BACKGROUND Hepatitis B virus(HBV)and hepatitis C virus(HCV)viral load(VL)estimation is essential for the management of both HBV and HCV infections.Due to a longer turnaround time for VL estimation,many patients drop o...BACKGROUND Hepatitis B virus(HBV)and hepatitis C virus(HCV)viral load(VL)estimation is essential for the management of both HBV and HCV infections.Due to a longer turnaround time for VL estimation,many patients drop out from the cascade of care.To achieve the global goals of reducing morbidity and mortality due to HBV/HCV and moving towards their elimination by 2030,molecular diagnostic platforms with faster and random(i.e.single sample)access are needed.AIM To evaluate the performance of the recently launched NeuMoDx 96 random access system with the conventional COBAS^(■)AmpliPrep/COBAS TaqMan system for HBV and HCV VL estimation.METHODS Archived once-thawed plasma samples were retrieved and tested on both platforms.Correlation between the assays was determined by linear regression and Bland-Altman analysis.The study included samples from 186 patients,99 for HBV of which 49 were true infected HBV cases(hepatitis B surface antigen,antihepatitis B core antibody,and HBV DNA-positive)and 87 for HCV assay in which 39 were true positives for HCV infection(anti-HCV and HCV RNA-positive).RESULTS The median VL detected by NeuMoDx for HBV was 2.9(interquartile range[IQR]:2.0-4.3)log_(10)IU/mL and by COBAS it was 3.70(IQR:2.28-4.56)log_(10)IU/mL,with excellent correlation(R2=0.98).In HCV,the median VL detected by NeuMoDx was 4.9(IQR:4.2-5.4)log_(10)IU/mL and by COBAS it was 5.10(IQR:4.07-5.80)log_(10)IU/mL with good correlation(R2=0.96).CONCLUSION The overall concordance between both the systems was 100%for both HBV and HCV VL estimation.Moreover,no genotype-specific bias for HBV/HCV VL quantification was seen in both the systems.Our findings reveal that NeuMoDx HBV and HCV quantitative assays have shown overall good clinical performance and provide faster results with 100%sensitivity and specificity compared to the COBAS AmpliPrep/COBAS TaqMan system.展开更多
Heart failure(HF) following liver transplant(LT) surgery is a distinct clinical entity with high mortality. It is known to occur in absence of obvious risk factors. No preoperative workup including electrocardiogram, ...Heart failure(HF) following liver transplant(LT) surgery is a distinct clinical entity with high mortality. It is known to occur in absence of obvious risk factors. No preoperative workup including electrocardiogram, echocardiography at rest and on stress, reasonably prognosticates the risk. In patients of chronic liver disease, cirrhotic cardiomyopathy, alcoholic cardiomyopathy, and stress induced cardiomyopathy have each been implicated as a cause for HF after LT. However distinguishing one etiology from another not only is difficult, several etiologies may possibly coexist in a given patient. Diagnostic dilemma is further compounded by the fact that presentation and management of HF irrespective of the possible underlying cause, remains the same. In this case series, 6 cases are presented and in the light of existing literature modification in the preoperative workup are suggested.展开更多
Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the comple...Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the complex relations between different cell types, generation of adequate vasculature, and immunological complications are road blocks in generation of bioengineered organs, while immunological complications limit the use of humanized organs produced in animals. Recent developments in induced pluripotent stem cell (iPSC) biology offer a possibility of generating human, patient-specific organs in non-human primates (NHP) using patient-derived iPSC and NHP-derived iPSC lacking the critical developmental genes for the organ of interest complementing a NHP tetraploid embryo. The organ derived in this way will have the same human leukocyte antigen (HLA) profile as the patient. This approach can be curative in genetic disorders as this offers the possibility of gene manipulation and correction of the patient's genome at the iPSC stage before tetraploid complementation. The process of generation of patient-specific organs such as the liver in this way has the great advantage of making use of the natural signaling cascades in the natural milieu probably resulting in organs of great quality for transplantation. However, the inexorable scientific developments in this direction involve several social issues and hence we need to educate and prepare society in advance to accept the revolutionary consequences, good, bad and ugly.展开更多
AIM To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis(UC).METHODS A prospective randomized double-blind placebo-controlled trial comparing the re...AIM To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis(UC).METHODS A prospective randomized double-blind placebo-controlled trial comparing the remission inducing effect of oral curcumin and mesalamine 2.4 g with placebo and mesalamine 2.4 g in patients of ulcerative colitis with mild to moderate severity was conducted from January 2003 to March 2005. The included patients received 1 capsule thrice a day of placebo or curcumin(150 mg) for 8 wk. Patients were evaluated clinically and endoscopically at 0,4 and 8 wk. The primary outcome was clinical remission at 8 wk and secondary outcomes were clinical response, mucosal healing and treatment failure at 8 wk. The primary analysis was intention to treat worst case scenario(ITT-WCS).RESULTS Of 300 patients with UC, 62 patients(curcumin: 29, placebo: 33) fulfilled the inclusion criteria and were randomized at baseline. Of these, 21 patients did not complete the trial, 41 patients(curcumin: 16, placebo: 25) finally completed 8 wk. There was no significant difference in rates of clinical remission(31.3% vs 27.3%, P = 0.75), clinical response(20.7% vs 36.4%, P = 0.18), mucosal healing(34.5% vs 30.3%, P = 0.72), and treatment failure(25% vs 18.5%, P = 0.59) between curcumin and placebo at 8 wk.CONCLUSION Low dose oral curcumin at a dose of 450 mg/d was ineffective in inducing remission in mild to moderate cases of UC.展开更多
BACKGROUNDMalnutrition affects 40%-90% of patients with cirrhosis of the liver. L3 skeletalmuscle index (L3SMI) is presently accepted as the most objective and quantitativemeasure available for sarcopenia, a surrogate...BACKGROUNDMalnutrition affects 40%-90% of patients with cirrhosis of the liver. L3 skeletalmuscle index (L3SMI) is presently accepted as the most objective and quantitativemeasure available for sarcopenia, a surrogate marker of malnutrition. L3SMIapplication is, however, limited by non-availability of computed tomographyscanning in remote areas, cost, need for extensive training, and the risk ofexposure to radiation. Therefore, an alternative dependable measure with wideravailability is needed. Malnutrition causes sarcopenia not only in skeletal musclesbut also in other muscular structures such as the psoas muscle, diaphragm andtongue. We therefore hypothesised that the tongue, being easily accessible forinspection and for measurement of thickness using ultrasonography, may be usedto document sarcopenia.AIMTo measure and compare tongue thickness in healthy individuals and in patientswith cirrhosis of the liver and to study its correlation with conventionalprognostic scores for patients with cirrhosis of the liver.METHODSTongue thickness was measured using ultrasonography. One hundred twentysubjects of either gender aged 18 to 65 years were studied, with 30 subjects in eachgroup. The tongue thickness was compared between groups based on “ChildTurcotte Pugh” (CTP) scores. The correlations between measured tonguethickness and “Model for end stage liver disease” (MELD) score and between age and measured tongue thickness were also assessed.RESULTSMean tongue thickness (mean ± SD) in patients with CTP class A, B and C was4.39 ± 0.39 cm, 4.19 ± 0.53 cm, and 3.87 ± 0.42, respectively, and was 4.33 ± 0.49 cmin normal healthy individuals. Significant differences were seen in tonguethickness between patients with CTP class C and those with CTP class A and B (P< 0.05). Patients with CTP class C also had a significantly reduced tonguethickness than normal individuals (P < 0.05). However, no significant differencewas seen in tongue thickness between patients with CTP class A and B andnormal individuals. A statistically significant, negative correlation was foundbetween MELD score and tongue thickness (r = -0.331) (P < 0.001). No correlationwas observed between L3SMI and MELD score (r = 0.074, P = 0.424). L3SMI(mean ± SD) in healthy subjects was 39.66 ± 6.8 and was 38.26 ± 8.88 in patientswith CTP class C, and the difference was not significant. No significant correlationwas found between age of the patients and tongue thickness. Intra-classcorrelation coefficient was used to determine the reliability of the tonguethickness measurements. The intra-class correlation coefficient was 0.984 (95%CI:0.979-0.989) and was indicative of good reliability.CONCLUSIONTongue thickness measured by ultrasonography, correlates significantly with theseverity of liver disease, as assessed by CTP and MELD scores. The patients with aCTP score ≥ 10 have significantly reduced tongue thickness as compared tonormal individuals and those with less severe liver disease and CTP scores of 5-9.No significant difference in tongue thickness was found between healthyindividuals and CTP class A and B patients.展开更多
The displacement of spleen from its normal location to other places is known as wandering spleen(WS)and is a rare disease.The repeated torsion of WS is due to the presence of long pedicle and absence/laxity of anchori...The displacement of spleen from its normal location to other places is known as wandering spleen(WS)and is a rare disease.The repeated torsion of WS is due to the presence of long pedicle and absence/laxity of anchoring ligaments.A WS is an extremely rare cause of left-sided portal hypertension(PHT)and severe gastric variceal bleeding.Left-sided PHT usually occurs as a result of splenic vein occlusion caused by splenic torsion,extrinsic compression of the splenic pedicle by enlarged spleen,and splenic vein thrombosis.There is a paucity of data on WSrelated PHT,and these data are mostly in the form of case reports.In this review,we have analyzed the data of 20 reported cases of WS-related PHT.The mechanisms of pathogenesis,clinico-demographic profile,and clinical implications are described in this article.The majority of patients were diagnosed in the second to third decade of life(mean age:26 years),with a strong female preponderance(M:F=1:9).Eleven of the 20 WS patients with left-sided PHT presented with abdominal pain and mass.In 6 of the 11 patients,varices were detected incidentally on preoperative imaging studies or discovered intraoperatively.Therefore,pre-operative search for varices is required in patients with splenic torsion.展开更多
Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascul...Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.展开更多
AIM:To evaluate the efficacy and safety of adjunctive mosapride citrate for bowel preparation before colonoscopy. METHODS:We conducted a randomized,double-blind, placebo-controlled study with mosapride in addition to ...AIM:To evaluate the efficacy and safety of adjunctive mosapride citrate for bowel preparation before colonoscopy. METHODS:We conducted a randomized,double-blind, placebo-controlled study with mosapride in addition to polyethylene glycol(PEG)-electrolyte solution.Of 250 patients undergoing colonoscopy,124 were randomized to receive 2 L PEG plus 15 mg of mosapride citrate (mosapride group),and 126 received 2 L PEG plus placebo(placebo group).Patients completed a questionnaire reporting the acceptability and tolerability of the bowel preparation process.The efficacy of bowel preparation was assessed by colonoscopists using a 5-point scale based on Aronchick's criteria.The primary end point was optimal bowel preparation rates(scores of excellent/good/fair vs poor/inadequate). RESULTS:A total of 249 patients were included in the analysis.In the mosapride group,optimal bowel preparation rates were significantly higher in the left colon compared with the placebo group(78.2%vs 65.6%,P<0.05),but not in the right colon(76.5%vs 66.4%,P=0.08).After excluding patients with severe constipation,there was a significant difference in bowel preparation in both the left and right colon(82.4%vs 66.7%,80.8%vs 67.5%,P<0.05,P<0.01).The incidence of adverse events was similar in both groups. Among the subgroup who had previous colonoscopy experience,a significantly higher number of patients in the mosapride group felt that the current preparation was easier compared with patients in the placebo group(34/72 patients vs 24/74 patients,P<0.05). CONCLUSION:Mosapride citrate may be an effective and safe adjunct to PEG-electrolyte solution that leads to improved quality of bowel preparation,especially in patients without severe constipation.展开更多
Budd-Chiari syndrome(BCS) consists of a group of disorders with obstruction of hepatic venous outflow leading to increased hepatic sinusoidal pressure and portal hypertension.Clinically,two forms of disease(acute and ...Budd-Chiari syndrome(BCS) consists of a group of disorders with obstruction of hepatic venous outflow leading to increased hepatic sinusoidal pressure and portal hypertension.Clinically,two forms of disease(acute and chronic) are recognized.Mostly the patients present with ascites,hepatomegaly,and portal hypertension.In acute disease the liver is enlarged with thrombosed hepatic veins(HV) and ascites,whereas in the chronic form of the disease there may be membranous occlusion of HV and/or the inferior vena cava(IVC),or there may be short or long segment fibrotic constriction of HV or the suprahepatic IVC.Due to advances in radiological interventional techniques and hardware,there have been changes in the management protocol of BCS with surgery being offered to patients not suitable for radiological interventions or having acute liver failure requiring liver transplantation.The present article gives an insight into various imaging findings and interventional techniques employed in the management of BCS.展开更多
AIM:To evaluate the possibility of reducing the volume of polyethylene glycol(PEG)-electrolyte solution using adjunctive mosapride citrate for colonoscopy preparation. METHODS:This was a single-center,prospective, ran...AIM:To evaluate the possibility of reducing the volume of polyethylene glycol(PEG)-electrolyte solution using adjunctive mosapride citrate for colonoscopy preparation. METHODS:This was a single-center,prospective, randomized,investigator-blinded,non-inferiority study involving 252 patients of both sexes,aged from 20 to 80 years,scheduled for screening or diagnostic colonoscopy in our department.A total of 126 patients was randomized to receive 1.5 L PEG-electrolyte solution plus 15 mg of mosapride(1.5 L group),and 126 received 2 L PEG-electrolyte solution plus 15 mg of mosapride(2 L group).Patients completed a questionnaire on the acceptability and tolerability of the bowel preparation process.The efficacy of bowel preparation was assessed using a 5-point scale based on the Aronchick scale.The primary end point was adequate bowel preparation rates(score of excellent/good/fair) vs(poor/inadequate).Acceptability and tolerability,as well as disease detection,were secondary end points. RESULTS:A total of 244 patients was included in the analysis.There were no significant differences between the 2 L and 1.5 L groups in age,sex,body mass index, number of previous colonoscopies,and the preparation method used previously.The adequate bowel preparation rates were 88.5%in the 2 L group and 82.8%in the 1.5 L group[95%lower confidence limit(LCL)for the difference=-14.5%,non-inferiority P=0.019]in the right colon.In the left colon,the adequate bowel preparation rates were 89.3%in the 2 L group and 81.1%in the 1.5 L group(95%LCL=-17.0%,non-inferiority P=0.066).Compliance,defined as complete (100%)intake of the PEG solution,was significantly higher in the 1.5 L group than in the 2 L group(96.8% vs 85.7%,P=0.002).The proportion of abdominal distension(none/mild/moderate/severe)was significantly lower in the 1.5 L group than in the 2 L group (36/65/22/3 vs 58/48/18/2,P=0.040).Within the subgroup who had undergone colonoscopy previously, a significantly higher number of patients in the 1.5 L group than in the 2 L group felt that the current preparation was easier than the previous one(54.1%vs 28.0%,P=0.001).The disease detection rate was not significantly different between the two groups. CONCLUSION:Although the 1.5 L group had better acceptability and tolerability,15 mg of mosapride may be insufficient to compensate for a 0.5-L reduction of PEG solution.展开更多
Extrahepatic portal vein obstruction(EHPVO) is a primary vascular condition characterized by chronic long standing blockage and cavernous transformation of portal vein with or without additional involvement of intrahe...Extrahepatic portal vein obstruction(EHPVO) is a primary vascular condition characterized by chronic long standing blockage and cavernous transformation of portal vein with or without additional involvement of intrahepatic branches, splenic or superior mesenteric vein. Patients generally present in childhood with multiple episodes of variceal bleed and EHPVO is the predominant cause of paediatric portal hypertension(PHT) in developing countries. It is a pre-hepatic type of PHT in which liver functions and morphology are preserved till late. Characteristic imaging findings include multiple parabiliary venous collaterals which form to bypass the obstructed portal vein with resultant changes in biliary tree termed portal biliopathy or portal cavernoma cholangiopathy. Ultrasound with Doppler, computed tomography, magnetic resonance cholangiography and magnetic resonance portovenography are non-invasive techniques which can provide a comprehensive analysis of degree and extent of EHPVO, collaterals and bile duct abnormalities. These can also be used to assess in surgical planning as well screening for shunt patency in post-operative patients. The multitude of changes and complications seen in EHPVO can be addressed by various radiological interventional procedures. The myriad of symptoms arising secondary to vascular, biliary, visceral and neurocognitive changes in EHPVO can be managed by various radiological interventions like transjugular intra-hepatic portosystemic shunt, percutaneous transhepatic biliary drainage, partial splenic embolization, balloon occluded retrograde obliteration of portosystemic shunt(PSS) and revision of PSS.展开更多
Restorative proctocolectomy is the most common surgical option for patients with familial adenomatous polyposis(FAP). However,adenomas may develop in the ileal pouch mucosa over time,and even carcinoma in the pouch ha...Restorative proctocolectomy is the most common surgical option for patients with familial adenomatous polyposis(FAP). However,adenomas may develop in the ileal pouch mucosa over time,and even carcinoma in the pouch has been reported. We therefore reviewed the prevalence,nature,and treatment of adenomas and carcinoma that develop after proctocolectomy in the ileal pouch mucosa in patients with FAP. In 25 reports that were reviewed,the incidence of adenomas in the ileal pouch varied from 6.7% to 73.9%. Several potential factors that favor the development of pouch polyposis have been investigated,but many remain controversial. Nevertheless,it seems certain that the age of the pouch is important. The risk appears to be 7%to 16% after 5 years,35% to 42% after 10 years,and75% after 15 years. On the other hand,only 21 cases of ileal pouch carcinoma have been recorded in the literature to date. The diagnosis of pouch carcinoma was made between 3 to 20 years(median,10 years) after pouch construction. Although the risk of malignant transformation in ileal pouches is probably low,it is not negligible,and the long-term risk cannot presently be well quantified. Regular endoscopic surveillance,especially using chromoendoscopy,is recommended.展开更多
AIM To determine whether addition of simvastatin could be an important pharmacological rescue therapy for carvedilol non-responders. METHODS One hundred and two consecutive patients of cirrhosis of liver with signific...AIM To determine whether addition of simvastatin could be an important pharmacological rescue therapy for carvedilol non-responders. METHODS One hundred and two consecutive patients of cirrhosis of liver with significant portal hypertension were included. Hepatic venous pressure gradient(HVPG) was measured at the base line and after proper optimization of dose; chronic response was assessed at 3 mo. Carvedilol non-responders were given simvastatin 20 mg per day(increased to 40 mg per day at day 15). Carvedilol plus simvastatin was continued for 1 mo and hemodynamic response was again measured at 1 mo.RESULTS A total of 102 patients with mean age of 58.3 ± 6.6 years were included. Mean baseline HVPG was 16.75 ± 2.12 mmH g and after optimization of dose and reassessment of HVPG at 3 mo, mean reduction of HVPG from baseline was 5.5 ± 1.7 mm Hg and 2.8 ± 1.6 mm Hg among responders and non-responders respectively(P < 0.001). Addition of simvastatin to carvedilol non-responders resulted in significant response in 16 patients(42.1%) and thus overall response with carvedilol and carvedilol plus simvastatin was seen in 78 patients(80%). Two patients were removed in chronic protocol study with carvedilol and three patients were removed in carvedilol plus simvastatin study due to side effects.CONCLUSION Addition of simvastatin to carvedilol non-responders may prove to be an excellent rescue therapy in patients with portal hypertension.展开更多
Liver transplantation has been associated with massive blood loss and considerable transfusion requirements. Bleeding in orthotopic liver transplantation is multifactorial. Technical difficulties inherent to this comp...Liver transplantation has been associated with massive blood loss and considerable transfusion requirements. Bleeding in orthotopic liver transplantation is multifactorial. Technical difficulties inherent to this complex surgical procedure and pre operative derangements of the primary and secondary coagulation system are thought to be the principal causes of perioperative hemorrhage. Intraoperative practices such as massive fluid resuscitation and resulting hypothermia and hypocalcemia secondary to citrate toxicity further aggravate the preexisting coagulopathy and worsen the perioperative bleeding. Excessive blood loss and transfusion during orthotopic liver transplant are correlated with diminished graft survival and increased septic episodes and prolonged ICU stay. With improvements in surgical skills, anesthetic technique, graft preservation, use of intraoperative cell savers and overall perioperative management, orthotopic liver transplant is now associated with decreased intra operative blood losses. The purpose of this review is to discuss the risk factors predictive of increased intra operative bleeding in patients undergoing orthotopic liver transplant.展开更多
AIM: To determine the predictors of 50 d in-hospital mortality in decompensated cirrhosis patients with spontaneous bacterial peritonitis(SBP).METHODS: Two hundred and eighteen patients admitted to an intensive care u...AIM: To determine the predictors of 50 d in-hospital mortality in decompensated cirrhosis patients with spontaneous bacterial peritonitis(SBP).METHODS: Two hundred and eighteen patients admitted to an intensive care unit in a tertiary care hospital between June 2013 and June 2014 with the diagnosis of SBP(during hospitalization) and cirrhosis were retrospectively analysed. SBP was diagnosed by abdominal paracentesis in the presence of polymorphonuclear cell count ≥ 250 cells/mm3 in the peritoneal fluid. Student's t test, multivariate logistic regression, cox proportional hazard ratio(HR), receiver operating characteristics(ROC) curves and Kaplan-Meier survival analysis were utilized for statistical analysis. Predictive abilities of several variables identified by multivariate analysis were compared using the area under ROC curve. P < 0.05 were considered statistical significant. RESULTS: The 50 d in-hospital mortality rate attributable to SBP is 43.11%(n = 94). Median survival duration for those who died was 9 d. In univariate analysis acute kidney injury(AKI), hepatic encephalopathy, septic shock, serum bilirubin, international normalized ratio, aspartate transaminase, and model for end-stage liver disease- sodium(MELD-Na) were significantly associated with in- hospital mortality in patients with SBP(P ≤ 0.001). Multivariate coxproportional regression analysis showed AKI(HR = 2.16, 95%CI: 1.36-3.42, P = 0.001) septic shock(HR = 1.73, 95%CI: 1.05-2.83, P = 0.029) MELD-Na(HR = 1.06, 95%CI: 1.02-1.09, P ≤ 0.001) was significantly associated with 50 d in-hospital mortality. The prognostic accuracy for AKI, MELD-Na and septic shock was 77%, 74% and 71% respectively associated with 50 d inhospital mortality in SBP patients.CONCLUSION: AKI, MELD-Na and septic shock were predictors of 50 d in-hospital mortality in decompensated cirrhosis patients with SBP.展开更多
Hepatitis E virus(HEV)is an important cause of repeated waterborne outbreaks of acute hepatitis.Recently,several extrahepatic manifestations(EHMs)have been described in patients with HEV infection.Of these,neurologica...Hepatitis E virus(HEV)is an important cause of repeated waterborne outbreaks of acute hepatitis.Recently,several extrahepatic manifestations(EHMs)have been described in patients with HEV infection.Of these,neurological disorders are the most common EHM associated with HEV.The involvement of both the peripheral nervous system and central nervous system can occur together or in isolation.Patients can present with normal liver function tests,which can often be misleading for physicians.There is a paucity of data on HEV-related neurological manifestations;and these data are mostly described as case reports and case series.In this review,we analyzed data of 163 reported cases of HEV-related neurological disorders.The mechanisms of pathogenesis,clinico-demographic profile,and outcomes of the HEV-related neurological disorders are described in this article.Nerve root and plexus disorder were found to be the most commonly reported disease,followed by meningoencephalitis.展开更多
Three-dimensional(3D)organoids derived from pluripotent or adult tissue stem cells seem to possess excellent potential for studying development and disease mechanisms alongside having a myriad of applications in regen...Three-dimensional(3D)organoids derived from pluripotent or adult tissue stem cells seem to possess excellent potential for studying development and disease mechanisms alongside having a myriad of applications in regenerative therapies.However,lack of precise architectures and large-scale tissue sizes are some of the key limitations of current organoid technologies.3D bioprinting of organoids has recently emerged to address some of these impediments.In this review,we discuss 3D bioprinting with respect to the use of bioinks and bioprinting methods and highlight recent studies that have shown success in bioprinting of stem cells and organoids.We also summarize the use of several vascularization strategies for the bioprinted organoids,that are critical for a complex tissue organization.To fully realize the translational applications of organoids in disease modeling and regenerative medicine,these areas in 3D bioprinting need to be appropriately harnessed and channelized.展开更多
Recent evidence points towards the role of genotype to understand the phenotype,predict the natural course and long term outcome of patients with progressive familial intrahepatic cholestasis(PFIC).Expanded role of th...Recent evidence points towards the role of genotype to understand the phenotype,predict the natural course and long term outcome of patients with progressive familial intrahepatic cholestasis(PFIC).Expanded role of the heterozygous transporter defects presenting late needs to be suspected and identified.Treatment of pruritus,nutritional rehabilitation,prevention of fibrosis progression and liver transplantation(LT)in those with end stage liver disease form the crux of the treatment.LT in PFIC has its own unique issues like high rates of intractable diarrhoea,growth failure;steatohepatitis and graft failure in PFIC1 and antibody-mediated bile salt export pump deficiency in PFIC2.Drugs inhibiting apical sodium-dependent bile transporter and adenovirus-associated vector mediated gene therapy hold promise for future.展开更多
Adults have approximately 20 feet of small intestine,which is the primary site for absorbing essential nutrients and water.Resection of the intestine for any medical reason may result in short bowel syndrome(SBS),lead...Adults have approximately 20 feet of small intestine,which is the primary site for absorbing essential nutrients and water.Resection of the intestine for any medical reason may result in short bowel syndrome(SBS),leading to loss of major absorptive surface area and resulting in various malabsorption and motility disorders.The mainstay of treatment is personalized close dietary management.Here we present SBS with its pathophysiology and different nutritional management options available.The central perspective of this paper is to provide a concise review of SBS and the treatment options available,along with how proper nutrition can solve major dietary issues in SBS and help patients recover faster.展开更多
Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ...Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ethambutol.Although good results are seen with this treatment in general,the management of patients with underlying cirrhosis is a challenge.The underlying depressed immune response results in alterations in many diagnostic tests.The tests used for latent TB have many flaws in this group of patients.Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis.Frequency of hepatotoxicity is increased in patients with liver cirrhosis,frequently leading to severe liver failure.There are no established guidelines for the treatment of TB in relation to the severity of liver disease.There is no consensus on the frequency of liver function tests required or the cutoff used to define hepatotoxicity.No specific treatment exists for prevention or treatment of hepatotoxicity,making monitoring even more important.A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.展开更多
文摘BACKGROUND Hepatitis B virus(HBV)and hepatitis C virus(HCV)viral load(VL)estimation is essential for the management of both HBV and HCV infections.Due to a longer turnaround time for VL estimation,many patients drop out from the cascade of care.To achieve the global goals of reducing morbidity and mortality due to HBV/HCV and moving towards their elimination by 2030,molecular diagnostic platforms with faster and random(i.e.single sample)access are needed.AIM To evaluate the performance of the recently launched NeuMoDx 96 random access system with the conventional COBAS^(■)AmpliPrep/COBAS TaqMan system for HBV and HCV VL estimation.METHODS Archived once-thawed plasma samples were retrieved and tested on both platforms.Correlation between the assays was determined by linear regression and Bland-Altman analysis.The study included samples from 186 patients,99 for HBV of which 49 were true infected HBV cases(hepatitis B surface antigen,antihepatitis B core antibody,and HBV DNA-positive)and 87 for HCV assay in which 39 were true positives for HCV infection(anti-HCV and HCV RNA-positive).RESULTS The median VL detected by NeuMoDx for HBV was 2.9(interquartile range[IQR]:2.0-4.3)log_(10)IU/mL and by COBAS it was 3.70(IQR:2.28-4.56)log_(10)IU/mL,with excellent correlation(R2=0.98).In HCV,the median VL detected by NeuMoDx was 4.9(IQR:4.2-5.4)log_(10)IU/mL and by COBAS it was 5.10(IQR:4.07-5.80)log_(10)IU/mL with good correlation(R2=0.96).CONCLUSION The overall concordance between both the systems was 100%for both HBV and HCV VL estimation.Moreover,no genotype-specific bias for HBV/HCV VL quantification was seen in both the systems.Our findings reveal that NeuMoDx HBV and HCV quantitative assays have shown overall good clinical performance and provide faster results with 100%sensitivity and specificity compared to the COBAS AmpliPrep/COBAS TaqMan system.
文摘Heart failure(HF) following liver transplant(LT) surgery is a distinct clinical entity with high mortality. It is known to occur in absence of obvious risk factors. No preoperative workup including electrocardiogram, echocardiography at rest and on stress, reasonably prognosticates the risk. In patients of chronic liver disease, cirrhotic cardiomyopathy, alcoholic cardiomyopathy, and stress induced cardiomyopathy have each been implicated as a cause for HF after LT. However distinguishing one etiology from another not only is difficult, several etiologies may possibly coexist in a given patient. Diagnostic dilemma is further compounded by the fact that presentation and management of HF irrespective of the possible underlying cause, remains the same. In this case series, 6 cases are presented and in the light of existing literature modification in the preoperative workup are suggested.
文摘Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the complex relations between different cell types, generation of adequate vasculature, and immunological complications are road blocks in generation of bioengineered organs, while immunological complications limit the use of humanized organs produced in animals. Recent developments in induced pluripotent stem cell (iPSC) biology offer a possibility of generating human, patient-specific organs in non-human primates (NHP) using patient-derived iPSC and NHP-derived iPSC lacking the critical developmental genes for the organ of interest complementing a NHP tetraploid embryo. The organ derived in this way will have the same human leukocyte antigen (HLA) profile as the patient. This approach can be curative in genetic disorders as this offers the possibility of gene manipulation and correction of the patient's genome at the iPSC stage before tetraploid complementation. The process of generation of patient-specific organs such as the liver in this way has the great advantage of making use of the natural signaling cascades in the natural milieu probably resulting in organs of great quality for transplantation. However, the inexorable scientific developments in this direction involve several social issues and hence we need to educate and prepare society in advance to accept the revolutionary consequences, good, bad and ugly.
文摘AIM To evaluate the role of oral curcumin in inducing clinical remission in patients with mild to moderate ulcerative colitis(UC).METHODS A prospective randomized double-blind placebo-controlled trial comparing the remission inducing effect of oral curcumin and mesalamine 2.4 g with placebo and mesalamine 2.4 g in patients of ulcerative colitis with mild to moderate severity was conducted from January 2003 to March 2005. The included patients received 1 capsule thrice a day of placebo or curcumin(150 mg) for 8 wk. Patients were evaluated clinically and endoscopically at 0,4 and 8 wk. The primary outcome was clinical remission at 8 wk and secondary outcomes were clinical response, mucosal healing and treatment failure at 8 wk. The primary analysis was intention to treat worst case scenario(ITT-WCS).RESULTS Of 300 patients with UC, 62 patients(curcumin: 29, placebo: 33) fulfilled the inclusion criteria and were randomized at baseline. Of these, 21 patients did not complete the trial, 41 patients(curcumin: 16, placebo: 25) finally completed 8 wk. There was no significant difference in rates of clinical remission(31.3% vs 27.3%, P = 0.75), clinical response(20.7% vs 36.4%, P = 0.18), mucosal healing(34.5% vs 30.3%, P = 0.72), and treatment failure(25% vs 18.5%, P = 0.59) between curcumin and placebo at 8 wk.CONCLUSION Low dose oral curcumin at a dose of 450 mg/d was ineffective in inducing remission in mild to moderate cases of UC.
文摘BACKGROUNDMalnutrition affects 40%-90% of patients with cirrhosis of the liver. L3 skeletalmuscle index (L3SMI) is presently accepted as the most objective and quantitativemeasure available for sarcopenia, a surrogate marker of malnutrition. L3SMIapplication is, however, limited by non-availability of computed tomographyscanning in remote areas, cost, need for extensive training, and the risk ofexposure to radiation. Therefore, an alternative dependable measure with wideravailability is needed. Malnutrition causes sarcopenia not only in skeletal musclesbut also in other muscular structures such as the psoas muscle, diaphragm andtongue. We therefore hypothesised that the tongue, being easily accessible forinspection and for measurement of thickness using ultrasonography, may be usedto document sarcopenia.AIMTo measure and compare tongue thickness in healthy individuals and in patientswith cirrhosis of the liver and to study its correlation with conventionalprognostic scores for patients with cirrhosis of the liver.METHODSTongue thickness was measured using ultrasonography. One hundred twentysubjects of either gender aged 18 to 65 years were studied, with 30 subjects in eachgroup. The tongue thickness was compared between groups based on “ChildTurcotte Pugh” (CTP) scores. The correlations between measured tonguethickness and “Model for end stage liver disease” (MELD) score and between age and measured tongue thickness were also assessed.RESULTSMean tongue thickness (mean ± SD) in patients with CTP class A, B and C was4.39 ± 0.39 cm, 4.19 ± 0.53 cm, and 3.87 ± 0.42, respectively, and was 4.33 ± 0.49 cmin normal healthy individuals. Significant differences were seen in tonguethickness between patients with CTP class C and those with CTP class A and B (P< 0.05). Patients with CTP class C also had a significantly reduced tonguethickness than normal individuals (P < 0.05). However, no significant differencewas seen in tongue thickness between patients with CTP class A and B andnormal individuals. A statistically significant, negative correlation was foundbetween MELD score and tongue thickness (r = -0.331) (P < 0.001). No correlationwas observed between L3SMI and MELD score (r = 0.074, P = 0.424). L3SMI(mean ± SD) in healthy subjects was 39.66 ± 6.8 and was 38.26 ± 8.88 in patientswith CTP class C, and the difference was not significant. No significant correlationwas found between age of the patients and tongue thickness. Intra-classcorrelation coefficient was used to determine the reliability of the tonguethickness measurements. The intra-class correlation coefficient was 0.984 (95%CI:0.979-0.989) and was indicative of good reliability.CONCLUSIONTongue thickness measured by ultrasonography, correlates significantly with theseverity of liver disease, as assessed by CTP and MELD scores. The patients with aCTP score ≥ 10 have significantly reduced tongue thickness as compared tonormal individuals and those with less severe liver disease and CTP scores of 5-9.No significant difference in tongue thickness was found between healthyindividuals and CTP class A and B patients.
文摘The displacement of spleen from its normal location to other places is known as wandering spleen(WS)and is a rare disease.The repeated torsion of WS is due to the presence of long pedicle and absence/laxity of anchoring ligaments.A WS is an extremely rare cause of left-sided portal hypertension(PHT)and severe gastric variceal bleeding.Left-sided PHT usually occurs as a result of splenic vein occlusion caused by splenic torsion,extrinsic compression of the splenic pedicle by enlarged spleen,and splenic vein thrombosis.There is a paucity of data on WSrelated PHT,and these data are mostly in the form of case reports.In this review,we have analyzed the data of 20 reported cases of WS-related PHT.The mechanisms of pathogenesis,clinico-demographic profile,and clinical implications are described in this article.The majority of patients were diagnosed in the second to third decade of life(mean age:26 years),with a strong female preponderance(M:F=1:9).Eleven of the 20 WS patients with left-sided PHT presented with abdominal pain and mass.In 6 of the 11 patients,varices were detected incidentally on preoperative imaging studies or discovered intraoperatively.Therefore,pre-operative search for varices is required in patients with splenic torsion.
文摘Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.
文摘AIM:To evaluate the efficacy and safety of adjunctive mosapride citrate for bowel preparation before colonoscopy. METHODS:We conducted a randomized,double-blind, placebo-controlled study with mosapride in addition to polyethylene glycol(PEG)-electrolyte solution.Of 250 patients undergoing colonoscopy,124 were randomized to receive 2 L PEG plus 15 mg of mosapride citrate (mosapride group),and 126 received 2 L PEG plus placebo(placebo group).Patients completed a questionnaire reporting the acceptability and tolerability of the bowel preparation process.The efficacy of bowel preparation was assessed by colonoscopists using a 5-point scale based on Aronchick's criteria.The primary end point was optimal bowel preparation rates(scores of excellent/good/fair vs poor/inadequate). RESULTS:A total of 249 patients were included in the analysis.In the mosapride group,optimal bowel preparation rates were significantly higher in the left colon compared with the placebo group(78.2%vs 65.6%,P<0.05),but not in the right colon(76.5%vs 66.4%,P=0.08).After excluding patients with severe constipation,there was a significant difference in bowel preparation in both the left and right colon(82.4%vs 66.7%,80.8%vs 67.5%,P<0.05,P<0.01).The incidence of adverse events was similar in both groups. Among the subgroup who had previous colonoscopy experience,a significantly higher number of patients in the mosapride group felt that the current preparation was easier compared with patients in the placebo group(34/72 patients vs 24/74 patients,P<0.05). CONCLUSION:Mosapride citrate may be an effective and safe adjunct to PEG-electrolyte solution that leads to improved quality of bowel preparation,especially in patients without severe constipation.
文摘Budd-Chiari syndrome(BCS) consists of a group of disorders with obstruction of hepatic venous outflow leading to increased hepatic sinusoidal pressure and portal hypertension.Clinically,two forms of disease(acute and chronic) are recognized.Mostly the patients present with ascites,hepatomegaly,and portal hypertension.In acute disease the liver is enlarged with thrombosed hepatic veins(HV) and ascites,whereas in the chronic form of the disease there may be membranous occlusion of HV and/or the inferior vena cava(IVC),or there may be short or long segment fibrotic constriction of HV or the suprahepatic IVC.Due to advances in radiological interventional techniques and hardware,there have been changes in the management protocol of BCS with surgery being offered to patients not suitable for radiological interventions or having acute liver failure requiring liver transplantation.The present article gives an insight into various imaging findings and interventional techniques employed in the management of BCS.
文摘AIM:To evaluate the possibility of reducing the volume of polyethylene glycol(PEG)-electrolyte solution using adjunctive mosapride citrate for colonoscopy preparation. METHODS:This was a single-center,prospective, randomized,investigator-blinded,non-inferiority study involving 252 patients of both sexes,aged from 20 to 80 years,scheduled for screening or diagnostic colonoscopy in our department.A total of 126 patients was randomized to receive 1.5 L PEG-electrolyte solution plus 15 mg of mosapride(1.5 L group),and 126 received 2 L PEG-electrolyte solution plus 15 mg of mosapride(2 L group).Patients completed a questionnaire on the acceptability and tolerability of the bowel preparation process.The efficacy of bowel preparation was assessed using a 5-point scale based on the Aronchick scale.The primary end point was adequate bowel preparation rates(score of excellent/good/fair) vs(poor/inadequate).Acceptability and tolerability,as well as disease detection,were secondary end points. RESULTS:A total of 244 patients was included in the analysis.There were no significant differences between the 2 L and 1.5 L groups in age,sex,body mass index, number of previous colonoscopies,and the preparation method used previously.The adequate bowel preparation rates were 88.5%in the 2 L group and 82.8%in the 1.5 L group[95%lower confidence limit(LCL)for the difference=-14.5%,non-inferiority P=0.019]in the right colon.In the left colon,the adequate bowel preparation rates were 89.3%in the 2 L group and 81.1%in the 1.5 L group(95%LCL=-17.0%,non-inferiority P=0.066).Compliance,defined as complete (100%)intake of the PEG solution,was significantly higher in the 1.5 L group than in the 2 L group(96.8% vs 85.7%,P=0.002).The proportion of abdominal distension(none/mild/moderate/severe)was significantly lower in the 1.5 L group than in the 2 L group (36/65/22/3 vs 58/48/18/2,P=0.040).Within the subgroup who had undergone colonoscopy previously, a significantly higher number of patients in the 1.5 L group than in the 2 L group felt that the current preparation was easier than the previous one(54.1%vs 28.0%,P=0.001).The disease detection rate was not significantly different between the two groups. CONCLUSION:Although the 1.5 L group had better acceptability and tolerability,15 mg of mosapride may be insufficient to compensate for a 0.5-L reduction of PEG solution.
文摘Extrahepatic portal vein obstruction(EHPVO) is a primary vascular condition characterized by chronic long standing blockage and cavernous transformation of portal vein with or without additional involvement of intrahepatic branches, splenic or superior mesenteric vein. Patients generally present in childhood with multiple episodes of variceal bleed and EHPVO is the predominant cause of paediatric portal hypertension(PHT) in developing countries. It is a pre-hepatic type of PHT in which liver functions and morphology are preserved till late. Characteristic imaging findings include multiple parabiliary venous collaterals which form to bypass the obstructed portal vein with resultant changes in biliary tree termed portal biliopathy or portal cavernoma cholangiopathy. Ultrasound with Doppler, computed tomography, magnetic resonance cholangiography and magnetic resonance portovenography are non-invasive techniques which can provide a comprehensive analysis of degree and extent of EHPVO, collaterals and bile duct abnormalities. These can also be used to assess in surgical planning as well screening for shunt patency in post-operative patients. The multitude of changes and complications seen in EHPVO can be addressed by various radiological interventional procedures. The myriad of symptoms arising secondary to vascular, biliary, visceral and neurocognitive changes in EHPVO can be managed by various radiological interventions like transjugular intra-hepatic portosystemic shunt, percutaneous transhepatic biliary drainage, partial splenic embolization, balloon occluded retrograde obliteration of portosystemic shunt(PSS) and revision of PSS.
文摘Restorative proctocolectomy is the most common surgical option for patients with familial adenomatous polyposis(FAP). However,adenomas may develop in the ileal pouch mucosa over time,and even carcinoma in the pouch has been reported. We therefore reviewed the prevalence,nature,and treatment of adenomas and carcinoma that develop after proctocolectomy in the ileal pouch mucosa in patients with FAP. In 25 reports that were reviewed,the incidence of adenomas in the ileal pouch varied from 6.7% to 73.9%. Several potential factors that favor the development of pouch polyposis have been investigated,but many remain controversial. Nevertheless,it seems certain that the age of the pouch is important. The risk appears to be 7%to 16% after 5 years,35% to 42% after 10 years,and75% after 15 years. On the other hand,only 21 cases of ileal pouch carcinoma have been recorded in the literature to date. The diagnosis of pouch carcinoma was made between 3 to 20 years(median,10 years) after pouch construction. Although the risk of malignant transformation in ileal pouches is probably low,it is not negligible,and the long-term risk cannot presently be well quantified. Regular endoscopic surveillance,especially using chromoendoscopy,is recommended.
文摘AIM To determine whether addition of simvastatin could be an important pharmacological rescue therapy for carvedilol non-responders. METHODS One hundred and two consecutive patients of cirrhosis of liver with significant portal hypertension were included. Hepatic venous pressure gradient(HVPG) was measured at the base line and after proper optimization of dose; chronic response was assessed at 3 mo. Carvedilol non-responders were given simvastatin 20 mg per day(increased to 40 mg per day at day 15). Carvedilol plus simvastatin was continued for 1 mo and hemodynamic response was again measured at 1 mo.RESULTS A total of 102 patients with mean age of 58.3 ± 6.6 years were included. Mean baseline HVPG was 16.75 ± 2.12 mmH g and after optimization of dose and reassessment of HVPG at 3 mo, mean reduction of HVPG from baseline was 5.5 ± 1.7 mm Hg and 2.8 ± 1.6 mm Hg among responders and non-responders respectively(P < 0.001). Addition of simvastatin to carvedilol non-responders resulted in significant response in 16 patients(42.1%) and thus overall response with carvedilol and carvedilol plus simvastatin was seen in 78 patients(80%). Two patients were removed in chronic protocol study with carvedilol and three patients were removed in carvedilol plus simvastatin study due to side effects.CONCLUSION Addition of simvastatin to carvedilol non-responders may prove to be an excellent rescue therapy in patients with portal hypertension.
文摘Liver transplantation has been associated with massive blood loss and considerable transfusion requirements. Bleeding in orthotopic liver transplantation is multifactorial. Technical difficulties inherent to this complex surgical procedure and pre operative derangements of the primary and secondary coagulation system are thought to be the principal causes of perioperative hemorrhage. Intraoperative practices such as massive fluid resuscitation and resulting hypothermia and hypocalcemia secondary to citrate toxicity further aggravate the preexisting coagulopathy and worsen the perioperative bleeding. Excessive blood loss and transfusion during orthotopic liver transplant are correlated with diminished graft survival and increased septic episodes and prolonged ICU stay. With improvements in surgical skills, anesthetic technique, graft preservation, use of intraoperative cell savers and overall perioperative management, orthotopic liver transplant is now associated with decreased intra operative blood losses. The purpose of this review is to discuss the risk factors predictive of increased intra operative bleeding in patients undergoing orthotopic liver transplant.
文摘AIM: To determine the predictors of 50 d in-hospital mortality in decompensated cirrhosis patients with spontaneous bacterial peritonitis(SBP).METHODS: Two hundred and eighteen patients admitted to an intensive care unit in a tertiary care hospital between June 2013 and June 2014 with the diagnosis of SBP(during hospitalization) and cirrhosis were retrospectively analysed. SBP was diagnosed by abdominal paracentesis in the presence of polymorphonuclear cell count ≥ 250 cells/mm3 in the peritoneal fluid. Student's t test, multivariate logistic regression, cox proportional hazard ratio(HR), receiver operating characteristics(ROC) curves and Kaplan-Meier survival analysis were utilized for statistical analysis. Predictive abilities of several variables identified by multivariate analysis were compared using the area under ROC curve. P < 0.05 were considered statistical significant. RESULTS: The 50 d in-hospital mortality rate attributable to SBP is 43.11%(n = 94). Median survival duration for those who died was 9 d. In univariate analysis acute kidney injury(AKI), hepatic encephalopathy, septic shock, serum bilirubin, international normalized ratio, aspartate transaminase, and model for end-stage liver disease- sodium(MELD-Na) were significantly associated with in- hospital mortality in patients with SBP(P ≤ 0.001). Multivariate coxproportional regression analysis showed AKI(HR = 2.16, 95%CI: 1.36-3.42, P = 0.001) septic shock(HR = 1.73, 95%CI: 1.05-2.83, P = 0.029) MELD-Na(HR = 1.06, 95%CI: 1.02-1.09, P ≤ 0.001) was significantly associated with 50 d in-hospital mortality. The prognostic accuracy for AKI, MELD-Na and septic shock was 77%, 74% and 71% respectively associated with 50 d inhospital mortality in SBP patients.CONCLUSION: AKI, MELD-Na and septic shock were predictors of 50 d in-hospital mortality in decompensated cirrhosis patients with SBP.
文摘Hepatitis E virus(HEV)is an important cause of repeated waterborne outbreaks of acute hepatitis.Recently,several extrahepatic manifestations(EHMs)have been described in patients with HEV infection.Of these,neurological disorders are the most common EHM associated with HEV.The involvement of both the peripheral nervous system and central nervous system can occur together or in isolation.Patients can present with normal liver function tests,which can often be misleading for physicians.There is a paucity of data on HEV-related neurological manifestations;and these data are mostly described as case reports and case series.In this review,we analyzed data of 163 reported cases of HEV-related neurological disorders.The mechanisms of pathogenesis,clinico-demographic profile,and outcomes of the HEV-related neurological disorders are described in this article.Nerve root and plexus disorder were found to be the most commonly reported disease,followed by meningoencephalitis.
文摘Three-dimensional(3D)organoids derived from pluripotent or adult tissue stem cells seem to possess excellent potential for studying development and disease mechanisms alongside having a myriad of applications in regenerative therapies.However,lack of precise architectures and large-scale tissue sizes are some of the key limitations of current organoid technologies.3D bioprinting of organoids has recently emerged to address some of these impediments.In this review,we discuss 3D bioprinting with respect to the use of bioinks and bioprinting methods and highlight recent studies that have shown success in bioprinting of stem cells and organoids.We also summarize the use of several vascularization strategies for the bioprinted organoids,that are critical for a complex tissue organization.To fully realize the translational applications of organoids in disease modeling and regenerative medicine,these areas in 3D bioprinting need to be appropriately harnessed and channelized.
文摘Recent evidence points towards the role of genotype to understand the phenotype,predict the natural course and long term outcome of patients with progressive familial intrahepatic cholestasis(PFIC).Expanded role of the heterozygous transporter defects presenting late needs to be suspected and identified.Treatment of pruritus,nutritional rehabilitation,prevention of fibrosis progression and liver transplantation(LT)in those with end stage liver disease form the crux of the treatment.LT in PFIC has its own unique issues like high rates of intractable diarrhoea,growth failure;steatohepatitis and graft failure in PFIC1 and antibody-mediated bile salt export pump deficiency in PFIC2.Drugs inhibiting apical sodium-dependent bile transporter and adenovirus-associated vector mediated gene therapy hold promise for future.
文摘Adults have approximately 20 feet of small intestine,which is the primary site for absorbing essential nutrients and water.Resection of the intestine for any medical reason may result in short bowel syndrome(SBS),leading to loss of major absorptive surface area and resulting in various malabsorption and motility disorders.The mainstay of treatment is personalized close dietary management.Here we present SBS with its pathophysiology and different nutritional management options available.The central perspective of this paper is to provide a concise review of SBS and the treatment options available,along with how proper nutrition can solve major dietary issues in SBS and help patients recover faster.
文摘Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ethambutol.Although good results are seen with this treatment in general,the management of patients with underlying cirrhosis is a challenge.The underlying depressed immune response results in alterations in many diagnostic tests.The tests used for latent TB have many flaws in this group of patients.Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis.Frequency of hepatotoxicity is increased in patients with liver cirrhosis,frequently leading to severe liver failure.There are no established guidelines for the treatment of TB in relation to the severity of liver disease.There is no consensus on the frequency of liver function tests required or the cutoff used to define hepatotoxicity.No specific treatment exists for prevention or treatment of hepatotoxicity,making monitoring even more important.A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.