Functional cure of chronic hepatitis B-hope or hype?

Chronic hepatitis B constitutes a substantial disease burden worldwide.The steps advocated by the World Health Organization in 2016 to eradicate hepatitis B by 2030 has failed to achieve significant progress,especially with respect to immu-nization coverage and linkage to care.The lack of governmental and public awar-eness regarding the long-term implications of hepatitis B burden cause under-funding of developmental projects.The presently approved treatment modalities have limited efficacy in complete viral eradication,hence the need for newer molecules to achieve functional cure(sustained undetectable hepatitis B surface antigen(HBsAg)and hepatitis B virus DNA in peripheral blood after a finite period of therapy).However,preliminary results from trials of novel therapies show their inadequacy to achieve this end by themselves but better performance with a low baseline serum HBsAg with nucleos(t)ide analogues(NA)treatment which need to be combined with/without pegylated interferon as an immu-nomodulator.Such therapy is limited by cost and adverse events and need to show incremental benefit over the standard of care(long-term NA therapy)with respect to efficacy and drug toxicities,making the development process tenuous.Thus,while such therapies continue to be tested,strategies should still focus on prevention of transmission by non-pharmaceutical measures,vaccination and increasing linkage to care.

In-hospital outcomes in COVID-19 patients with non-alcoholic fatty liver disease by severity of obesity:Insights from national inpatient sample 2020

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular diseases independently of other risk factors.However,data on its effect on cardiovascular outcomes in coronavirus disease 2019(COVID-19)hospitalizations with varied obesity levels is scarce.Clinical management and patient care depend on understanding COVID-19 admission results in NAFLD patients with varying obesity levels.AIM To study the in-hospital outcomes in COVID-19 patients with NAFLD by severity of obesity.METHODS COVID-19 hospitalizations with NAFLD were identified using International Classification of Disease-10 CM codes in the 2020 National Inpatient Sample database.Overweight and Obesity Classes Ⅰ,Ⅱ,and Ⅲ(body mass index 30-40)were compared.Major adverse cardiac and cerebrovascular events(MACCE)(all-cause mortality,acute myocardial infarction,cardiac arrest,and stroke)were compared between groups.Multivariable regression analyses adjusted for sociodemographic,hospitalization features,and comorbidities.RESULTS Our analysis comprised 13260 hospitalizations,7.3% of which were overweight,24.3% Class Ⅰ,24.1% Class Ⅱ,and 44.3% Class Ⅲ.Class Ⅲ obesity includes younger patients,blacks,females,diabetics,and hypertensive patients.On multivariable logistic analysis,Class Ⅲ obese patients had higher risks of MACCE,inpatient mortality,and respiratory failure than Class Ⅰ obese patients.Class Ⅱ obesity showed increased risks of MACCE,inpatient mortality,and respiratory failure than Class I,but not significantly.All obesity classes had non-significant risks of MACCE,inpatient mortality,and respiratory failure compared to the overweight group.CONCLUSION Class Ⅲ obese NAFLD COVID-19 patients had a greater risk of adverse outcomes than class Ⅰ.Using the overweight group as the reference,unfavorable outcomes were not significantly different.Morbid obesity had a greater risk of MACCE regardless of the referent group(overweight or Class Ⅰ obese)compared to overweight NAFLD patients admitted with COVID-19.

Helicobacter pylori : Friend or foe?

Helicobacter pylori(H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is "anyone with a fear of gastric cancer" which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive(more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection.

Intraductal ultrasound substantiates diagnostics of bile duct strictures of uncertain etiology

AIM:To report the largest patient cohort study investigating the diagnostic yield of intraductal ultrasound (IDUS) in indeterminate strictures of the common bile duct.METHODS:A patient cohort with bile duct strictures of unknown etiology was examined by IDUS.Sensitivity,specificity and accuracy rates of IDUS were calculated relating to the definite diagnoses proved by histopathology or long-term follow-up in those patients who did not undergo surgery.Analysis of the endosonographic report allowed drawing conclusions with respect to the T and N staging in 147 patients.IDUS staging was compared to the postoperative histopathological staging data allowing calculation of sensitivity,specificity and accuracy rates for T and N stages.The endoscopic retrograde cholangio-pancreatography and IDUS procedures were performed under fluoroscopic guidance using a side-viewing duodenoscope (Olympus TJF 160,Olympus,Ltd.,Tokyo,Japan).All procedures were performed under conscious sedation (propofol combined with pethidine) according to the German guidelines.For IDUS,a 6 F or 8 F ultrasound miniprobe was employed with a radial scanner of 15-20 MHz at the tip of the probe (Aloka Co.,Tokyo,Japan).RESULTS:A total of 397 patients (210 males,187 females,mean age 61.43 ± 13 years) with indeterminate bile duct strictures were included.Two hundred and sixty-four patients were referred to the department of surgery for operative exploration,thus surgical histopathological correlation was available for those patients.Out of 264 patients,174 had malignant disease proven by surgery,in 90 patients benign disease was found.In these patients decision for surgical exploration was made due to suspicion for malignant disease in multimodal diagnostics (computed tomography scan,endoscopic ultrasound or magnetic resonance imaging).Twenty benign bile duct strictures were misclassified by IDUS as malignant while 14 patients with malignant strictures were initially misdiagnosed by IDUS as benign resulting in sensitivity,specificity and accuracy ratesof 93.2%,89.5% and 91.4%,respectively.In the subgroup analysis of malignancy prediction,IDUS showed best performance in cholangiocellular carcinoma as underlying disease (sensitivity rate,97.6%) followed by pancreatic carcinoma (93.8%),gallbladder cancer (88.9%) and ampullary cancer (80.8%).A total of 133 patients were not surgically explored.32 patients had palliative therapy due to extended tumor disease in IDUS and other imaging modalities.Ninety-five patients had benign diagnosis by IDUS,forceps biopsy and radiographic imaging and were followed by a surveillance protocol with a follow-up of at least 12 mo;the mean follow-up was 39.7 mo.Tumor localization within the common bile duct did not have a significant influence on prediction of malignancy by IDUS.The accuracy rate for discriminating early T stage tumors (T1) was 84% while for T2 and T3 malignancies the accuracy rates were 73% and 71%,respectively.Relating to N0 and N1 staging,IDUS procedure achieved accuracy rates of 69% for N0 and N1,respectively.Limitations:Pretest likelihood of 52% may not rule out bias and overinterpretation due to the clinical scenario or other prior performed imaging tests.CONCLUSION:IDUS shows good results for accurate diagnostics of bile duct strictures of uncertain etiology thus allowing for adequate further clinical management.

Inflammatory bowel disease in India- Past, present and future

There is rising incidence and prevalence of inflammatory bowel disease(IBD) in India topping the Southeast Asian(SEA) countries. The common genes implicated in disease pathogenesis in the West are not causal in Indian patients and the role of "hygiene hypothesis" is unclear. There appears to be a North-South divide with more ulcerative colitis(UC) in north and Crohn's disease(CD) in south India. IBD in second generation Indian migrants to the West takes the early onset and more severe form of the West whereas it retains the nature of its country of origin in migrants to SEA countries. The clinical presentation is much like other SEA countries(similar age and sex profile, low positive family history and effect of smoking, roughly similar disease location, use of aminosalicylates for CD, low use of biologics and similar surgical rates) with some differences(higher incidence of inflammatory CD, lower perianal disease, higher use of aminosalicylates and azathioprine and lower current use of corticosteroids). UC presents more with extensive disease not paralleled in severity clinically or histologically, follows benign course with easy medical control and low incidence of fulminant disease, cancer, complications, and surgery. UC related colorectal cancer develop in an unpredictable manner with respect to disease duration and site questioning the validity of strict screening protocol. About a third of CD patients get antituberculosis drugs and a significant number presents with small intestinal bleed which is predominantly afflicted by aggressive inflammation. Biomarkers have inadequate diagnostic sensitivity and specificity for both. Pediatric IBD tends to be more severe than adult. Population based studies are needed to address the lacunae in epidemiology and definition of etiological factors. Newer biomarkers and advanced diagnostic techniques(in the field of gastrointestinal endoscopy, molecular pathology and genetics) needs to be developed for proper disease definition and treatment.

Association between thyroid function and gallstone disease

AIM： To investigate those associations using data of the population-based Study of Health in Pomerania. METHODS： A study population of 3 749 residents aged 20-79 years without previously diagnosed thyroid disease was available for analyses. Serum TSH was used to assess thyroid function. Cholelithiasis was defined by either a prior history of cholecystectomy or the presence of gallstones on ultrasound. Logistic regression was performed to analyze independent associations between thyroid function and cholelithiasis. RESULTS： There were 385 persons （10.3%） with low （〈0.3 mIU/L）, 3 321 persons （88.6%） with normal and 43 persons （1.2%） with high serum TSH levels （〉3 mIU/L）. The proportion of cholelithiasis among males and females was 14.4% and 25.3%, respectively. Among males, there was an independent relation between high serum TSH and cholelithiasis （OR 3.77; 95%-CI 1.06-13.41; P〈0.05）. Also among males, there was a tendency towards an elevated risk of cholelithiasis in persons with low serum TSH （OR 1.40; 95%-CI 0.96-2.02; P= 0.07）. In the female population, no such relation was identified. CONCLUSION： There is an association between thyroid and gallstone disease with a gender-specific relation between hypothyroidism and cholelithiasis.

Comparative analysis of ERCP,IDUS,EUS and CT in predicting malignant bile duct strictures

AIM: To compare endoscopic retrograde cholangio-pancreatography (ERCP), intraductal ultrasound (IDUS), endosonography (EUS), endoscopic transpapillary forceps biopsies (ETP) and computed tomography (CT) with respect to diagnosing malignant bile duct strictures.

Assessment of the correlation between serum prolidase and alpha-fetoprotein levels in patients with hepatocellular carcinoma

AIM: To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma(HCC).METHODS: Sixty-eight patients with HCC(mean age of 69.1 ± 10.1), 31 cirrhosis patients(mean age of59.3 ± 6.3) and 33 healthy volunteers(mean age of51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein(AFP) values with HCC clinicopathological features, such as tumor size,number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion(diameters; ≤ 3 cm, 3-5 cmand ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer(BCLC)criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alphafetoprotein levels were kept at-80 ℃ until use.Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay.RESULTS: In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number,presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls(P <0.001). Prolidase levels were significantly associated with tumor size and number(P < 0.001, P = 0.002,respectively). Prolidase levels also differed in patients in terms of BCLC staging classification(P < 0.001).Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis(P < 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately(P = 0.032,P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation(r = 0.616; P< 0.001) between prolidase and AFP values in terms of tumor size, number and BCLC staging classification,whereas the presence of macrovascular invasion did not show a positive association with serum prolidase and AFP levels.CONCLUSION: Considering the levels of both serum prolidase and AFP could contribute to the early diagnosing of hepatocellular carcinoma.

Association between thrombotic risk factors and extent of fibrosis in patients with non-alcoholic fatty liver diseases

AIM: To evaluate the prevalence of genetic and acquired prothrombotic risk factors and their association with the extent of fibrosis and fatty infiltration in patients with non-alcoholic fatty liver disease (NAFLD).METHODS: Forty-four patients with chronic hepatitis (28 men and 16 women, with mean age of 45±11 and 49±12 years, respectively) constituted the patient population of this study. The groups were divided as follows: 15 patients with fatty liver (FL); 15 with non-alcoholic steatohepatitis (NASH); 14 with chronic viral hepatitis (CH) diagnosed by histology and liver technetium scan or ultrasound; and 10 healthy individuals. Thrombophilic, coagulation factors and genetic mutations were diagnosed by standard hemostatic and molecular coagulation assays.RESULTS: Activated protein C (APC) resistance and protein S were the most prevalent thrombotic risk factors (6% and 10% in NAFLD vs 21% and 14% in CH; P＜0.01 and P＜0.05, respectively). One thrombotic risk factor was identified in 41% of patients (23% mild fibrosis, 18% severe fibrosis) and two thrombotic risk factors in 6% of patients with NAFLD and severe fibrosis. While no differences in APC ratio, lupus anticoagulant, fibrinogen, factor V Leiden,prothrombin, and MTHFR mutation were found. Protein S levels were significantly lower in NASH patients than in patients with FL alone (92±19 vs106±2, P＜0.01). Protein C levels were markedly higher in patients with NAFLD and mild or severe fibrosis as compared to the patients with CH, respectively (128±40 vs96±14, P＜0.001 or 129±36 vs 88±13, P＜0.01).CONCLUSION: Up to 46% of patients with NAFLD may have thrombotic risk factors, and the presence of thrombotic risk factors is correlated with the extent of hepatic fibrosis,suggesting a crucial role of the coagulation system in the pathogenesis of hepatic fibrosis.

Molecular phenotypes of human parvovirus B19 in patients with myocarditis

AIM:To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy(DCM).METHODS:Endomyocardial biopsies(EMBs) from 498 B19V-positive patients with myocarditis and DCMwere analyzed using molecular methods and functional experiments.EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers.Control tissues were obtained at autopsy from 34 victims of accidents,crime or suicide.Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining.Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay(ELISA).B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction(PCR).For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism(RFLP)-PCR was established.B19V-genotyping was verified by direct DNAsequencing and sequences were aligned using BLAST and BioEdit software.B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments.Transfection experiments were conducted using human endothelial cells 1.Luciferase reporter assays were performed to determine B19Vreplication activity.Statistical analysis and graphical representation were calculated using SPSS and Prism5 software.RESULTS:The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy(iCMP) compared to uninflamed DCM(59.6% vs 35.3%)(P < 0.0001).The detection of B19V-mRNA replication intermediates proved that replication of B19V was present.RFLP-PCR assays showed that B19V-genotype 1(57.4%) and B19V-genotype 2(36.7%) were the most prevalent viral genotypes.B19V-genotype 2 was observed more frequently in EMBs with iCMP(65.0%) compared to DCM(35%)(P = 0.049).Although there was no significant difference in gender-specific B19V-loads,women were more frequently infected with B19V-genotype 2(44.6%) than men(36.0%)(P = 0.0448).Coinfection with B19V and other cardiotropic viruses was found in 19.2% of tissuesamples and was associated with higher B19V viral load compared to B19V-monoinfected tissue(P = 0.0012).The most frequent coinfecting virus was human herpes virus 6(HHV6,16.5%).B19V-coinfection with HHV6 showed higher B19V-loads compared to B19V-monoinfected EMBs(P = 0.0033),suggesting that HHV6 had transactivated B19V.In vitro experiments confirmed a 2.4-fold increased B19V P6-promoter activity by the HHV6 U94-transactivator.CONCLUSION:The finding of significantly increased B19V loads in patients with histologically proven cardiac inflammation suggests a crucial role of B19V-genotypes and reactivation of B19V-infection by HHV6-coinfection in B19V-associated iCMP.Our findings suggest that B19V-infection of the human heart can be a causative event for the development of an endothelial cell-mediated inflammatory disease and that this is related to both viral load and genotype.

Ileal gallstone obstruction:Single-balloon enteroscopic removal

Gallstone-induced ileus is a rare complication of cholelithiasis.Since localization of gallstones impacted in the small bowel,especially in the ileum,prevents access by conventional endoscopy in most cases,the mainstay of treatment remains surgical.Recent invention of double-and single-balloon enteroscopy has added much to the ability of imaging the small bowel and enables endoscopically directed therapy.Herein,for the first time,we report a successful endoscopic calculus removal via peroral single-balloon enteroscopy in an 81-year-old woman suffering from gallstone ileus of the ileum.

Prospective observational multicenter study to define a diagnostic algorithm for biliary candidiasis

AIM:To develop an algorithm to improve the diagnosis and treatment of patients with biliary candidiasis.METHODS:We performed a prospective study of 127patients who underwent endoscopic retrograde cholangiopancreatography,for various biliary disorders,at 3 tertiary referral centers in Germany from July 2011through July 2012(ClinicalTrials.gov:NCT01109550).Bile,buccal,and stool samples were collected.When indicated,endoscopic transpapillary bile duct biopsies were performed to clarify the etiology of bile duct strictures and to prove invasive fungal infections.RESULTS:Candida species were detected in 38 of the 127 bile samples(29.9%).By multivariate analysis patients’age and previous endoscopic sphincterotomy were independent risk factors for biliary candidiasis(P<0.05).Patients with immunosuppression(P=0.058)and recent long-term antibiotic therapy(>7 d)(P=0.089)tend to be at risk for biliary candidiasis.One patient was negative in mycological culture of bile fluid but invasive biliary candidiasis was diagnosed histologically.Of Candida subspecies detected,36.7%were azole-resistant,such as C glabrata.Eight patients received anti-mycotic therapy,based on our algorithm.Of these,3 had cancer with biliary tract involvement,2had secondary sclerosing cholangitis,1 had retroperitoneal fibrosis,and 5 had septicemia.In all patients contamination was ruled out by smears of the endoscope channel.CONCLUSION:Gastroenterologists should be aware of frequent candida colonization in patients with cholangitis and biliary disorders.Our suggested algorithm facilitates the further clinical management.

Detection and characterization of murine colitis and carcinogenesis by molecularly targeted contrast-enhanced ultrasound

AIM To study mucosal addressin cellular adhesion molecule-1(MAd CAM-1) and vascular endothelial growth factor(VEGF)-targeted contrast enhanced ultrasound(CEUS) for the assessment of murine colitis and carcinogenesis. METHODS C57BL/6 mice were challenged with 3% dextran sodium-sulfate(DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents. MAd CAM-1-targeted contrast agent was used to detect and quantify MAd CAM-1 expression. Inflammatory driven colorectal azoxymethane(AOM)/DSS-induced carcinogenesis was examined on day 42 and 84 using VEGF-targeted contrast agent. Highly specific tissue echogenicity was quantified using specialized software. Sonographic findings were correlated to tissue staining, western blot analysis and immunohistochemistry to quantify the degree of inflammation and stage of carcinogenesis. RESULTS Native ultrasound detected increased general bowel wall thickening that correlated with more progressed and more severe DSS-colitis(healthy mice: 0.3 mm ± 0.03 vs six days DSS: 0.5 mm ± 0.2 vs nine days DSS: 0.6 mm ± 0.2, P < 0.05). Moreover, these sonographic findings correlated well with clinical parameters such as weight loss(r2 = 0.74) and histological damage(r2 = 0.86)(P < 0.01). In acute DSS-induced murine colitis, CEUS targeted against MAd CAM-1 detected and differentiated stages of mild, moderate and severe colitis via calculation of mean pixel contrast intensity in decibel(9.6 d B ± 1.6 vs 12.9 d B ± 1.4 vs 18 d B ± 3.33, P < 0.05). Employing the AOM/DSSinduced carcinogenesis model, tumor development was monitored by CEUS targeted against VEGF and detected a significantly increased echogenicity in tumors as compared to adjacent healthy mucosa(healthy mucosa, 1.6 d B ± 1.4 vs 42 d, 18.2 d B ± 3.3 vs 84 d, 18.6 d B ± 4.9, P < 0.01). Tissue echogenicity strongly correlated with histological analysis and immunohistochemistry findings(VEGF-positive cells in 10 high power fields of healthy mucosa: 1 ± 1.2 vs 42 d after DSS start: 2.4 ± 1.6 vs 84 d after DSS start: 3.5 ± 1.3, P < 0.01). CONCLUSION Molecularly targeted CEUS is a highly specific and noninvasive imaging modality, which characterizes murine intestinal inflammation and carcinogenesis in vivo.

Digital single-operator video cholangioscopy improves endoscopic management in patients with primary sclerosing cholangitis-a retrospective observational study

BACKGROUND Patients with primary sclerosing cholangitis(PSC)are at a high risk of developing cholestatic liver disease and biliary cancer,and endoscopy is crucial for the complex management of these patients.AIM To clarify the utility of recently introduced digital single-operator video cholangioscopy(SOVC)for the endoscopic management of PSC patients.METHODS In this observational study,all patients with a history of PSC and in whom digital SOVC(using the SpyGlass DS System)was performed between 2015 and 2019 were included and retrospectively analysed.Examinations were performed at a tertiary referral centre in Germany.In total,46 SOVCs performed in 38 patients with a history of PSC were identified.The primary endpoint was the evaluation of dominant biliary strictures using digital SOVC,and the secondary endpoints were the performance of selective guidewire passage across biliary strictures and the diagnosis and treatment of biliary stone disease in PSC patients.RESULTS The 22 of 38 patients had a dominant biliary stricture(57.9%).In 4 of these 22 patients,a cholangiocellular carcinoma was diagnosed within the stricture(18.2%).Diagnostic evaluation of dominant biliary strictures using optical signs showed a sensitivity of 75%and a specificity of 94.4%to detect malignant strictures,whereas SOVC-guided biopsies to gain tissue for histopathological analysis showed a sensitivity of 50%and a specificity of 100%.In 13%of examinations,SOVC was helpful for guidewire passage across biliary strictures that could not be passed by conventional methods(technical success rate 100%).Biliary stone disease was observed in 17.4%of examinations;of these,in 37.5%of examinations,biliary stones could only be visualized by SOVC and not by standard fluoroscopy.Biliary stone treatment was successful in all cases(100%);25%required SOVC-assisted electrohydraulic lithotripsy.Complications,such as postinterventional cholangitis and pancreatitis,occurred in 13%of examinations;however,no procedure-associated mortality occurred.CONCLUSION Digital SOVC is effective and safe for the endoscopic management of PSC patients and may be regularly considered an additive tool for the complex endoscopic management of these patients.

<i>Chryseobacterium indologenes</i>Bacteremia: Clinical and Microbiological Characteristics of an Emerging Infection

Purpose: Since Chryseobacterium indologenes (C. indologenes) is a rare human pathogen, its clinical significance has not yet been fully established. C. indologenes contamination of medical devices involving fluids and of surgical implants has led to an increasing number of serious infectious reported in recent years, mainly in patients in extremes ages and an immunocompromised state. In this study, we describe the clinical and microbiological characteristics of seven adult patients with C. indologenes bacteremia treated in a tertiary medical center in Israel over a six-year period. Methods: Adult patients hospitalized in Rabin Medical Center, Israel, with a blood culture positive for C. indologenes during the period 2009-2014 were identified retrospectively and their medical records were reviewed. Results: Seven episodes of C. indologenes bacteremia in seven patients were identified during the study period. Five patients were females;the mean age was 76.8 years (41 - 92). Serious underlying conditions were present in all patients. All patients but one, presented after a recent invasive healthcare related intervention. Two patients required mechanical ventilation. Two patients died. All but one isolates were susceptible to ciprofloxacin. Conclusions: Despite our limited number of cases, to the best of our knowledge, our study serves as the largest cohort of adult patients with C. indologenes bacteremia reported in recent years.

Crohn's disease complicated by intestinal infection with methicillin-resistant Staphylococcus aureus

We report on a 24-year-old male patient with history of bloody diarrhea, abdominal pain and vomiting. Endoscopy revealed massive ulcerative discontinuous proctosigmoiditis with deep, sharply demarcated epithelial denudations and enterotoxigenic methicillin-resistant Staphylococcus aureus (MRSA) was detected in mucosal biopsies. After treatment with linezolide and steroids, a significant amelioration of colitis was detected and testing for MRSA became negative. In face of the case presented here, we suggest that in patients with refractory inflammatory bowel disease (IBD), microbiological assessment should be performed to detect a possible Staphylococcus aureus infection in order to initiate an antimicrobial treatment in addition to IBDspecific treatment.

A typical presentation of a rare cause of obscure gastrointestinal bleeding

A 52-year-old white woman had suffered from intermittent gastrointestinal (GI) bleeding for one year. Upper GI endoscopy, colonoscopy and peroral doubleballoon enteroscopy (DBE) did not detect any bleeding sour ce, suggesting obscure GI bleeding. However, in video capsule endoscopy a jejunal ulceration without blee ding signs was suspected and this was endoscopically conf irmed by another peroral DBE. After transfusion of packed red blood cells, the patient was discharged from our hospital in good general condition.Two weeks later she was readmitted because of another episode of acute bleeding. Multi-detector row computed tomography with 3D reconstruction was performed revealing a jejunal tumor causing lower gastrointestinal bleeding. The patient underwent exploratory laparotomy with partial jejunal resection and end-to-end jejunostomy for reconstruction. Histological examination of the specimen confirmed the diagnosis of a low risk gastrointestinal stromal tumor (GIST). Nine days after surgery the patient was discharged in good health. No signs of gastrointestinal rebleeding occurred in a followup of eight months. We herein describe the comp lex presentation and course of this patient with GIST and also review the current approach to treatm ent.

Cyanocobalamin and 25-Hydroxy Vitamin D Levels in Gout Patients: An Overlooked Issue

Gout is one of the most frequent type of inflammatory arthritis in developed countries. The elevation of serum uric acid levels and the deposition of monosodium urate crystals in joints and/or soft tissues are the mechanisms of pathogenesis. Uric acid is a product of the metabolic cleavage of purine nucleotides and organ meats, beef, pork, and lamb, anchovies, sardines, herring, mackerel, scallops, gravy and beer are known to be very rich in purine. On the other hand, some of these foods are also the main sources of vitamin B12 (cyanocobalamin). As a chronic inflammatory arthritis corticosteroids are frequently prescribed for gout patients, meaning a higher risk for osteoporosis which may be blocked by daily calcium and vitamin D replacement. However, there are no recommendations about screening or replacement of Gout patients for vitamin D and B12. Herein, we evaluated our patients retrospectively to document their vitamin levels and also to find the factors associated with vitamin deficiency. Totally, 90 patients, 71 (79.9%) male and 19 (20.1%) female patients with a median diagnostic age of 55 (19 - 80) were included. Thirty six (40%) patients were newly diagnosed (group 1) but 54 (60%) patients had established diseases (group-2) with median disease duration of 36 (11-240) months. Nearly half (47.2%) of the patients in group-1 and 37% of the patients in group-2 had vitamin B 12 deficiency. Similarly, 38.9% in each group had vitamin D deficiency and 52.8% in group-1 and 44.4% in group-2 had vitamin D insufficiency. In conclusion, we strongly recommend routine screening and replacement of vitamin B12 and D for patients with Gout.

Biologic Agents in Behcet’s Disease:Our Experience and Review of the Literature

Behcet’s disease (BD) is a large vessel vasculitis with a wide range of clinical manifestations. Some of these manifestation may be life threatening and rapid suppression of the inflammation with effective immunosuppressive agent is crucial. There are traditional drugs with different response rates and all have efficacy on different manifestations of the disease. The most frightening manifestations of the disease are ocular, neurologic, intestinal and vascular types of involvement. Besides benign and easily treated manifestations there are also refractory cases with complicated involvement. The novel biologic agents have been used for these resistant patients and favorable response rates have been reported. In this review, we have shared our experience with biologic agents in BD and also reviewed the literature for the efficacy and safety for these novel agents for refractory patients.

Parasympathetic Dysfunction in Black African Patients with Heart Failure:A Cross-Sectional Study in Sub-Saharan Africa

Background: Heart Failure (HF) is a major public health problem worldwide. Neurohormonal changes associated with HF are current therapeutic targets. The parasympathetic system in HF has not been well studied especially in black Africans. Aim: This study aimed to report on the prevalence and determinants of parasympathetic dysfunction in patients with heart failure in sub-Saharan Africa. Methods: We conducted a cross-sectional study between December 2017 and April 2018 in the outpatient and inpatient departments in two teaching hospitals in Yaounde-Cameroon. Cases were patients with HF matched with controls without HF according to age, sex, and risk factors (hypertension, diabetes, and obesity). We assessed the parasympathetic function via the Deep Breathing Test using an electrocardiograph. Results: We recruited 35 patients in each group. The mean age was 57 ± 11.68 years. Vagal dysfunction was seen in 51.4% of cases and 11.4% of controls (aOR: 10.1 [95% CI: 2.7 - 38.3], p = 0.001). This risk increased with the severity of HF-aOR: 11.8, [95% CI: 1.8 - 77.9], p = 0.01 for dyspnea stage III-IV, and aOR: 9.27, [95% CI: 1.3 - 65.3], p = 0.025) for HF with reduced Ejection fraction. This risk was not associated with the classic cardiovascular risk factors. Conclusion: Parasympathetic dysfunction as assessed with the Deep Breathing Test was seen in over half of the patients with HF and this was associated with the severity and type of HF.