reach developmental milestones and had no new symptoms or concerning physical exam findings. The family was counseled on the possibility of the patient developing an autosomal recessive condition due to unmasking caused by the UPD. Overall, however, her prognosis is good based on her reassuring first two visits. |
pmc-6302456-1 | A 45-year-old man presented with decreased right visual acuity (VA) accompanied by periocular pain lasting for 1 week. Ophthalmological examination revealed that the patient’s right eye was only able to perceive light (best-corrected VA, light perception/0.9 in decimals, measured using a Snellen chart) and had relative afferent pupillary defect of grade 3, diffuse disc swelling, and inferior disc hemorrhage. Neurological examination showed normal muscle strength in all extremities, no sensory deficits, normoactive deep tendon reflexes, and no signs of bladder or bowel dysfunction. Orbit MRI revealed T2 high signal intensities and diffuse contrast enhancement along the right anterior and posterior optic nerve, as well as perineural enhancement [] (Fig. -a and b). The results of cerebrospinal fluid (CSF) analysis showed a red blood cell count of 0/μL, a white blood cell count of 1/μL, and a protein level of 27 mg/dL. CSF oligoclonal band measured by isoelectric focusing was negative and IgG index was 0.64. The result of a serum AQP4-IgG flow cytometry assay using AQP4-M23-expressing live cells was negative []. Right ON was suspected, and intravenous methylprednisolone (1000 mg pulse therapy) for 5 days followed by oral prednisolone (60 mg daily) were prescribed. The right VA of the patient was improved to 0.5 (visual Functional System score improved to 2 from 5).
The second right ON attack (0.15/1.0) occurred 4 months after the first ON when the prednisolone dose had been tapered to 10 mg daily. Thus, azathioprine 50 mg twice per day was started in a remission state between the second and third ON (4 months prior to the third ON). The average thickness of a retinal nerve fiber layer measured by spectral-domain optical coherence tomography was decreased in the right eye (right 51 μm and left 105 μm) (Fig. -a). The third (hand movement/0.9) and fourth (finger count/1.2) right ON attacks occurred 6 and 10 months after the second ON, respectively, while the prednisolone dose was maintained at 5 mg daily and azathioprine was 75 mg twice per day. Following these attacks, the patient developed left central serous chorioretinopathy (0.15/0.9) associated with long-term steroid use. The 25 mg dose of prednisolone was thus tapered out at this point. Nevertheless, right ON recurred 2 months later for a fifth time (hand movement/0.9) when the patient was under azathioprine treatment only. At this time, the patient developed monocular blindness. The pattern-reversal visual evoked potential showed an abnormal waveform in the right eye with diminished amplitude. The left eye presented a relatively preserved response with prolonged P100 latency (118 ms) (Fig. -b). Serum from the patient sampled at the time of the fifth ON attack was tested for MOG-IgG1 using a cell-based assay utilizing full-length human MOG (Radcliffe Hospital, Oxford, UK) []. The result of this test was positive.
Despite continued immunosuppressive treatment and due to the repeated ON attacks and the side effect of the steroid (chorioretinopathy), the patient was administered RTX (375 mg/m2, 3 weekly infusion for induction and 3 maintenance doses under CD19+ B-cell monitoring over 29 months). Although one mild ON attack (no light perception/1.2) occurred in the patient’s right eye during RTX treatment, the rate of relapse decreased markedly and the patient’s visual function was well-maintained. However, 32 months after the initiation of RTX treatment, we became unable to maintain RTX treatment due to insurance issues (denial for reimbursement). As a result, the treatment was switched to mycophenolate mofetil (250 mg twice per day) combined with oral prednisolone (5 mg every other day). The patient’s CD19+ B-lymphocyte level was restored to 2 and 4% at 9 and 11 months after the last RTX infusion, respectively. Subsequently, 2 more left ON attacks (hand movement/1.0 and hand movement/0.15) occurred within a one-month interval (Fig. -c and 1-D). The titer of MOG-IgG1 was measured by a geometric mean fluorescence (G-mean) ratio of the MOG-expressing cells bound to IgG1 using in-house flow cytometry. The G-mean ratio was calculated for each sera as followings: G-mean values of the patient’s sera / G-mean values of the healthy control. The titer was not associated with the continuation or cessation of the RTX treatment (Fig. -e). |
pmc-6302502-1 | 44-year-old man had a history of trauma and splenectomy dating back to 2008 due to a high fall accident injury. The patient came to our hospital for routine follow-up health check for trauma. During the interview with the doctor, the patient had complaints of fatigue, flu-like symptoms and occasionally had the sense of thoracalgia for about a week. During the physical examination, a well healed laparotomy scar measuring about 10 cm in the upper left abdomen was identified. No spleen was palpable when palpation of left costal region was conducted by the doctor. No other significant findings were identified. All laboratory findings were within normal range. Hematology and biochemistry tests were within normal range. All other laboratory findings were within normal range too. Pulmonary function tests and cardiovascular examination showed the normal state. Plain chest computed tomography (CT) with an attenuation value 52HU was performed. There were multiple nodules under the left upper lobe tongue segment, lower lobe basal segment subpleural and right diaphragmatic, partial fusion showed wavy changes with uniform density. There were clear boundary and enhanced scanning lesions, measuring up to 18 mm, suggesting suspicious for primary lung cancer. There were old fractures of the left side 9th and 10th ribs, and no right sided pulmonary lesions or mediastinal lymphadenopathy were seen on CT. Contrast-enhanced CT scans showed obvious enhancement in soft tissue masses (Fig. ).
Based on CT imaging, the surgery of left thoracic exploration and lumpectomy of the chest wall was planned to relief symptom, remove masses. After discussed with patient. Via video-assisted thoracic surgery (VATS) was performed to remove the masses. During the operation, we found mass on the surface of the upper lobe of the left lung, and a large number of nodules that scattered on the surface of left lung surface, diaphragm and mediastinal pleura. The largest nodule was tough in texture, regular in shape, and was measured about 1.82.0 cm on pleura. (Fig. ) We completely removed this biggest mass and other masses on left pleura through thoracotomy. After careful hemostasis, a chest tube was placed in the seventh intercostal space at the mid-axillary line and attached to an underwater seal. The left lung was re-inflated under direct vision. On the third day after surgery, the chest drain was removed after minimal drainage.
The patient had an excellent recovery after surgery and was discharged properly. Final pathological findings: (Fig. ) on H&E slide, the mass was consisted of red pulp and white pulp of spleen with splenic corpuscle and spleen trabecular structure, which showed viable splenic tissue. Immunohistochemically, cells of masses were CK(−)、CD3(T cell+)、CD20(B cell+)、TTF-1(−)、Syn(−)、Ki-67(+,5%)、CD34(sinusoid+)、CD8(sinusoid+)、CD1a(−)、S-100(−)、CD68(sinusoid+) (Fig. ). The final pathological diagnosis was splenosis without malignancy. |
pmc-6302511-1 | A 27-year-old male was admitted to our unit upon presentation of a painless mass in the right groin in April 2015. Biopsies of the lesion revealed lymphoma, and antibodies against HIV were positive. He refused to accept any treatment for the concomitant HIV infection. In the following 3 months, the mass became larger and ulcers formed on the skin. In addition, the right thigh also became involved. He suffered from recurrent fever, with a body temperature fluctuating from 38 to 40.5 °C, and his body weight decreased by approximately 12 kg within 3 months.
In August 2015, a biopsy of the mass aspirate showed BL, and the immunohistochemical results were positive for CD20 and EBV-encoded RNA (EBER)1/2. In addition, a bone marrow biopsy showed the total chromosomes to be normal, whereas the percentage of unidentified cells was 1.8%.
Using positron emission tomography–computed tomography (PET–CT), we found increased abnormal metabolism of fludeoxyglucose (FDG) in the right groin; the region had dimensions (in cm) of 12.0 × 16.5 × 27.0, and the boundaries were not clear. The right thigh, anterior to the bilateral mandible, neck, axillary, retroperitoneal vessel, right iliac fossa, pelvic wall, and right inguinal lymph nodes shown increased metabolism of FDG. A blood count showed abnormal levels of lactate dehydrogenase (LDH; 1579 U/L) as well as a white blood cell (WBC) count of 4.42 × 109/L, a neutrophil count of 2.92 × 109/L, a hemoglobin level of 122 g/L, and platelet count of 330 × 109/L. The patient was diagnosed as having stage IV BL.
The HIV RNA load was 51,386 copies/mL, and the CD4+ T cell count was 107 cells/μL at the time of BL diagnosis. In addition, the patient was co-infected with EBV, and the EBV DNA load was 4.09 × 104 copies/mL. No other serious opportunistic infections were present, and the CD4+ T cell count was < 200 cells/μL; therefore, he was started on cART immediately with lamivudine (300 mg daily), tenofovir (300 mg daily), and efavirenz (600 mg daily) on the 25th of August 2015. These medications were not changed, and drug resistance did not occur.
The patient was started on a standard dose of rituximab, piraubicin, vincristine, etoposide, cyclophosphamide, and prednisone acetate (R-EPOCH) chemotherapy on the 31st of August 2015 (day 0). The patient developed a fever on the 6th of September because of a Staphylococcus aureus infection in his ulcer, based on a drug-sensitivity test. The patient is allergic to penicillin; therefore, he received lincomycin (400 mg, q.d.s.). Local debridement was performed every day, and his temperature returned to normal 7 days after treatment. Lincomycin was stopped on day 16 because of a continuous negative result in blood culture. He was diagnosed with agranulemia (neutrophil count = 0.01 × 109/L) on day 13, and granulocyte-colony stimulating factor (G-CSF; 150 μg, q.d.s) was given until the neutrophil count reached 0.5 × 109/L. Meanwhile, he suffered a pulmonary infection and meropenem (0.5 g, b.d.s.) was added until the symptoms were controlled completely (achieved on day 30). A bone marrow biopsy showed that proliferation of the bone marrow was active, and abnormal cells were not detected.
The second cycle of chemotherapy comprised rituximab, methotrexate, and cytosine arabinoside (Ara-C). It was started on the 21st of September (day 22) and stopped on the 23rd of September (day 24). No serious complications occurred, and the EBV DNA load was reduced to 5 × 103 copies/mL on day 30.
From the 9th of October (day 40) to the 23rd of October (day 54), he received a third cycle of chemotherapy with rituximab, cyclophosphamide, vinorelbine, pirarubicin, and dexamethasone (R + HyperCVAD). The EBV DNA load was undetectable after the third cycle of chemotherapy.
From the 30th of October (day 61) to the 1st of November (day 63), a fourth cycle of chemotherapy (rituximab plus methotrexate/Ara-C (R-MA)) was undertaken. In addition, six intrathecal injections of methotrexate, Ara-C, and dexamethasone were used during the second and fourth cycles of chemotherapy. After the fourth cycle of chemotherapy, the HIV RNA load was < 40 copies/mL, the CD4+ T cell count was 193 cells/μL, and the LDH level was 91 U/L. PET–CT showed that the tumor volume in the right groin and the maximum standardized uptake value (SUVmax) were reduced significantly, which suggested that tumor activity had been inhibited (Fig. a).
During the second and fourth cycles of chemotherapy, when the neutrophil count was < 0.5 × 109/L, G-CSF (150 μg, q.d.s.) was administered until the neutrophil count reached 0.5 × 109/L. Symptoms of myelosuppression were treated by infusion of packed red blood cells (RBCs) and concentrated platelets, and oral mucositis was treated by gargling with chlorhexidine. The details of the chemotherapy regimens are summarized in Fig. . |
pmc-6302768-1 | Here, we report an 11 years-old girl, second daughter of healthy non-consanguineous parents of Portuguese origin. She presented with very severe vesiculo-pustular rash in the 1st week of life (Figure ). Biopsy showed dermis infiltration by CD68+CD163+S100–CD1a–histiocytes and a presumptive diagnosis of juvenile xanthogranuloma was made. At the age of 2 months, she started bloody diarrhea and early-onset IBD was diagnosed based on the endoscopic and histologic findings. The bowel disease improved after treatment with prednisolone and maintenance with azathioprine. Nevertheless, she continued to have recurrent episodes of blistering skin rash and presented recurrent chest infections. At the age of 3 years she started to have recurrent eye inflammation that was associated with ocular hypertension. Systemic xanthogranuloma was suspected and she was treated with vinblastine, 6-mercaptopurine, methotrexate, and steroids. Her symptoms did not resolve and she had more frequent infections, including acute otitis media, recurrent chronic sinusitis, recurrent pneumonia, and on one occasion, pulmonary Aspergillus infection that responded to itraconazole. Cutis laxa was evident since she was 6 years-old (Figure ) and progressive sensorineural deafness was diagnosed at the age of 7, requiring a hearing-assistive device. Immunological analysis at that age revealed low IgM and IgA, absent responses to protein antigens and low B cells, with almost absent class-switched memory B cells. T-cell proliferation responses were preserved. No auto-antibodies were found (Table ). Whole blood stimulation assays showed a strongly reduced production of IFN-γ and IL-17 in response to polyclonal T-cell stimulation and reduced production of IL-10 and IL-1β after LPS stimulation (Figure ). However, there was a significant innate induction of IL-6 and TNFα in response to various TLR agonists including LPS, PAM 2/3, Flagellin, and CL-097 (Supplementary Figure and Supplementary Table ). She started prophylactic co-trimoxazole, immunoglobulin replacement, as well as low dose steroids (5 mg every other day) and hydroxychloroquine (Figure ), which led to substantial improvement. Nevertheless, since the age of 10 years she started to have several relapses of eye inflammation, skin rash, and pulmonary inflammation (interstitial pneumonitis) that improved only partially with high-dose steroids. Anakinra (IL1-receptor antagonist) and canakinumab (IL1β monoclonal antibody) were tried without any effect. In view of the excellent results of the use of JAK inhibitors in auto-inflammatory diseases (), and given that PLCγ2 requires upstream signaling events for its activation, we have very recently decided to treat the patient with ruxolitinib as a bridge to hematopoietic stem cell transplantation.
To uncover genetic basis of the disease, we used whole exome sequencing and identified a heterozygous missense L848P mutation in the PLCG2 gene. Sanger sequencing showed that this mutation appeared de novo in the patient, while being absent from both parents and a healthy sibling (Figures ). The mutation affected amino acid residue Leu848 in the split pleckstrin homology (spPH) domain of the PLCγ2 protein that is conserved in most vertebrates (Figure ). The L848P mutation is unique to this patient: it was never found in humans, e.g., it is absent from more than 120,000 subjects in the gnomAD database (). Interestingly, DNA polymorphism rs114618894 that has ~2% frequency in Africans affects the same amino acid residue leading to the L848F substitution. Bioinformatics analysis predicted that the patient's mutation L848P was damaging (e.g., SIFT = 0.99, MutationTaster = 0.99), while L848F was neutral. We used I-Tasser () to model the PLCγ2 protein fragment between amino acids 770 and 1044 containing the L848P and L848F substitutions and found that L848P is predicted to affect the PLCγ2 structure, while L848F had only minimal impact (Figure ). The spPH domain contributes to auto-inhibition and also binds Rac. A mutation in this domain has been shown to cause gain of function leading to severe auto-inflammatory disease in mice (). Furthermore, an activating spPH mutation L845F, which is close to residue L848, has been described in cancer resistance to Ibrutinib, the drug acting on Btk upstream of PLCγ2 (). In order to test the functional effect of the newly found L848P mutation, we cloned PLCγ2 and introduced by site directed mutagenesis L848P or the previously reported APLAID mutation S707Y. We transfected these constructs into COS-7 cells and measured IP production. In this standard cellular assay, both L848P and S707Y mutants showed increased basal and EGF-stimulated activity in comparison to wild-type PLCγ2 (Figure ). Taken together, our data show that L848P is a de novo gain-of-function mutation that is very likely to have caused the disease in our patient. |
pmc-6303855-1 | An 83-yr-old male patient presented to our department due to severe abdominal pain for 8 h, especially the peripheral umbilicus. The pain showed no obvious attention when changing the body position. On physical examination, no tenderness or rebound tenderness was felt in the peripheral umbilicus. Abdominal contrast enhanced CT scan indicated intussusception in the duodenum and the upper segment of jejunum, as well as internal hernia (Fig. ). He received no abdominal surgery before. Besides, he complaint of progression in the abdominal pain, and then laparoscope was carried out which showed left-sided paraduodenal hernia (Fig. a). The motion of the intestinal canal involved by hernia was poor. Subsequently, the patient was transferred to celiotomy, during which slight ischemic changes were noticed in the intestinal canal. A hernial orifice was noticed in the left orifice of the duodenum (Fig. b). No obvious intestinal necrosis was identified, the hernial sac wall was resected and the orifice was completely cut (Fig. c). The patient was followed up for 2 two years until now with no recurrence. Written informed consent was obtained from the patient. The study protocols were approved by the Ethical Committee of the Taizhou Central Hospital. |
pmc-6303859-1 | An otherwise healthy 52-year-old male (172 cm tall and weighing 74 kg) was scheduled to undergo video-assisted upper lobectomy for left lung cancer.
Thoracic paravertebral block (TPVB) was planned using an Esaote ultrasound machine ((MyLab™Alpha, Esaote, Italy) and a low-frequency curvilinear transducer. We chose to perform the TPVB using the out-of-plane parasagittal approach since that is our department’s custom. After placing the patient in the right lateral position, the transducer was placed 2.5 cm lateral to the midline in a sagittal orientation, slightly oblique toward lateral []. Paravertebral space (PVS) between the T4 and T5 transverse processes was detected. This location was between the superior costotransverse ligament and the pleura. A 5-cm 22 G needle (Stimplex®D, B. Braun, Germany) was inserted at the lateral side of the transducer slightly toward medial. During the advancement, the needle tip was not visualised on the ultrasound screen. Only tissue displacement could be seen. Several attempts were performed. At the last attempt, the needle tip was visualised just below the superior costotransverse ligament in the middle of PVS. After a further advancing the needle, anterior displacement of the pleura in the centre of T4–5 PVS was visualised upon injection of the saline. Just before the local anaesthetics were available to be administered, aspiration of red blood was identified. The TPVB in this T4 level was discontinued. Again, we detected the T6 paravertebral level, the technique was the same as that in the T4 level. This time, the entire procedure was uneventful. Appropriate needle tip location was confirmed by displacement of pleura with widening of the intercostal space after injection of the saline. Aspiration through the needle was negative. Fifteen millilitres of 0.4% ropivacaine was injected. During the whole procedure the patient did not have any discomfort, pain or sign of pleural irritation. He was haemodynamically stable.
When the chest cavity was entered, the surgeon found that in the left PVS underlying the pleura, there was a bulging, column-shaped haematoma extending from T1 to T12 with concomitant spread into the left T4–5 intercostal space to the post-axillary line (Fig. ). No injury to the lung tissue was identified. The haematoma was left untouched. One gram of tranexamic acid was infused over 15 min. The operation was carried out as according to routine protocol and was uneventful.
Following the operation, the patient was started on an intravenous patient-controlled analgaesia (PCA) with sufentanil. On postoperative day 1, the patient complained of severe dynamic pain of 8/10 on a numeric rating score in the nipple area that was not alleviated by the intravenous PCA. Rescue analgaesia was given. A neurologic examination revealed intact sensory function in the T4 dermatome bilaterally and diminished sensation in the left T5-T7 dermatomes. The patient made a full recovery with no neurological sequelae and was discharged one week later. |
pmc-6303890-1 | A man in his late 60s with a history of Stage I melanoma of the upper thigh, for which he had undergone wide local excision and negative sentinel lymph node biopsy 2 years prior, presented with new metastatic disease. On imaging, he was found to have lesions of the lung, liver, vertebrae, and brain. Fine needle aspiration of a thoracic lymph node confirmed metastatic melanoma. Next generation sequencing was notable for BRAF V600E mutation.
The patient started treatment with combination ipilimumab and nivolumab. While undergoing immunotherapy, the patient also received radiation to his T7-T10 vertebral metastases (30 Gray (Gy) in 10 fractions) and had stereotactic radiosurgery (SRS) to 16 brain metastases. Spinal irradiation was performed with a 3D conformal technique using opposed anterior-posterior/ posterior-anterior fields. The maximum dose to the spinal canal was 33.5 Gy.
Magnetic resonance imaging (MRI) of the brain following SRS showed marked treatment response. Re-staging computed tomography (CT) of the chest, abdomen, and pelvis, performed 2 months after his initial staging scans, also showed major systemic response. Prior to starting his fourth cycle of ipilimumab and nivolumab, the patient noted the onset of intermittent numbness and tingling of the soles of his feet, with gradual ascension to his knees over the next 2 months.
MRI brain 1 month later showed a new punctate cerebellar metastasis, which was treated using SRS. Positron emission tomography (PET)/CT demonstrated resolution of numerous hyper-metabolic lesions with a remaining area of increased focal uptake in the left ischial tuberosity (Fig. ). Given evidence of disease progression in the ischial tuberosity but not other systemic areas, the patient transitioned to pembrolizumab and received radiation to his ischial lesion. Approximately 2 weeks after starting pembrolizumab, the patient noted gait instability and ataxia, and further ascension of numbness to the level of his hips. At that time, he was still able to ambulate independently with the assistance of walking sticks. One month after starting pembrolizumab, the patient presented to the emergency department (ED) with 1 day of urinary retention and fecal incontinence. A spinal MRI was performed which showed T2 signal abnormality and patchy enhancement in the thoracic spinal cord (T5 to T10) concerning for myelitis or radiation necrosis without evidence of tumor or malignant cord compression. The T2 signal abnormality corresponded with the thoracic spinal radiation field (Fig. ). Given that the lesion was enhancing and initially confined to the radiation field, radiation necrosis was favored at that time.
The patient’s immunotherapy was discontinued, steroids (dexamethasone 8 mg twice daily) were initiated, and two doses of bevacizumab (for possible radiation necrosis) were administered, without improvement. Lumbar puncture was deferred due to recent bevacizumab. Given the lack of improvement to optimal therapy for radiation necrosis, transverse myelitis was then favored. Results of serologic evaluation of metabolic (vitamin B12, thyroid stimulating hormone), infectious (human immunodeficiency virus, rapid plasma reagin), and autoimmune (anti-nuclear antibodies, anti-Ro/La, aquaporin-4 immunoglobulin G, erythrocyte sedimentation rate, C-reactive protein) etiologies of transverse myelitis were normal. The patient was trialed on high-dose intravenous methylprednisolone (1000 mg daily for 5 days) for transverse myelitis. His lower extremity numbness and gait instability progressed and he started plasmapheresis.
Following 15 sessions of plamapheresis, a dose of cyclophosphamide 1000 mg/m2 was added but the patient continued to decline with worsening urinary retention, bilateral lower extremity spasticity, and complete loss of lower extremity sensation to T5. He did not have upper extremity involvement. Cerebrospinal fluid (CSF) analysis at that time was remarkable for elevated protein (total protein, 99 mg/dL; institutional normal range, 15–45 mg/dL) and negative for malignant cells. Myelin basic protein was elevated at 31.6 ng/mL (normal < 5.5), and oligoclonal bands were matched in the serum and CSF, consistent with an ongoing systemic immune reaction. CSF albumin index was mildly elevated, suggestive of slight impairment of the blood-CSF barrier. Serum studies for antibodies to human T-lymphotropic virus (HTLV) I and II, and a paraneoplastic panel (anti-NR1, anti-GAD65, anti-alpha 3AChR, anti-LGI1, anti-VGCC, anti-VGKC, anti-CASPR2, anti-amphiphysin, anti-CV2, anti-Hu, anti-Ma, anti-Ta, anti-recoverin, anti-Ri, anti-Yo, anti-Zic4) were negative. A serum IL-6 level was normal. A serum TNF-alpha level was not obtained. MRI of the brain demonstrated two new intracranial metastases. MRI of the spine showed progression of transverse myelitis from T3 to T11 (Fig. c), now clearly outside the radiation field. Body PET/CT revealed worsening osseous metastatic lesions; therefore the patient began dabrafenib and trametinib. Given his ascending transverse myelitis despite optimal therapy other options including tocilizumab and infliximab were considered. Based on the low IL-6 level, the patient was started on infliximab. Spinal MRI 3 weeks after the first dose of infliximab showed a dramatic reduction of the level of the T2 cord signal abnormality back to T6 to T10 (Fig. d) with corresponding improvement in sensory level and muscle spasms. Continued treatment with infliximab led to additional incremental gains on imaging but without further clinical improvement. He subsequently developed systemic progression on dabrafenib and tremetinib (but with stable central nervous system disease) and ultimately succumbed to his disease. |
pmc-6303906-1 | A 69-year-old Korean housewife presented to the ED with cardiac arrest. She had no past medical, social, or environmental risk factors and no family history of cardiac disease. She visited a local pain clinic and underwent epidural analgesia 74 min before visiting the ED. She lost consciousness, and cardiac arrest occurred 35 min after the procedure. She had initial asystole. The emergency medical services team performed CPR and transported her to the ED. She arrived at the ED with asystole and no measurable vital signs. Her GCS score was 3 points. Her pupils were fully dilated, and all brainstem reflexes were lost. Successful ROSC was achieved after 6 min of CPR. Her blood pressure was 225/150 mmHg, and her heart rate was 104 beats per minute. Brain CT after ROSC demonstrated extensive anoxic brain damage and pneumocephalus, bilateral middle and lower frontal convexity, and Sylvian fissures (Fig. ). The patient was admitted to the ICU, and post-cardiac arrest care interventions were performed. Her metabolic acidosis progressed, and she underwent continuous renal replacement therapy for 15 days. Electroencephalography showed diffuse cerebral dysfunction. On the 31st day of hospitalization, she was transferred to a long-term care facility with CPC 4 status. She died 14 days after leaving the hospital. |
pmc-6303948-1 | A previously healthy 21 year old Asian male working as a waiter in a tourist hotel presented with fever, arthalgia, myalgia and progressively reducing urine output over four days. He developed shortness of breath with non-productive cough following hospital admission and was electively intubated due to respiratory failure. There was no obvious history of leptospirosis exposure. He had no significant past medical or surgical history. He was not on any long term medication and with the onset of fever had self-medicated with paracetamol but in correct dose and correct time intervals. There was no significant family history of neurological disease or lung disease. He is a non-alcoholic, non-smoker and does not abuse illicit drugs. He denied any high risk sexual behaviour.
On examination he was febrile, tachypnoeic and pale. There was icterus with conjunctival injection. He was haemodynamically stable. Lungs had bilateral diffuse coarse crepitations and was desaturating on air prior to intubation. Examination of the abdomen was unremarkable. Neurological examination was normal at this point.
Arterial blood gas analysis showed evidence of type two respiratory failure with mixed respiratory and metabolic acidosis. Chest x-ray showed bilateral diffuse pulmonary shadowing and high resolution computed tomography(HRCT) of chest showed features suggestive of pulmonary haemorrhages. With the suggestive clinical picture, even with the absence of exposure to leptospirosis he was started on intravenous ceftriaxone empirically along with high dose intravenous methyl prednisolone pulses (500 mg daily for 3 days) for the treatment of pulmonary haemorrhages. Initial full blood count had neutrophil leucocytosis (white blood cells 16,000/uL, neutrophils 85%, lymphocytes 12%) with thrombocytopenia (platelet count 98,000/uL). Haemoglobin was normal (13.5 g/dL). Initial urine full report had 45–50 pus cells and 2–3 red cells per high power field. There was sub nephrotic range proteinuria (urine protein to creatinine ratio 2.5 g/mmol). Ultrasound scan showed acute renal parenchymal changes. Serum creatinine was high ranging from 256 umol/L and 768 umol/L) where regular haemodialysis was initiated.
After two weeks of the onset of the illness while he was being weaned off from the ventilatory support with improvement of pulmonary haemorrhages, he developed sudden severe lower limb weakness followed by upper limb weakness over one day. There was no diplopia. Assessment of dysphagia and bladder involvement was difficult at that point due to the indwelling nasogastric tube and the urinary catheter. Limb weakness then progressed to respiratory muscle weakness and required continued ventilatory support.
Examination at this point revealed flaccid weakness of both upper and lower limbs with global areflexia. There was no sensory impairment. Pupils were dilated with sluggish pupillary response and there was disc swelling bilaterally on examination of the optic fundi. Following recovery patient had permanent visual impairment (visual acuity 6/60 bilaterally) with pale optic discs. Other cranial nerves were normal.
With the development of neurological symptoms nerve conduction studies were performed which showed evidence of sensory motor demyelinating type polyneuropathy suggestive of AIDP type GBS. Cerebrospinal fluid analysis done on the 10th day from the onset of neurological symptoms showed cyto-protein dissociation. He was started on intravenous immunoglobulin 0.4 g/kg/day.
By day 18 of the illness there was progressive thrombocytopenia (lowest platelet count 15,000/uL) and severe anaemia (haemoglobin 5.6 g/dL). His lactate dehydrogenase (LDH 950 U/L) and indirect bilirubin was high with blood picture evidence of microangiopathic haemolytic anaemia. Direct antiglobulin test was negative. Prothrombin time and activated partial thromboplastin time was within the normal range throughout the hospital stay. Diagnosis of TTP was made and plasmapheresis was initiated as it would treat both TTP and GBS. Human immunodeficiency virus antibodies, the Venereal Disease Research Laboratory test, Mycoplasma antibodies, Epstein Barr and Cytomegalovirus antibodies were negative. Magnetic Resonance Imaging (MRI) brain with Magnetic Resonance Angiogram (MRA), and Magnetic Resonance Venogram (MRV) brain was normal. Renal biopsy showed focal glomerular necrosis and acute tubular injury together with some evidence of infection. A 15 panel leptospirosis Microscopic Agglutination Test (MAT) done on day 8 of the illness revealed a high titre for leptospira antigen serogroup Semaranga (strain Patoc) (1:1280) followed by serogroup Australis (strain Australis) (1:640) and serogroup Autumnalis (strain Bankgkinang) (1:320) while serovars bataviae, bakeri, ratnapura, hardjo, icterohaemorrhagiae, pyrogenes, pomona, hebdomadid, cynopteri, canicola, javanka and Sarmin had insignificant titres (< 1:20). In the convalescent phase MAT titres had increased to a four fold rise for serovars patoc, australis and bangkinang diagnosing leptospirosis.
Intravenous Ceftriaxone was continued for 14 days. Neurological improvement was noted following 14 cycles of plasmapheresis and he recovered from TTP by 12 cycles of plasmapheresis. But complete neurological recovery was not achieved at the end of the hospital stay and he was planned for long term neurological rehabilitation and he ended with permanent bilateral visual loss. He was dialysis dependent on discharge from the hospital due to progression to chronic kidney disease. |
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.