Modulation of microbiota as treatment for intestinal inflammatory disorders: An uptodate

Alterations of intestinal microflora may significantly contribute to the pathogenesis of different inflammatory and autoimmune disorders. There is emerging interest on the role of selective modulation of microflora in inducing benefits in inflammatory intestinal disorders, by as probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation(FMT). To summarize recent evidences on microflora modulation in main intestinal inflammatory disorders, Pub Med was searched using terms microbiota, intestinal flora, probiotics, prebiotics, fecal transplantation. More than three hundred articles published up to 2015 were selected and reviewed. Randomized placebo-controlled trials and meta-analysis were firstly included, mainly for probiotics. A meta-analysis was not performed because of the heterogeneity of these studies. Most of relevant data derived from studies on probiotics, reporting some efficacy in ulcerative colitis and in pouchitis, while disappointing results are available for Crohn's disease. Probiotic supplementation may significantly reduce rates of rotavirus diarrhea. Efficacy of probiotics in NSAID enteropathy and irritable bowel syndrome is still controversial. Finally, FMT has been recently recognized as an efficacious treatment for recurrent Clostridium difficile infection. Modulation of intestinal flora represents a very interesting therapeutic target, although it still deserves some doubts and limitations. Future studies should be encouraged to provide new understanding about its therapeutical role.

Golgi protein-73:A biomarker for assessing cirrhosis and prognosis of liver disease patients

BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.

Endotics system vs colonoscopy for the detection of polyps

AIM: To compare the endotics system (ES), a set of new medical equipment for diagnostic colonoscopy, with video-colonoscopy in the detection of polyps. METHODS: Patients with clinical or familial risk of colonic polyps/carcinomas were eligible for this study. After a standard colonic cleaning, detection of polyps by the ES and by video-colonoscopy was performed in each patient on the same day. In each single patient, the assessment of the presence of polyps was performed by two independent endoscopists, who were randomly assigned to evaluate, in a blind fashion, the presence of polyps either by ES or by standard colonoscopy. The frequency of successful procedures (i.e. reaching to the cecum), the time for endoscopy, and the need for sedation were recorded. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the ES were also calculated. RESULTS: A total of 71 patients (40 men, mean age51.9 ± 12.0 years) were enrolled. The cecum was reached in 81.6% of ES examinations and in 94.3% of colonoscopies (P = 0.03). The average time of endoscopy was 45.1 ± 18.5 and 23.7 ± 7.2 min for the ES and traditional colonoscopy, respectively (P < 0.0001). No patient required sedation during ES examination, compared with 19.7% of patients undergoing colonoscopy (P < 0.0001). The sensitivity and specificity of ES for detecting polyps were 93.3% (95% CI: 68-98) and 100% (95% CI: 76.8-100), respectively. PPV was 100% (95% CI: 76.8-100) and NPV was 97.7% (95% CI: 88-99.9). CONCLUSION: The ES allows the visualization of the entire colonic mucosa in most patients, with good sensitivity/specificity for the detection of lesions and without requiring sedation.

Diagnostic accuracy of enhanced liver fibrosis test to assess liver fibrosis in patients with chronic hepatitis C

BACKGROUND:The prognosis and clinical management of patients with chronic liver diseases are closely related to the severity of liver fibrosis.Liver biopsy is considered the gold standard for the staging of liver fibrosis.However,it is an invasive test sometimes related to complications.This study aimed to assess the diagnostic value of enhanced liver fibrosis(ELF) test to predict liver fibrosis in patients with chronic hepatitis C.METHODS:This study included 162 patients with liver disease and 67 healthy controls.Hyaluronic acid,tissue inhibitor of matrix metalloproteinase type 1,and amino-terminal propeptide type III procollagen were measured by enzymelinked immunosorbent assay with the ELF test ADVIA Centaur(Siemens Healthcare Diagnostics Inc.).Fibrosis stage was determined using the Metavir scoring system.RESULTS:In our study,for the diagnosis of significant fibrosis(Metavir F≥2) a cut-off value 】7.72 provides a sensitivity of 93.0% and a specificity of 83.0%.The areas under the receiver operator characteristic curve,sensitivity,specificity,and positive and negative predictive values were 0.94,93.3%,81.0%,93.3%,and 81.0%,respectively(P【0.001).For the diagnosis of cirrhosis(Metavir F=4) a cut-off value 】9.3 provides a sensitivity of 93.0% and a specificity of 86.0%.The areas under the receiver operator characteristic curve,sensitivity,specificity,and positive and negative predictive values were 0.94,79.1%,90.8%,75.6%,and 92.3%,respectively(P【0.001).CONCLUSIONS:The ELF test is a promising non-invasive method for assessing liver fibrosis in patients with chronic hepatitis C.It is effective in the diagnosis of both fibrosis and cirrhosis.

Effect of IBD sera on expression of inducible and endothelial nitric oxide synthase in human umbilical vein endothelial cells

AIM： To study the expression of endothelial and inducible nitric oxide synthases （eNOS and iNOS） and their role in inflammatory bowel disease （IBD）. METHODS： We examined the effect of sera obtained from patients with active Crohn＇s disease （CD） and ulcerative colitis （UC） on the function and viability of human umbilical vein endothelial cells （HUVEC）. HUVECs were cultured for 0-48 h in the presence of a medium containing pooled serum of healthy controls, or serum from patients with active CD or UC. Expression of eNOS and iNOS was visualized by immunofluorescence, and quantified by the densitometry of Western blots. Proliferation activity was assessed by computerized image analyses of Ki-67 immunoreactive cells, and also tested in the presence of the NOS inhibitor, 10^-4 mol/L L-NAME. Apoptosis and necrosis was examined by the annexin-V-biotin method and by propidium iodide staining, respectively. RESULTS： In HUVEC immediately after exposure to UC, serum eNOS was markedly induced, reaching a peak at 12 h. In contrast, a decrease in eNOS was observed after incubation with CD sera and the eNOS level was minimal at 20 h compared to control （18%±16% vs 23%± 15% P〈0.01）. UC or CD serum caused a significant increase in iNOS compared to control （UC： 300%±21%; CD： 275% ± 27% vs 108% ± 14%, P〈0.01）. Apoptosis/necrosis characteristics did not differ significantly in either experiment. Increased proliferation activity was detected in the presence of CD serum or after treatment with L-NAME. Cultures showed tube-like formations after 24 h treatment with CD serum. CONCLUSION： IBD sera evoked changes in the ratio of eNOS/iNOS, whereas did not influence the viability of HUVEC. These involved down-regulation of eNOS and up-regulation of iNOS simultaneously, leading to increased proliferation activity and possibly a reduced antiinflammatory protection of endothelial cells.

Efficient management of secondary haemophagocytic lymphohistiocytosis with intravenous steroids and γ-immunoglobulin infusions

BACKGROUND Secondary haemophagocytic lymphohistiocytosis(sHLH)is a rare lifethreatening condition mainly associated with underlying infections,malignancies,and autoimmune or immune-mediated diseases.AIM To analyse all sHLH cases that were diagnosed and managed under real-world circumstances in our department focusing on the treatment schedule and the outcome.METHODS Prospectively collected data from all adult patients fulfilling the criteria of sHLH who diagnosed and managed from January 1,2010 to June 1,2018,in our department of the tertiary care university hospital of Larissa,Greece,were analysed retrospectively(n=80;52%male;median age:55 years).The electronic records and/or written charts of the patients were reviewed for the demographic characteristics,clinical manifestations,underlying causes of sHLH,laboratory parameters,treatment schedule and 30-d-mortality rate.Most of patients had received after consent intravenousγ-immunoglobulin(IVIG)for 5 d(total dose 2 g/kg)in combination with intravenous steroid pulses followed by gradual tapering of prednisolone.RESULTS Seventy-five patients(94%)reported fever>38.5°C,47(59%)had liver or spleen enlargement and 76(95%)had ferritin>500 ng/mL including 20(25%)having considerably high levels(>10000 ng/mL).Anaemia and thrombocytopenia occurred in 72%and leucopoenia in 47%of them.Underlying infections were diagnosed in 59 patients(74%)as follows:leishmaniasis alone in 15/80(18.9%),leishmaniasis concurrently with Coxiella Burnetti or non-Hodgkin lymphoma in 2/80(2.5%),bacterial infections in 14/80(17.5%)including one case with concurrent non-Hodgkin lymphoma,viral infections in 13/80(16.3%),fungal infections in 2/80(2.5%),infections by mycobacteria in 1/80(1.3%)and unidentified pathogens in 12/80(15%).Seventy-two patients(90%)had received combination treatment with IVIG and intravenous steroids.Overall,sHLH resolved in 76%of patients,15%died within the first month but 82.5%of patients were still alive 6 mo after diagnosis.Univariate analysis showed older age,anaemia,thrombocytopenia,low fibrinogen,disseminated intravascular coagulation(DIC),and delay of diagnosis as factors that negatively affected remission.However,multivariate analysis showed low platelets and DIC as the only independent predictors of adverse outcome.CONCLUSION sHLH still carries a remarkable morbidity and mortality.Underlying infections were the major cause and therefore,they should be thoroughly investigated in patients with sHLH.Early recognition and combination treatment with IVIG and corticosteroids seem an efficient treatment option with successful outcome in this life-threatening condition.

Application of Optical Methods in Blood Studies upon Evaluation of Severity Rate of Diffuse Liver Pathology

Possible early diagnostic application of optical methods (dielectrophoresis, spectral and imaging ellipsometry, Fourier-transform infrared spectroscopy, Raman spectroscopy) in studies of red blood cells and serum of patients with diffuse liver disease with varying degrees of fibrosis has been evaluated. Application of combined optical methods was confirmed to significantly improve the performance of sensitivity, specificity, and accuracy index as well as to achieve the reliable results in diagnosis of both severe fibrosis and slight ulterior liver fibrosis. Identified diagnostic potential of optical methods can be effectively utilized in noninvasive screening evaluation of stages of diffuse liver disease of various geneses.

Sarcopenia in heart failure： mechanisms and therapeutic strategies

Chronic heart failure （CHF） is a highly prevalent condition among the elderly and is associated with considerable morbidity, institution-alization and mortality. In its advanced stages, CHF is often accompanied by the loss of muscle mass and strength. Sarcopenia is a geriatric syndrome that has been actively studied in recent years due to its association with a wide range of adverse health outcomes. The goal of this review is to discuss the relationship between CHF and sarcopenia, with a focus on shared pathophysiological pathways and treatments. Mal- nutrition, systemic inflammation, endocrine imbalances, and oxidative stress appear to connect sarcopenia and CHF. At the muscular level, alterations of the ubiquitin proteasome system, myostatin signaling, and apoptosis have been described in both sarcopenia and CHF and could play a role in the loss of muscle mass and function. Possible therapeutic strategies to impede the progression of muscle wasting in CHF patients include protein and vitamin D supplementation, structured physical exercise, and the administration of angiotensin-converting enzyme inhibitors and β-blockers. Hormonal supplementation with growth hormone, testosterone, and ghrelin is also discussed as a potential treatment.

Colon capsule endoscopy: Advantages, limitations and expectations. Which novelties?

Since the first reports almost ten years ago, wireless capsule endoscopy has gained new f ields of application. Colon capsule endoscopy represents a new diagnostic technology for colonic exploration. Clinical trials have shown that colon capsule endoscopy is feasible, accurate and safe in patients suffering from colonic diseases and might be a valid alternative to conventional colonoscopy in selected cases such as patients refusing conventional colonoscopy or with contraindications to colonoscopy or when colonoscopy is incomplete. Despite the enthusiasm surrounding this new technique, few clinical and randomized controlled trials are to be found in the current literature, leading to heterogeneous or controversial results. Upcoming studies are needed to prove the substantial utility of colon capsule endoscopy for colon cancer screening, especially in a low prevalence of disease population, and for other indications such as inflammatory bowel disease. Possible perspectives are critically analysed and reported in this paper.

Cutaneous manifestations in celiac disease

Celiac disease （CD） is an autoimmune gluten-dependent enteropathy characterized by atrophy of intestinal villi that improves after gluten-free diet （GFD）. CD is often associated with extra-intestinal manifestations; among them, several skin diseases are described in CD patients. The present review reports all CD-associated skin manifestations described in the literature and tries to analyze the possible mechanisms involved in this association. The opportunity to evaluate the possible presence of CD in patients affected by skin disorders is discussed.

Intestinal permeability after Mediterranean diet and low-fat diet in non-alcoholic fatty liver disease

BACKGROUND In non-alcoholic fatty liver disease(NAFLD), a high-fat or high-fructose diet increases intestinal permeability and promotes derangement of the gut-liver axis.We hypothesize that, diet could be able to modulate intestinal permeability in patients with NAFLD.AIM To detect diet-induced modification of intestinal permeability in patients with NAFLD undergoing a Mediterranean diet or a low-fat diet.METHODS The current study was a dietary intervention for non-diabetic, patients with biopsy-verified NAFLD and increased transaminases. A crossover design was employed: participants underwent 16 weeks of Mediterranean diet, 16 wk of free wash-out, and 16 weeks of low-fat diet. Both diets were hypocaloric and no consumption of supplements was allowed. All patients were followed bimonthly by a dietitian. Evaluations of clinical and metabolic parameters were completed at baseline and at the end of each dietary period. Intestinal permeability was assessed by chromium-51 ethylene diamine tetraacetate excretion testing(51 CrEDTA).RESULTS Twenty Caucasian patients, 90% male, median age 43 years, body mass index(BMI) 30.9, with biopsy-verified NAFLD were enrolled. At the end of 16 weeks of a Mediterranean diet, a significant reduction in mean body weight(-5.3 ± 4.1 kg,P = 0.003), mean waist circumference(-7.9 ± 4.9 cm, P = 0.001), and mean transaminase levels [alanine aminotransferase(ALT)-28.3 ± 11.9 IU/L, P =0.0001; aspartate aminotransferase(AST)-6.4 ± 56.3 IU/L, P = 0.01] were observed. These benefits were maintained after 16 wk of wash-out and also after16 wk of low-fat diet, without further improvements. Fourteen of the 20 patients had intestinal permeability alteration at baseline(mean percentage retention of51 Cr-EDTA = 5.4%), but no significant changes in intestinal permeability were observed at the end of the 16 wk of the Mediterranean diet or 16 wk of the low-fat diet.CONCLUSION Mediterranean diet is an effective strategy for treating overweight, visceral obesity and serum transaminase in patients with NAFLD. If the Mediterranean diet can improve intestinal permeability in patients with NAFLD, it deserves further investigation.

Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis

To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients. METHODSSera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA. Markers of lipopolysaccharide (LPS) exposure [LPS binding protein (LBP)] and various anti-microbial antibodies [anti-OMP Plus IgA and endotoxin core IgA antibody (EndoCAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99 (14-106) mo]. One hundred and fifty-three healthy subjects (HCONT) and 172 ulcerative colitis (UC) patients were the controls. RESULTSA total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA IgA, AAA IgG, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA and AAA IgG (P < 0.001, for both) and AGA IgG (P = 0.01, for both) but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups. In survival analysis, AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15 (1.27-20.86), P = 0.022 or for the Mayo risk score (HR = 4.24 (0.99-18.21), P = 0.052]. AAA IgA-positivity was significantly associated with higher frequency of anti-microbial antibodies (P < 0.001 for EndoCab IgA and P = 0.012 for anti-OMP Plus IgA) and higher level of the enterocyte damage marker (median I-FABPAAA IgA posvsneg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level. CONCLUSIONPresence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC.

Direct oral anticoagulant administration in cirrhotic patients with portal vein thrombosis:What is the evidence?

In recent years,the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has evolved.Currently,it is known that in cirrhotic patients,the hemostatic system is rebalanced,which involves coagulation factors,fibrinolysis and platelets.These alterations disrupt homeostasis,skewing it toward a procoagulant state,which can lead to thromboembolic manifestations,especially when hemodynamic and endothelial factors co-occur,such as in the portal vein system in cirrhosis.Portal vein thrombosis is a common complication of advanced liver cirrhosis that negatively affects the course of liver disease,prognosis of cirrhotic patients and success of liver transplantation.It is still debated whether portal vein thrombosis is the cause or the consequence of worsening liver function.Anticoagulant therapy is the mainstay treatment for acute symptomatic portal vein thrombosis.In chronic portal vein thrombosis,the role of anticoagulant therapy is still unclear.Traditional anticoagulants,vitamin K antagonists and low-molecular-weight heparin are standard-of-care treatments for portal vein thrombosis.In the last ten years,direct oral anticoagulants have been approved for the prophylaxis and treatment of many thromboembolicrelated diseases,but evidence on their use in cirrhotic patients is very limited.The aim of this review was to summarize the evidence about the safety and effectiveness of direct oral anticoagulants for treating portal vein thrombosis in cirrhotic patients.

Long-term prognosis in patients with severe late radiation enteropathy:A prospective cohort study

AIM: To assess persistent symptoms and mortality in a cohort of patients with severe (grade 3-4) radiation enteropathy,59 patients were followed up after 15-18 years. METHODS: Fifty-nine patients were prospectively enrolled by twelve surgical departments. Primary malignant disease,radiation therapy and surgical management were recorded at inclusion. The cause of death or persistence of symptoms was examined in public death records or by interview of survivors. RESULTS: Thirty-nine patients had received radiation therapy for gynaecological cancers,twelve for urological cancers,four for gastrointestinal cancers and four for other malignancies. Forty-five patients (76%) required surgical intervention. Complications occurred in 11 (25%) operated patients. Forty-seven patients had died at the time of follow-up,seven (12%) died as a direct result of radiation enteropathy,while radiation enteropathy contributed to death in an additional seven patients. Four of the twelve surviving patients suffered from chronic debilitating symptoms of radiation enteropathy,while three had moderate symptoms. CONCLUSION: Patients with severe delayed radiation enteropathy have a high risk of persistence of symptoms after surgery. At least one in ten patients dies from radiation-induced bowel injury.

Pulmonary or otolaryngologic extraesophageal manifestations in patients with gastroesophageal reflux disease

The extraesophageal manifestations of gastroesophageal reflux disease that are similar to a heart attack or gastric diseases are well known, while those categorized as pulmonary or otolaryngological are less known and less studied. In this article, we introduce this less known aspect of gastroesophageal reflux.

Relapsing polychondritis with p-ANCA associated vasculitis: Which triggers the other?

Relapsing polychondritis(RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody(ANCA) associated vasculitis(AAV). We report three cases of RP with p-ANCA positive AAV. In the first patient RP developed 1.5 years after the onset of AAV. In the others the signs of RP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia,which raises the possibility of associated hemophagocytic syndrome. In the setting of RP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease.

Can chronic gastritis cause an increase in fecal calprotectin concentrations?

AIM:To evaluate fecal calprotectin concentrations(FCCs) in subjects with chronic gastritis and the correlation between FCCs and gastritis activity score.METHODS:FCCs were measured in 61 patients with histological diagnosis of gastritis and in 74 healthy volunteers.Histological grading of gastritis was performed according to the updated Sydney gastritis classification.Patients were subdivided into 2 groups according to the presence/absence of an active gastritis.Patients with chronic active gastritis were divided into 3 subgroups on the basis of the activity score(mild,moderate,marked).FFCs in relation to Helicobacter pylori(H.pylori) infection and proton pump inhibitor(PPI) use were also evaluated.RESULTS:FCCs in patients with chronic active gastritis were not significantly different to FCCs either in subjects with non active gastritis or in healthy controls.Among patients with chronic active gastritis(even marked),FCCs did not significantly differ according to activity score.No significant differences in FCCs were found when considering H.pylori,as well as when considering PPI chronic use.CONCLUSION:FCCs were not significantly increased in subjects with chronic gastritis,even in those patients with a marked neutrophil infiltration.

HLA variants related to primary sclerosing cholangitis influence rejection after liver transplantation

AIM: To investigate influence of human leukocyte antigen (HLA) and killer immunoglobuline-like receptor (KIR) genotypes on risks of acute rejection (AR) after liver transplantation (LTX).

Circulating extracellular vesicles:friends and foes in neurodegeneration

Extracellular vesicles have been identified as pivotal mediators of intercellular communication with critical roles in physiological and pathological conditions.Via this route,several molecules(e.g.,nucleic acids,proteins,metabolites) can be transferred to proximal and distant targets to convey specific information.Extracellular vesicle-associated cargo molecules have been proposed as markers of several disease conditions for their potential of tracking down the generating cell.Indeed,circulating extracellular vesicles may represent biomarkers of dysfunctional cellular quality control systems especially in conditions characterized by the accrual of intracellular misfolded proteins.Furthermore,the identification of extracellular vesicles as tools for the delivery of nucleic acids or other cargo molecules to diseased tissues makes these circulating shuttles possible targets for therapeutic development.The increasing interest in the study of extracellular vesicles as biomarkers resides mainly in the fact that the identification of peripheral levels of extracellular vesicle-associated proteins might reflect molecular events occurring in hardly accessible tissues,such as the brain,thereby serving as a "brain liquid biopsy".The exploitation of extracellular vesicles for diagnostic and therapeutic purposed might offer unprecedented opportunities to develop personalized approaches.Here,we discuss the bright and dark sides of extracellular vesicles in the setting of two main neurodegenerative diseases(i.e.,Parkinson's and Alzheimer's diseases).A special focus will be placed on the possibility of using extracellular vesicles as biomarkers for the two conditions to enable disease tracking and treatment monitoring.

A Study on Stroke in Young and Elderly in Rajiv Gandhi Government General Hospital, Chennai

Stroke is a devastating and disabling cerebrovascular disease with some amount of residual deficit leading onto economic loss. Recent Indian studies have shown a stroke prevalence rate of 471.58/100,000 population. This study was undertaken to analyse the clinical profile and to arrive at important factors contributing to stroke in 45 years group. This is a descriptive, retrospective cross—sectional study carried out on acute CVA patients, admitted to the I.I.M., RGGGH, Chennai. 150 patients were studied over a period of 3 months in the 2011. 20% of /= 45 years constituted our study population. 18.4% and 22.2% of males and females respectively were young stroke patients. Only 33.3% of patients were brought to the hospital within 6 hours. 90% patients had mild GCS score (>/=13/15) and presented with hemiplegia 76% and 18% had infarct and intracerebral hemorrhage(ICH) respectively. Risk factors: Type A personality (70.7%), Tobacco (60.7%) and Alcohol (44.7%) abuse, Systemic Hypertension (60.7%), Diabetes Mellitus (33.3%), Cardiac disorders (14%). Stroke was seen to be more common in >45 years but still young stroke carries paramount importance due to loss of productive years in these patients. Female predominance was seen in young stroke, with particular reference to puerperal period. Among the comorbid illness systemic hypertension followed by cardiac disorders had important contributing role in young strokes. Most of the patients with infarct and ICH were tobacco and alcohol abusers respectively. A holistic approach encompassing further research in factors involved in young stroke, public awareness, behavioural modification and comorbid medical illness management is the need for the hour.