A 60 - year - old white Brazilian man , with controlled hypertension and stage 2 obesity presented to our institution with a complaint of progressive fatigue with moderate to light exertion of approximately 1 year ’s duration . During that period , he had undergone myocardial perfusion scintigraphy without evidence of obstructive ischemic disease . He had no clinical evidence of systolic heart failure . He had undergone biological mitral valve replacement 3 years previously for mitral valve stenosis and had undergone ablation of atrioventricular nodal reentry tachycardia 18 months previously . At the time of valve replacement , there was no reported evidence of pulmonary arterial hypertension . The patient ’s medication list included aspirin 100 mg / day , carvedilol 50 mg / day , atorvastatin 10 mg / day , and losartan 25 mg / day . His echocardiogram showed normal function of a mitral prosthesis , global left ventricular systolic function within normal limits ( left ventricular ejection fraction 62 % measured using the Teichholz method ) , stage I diastolic dysfunction , and mean pulmonary arterial systolic blood pressure of 50 mmHg . In the 6 - minute walk test , the patient walked 104 meters ( Table 1 ) . Catheterization of his right heart chambers and pulmonary arteries confirmed the diagnosis of pulmonary hypertension ( Table 2 ) . During the follow - up period , therapy with nifedipine and sildenafil was not tolerated secondary to orthostatic hypotension . The patient was referred for radiofrequency ablation of the pulmonary artery trunk for the treatment of refractory pulmonary hypertension . The procedure was performed in the catheterization laboratory with direct visualization using fluoroscopy and radiopaque contrast dye . The patient remained under unconscious sedation . Catheterization of the right femoral artery via the standard Seldinger technique was performed using an 8 - French valved short sheath after subcutaneous injection of a local anesthetic . Subsequently , this sheath was replaced with a steerable long sheath ( Agilis ® ; St. Jude Medical , St. Paul , MN , USA ) using the standard over - the - wire technique . Unfractionated heparin was administered intravenously , targeting an activated coagulation time between 250 and 350 seconds . Electroanatomic reconstruction of both the right ventricular outflow tract and pulmonary artery was performed using the EnSite Velocity Cardiac Mapping System ( St. Jude Medical ) under direct fluoroscopic visualization , and a merger was made with the formatted image obtained by performing cardiac computed tomography angiography ( Fig.1 ) . The Agilis ® sheath was advanced into the right ventricular outflow tract just before reaching the pulmonary valve . Through this long sheath , we introduced an ablation catheter with an open irrigated tip ( St. Jude Medical ) . The parameters used for each application according to our protocol were as follows : power of 5 W , maximum temperature of 48 ° C , 60 - second duration in each spot , maximum impedance variation of 10 % from baseline values , and an irrigation flow rate of 17 ml / minute , which created a circle in the pulmonary artery trunk . The patient was discharged the next morning . No noteworthy changes before or after the procedure or before discharge in the patient ’s radiographic or echocardiographic laboratory parameters were seen . The patient ’s blood pressure in both the right heart chambers and the pulmonary artery were determined using catheterization before and at 3 and 6 months after the procedure . The results are shown in Table 2 . At the patient ’s 3 - month follow - up examination , he showed an improvement in functional class for fatigue with major exertion . He also demonstrated an increased distance walked in the 6 - minute walk test and reduction of the pressures in both the right cavities and the pulmonary artery . Currently , with 6 months of clinical follow - up , he has maintained his improvement in functional classification and is pedaling his bicycle .


A 35 - year - old woman was admitted with a 5 - day history of increasing drowsiness , fatigue , personality changes , generalised weakness and deteriorating mobility . Her medical history included a 10 - year history of schizo - affective disorder , lithium - induced diabetes insipidus and hypothyroidism . Her medications included sodium valproate 1 g twice daily , carbamazepine , quetiapine and lithium . On admission , the patient was drowsy , difficult to rouse ( sleeping all night and in the afternoon ) . Her Glasgow Coma Scale ( GCS ) was 14/15 , her abbreviated mini - mental test score was 6/10 and she was noted to be slow in her responses . Neurological examination showed reduced power in her lower limbs ( 3–4/5 ) in a pyramidal distribution , and brisk reflexes with intact sensation in all modalities . Cardiovascular , respiratory and gastrointestinal examinations were unremarkable and there were no demonstrable features of hepatic disease . Routine biochemistry was unremarkable . The patient 's alanine transaminase was 7 u / L ( 1–15 ) , alkaline phosphatase 61 u / L ( 30–130 ) , γ - glutamyl transferase 17 u / L ( < 45 ) and bilirubin was 6 μmol / L ( < 21 ) . She had normal serum B12 and folate levels , and normal thyroid function tests . Serum lithium levels were within the therapeutic range . Her serum ammonia was 47 μmol / L ( 11.2–35.4 ) and valproate concentrations were elevated 140 mg / L ( 50–100 ) . Brain imaging including CT and MRI did not show any haemorrhage or intracranial mass . Lumbar puncture demonstrated clear cerebrospinal fluid ( white cell count < 1×106 / L , protein 0.25 g / L ( 0.2–0.4 ) ) . EEG demonstrated mild variable slowing and irregularity of background activity ( likely due to medication ) . The differential diagnosis included encephalitis , Guillain - Barré syndrome and acute disseminated encephalomyelitis ( ADEM ) , which were excluded through our investigations . In view of the raised valproate and ammonia levels , a diagnosis of valproate hyperammonaemic encephalopathy ( VHE ) was made at this point The dose of sodium valproate was reduced by half rather than being completely withdrawn . This was due to the complex and challenging nature of managing the patient 's schizo - affective disorder . Within 3 days , there was evident clinical improvement in her mental status . The patient was able to sit and communicate with the team , and her abbreviated mental test score improved to 10/10.The serum ammonia normalised and valproate levels decreased to the therapeutic range . After 4 days she was discharged home . Results of investigations of her urea cycle were awaited . Three weeks postdischarge , the patient was clinically stable in terms of mental functioning , having had no further episodes of confusion or drowsiness . However , she continued to have fatigue and walking difficulties ( due to residual leg weakness ) . Results of her serum amino acids revealed that our patient had carnitine deficiency evident by low acyl - carnitine , low free serum carnitine ( 14.2 μmol / L , normal range : 23–52 ) and low total serum carnitine ( 19.9 μmol / L , normal range : 27–63 ) . She was started on oral carnitine 1 g twice daily . Within 2 weeks , her symptoms resolved completely with normalisation of serum carnitine levels ( free carnitine 25.2 μmol / L and total carnitine of 41.3 μmol / L ) . The sodium valproate was initially stopped completely , but due to a serious relapse of the patient 's schizo - affective disorder , it was restarted and she is now well on valproate 1 g once daily and long - term carnitine supplements .


A 77 - year - old woman with dysphagia presented with a two - week history of rash characterized by brown plaques with erythematous borders and overlying thick scales involving the face and a prior percutaneous endoscopic gastrostomy ( PEG ) tube site ( Fig.1a , c ) . No oral or conjunctival involvement was present . She had been receiving parenteral nutrition for two months following removal of the PEG tube due to infection . Although the differential diagnosis included drug hypersensitivity , autoimmune disorders and nutritional deficiency , the rash appearance was most consistent with acrodermatitis enteropathica - like eruption secondary to zinc deficiency . Her serum zinc level was 12 mcg / dL ( normal , 55–150 mcg / dL ) , and the rash resolved within one week of parenteral zinc supplementation ( Fig.1b , d ) . Zinc is essential for protein synthesis and wound healing . Acrodermatitis enteropathica presents in infancy as a periorificial desquamative dermatitis , resulting from an autosomal recessive mutation that impairs zinc absorption . A similar syndrome may occur due to nutritional zinc deficiency , and has been reported in the setting of parenteral nutrition that fails to include zinc supplementation ; a prompt response to supplementation helps to confirm the diagnosis . A recent national shortage of parenteral zinc in the United States likely contributed to this patient ’s presentation .


A 42 - year - old woman presented with a right breast lump , lower back pain , loss of height , marked kyphosis and hepatomegaly . Core biopsies from the breast lump showed ductal carcinoma in situ ( sample labelled P1.1 ; Supplementary Fig.1 and Supplementary Table 1 ) . An additional biopsy from an ipsilateral axillary lymph node ( P1.2 ) revealed metastatic ductal adenocarcinoma ( ER+ ( 8/8 ) and HER2 + ( 3 + ) ) . Computed tomography scan revealed widespread metastatic disease in bones , pleura and liver ( Supplementary Fig.2 and Supplementary Table 2 ) . The patient was started on treatment with trastuzumab and taxane - based chemotherapy , with a significant partial response ( Supplementary Fig.3 ) . After induction chemotherapy , she was maintained on tamoxifen and trastuzumab . After 19 months on treatment , she presented with seizures and head computed tomography revealed a large metastasis in the left frontal lobe ( Supplementary Fig.4 ) , which was resected ( M2.1 ) . Therapy with tamoxifen and trastuzumab was continued and collection of plasma samples was initiated ( samples T1 – T9 ) . Four months after surgery , she had enlarging liver lesions and a new metastatic deposit in the left ovary ( Supplementary Fig.5 ) . Treatment was switched to a combination of lapatinib and capecitabine , resulting in stable disease for 12 months ( Supplementary Fig.6 ) . General deterioration then occurred , with disease progression in the chest ( new pulmonary nodules , bilateral pleural effusions and posterior chest wall mass , Supplementary Fig.7 ; Eastern Cooperative Oncology Group performance status 2–3 ) . Treatment was stopped and the patient died ∼4 months later . Tumour samples were obtained at diagnosis from the primary breast site ( P1.1 ) and an axillary lymph node ( P1.2 ) ; after 19 months from the brain metastasis area ( M2.1 ) ; and at autopsy after 3 years on treatment ( from the primary breast site , and from metastatic deposits in the chest , liver , ovary and vertebrae , labelled P3.1 and M3.1 – M3.4 , respectively ) . Serial plasma samples were obtained over the last 500 days of clinical follow - up ( T1 – T9 ) . Tumour and plasma samples collected and the clinical course are summarized in Fig.1a , b.


A 60 - year - old man who underwent colonoscopy was found to have a 2 cm sessile polyp that was located 10 cm from the anal verge and successfully removed . The polyp was a tubulovillous adenoma with focal high - grade dysplasia . A flexible sigmoidoscopy performed three months later , as well as a repeat colonoscopy one year after the initial colonoscopy , were both negative for recurrence . A colonoscopy performed three years after the initial colonoscopy revealed a sessile polyp , 3 cm in size , at 10 cm from the anal verge . Biopsies were taken and reported to be fragments of a villous adenoma with low - grade dysplasia . Due to the previous high - grade dysplasia , relatively rapid recurrence and concern that a cancer may have been missed by sampling error , a pelvic magnetic resonance imaging ( MRI ) scan and an endoscopic ultrasound ( EUS ) were performed before definitive excision . The MRI revealed an invasive rectal mass involving the muscularis propria but without breach of the adventitia , consistent with a T2 rectal carcinoma ( Figure 1 ) . No pelvic lymphadenopathy was detected . The EUS revealed a rectal mass involving the mucosa and submucosa , with no involvement of the muscularis propria ( Figure 2 ) . The results of the MRI and EUS , as well as the surgical versus endoscopic resection treatment options , were discussed with the patient , who opted for a surgical resection . The patient underwent a low anterior resection and end - to - end anastomosis with loop ileostomy . Pathology review of the resected rectosigmoid revealed a villous adenoma with low - grade dyplasia . There was no evidence of muscularis propria invasion , and a total of five pericolic and two mesorectal lymph nodes were excised and deemed benign . The patient underwent ileostomy reversal five months later . He remains asymptomatic with no recurrence of tumours .


A 57 - year - old Jewish man with Crohn 's disease ( CD ) of the ileum diagnosed at the age of thirteen , presented with multiple nonmelanoma skin cancers ( NMSCs ) ; these had developed over the past 16 years coinciding with the initiation of a prolonged course of the thiopurine 6 - mercaptopurine ( mercaptopurine , 6 - MP ) . He was diagnosed with a total of 84 NMSC : 72 NMSC at our clinic , 12 from other clinics . He was also awaiting biopsy and removal for additional lesions . His CD was initially treated with sulfasalazine and intermittent steroids at diagnosis , but for the past 20 years he had been taking 6 - MP daily . In the first ten years after beginning 6 - MP he developed 30 NMSC ; 14 were squamous cell carcinoma ( SCC ) and 16 were basal cell carcinoma ( BCC ) . The patient was then treated elsewhere for the subsequent ten years . This past year , however , he returned to the clinic with over 100 new lesions suggestive of malignancy on his torso and extremities . Subsequent to this exam , he had 42 biopsy - proven lesions of NMCS ; 20 were SCC and 22 were BCC . In addition , three of the SCCs were moderately differentiated and two were poorly differentiated and some of his larger skin cancers have necessitated Mohs surgery and xenografting . The largest of his lesions was pretibial and measured 64x53 mm ( Figure 1 ) . He was awaiting biopsy for many other suspicious lesions . The patient had Fitzpatrick II skin type and admitted to excessive sun exposure for 25 years in Hawai‘i . Early on he did not use sunscreen , and would sail a catamaran during peak sun hours . He also revealed that his mother had one skin cancer lesion removed and denied ever having been a smoker . Within the past year he discontinued 6 - MP and began using mesalamine ( Pentasa ) and later adalimumab ( Humira ) hoping to attenuate the progression of NMSC , and continued to have monthly skin exams . Overall , he was hospitalized 16 times for his CD , but never required any intestinal resection . Unfortunately , in his most recent hospitalization he was diagnosed with metastatic adenocarcinoma of the small bowel , and passed away shortly after .


A 56 - year - old man presented with a 2 - year history of dysphagia . He was diagnosed with a middle thoracic oesophageal squamous cell carcinoma by both a gastroscopy and a biopsy . A chest computed tomography ( CT ) scan showed an enlarged azygos vein ( a diameter of 2.5 cm ) that was a continuation of the IVC ( Fig.1a , b ) . A CT scan of the abdomen showed a defect in the suprarenal segment of the inferior vena cava and direct drainage of the hepatic vein into the right atrium . After consultation with the thoracic surgery department clinicians and the anaesthesiology department , we decided to perform a McKeown oesophagectomy . The patient was anaesthetised with a double - lumen tube and underwent a standard posterolateral thoracotomy by traditional open surgery . We first performed the jugular and femoral vein percutaneous puncture to create a veno - venous bypass and then connected the pressure sensor system to the monitor . The monitor displayed the real - time pressure value of the jugular vein and the femoral vein . Macroscopically , the diameter of the azygos arch was approximately 2.5 cm ( Fig.1c ) , and the superior edge of the tumour adhered tightly to the arch of the azygos vein . When the arch of the azygos vein was pulled with a rubber hose to dissociate it from the carcinoma , the monitor showed that the femoral vein pressure increased to 52 mmH2O ; the pressure returned to a normal value when we opened the bypass between the femoral vein and the jugular vein ( Fig.2 ) . The surgery was performed smoothly , without injury to the azygos vein , and the postoperative recovery was uneventful . The pathology of the resected specimen showed a poorly differentiated squamous cell carcinoma and no evidence of malignancy in 15 of the lymph nodes . After 5 months of follow - up , the patient was asymptomatic , with no evidence of recurrent disease either clinically or on CT .


A 39 - year - old Korean male come to our hospital complaining of cough , myalgia , and fever that had lasted for 5 days . He was a company worker and denied any previous medical histories . He was a current smoker and drank alcohol about once a month . His vital signs were : blood pressure , 100/60 mmHg , heart rate , 100 / min , respiratory rate , 25 breaths / min , and body temperature , 39 ° C . On the physical examination , decreased breathing sound was noted in the right lower lung . Laboratory tests revealed a c - reactive protein ( CRP ) level of 119 mg / dL , a total bilirubin level of 1.8 mg / dL , and alanine transaminase and aspartate transaminase levels of 250 and 172 IU / L , respectively . His platelet count was 98,000 / mm3 , while his white cell count was 8150 / mm3 ( neutrophil : 85 % ) . In the arterial blood gas analysis checked in room air , pH , PaCO2 , PaO2 , bicarbonate , and oxygen saturation levels were 7.50 , 34 mmHg , 67 mmHg , 26.5 mmol / L , and 95 % , respectively . A test for the human immunodeficiency virus was negative . Mycoplasma and Chlamydia antibodies were negative . Streptococcal and Legionella urinary antigens were negative . Anti - nuclear and anti - neutrophilic cytoplasmic antibodies were also negative . A chest X - ray showed consolidation in the right mid to lower lung fields . Chest computed tomography showed consolidation with surrounding ground glass opacity in the right middle lobe with a small amount of pleural effusion in the right hemithorax ( Fig.1 ) . Abdominal sonography revealed no abnormal finding in the hepatobiliary system . We began to administer 4 L / min of oxygen nasally and empirical antibiotics with third generation cephalosporin and macrolide following a diagnosis of community - acquired pneumonia . On the second day in the hospital , the patient ’s fever was sustained and he complained of dyspnea . His hypoxemia was aggravated such that he required 7 L / min of oxygen via a simple mask and the consolidation and pleural effusion had markedly progressed ( Fig.2a ) . We performed bronchoscopy and thoracentesis . Multiplex real - time reverse transcriptase polymerase chain reaction ( RT - PCR ) for respiratory viruses using bronchoalveolar lavage fluid was positive for human adenovirus while other microbiological studies were negative . Pleural fluid was lymphocyte - dominant exudate and was also positive for human adenovirus . Under the diagnosis of adenovirus pneumonia , we started antiviral therapy with oral ribavirin 400 mg q 12 h while maintaining antibiotics . On hospital day 4 , his fever had subsided and symptoms were much improved . The transaminase levels , CRP and platelet counts gradually normalized ( Fig.3 ) . A follow - up chest X - ray was clear ( Fig.2b ) and he was discharged in hospital day 13 without any complications .


Here , we describe another case in a 60 - year - old man from San Francisco who had consumed raw pork while traveling in the Philippines . In June 2003 , this man became ill with fever , diaphoresis , headache , nausea , and anorexia . He had just returned from a 7 - month vacation in the Philippines . Three days after symptoms onset , his physician prescribed doxycycline . Symptoms continued and he was admitted to a local hospital 5 days later with a fever of 38.9 ° C , nuchal rigidity , headache , and general malaise . The patient described no recent contact with sick persons ; past medical history was unremarkable . On physical examination , he was somnolent but fully oriented , with no focal findings on neurologic examination and only slight nuchal rigidity . He had a leukocyte count of 21,000 / mm3 , including 16,400 / mm3 neutrophils . Cerebrospinal fluid ( CSF ) showed leukocyte count of 487 / μL with 80 % polymorphonuclear cells and 18 % lymphocytes , and glucose and protein levels < 20 mg / dL and < 167 mg / dL , respectively . Gram stain of CSF showed gram - positive cocci in pairs ( Figure ) . Empiric therapy ( ceftriaxone , vancomycin , and ampicillin ) for bacterial meningitis was begun . Computed tomographic scan of the head showed only sinusitis ; findings of chest radiograph and transesophageal echocardiogram were negative . On hospital day 2 , blood cultures grew gram - positive cocci in pairs and chains . The organism was catalase - negative , bile esculin - negative , and pyrrolidonyl aminopeptidase - negative , consistent with Streptococcus spp . A latex agglutination test did not detect Streptococcus pneumoniae antigen . Antimicrobial susceptibility testing showed that the isolate was sensitive to penicillin ( MIC = 0.03 ) , ceftriaxone , and vancomycin but resistant to tetracycline and clindamycin . Antimicrobial therapy was changed to penicillin G , 24 million units intravenously per day . On hospital day 5 , the patient complained of hearing loss in his left ear . Results of nasopharyngeal endoscopy were negative . By hospital day 7 , the organism was identified by the API 20 Strep System ( bioMerieux , Marcy l’Etoile , France ) , as S. suis serotype 2 . The patient subsequently stated that he was a butcher with a culinary preference for partially cooked pork , which he had eaten in the Philippines until the week prior to onset of symptoms . On hospital day 9 , a formal audiology evaluation showed severe bilateral sensorineural high - frequency hearing loss ( – 70 dB ) . The patient completed a 10 - day course of parenteral antimicrobial drugs and was discharged on continued oral therapy with close followup . Two months after discharge , the patient reported much improved hearing without other sequelae .


A 5 - year - old Caucasian male presented to the Children ’s Emergency Department with epistaxis , bleeding from the dental extraction site and a widespread purpuric rash , secondary to acute idiopathic thrombocytopenia . Two days prior to this , he developed a generalised chickenpox rash . While in the department it was noted that his heart rate ranged between 50 and 60 beats per min , he was otherwise haemo - dynamically stable with a normal blood pressure and oxygen saturations in air . He had a short systolic murmur grade 2/6 at the left sternal border . He had no clinical evidence of myocarditis or heart failure . He had extensive generalised petechiae and purpuric rash ( figure 1 ) secondary to acute thrombocytopenia presumed to be due to varicella infection . Apparently he was healthy prior to this admission . There was no history of maternal lupus . An ECG was performed which showed complete heart block ( figure 2 ) . He was admitted to the high dependency unit for close overnight monitoring . The presumed diagnosis was complete heart block secondary to varicella infection.1 2 The initial investigation showed normal electrolytes , calcium , phosphate , glucose and magnesium levels . The full blood count showed a normal haemoglobin and white cell count . But the platelet count was low that is , 13×109 / l. The platelet count normalised within 10 days without any intervention . The antinuclear antibody titres and the autoimmune screen were negative . Maternal autoimmune screen was negative . The echocardiogram showed a structurally normal heart and follow - up 24 h tape showed persistence of complete heart block . Following these investigations a diagnosis of congenital complete heart block was made . On follow - up after 6 months his heart rate remains between 50 and 60 beats per min , but he remains asymptomatic without any intervention . The need for a pacemaker is being considered on follow - up . The incidental finding of complete heart block was congenital in aetiology with no association with varicella infection or acute thrombocytopenia . This case highlights that asymptomatic late - presenting congenital complete heart block must be considered as a differential diagnosis in children presenting with asymptomatic bradycardia to the emergency department .


A 31 - year - old man developed diabetes insipidus with urine volume up to 10 to 20 L every 24 hours in 2003 . Four years later , he complained of fatigue , anorexia , jaundice and pruritus , and a symptomatic occipital mass . Laboratory tests showed an abnormal liver enzyme ( Table 1 ) , the patient was negative for hepatitis viruses . As shown in Fig.1 , abdominal MRI showed multiple low - density lesions in the liver on the T1 - weighted image and obvious expansion of the intrahepatic bile duct on the T2 - weighted image . Magnetic resonance cholangiopancreatography revealed multifocal intrahepatic bile duct strictures and dilatation , but the common hepatic duct was normal , it was highly suggestive of SC . The neurohypophyseal area MRI showed the thickened hypothalamic nuclei and a low - density signal of 4.9 × 5.6 mm in size in the hypothalamic - pituitary area . A multisystem , high - risk organ LCH was confirmed after occipital mass was biopsied in the local hospital , the patient was given ursodeoxycholic acid 150 mg 3 times a day . Then , he began to receive a course of COEP chemotherapy ( cyclophosphamide , 1000 mg ; vincristine , 2 mg ; epirubicin , 90 mg ; and prednisone , 90 mg ) in 2009 . However , on the 5th day of the 1st COEP chemotherapy , the patient appeared to severe liver function injury with an obvious increase of serum bilirubin ( Table 1 ) . He refused further chemotherapy . One year later , the patient developed liver decompensation with bleeding esophageal varices , ascites , and splenomegaly , and he was referred to LT ( Model for End Stage Liver Disease score 17 ) . He underwent successful orthotopic LT in November 2011 in our center , and the donor came from voluntary deceased citizen organ donation in China . Liver histopathology after LT revealed micronodular cirrhosis with SC and positive immunostaining ( CD1a and S100 ) , suggestive of LCH involving in the liver ( Fig.2 ) . Postoperatively , the man continued to be immunosuppressed with tacrolimus and mycofenolate mofetil . The patient is currently well with normal liver function and no evidence of recurrence of LCH for 4 and a half years follow - up .


A 50 - year old man with a history of metastatic mucinous appendiceal adenocarcinoma presents for evaluation of a desquamating rash on his face that has spread to his scalp , inguinal region , and perineum over the past 4 months ( Figure 1 ) . The rash has been accompanied by diffuse alopecia of the face , scalp , axilla , and groin . There was no improvement in the rash despite multiple rounds of oral fluconazole , topical antibiotic ointment , and intravenous antibiotics . Prior to the development of his rash , he completed neoadjuvant chemotherapy followed by surgical resection . He underwent colostomy after he failed surgical correction for an enterocutaneous fistula , and he has required total parenteral nutrition ( TPN ) for the past year . He did not notice any significant changes in ostomy output during this time . Dermatological examination reveals widespread erythematous plaques on the face , scalp , and medial aspect of thighs bilaterally and scattered papules with scaling on face , scalp , chest , and back . Diffuse , non - scarring alopecia is present on the face , scalp , axillae , and groin . The patient had acquired AE , a rare dermatologic condition caused by zinc deficiency . This patient developed acquired zinc deficiency in the setting of inadequate zinc supplementation in TPN . The patient had not received trace elements for approximately one year due to a national shortage . The key to the correct diagnosis of acquired AE is the combination of desquamating rash coupled with alopecia in the setting of chronic supplemental alimentation . Although it is reasonable to consider a skin biopsy , a skin biopsy would not definitively establish the diagnosis . A paraneoplastic panel could be considered , but it would delay diagnosis , and the presentation is most consistent with nutritional deficiency . It is not appropriate to start a topical steroid cream until a diagnosis is determined . The patient had a zinc level of 29 ug / dL ( normal range 56 - 134 ug / dL ) . He received zinc supplementation in his TPN , and within one month , the patient had complete resolution of rash and fatigue , and gradual return of hair growth ( Figure 2 ) . Repeat zinc level following supplementation was 90 ug / dL. Although the patient recovered from his zinc deficiency , he later passed away .


The patient was a 3 - year - old girl with the following features of VACTERL association : absent C1 vertebra , supernumerary lumbar vertebrae , hypoplastic sacrum / coccyx , fatty filum terminale with tethered spinal cord , and three fused ribs ; an anorectal malformation including a cloaca consisting of a common urogenital sinus and a duplex vagina with midline septum ; type C TE fistula ; right renal agenesis with moderate left hydronephrosis and vesicoureteral reflux . She had no cardiac or limb malformations , and no other major organ anomalies . Both she and her father were additionally clinically diagnosed with hypermobile type Ehlers – Danlos syndrome , but family history was otherwise noncontributory . The diagnosis of hypermobile type Ehlers – Danlos was based on the patient ’s hypermobility ( 9/9 on the Beighton hypermobility scale ) , very soft , fragile skin with unusual scarring , and poor skin healing . Skin biopsy was not performed , but testing on peripheral blood did not reveal mutations associated with other forms of Ehlers – Danlos syndrome . Microarray analysis initially showed a maternally - inherited deletion at 4q35.1 detected with one clone and confirmed by FISH ( RP11 - 173M11 ) . Subsequent performance of an 180 K custom oligonucleotide microarray ( Baylor College of Medicine Medical Genetics Laboratories ) refined the deleted region deletion to a maximum size of 1.37 Mb , with karyotype revised to 46,XX , arr cgh 4q35.1q35.2 ( 187,321 - 768 - 188,694 - 589 ) 3 1 . Genes in the deleted region , which contains a number of much smaller copy number variations ( CNVs ) identified in normal controls , include CYP4V2 , KLKB2 , F11 , MTRNR1A , and FAT1 , none of which can be clearly related to her phenotype , especially as her mother , from whom the deletion was inherited , is unaffected . Evidence for mitochondrial dysfunction began at 13 months of age with progressive muscle weakness , autonomic dysregulation , hypoglycemic episodes , exocrine pancreatic dysfunction , and decline of gastrointestinal function , eventually leading to total parenteral nutrition dependency due to visceral hyperalgesia , dysmotility , and malabsorption . Muscle biopsy showed a mild increase in fiber size variability but no other findings consistent with mitochondrial disease , including via electron microscopy . However , analysis of electron transport chain ( ETC ) activity showed normal activity of complexes I , II , and III , but complex IV , or cytochrome c oxidase , activity was 45.4 lmol / min / g weight , well below the control range ( 148.9 + /− 67.2 lmol / min / g weight ) . Repeat ETC analysis in isolated mitochondria confirmed a profound and reproducible complex IV deficiency . Citrate synthase activity and content in both ETC analyses were normal , confirming good sample quality and normal mitochondrial content . Whole mitochondrial genome sequencing , and sequencing of DNA Polymerase Gamma 1 and 2 ( POLG1 and POLG2 ) and Thymidine Phosphorylase did not reveal abnormalities .


A 26 - year - old woman was seen in the emergency department ( ED ) for chest pain and hypertension . She was found to have a urinary tract infection and was sent home with an antibiotic and thiazide diuretic . Two days later , she returned with epigastric pain , nausea , emesis and myalgias . The patient had no significant medical history and denied cardio - respiratory symptoms ; however , she complained of a low exercise tolerance for the last year . There was no family history of cardiac or pulmonary disease or of sudden cardiac death . She was born in the USA and had neither travelled recently nor had any sick contacts . On examination , she was hypertensive ( 170/105 mm Hg ) , tachycardic ( 125 bpm ) , had dry mucous membranes and appeared ill looking . She was found to have an elevated serum creatinine of 160 μmol / l ( normal 60–110 μmol / l ) . After receiving 1.5 l of intravenous fluids for presumed volume depletion and prerenal azotaemia she became short of breath . Crackles were noted on auscultation of her chest and a portable chest film demonstrated hazy infiltrates that likely represented pulmonary oedema . She then developed hypotension with systolic pressures in the 90s . Non - invasive positive pressure ventilation was initiated . An ECG demonstrated sinus tachycardia with a rate of 130 bpm and minimal ST depression on the precordial leads . In consultation with a cardiologist , the patient received 40 mg of intravenous furosemide . An echocardiogram demonstrated global hypokinesis with a left - ventricular ejection fraction < 10 % ( see figure 1 ) . The patient was transferred to the intensive care unit where she became more anxious and tachycardic to 170 bpm . She was intubated and sedated . Despite the placement of a Foley catheter and administration of intravenous loop diuretics , she remained anuric for the first 12 h of hospitalisation . She developed signs of acute kidney injury with a creatinine that increased to 350 μmol / l within the first 24 h of hospitalisation . She received norepinephrine and milrinone to improve cardiac output . On the second day of hospitalisation , she was evaluated by a cardiologist and cardiothoracic surgeon for emergent circulatory support as she had developed signs of poor tissue perfusion with a lactic acidosis ( 8.4 mmol / l ; normal < 2.2 mmol / l ) and transaminitis with aspartate aminotransferase / alanine transaminase > 150 IU / l ( normal < 40 U / l ) . She was taken to the cardiac catheterisation laboratory for emergent right heart catheterisation and biopsy to exclude acute myocarditis . Over the next few days , she was gently fluid resuscitated ( guided by bioreactance non - invasive cardiac output ) , the pressors were gradually weaned off and she became non - oliguric . She slowly regained renal function and organ perfusion improved with resolution of the lactic acidosis and a decrease in liver transaminases . On hospital day 5 she was transferred to the medical ward and was eventually discharged home on non - selective β blockade , an ACE inhibitor and nitrate with planned follow - up at the heart - failure clinic . The patient returned to the ED 4 days later with an elevated blood pressure , nausea and abdominal pain . A contrast scan of her abdomen revealed pancreatitis and an adrenal mass . During her treatment for pancreatitis she began to have paroxysms of headaches , nausea , emesis and abdominal pain with corresponding hypertension to the 220s systolic and tachycardia to 120s with a baseline systolic pressure of 90–110 mm Hg ( see figure 2 ) . Her urinary and plasma catecholamines were elevated and confirmed on repeat testing . She was given aggressive fluid rehydration and α and β blockade for a planned adrenalectomy . Prior to surgery her left - ventricular ejection fraction had improved to 55 % on medical management ( see figure 1 ) . Pathology of her adrenal gland was consistent with a non - malignant pheochromocytoma ( see figure 3 ) .


A 59 - year - old man was referred to the general surgery department of our hospital for a one - month history of progressive dysphagia for solids , which was not associated with malnutrition or significant weight loss . The patient had recently undergone esophagogastroduodenoscopy in another hospital , which revealed a bleeding , ulcerative lesion in the middle third of the esophagus , but no biopsy had been collected . The medical past history included COPD diagnosed in 1999 and a myocardial infarction in 2002 . The patient had smoked approximately 25 cigarettes per day for several years . Physical examination was unremarkable . Computed tomography ( CT ) of the chest and abdomen revealed stenosis involving a 5 - cm segment of the middle third of the esophagus with no other lesions in the thoracic or abdominal organs . Barium studies disclosed a swelling in the esophageal wall 7 cm above the cardia with an ulcerative pattern , which reduced the diameter of the lumen to 5 mm . An endoscopic biopsy of the oesophageal mass demonstrated poorly differentiated ( G3 ) squamous cell carcinoma . Mid - distal esophagectomy was performed with oesophagogastric anastomosis and gastric tube reconstruction . Pathological examination of the surgical specimen confirmed the biopsy diagnosis of poorly differentiated ( G3 ) SCC . The tumor , which measured 3 cm of length , had infiltrated the oesophageal wall and the surrounding paraesophageal fat . Surgical margins were tumor - free , as the seven perigastric limph - nodes dissected ( pT3 N0 ) . The postoperative period was quite unremarkable , and a contrast enhanced x - ray obtained on the 9th POD showed normal esophageal and gastric transit . On the 14th POD , the patient was discharged with an oncology referral for routine medical follow - up . Nine months after the operation , CT and esophagogastroduodenoscopy were repeated . The imaging study revealed mild splenomegaly with multiple nonspecific nodules within the organ ( Figure 1 ) . The patient was virtually asymptomatic with the exception of a vague sensation of mild discomfort in the left upper quadrant of the abdomen . FNAC of the spleen revealed a pattern of numerous inflammatory cells admixed with large cells displaying immunohistochemical positivity for several cytokeratins ( Figure 2 ) . The specimen was Gram stain - negative . A bone - marrow biopsy was negative for metastatic involvement . The diagnosis was isolated metastases of the spleen with inflammatory and necrotic alterations . The patient was referred to our centre for splenectomy , which was performed as a routine procedure to role out , also , a spontaneous rupture of the spleen . On 12th December 2007 , the patient had transabdominal total splenectomy with splenic and celiac artery lymph node dissection . The postoperative course was uneventful . On the 7th postoperative day , Doppler ultrasonography revealed portal - tree patency with no signs of thrombosis . Ten days later , the patient was discharged with a stable platelet count ( 780,000 / mm3 ) , Hb 10.9 g / dL , and a WBC count of 16,500 / mm3 . Pathological examination of the spleen described multiple nodules containing medium to large - sized cells , some of which were keratinized . The nodules were mostly solid with areas of central necrosis ( Figure 3 ) . The findings were consistent with metastases of SCC . Thereafter , the patient was referred to the oncology department of our hospital , where he received two 3 - day cycles ( separated by a 3 - week interval ) of systemic chemotherapy based on 5 - fluorouracil ( 800 mg / day IV ) and cisplatin ( 20 mg / day ) . Three months after the splenectomy , multiple liver metastases were seen on the CT scan , and cutaneous metastases were also present . The patient died 9 months later .


A 72 - year - old woman underwent RF ablation for the treatment of a metachronous solitary liver metastasis from rectal adenocarcinoma , which had been treated 18 mo before with preoperative chemoradiotherapy and anterior resection . The lesion was located in segment VIII . The procedure went well and the patient was initially haemodynamically stable . One hour later her condition suddenly worsened . She was clinically dizzy and had fatigue and pallor . We detected hypotension and tachycardia . Emergency blood tests showed a haemoglobin level of < 7 g / dL and markedly elevated transaminase levels . A computed tomography examination revealed an accumulation of intraperitoneal fluid in the pelvis and two liver haematomas . The images showed two liver lacerations , one following the path of the needle ( Figure (Figure1A1A--C)C ) and another , unexplained laceration leading away from the first ( Figure (Figure2).2 ) . The patient had no serious coughing or hiccupping after the RF treatment , or any other complications that might have caused increased abdominal pressure and tumour rupture . Subsequently , the patient received a blood transfusion and close monitoring . She was haemodynamically stable after the second blood transfusion and completely recovered 24 h later . The patient remained in bed for 1 wk . No surgical intervention was required .


An 8 - year - old boy was referred for evaluation of fatigue . He was born at term weighing 4 kg to non - consanguineous parents and attained normal early developmental milestones . Height and weight were on the 10th and 50th centiles , respectively . Preliminary examination was remarkable only for hepatomegaly extending 3.5 cm below the right costal margin . Initial laboratory evaluation revealed normochromic normocytic anaemia ( haemoglobin 7.8 g / dL ( 11.5–16 ) , mean corpuscular volume ( MCV ) 85.8 fL ( 75–87 ) and mean corpuscular haemoglobin ( MCH ) 25.4 pg ( 25–35 ) ) with marked anisocytosis ( red - cell distribution width ( RDW ) 29 % ( 11–14.5 ) ) . Hypochromia and teardrops were evident on a blood film . Leucopoenia was also a feature ( white cell count 2.9×109 / L ( 4.5–13.5 ) , neutrophils 1.7×109 / L ( 2–7.5 ) and lymphocytes 0.8×109 / L ( 1.5–4 ) ) . A bone marrow aspirate and biopsy revealed a hypercellular marrow with erythroid hyperplasia . An iron stain revealed that approximately 50 % of erythroblasts were ringed sideroblasts . Marrow cytogenetics were normal including fluorescence in situ hybridisation studies of chromosomes 5q , 7 and 8 and flow cytometry did not detect a blast population . Serum copper and lead were normal , as were blood smears on the proband ’s parents and sister . Analysis of several genes responsible for hereditary SA ( ALAS2 , ABC7 , FECH and PUS1 ) revealed no reported pathogenic variants . Fasting lactate was elevated at 3.8 mmol / L. Neurological examination identified upper motor neuron signs in the lower limbs bilaterally ; however , cerebellar signs were negative . MRI of the brain demonstrated volume loss with slight prominence of the cerebellar folia . Urine organic acids revealed elevated 3 - methylglutaconate and 3 - methylglutarate . The lactate : pyruvate ratio was elevated ( 30:1 ) . Muscle biopsy revealed a structurally normal muscle and biochemical assay of respiratory chain components resulted in a diagnosis of partial complex IV deficiency . He subsequently commenced a high - fat diet and coenzyme Q with a resultant improvement in energy . Analysis of mtDNA in leucocytes and muscle utilising PCR did not reveal a deletion . Carnitine , vitamin A , thiamine , pyridoxine , folate and uridine were supplemented without improvement in his anaemia . Haemoglobin levels fell to 4.4 g / dL , leading to occasional and then regular three - weekly red cell transfusions . With repeated transfusions , ferritin rose to 1700 µg / L , necessitating iron chelation . Peak growth hormone and cortisol to insulin - induced hypoglycaemia were 30.9 mU / L ( normal > 20 ) and 447 nmol / L ( normal > 500 ) , respectively , at age 13 years . Thyroid function was normal . Repeat peak cortisol was 384 nmol / L following adrenocorticotropic hormone ( ACTH ) stimulation . Plasma renin activity was elevated to 15 ng / mL / h , and adrenal androgens were below the lower limit of assay detection . A urinary steroid profile was qualitatively normal , as was an abdominal ultrasound . Hydrocortisone 5 mg twice daily and fludrocortisone 100 µg daily were initiated . Adrenal autoantibodies to 21 - hydroxylase were negative and very - long - chain fatty acids were normal . The patient has recently developed a renal tubular Fanconi syndrome including glycosuria , hypokalaemia , hypophosphataemia with low maximal tubular reabsorption of phosphate and a generalised aminoaciduria . In addition , he was incidentally noted to have hyperglycaemia during an admission for percutaneous endoscopic gastrostomy insertion . Glycated haemoglobin was elevated to 62 mmol / mol ( 7.8 % ) despite rapid red cell turnover . Pancreatic autoantibodies were negative ( glutamic acid decarboxylase , anti - insulin , anti - islet antigen 2 and pancreatic islet cell antibodies ) . He is maintained on twice daily insulin detemir with satisfactory glycaemic control with fructosamine 161 µmol / L ( 205–285 ) .


A 48 - year - old man presented at our hospital complaining of intracranial bruits . The cranial nerve and laboratory examinations were normal . A DVAF was considered , conventional digital subtraction angiography was performed , which showed a Cognard II DVAF in the location of right hypoglossal canal ( HC ) . The DVAF was fed by the meningeal branches of the bilateral ascending pharyngeal arteries , and the right anterior condylar veins within the hypoglossal canal that was the fistulous point mainly drained into the jugular vein . Endovascular treatment was insisted upon by the patient because of the associated intolerable intracranial bruit . Treatment was performed by transarterial approach under general anesthesia using a biplane angiographic unit . Standard coaxial techniques were used . The guide catheter was navigated into the left ascendingtrawt pharyngeal artery . Marathon flow directed catheter ( eV3 ) was subsequently navigated over a Mirage.008 microwire ( eV3 ) to reach as near as possible to the fistula . The microcatheter was flushed with 10 mL of normal saline . The dead space of the microcatheter was subsequently filled with dimethyl sulfoxide ( DMSO ) . Onyx-18 was then injected over two minutes to fill the microcatheter and to replace the DMSO in the dead space . The injection was stopped until unwanted flow into branches of the right ascending pharyngeal artery was observed . The follow - up angiogram showed no residual shunt ( Figure 1 ) . The intracranial bruits disappeared immediately after the operation . For the toxicity of DMSO , 10 mg dexamethasone was intravenously injected for three days . On the second day after endovascular treatment , the patient complainted of difficulty moving his tongue to the left . Cranial nerve examination was only significant for a right hypoglossal nerve palsy . The patient was discharged from our hospital four days after treatment without continuative pharmacotherapy . At two months follow - up , the patient 's main complaint were difficulty swallowing ( dysphagia ) and slurred speech ( dysarthria ) . In addition , his tongue deviated toward the right during tongue protrusion , and marked right - sided hemiatrophy was observed ( Figure 2 ) . The cranial nerve examation showed right hypoglossal nerve palsy persisted . We telephone the patient at three months follow - up and requested a vocal cord evaluation by an ENT specialist in a local hospital . Vocal cord paralysis was not found , and there was no evidence of vagus nerve dysfunction . Oral Vitamin B12 was used and his prognosis was still at a long follow - up .


A 53 - year - old woman presented to our institution with progressive abdominal distention and irregular vaginal bleeding of several weeks ’ duration . A contrast CT abdomen and pelvis revealed an ill - defined , irregular mass in the lower uterine / cervical region ( Figure 1 ) . There were multiple peritoneal and omental masses , enlarged pelvic and paraaortic lymph nodes , and large - volume ascites . The initial CBC was significant for hemoglobin of 9.2 g / dL , leukocytosis of 36 790 per microliter , and thrombocytosis of 625 000 per microliter . Serum calcium was elevated at 13.1 mg / dL. BUN and creatinine were within normal limits . Hepatic function was within normal limits . A pelvic exam revealed a fungating vaginal mass . The patient underwent biopsies of the endometrium and the vaginal mass , which revealed a high - grade tumor with predominantly oval - shaped cells . Immunohistochemical staining was positive for vimentin , CD10 , and cyclin D1 , consistent with a diagnosis of high - grade endometrial stromal sarcoma ( Figure 2 ) . The tumor was negative for ER , with rare cells positive for PR . Although immunohistochemical staining for cytokeratins was negative , a biphasic component could not be entirely ruled out given the small size of the biopsy specimen relative to the tumor . The patient ’s Ca125 was markedly elevated at 1624 U / mL ( nl ≤34 ) . Contrast CT chest revealed a right - sided pleural effusion but no suspicious nodules or lymphadenopathy . The patient was deemed to have operable disease and was scheduled for debulking surgery . However , preoperative laboratory studies showed that her serum calcium had further increased to 19.2 mg / dL. She had also developed evidence of acute kidney injury , with her BUN rising to 37 mg / dL and creatinine to 1.81 mg / dL. On physical exam , she was noted to be lethargic , with dry mucous membranes . The surgery was cancelled due to the patient ’s medical instability . Further workup revealed an elevated PTHrP of 301 pg / mL ( nl 14–27 ) , a depressed PTH level of 3 pg / mL ( nl 15–65 ) , and a depressed 25 - OH vitamin D level of 16 ng / mL ( nl 30–100 ) , consistent with humoral hypercalcemia of malignancy . The patient was treated with pamidronate , calcitonin , and intravenous fluids . She eventually required temporary hemodialysis and denosumab for refractory hypercalcemia . The patient improved with regard to her electrolyte abnormalities . Given the extent of her disease , she was planned for neoadjuvant chemotherapy followed by surgery if a good response was achieved . She was started on a regimen of carboplatin and paclitaxel , which she received for 3 cycles . She also had palliative radiation to the uterus to control bleeding . However , her disease failed to respond significantly to chemotherapy , and she ultimately died from complications of malignancy .


This 73 - year - old female , with a history of coronary artery disease and situs inversus , had recently noticed left arm exercise weakness . The magnetic resonance angiogram and computer tomography of the upper limb vessels showed critical stenosis of the left - side SCA with calcification near the orifice ( Fig.1 ) . Percutaneous revascularization was done via right femoral artery approach , and severe left SCA stenosis was confirmed ( Fig.2A ) ( Supplementary Video 1 , only online ) . Direct stenting in the left SCA was carried out with a balloon - expansible Express LD 10×25 mm stent ( Boston Scientific Corporation , Natick , MA , USA ) ( Fig.2B ) up to 8 atmospheres for 13 seconds . However , severe shortness of breath and hypotension developed after stenting . The blood pressure was down to 88/56 , and the heart rate was up to 90 . The oxygen saturation was down to 74 % . Emergent intubation , fluid infusion , inotropic agent with norepinephrine were given . The immediate angiography showed vascular perforation in the stented segment of left SCA ( Fig.2C ) ( Supplementary Video 2 , only online ) . Emergency balloon inflation within the stent was done with an 8×40 mm balloon . The cardiovascular surgeon was also consulted . However , due to the high surgical risk of bypass , endovascular treatment was suggested . We decided to do a retrograde approach through the left brachial artery by surgical cut - down . Since there was no suitable graft stent in our cath lab , we modified and cut the iliac extension of self - expanding Endurant II graft stent 10×82 mm ( Medtronic , Inc. , Minneapolis , MN , USA ) , which was originally designed to treat abdominal aortic aneurysms ( AAA ) , to a suitable length ( around 30 mm ) ( Fig.3 ) . After retrograde wiring , an operator - modified Endurant II graft stent was deployed in the stent segment ( Fig.2D ) and the perforation was sealed successfully . After stenting of the graft stent , however , slow flow of left common carotid artery ( LCCA ) was noted , and angiography confirmed the near total occlusion of the LCCA , occluded by the SCA graft stent ( Fig.2E ) ( Supplementary Video 3 , only online ) . A firm wire ( Conquest pro , Asahi Inc , Seto , Japan ) was successfully advanced outside the graft stent and into the LCCA . Despite sequent balloon dilations at the bifurcation site , the flow to the LCCA was still poor . Intravascular ultrasound also confirmed the severe compromise of the LCCA ostium which was caused by the graft stent ( Fig.2F ) . Therefore , we put a balloon - expansible carotid stent , Express 7×37 mm ( Boston Scientific Corporation ) , from the LCCA to the left brachiocephalic artery ( Fig.4A ) . TIMI III flow of the LCCA was restored after stenting ( Fig.4B - E ) ( Supplementary Video 4 , only online ) . Intravascular ultrasound also confirmed proper expansion of the LCCA stent ( Fig.4F ) . The follow - up chest radiography revealed left - side hemothorax . After thoracocentesis with drainage and proper care , the patient was discharged . Till now , the patient has been free from symptoms for six months .


A 62 - year - old female presented to the outpatient department of Wuhan Central Hospital of Tongji Medical College in September 2015with a complaint of recurrent infections in the umbilical region . She reported abdominal pain similar to a burning sensation that accompanied the discharge of faecal matter . These symptoms and signs waxed and waned but lasted for 5years . Our attention was piqued by the fact that the patient ’s family described the patient as an individual who cried easily . The patient had no history of diarrhoea , constipation or other abdominal disturbances . No surgical treatment was mentioned in her prior medical history . Acoordinated physical examination revealed normal vital signs . An external fistula was located in the umbilical region with redness of the surrounding skin . Morphological examination indicated that fistula secretions mainly consisted of small intestinal juice . The abdominal wall was soft , with no tenderness . Bowel sounds were regular . Escherichia coli and Enterococcus faecalis were detected in the fistula secretion culture . Other findings from laboratory examinations were normal . A CT scan of the abdomen revealed that part of the intestinal wall was adhered to the abdominal wall in the navel region , although no bowel obstruction was detected ( Fig.1 ) . A presumptive diagnosis of ECF was reached ; this diagnosis was mainly based on digital radiography of the fistulous tract conducted using iopamidol-370 as a contrast agent . This procedure was performed under local anaesthesia and revealed that the distal ileum approximately 40 cm from the ileocaecal junction was entrapped ( Fig.2 ) . The patient agreed to surgery after a clear preoperative conversation . She understood the operative risk factors and signed an informed consent . After bowel preparation , the patient received an exploratory laparotomy . The abdominal cavity was completely exposed , and a loop of the terminal ileum ( approximately 40 cm proximal to the ileocaecal junction ) was found entrapped in the internal hernia ring ; this finding was consistent with the preoperative contrast image . The defect in the abdominal wall was less than 1.0 cm , and an extremely small portion of the bowel wall was stuck and could not be retrieved back into the cavity ( Fig.3 ) . Nonetheless , this defect resulted in perforation over the loop ( Fig.4 ) . Side - to - side ileo - ileal anastomosis was completed by utilizing a 75 mm linear stapler to remove the affected ileum segment . The internal hernia ring was closed with plication sutures instead of via mesh repair due to the patient ’s small defect and infection risk . The abdominal cavity was thoroughly cleaned with saline solution , and a rubber drainage tube was placed in the pelvis . The scar tissue was removed to improve wound healing ; subsequently , relaxation sutures were available to close the abdomen in layers . A final diagnosis of Richter ’s hernia presenting as spontaneous ECF was reached . The patient was discharged 2 weeks after surgery without serious complications . No hernia recurrence was observed during 10 months of follow - up .


A 70 - year - old man was referred to our hospital for gastric cancer that was detected during screening by esophagogastroduodenoscopy ( EGD ) . No significant medical history was identified , except dysuria caused by bladder contraction . Initial laboratory data showed a serum level of AFP of 32.3 ng / mL ( normal range : 0 - 15 ng / mL ) , but no other abnormality , which included other tumor markers , such as , carcinoembryonic antigen ( CEA ) and carbohydrate antigen 19 - 9 ( CA19 - 9 ) . EGD revealed a 5 - cm ulcerofungating mass that was comprised of three septate ulcers in the greater curvature of the gastric antrum . A pathological examination of endoscopic biopsy tissues confirmed the presence of moderately differentiated tubular adenocarcinoma . Subsequent abdominopelvic computed tomography visualized a gastric mass with deep ulceration in the gastric antrum with perigastric lymph node enlargement . No metastatic lesions were observed in the liver , lung or peritoneum , and chest radiography showed no significant findings . Radical subtotal gastrectomy with D2 lymph node dissection and Billroth II gastrojejunostomy were performed . Grossly , the resected specimen contained double lesions : the first was a 5.8 cm × 3.2 cm ulcerofungating mass in the antrum , with extensive hemorrhage and light gray fibrosis ; and the second was a nearby 2.5 cm × 2.0 cm ulcerative lesion ( Figure 1 ) . Microscopically , massive numbers of pleomorphic , bizarre tumor cells with hemorrhage ( syncytiotrophoblasts and cytotrophoblasts ) were observed in the first lesion . Hematoxylin and eosin ( HE)-stained tissues revealed a bubbly purple cytoplasm and giant nuclei at a magnification of 40 × ( Figure 2A ) and 100 × ( Figure 2B ) . The tumor involved the proper muscle layer ( T2a ) and metastasis was found in four of 56 regional lymph nodes ( N1 ) . Immunohistochemical staining showed positive immunoreactivity for β - human chorionic gonadotropin ( HCG ) ( Figure 3A ) and focal positivity for AFP ( Figure 3B ) . These findings confirmed the presence of gastric choriocarcinoma that contained small foci of an AFP - producing adenocarcinoma . The second lesion was moderately differentiated tubular adenocarcinoma , which extended to the submucosal layer ( T1b ) . It was close to , but distinct from the first lesion , which was negative by immunohistochemical staining for β - HCG and AFP . The patient had an uneventful postoperative course and was discharged on postoperative day 9 . Two weeks later , his HCG level was 176 mIU / mL ( normal range : 0 - 10 mIU / mL ) and his AFP level was 10.0 ng / mL. Six cycles of adjuvant chemotherapy with capecitabine ( Xeloda ; Hoffmann - La Roche Inc. , Nutley , NJ , USA ) was started at 2500 mg / m2 per day for 14 d / cycle . After two cycles , his β - HCG level had declined to < 3 mIU / mL , and has since remained at this level . No recurrence or distant metastasis had occurred at his 4 - year postoperative follow - up .


A 51 - year - old G1P1 Caucasian female with lifelong neurogenic bladder secondary to spina bifida occulta was referred for symptoms of constipation and ( FI ) . She averaged one Bristol Type 1–2 stool every 5 days requiring frequent manual disimpaction . Additionally , she reported twice weekly episodes of urgent fecal seepage , which required the use of daily continence pads . Her symptoms did not improve with the addition of psyllium and bisacodyl suppositories . A defecography suggested atrophy of the puborectalis and poor squeeze with EAS muscle atrophy . Anorectal manometry ( ARM ) showed a normal resting pressure with no augmentation of squeeze pressure , consistent with weak EAS ( Figure 1 ) . During bearing down , fixed perineal descent was noted with the inability to widen the posterior anorectal angle and poor evacuation of contrast with straining , consistent with DD . With pushing , ARM similarly demonstrated type IV DD , which is classified as inability to generate adequate propulsive forces along with absent or incomplete relaxation of the anal sphincter [ 8 ] ( Figure 2 ) . Reflex and sensory testing indicated an intact rectoanal inhibitory reflex and rectal hypersensitivity . The patient failed management with home and conventional biofeedback therapy . Following a successful trial of temporary SNS with improvement in FI symptoms by 75 % , the patient had a permanent SNS placed . One year later , the patient reports sustained improvement in constipation and FI symptoms .


A woman in her 60s was found to have screen detected invasive lobular breast carcinoma of the right breast and invasive ductal carcinoma , no special type , of the left breast . Staging CT imaging prior to mastectomy showed a 12 cm pelvic mass which on initial impression was thought to be a fibroid uterus . Associated postmenopausal bleeding led to pelvic ultrasound , hysteroscopy and biopsy . The biopsy showed undifferentiated sarcoma , unclassifiable with immunohistochemistry . Following discussion at a multidisciplinary team meeting it was felt that the uterine tumour was a separate primary malignancy rather than metastasis from the breast . Hysterectomy and bilateral salpingo - oophorectomy was performed for both treatment purposes and to fully categorise the malignancy to guide further adjuvant therapy . Histological examination of the resection specimen showed a partially necrotic tumour with a discrete outline located within and extending throughout the myometrium . The tumour was composed of malignant spindle cells ( figure 1A ) , with an intermittent component of pleomorphic cells with abundant eosinophilic cytoplasm . Plentiful osteoclast - like giant cells were present ( figure 1B ) . Mitoses were numerous and structurally abnormal forms were common . Neoplastic cells were surrounded by hyaline osteoid matrix and foci of coarse neoplastic woven bone ( figure 1C ) . Generous sampling of the tumour showed no admixed neoplastic epithelial elements , thus ruling out the more common carcinosarcoma ( malignant mixed Müllerian tumour ) . Tumour cells showed immunohistochemical expression for vimentin , smooth muscle actin ( SMA ) , desmin ( focally ) and CD99 . Epithelial markers were not expressed . The morphological and immunohistochemical appearances were in keeping with primary uterine osteoblastic variant of osteosarcoma . Unfortunately , despite treatment , further CT imaging showed the development of multiple peritoneal and pulmonary deposits , confirmed on biopsy to be metastatic osteosarcoma . The patient received palliative chemotherapy and died several months later .


A 37 - year - old Caucasian man was referred to our department from an external hospital because of severe abdominal pain of unclear aetiology . The patient suffered from Friedreich 's ataxia.1 2 His most recent transthoracic echocardiography , performed on the day of admission , showed a dilated cardiomyopathy , impaired left ventricular function with an ejection fraction of 30 % and a pulmonary artery pressure of 55 mm Hg ; all findings were unchanged from previous examinations . At that time , he lived alone in a residential home and was mobile using a wheelchair . On arrival at our emergency department , the patient was somnolent and disoriented . His axillary body temperature was 35.7 ° C and his arterial blood pressure 125/89 mm Hg , with a pulse rate of 84 rhythmic beats / min . He complained of an increasing , diffuse abdominal pain during the whole day , combined with absence of appetite and vomiting on a single occasion . His daily medication was perindopril 2.5 mg , torasemide 7.5 mg and esomeprazole 40 mg . On physical examination , we found a tender abdomen with painful epigastric palpation . Normal bowel sounds were auscultated in the upper right and lower left quadrants . The renal bed was free of pain on palpation . On cardiac auscultation , a 2/6 systolic murmur was audible . Lung auscultation showed normal respiration . Laboratory findings were slightly elevated C reactive protein ( CRP ) of 16 mg / l ( normal : < 5 mg / l ) , elevated troponin - T - hs of 0.070 µg / l ( normal : < 0.014 µg / l ) and highly elevated pro - B - type natriuretic peptide of 7382 pg / ml ( normal : < 63 pg / ml ) . Kidney function parameters were in the upper normal range , with creatinine of 100 µmol / l and a calculated glomerular filtration rate of 73 ml / min . Blood count revealed leucocytosis of 15.6×109 / litre . Regarding thyroid function , thyroid - stimulating hormone , f - T3 and f - T4 were in the reference range . Urine analysis showed no pathology . In abdominal sonography , all organs were normal , especially the kidneys . No free fluid was detected ( figure 1 ) . As the severe pain persisted all night , despite analgesia with paracetamol 1 g , metamizole 1 g and pethidine 75 µg , a contrast - enhanced abdominal CT was performed revealing infarction of the right kidney , which appeared as a hypodense area although kidney arteries and veins were assessed as open ( figures 2 and 3 ) . Cardiac dysfunction is the most frequent cause of death in patients affected by Friedreich 's ataxia , most commonly from congestive heart failure or arrhythmia . Renal artery embolism is not a rare event in these patients . However , other non - abdominal viscous causes of severe diffuse abdominal pain such as porphyria , familial Mediterranean fever , diabetic ketoacidosis , tocopherol deficiency also had to be excluded . The negative cardiolipin test excluded tabetic crises . No evidence for pre - existing porphyria was encountered for example , quantitative determination of δ - aminolevulinic acid , porphobilinogen and porphyrin in 24 - h urine was negative . Further genetic diagnosis regarding , for example , clotting disorder , was also not conclusive . Hypovitaminosis was not present . The patient had no endocrinopathies , for example , no diabetes and no evidence for hypothyreosis or hyperthyreosis . The patient was hospitalised without delay at the department of nephrology . Immediate anticoagulation with heparin was initiated and later replaced by lifelong oral anticoagulation with phenprocoumon . During 11 days of hospitalisation , no complications occurred . Kidney function parameters remained normal . Transoesophageal echocardiography on the fifth day showed no cardiac thrombus and no patent foramen ovale . Deep vein thrombosis was excluded with duplex sonography . Anticardiolipin antibody testing and genetic testing regarding clotting disorders were both negative . Urine tests revealed no evidence of porphyria . During hospitalisation the patient remained stable regarding cardiological function , while diuretics were adjusted according to the fluid balance . The patient had already been treated with levofloxacin for pneumonic infection prior to hospitalisation . The antibiotic treatment was continued because of increasing inflammatory parameters in the further course of disease . A CRP increase of up to 200 mg / l was interpreted as an inflammatory response to renal infarction . By discharge , laboratory parameters were significantly decreased .


A 58 - year - old man had been suffering from general fatigue and severe anemia for several months . His hemoglobin levels were 6.6 g / dl ( normal range : 12–16 g / dl ) . He had no medical history and did not take any medicine . Esophagogastroduodenoscopy and colonoscopy did not reveal any significant bleeding . Abdominal computer tomography revealed a 2 - cm hypervascular tumor in the small intestine ( Fig.1 ) . Oral DBE detected a 2 - cm - diameter reddish , submucosal tumor - like lesion with surface ulceration in the jejunum , approximately 20 cm away from the Treitz ligament ( Fig.2 ) . We did not perform biopsy because it can be difficult to stop bleeding in the case of hypervascular lesions . Under the diagnosis of a small bowel tumor , gastrointestinal stromal tumor ( GIST ) , malignant lymphoma , or cancer , we performed laparoscopic - assisted segmental resection of the jejunum with the dissection of lymph nodes . Examination of the resected tumor showed that it measured 19 × 16 mm in diameter ( Fig.3 ) . Histology revealed the proliferation of blood capillaries and granulation tissue , which was consistent with PG ( Fig.4 ) . The patient was discharged on postoperative day 9 without complication and his anemia improved gradually without the need for oral iron after surgery .


An 18 - year - old male was diagnosed with attention - deficit hyperactivity disorder ( ADHD ) in 2005 . He was overweight with a body mass index ( BMI ) of 40 . He was started on quetiapine fumarate ( Seroquel ® ) 900 mg daily in April 2005 and methylphenidate ( Concerta ® ) 54 mg daily in September 2005 . In the beginning of August 2006 he was admitted to his local hospital with severe dyspnoea , tachypnea , tachycardia , and cyanosis . On admission the blood pressure was 120/80 mmHg , and the arterial blood gas revealed a pH of 7.45 , pCO2 of 3.55 kPa , paO2 of 7.76 kPa , and BE of −5.1 mmol / l. C - reactive protein was not elevated . The chest X - ray showed an enlarged heart . He developed hemoptysis and was treated with unfractionated heparin in suspicion of pulmonary embolism . He subsequently developed cardiogenic shock and was treated with vasoactive drugs . In spite of the treatment he became oliguric and his liver enzymes were rising . He was referred to our hospital for further treatment . On admission the blood pressure was 90/60 mmHg , despite infusion with noradrenaline . His heart rate was 130 / minute and his temperature was 38.4 ° C . A thoracic computed tomography scan did not show pulmonary embolism . Echocardiography revealed biventricular failure and left ventricular end diastolic diameter was 7 cm . The left ventricle was severely hypokinetic with an ejection fraction ( EF ) of 20%–25 % . The left ventricular end diastolic pressure was markedly elevated , and there was a moderate mitral regurgitation . Intermittent hemodialysis was initiated . His liver function improved slightly , but despite dialysis the renal function deteriorated with increasing creatinine values . After three days there was a further worsening of the left ventricular systolic function with an ejection fraction of 10%–12 % and marked pulmonary hypertension with systolic pulmonary pressure estimated to 30 mmHg . The clinical picture resembled dilated cardiomyopathy with low output failure causing renal and liver failure . We suspected drug - induced cardiomyopathy and methylphenidate and quetiapine fumarate were discontinued . Screening for infectious pathogens , immunological markers , and iron or amyloid deposition were all negative . After three days he was transferred to the National Hospital ( Rikshospitalet , Oslo ) with ongoing noradrenaline and dobutamine infusions . Shortly after admission an intraaortic balloon pump ( IABP ) was inserted and noradrenaline was replaced by nitroprusside . Coronary angiography was normal . Endomyocardial biopsy from the right ventricle did not reveal any distinct myocardial pathology . On treatment with IABP , nitroprusside , and dialysis , the clinical situation gradually improved and the liver function returned to normal . His renal function also improved with increasing diuresis and creatinine fell from 798 to 98 μmol / l. His EF was still markedly reduced ( 15 % ) . Because of behavioral problems and adipose stature , he was denied a heart transplant . He was treated with IABP for 26 days , and after 28 days he was transferred back to our hospital . At that time his liver and renal functions were normal . He was treated with an angiotensin - converting enzyme ( ACE)-inhibitor , a beta - blocker , and diuretics . During the following two weeks his clinical status improved and he was subsequently discharged to his home . The echocardiography still showed markedly dilated left ventricle with EF of 20 % . In March 2007 , his clinical status was improved and he was in function class II ( New York Heart Association ) with an EF estimated by echocardiography to 30%–35 % .


Our patient ( ID 73387 ) is a female child , born by an emergency caesarean section at 34 weeks of gestation to consanguineous , first - cousin British Pakistani parents . Antenatal scans showed that she was small for her gestation , weighing 1.19 kg at birth with a head circumference of 26.7 cm , considerably below the 0.4th centile . Induction of labour had been attempted because of the growth retardation but had failed , leading to the emergency caesarean section . The Apgar scores were 4 at 1 min , 7 at 5 min and 9 at 10 min . She was admitted to the neonatal intensive care unit for continuous positive airway pressure ventilation . At a few hours of age , she developed a severe lactic acidosis . The initial lactic acid concentration was 22 mmol / l and subsequently increased to 63 mmol / l ( normal range , 0.7–2.1 mmol / l ) . She was treated with intravenous infusions of sodium bicarbonate and Tris - hydroxymethyl aminomethane ( THAM ) , but it was never possible to correct the metabolic acidosis . She also developed hypoglycaemia within hours of birth that was corrected with an intravenous infusion of 15 % glucose ( 7.8 mg / kg / min ) . The ammonia concentration was normal . Urine organic acid profile showed massive excretion of lactic acid and increased phenolic acids , especially hydroxyphenyllactate . Plasma amino acids showed raised concentrations of alanine and glutamine ( 1567 and 1369 μmol / l , respectively ) , consistent with the lactic acidosis ; several other amino acids were also mildly increased . There was gross generalised aminoaciduria . Blood acylcarnitine analysis was normal . Echocardiography showed a structurally normal heart and good ventricular function . Cranial ultrasound showed bilateral intraventricular cysts within the frontal horns and anterior portions of the lateral ventricles . The left - sided cysts were larger , up to 15 mm in diameter , whereas the largest cyst on the right was 8 mm in diameter . The choroid plexuses were hyperechoic and irregular , suggesting previous intraventricular haemorrhage . Abdominal ultrasound showed a distended urinary bladder but was otherwise unremarkable . There was severe coagulopathy with an extended prothrombin time of 47.7 s ( normal 12.3–16.6 s ) , a very low plasma albumin of 7 g / l ( normal 35–50 g / l ) , otherwise normal liver function tests but a raised creatine kinase of 2700 U / l ( normal < 300 U / l ) . She was transferred to a tertiary centre because of her worsening metabolic acidosis . She started having seizures at ∼48 h of age . Despite infusions of bicarbonate and THAM , her acidosis continued to worsen . Muscle and skin biopsies were performed and the family agreed to the withdrawal of intensive care treatment . She died aged 55 h. All documented studies were approved and performed under the ethical guidelines issued by each of our Institutions for clinical studies , with written informed consent obtained from the family .


A 66 - year - old Caucasian woman with a history of hypertension was admitted to our hospital with a recent diagnosis of Burkitt lymphoma . Her lactate dehydrogenase level was high and the diameter of her mediastinal mass was more than 10 cm . Her physical examination was normal , and basal electrocardiography ( ECG ) showed sinus rhythm with a heart rate of 72 beats / minute . Two - dimensional transthoracic echocardiography ( TTE ; Siemens , Acuson Sequoia , C512 ) revealed normal biventricular functions with an LV ejection fraction ( LVEF ) of 60 % , mild mitral and tricuspid regurgitation , and moderate pericardial effusion . A risk assessment of the patient put her into a high - risk category and she underwent rituximab - hyperfractionated - cyclophosphamide - vincristine - doxorubicin - dexamethasone ( R - Hyper - CVAD ) chemotherapy protocol . Her laboratory values are summarized in Table 1 . She received high - dose cyclophosphamide 300mg / m2 twice daily for 3 days , doxorubicin 25mg / m2 / day for 2 days , rituximab 375mg / m2 / day for 1 day , dexamethasone 40mg / day for 4 days , and vincristine 2mg / day for 2 days . The total treatment dose of cyclophosphamide and doxorubicin received was 1800mg / m2 and 50mg / m2 , respectively . She was given allopurinol 300mg / day perorally , sodium bicarbonate ( 8.4 % , 10 flacon / day ) infusion for 24 hours before chemotherapy , and mesna 600mg / m2 / day for 2 days as prophylaxis against tumor lysis syndrome and hemorrhagic cystitis , respectively . She also received granisetron 2mg / day and lansoprazole 30mg / day as antiemetogenic and gastric prophylaxis , respectively . The patient developed dyspnea on the seventh day of therapy . A physical examination revealed blood pressure of 100/60mmHg and a heart rate of 110 beats / minute . On chest auscultation , no inspiratory sounds were heard at lower zones and inspiratory crackles were heard at middle zones . Neither cardiac murmurs nor S3 were heard . An ECG showed low voltage in the limb and precordial leads . TTE showed diffusely increased myocardial echogenicity , mild pericardial effusion , and generally impaired biventricular systolic functions with an LVEF 31 % and right ventricular mid - apical akinesis . Manifest pleural effusion was also detected . Drug - induced cardiotoxicity ( myocarditis ) was suspected . Furosemide and ramipril were started . The beta - blocker therapy the patient was already taking for hypertension was continued . After 12 days , TTE showed an LVEF of 37 % and normal right ventricular functions . Her dyspnea decreased and she was discharged on day 20 . After 1 month , TTE showed normal biventricular functions with an LVEF of 60 % . After the first course of the R - Hyper - CVAD chemotherapy protocol , she underwent a high - dose methotrexate and cytarabine cycle . She had severe neutropenia and pneumonia . She had no cardiac failure symptoms during this chemotherapy course , but she declined another course of chemotherapy . She is still in remission despite the abbreviated course of chemotherapy .


A 46 - year - old Caucasian woman of Ashkenazi Jewish descent presented with the chief complaint of severe and constant throbbing pain in her left posterior mandible . She reported that her pain was aggravated by chewing , and started months before the initial consultation visit . Visual analog scale of pain was reported 7/10 at the day of the visit . Past medical history was remarkable for Gaucher disease , left hip replacement , gall bladder removal , herniorrhaphy , spleen abscess drainage , hepatitis C infection , and asthma . Social history was significant for 20 pack - years of cigarette smoking . Her family history was unremarkable for any hereditary or systemic diseases . Her medications included the oral antiresorptive drug alendronate for early osteoporosis associated with Gaucher disease ( 70 mg weekly for 2 years ) , calcium supplements , loratadine , hydromorphone , esomeprazole , promethazine , levalbuterol , carisoprodol , fluticasone and ibuprofen . She reported that she had been on enzyme replacement therapy ( ERT ) intermittently for several years to treat her Gaucher disease which was diagnosed 20 years prior . She received intravenous injections twice a month for ERT and recounted fatigue after each infusion . She also reported receiving antibiotic and analgesic medications for her pain months ago but they were not helpful . Head and neck examination , cranial nerve examination and vital signs were within normal limits . Intraoral examination was completed using percussion testing , vitality testing and probing for evaluation of her mandibular posterior teeth in the region of the chief complaint . Her left mandibular first molar was endodontically treated 3 years prior and tested non - vital , while her remaining mandibular teeth were normal on vitality testing with evaluation of several opposing non - restored and non - carious teeth as internal controls . Gingival tissues in both jaws were non - inflamed and there was no gross evidence of plaque or calculus . Periodontal pockets in her mandible ranged from 4 to 6 mm with no significant bony defects . Full mouth dental X - rays and a panoramic radiograph were taken and showed relatively well - defined radiolucent lesions in multiple regions of the mandible bilaterally , with a pseudocystic ( multilocular ) appearance ; cone - beam computed tomography confirmed these findings and revealed a large lytic lesion of her left posterior mandible in the region of her chief complaint ( Figure 1).Our clinical and radiographic differential diagnosis for her chief complaint included chronic apical periodontitis , radicular cyst , central giant cell granuloma , keratocystic odontogenic tumor , ameloblastoma , odontogenic fibroma , neuralgia / neuropathy or mandibular involvement of Gaucher disease given her medical history . Our findings were discussed with the patient and written consent was obtained for surgical biopsy of her left mandible with local anesthesia for more definitive diagnosis . A four - corner gingival flap buccally was reflected in her posterior left mandible extending from the canine to the second molar , and cortical bone was removed with a surgical bur to create a window for access to the lesion . Pathologic soft tissue was evident through the access window . The entire pathologic soft tissue along with the bone from the access window was submitted to the pathology laboratory for histological evaluation . Histopathological findings revealed infiltration of jawbone marrow with fibrous connective tissue containing abundant Gaucher cells ( Figure 2 ) . There was no evidence of abscess or neutrophils , granuloma or malignancy . Postoperative healing was uneventful , and the patient reported resolution of her chief complaint and symptomatology at 1 - month follow - up . She was referred to her physician for consultation and further evaluation as related to her Gaucher disease status following our findings . She was again treated with ERT and at 1 - year re - evaluation was still symptom free in her oral cavity .


A 69 - year - old woman with a history of hypertension presented with a generalized petechial rash and shortness of breath of 3 days duration . The rash was nonpruritic , painless , and started at the thighs , but rapidly disseminated to the rest of the body . She had progressive dyspnea on exertion , with a significant decrease in exercise tolerance . She denied fever , headache , dizziness , hemoptysis , or bleeding from anywhere . There was no history of new drug use , unusual food intake , contact with any sick persons , or recent travel . Her only medication was enalapril , which she had been taking for several years . The patient denied any use of recreational drugs , tobacco , or alcohol . On admission , she was afebrile , normotensive with mild tachypnea ( respiratory rate of 22 breaths per minute ) . Physical examination revealed scattered petechial rash , more prominent in lower extremities , nonpalpable and nonblanching . Chest auscultation revealed coarse crackles bilaterally . Cardiovascular , abdominal , and neurological examinations were normal . There was no palpable lymphadenopathy or visceromegaly . Laboratory examination revealed thrombocytopenia ( platelets 7000 / μL ) , anemia ( hemoglobin 10.8 mg / dL and hematocrit 34 % ) , and leukocytosis ( white blood cells [ WBCs ] 11,600 / μL ) . The coagulation profile was normal , which excluded disseminated intravascular coagulation . Arterial blood gas on ambient air revealed a partial pressure of oxygen ( PaO2 ) of 64 Torr , a partial pressure of carbon dioxide ( PaCO2 ) of 37 Torr ( pH 7.45 ) , and an increased alveolar - arterial gradient ( 44 Torr ) . Diffuse airspace consolidation was found on chest roentgenogram ( Fig.1A ) . Computed tomography ( CT ) of the chest showed diffuse ground glass alveolar opacities and patchy infiltrates ( Fig.1B , C ) . She was started on broad - spectrum antibiotics and received intravenous steroids . Peripheral smear showed giant platelets and occasional small platelet clumps , with no schistocytes . A flexible fiber - optic bronchoscopy ( FFB ) showed normal mucosa with no endobronchial lesions ( Fig.2A ) . Serial aliquots of BAL fluid ( BALF ) turned more hemorrhagic , confirming the bronchoscopic diagnosis of DAH ( Fig.2B ) . Cytology of BALF showed a substantial amount of hemosiderin - laden macrophages , further supporting the diagnosis . All BALF cultures and gram stains were negative . The patient remained with severe thrombocytopenia and hypoxia despite steroids and platelets transfusion . High doses of pulse steroids and intravenous immunoglobulins ( IVIGs ) were added with clinico - radiological improvement . A bone marrow aspirate was morphologically normal . Additional laboratory studies failed to reveal an etiology for secondary thrombocytopenia ( Table 1 ) , supporting the diagnosis of ITP . Steroids were gradually tapered . Repeat chest radiograph showed almost complete resolution of bilateral infiltrates ( Fig.3 ) . Platelet count returned to normal by week 10 after admission without any additional therapies ( Fig.4 ) .


An 84 - year - old male patient with a history of coronary artery disease and right coronary artery ( RCA ) stenting was admitted to our university hospital in February 2012 because of progressive dyspnoea and recurring syncopes . Cardiological work - up revealed a grade III severe symptomatic aortic stenosis . Due to relevant comorbidities ( logistic EuroSCORE of 19 points ) and severe femoral arteriopathy , he was scheduled for trans - subclavian TAVI . After successful implantation of a CoreValve prosthesis ( Medtronic ) [ Medtronic World Headquarters Medtronic Parkway Minneapolis , Minnesota , USA ] ( diameter 31 mm ) and initial discharge , he was referred back to the hospital because of dyspnoea due to bilateral pleural effusions . Transoesophageal echocardiography ( TEE ) showed a severe mitral regurgitation ( MR ) , which was subsequently treated by interventional mitral valve repair using the MitraClip ( Abbott Vascular , Abbott Laboratories , Abbott Park , Illinois , U.S.A. ) and procedurally dependent atrial septal defect ( ASD ) closure AMPLATZER ™ PFO Occluder ( St. Jude Medical GmbH , Helfmann - Park 7 , Eschborn , Germany ) . Two weeks after secondary discharge , the patient developed progressive heart failure in combination with acute renal failure . Immediate echocardiography revealed a moderate - to - severe aortic regurgitation and recurrent severe MR . Valvular defects resulted from a slight but significant aortic valve prosthesis migration towards the left ventricular outflow tract , which had caused aortic paravalvular leakage and partial posterior mitral leaflet detachment ( Fig.1 ) . As a consequence of these findings , the patient was transferred to our cardiac surgery department . Preoperative coronary angiography revealed a progression of the coronary artery disease . Consequently the patient was scheduled for conventional aortic and mitral valve replacement , as well as coronary artery bypass surgery . The operation was performed via median sternotomy . On initialization of cardiopulmonary bypass , the ascending aorta was opened for exploration of the aortic valve ( Fig.2A ) . After careful removal of the CoreValve prosthesis , an Edwards Perimount aortic valve prosthesis ( diameter 25 mm ) was implanted . After vein - grafting of the circumflex coronary artery , the mitral valve was explored via the left atrium and excised with the attached clip . Thereafter , an Edwards Perimount mitral valve prosthesis ( diameter 31 mm ) was implanted . More recently , the atrial septal occluder was removed prior to direct closure of the resulting septal defect with a single - suture line ( Fig.2B ) . Intraoperative echocardiography revealed adequate function of both prostheses and the operation was completed in the usual manner . During the postoperative phase , the patient recovered well from surgery although hospitalization was prolonged by transient renal failure and recurring pleural effusions . After a month of postoperative care , the patient was discharged from hospital to rehabilitation in a good condition , without signs for heart failure . At follow - up three months after surgery , the patient was still in a cardiopulmonary stable condition , undergoing additional physiotherapy .


A 22 - year - old Tibetan man without significant past medical history was diagnosed with pulmonary tuberculosis ( PTB ) in a routine medical examination and received anti - TB therapy that included isoniazid ( INH , 300 mg / d ) , RMP ( 450 mg / d ) , ethambutol ( EMB , 750 mg / d ) , and pyrazinamide ( PZA , 1500 mg / d ) . After 1 week of continuous therapy , he was admitted to the Tibet People 's Hospital with nasal hemorrhage and the platelet ( PLT ) count was 0.4 × 109 / L ( normal range , 100–300 × 109 / L ) . Epistaxis was cured after symptomatic treatment . Two days later , he developed hematochezia , hematuria , and purpura , and required transfusion of fresh - frozen plasma and platelets in another local hospital . Four days later ( November 18 , 2015 ) , he was transferred to the West China Hospital due to the ineffective treatment . On physical examination , he presented with pallor , mild jaundice on the sclera , purpura , tachycardia ( heart rate 132 / min ) and weak breath sounds at the base of the left lung . Laboratory results on admission indicated DIC : prothrombin time ( 17.8 seconds ; normal range , 9.6–12.8 seconds ) , international normalized ratio ( 1.53 ; normal range , 0.88–1.15 ) , fibrinogen ( 1.13 g / L ; normal range , 2.0–4.0 g / L ) , D - dimers ( 23.45 mg / L ; normal range , < 0.55 mg / L ) , fibrin degradation product ( 60.4 mg / L ; normal range,<5 mg / L ) , and PLT ( 2 × 109 / L ; normal range , 100–300 × 109 / L ) . Other abnormal data were as follows : white blood cell ( WBC , 48.38 × 109 / L ; normal range , 3.5–9.5 ) , hemoglobin ( 65 g / L ; normal range , 130–175 g / L ) , total bilirubin ( 30.8 umol / L ; normal range , 5.0–28.0 umol / L ) , direct bilirubin ( 16.6 umol / L ; normal range , < 8.8 umol / L ) , aspartate aminotransferase ( 75 U / L ; normal range , < 40 U / L ) , alanine aminotransferase ( 293 U / L ; normal range , < 50 U / L ) , lactate dehydrogenase ( 380 U / L ; normal range , 110–220 U / L ) , serum urea nitrogen ( 13.01 mmol / L ; normal range , 3.2–7.79 mmol / L ) , C - reactive protein ( 16.70 mg / L ; normal range , < 5 mg / L ) , complement 3 ( 0.41 g / L ; normal range , 0.785–1.520 g / L ) , and complement 4 ( 0.0797 g / L ; normal range , 0.145–0.360 g / L ) . Routine urine test showed blood cell > 330 Cell / uL , leukocyte 250 Cell / uL , protein 2 g / L , and urobilinogen 70 umol / L. Routine stool test showed red blood cell 4+/HP , white blood cell 1+/HP , occult blood test ( + ) . T - SPOT result was positive . Real - time polymerase chain reaction analysis for mycobacterium TB on sputum was positive . Acid fast stain test of a sputum smear was negative . Chest computed tomography ( CT ) on admission ( November 18 , 2015 ) ( Fig.1 ) showed infiltrates on the upper lobe of the left lung , left pleural effusion , and pericardial effusion , accompanied by enlargement of mediastinal lymph nodes . Abdominal ultrasound showed a small amount of fluid adjacent to the liver and spleen . Serologic markers were negative for acute or chronic viral hepatitis , HIV , direct Coomb test , and autoimmune hepatitis . Peripheral blood film and culture were negative . Bone marrow smear and medulloculture were also negative . The antituberculosis drugs were discontinued immediately after admission . Besides fasting , he was initiated with infusion of fresh - frozen plasma , platelet , packed red blood cells , intravenous immune globulin , recombinant human thrombopoietin , omeprazole , and polyene phosphatidylcholine as well as nutrition supportive treatment . Five days after fasting ( November 23 , 2015 ) , the patient started a therapy consisting of EMB , moxifloxacin , and amikacin , while he had no further active hemorrhage . Eight days after admission ( November 26 , 2015 ) , the platelet counts had risen gradually . INH ( 200 mg / d , intravenously guttae ) was administered on 24 days after admission ( December 11 , 2015 ) , while his liver function tests and platelet counts returned to normal . The main laboratory features are summarized in Table 1 . One month later ( December 17 , 2015 ) , reviewed chest CT ( Fig.1 ) indicated the infiltration , hydrothorax , and pericardial effusion were absorbed well . Almost about 4 weeks after admission , the patient recovered and left hospital with INH ( 300 mg / d ) , EMB ( 750 mg / d ) , levofloxacin ( 500 mg / d ) , and streptomycin ( 750,000 U / d , intramuscular injection ) . There was no recurrence of DIC or hemorrhage during 8 months of follow - up . Unfortunately , the patient refused a follow - up chest CT after his discharge . Table 2 shows the timeline of this case .


A 60 - year - old male visited our outpatient clinic with a mass on his left hip . He had diabetes and alcoholic hepatitis . On physical examination , a large mass measuring 10 cm in diameter was observed on his hip and an approximate 5 cm left inguinal lymph node was palpable ( Figure 1 ) . Serum tumor markers , including CEA and CA 19 - 9 , were within normal limits , whereas serum amylase ( 227 IU / L , normal range 43 - 116 IU / L ) , lipase ( 378 IU / L , normal range 7 - 60 ) , fasting blood sugar ( 144 mg / dL , normal range , 70 - 100 mg / dL ) , and liver function test levels [ including aspartate aminotransferase ( 178 IU / L , normal range , 7 - 38 IU / L ) , alanine aminotransferase ( 225 IU / L ; normal range , 4 - 43 IU / L ) , and serum alkaline phosphatase ( 370 IU / L , normal range , 103 - 335 IU / L ) ] were all above normal ranges . An abdominal computerized tomography ( CT ) scan demonstrated not only a left hip mass and an enlarged left inguinal lymph node , but also a huge heterogeneous enhancing mass on the body of the pancreas ( Figure 2 ) . On a PET scan , additional metastases were not found . We planned a staged surgery and performed a hip and inguinal mass excision on December 19 , 2014 . The histopathological report revealed a metastatic small cell neuroendocrine carcinoma with a maximal diameter of 10.5 cm on the buttock mass and a 7 cm growth on an inguinal lymph node . The mitotic index was over 50 mitoses per 50 HPF and the Ki-67 index measured at 50 % . On January 21 , 2015 , we performed a total pancreatectomy and a total gastrectomy , with the findings revealing a tumor of the body of the pancreas about 9 cm × 6 cm in diameter involving the left gastric artery , splenic artery , and splenic vein . The histopathological report was the same as that of a metastatic lesion . Additionally , the tumor had spread to 8 of the 32 lymph nodes ( Figure 3 ) . On the 7th post - operative day , the patient developed a high fever and leukocytosis . We administered an abdominal CT scan , which revealed infected fluid collection in the lesser sac and a 4.7 cm - sized recurring mass which was detected at the operative bed of the left hip ( Figure (Figure4).4 ) . After infection of the abdominal cavity was treated by antibiotics , we removed the left hip recurring mass on February 3 , 2015 . The histopathology was the same as in the previous report ; with a maximum diameter of 7.5 cm . The patient was discharged without other complications on February 9 , 2015 . He is currently receiving chemotherapy based on etoposide and cisplatin treatment .