The 21 - year - old patient presented to the closest emergency department at 8 PM for nausea , numbness of the left limbs , incoordination of walking and dysarthria , with the symptomatology installed in a progressive mode 4 hours before presentation . The nausea was the initial symptom , starting at 4 PM ( without headache , nuchal pain , or vomit ) and then , after 5.30 PM , the numbness of the left limbs and the incoordination of walking and by 7 PM dysarthria was added to the entire clinical constellation . The patient did not have a medical history or a current medication . He was a student . He did not smoke and did not use recreational drugs . He only drank alcohol occasionally . There was no family history of thromboembolism , cardiovascular problems , or hematologic diseases . He was first evaluated by a neurosurgeon in the emergency unit and had a brain CT scan that highlighted infracentimetric hypodensity in the thalamic nucleus , on the left side and at the level of the right cerebellar hemisphere in the PICA territory , and also a chest X - ray that revealed a widened projection area of the right side hilum , without any other pathological findings . Following this evaluation , he was sent to the National Institute of Neurology and Cerebrovascular Diseases for consultation and special treatment . During the ambulance transportation , he had repeated episodes of vomiting . The initial physical examination ( at 10 P.M ) showed normal vital signs : blood pressure 130/ 80mmHg , heart rate 100 beats per minute and normal body temperature 36,8 ° C . The cardiopulmonary exam was normal . No carotid bruits were registered . The neurological examination was notable for normal orientation . The patient had equal , reactive pupils , divergent strabismus to the left eye , horizontal nystagmus , normal deglutition , mild paresis of the left arm , ataxia of all limbs , with an accent on the left extremities , numbness of the left limbs , bilateral response present at all deep tendons reflex , Babinski sign on the left side , stereotypical language . The patient was able to repeat a few words and fragment of phrases and to perform simple commands of medium complexity . The laboratory analysis highlighted a normal hemoleucogram , normal blood glucose level 9,11 mmol/ L ( normal range 3,9 - 5,8mmol/ L ) , serum creatinine 0,69mmol/ L ( range 0,5 - 0,9mmol/ L ) , total serum cholesterol 5,2mmol/ L ( normal range < 5,2 mmol/ L ) . The tests for thrombophilia were negative . He also presented a normal sinus rhythm on the ECG . The brain CT performed at the first emergency unit , as mentioned above , revealed a infracentimetric hypodensity at the level of the left thalamic nucleus and at the level of the right cerebellar hemisphere in the PICA territory . Doppler ultrasound for cerebral and cervical blood vessels highlighted the marked frena in the flow velocities of the V2 segment of the right vertebral artery , an accentuated aspect in the high V2 segments with the complete disappearance of the flow in the V3 segment , without carotid atheromatous lesions or modifications of the trajectories or the arterial caliber . Overall , there was a possibility of a dissection of the right vertebral artery in the higher segments with indication of cerebral and angio MRI . Cerebral and angio MRI showed : areas with T2 , FLAIR hypersignal , with an important restriction of diffusion and low ADC , situated in the right cerebellar area of the postero - inferior territory , anterior bilateral cerebellar territory , left cerebellar peduncle , both right > left thalamic nuclei , as well as subcortical occipital bilateral , with an ischemic aspect that was recently constituted in the vertebrobasilar territory . T1 FS hypersignal was present on the entire intracranial segment of the right vertebral artery and the cranio - spinal junction . On the angiographic arterial 3D TOF sequence , the presence of the rapid flow of the right vertebral artery could be viewed , up to the C2 segment , where there was a progressive pinch out with an aspect of flute beak shape . Distal of this level , there was an absence of the rapid flow signal and also a lack of right PICA visualization . The MRI aspect suggested a subacute dissection of the right vertebral artery . The cerebral ventricular system had normal dimensions , shape , and topography . The pericerebral fluid spaces and the basal cisterns were normal . Conclusions : there were some ischemic lesions recently constituted in the vertebrobasilar territory and also a subacute dissection of the right vertebral artery . Heparin administration was started immediately in the process of hospitalization because of the dissection . The APTT value was kept in the range of 50 - 70 seconds . Also , the prophylactic therapy for stress ulcer was performed . After 7 days from the debut , the patient was transitioned to acenocumarol for long - term anticoagulation . The treatment with acenocumarol was instituted with the heparin overlap until getting the INR therapeutic in the 2 - 3 intervals . The evolution was favorable , the patient regaining the verbal fluency and the capacity for autonomy in movement . The ataxia was remitted at the right limbs and persisted at the left extremities , but registered a lot of improvement . The patient was discharged home with the recommendation to continue the treatment with Acenocumarol for 6 months with clinical , paraclinical and treatment reevaluation at 6 months . The follow up was not possible because the patient did not return to the hospital after 6 months .


A 35 - year - old woman presented to the medical emergency department with low - grade fever for 3 weeks , vomiting for 1 week and anuria for 3 days . She also reported dysuria and breathlessness for 1 week . There was no history of decreased urine output , dialysis , effort intolerance , chest pain or palpitation , dyspnoea and weight loss . Menstrual history was within normal limit but she reported gradually progressive loss of appetite . Family history included smoky urine in her younger brother in his childhood , who died in an accident . On general survey , the patient was conscious and alert . She was dyspnoeic and febrile . Severe pallor was present with mild pedal oedema . Blood pressure was 180/100 mm Hg and pulse rate of 116 / min regular . No evidence of jaundice , clubbing cyanosis or lymphadenopathy was found . Physical examination revealed bibasilar end - inspiratory crepitations in lungs and suprapubic tenderness . There was no hepatosplenomegaly or ascites . Cardiac examination was normal . She was found to have severe bilateral hearing loss , which was gradually progressive for 5 years . The fundi were bilaterally pale . The patient was referred to the department of ophthalmology for a comprehensive eye examination . Her visual acuity was documented as 6/18 in both eyes with no obvious lenticular opacity . Slit - lamp examination showed bilateral anterior lentiglobus ( figure 1 ) with posterior lenticonus ( figure 2 ) . Distant direct ophthalmoscopy revealed oil droplet sign ( a suggestive confirmation of the presence of lenticonus ) ; and peripheral retina revealed multiple yellowish white lesion - like flecks in the mid - periphery , and few blot haemorrhages indicative of hypertensive changes ( figures 3 and 4 ) .


A 23 year old white male with a 4 year history of Crohn 's disease presented with an acute two day history of malaise , fever , abdominal pain , vomiting and stomal diarrhoea . He complained of joint pains affecting the shoulders , elbows , wrists , metacarpophalangeals , knees and ankles . There was also a rash on the elbows , ankles and feet , which began as erythematous macules and evolved to vesico - pustular lesions followed by crusting . There was no history of sexual exposure or any intercurrent infection . He was on no regular medication , but had discontinued Pentasa 4 months earlier . One month earlier he had undergone a laparotomy to excise a complex ileo - cutaneous fistula with blind tracts , and two weeks earlier a defunctioning ileostomy had been created in view of persistent abdominal pain . The cutaneous fistula had been present for a year , but was associated with a terminal ileal stricture and ileo - rectal fistula of at least 2 years duration . His bowel disease had been resistant to immunosuppressive drugs including azathioprine , corticosteroiods and three infusions of Infliximab a year earlier . There had been no extra - intestinal manifestations . On admission to the hospital , he was thin , afebrile with a resting tachycardia of 125 / minute . The rest of the cardio - respiratory examination was normal . The abdomen was minimally tender around the ileostomy without guarding or rebound tenderness . Examination of the skin revealed some pustules and crusts around the elbows , ankles and feet ( Fig 1 and 2 ) . The buttocks were spared . There were clinical signs of synovitis of the wrists , proximal interphalangeal and metacarpophalangeal joints , and also both ankles . Results of the laboratory tests showed a haemoglobin of 13.1 gm / dl , white blood count 15.8 × 109 / L , platelets 585 × 109 / L , C- reactive protein 37.7 mg / L and erythrocyte sedimentation rate 69 mm / hr . Urea and electrolytes , complement , urine analysis and microscopy were normal . Rheumatoid factor , antinuclear and antineutrophil cytoplasmic antibodies , cryoglobulins and Hepatitis B and C serology were negative . Transthoracic echocardiogram showed no signs of endocarditis , and multiple blood cultures were sterile . A skin biopsy from the ankle revealed a perivascular lymphohistiocytic infiltrate with prominent neutrophils and associated fibrinoid necrosis of vessels consistent with ' leukocytoclastic ' vasculitis . He was commenced on 60 mg prednisolone per day leading to prompt and complete resolution of all features . The dose of prednisolone was rapidly tapered over the course of one month by the patient , faster than advised but without any recurrence over the following 3 years .


A 68 - year - old man was referred by his optometrist to HES with suspected LTG due to repeatedly irregular visual field test results , advanced optic disc cupping , normal intraocular pressures ( IOPs ) and a family history of glaucoma . The patient subjectively felt that vision in his ‘ good ’ left eye ( LE ) , which normally had a visual acuity of 6/6 N5 , started to deteriorate 6 months earlier ; at the point of referral it was best corrected to 6/7.5 N6 . His right eye ( RE ) was known to be amblyopic with a visual acuity of 6/18 N12 . His medical history included considerable risk factors for systemic vasculopathy , such as hypertension , hypercholesterolaemia , 50 pack - years of smoking and type 2 diabetes with no diabetic retinopathy . Despite detailed questioning , he denied any new systemic symptoms apart from experiencing increased lethargy . Clinical examination at HES revealed advanced bilateral cupped optic discs with a cup - to - disc ratio right 0.9 ( 90 % ) and left 0.8 ( 80 % ; figure 1 ) . Furthermore , the findings from the referring optometrist of equal and reactive pupils , normal eye movements and IOPs in mid - teens were confirmed . Computerised perimetry showed constricted visual fields in both eyes , albeit with considerably raised false - negative error rates in excess of 30 % ( figure 2A ) . Since this can be a result of poor concentration and attention span with testing compounded , especially with an amblyopic RE , the field test was repeated 4 weeks later with similar results ( figure 2B ) . At this visit , the patient experienced further deterioration of his ‘ good ’ LE . Visual acuities measured 6/24 ( loss of one Snellen line ) N36 in his amblyopic RE , and 6/18 ( loss of two Snellen lines ) N36 in his LE , which now also showed depressed colour vision . An urgent scan of the patient 's head and orbit was requested to rule out a compressive lesion and blood analysis was carried out to screen for other causes of optic neuropathy including vitamin B12 , folate levels and inflammatory markers . MRI revealed a large mass centred at the pituitary fossa measuring approximately 4.5 cm×5.1 cm× 4.8 cm ( figure 3A – C ) extending into the suprasellar cistern and infrasellar sphenoid sinuses . The optic chiasm and both optic nerves were displaced superiorly and compressed on both sides . The mass showed heterogeneous T1 and T2 signals with multiple fluid levels most likely due to previous haemorrhage and low - signal components suggesting calcifications . The appearance was probably due to a craniopharyngioma or haemorrhagic pituitary adenoma . The patient was referred urgently to the neurosurgery unit and was found to have markedly raised prolactin levels of greater than 200 000 mIU / L , confirming the diagnosis of a giant prolactinoma . In cooperation with the local endocrinology service , he was started on cabergoline 500 µg and dexamethasone 8 mg . Within a week this led to a dramatic improvement of the patient 's visual fields and acuities to 6/18 RE and to 6/9 LE . His prolactin levels showed a similar dramatic response with levels coming down to 336 mIU / L. Three months later his visual acuity in his RE and LE were 6/18 and 6/5 , respectively , and visual field examination showed striking recovery with almost normal results ( figure 2C ) .


On December 28 , 2014 , a 70 - year - old man complaining of abdominal pain , dizziness , and nausea was referred to the Hebei General Hospital , Hebei , China . Gastroscopy showed irregular hemorrhagic ulcerative lesions extending from the gastric body to the lesser curvature and pyloric stenosis of the stomach . Gastric biopsy revealed adenocarcinoma . On January 7 , 2015 , palliative gastrectomy plus Roux - en - Y near esophagojejunostomy were performed . Diffuse enlarged para - aortic and anterior superior pancreatic lymph nodes , as well as lymph nodes around the common hepatic artery , could not be resected . Postoperative pathology demonstrated moderately differentiated gastric adenocarcinoma ( Fig.1A ) . Immunohistochemistry showed the following : human epidermal growth factor receptor 2 ( HER-2 ) ( + ) , vascular endothelial growth factor ( VEGF ) ( + ) , CD31 ( + ) , CD105 ( + ) ( Fig.1B – E ) , triple positive ( TP ) ( + ) , glutathione S - transferase π ( GST - π ) ( + + + ) , topoisomerase enzyme II α ( TOPOII α ) , P53 ( – ) , and Ki-67 ( 70 % ) . The diagnosis was stage IV gastric adenocarcinoma with multiple lymphnodes metastases ( T4N2M1 ) . The patient was administered 1 cycle of chemotherapy with oxaliplatin and S-1 ; however , the treatment was terminated , as the patient could not tolerate the associated gastrointestinal disturbances . On February 2 , 2015 , adjuvant radiotherapy was administered . Before radiotherapy , positron - emission tomography computed tomography ( PET - CT ) showed extensive distant metastasis ( left supraclavicular and mediastinal lymph nodes , and lymph nodes throughout the abdominal cavity ) . The patient 's Eastern Cooperative Oncology Group ( ECOG ) performance status was 2 , and his body mass index ( BMI ) was 19 ; therefore , he was considered to be at risk of malnutrition . Oral apatinib 850 mg once a day combined with and following radiotherapy was prescribed . Informed consent was obtained from the patient prior to treatment . In an attempt to improve tolerance to treatment , palliative intensity modulated radiation therapy ( IMRT ) was used . The patient received a dose of 64 Gy in 30 fractions to the mediastinum and doses of 52 Gy in 26 fractions to the other abdominal metastatic lesions ( n = 5 ) . The left supraclavicular lymph node was treated with apatinib alone ( Figs.2 and 3A – C ) . A PET - CT scan performed 2 weeks after radiotherapy showed an 80 % reduction in the maximum standardized uptake value ( SUVmax ) of 2 - deoxy-2-[[18]F]fluoro - d - glucose ( FDG ) . FDG uptake was higher in the left supraclavicular lymph node compared to the metastatic regions treated with concurrent apatinib and radiation therapy . According to Response Evaluation Criteria in Solid Tumors ( RECIST ) , the clinical effect was partial response ( Fig.2 ) . The patient received further radiotherapy ( 66 Gy in 28 fractions ) to the left supraclavicular lymph node due to residual metastasis . Tumor markers and biochemical analyses were evaluated every 2 months . Two months after therapy , chest , and abdominal CT scans indicated stable disease ; anemia and gastrointestinal symptoms had improved , ECOG performance status was 0 , and BMI was 22 . Hematologic toxicity , hypertension , renal dysfunction , proteinuria , and hand – foot syndrome were not observed during apatinib therapy . In September 2015 , a follow - up examination showed increased carbohydrate antigen ( CA ) 125 and ferritin ; however , gastroscopy and abdominal CT revealed no abnormalities . In November 2015 , the patient had difficulty swallowing and experienced intermittent hematochezia . Apatinib was terminated due to gastrointestinal bleeding . Gastroscopy revealed anastomotic stenosis due to gastric cancer and intragastric hemorrhage ( Fig.3D – F ) . The patient and his family refused chemoradiotherapy . Symptomatic treatment with a hemostatic drug and best supportive care were prescribed . After 1 week of therapy , hemorrhaging was resolved . One month later , the patient again experienced intermittent hematochezia . On December 20 , 2015 , PET - CT demonstrated extensive metastasis . The patient and his family requested best supportive care . On April 16 , 2016 , the patient died due to pulmonary infection .


A 33 - year old woman presented to our cardiology service with signs and symptoms of congestive heart failure . Her medical history was unremarkable , however a year ago and soon after her third child delivery , she had been admitted in another hospital for acute pulmonary oedema after labor . Cor triatriatum with obstructive behavior causing pulmonary hypertension had bee diagnosed , while the left ventricle was structurally and functionally intact . The patient at that time denied surgey and had been discharged on medical therapy . At present admission the patient presented with NYHA functional class III , symptoms of heart failure and palpittions as a result of persistent atrial flutter . On physical examination a loud pulmonary component of the 2nd heart sound and a diastolic murmur was heard in the mitral area . Signs of right - sided heart failure were absent . A transthoracic echocardiography revealed a moderately dilated left ventricle ( LV ) , globally hypokinetic , with severely impaired systolic function ( EF estimated ≥30 % ) . Left atrium ( LA ) was dilated , with a mobile , membrane - like echogenic structure into it . Transesophageal echocardiogram ( TEE ) documented a fibromuscular membrane across the LA , dividing it into two compartments , a proximal one receiving the pulmonary venous flow and a distal one containing the left atrial appendage ( LAA ) . The two chambers communicated via a non - restrictive orifice , but the membrane prolapsed towards the mitral valve inflow causing severe obstruction . Mitral valve appeared normal , with mild regurgitation . Patent foramen ovale ( PFO ) , atrial septal defect ( ASD ) and anomalous venous connections were ruled out and the diagnosis of cor triatriatum was reconfirmed . Magnetic resonance imaging ( MRI ) of the heart also revealed the fibromuscular septum into the left atrium and the low left ventricular ejection fraction [ ( LVEF ) 30 % , cardiac index 1,6 L / min / m2 , cardiac output 2,7 L / min ] ( figure 1 ) . Coronary angiography showed normal coronary arteries . With these findings the patient was scheduled for surgery . Anesthetic induction was achieved with standard technique including administration of sodium pentothal , sevofluorane , fentanyl and muscle relaxant . Invasive monitoring included the use of right radial arterial lines , a pulmonary artery catheter and a foley catheter with temperature probe to measure bladder temperature as an indicator of core body temperature . Transesophageal echocardiography ( TEE ) was also instituted . Surgery was performed through a median sternotomy . Connection to cardiopulmonary bypass ( CPB ) was achieved by standard ascending aorta and bicaval cannulation . Mildly hypothermic ( 32 ° C ) CPB was established . Cold blood cardioplegia was administered in an antegrade fashion through the aortic root after clamping the aorta . The interatrial groove was developed and the common pulmonary venous chamber of the left atrium was opened through a vertical incision anterior to the right pulmonary veins , exactly as for mitral valve surgery . After insertion of a self - retaining retractor to facilitate exposure , the diaphragm was exposed and the central hole in it was identified . A preliminary incision out from the hole improved exposure for the definitive excision . Orifices of the pulmonary veins on both sides were located . Position of the atrial septum was also identified by a small opening in the right atrium and by inserting a curved clamp to displace the septum into the common pulmonary venous chamber of the left atrium . There was no atrial septal defect or patent foramen ovale . The diaphragm was then easily completely excised exposing the mitral valve ( figure 2 ) . The left atrial appendage was closed from inside the left atrium using a running 3 - 0 polypropylene suture to prevent future thrombus formation . The atriotomy incisions were closed , the heart having been filled with blood before the last few sutures were placed . The patient was rewarmed , the aortic cross - clamp was removed and additional de - airing was carried out in the usual manner . CPB was terminated with minimal inotropic support , involving milrinone and levophed with good hemodynamics . The postoperative course was uneventful and the patient was extubated after 12 hours and discharged from the hospital on the fifth postoperative day . At 3 months follow - up , the patient was asymptomatic ( NYHA class I ) , in sinus rhythm . TTE and MRI revealed a mildly dilated LV with great improvement in systolic function and an estimated LVEF of 50 % .


A 67 - year - old woman was sent to emergency department because of fever and sore throat . Her medical history included ESRD with regular hemodialysis 3 times per week for 15 years , hyperuricemia and gout . She also had comorbidity such as dyslipidemia , hypertension , secondary hyperparathyroidism , and diabetes . The hemogram revealed a white blood cell count ( WBC ) of 700 / μL , with 2 % neutrophils , 94 % lymphocytes and 2 % monocytes , hemoglobin 11.1 g / dL , and platelet count , 131,000 / μL. Under the impression of febrile neutropenia and acute pharyngitis , she was admitted to our hematologic ward for further survey and management . Broad - spectrum antibiotics with piperacillin 2 g and tazobactam 0.25 gm i.v . q8h had been administered and her infection sign resolved gradually . Upon admission , we reviewed her oral medication : glipizide 5 mg tid , saxagliptin 2.5 mg qd , fenofibrate 600 mg qd , aluminum hydroxide 324 mg tid , folic acid 5 mg qd , calcium carbonate 1000 mg tid , and febuxostat 40 mg qd . Besides , she also received epoetin - beta 2000 iu i.v.tiw . Except for febuxostat , all the other drugs had been used for more than 1 year . Febuxostat was administered 2½ months before admission for inadequate serum uric acid control by allopurinol 50 mg qd . Two weeks before febuxostat exposure , routine laboratory test revealed WBC 6000 / μL and serum uric acid level 9.8 mg / dL. Febuxostat was discontinued thereafter due to the causal relationship of agranulocytosis can not be excluded . Besides , we also surveyed viral infection and autoimmune disorder . There were no clinical or laboratory evidence of Epstein – Barr virus , cytomegalovirus , or human immunodeficiency virus infections ; antinuclear antibody ( ANA ) and antiextractable nuclear antigen ( anti - ENA ) were both negative . Bone marrow examination during hospitalization showed hypocellular marrow with a marked decrease in myeloid component but no evidence of hematologic neoplasms . Chromosome analysis of bone marrow was normal karyotype . The patient denied history of radiation or chemicals exposure . After stopping febuxostat for 17 days , her neutropenia improved significantly ( WBC 2100 / μL , and neutrophil 66 % ) , without any granulocyte colony - stimulating factor ( G - CSF ) support . After discharge , her WBC and differential count was completely normal during follow - up ( Fig.1 ) . This study was approved by our institutional review board .


An 11 - year - old boy presented with a history of headaches and vomiting that had been present for several months . Physical examination showed papilledema without the presence of any other neurological deficits . Magnetic resonance imaging ( MRI ) revealed a large prepontine mass with dorsal displacement of the brainstem and a secondary obstructive hydrocephalus due to compression of the aqueduct . The lesion had an inhomogeneous hypointense aspect on the T1 - weighted image ( T1WI ) and an inhomogeneous hyperintense aspect on the T2 - weighted image ( T2WI ) . After administration of IV gadolinium , there was some inhomogeneous enhancement ( Fig.1 ) . Computed tomography ( CT ) imaging showed no bone involvement . During the first operation , a ventriculoperitoneal shunt was inserted into the right lateral ventricle to treat the hydrocephalus . A careful study of the MRI suggested that this infra- and supratentorially located tumour might be resected through a single approach . A left frontotemporal transsylvian approach was performed to gain access to the tumour . The tumour had well - defined margins and was entirely located in the intradural plane . There were no attachments to the cranial nerves or brainstem . A macroscopic complete resection was performed . Postoperatively , the patient had developed a left oculomotor nerve palsy , which completely recovered within the next 4 weeks . The postoperative MRI showed a complete removal of the tumour ( Fig.2 ) . After careful consideration by a multidisciplinary team , we decided that there was no indication for postoperative radiation therapy . At follow - up one and a half years later , the patient was found to have remained asymptomatic . There were no signs of tumour recurrence on the MRI scan . At a follow - up of more than 6 years after treatment , there were still no signs of tumour recurrence on the MRI scan . Histological examination showed a slightly lobulated tumour consisting of a chondromyxoid matrix . The tumour cells showed a vacuolated and pale cytoplasm . Moderate nuclear polymorphism was observed but no obvious mitotic activity ( Fig.3 ) . Some calcifications were seen . The tumour cells stained positive for pan - keratin , S-100 and epithelial membrane antigen ( EMA ) . These findings suggest a histopathological diagnosis of chordoma .


A 56 - year - old African American man who initially presented with diarrhea , weight loss and painless jaundice , was subsequently found to have adenocarcinoma of the head of pancreas . An initial workup revealed localized cancer with no evidence of distant metastases . He then underwent pancreaticoduodenectomy with complete surgical resection of a 5 cm moderately differentiated pancreatic adenocarcinoma . Although our patient underwent complete surgical resection , a pathological examination revealed a neoplastic invasion of the resected adjacent organs , and one out of the seven resected lymph nodes contained cancer ( T3N1M0 ) . At that point , the oncology department recommended to proceed with adjuvant chemotherapy with gemcitabine ( 1000mg / m2 IV on days 1 , 8 , 15 on a 28 - day cycle for six cycles ) to try to reduce the likelihood of recurrence . However , after completing two cycles ( a total of six doses ) of chemotherapy , he presented to the emergency department with worsening exertional dyspnea , three - pillow orthopnea , paroxysmal nocturnal dyspnea and fatigue . His physical examination revealed an elevated jugular venous pressure ( JVP ) ( 10 cm above the sternal angle ) , bibasilar rales and +2 pitting edema of both lower extremities . Cardiac auscultation revealed a gallop rhythm with an S3 and a grade 3 holosystolic murmur over precordium . A chest X - ray showed cardiomegaly with mild to moderate - sized right - sided pleural effusion . It was thought that his presentation was consistent with fluid overload secondary to congestive heart failure ( CHF ) and he was started on intravenous ( IV ) furosemide with partial improvement in his symptoms . The next day , a two - dimensional echocardiography ( 2D Echo ) was performed , which showed left ventricular ejection fraction ( LVEF ) of 15 to 20 percent with global hypokinesia along with moderate mitral regurgitation . Given the findings of 2D Echo and the absence of significant risk factors for coronary artery disease ( CAD ) and ischemic cardiomyopathy ( CMP ) , it was concluded that our patient ’s CMP was related to the recent use of gemcitabine . Our patient was then started on carvedilol and an angiotensin - converting enzyme inhibitor in addition to diuretics and he was discharged from the hospital two days later in a euvolemic state . At that point , the cardiology department recommended stopping further chemotherapy with gemcitabine . The oncology department advised further testing to rule out ischemia as a cause of CMP as , in their opinion , chemotherapy with gemcitabine was the only option to reduce the risk of recurrence in this patient . Two weeks later , our patient underwent myocardial perfusion imaging ( MPI ) , which showed a fixed small- to moderate - sized inferior wall defect without any evidence of active ischemia . The ejection fraction ( EF ) on MPI was calculated to be around 17 to 20 percent with severe global hypokinesia . Our patient was continued on standard heart failure therapy with one more admission to the hospital for CHF exacerbation about two months later . He responded well to IV furosemide and adjustment of heart failure therapy . A 2D Echo was repeated a few months later and it showed improvement in systolic function with an LVEF of 40 percent . Due to his poor functional status and underlying CMP , further gemcitabine chemotherapy was stopped . Later , our patient developed a recurrence of his pancreatic cancer ; he refused further chemotherapy and decided to proceed with palliative care . Although the exact etiology of our patient ’s dilated cardiomyopathy remains unclear , gemcitabine remains the most likely culprit . The temporal relationship of his symptoms to the initiation of gemcitabine chemotherapy ; the lack of risk factors for ischemic CMP and prior history of CAD , finding of global hypokinesia on 2D Echo , absence of ischemia on MPI ; and improvement in his systolic function after discontinuation of gemcitabine were all consistent with gemcitabine - induced cardiomyopathy .


A 66 - year - old man was admitted into our Hospital in November 2008 with splenomegaly , a high red cell count , and subnormal serum erythropoietin levels . Cytogenetic analysis showed a normal male karyotype . Molecular studies were negative for the BCR - ABL1 rearrangement , but revealed the JAK2V617F mutation with an allele burden of 44.9 % . A diagnosis of PV was made on the basis of a morphological bone marrow analysis according to the WHO 2008 criteria . The patient was started on aspirin , hydroxyurea , and phlebotomies , all of which were well tolerated . Six years later , an abdominal ultrasound scan revealed the presence of dense bilateral perinephric infiltration , which was confirmed by a whole - body computed tomography ( CT ) scan , and a fluotine-18 fluordeoxyglucose positron emission tomography ( F - FDG - PET ) scan demonstrated increased glucose uptake in the medullary channels of both humeri and femurs . Morphological bone marrow analysis confirmed the previous diagnosis of PV and showed no evident change in the grading of bone marrow fibrosis ( MF-0 according to the EUMNET consensus),13 whereas cytogenetic analysis revealed the following complex male karyotype : 47,XY,+9[2/20],47,XY , add(6)(p25),+9[2/20],46,XY[16/20 ] . The histological nature of the perinephric infiltration was identified by means of a CT - guided core biopsy of the lesion . Morphological analysis demonstrated the accumulation of foamy histiocytes that were positive for CD68 and negative for the dendritic cell markers CD1a and S100 , surrounded by fibrosis and a scanty lympho - monocytic infiltrate ( Figure (Figure1).1 ) . The detection of the BRAFV600E mutation led to a diagnosis of ECD . Cardiac magnetic resonance imaging ( MRI ) revealed pseudo - tumoral infiltration of the atrioventricular wall,14 and a bone scan showed symmetrically irregular radiotracer uptake in the long bones of the limbs consistent with ECD ( Figure (Figure22)2 ; the findings of cerebral and pulmonary imaging were negative . In accordance with the most recent guidelines for the treatment of ECD,1 the patient started therapy with pegylated interferon ( IFN)-alpha and , after 3 months of treatment , a new abdominal ultrasound scan revealed the complete resolution of the dense bilateral perinephric infiltration , and the normalization of the blood cell counts was achieved .


A 60 - year - old Caucasian woman with no significant medical history developed exercise intolerance , fatigue and shortness of breath on exertion over the several months prior to her presentation to our outpatient clinic . At the time of presentation , she also reported of dry cough , orthopnea , paroxysmal nocturnal dyspnoea , generalised weakness and intermittent numbness of her hands and feet . Social history was negative for smoking , alcohol or illicit drugs . Physical examination was unremarkable , except for jugular venous distension , audible S1 and S2 sounds , bilateral crackles on lung auscultation and bilateral pitting oedema . Chest X - ray showed cardiomegaly , pulmonary oedema and small - sized bilateral pleural effusions . A 12 - lead ECG demonstrated normal sinus rhythm , low - voltage complexes and extreme right - axis deviation ( figure 1 ) . Transthoracic echocardiogram ( TTE ) demonstrated asymmetric biventricular hypertrophy with preserved ejection fraction of 60 % , elevated right - ventricular systolic pressure of 36 mm Hg and abnormal myocardial texture , described as ‘ granular sparkling ’ ( figure 2 ) . Coronary CT angiogram demonstrated normal coronary arteries . Subsequently , cardiac MRI demonstrated early and diffuse subendocardial delayed enhancement , concerning for infiltrative myocardial disease and for diffuse biventricular hypertrophy , with normal ejection fraction ( figure 3 ) . The patient underwent right heart catheterisation with endomyocardial biopsy , revealing diffuse amyloidosis with amorphous proteinaceous material around cardiac myocytes and within blood vessels , which was positive for Congo red stain ( figure 4 ) . Subsequent laboratory evaluation registered elevated , free λ light chains ( 86.3 mg / L ( normal : 5.7–26.3 mg / L ) ) and positive Bence - Jones protein ( 0.37 g/24 h ) in the urine . Bone marrow biopsy revealed greater than 10 % infiltration of CD19− CD56 + CD138 + plasma cells with reversal of marrow κ / λ ratio ( < 1:2 , normal : 2:1 ) , consistent with MM . The patient was eventually diagnosed with systemic AL amyloidosis with advanced , stage III , cardiac amyloidosis due to underlying MM . Given her advanced cardiac amyloidosis , the patient was deemed a poor candidate for autologous stem - cell transplantation . The patient was started on systemic chemotherapy with melphalan and dexamethasone . Despite receiving standard therapy for heart failure — including diuretics , β - blockers and ACE inhibitors — the patient 's condition continued to worsen and she succumbed to sudden cardiac death .


A 35 - year - old woman presented to the ear , nose and throat outpatient department with headache and a blocked left - sided nasal canal with epistaxis for 2 years . Medical history revealed secondary amenorrhoea for the past 19 years with regression of secondary sexual characteristics with no galactorrhoea . Physical and ophthalmological examinations were within normal limits . Nasal examination revealed a left - sided choanal mass . As the mass was bleeding on palpation , imaging was advised prior to performing a biopsy . MRI of the head showed a sellar and infra - sellar mass extending into the nasopharynx ( figure 1 ) . The patient was then referred to the endocrinologist for further hormonal investigation . Her serum prolactin was very high—7443 µg / L ( N<20 ) . Other pituitary hormones were within normal limits . A final diagnosis of giant prolactinoma was made and the patient was prescribed cabergoline 0.25 mg twice per week with the associated risks explained in advance .


A 76 - year - old Japanese man had experienced a decreased appetite , nausea , and abdominal distension since late February 2011 . The patient passed loose , soft stools that were not watery once daily . The results of blood tests performed by the primary care physician ( PCP ) between April and June were all normal , but upper and lower gastrointestinal endoscopy showed atrophic gastritis . Therefore , we assessed the patient for Helicobacter pylori antibodies and performed the rapid urease test and a histopathological evaluation , all of which were negative . In June , the patient received medication from a mental health clinic , but because the symptoms did not improve and his body weight further decreased by 23 kg , he stopped the medication ; he was referred to our department in November . The patient had been suffering from hypertension since his 30s . Amlodipine ( 5 mg / day ) administration was initiated in 2005 , and olmesartan from May 2008 ; the patient is currently receiving 30 mg / day of olmesartan . He denied the use of any other new medications or nonsteroidal anti - inflammatory drugs . He had no history of smoking or alcohol consumption . Physical examination showed that the patient had a height of 165 cm , a body weight of 47 kg , and body mass index of 17 kg / m2 . His body temperature was 36.3 ℃ ; pulse rate , 101 / min ; blood pressure , 101/81 mmHg ; respiratory rate , 12 breaths / min ; and saturation from pulse oximetry ( SpO2 ) was 98 % . The patient had no heart murmur , third heart sound or jugular venous distension . The patient had bilateral pitting edema on his lower legs and presented with unilateral gaze - evoked nystagmus as well as a mildly reduced tactile sensation and thermal nociception in the toes and dorsal regions of both feet . Moreover , the finger - to - nose test results and tandem gait were poor , and his patellar and Achilles tendon reflexes had disappeared . Confabulation was observed in the patient , and the revised Hasegawa Dementia Scale ( HDS - R ) score was 17/30 ( cut - off point : 20 ) . The hematologic findings were as follows : white blood cell count , 6,200 /μL ; hemoglobin level , 12.5 g / dL ; mean corpuscular volume , 88.4 ; platelet count , 230,000 /μL ; sodium level , 136 mEq / L ; potassium level , 3.8 mEq / L ; chlorine level , 103 mEq / L ; iron level , 57 μg / dL ( reference value : 64 - 187 μg / dL ) ; ferritin level , 366 ng / mL ( reference value : 50 - 200 ng / mL ) ; B - type natriuretic peptide ( BNP ) level , 125.3 pg / mL ( reference value : -18.4 pg / mL ) ; and vitamin B1 level , 8 ng / mL ( reference value : 24 - 66 ng / mL ) . An electrocardiogram was normal and chest X - rays showed a normal cardiothoracic ratio ( 40.8 % ) without either pulmonary congestion or pleural effusion . Cranial fluid - attenuated inversion recovery - magnetic resonance imaging findings revealed periaqueductal hyperintensities ( Fig.1 ) ; therefore , Wernicke encephalopathy was diagnosed . Moreover , as sinus tachycardia and a tendency towards hypotension were noted , no clear symptoms of heart failure or dehydration were observed ; it was thus inferred that the vitamin B1 deficiency had likely played a role in both of the conditions . The antihypertensive agents were discontinued , and 10 days after the intravenous administration of vitamin B1 , the patient 's loss of appetite , nausea , and gait disturbance disappeared , and his body weight increased by 3 kg . Nystagmus was ameliorated on physical examination , but the patient still had confabulations , and the HDS - R score and absence of deep tendon reflexes did not improve . Since the gastrointestinal symptoms were ameliorated and his blood pressure increased to 160/90 mmHg , the PCP resumed the administration of olmesartan on late December , 2011 . One week later , the patient complained of recurrent decreased appetite and nausea . After experiencing diarrhea ( five bowel movements during a 2 - day period ) , he passed soft stools once daily , and his body weight decreased to 47 kg so he came to our hospital again 3 weeks after the resumption of olmesartan for treatment . His vital signs were as follows : body temperature , 35.1 ℃ ; pulse rate , 93 / min ; and blood pressure , 132/75 mmHg . The neurologic findings showed no worsening of his symptoms . The laboratory findings were as follows : sodium level , 139 mEq / L ; potassium level , 2.9 mEq / L ; and chlorine level , 116 mEq / L. Hyperchloremia was noted , and the serum sodium level minus chloride level ( 139 - 116 ) was 23 mEq / L ; additionally , the arterial blood gas findings were as follows : pH , 7.25 ; PCO2 , 25 mmHg , and HCO3 , 11 mmol / L. The urinalysis findings were as follows : sodium level , 15 mEq / L ; potassium level , 13 mEq / L ; chlorine level , 100 mEq / L ; and urine anion gap , -72 mEq / L , and there was no apparent increase in bowel movements ; however , this seemed to be due to the absence of HCO3- from the gastrointestinal tract ( 6 ) . Plain abdominal radiography and abdominal computed tomography findings revealed the continuous dilation of the entire intestinal tract ( Fig.2 ) ; therefore , the patient was diagnosed with intestinal pseudo - obstruction . After discontinuing olmesartan , the nausea and body weight decreases were promptly ameliorated . Duodenal biopsy findings after discontinuing olmesartan showed that the inflammation observed before discontinuation as well as the fold structure had both clearly ameliorated ( Fig.3 ) .


A 28 - year - old woman was referred with a 4 - week history of continuous , moderate right upper quadrant pain associated with jaundice , as well as weight loss ( 10 kg over 3 months ) and a liver mass identified by ultrasonography . The pain sensation seemed different from previous colicky attacks the patient had experienced before she underwent laparoscopic cholecystectomy 7 years previously . On physical examination , she was obese ( body mass index 37.8 ) , with icterus noted over the conjunctivae , oral mucosa and skin . Imaging modalities included computed tomography ( CT ) , positron emission tomography ( PET ) and endoscopic cholangiopancreatography ( ERCP ) ( Fig.1 ) . The patient underwent exploratory laparotomy . Intraoperative ultrasonography revealed a cystic lesion measuring 3.5 2.5 cm within the central portion of the liver , anterior to the porta hepatis . Intraoperative cholangiography demonstrated an extensive stricture obliterating the left hepatic duct , with partial occlusion of the right hepatic duct . An extended left lobectomy was done en bloc with the biliary confluence . On frozen - section examination , all margins of the excised specimen were free of malignant cells . Reconstruction was performed with a Roux - en - Y cholangiojejunostomy to 3 second bile duct radicals in the right side . Intraoperatively , radiotherapy was applied to the surgical margins . After this , the patient underwent 6 weeks of image - guided external beam radiation centred on the resection field labelled at surgery . The final pathology described this tumour as an infiltrating , moderately differentiated squamous cell carcinoma associated with severe dysplasia of the bile - duct epithelium ( Fig.2 ) . The patient recovered without complications and was doing well 18 months after the initial surgical procedure , with an unremarkable CT scan .


A 45 - year - old lady sought dermatology consultation for severely tender erythematous vesicles and bullae over back , chest and arms . These were sudden in onset associated with fever , nausea and malaise . Along with this she also complained of pain in upper abdomen . There was no history of receiving any drugs prior to the onset of lesions . She did not report any significant weight loss or loss of appetite . On physical examination , her temperature was 38 ° C , pulse rate was 100 / min and blood pressure was 126/72 mm Hg . There were multiple coalescing vesicles and bullae over upper back , chest and arms distributed symmetrically showing areas of pustulation and necrosis . Surrounding them were multiple pseudovesicular satellite papule ( figure 1A , B ) . On per abdominal examination mild tenderness was present in the right hypochondrium . Patient 's initial laboratory investigations showed a total leucocyte count of 12 000 cells / mm3 with 75 % neutrophils . The haemoglobin level was 14.3 gm% and erythrocyte sedimentation rate was 30 mm / h. Liver function test , kidney function test and C reactive protein levels were within normal limits . Gram stain from purulent exudates showed only neutrophils without any organisms and culture did not show any growth after 72 h of incubation . A lesional skin biopsy taken from the satellite papule showed neutrophilic infiltration in dermis with papillary dermal oedema and spongiosis ( figure 2A , B ) . Abdominal ultrasonography revealed intraluminal gall bladder mass suggestive of malignancy . On the basis of these findings a final diagnosis of SS associated with gall bladder malignancy was made . She was started on oral prednisolone in dose of 40 mg daily along with symptomatic treatment . Her cutaneous lesions responded dramatically and subsided completely after 1 week of treatment ( figure 3A , B ) . Dose of prednisolone was tapered and an open cholecystectomy was performed . Histopathology of excised tissue confirmed it to be well - differentiated gall bladder adenocarcinoma forming glands and papillae infiltrating the muscularis propria superficially . Cystic duct cut margins were free of tumour ( figure 2C , D ) . Patient 's postoperative period was uneventful and she was discharged on tapering doses of prednisolone with advice to follow - up periodically .


The affected individual , a male , was the fourth child born to an Arab Muslim family of Palestinian origin . Parents are first cousins . One sibling , a girl died at the age of 1 month due to SIDS according to parents , without any investigation . Informed consent for muscle , skin biopsy and exome sequencing was obtained from the parents , and the study was approved by the local institutional review board . During pregnancy , the patient was suspected to have IUGR and was delivered by Cesarian section at 36 + 2 gestational weeks with Apgar scores 9 and 10 . Birth weight was 2.3 kg ( 10th percentile ) and head circumference 32 cm ( 10th percentile ) . Physical exam after birth , detected a systolic murmur 3/6 . On the first day of life , the patient developed metabolic acidosis with lactate level of 27 mm ( normal range 0.5–2.4 mm ) and elevated ammonia levels 277 μm ( normal range 10–60 μm ) . Metabolic work up showed normal acylcarnitines , elevated alanine level 1400 μm ( normal < 700 μm ) , and urine organic acids showed increased lactic acidosis and ketones . Chest X - ray revealed cardiomegaly , and cardiac Echo revealed symmetrical left ventricular hypertrophy tricuspid regurge and pulmonary hypertension . The patient was transported to the NICU and treated with bicarbonate , acetate and diuretics . At the age of 4 days , quadriceps muscle biopsy was performed . Pathology showed decreased cytochrome c oxidase stain . Brain ultrasound performed at age 5 days was normal . Subsequently , head circumference grew rapidly adding 13 centimeters by age 35 days , repeated brain US revealed dilated ventricles confirmed by head CT , which also showed subcortical and white matter cortical hemorrhage in the occipital region . At 15 weeks , a ventriculoperitoneal ( VP ) shunt was inserted . Head CT performed at age 2 years showed prominent dilatation of the ventricles ( Figure 1 ) . Due to hypotonia with feeding difficulties and recurrent aspirations , a percutaneous endoscopic gastrostomy ( PEG ) feeding tube was inserted at age 10 weeks . Eye examination at the age of 15 weeks revealed cortical blindness . Hearing test ABR was normal . Repeated cardiac Echo continued to show mild tricuspid regurge , mild left ventricular hypertrophy ( LVH ) and pulmonary hypertension ( PHTN ) in the first months of life . At the age of 4 months , he started developing hypertrophic obstructive cardiomyopathy , he was started on diuretics and beta blockers and later calcium channel blockers were added ; follow - up Echo at the age of 2 years revealed improvement in the LVH and no PHTN . Coenzyme Q10 supplementation ( 60 mg twice daily ) was initiated at 4 months but discontinued by the parents . In the following months , the patient was admitted several times to the hospital mainly due to chest infections , shunt malfunctioning and fevers . He died at the age of 30 months due to severe hypoxemia after a febrile illness with chest infection and pulmonary edema ; parents refused mechanical ventilation and refused reanimation .


A 38 - year - old woman presented to our Emergency Department with severe abdominal pain . She had no history of drug use or constipation . She said that she had intermittent bloody diarrhea . Physical examination revealed rebound tenderness and guarding over the abdomen . Stool microscopy was negative for amoeba trophozoites or any parasites . Fecal occult blood was found . Sedimentation was 27 mm / s , CRP ( nephelometry ) was 65.6 mg / L ( normal range 0–5 ) , anti - nuclear antibody was 0.4 ( 0–0.8 negative ) , anti - ds DNA < 10 ( < 20 negative ) , white blood cell count was 14.98 ( normal range 4–10 ) , hemoglobin level was 10.9 , neutro - phil count was 13.14 , platelet count was 473 ( 100–300 ) , urea level was 17 mg / dl , BUN level was 7.94 mg / dl , creatinine level was 0.56 mg / dl , AST was 20 U / L , and ALT was 24 U / L. HIV was negative . Abdominal ultrasound scanning showed free fluid at the right paracolic , perihepatic , left paracolic gutters and pelvis . Upon detection of air - fluid level and free air under the diaphragm on erect abdominal x - ray , emergency laparotomy was performed . In the operation , multiple perforation areas were found in the sigmoid colon , descending colon , and transverse colon . Wide resection of the transverse colon with descending and sigmoid colon resection was undertaken ( Figure 1 ) . Pathergy test was positive . The patient had recurrent oral and genital aphthous ulcers 4–5 times within the past year . Eye examination results were normal . Computed tomography revealed extensive thrombus within the inferior vena cava extending through the right and middle hepatic vein ( Figure 2 ) . The patient received corticosteroid , anticoagulant , and immunosuppressive therapy . Our patient is still alive and healthy 53 weeks later ( Figure 3 ) . In macroscopy , the transverse colon was 50 cm and sigmoid and descending colon specimens were 27 cm in length . Specimens of both colon segments were 4 cm in diameter . Perforation areas were evident in the serosal surface . Colonic wall and bowel mucosa was edematous and hyperemic . Plicae were regular in their course . There were 3 roundish , punched - out perforations in the transverse colon and 4 in the descending and sigmoid colon , which were somewhat separate from the colonic wall , with the largest being 2 cm in diameter ( Figure 4 ) . There were multiple ulcers ( the largest was 1 cm in diameter ) in different locations , which were not merging together , and were somewhat separate from the surrounding mucosa via a certain limit , covered with exudate and surrounded by a hyperemic region . There were no macroscopic lymph nodes in the serosa . Numerous samples were taken from ulcerated and perforated regions and normal mucosa . The samples were submitted for routine microscopic tissue follow - up . Hematoxylin - eosin , tissue Giemsa and PAS - stained slides were prepared for examination . In microscopic examination , there were neutrophil leukocyte and lymphocyte reaction around and within the walls and lumens of arterioles , and venules around the perforated and ulcerated lesions ( Figures 5 and and6).6 ) . There were well - organized thrombi and intimal proliferation within some vessels ( Figures 7 and and8).8 ) . There was marked acute peritonitis . Surface epithelium and colonic crypts were regular within the colonic mucosa apart from the ulcerated or perforated lesions . Samples were free of parasites or their eggs .


A 13 year - old boy presented with a 1 month history of intermittent episodes of small volume epistaxis . There was no significant past medical , surgical or family history . Physical examination revealed a left palatal fleshy mass centered at left posterior molars . A nasoendoscopic examination demonstrated a large swelling on the floor of left anterior nasal space , involving the left inferior meatus and abutting the inferior turbinate . Computed Tomography ( CT ) of the paranasal sinuses showed a lobulated , expansile lytic lesion of left maxilla [ Fig 1 ] with a lucent center and peripheral calcifications . The lesion was associated with a large soft tissue component that demonstrated mild heterogeneous contrast enhancement . The lesion was centered at the left maxillary alveolus , involving the left hard palate , inferior part of the anterior left maxillary wall and medial left maxillary wall . The lesion also involved the roots of the left maxillary molars and pre - molars and was abutting the left orbital floor , with no gross orbital invasion . The patient subsequently underwent 18 - FDG PET - CT study . The mass centered in left maxilla was hypermetabolic , with index SUVmax 9.7 [ Fig 2 ] . There was no FDG - avid metastatic disease . A trans - oral incisional biopsy of the left palatal mass was performed and was suggestive of a preliminary diagnosis of mesenchymal chondrosarcoma , as evidenced by a biphasic pattern featuring sheets of small round cells with hemangiopericytoma - like vascular pattern and mature cartilaginous islands . The patient underwent left subtotal maxillectomy via lateral rhinotomy and translabial approach . The final histology was conclusive of a 5 cm high - grade ( Grade 3 ) mesenchymal chondrosarcoma . One of the resection margins was positive for tumor involvement and the patient was planned for adjuvant chemotherapy .


A 7 - year - old boy with Goldenhar syndrome with post - natal genetic diagnosis was referred to our Department of Radiology for imaging study of the temporal bone . The patient underwent a 3D - CT scan . Brilliance CT-64 - channel ( Philips Medical Systems , Amsterdam , The Netherlands ) was employed . The protocol generated 120 kV and a current of 150 mA. Slice thickness of the images was 1 - mm with a 0.5 - mm increment . Images in DICOM format were processed on a PC using commercial software , obtaining a three - dimensional reconstruction of skeletal structures . The 3 - dimensional reconstruction of the skin plans showed hypoplasia of the auricle that on the right side consisted of a simple dysmorphic rough . The left auricle had regular dimensions and morphology . Atresia of the right auditory conduit and a normal left auditory conduit were observed . The upper images showed partial ossification of the cranium typical in paediatric age . Description of the profile : typical II class very convex profile with interposition of the inferior lip and a reduced neck - chin angle.(Fig.1 ) . Skeletal studies show that the mandibular condyle , ramus and corpus were shorter on the affected side . Tilting of oral rhyme , occlusal plane and mandibular plane were evident . Number or form abnormalities were not found during mixed dentition . Mandibular condyles and temporo - mandibular joints seemed to be asymmetric , and in particular the right condyle was deformed , shorter and wider than the other side ( mandibular condyle dimensions were 11 × 7 mm right and 14 × 7 mm left ) . The 3 - dimensional reconstruction of the skeleton planes showed the different morphology of the right and left hemimandibula . Mandibular 3 - dimensional reconstruction showed in detail the shift of the medial axis to the hypoplastic right side and the asymmetry of the right mandibular condyles that appears dysmorphic short and wide in axial and coronal scansions ( Figs.2 , 3 ) . The study of the temporal bone showed on the right side an external auditory canal atresia , hypoplasia of tympanic cavity that was not pneumatized and occupied by dense materials from soft parts . No pneumatization was present in right mastoid cells . Left external auditory canal dimensions and morphology were normal . The left tympanic cavity was normally formed and totally occupied by dense materials from soft tissues . Both right and left ears presented minor hypoplasia of auricle bones in the right side . In agreement with the resolution of our instrument , normal representation of the malleus head that seemed articulated with a dysmorphic rough of a deformed incus was observed ; it was impossible to see the staples . The left malleus and incus were visible and appeared to be articulated in an abnormal manner ( reduce contact surface ) ; the staples was difficult to observe but seemed to have regular morphology . Dimensions and morphology of cochlea semicircular canals , vestibulum and utriculum were unaltered ( Figs.4-7 ) . In conclusion , through 3D - CT valuation of this young patient we observed asymmetry of the condyles ; in particular , the right condyle was dysmorphic , short and wide ; the auricle of the right external ear was hypoplastic , only a dysmorphic rough was present ; the right middle ear had a hypoplastic tympanic cavity ; the right internal ear has an atresic auditory conduit .


A 55 - year - old woman was referred to our hospital because of a suspicion of mediastinal tumor incidentally found through a medical - checkup plain X - ray photography ( X - P ) ( Figure (Figure1A).1A ) . Chest MRI revealed a 3 cm diameter tumor which seemed to connect to the right lobe of thyroid and projected into the mediastinum ( Figure 1B ) . By 123I - RI , no unusual accumulation was detected ( Figure 1C ) . A fine needle aspiration biopsy , which is viewed as the “ gold standard ” for diagnosis in most cases , was tried but could not reach a conclusive diagnosis . Thereby , 18F - FDG - PET was performed and a high accumulation was revealed with standardized uptake value ( SUV ) of 3.8 ( Figure 1D ) . Thus , as a possibility of malignancy could not be excluded , the right lobe excision procedure for thyroid gland was enforced . The obtained tumor was continuous to the right lobe as expected . The surface was flat and smooth and the exfoliation from the circumference organization was easy ( Figure 2A ) . Microscopically , the encapsulated tumor consisted of atypical large - sized follicles without malignant characteristics , the background thyroid tissue showing no remarkable change ( Figure 2B ) . Thus , histological diagnosis was follicular thyroid adenoma . Ethical approval was not thought to be necessary because all the clinical course of the case was completely within usual medical cares . Informed consent was given from the case on each occasion of diagnostic examinations and therapeutic procedures .


A 30 - year - old female ( 65 kg ) underwent rhinoplasty under general anaesthesia , which was induced using a combination of a bolus of Remifentanyl ( 0.5 μg / kg ) and Propofol 2 mg / kg . Muscle paralysis was obtained with Cisatracurium ( 0.15 μg / kg ) . Transoral intubation was performed with a Macintosh blade ( No.3 ) and a size 7 mm diameter reinforced tracheal tube was easily and gently placed in the trachea , on the first attempt and was then fixed to the right corner of the mouth . No problems were encountered during laryngoscopy and intubation . The cuff of the tube was inflated with a pressure ≤ 20 cm H2O. No adjustment of cuff volume was made intra - operatively . N2O was not used for inhalation anaesthesia . The throat pack was placed in the pharynx to avoid the passage of blood in the aero - digestive tract . General anaesthesia was maintained with Sevofluorane in oxygen / air and Remifentanyl in continuous infusion 0.25 μg / kg / min . Moderate arterial hypotension was maintained with a cuff systolic artery pressure of approximately 90 mmHg . The operation was carried out in a semi - supine position with the head slightly inclined forward and laterally and trunk slightly elevated . Duration of the operation was 100 minutes . The patient was extubated , after removal of the throat pack without problems . The following day the patient complained of difficulty in swallowing , dysphonia and hoarseness . Examination revealed deviation of the tongue to the right side and vocal cord paralysis , expression of hypoglossal and recurrent laryngeal nerve injury without local oedema or haematoma . The movements of the pharynx and soft palate were normal . Meticulous neurological examination , including also magnetic resonance imaging ( MRN ) revealed no other evidence of central or cranial nerve involvement . Conservative management included steroids , vitamins together with speech and swallowing therapy . Full recovery of lingual and laryngeal functions was obtained within four months after surgery .


A 3 - month - old infant from the UAE with a genetically - confirmed diagnosis of Jarcho - Levin syndrome and dependent on mechanical ventilation since birth was admitted to our centre for the implantation of VEPTRs . We received an intubated patient , mechanically ventilated in a volume - controlled mode , with a 0.30–0.45 fraction of inspired oxygen ( FiO2 ) ( peak inspiratory pressures ( PIP ) of 23–45 cm H2O , positive end - expiratory pressure ( PEEP ) of 7 cm H2O , backup respiratory rate ( RR ) of 34 ) . A chest X - ray of the thorax was performed on admission ( figure 1A ) , and a month after the first surgery ( figure 1B ) , showing improvement of the bilateral posterior atelectasis in the base of the lungs . Owing to the difficulty of progressing in the weaning process from mechanical ventilation after the VEPTRs were implanted to expand the thorax , a bronchoscopy was performed , showing bronchomalacia predominantly in both upper lobar bronchi . As prolonged mechanical ventilation was expected , a tracheostomy was previously performed . After an initial CT scan ( figure 2A ) , a follow - up CT scan ( figure 2B ) a month after the surgery showed a resolution of the posterior - basal atelectasis , coinciding with a decrease of FiO2 to 0.21 . Postoperatively , the patient was on the Servo - i ventilator in a volume - controlled mode and needed variable PIPs between 25 and 45 cm H2O and PEEP values of 7–11 cm H2O. During the attempts to wean the patient off the ventilator in the following months , he was unable to activate the inspiratory flow trigger and required significant sedoanalgesia to adapt to the ventilator due to repeated episodes of desaturation , on some occasions with bradycardia , associated to bronchial collapse . He continued to have asynchrony which required boluses of sedation in addition to existing medications . He initially received fentanyl and midazolam through a continuous infusion pump with progressive increase in the doses as well as continuous cisatracurium as a muscular relaxant to adapt to mechanical ventilation ( figure 3 ) . As clinical stabilisation was achieved , the muscular relaxant was withdrawn and a progressive decrease of sedation was initiated along with a change in the drug regimen . During this period , the patient developed an ocular flutter which was attributed to a pharmacological cause after neurological alterations were ruled out with normal EEG , ophthalmoscopy , metabolic workup and cranial MRI . At 5 months of age , the NAVA mode started to improve the patient 's adaptation to the ventilator through the use of a neural trigger . The NAVA catheter additionally costs around € 200 per catheter ; according to the manufacturer it should be changed every 5 days . It was required for 7 months ; nevertheless the catheters were changed every 15 days without observing a deterioration of the Edi signal . According to the literature , Jarcho - Levin syndrome does not appear with mental retardation and life expectancy is pretty long , so ethically , we considered that this patient should have an opportunity to overcome his thoracic insufficiency if it were technically possible . Tachypnoea was initially observed with a RR of 55 without other signs of increase in his work of breathing and his RR eventually returned to normal for his age ( 40 ) over the next few days . The synchrony achieved with the ventilator allowed a progressive decrease of the sedoanalgesia he received until it was completely withdrawn in 10 days ; and the need for extra boluses of sedation was reduced to zero . Concurrently to the reduction of sedation , his ocular flutter disappeared and he showed significant progress in his psychomotor development . The settings used were : NAVA level of 1 cm H2O/µV , PEEP 11 cm H2O , Edi trigger 0.5 µV. The patient had tidal volumes ( Vt ) of 6–7 mL / kg ( figure 3 ) . After 10 days on the NAVA mode , he did not require any type of sedation and the sporadic episodes of bronchial collapse were resolved with a quick increase of PEEP to 20 cm H2O or manual ventilation with the self - inflating bag . Once he was stabilised on the NAVA mode , his PIPs oscillated between 15 and 45 cm H2O with a NAVA level of 0.4 and Edi peaks between 15 and 100 µV. A posterior pulmonary CT scan performed 2 months after the first surgery , 1 month after starting NAVA and prior to the first thoracic expansion , showed a significant reduction in the posterobasal atelectases previously observed ( figure 2B ) . When he turned 1 year old , after several attempts with different devices Trilogy 100 ( Philips ) , Astral 150 ( ResMed ) , the patient finally tolerated mechanical ventilation with a home ventilator ( Monnal T-50 , Air Liquide ) in a volume assisted / controlled mode with the following settings : Vt 80 mL ( 9 mL / kg ) , PEEP 10 cm H2O , flow trigger 0.5 L / min . His PIPs were around 30 cm H2O. He did not tolerate a decrease of PEEP below 9 cm H2O or short disconnections from the ventilator . Currently , the patient is 19 months old , is able to walk and his neurodevelopment seems to be normal .


A 27 years old , male , right handed , was admitted for a 2 years history of very frequent gelastic seizures . The patient described aura – like symptoms : especially warmth throughout the face and dizziness that preceded the seizure and he denied any affective connotation . Some of the seizures consisted only of a brief period of laughter without any motor involvement , but a typical seizure would consist of sudden laughter accompanied by simple motor partial seizures in both arms , more often being involved his left arm , without impairment of his consciousness state , which lasted less than 1 minute . He had no previous past medical or social history other than being a smoker : 10–15 cigarettes per day . The frequency of the seizures was initially low , but increased progressively over time to about 8–10 seizures / day , despite anti – epileptic treatment – at the time of admission he was taking Keppra – Levetiracetam 3 x 250 mg / day and Phenytoin 3 x 100 mg / day . With the Neurology Electrophysiology Department assistance we have been able to record a couple of seizures on the Video – EEG His neurological examination was normal . Diagnosis was made on native CT scan : minimal hypodense frontal right paramedian lesion ( Figure 1A ) , cerebral MRI ( Figure 1 B – F ) showed a small right parenchymal homogeneous lesion 16/22/15 mm , well delimited , involving gyrus cinguli , without perilesional edema and mass effect , hyperintense both on T1 and T2 MR sequences , non – enhancing after Gadolinium . The cerebral lesion was also documented on EEG and video – EEG recordings : 3 seizures with medio – frontal origin and rare interictal epileptiform elements were recorded ( Figure 1I ) Using an interhemispheric microsurgical approach , above the corpus callosum and the right pericallosal artery , at the level of gyrus cinguli , a yellow – gray , infiltrative tumour , having a moderate vascularisation had been identified and totally removed . The anatomo – pathological analysis revealed a grade Ⅱ astrocytoma . The patient recovered very well , without deficits , no gelastic seizures or epileptic manifestations ; three months after operation he is still free of seizures . A control postop CT revealed no tumor ( 1 G , H )


The 36 - year - old male patient in this case had a 6 - year history of diffuse cutaneous SSc ( Fig.1 ) and had not received regular follow - up or medication therapy . He had experienced malaise , poor appetite , and progressive shortness of breath for 1 month and oligouria for 3 days . He was admitted to our hospital with renal failure and pulmonary edema . In the emergency department , his blood pressure , pulse rate , and respiratory rate were 174/127 mm Hg , 88 / min , and 22 / min , respectively . Laboratory analysis revealed the following values : white blood cell count , 7730 / μL ( 3500–11,000 / μL ) ; hemoglobin , 8.6 g / dL ( 12–16 g / dL ): platelet count , 87000 / μL ( 150,000–400,000 / μL ) ; blood urea nitrogen , 78 mg / dL ( 6–21 mg / dL ) ; creatinine , 8.9 mg / dL ( 1.1–1.5 mg / dL ) ; calcium , 8.2 mg / dL ( 8.8–10.3 mg / dL ) ; phosphorus , 5.4 mg / dL ( 2.7–4.5 mg / dL ) ; haptoglobin , < 6.56 mg / dL ( 30–200 mg / dL ) ; and lactate dehydrogenase , 547 U / L ( 106–211 U / L ) . A routine urinalysis revealed a proteinuria score of 2 + ( 200 mg / dL ) , white blood cell count of 3–5 / high power field , and red blood cell count of 25–50 / high power field . The autoimmune profile indicated an antinuclear antibody level of 1:320 ( speckles ; normal , < 1:40 ) . Tests for anti - Scl70 , anti - double - stranded DNA , anti - Ro , anti - La , and anticardiolipin antibodies were all negative . Kidney echogram showed a decreased bilateral kidney size without hydronephrosis . Despite the chronic changes visible on the echogram , the patient had developed acute pulmonary edema and oligouria only 3 days before admission . Accordingly , a clinical diagnosis of acute - on - chronic renal failure was made . A further diagnosis of SRC was supported by the presence of renal failure with microangiopathic hemolytic anemia and hypertension , and the patient was started on captopril therapy . The sustained deterioration in renal function and anuria had led to a requirement for regular hemodialysis from admission . After 3 days , captopril was changed to amlodipine because the patient developed a severe , intolerable cough thought to be associated with captopril . His systolic blood pressure was controlled between 140 and 180 mm Hg . At approximately 3 weeks after the initiation of maintenance hemodialysis , the patient newly developed a generalized tonic - clonic seizure disorder . A brain computed tomography ( CT ) scan revealed a small lacunar infarct over the left basal ganglion without intracranial hemorrhage or large infarct . The seizure resolved spontaneously without anticonvulsants , and the patient was finally discharged home without incident and scheduled for regular hemodialysis thrice weekly . However , at 1 week after discharge , the patient developed a sudden - onset headache and vomiting with confusion and recurrence of the generalized tonic - clonic seizure . He presented at the emergency department with a blood pressure of 183/100 mm Hg , platelet count of 149,000 / μL , serum LDH of 332 U / L , and a peripheral blood smear containing 2–3 schizocytes / HPF ( Fig.2 ) . Brain CT revealed no interval change , and lumbar puncture revealed traumatic tapping only . Cerebrospinal fluid cultures were negative for bacteria , mycobacteria , and viruses . Brain magnetic resonance imaging ( MRI ) showed bilateral hyperintensity in the occipital and parietal lobes on a fluid - attenuated inversion recovery ( FLAIR ) sequence ( Fig.3 ) . Finally , the patient was diagnosed with PRES . We resumed captopril therapy at a dose of 25 mg thrice daily . As it was difficult to differentiate SRC from TTP , we also considered plasma exchange treatment . However , the patient 's mental status returned to normal within 3 days in the absence of plasma exchange , and a follow - up MRI of the brain 2 months later showed complete resolution of cerebral edema ( Fig.4 ) . Therefore , SRC - related PRES was confirmed . Although the patient experienced a full neurologic recovery , his renal function did not improve and he remained dialysis dependent .


The proband is a 19 - year - old woman , first child of healthy unrelated parents . Her family history was unremarkable . She was born at term after a normal pregnancy . The perinatal period was uneventful and her early development was referred to as normal , but after 1 year of age , psychomotor delay became evident . She started walking autonomously at 22 months , with poor balance and frequent falls . At 3 years of age , she developed a demyelinating sensorimotor neuropathy and a brain MRI disclosed supratentorial leukodystrophy . During her childhood , the clinical signs remained stable . At 10 years , her walking difficulties worsened , and limb weakness and tremor ensued . The neurological evaluation showed dysarthria , dysmetria , ataxic gait and hyporeflexia in the four limbs with muscle wasting . She was able to walk alone only for a few steps with an ataxic gait . Mild cognitive impairment was documented ( IQ 75 , WISC - R scale ) . Histological analysis of a muscle biopsy showed hypo / atrophy of fibres . The clinical evolution was slowly progressive . At her last follow - up examination , at 19 years of age , she was able to walk alone only with ankle - foot orthotic aids and had developed a marked dorsal - lumbar scoliosis . Other clinical signs were stable . Neurophysiological studies confirmed worsening of her mixed axonal demyelinating peripheral neuropathy . Brain and spinal cord MRI showed mild extension of signal abnormalities and extensive cavitations in the cerebral white matter ; the cerebellum and brainstem were spared but the spinal cord was thin with no obvious focal lesions ( figure 1A ) . Plasma lactate was 2.9 mM ( n.v . < 2.1 ) .


A 67 - year - old Japanese female presented with a left buttock tumor , which had been first detected approximately 1 year earlier , and had recently gradually enlarged . Physical examination revealed a relatively well - circumscribed skin - colored tumor with hyperkeratosis , measuring 43 x 38 mm in diameter , in her left buttock . The biopsy specimen revealed Bowen ’s disease ( squamous cell carcinoma in situ ) , and subsequently , total resection of the tumor was performed . Histopathological study of the resected specimen revealed proliferation of atypical squamous cells in the entire layer of the acanthotic epidermis accompanied by hyperparakeratosis ( Figure 1A ) . These atypical squamous cells had enlarged and hyperchromatic nuclei ( Figure 1B ) , and multinucleated atypical squamous cells were also present . Mitotic figures were scattered and present in the upper portion of the epidermis . Atypical mitotic figures were also observed ( Figure 1B ) . No invasive neoplastic growth was noted ( Figure 1A ) . Approximately 95 % of the lesion was composed of the above - mentioned Bowen ’s disease ( squamous cell carcinoma in situ ) , and superficial sebaceous carcinoma was present in the central area of the lesion . This latter component was composed of proliferation of nests of atypical cells with vacuolated clear cytoplasm and large nuclei containing conspicuous nucleoli ( Figure 1C , ,1D).1D ) . Sebaceous carcinoma had invaded into the superficial reticular dermis ( Figure 1C ) . Moreover , atypical cells containing vacuolated cytoplasm were present within the lesion of Bowen ’s disease adjacent to the sebaceous carcinoma ( Figure 1E ) . Immunohistochemical studies were performed using an autostainer ( Ventana ) by the same method as previously reported [ 9 - 12 ] . Epithelial membrane antigen ( EMA ) , cytokeratin 7 , and adipophilin were expressed in the sebaceous carcinoma component , but not in Bowen ’s disease ( Figure 2A ) . Androgen receptor was also expressed in some of the tumor cells of the sebaceous carcinoma , but not in Bowen ’s disease . Moreover , atypical vacuolated cells within the lesion of Bowen ’s disease were also positive for adipophilin ( Figure 2B ) . Overexpression of p53 protein was observed in both the sebaceous carcinoma and Bowen ’s disease . Accordingly , an ultimate diagnosis of sebaceous carcinoma associated with Bowen ’s disease was made .


A woman in her early 70s presented to our emergency room 30 min after her husband expired with 8/10 , substernal chest pain with concurrent diaphoresis and dyspnoea . The patient 's husband had an out - of - hospital cardiac arrest earlier that day and was brought to our emergency room and subsequently admitted to the coronary care unit . He had recurrent ventricular fibrillation and could not be successfully resuscitated . The patient 's medical history included hypertension and hypothyroidism . She denied having had a similar episode of pain . She had regular appointments with her primary care physician . Her medication included oral furosemide 20 mg and levothyroxine 100 µg , both once daily . She denied allergies . On presentation , the patient was afebrile , with a blood pressure of 105/55 , heart rate of 93 bpm , respiratory rate of 20 / min and an oxygen saturation of 98 % on room air . On physical examination , she was in significant distress due to pain . Her skin was warm and moist , with minimal crackles in bilateral bases , regular rate and rhythm , 2/6 systolic murmur of the apex without radiation , no rubs , elevated jugular vein distention of 8 cm , strong peripheral pulses and no peripheral oedema . The abdomen was soft , non - tender , non - distended , with bowel sounds , and the patient was alert and oriented without focal neurological deficits . The complete blood count , basic metabolic panel and coagulation tests were within normal limits . The cardiac enzymes were increased with a troponin I of 2.59 ng / mL ( normal range 0.015–0.045 ng / mL ) , creatine phosphokinase of 84 U / L ( normal range 26–192 U / L ) . ECG on admission revealed normal sinus rhythm with 2–3 mm ST segment elevations in leads V2 – V3 and Q waves in leads V1 – V3 , suggestive of anterior wall infarct ( figure 2 ) . An echocardiogram revealed left ventricular ejection fraction of 30–35 % with mild concentric left ventricular hypertrophy , akinesis of the apex and 2/3 of the inferoseptum and apical inferior - anterior wall segments , suggesting ischaemic damage at the left anterior descending artery distribution versus takotsubo cardiomyopathy ( figures 3 and 4 ) . The patient received aspirin 162 mg and prasugrel 60 mg , and was taken to the cardiac catheterisation laboratory . The angiogram showed non - obstructive coronary artery disease with luminal irregularities ( figures 5 and 6 ) . The left ventriculography showed an ejection fraction of 35 % with akinesis of apical wall and hyperkinesis of basal segments ( figures 7 and 8) . The patient remained haemodynamically stable and was started on oral heart failure medications , including lisinopril 2.5 mg daily and metoprolol tartrate 12.5 mg two times a day . Her pain and shortness of breath resolved and she was discharged home after 48 h of hospitalisation in stable condition . A repeat echocardiogram 2 months later showed resolution of her cardiomyopathy and an ejection fraction of 65–70 % , with normal left ventricular motion .


A 64 - year - old female was found lying down after 10–12 hours of binge drinking . She was taken to an outlying emergency department ( ED ) , and subsequently transferred to our hospital with mental status changes and respiratory distress and hypoxia for further management . She had a past history of rheumatoid arthritis , congestive heart failure , controlled hypertension , and alcoholism . She smoked two packs a day for the past 50 years . On presentation , she had a blood pressure of 176/80 mm / Hg , heart rate of 80 bpm , respirations 24 bpm , temperature 98 ° F ( 36.7 ° C ) . Arterial blood gases on room air showed a pH of 7.30 , PaCO2 60 , PaO2 61 mm / Hg , H−CO3 29 mEq / L , and saturation 92 % which improved to 95 % with oxygen by a high flow non - rebreather mask . On physical examination she was lethargic , disoriented , dysarthritic , but without neurological focalization . Scattered expiratory wheezes were noted bilaterally along with normal heart sounds . The remaining results of her physical examination and routine laboratory results were unremarkable with the exception of a leukocyte count of 14,000 / dL with 88 % neutrophils . Repeated vitals signs were consistent with a normal blood pressure but evidence of tachycardia in the monitor . Repeated ABG ’s on the non - rebreather mask showed : pH 7.22 , PaCO2 78 , PaO2 140 mm Hg , H−CO3 30 mEq / L , and hemoglobin SaO2 97 % . In the ED she was started on IV steroids and antibiotics for a COPD exacerbation . As part of the diagnostic workup , she underwent a chest x ray that did not show any infiltrates or any major abnormal findings . The ECG was only significant for sinus tachycardia . Given the negative findings on chest x ray , sinus tachycardia on ECG , and an increased A - a gradient , the patient was sent for a spiral chest CT with contrast to rule out a pulmonary embolism . During CT about 100–150 mL of air was inadvertently injected through the right antecubital vein using a power contrast injector ( estimated by the technician and approximation of volumes on available imaging ) . Concurrent imaging ( CT ) showed a significant amount of air in the right atrium and right ventricular cavity ( Figure 1 ) , and air mixed with contrast in the main pulmonary artery and its proximal branches divisions of the pulmonary circulation ( Figure 2 ) . Concurrently , a filling defect was noted in the right lower lobe artery consistent with pulmonary thromboembolism ( Figures 3 , ,4).4 ) . The patient maintained hemodynamic stability with Trendelenburg , and left lateral decubitus positioning ( Durant ’s maneuver ) , and supportive care alone and she was transferred to the intensive care unit ( ICU ) for observation . Her respiratory distress worsened , and she was placed temporarily on non - invasive positive pressure ventilation ( NIPPV ) without improvement and a few hours later she was intubated and placed on mechanical ventilation . Intravenous full dose heparin infusion ( initial bolus , 80 units / kg , followed by 18 units / kg / hour ) was initiated for treatment of concurrent thromboembolism . Echocardiography did not show any evidence of right or left ventricular failure . Subsequent echocardiography done 24 hours later did not show any evidence of intracardiac air and complete resolution of the air embolism . During the next 48 hours , she remained hemodynamically stable with no requirements of vasoactive agents . She was finally extubated 48 hours after the initial presentation . She was later discharged home on warfarin with subsequent outpatient follow - up .


A 46 - year - old woman with a history of Graves ' disease ( GD ) was transferred to our emergency department on suspicion of DKA . She had noticed polydipsia , polyuria , and fatigue approximately four months prior to admission . She had also been suffering from a 1 - month complaint of appetite loss , approximately 7 kg weight loss , fatigue , nausea , and sweating . Her medical history included GD , diagnosed at 42 years of age and managed with methimazole . However , she had poor compliance with anti - thyroid drugs . She denied a family history of thyroid diseases or diabetes . Three days before admission , she was also diagnosed with influenza A at a nearby hospital , and oseltamivir phosphate was prescribed . At the emergency department , she presented with drowsiness and a body temperature of 37.0 ℃ , blood pressure of 90/60 mmHg , heart rate of 200 bpm , respiratory rate of 32 breaths / min , oxygen saturation of 99 % in 5 L nasal air , and a Glasgow coma scale ( GCS ) score of 14 . Her clinical examination revealed a diffuse goiter with bilateral exophthalmoses . Her lungs were clear when auscultated . Her abdomen was soft and non - tender . Her skin was warm and wet . She had no lower extremity edema . The electrocardiogram showed marked tachycardia with atrial fibrillation , and a chest radiograph was normal . The laboratory data are shown in Table 1 . Her initial laboratory data demonstrated marked metabolic acidosis , an increased plasma glucose level of 472 mg / dL , an increased HbA1c level of 13.7 % , an increased free triiodothyronine level of 6.440 pg / mL , and a free thyroxine level of 2.830 ng / dL , with a suppressed thyrotropin ( TSH ) level of 0.005 μIU / mL. She scored 55 on the diagnostic criteria of Burch & Wartofsky for thyroid storm , and the diagnostic criteria of the Japan Thyroid Association for thyroid storm were also satisfied , since she had thyrotoxicosis , symptoms involving the central nervous system , tachycardia , and gastrointestinal symptoms ( 4 ) . Accordingly , she was diagnosed with DKA and thyroid storm and admitted to the medical intensive care unit for further monitoring and treatment . The clinical course is shown in Figure . She was treated with an intravenous insulin drip and aggressive intravenous fluid therapy . The thyroid storm with GD was treated with intravenous hydrocortisone 100 mg every 8 hours , oral potassium iodine 50 mg every 6 hours , and oral methimazole 20 mg every 6 hours . Since she had a history of asthma , landiolol hydrochloride , a short - acting beta - adrenoceptor blocker , was used at 4 - 12 μg / kg / min to control her heart rate . By Day 3 , her tachycardia had resolved , and landiolol hydrochloride was discontinued . On Day 6 , the white blood cell count had decreased to 2,800 cells / mm3 [ neutrophils , 44.2 % ( 1,238 cells / mm3 ) ] . Methimazole was discontinued because methimazole - induced neutropenia was suspected . The patient was referred to an endocrine surgeon , and thyroidectomy was performed on Day 32 . She was discharged from the hospital on Day 37 and maintained on multiple daily insulin infusion and levothyroxine sodium hydrate . Further immunological investigation revealed elevated levels of anti - glutamic acid decarboxylase ( GAD ) antibody , anti - insulinoma antigen 2 ( IA-2 ) antibody , and insulin autoantibody , consistent with T1D. The intravenous glucagon stimulation test was performed with blood samples for glucose and C - peptide taken at baseline and 6 minutes . Her plasma glucose levels were 139 and 152 mg / dL at baseline and 6 minutes , respectively . The corresponding serum C - peptide levels were 0.8 and 1.3 ng / mL at baseline and 6 minutes , respectively .


We present the case of a 16 - year - old girl , admitted to our clinic with severe abdominal pain , loss of appetite , nausea , and vomiting . The anamnesis revealed that the girl comes from a family of potters , and that she also participated in the process of pottery , her father being diagnosed with lead poisoning 2 years before . The patient 's personal history underlined that approximately 1 year ago she presented with severe abdominal pain , being diagnosed with acute appendicitis and she underwent appendectomy , but the pain persisted , thus due to family history of lead poisoning , the suspicion of saturnine colic rose , and she was diagnosed with lead poisoning ( urinary lead : 219 μg / L ) , but she received only symptomatic treatment . Approximately 3 weeks before admission to our clinic , she was admitted to the regional hospital with another episode of saturnine colic ( blood lead : 113.2 μg / dL ) , and chelation therapy with EDTA ( 4 days before the admission in our clinic ) was initiated , with a dose of 2 tablets daily , one in the morning and one in the evening associated with calcium supplements . The clinical examination performed at the time of admission revealed the following pathological elements : influenced general status , ailing face , jaundice of the sclera , blue pigmentation of the nails , painful abdomen at palpation , and weight : 45 kg . The laboratory test performed upon admission revealed hypochromic anemia ( hemoglobin ( Hb ): 10.9 g / dl , hematocrit ( Htc ): 31.6 % , medium cellular volume ( MCV ): 77.6 fL ) , increased level of liver transaminases ( alanine - aminotransferase ( ALAT ): 158.9 U / L , aspartate - aminotransferase ( ASAT ): 63 U / L , gamma - glutamyl - transferase ( GGT ): 128 U / L ) , conjugated hyperbilirubinemia ( direct bilirubin ( DBi ): 1.432 mg / dL ) , hyponatremia ( Na : 132 mmol / L ) , and hypopotassemia ( K : 2.85 mmol / L ) . The systolic arterial pressure was 156 mm Hg , and the diastolic was 96 mm Hg . The blood lead level was 66.28 μg / dL , the urinary one was 419.7 μg / L ( normal < 50 μg / L ) and the value of delta - aminolevulinic acid was 7.66 mg / L ( normal < 4.5 mg / L ) . We also performed abdominal ultrasound which revealed a disappearance of the delimitation between the cortical and medullar parts in both kidneys . We requested consultation from an occupational healthcare specialist , who recommended the continuation of chelation therapy with EDTA , increasing the dose at 4 tablets / day . We also required a neurological consultation , and the specialist established the diagnosis of behavioral disorders with depressive elements , and recommended psychotherapy . Based on all these clinical and laboratory findings , we established the diagnosis of lead poisoning . We initiated an intense i.v . hydration in order to favor lead elimination , approximately 3 liters per 24 hours initially , and we decreased progressively the quantity once she ceased to vomit , and she was able to consume liquids . We associated diuretics , initially furosemide by vein , but the values of the arterial pressure persisted above the upper limit , therefore we were forced to introduce also an angiotensin - converting enzyme inhibitor , with the remission of arterial hypertension . Regarding the liver function , we administered amino acids intravenously , associated with liver protectors by mouth . We also administered vitamins of the B complex in order to improve the neurological impairment . The evolution was slightly favorable , in the first 3 days after the admission , the patient continued to present severe abdominal pain , vomiting , and she also complained of pain in the lumbar area . All the laboratory parameters presented normalization of the values after approximately 10 days of treatment . On the 6th day of admission , we ceased the chelation therapy with EDTA . We also repeated the blood and urinary lead levels . The blood level was 45.57 μg / dL , and the urinary one was 836.4 μg / L before discharging the patient . The abdominal ultrasound reevaluation revealed no pathological modifications . After 14 days of admission , the patient was discharged without any complaints , and we recommended no further exposure to lead , avoiding the contact and the working in the pottery process . The long - term outcome of this case depends on further exposure to this heavy metal . Nevertheless , we intend to repeat the blood lead levels after 12 and 24 months , assessing also the renal ( urea , creatinine , urinary exam ) and hepatic functions ( ASAT , ALAT , GGT , bilirubin ) .


A 68 - year - old man referred to the Internal Medicine Department of Razi Hospital in Rasht ( a city in the north of Iran ) with a hypogastric region discomfort , especially in the right lower quadrant for one month . The pain was a colicky form which had a few episodes each day , each episode lasting for 4–5 minutes . The pain radiated to the back and was alleviated by resting to one side . No association between the pain , defecation , and eating were reported . Furthermore , the patient complained of a 2–3 kg weight loss over the last one month followed by anorexia . However , no symptoms of nausea , vomiting , fever , or shaking chills were demonstrated . He was first admitted to another center for a week , then was referred to our hospital for further evaluation . The patient had undergone a surgery for prostatectomy seven years before his presentation to our center . Also , he had a history of endoscopy five years earlier due to dyspepsia , which was found to be Helicobacter pylori positive at that time and which was eradicated after a treatment course . No history of HIV , diabetes , smoking , or alcohol consumption was recorded . His vital signs were normal at the time of admission . On physical examination , the abdomen was soft , there was no distention , and bowel sounds were normoactive . However , tenderness in the right lower quadrant of the abdomen with no rebound state was noted . The peripheral blood analysis is shown in Table 1 . Stool examination , urine analysis , and evaluation of electrolytes were all normal . An abdominal CT scan showed a well - demarcated and homogenous solitary mass in the cecum with no distention in the ileum . The ileum wall was thickened ( Figure 1 ) . A colonoscopy revealed a large mass like lesion in the cecum ( Figure 2 ) ; during the procedure a biopsy was taken from the cecum . The lamina propria was infiltrated by a number of PMNCs admixed by some eosinophils ( Figure 3 ) . Immunohistochemical evaluation was positive for vimentin and CD68 . C - Kit ( CD117 ) was negative while CD34 , smooth muscle actin ( SMA ) , and ALK were focally positive . There were no reports of cyclin D1 , desmin , or pancytokeratin ( Figure 4).When the colonoscopy was performed , the evidences of invasive obstruction lead us to the suspicion of a malignant tumor . After pathological confirmation of IMT , the patient was referred for surgery in order to remove the mass . On surgery , approximately 40 mL ascites were found in the abdomen . A mass was seen in the cecum with ileocolic intussusception . Afterwards , the patient underwent right hemicolectomy with an end - to - end anastomosis of ileocolic . No enlarge lymph nodes were observed . The patient was discharged seven days after surgery and had no complications during follow - up .


A woman aged 31 years , G2P2 , without any pathological past history , with good prenatal care , with a normal prenatal analysis , blood pressure during the follow - up was normal , admitted for elective caesarian section at 38 weeks of amenorrhea . During realization of the spinal anesthesia the patient presented peak of the hypertensive ( 180/100 mm Hg ) which normalized after a few minutes without treatment . In post - partum , after 12 hours of the caesarian section the lady presented a severe headache with apyrexia then she developed three episodes of generalized tonico - clonic convulsions . The 1st convulsion ceased 1 min after the measures of resuscitation and injection of diazepam IV . The post - critical clinical examination found an afebrile patient and blood pressure at 140/90 mmHg and with Glasgow coma scale at 14 without any neurological deficit , there was no neck rigidity , diuresis was preserved . The examination of urines by urinary strip was positive ( + + + ) . The 2nd and 3th convulsive crisis stoped spontaneously within few seconds . Laboratory findings of HELLP syndrome include raised liver enzymes ( ASAT 525 IU / L and ALAT 214 IU / L ) , hemolysis ( hemoglobinemia in 7 mg / dl ) and low platelet count ( 44 000 platelet / mL ) . Other investigations included the renal function tests , the inflammatory markers , the thyroid hormones were normal . The viral serology was negative . The patient was transferred to intensive care unit ; she was treated immediately by magnesium sulfate associated to calcium channel blocker ( nicardipine ) , antiepileptic ( phenobarbital ) and preventive dose of low molecular weight heparin . The anemia and thrombopenia corrected by transfusion of packed red blood cells and platelet respectively . The magnetic resonance imaging ( MRI ) , realized one hour after the first episode of convulsion showed zones in hyposignal T1 , hypersignal T2 and flair sequences , interesting the cerebral cortex , parietal and occipital sub - cortical and the white matter . Intracranial venous sinuses were permeable . The diagnosis of the PRES syndrome secondary to the severe preeclampsia immediate post - partum was retained ( Figure 1 ) . The electroencephalogram ( EEG ) realized in the second day did not showed anomaly . The evolution was marked by the normalization of blood pressure , the normalization of the neurological state and of the biological analysis . The patient discharged in good condition on day 5 , with beta - blocker and sodium valproate maintained during three months . THE MRI of the controle made three months later showed complete resolution of cerebral edema Figure 2 .