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Background & Aims: Acute decompensation (AD) of cirrhosis is a heterogeneous clinical entity associated with moderate mortality. In some patients, this condition develops quickly into the more deadly acute-on-chronic liver failure (ACLF), in which other organs such as the kidneys or brain fail. The aim of this study was to characterize the blood lipidome in a large series of patients with cirrhosis and identify specific signatures associated with AD and ACLF development. Methods: Serum untargeted lipidomics was performed in 561 patients with AD (518 without and 43 with ACLF) (discovery cohort) and in 265 patients with AD (128 without and 137 with ACLF) in whom serum samples were available to perform repeated measurements during the 28-day follow-up (validation cohort). Analyses were also performed in 78 patients with AD included in a therapeutic albumin trial (43 patients with compensated cirrhosis and 29 healthy individuals). Results: The circulating lipid landscape associated with cirrhosis was characterized by a generalized suppression, which was more manifest during AD and in non-surviving patients. By computing discriminating accuracy and the variable importance projection score for each of the 223 annotated lipids, we identified a sphingomyelin fingerprint specific for AD of cirrhosis and a distinct cholesteryl ester and lysophosphatidylcholine finger-print for ACLF. Liver dysfunction and infections were the prin-cipal net contributors to these fingerprints, which were dynamic and interchangeable between patients with AD whose condition worsened to ACLF and those who improved. Notably, blood lysophosphatidylcholine levels increased in these patients after albumin therapy. Conclusions: Our findings provide insights into the lipid land-scape associated with decompensation of cirrhosis and ACLF progression and identify unique non-invasive diagnostic bio-markers of advanced cirrhosis. Lay summary: Analysis of lipids in blood from patients with advanced cirrhosis reveals a general suppression of their levels in the circulation of these patients. A specific group of lipids known as sphingomyelins are useful to distinguish between patients with compensated and decompensated cirrhosis. Another group of lipids designated cholesteryl esters further distinguishes patients with decompensated cirrhosis who are at risk of developing organ failures. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

Acute liver failure is a life-threatening illness precipitated by an acute liver injury in patients with no pre-existing liver disease. Acute viral hepatitis and drug-induced liver injury account for most cases, the clinical course characterized by the development of coagulopathy and hepatic encephalopathy, often progressing to multi-organ disease, which is associated with high fatality rates. The outcomes have improved significantly over time with improving standards of organ system support and access to liver transplantation for very sick individuals. The King's College criteria are the most commonly used tool for determination of prognosis and consideration for transplantation. Prompt diagnosis, immediate initiation of supportive care and aetiology-specific treatment, where applicable, as well as early discussions and transfer to a transplant centre, are the keys to successful outcome.

Empirical antibiotic therapy in patients with spontaneous bacterial peritonitis (SBP) is common as pathogen(s) are identified in only 5%-20% patients using conventional culture-based techniques. Metagenome next-generation sequencing (mNGS) test is a promising approach for the diagnosis of infectious disease. The clinical application of mNGS for infected ascites in cirrhotic patients is rarely reported. Here, we describe three cases to preliminarily explore the potential role of mNGS for microbiological diagnosis of ascites infection in an exploratory manner. The clinical performance of ascites mNGS in cirrhotic patients remains to be further evaluated.

Outcome expectations of direct pulp capping in carious teeth are obscured by a clinically unknown infiltration and breakdown of the dental pulp tissue. Histologic studies showed that this soft tissue breakdown is related to the innate immune system. We hypothesized 1) that a neutrophil biomarker could predict the outcome of direct pulp capping and 2) that using sodium hypochlorite (NaOCl) as a lavage solution to remove necrotized infected pulp tissue could improve it. In this randomized trial in mature posterior teeth causing no or mild discomfort with carious pulpal exposures, pulpal fluid was collected to assess neutrophil gelatinase (matrix metalloproteinase 9 [MMP-9]) per total protein (TP) levels as a predictive local biomarker. Subsequently, the dentin-pulp wound was randomly washed with a 2.5% NaOCl or a physiologic saline solution (1:1 allocation), capped with mineral trioxide aggregate, and the tooth was immediately restored with a resin-based composite restoration. Ninety-six patients were included, and 84 individuals could be followed up to treatment failure or clinically confirmed pulp survival after a minimum of 1 y. The entire data were fitted to a Cox proportional hazards model to assess the influence of the observational variables MMP-9/TP and discomfort with the randomized lavage treatment on pulp survival. The Kaplan-Meier pulp survival rates after 1 y were 55% for saline and 89% for NaOCl lavage. The inflammatory state of the pulp tissue as reflected by MMP-9/TP levels and NaOCl lavage had a highly significant ( P

Introduction: Alcohol is a potent drug that causes acute and chronic changes in almost all neurochemical systems and heavy drinking can produce serious temporary psychological symptoms including depression, anxiety and psychoses. Alcoholism is clinically heterogenous disorder with variable age of onset, drinking patterns, severity and comorbidity with other mental disorders. There is a gender difference in many aspect of alcohol use. The aim of the study was to study the sociodemographic profile, severity, gender difference and psychiatric comorbidities in patient with alcohol dependence syndrome in Nepalese population. Material And Method: This is a hospital based study done in patients coming to Nepalgunj Medical College, Kohalpur over a period of one year from June 2019 to May 2020 on consecutive serial basis. Diagnosis of alcohol dependence was made based on International Classification of Disease-10 (ICD-10) criteria. Semi structured proforma and Severity of Alcohol Dependence Questionnaire (SADQ) was applied in those patients and recorded accordingly. The data was analyzed using SPSS. Results: Out of 40 patients studied (N-40), 37 (92.5 %) were male and 3 (7.5 %) were female. Alcohol dependence is most common in the age bracket of 30-39 (43.1%) followed by 40-49 (33.4 %) with mean age of 40.3 years and the mean age of duration of alcohol use being 13.45 years. The mean amount of alcohol consumed per day is 92.25 grams. The SADQ scores, age of first alcohol use, duration of alcohol use in years and daily amount of alcohol use in grams is significantly different between male and female. Similarly there is severe alcohol dependence in 75 % while moderate level in 25 % of study population. Regarding psychiatric comorbidities, 90 % have comorbid other substance use disorder followed by anxiety disorders in 37.5 %, personality disorders in 35 %, mood disorders in 32.5 %, deliberate self harm in 30 % and psychotic disorders in 12.5 %. Conclusion: Alcohol dependence is most commonly found in young and adults of various age group. Age of first alcohol use, duration of alcohol use in years and daily amount of alcohol use in grams is significantly different between male and female. Alcohol dependence is comorbid with multiple psychiatric entities.

To report the experience of liver transplantation (LT) for tyrosinemia type 1 (TT-1). Clinical data of children with TT-1 who underwent living donor LT between July 2009 and May 2020 were retrospectively analyzed. Data included pre-LT nitisinone therapy, graft type, post-LT complications, HCC incidence, and graft/patient survival. Nine children were diagnosed with TT-1 at a median age of 12 mo (6–54 mo). Nitisinone was started in 6 patients at a median age of 15 mo (6–42 mo), but all had frequent interruption of therapy due to logistics with drug procurement including its cost. Median age at transplantation was 5 y (2–11 y). Explant liver showed HCC in 5 patients (55% of total cohort). The graft and patient survival are 100% with median follow-up of 58 mo (24–84 mo). LT is curative for TT-1 and excellent results can be obtained in experienced centers. This is especially favorable in countries with limited resources where the cost of medical therapy is highly prohibitive, with lifelong diet restrictions and unclear long-term risk of HCC.

Liver transplantation represents a life-saving treatment for patients with decompensated cirrhosis, a severe condition associated with a high risk of waiting list mortality. When decompensation occurs rapidly in the presence of extrahepatic organ failures, the condition is called acute-on-chronic liver failure, which is associated with an even higher risk of death, though liver transplantation can also markedly improve survival in affected patients. However, there are still gaps in our understanding of how to optimise prioritisation and organ allocation, as well as survival among patients with acute-on-chronic liver failure (both before and after transplant). Moreover, it is urgent to address inequalities in access to liver transplantation in patients with severe alcoholic hepatitis and non-alcoholic steatohepatitis. Several controversies still exist regarding gender and regional disparities, as well as the use of suboptimal donor grafts. In this review, we aim to provide a critical perspective on the role of liver transplantation in patients with decompensated cirrhosis and address areas of ongoing uncertainty.

Newborn screening (NBS) is the process by which newborns are screened just after birth for disorders that can cause severe illness or death unless detected and treated early. At present, there is no national NBS program in India. Although the exact incidence in India is not known, approximately 4:1000 and 5:1000 are estimated to have hearing defects and congenital heart abnormalities, respectively, whereas the incidence of IEMs is estimated to be approximately 1:1000. This high incidence is due to high prevalence of consanguinity in our country. If undiagnosed and untreated many children develop mental retardation, learning disabilities, autism, dyslexia, behavioral abnormalities, and scholastic backwardness later in life. There is also considerable burden-financial and emotional on the parents to diagnose, treat, and manage these children. The most rational and cost-effective way of preventing such tragedies would be to have a NBS program which will detect most of the preventable or treatable, if not all IEMs and other genetic disorders. Hence, all hospitals in urban areas in India should initiate NBS at least for the common disorders: CH, CAH, and G6PD deficiency.

Inborn errors of metabolism are an important cause of non-communicable under-five childhood mortality. Lack of confirmatory ‘genomic’ results in the deceased index case due to unavailability of post-mortem biological samples, can pose challenges in reproductive counseling of the parents in future pregnancies. Our case describes a couple seeking preconception genetic counseling after they lost their previous child to biochemically diagnosed Citrullinemia type-1. We confirmed the genomic diagnosis of Citrullinemia type-1 through the post-mortem genetic analysis of the DNA retrieved from the preserved blood spots, 12-months later. Prenatal testing in the next pregnancy revealed the fetus to be a carrier for Citrullinemia type-1. This case report intends to raise the obstetricians’ and neonatologists’ awareness regarding DNA banking in fatal genetic disorders and the mandatory confirmatory genetic diagnosis for effective prenatal genetic counseling.

Background Recent trials in liver machine perfusion (MP) have revealed unique challenges beyond those seen in most clinical studies. Correct trial design and interpretation of data are essential to avoid drawing conclusions that may compromise patient safety and increase costs. Methods The International Liver Transplantation Society, through the Special Interest Group "DCD, Preservation and Machine Perfusion," established a working group to write consensus statements and guidelines on how future clinical trials in liver perfusion should be designed, with particular focus on relevant clinical endpoints and how different techniques of liver perfusion should be compared. Protocols, abstracts, and full published papers of clinical trials using liver MP were reviewed. The use of a simplified Grading of Recommendations Assessment, Development, and Evaluation working group (GRADE) system was attempted to assess the level of evidence. The working group presented its conclusions at the International Liver Transplantation Society consensus conference "DCD, Liver Preservation, and Machine Perfusion" held in Venice, Italy, on January 31, 2020. Results Twelve recommendations were proposed with the main conclusions that clinical trials investigating the effect of MP in liver transplantation should (1) make the protocol publicly available before the start of the trial, (2) be adequately powered, and (3) carefully consider timing of randomization in function of the primary outcome. Conclusions There are issues with using accepted primary outcomes of liver transplantation trials in the context of MP trials, and no ideal endpoint could be defined by the working group. The setup of an international registry was considered vital by the working group.

BACKGROUND AND AIMS We assessed the burden of nonalcoholic fatty liver disease (NAFLD)-related acute on chronic liver failure (ACLF) among transplant candidates in the United States, along with waitlist outcomes for this population. APPROACH AND RESULTS We analyzed the United Network for Organ Sharing registry from 2005 to 2017. Patients with ACLF were identified using the European Association for the Study of the Liver/Chronic Liver Failure criteria and categorized into NAFLD, alcohol-associated liver disease (ALD), and hepatitis C virus (HCV) infection. We used linear regression and Chow's test to determine significance in trends and evaluated waitlist outcomes using Fine and Gray's competing risks regression and Cox proportional hazards regression. Between 2005 and 2017, waitlist registrants for NAFLD-ACLF rose by 331.6% from 134 to 574 candidates (P

Background & Aims: Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe. Methods: This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019. Results: A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9-15%); and the United Kingdom and Spain had low rates (3-5%) (p 4 mmol/L (hazard ratio [HR] 3.14; 95% CI 1.37-7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or-2 and 50% for ACLF-3. Conclusion: The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more pre-cise prognostic assessment of patients with ACLF. Lay summary: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonised to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified to help select patients with favourable outcomes. (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All reserved.

Background: Penile cancer is now a rare condition. The low incidence of the disease makes a valid estimation of its prognosis difficult. In this study, we made an attempt and propose a nomogram to develop a prognostic rule that could predict the Cancer-Specific Mortality (CSM) free rates in patients with primary penile squalors cell carcinoma of the penis (PPSCC).Methods: This study included 1304 patients diagnosed with PPSCC between the years 2004 & 2011 and treated with penile tumor excision. Subjects were staged as per Surveillance, Epidemiology & End Results stage (SEER), American Joint Committee on Cancer (AJCC), TNM classification and tumor grade (TG). CSM free rates were determined. Univariate and multivariate Cox regression model was used to test the prediction of the CSM free rate. The predictive rule accuracy was created using the receiver operating characteristic curve. Results: The clinico-pathological profile depicts a mean age of 64.66 ± 14.38 yrs. The most common primary site involved was glans penis (n= 483, 37%) and the disease was most commonly diagnosed at AJCC stage I (n= 670, 51.4%) disease. The cumulative 5-year CSM free rates according to Fine & Gray, & Kaplan-Meier methods were 81.8% and 79.8%, respectively. The predictive accuracy as per SEER stage, AJCC stage, TNM stage alone were 68.8%, 70.3%, 72.3%, respectively. When TG was combined, the predictive accuracy increased to 72.8%, 73.1%, and 75.0%, respectively. TNM stage with TG was most accurate in predicting CSM free rate compared to other models. Conclusions: TNM stage with TG and AJCC stage with TG appear to have comparable accuracy to predict the CSM free rate in patients with PPSCC, the TNM stage with TG is the most accurate (75%) method to predict the CSM free rates. The addition of the TG variable improved the accuracy of these prognostic models.

Acute-on-Chronic Liver Failure Acute decompensation in patients with chronic liver disease is called acute-on-chronic liver failure. Usually, systemic inflammation from infection or an acute hepati...

In recent years, three-dimensional (3-D) printing technology has become a standard tool that is used in several medical applications such as education, surgical training simulation and planning, and doctor-patient communication. Although liver surgery is ideally complemented by the use of preoperative 3-D-printed models, only a few publications have addressed this topic. We report the case of a 29-year-old Caucasian woman admitted for a Klatskin tumor infiltrating the right portal vein requiring surgery that required complex vascular reconstruction. A life-sized liver model with colorful plastic vessels and realistic looking tumor was created with the aim of planning an optimal surgical approach. According to the 3-D model, we performed a right hepatic trisectionectomy, also removing enbloc the tract of portal vein encased by the tumor and the neoplastic thrombus, followed by a complex vascular reconstruction between the main portal vein and the left portal branch. After 22 months of follow-up, the patient was alive and continuing chemotherapy. The use of the 3-D models in liver surgery helps clarify several useful preoperative issues. The accuracy of the model regarding anatomical findings was high. In the case of complex vascular reconstruction strategies, rational use of 3-D printing technology should be implemented.

Patients with acute-on-chronic liver failure (ACLF) can be listed for liver transplantation (LT) because LT is the only curative treatment option. We evaluated whether the clinical course of ACLF, particularly ACLF-3, between the time of listing and LT affects 1-year post-transplant survival.We identified patients from the United Network for Organ Sharing database who were transplanted within 28 days of listing and categorized them by ACLF grade at waitlist registration and LT, according to the EASL-CLIF definition.A total of 3,636 patients listed with ACLF-3 underwent LT within 28 days. Among those transplanted, 892 (24.5%) recovered to no ACLF or ACLF grade 1 or 2 (ACLF 0-2) and 2,744 (75.5%) had ACLF-3 at transplantation. One-year survival was 82.0% among those transplanted with ACLF-3 vs. 88.2% among those improving to ACLF 0-2 (p 0.001). Conversely, the survival of patients listed with ACLF 0-2 who progressed to ACLF-3 at LT (n = 2,265) was significantly lower than that of recipients who remained at ACLF 0-2 (n = 17,631) at the time of LT (83.8% vs. 90.2%, p 0.001). Cox modeling demonstrated that recovery from ACLF-3 to ACLF 0-2 at LT was associated with reduced 1-year mortality after transplantation (hazard ratio0.65; 95% CI 0.53-0.78). Improvement in circulatory failure, brain failure, and removal from mechanical ventilation were also associated with reduced post-LT mortality. Among patients60 years of age, 1-year survival was significantly higher among those who improved from ACLF-3 to ACLF 0-2 than among those who did not.Improvement from ACLF-3 at listing to ACLF 0-2 at transplantation enhances post-LT survival, particularly in those who recovered from circulatory or brain failure, or were removed from the mechanical ventilator. The beneficial effect of improved ACLF on post-LT survival was also observed among patients60 years of age.Liver transplantation (LT) for patients with acute-on-chronic liver failure grade 3 (ACLF-3) significantly improves survival, but 1-year survival probability after LT remains lower than the expected outcomes for transplant centers. Our study reveals that among patients transplanted within 28 days of waitlist registration, improvement of ACLF-3 at listing to a lower grade of ACLF at transplantation significantly enhances post-transplant survival, even among patients aged 60 years or older. Subgroup analysis further demonstrates that improvement in circulatory failure, brain failure, or removal from mechanical ventilation have the strongest impact on post-transplant survival.

Tay-Sachs disease is an autosomal recessive lysosomal storage disorder cause by deficiency of enzyme Beta Hexosaminidase A and leading to accumulation of GM2 gangliosides mainly in CNS, results in progressive loss of neurological functions. We report a case of 14 month old male child presented to us with neuro-developmental regression, convulsions and bilateral cherry red spot on funduscopy. The diagnosis of Tay-Sachs disease was made by marked decrease level of enzyme Hexosaminidase A. Key words: Lysosomal storage disorder, GM2 gangliosides, neuro- regression, cherry red spot, Enzyme replacement therapy.

Background and aims: Severe indeterminate acute hepatitis (sIAH) is a poorly understood rare disease with no specific therapy. This study aims to define the clinicopathological characteristics of sIAH and the role of liver biopsy in determining prognosis. Methods: Patients with sIAH admitted to a single center between 2010 and 2019 were included. Histopathological patterns of liver biopsies were reviewed by 2 histopathologists, and key findings further were specified by multiplex immunofluorescence. Patients that died or underwent liver transplantation were analyzed as nonsurvivors. Results: Of 294 patients with acute hepatitis, 43 with sIAH were included. Seventeen (39.5%) underwent liver transplantation and 7 (16.2%) died within 3 months. Multilobular necrosis was the predominant histopathological feature, being significantly more frequent in nonsurvivors (62.5% vs 21.1%; P = .016). Necrotic areas showed low HNF4α and Ki67 expression but high expression of CK19 and cell death markers identifying areas of severe tissue injury and inadequate regenerative response. Patients with multilobular necrosis had higher international normalized ratio, Model for End-Stage Liver Disease, and Model for End-Stage Liver Disease-Sodium scores compared with those without (P values for all markers

Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF., info:eu-repo/semantics/published

Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF phenotype (AD-ACLF) defined by organ failure(s). Precipitants may induce AD. This multicenter, prospective, observational PREDICT study (NCT03056612) analyzes and characterizes the precipitants leading to both of these AD phenotypes., info:eu-repo/semantics/published

BACKGROUND Data are sparse on etiology specific outcomes on waitlist (WL) and post-transplant outcomes among patients with acute on chronic liver failure (ACLF). METHODS AND RESULTS In a retrospective cohort of 14,774 adults from United network for organ sharing (UNOS) database listed for Liver transplantation (LT) with cirrhosis and ACLF (January 2013-June 2019), 40% were due to alcohol-associated liver disease (ALD), followed by hepatitis C virus (HCV) at 20%, non-alcoholic steatohepatitis (19%), cryptogenic cirrhosis (7%), autoimmune hepatitis (5%), primary sclerosing cholangitis (PSC) at 3%, and 2% each for hepatitis B, primary biliary cholangitis (PBC), and metabolic etiology. Using competing risk analysis, cumulative risk of WL mortality was highest for PBC at 20.5% and lowest for PSC at 13.3%, P

BACKGROUND: Biliary complications (strictures and leaks), represent major limitations in living-donor liver transplantation. Mesenchymal stem cells (MSC) are a promising modality to prevent biliary complications owing to immunosuppressive and angiogenic properties. Our goal was to evaluate the safety of adipose-derived MSC delivery to biliary anastomoses in a porcine model. Secondary objectives were defining the optimal method of delivery (intraluminal vs extraluminal) and to investigate MSC engraftment, angiogenesis, and fibrosis. METHODS: Pigs were divided into three groups. Animals underwent adipose collection, MSC isolation, and expansion. Two weeks later, animals underwent bile duct transection, re-anastomosis, and stent insertion. Group 1 received plastic stents wrapped in unseeded vicryl mesh; Group 2 received stents wrapped in MSC-seeded mesh; Group 3 received unwrapped stents with the anastomosis immersed in an MSC-suspension. Animals were sacrificed one month after stent insertion when cholangiograms and biliary tissue were obtained. Serum was collected for liver biochemistries. Tissue was used for hematoxylin/eosin/trichrome staining and immunohistochemistry for MSC markers (CD44 and CD34) and a marker of neo-angiogenesis (CD31). RESULTS: There were no intra-operative complications. One pig died on post-operative day three due to acute cholangitis. All others recovered without complications. Cholangiography demonstrated no biliary leaks and minimal luminal narrowing. Surviving animals exhibited no symptoms, abnormal liver biochemistries, or clinically-significant biliary stricturing. Group 3 showed significantly greater CD44 and CD34 staining, indicating MSC engraftment. Fibrosis was reduced at the anastomotic site in Group 3 based on trichrome stain. CD31 staining of Group 3 was more pronounced, supporting enhanced neo-angiogenesis. CONCLUSION: Adipose-derived MSC were safely applied to biliary anastomoses. MSC were locally engrafted within the bile duct and may have beneficial effects in terms of fibrosis and angiogenesis.

Introduction: Carcinoma Penis is not an uncommon condition in a developing country like Nepal and comprises 1-10% of all the malignancies in males. In this study we analyzed the demographic and clinicopathological profile of penile cancer patients who visited our cancer center during specified period. Methods: This is a descriptive cross-sectional study, that altogether included 218 patients from January 2012 to December 2016 with penile cancer conducted at B P Koirala Memorial Cancer Hospital, Nepal. All the demographic and clinico-pathological data were collected and analyzed using SPSS 16.0 software. Tumor staging was standardized according to the American Joint Committee on Cancer system. Quantitative data were represented as mean and standard deviation whereas categorical variables were expressed as frequencies and percentages of an appropriate denominator. Results: Among 218 patients, the mean ± SD age was 53.94 ± 13.69 years. Most were married (88.07%), smokers (67.88%), had poor personal hygiene (70.64%) and had not completed primary school (71.64%). The predominant profession was agriculture (81.65%). Most of the patients (56.88%) were diagnosed in clinical stage III b (T1-3, N2). Management was circumcision alone in 5.5%, Wide local excision in 6.88%, partial penectomy in 66.97% patients, total penectomy with perineal urethrostomy in 11% of patients and 9.63% patients were sent for chemotherapy after initial biopsy for fixed and fungating inguinal nodes. Bilateral inguinal lymph node dissection was performed in 87.15% patients. Most of our patients were uncircumcised (90.82%) Squamous cell carcinoma was the commonest histopathology (98.6%). Conclusion: Penile cancer is more common among farmer with low socioeconomic status. The disease is already locally advanced and at the time of diagnosis. Surgery is the main modality of treatment.

Osseous metaplasia of inflammatory sinonasal polyp is an extremely rare entity. Correct preoperative diagnosis by noncontrast CT scan is needed to rule out other more common bony neoplasms in paranasal sinuses and for accurate surgical planning. Here, we present a case of 20-year-old patient with an antrochoanal polyp with osseous metaplasia. We describe the lesion and discuss the radiological differential diagnosis thereby providing a brief review of literature of the few published cases worldwide along with histopathological correlation.

Background Heart rate variability (HRV) is reduced in cirrhosis and in conditions of systemic inflammation. Whether HRV is associated with cirrhosis decompensation and development of acute-on-chronic liver failure (ACLF) is unknown. Aims To (a) validate wireless remote HRV monitoring in cirrhosis decompensation; (b) determine if severely reduced HRV is a surrogate for inflammation and progression of cirrhosis decompensation; (c) assess if measuring HRV determines prognosis in cirrhosis decompensation. Methods One hundred and eleven patients at risk of cirrhosis decompensation at two clinical sites were monitored for HRV. Standard deviation of all normal beat-beat intervals (SDNN) reflecting HRV was assessed using remote monitoring (Isansys Lifetouch) and/or Holter ECG recording. Clinical outcomes and major prognostic scores were recorded during 90-day follow-up. Results Reduced HRV denoted by lower baseline SDNN, correlated with severity of decompensation (median 14 (IQR 11-23) vs 33 (25-42); P

Osteochondroma is the most common benign bone tumor; however, the natural history of the lesion is still poorly understood. Symptomatic osteochondromas are treated with excision, but more often the indications are mainly cosmetic or fear of malignant transformation. There are few reports of spontaneous regression of solitary osteochondroma suggesting several theories causing their regression. We present one such case of a solitary osteochondroma of the humerus in an adolescent male, where a traumatic event resulted in the spontaneous resolution of the lesion. Level of evidence: V

Patients listed for liver transplantation (LT) as status 1a currently receive the highest priority on the waiting list. The presence of acute on chronic liver failure (ACLF) with three or more organs failing (ACLF-3) portends low survival without transplantation, which may not be reflected by the Model for End-Stage Liver Disease-Sodium (MELD-Na) score. We compared short-term waitlist mortality for patients listed status 1a and those with ACLF-3 at listing. Data were analyzed from the United Network for Organ Sharing database, years 2002–2014, for 3,377 patients listed status 1a and 5,099 patients with ACLF-3. Candidates with ACLF were identified based on the European Association for the Study of the Liver Chronic Liver Failure Consortium criteria. MELD-Na score was treated as a categorical variable of scores 40. We used competing risks regression to assess waitlist mortality risk. Evaluation of outcomes through 21 days after listing demonstrated a rising trend in mortality among ACLF-3 patients at 7 days (18.0%), 14 days (27.7%), and 21 days (32.7%) (P < 0.001) compared to a stable trend in mortality among individuals listed as status 1a at 7 days (17.9%), 14 days (19.3%), and 21 days (19.8%) (P = 0.709). Multivariable modeling with adjustment for MELD-Na category revealed that patients with ACLF-3 had significantly greater mortality (subhazard ratio, 1.45; 95% confidence interval, 1.31–1.61) within 14 days of listing compared to status-1a candidates. Analysis of the interaction between MELD-Na category and ACLF-3 showed that patients with ACLF-3 had greater risk of 14-day mortality than status-1a-listed patients, across all three MELD-Na categories. CONCLUSION: Patients with ACLF-3 at the time of listing have greater 14-day mortality than those listed as status 1a, independent of MELD-Na score; these findings illustrate the importance of early transplant evaluation and consideration of transplant priority for patients with ACLF-3.

PURPOSE To evaluate effectiveness of individualized, goal directed rehabilitation protocol in improving functional outcomes in children with developmental delay disorders in a region with limited rehabilitation accessibility and to explore if goal setting influences changes observed in functional levels. METHODS Children (6 months to 17 years) with developmental delay, who visited as out-patients to the Department of Physical Medicine and Rehabilitation and whose care givers were willing to participate in the study, were enrolled for a period of one year. Individualized rehabilitation protocol targeting the child's specific problems with a simultaneous home programme was performed. A single group pre-post study design was used to assess the protocol's effectiveness. OUTCOME MEASURES Goal attainment scale (GAS), Gross Motor Function Classification System (GMFCS) Level, Gross Motor Functional Measure (GMFM) and Manual Ability Classification System (MACS) were administered pre and post-intervention monthly for 3 months. Statistical analysis was done using SPSS statistics version-22. RESULTS Total of 32 children participated in the study. Significant differences between pre and post scores of GAS score (Wilcoxon's signed rank test [W value] = 4.937, p-value < 0.005), GMFCS (W value: -3.435, p-value < 0.005), GMFM (W value: 4.937, p-value < 0.005) and MAC score (W value: -4.714, p-value < 0.005) were noted at 3 months. No correlation was observed between the GAS pre-post score and GMFM, GMFCS and MAC pre-post scores. CONCLUSION An effective rehabilitation programme in children with developmental delay should be individualized and should be goal directed to achieve maximum functional improvement. Improvement in the goals set were independent of the improvement in functional outcome levels. Care-givers play a pivotal role in both individualization and goal setting for rehabilitation, especially in a region with limited rehabilitation accessibility.

Ammonia is thought to be central to the pathogenesis of hepatic encephalopathy (HE), but its prognostic role in patients with cirrhosis and acute decompensation is unknown. The aims of this study were to determine the relationship between ammonia levels and severity of HE and its association with organ dysfunction and short-term mortality. We identified 498 patients from two institutions as part of prospective observational studies in patients with cirrhosis. Plasma ammonia levels were measured on admission and Chronic Liver Failure-Sequential Organ Failure Assessment criteria were used to determine the presence of organ failures. The 28-day patient survival was determined. Receiver operating characteristic analysis was used to identify the cutoff points for ammonia values, and multivariable analysis was performed using the Cox proportional hazard regression model. The 28-day mortality was 43.4%. Plasma ammonia correlated with severity of HE (P < 0.001), was significantly higher in nonsurvivors (93 [73-121] versus 67 [55-89] µmol/L, P < 0.001), and was an independent predictor of 28-day mortality (hazard ratio, 1.009, P < 0.001). An ammonia level of 79.5 µmol/L had sensitivity of 68.1% and specificity of 67.4% for predicting 28-day mortality. An ammonia level of ≥79.5 µmol/L was associated with a higher frequency of organ failures (liver [P = 0.004], coagulation [P < 0.001], kidney [P = 0.004], and respiratory [P < 0.001]). Lack of improvement in baseline ammonia at day 5 was associated with high mortality (70.6%). Conclusion: Ammonia level correlates with not only the severity of HE but also the failure of other organs and is an independent risk factor for mortality; lack of improvement in ammonia level is associated with high risk of death, making it an important biomarker and a therapeutic target.

The effects of cannabis use in vulnerable persons with schizophrenia or schizoaffective disorder, continues to be elucidated.We compared 55 cannabis-only users (Group 1) with 462 non-substance users (Group 2) on measures of length of stay and number of psychiatric hospitalizations with a primary discharge diagnosis of schizophrenia or schizoaffective disorder using the Wilcoxon-Mann-Whitney non-parametric test for non-normal distributions, analysis of variance (ANOVA), and Poisson regression analysis.Group 1 had a mean length of stay of 6.15Cannabis use may not be a good predictor of length of stay, once covariates are considered, and mean number of hospitalizations in hospitalized patients with schizophrenia or schizoaffective disorder.

Hip fractures in elderly are commonly associated with osteoporosis and surgical outcome is influenced by its concurrent management. The purpose of our study is to determine the association between timing of bisphosphonate administration in inter-trochanteric (IT) fractures and fracture healing. Patients with IT fractures (aged≥50 years) and T-score ≤ -1.5 [WHO defines osteopenia as T-score between −1 and −2.5, and osteoporosis as T-score ≤ -2.5 on DEXA scan (which was obtained post-operatively in our cohort)], who underwent proximal femoral nailing were included. Patients were divided into three groups: group 1a-intravenous bisphosphonate {ivBP [zoledronic acid (ZA)]} given within one week, group 1b-ZA at six weeks and group 2-control group. Post-operative radiographs were assessed for reduction parameters [neck-shaft angle, tip-apex distance, reduction variance]. Radiological union was determined using RUSH score and functional outcome (at one year) with Modified Harris Hip Scores. 41 (23 males), 40 (15 males) and 42 (15 males) patients were included in groups 1a, 1b and 2, respectively (no statistical difference in sex distribution among the groups; p = 0.12). Mean age in groups 1a, 1b and 2 was 71.8 ± 8.1, 75.9 ± 8.5 and 72.3 ± 10.6 years (p = 0.09). There was no significant difference in the pattern of injuries (AO classification) among the groups (p = 0.72). Mean time to union in groups 1a, 1b and 2 was 13.7,13.7 and 14.2 weeks, respectively (p = 0.69). Mean time to union in AO types A1, A2 and A3 fractures was 13.2 ± 2.1, 13.7 ± 2.8 and 16.1 ± 4.9 weeks (p = 0.01). We did not observe any association between T-scores and fracture union (hip:p = 0.52, spine:p = 0.93).The functional outcome was similar among groups (p = 0.96). Early administration of ZA did not negatively influence fracture healing in patients undergoing fixation of IT fractures. Among the various other factors analyzed, there was a statistically significant association between the fracture type (AO type A3) and longer time to fracture union.

Acute-on-chronic liver failure (ACLF) occurs in hospitalised patients with cirrhosis and is characterised by multiorgan failures and high rates of short-term mortality. Without liver transplantation (LT), the 28-day mortality rate of patients with ACLF ranges from 18-25% in those with ACLF grade 1 to 68-89% in those with ACLF grade 3. It has become clear that patients with ACLF do not have equitable access to LT because of current allocation policies, which are based on prognostic scores that underestimate their risk of death and a lack of appreciation of the clear evidence of transplant benefit in carefully selected patients (who can have excellent post-LT outcomes). In this expert opinion, we provide evidence supporting the argument that patients with ACLF should be given priority for LT based on prognostic models that define the risk of death for these patients. We also pinpoint risk factors for poor post-LT outcomes, identify unanswered questions and describe the design of a global study, the CHANCE study, which will provide answers to the outstanding issues. We also propose the worldwide adoption of new organ allocation policies for patients with ACLF, as have been initiated in the UK and recommended in Spain.

BACKGROUND: Stroke related studies in Nepal are primarily hospital-based and mainly from the capital city. OBJECTIVES: We aimed to estimate the prevalence of stroke and stroke risk factors in the South-Western community of Nepal. METHODS: A cross-sectional study was conducted from May to August 2018 among 549 randomly selected Nepalese participants from diverse ethnicity, aged ≥15 years, in a region with the availability of neurological support facilities. Data were collected using a stroke questionnaire designed for the purpose. Stroke was identified by enumerators using the Balance-Eyes-Face-Arms-Speech-Time (BEFAST) scale, and a senior neurologist confirmed it. We assessed the presence of major risk factors associated with stroke. RESULTS: The crude and age-standardised prevalence of stroke were 2368 and 2967 per 100,000 respectively. Of all the surveyed participants, 61% (n=335) reported consumption of full-fat dairy products >3 days per week, 87.6% (n=481) reported a high intake of salt (>5 g/day), 83.6% (n=459) with a low intake of fruits and vegetables (

Systemic inflammation (SI) is involved in the pathogenesis of acute decompensation (AD) and acute-on-chronic liver failure (ACLF) in cirrhosis. In other diseases, SI activates tryptophan (Trp) degradation through the kynurenine pathway (KP), giving rise to metabolites that contribute to multiorgan/system damage and immunosuppression. In the current study, we aimed to characterize the KP in patients with cirrhosis, in whom this pathway is poorly known. The serum levels of Trp, key KP metabolites (kynurenine and kynurenic and quinolinic acids), and cytokines (SI markers) were measured at enrollment in 40 healthy subjects, 39 patients with compensated cirrhosis, 342 with AD (no ACLF) and 180 with ACLF, and repeated in 258 patients during the 28-day follow-up. Urine KP metabolites were measured in 50 patients with ACLF. Serum KP activity was normal in compensated cirrhosis, increased in AD and further increased in ACLF, in parallel with SI; it was remarkably higher in ACLF with kidney failure than in ACLF without kidney failure in the absence of differences in urine KP activity and fractional excretion of KP metabolites. The short-term course of AD and ACLF (worsening, improvement, stable) correlated closely with follow-up changes in serum KP activity. Among patients with AD at enrollment, those with the highest baseline KP activity developed ACLF during follow-up. Among patients who had ACLF at enrollment, those with immune suppression and the highest KP activity, both at baseline, developed nosocomial infections during follow-up. Finally, higher baseline KP activity independently predicted mortality in patients with AD and ACLF. Conclusion: Features of KP activation appear in patients with AD, culminate in patients with ACLF, and may be involved in the pathogenesis of ACLF, clinical course, and mortality., info:eu-repo/semantics/published

Background: Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up. Because little is known about the association of profile of systemic inflammation with clinical phenotypes of patients with AD cirrhosis, we aimed to investigate a battery of markers of systemic inflammation in these patients. Methods: Upon hospital admission baseline plasma levels of 15 markers (cytokines, chemokines, and oxidized albumin) were measured in 40 healthy controls, 39 compensated cirrhosis, 342 AD cirrhosis, and 161 ACLF. According to EASL-CLIF criteria, AD cirrhosis was divided into three distinct clinical phenotypes (AD-1: Creatinine, SCOPUS: ar.j, info:eu-repo/semantics/published

Background & Aims: Antibiotic resistance has been increasingly reported in patients with decompensated cirrhosis in single-center studies. Prospective investigations reporting broad epidemiological data are scarce. We aimed to analyze epidemiological changes in bacterial infections in patients with decompensated cirrhosis. Methods: This was a prospective evaluation of 2 series of patients hospitalized with decompensated cirrhosis. The Canonic series included 1,146 patients from Northern, Southern and Western Europe in 2011. Data on epidemiology, clinical characteristics of bacterial infections, microbiology and empirical antibiotic schedules were assessed. A second series of 883 patients from Eastern, Southern and Western Europe was investigated between 2017–2018. Results: A total of 455 patients developed 520 infections (39.7%) in the first series, with spontaneous bacterial peritonitis, urinary tract infections and pneumonia the most frequent infections. Nosocomial episodes predominated in this series. Nearly half of the infections were culture-positive, of which 29.2% were caused by multidrug-resistant organisms (MDROs). MDR strains were more frequently isolated in Northern and Western Europe. Extended-spectrum beta-lactamase-producing Enterobacteriaceae were the most frequent MDROs isolated in this series, although prevalence and type differed markedly among countries and centers. Antibiotic resistance was associated with poor prognosis and failure of antibiotic strategies, based on third-generation cephalosporins or quinolones. Nosocomial infection (odds ratio [OR] 2.74; p < 0.001), intensive care unit admission (OR 2.09; p = 0.02), and recent hospitalization (OR 1.93; p = 0.04) were identified as independent predictors of MDR infection. The prevalence of MDROs in the second series (392 infections/284 patients) was 23%; 38% in culture-positive infections. A mild increase in the rate of carbapenem-resistant Enterobacteriaceae was observed in this series. Conclusions: MDR bacterial infections constitute a prevalent, growing and complex healthcare problem in patients with decompensated cirrhosis and acute-on-chronic liver failure across Europe, negatively impacting on prognosis. Strategies aimed at preventing the spread of antibiotic resistance in cirrhosis should be urgently evaluated. Lay summary: Infections caused by bacteria resistant to the main antibiotic families are prevalent in patients with cirrhosis. This study demonstrates that this healthcare problem is increasing and extends through all European regions. Infections caused by these difficult to treat bacteria resolve less frequently and often cause the death of the patient. The type of resistant bacteria varies markedly among different hospitals., SCOPUS: ar.j, info:eu-repo/semantics/published

Modern medicine essentially arose as a response to the Industrial Revolution and the new kinds of microbes/viruses associated with it. With the mass movement of people to cities, the focus of medical systems was on tracking disease spread and rapid ways to contain it. This resulted in a changed approach towards health and medicine. Gradually it led to the hegemony of what will be referred to as modern (allopathic) systems of medicine (as against the traditional systems). Despite the age old traditional systems of medicine, bio-medicine became the predominant system of knowledge and practice, with its scientific empirical researches, its larger than life healthcare professionals, hospital systems and sophisticated marketing techniques. Traditional/indigenous systems of medicine, although continued to exist in some parts of the world, became the alternative systems. The focus was now on cure rather than prevention. With the COVID-19 pandemic unfolding quickly, the focus in India shifted once again to prevention and a more holistic approach to health. Being restricted at home due to the lockdown, the kitchen once again became the pharmacy, and an attempt was made towards a healthy lifestyle. The fear created by the pandemic and the social stigma that got attached to being sick (infected by the virus) changed the worldview of health and illness. As the conspiracy theories around the pandemic did the rounds, the fear of the disease became paramount. The vulnerable or potential patient became the enemy, the other. The fear not only of the disease but the associated consequences prompted the masses to combine multiple therapy systems. With no vaccine or cure for the novel coronavirus and millions infected, people turned yet again towards preventive health care. The paper focuses on how, in the absence of any system of medicine to dispel the fears around the pandemic, people resort to a mix of healthcare systems (without necessarily understanding their body of knowledge). It also focuses on current, popular perceptions of medicine, to understand whether the ‘new normal’ will be a medley of elements towards a holistic healthcare regime.

Traditionally, the complications of cirrhosis, namely variceal bleeding, ascites and hepatic encephalopathy, were thought to result predominantly from circulatory dysfunction and altered organ perfusion arising as a result of portal hypertension. Over the past 20 years, large, international prospective studies have indicated the importance of systemic inflammation and organ immunopathology as additional determinants of organ dysfunction in cirrhosis, which not only manifests in the liver, brain, circulation and the kidneys, but also the immune system, gut, muscles, adrenal glands, reproductive organs, heart and lungs. This review provides an overview of the traditional and emerging concepts around the initiation and maintenance of organ dysfunction in cirrhosis and proposes a new paradigm based upon a better understanding of acute decompensation of cirrhosis. The interaction between the traditional concepts and the emerging perspectives remains a matter of great interest and the basis for future research.