Use of machine learning-based integration to develop a monocyte differentiation-related signature for improving prognosis in patients with sepsis.

BACKGROUND: Although significant advances have been made in intensive care medicine and antibacterial treatment, sepsis is still a common disease with high mortality. The condition of sepsis patients changes rapidly, and each hour of delay in the administration of appropriate antibiotic treatment can lead to a 4-7% increase in fatality. Therefore, early diagnosis and intervention may help improve the prognosis of patients with sepsis. METHODS: We obtained single-cell sequencing data from 12 patients. This included 14,622 cells from four patients with bacterial infectious sepsis and eight patients with sepsis admitted to the ICU for other various reasons. Monocyte differentiation trajectories were analyzed using the "monocle" software, and differentiation-related genes were identified. Based on the expression of differentiation-related genes, 99 machine-learning combinations of prognostic signatures were obtained, and risk scores were calculated for all patients. The "scissor" software was used to associate high-risk and low-risk patients with individual cells. The "cellchat" software was used to demonstrate the regulatory relationships between high-risk and low-risk cells in a cellular communication network. The diagnostic value and prognostic predictive value of Enah/Vasp-like (EVL) were determined. Clinical validation of the results was performed with 40 samples. The "CBNplot" software based on Bayesian network inference was used to construct EVL regulatory networks. RESULTS: We systematically analyzed three cell states during monocyte differentiation. The differential analysis identified 166 monocyte differentiation-related genes. Among the 99 machine-learning combinations of prognostic signatures constructed, the Lasso + CoxBoost signature with 17 genes showed the best prognostic prediction performance. The highest percentage of high-risk cells was found in state one. Cell communication analysis demonstrated regulatory networks between high-risk and low-risk cell subpopulations and other immune cells. We then determined the diagnostic and prognostic value of EVL stabilization in multiple external datasets. Experiments with clinical samples demonstrated the accuracy of this analysis. Finally, Bayesian network inference revealed potential network mechanisms of EVL regulation. CONCLUSIONS: Monocyte differentiation-related prognostic signatures based on the Lasso + CoxBoost combination were able to accurately predict the prognostic status of patients with sepsis. In addition, low EVL expression was associated with poor prognosis in sepsis.

Prevalence of fatty liver disease after liver transplantation and risk factors for recipients and donors.

INTRODUCTION AND OBJECTIVES: Fatty liver disease (FLD) may develop in liver transplant recipients. We investigated the recipient and donor risk factors for FLD development after liver transplantation (LT). METHODS: A total of 108 liver transplant recipients (54 men [50.0%]; median age, 52 [20-68] years) treated from 2011-2020 was enrolled. Three recipients died at < 3 months as a result of infection or blood flow impairment, and were excluded from the long-term FLD study. On evaluation of 88 prospective living donors, fatty liver was observed in 21. The prevalence and risk factors for FLD and survival were evaluated. RESULTS: After LT, 28 of 105 recipients (26.7%) developed FLD. FLD was more common in patients with a high body mass index (BMI) and dyslipidemia (both p < 0.01), primary nonalcoholic steatohepatitis (p = 0.02), after living-donor LT (p = 0.03) and everolimus (EVL) use (p = 0.08). Factors predictive of FLD included EVL use and a high BMI (hazard ratios = 3.00 and 1.34; p = 0.05 and p < 0.01, respectively). Sixteen donors lost 6.5 kg (range: 2.0-16.0 kg) of body weight prior to LT. However, there were no cases of primary non-function, which did not affect the FLD prevalence. Development of FLD did not have a negative impact on LT outcome; the 5-year survival rate was 92.6%. CONCLUSIONS: Recipient factors were more important than donor factors for FLD onset after LT.

Albumin-Bilirubin Grade as a Novel Predictor of the Development and Short-Term Survival of Post-Banding Ulcer Bleeding Following Endoscopic Variceal Ligation in Cirrhotic Patients.

Background and Objectives: Endoscopic variceal ligation (EVL) is the primary and secondary treatment for acute esophageal variceal bleeding. Post-banding ulcer bleeding (PBUB) may lead to bleeding episodes following EVL, increasing mortality. The aim of this study was to evaluate the risk factors for PBUB and predict the 6-week mortality risk after PBUB. Materials and Methods: We retrospectively analyzed the data collected from cirrhotic patients with EVL from 2015 to 2017. The incidence of PBUB and the 6-week mortality rate were evaluated. Risk factors for PBUB and predictive factors for mortality after PBUB were analyzed. Results: A total of 713 patients were enrolled in this study. Among the studied subjects, the incidence of PBUB was 5.8% (N = 41). The 6-week mortality rate was 63.4% (26/41). In multivariate analysis, MELD score ≥20 (OR: 3.77, 95% CI: 1.94−7.33, p < 0.001), ALBI score of 3 (OR: 2.67, 95% CI: 1.34−5.3, p = 0.005) and the presence of gastric varices (OR: 2.1, 95% CI: 1.06−4.16, p = 0.03) were associated with the development of PBUB. Patients with ALBI grade 3 (OR: 4.8, 95% CI: 1.18−19.6, p = 0.029) and Child-Pugh scores B and C (OR: 16.67, 95% CI: 1.75−158.1, p = 0.014) were associated with 6-week mortality after PBUB. Conclusions: PBUB is a complication with low incidence but increased mortality following EVL. The ALBI grade is a useful score to predict not only the development of PBUB but also the 6-week mortality after PBUB.

NKG2D-DAP10 signaling recruits EVL to the cytotoxic synapse to generate F-actin and promote NK cell cytotoxicity.

Natural killer (NK) cells eliminate abnormal cells through the release of cytolytic granule contents. In this process, NK cells must adhere to target cells through integrin-mediated adhesion, which is highly dependent on the generation of F-actin. Ena/VASP-like (EVL) is an actin regulatory protein previously shown to regulate integrin-mediated adhesion in other cell types, but its role in NK cell biology is not known. Herein, we show that EVL is recruited to the NK cell cytotoxic synapse and is required for NK cell cytotoxicity. Significantly, EVL is involved in the generation of F-actin at the cytotoxic synapse, antibody-stimulated spreading, and NK cell-target cell adhesion. EVL interacts with WASP (also known as WAS) and VASP and is required for localization of both proteins to the synapse. Recruitment of EVL to points of cellular activation occurs through the receptor NKG2D-DAP10 (also known as KLRK1 and HCST, respectively) via a binding site previously implicated in VAV1 and Grb2 recruitment. Taken together, this study implicates DAP10-mediated Grb2 and VAV1 signaling in the recruitment of an EVL-containing actin regulatory complex to the cytotoxic synapse where it can promote F-actin nucleation leading to NK cell-mediated killing.

Spectrins: a structural platform for stabilization and activation of membrane channels, receptors and transporters.

This review focuses on structure and functions of spectrin as a major component of the membrane skeleton. Recent advances on spectrin function as an interface for signal transduction mediation and a number of data concerning interaction of spectrin with membrane channels, adhesion molecules, receptors and transporters draw a picture of multifaceted protein. Here, we attempted to show the current depiction of multitask role of spectrin in cell physiology. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé.

Non-cirrhotic portal hypertension - diagnosis and management.

NCPH is a heterogeneous group of liver disorders of vascular origin, leading to PHT with near normal HVPG. NCPF/IPH is a disorder of young adults or middle aged women, whereas EHPVO is a disorder of childhood. Early age acute or recurrent infections in an individual with thrombotic predisposition constitute the likely pathogenesis. Both disorders present with clinically significant PHT with preserved liver functions. Diagnosis is easy and can often be made clinically with support from imaging modalities. Management centers on control and prophylaxis of variceal bleeding. In EHPVO, there are additional concerns of growth faltering, portal biliopathy, MHE and parenchymal dysfunction. Surgical shunts are indicated in patients with failure of endotherapy, bleeding from sites not amenable to endotherapy, symptomatic hypersplenism or symptomatic biliopathy. Persistent growth failure, symptomatic and recurrent hepatic encephalopathy, impaired quality of life or massive splenomegaly that interferes with daily activities are other surgical indications. Rex-shunt or MLPVB is the recommended shunt for EHPVO, but needs proper pre-operative radiological assessment and surgical expertise. Both disorders have otherwise a fairly good prognosis, but need regular and careful surveillance. Hepatic schistosomiasis, CHF and NRH have similar presentation and comparable prognosis.

mTOR inhibitors after lung transplantation: a real-life experience.

Background: The mammalian target of rapamycin (mTOR) inhibitors in combination with calcineurin inhibitors (CNIs), antimetabolites and corticosteroids for immunosuppression after lung transplantation (TPL) have gained importance in patients with chronic kidney disease (CKD). The goal of this study was to characterize lung transplant recipients (LTR) treated with mTOR inhibitors, with a special focus on kidney function. Methods: LTR transplanted at the University Hospital Zurich between December 1992 and April 2022 were analyzed. Demographics, estimated glomerular filtration rate (eGFR) before and after mTOR initiation, TPL circumstances, immunosuppressive regimens, and allograft function were recorded. We used linear regression to calculate the Mitch curves and a linear mixed-effects model to compare the eGFR. Results: Of all LTR, 70/593 (12%) received mTOR inhibitors. Intolerance or adverse events of antimetabolites were the most common indications for mTOR inhibitor introduction. Discontinuation in 34/70 (49%) was often related to planned or urgent surgery to prevent impaired wound healing. The majority of patients had a preserved baseline eGFR at mTOR inhibitor introduction with CKD Kidney Disease Improving Global Outcomes (KDIGO) stage G1 or 2. The mean annual eGFR decline changed significantly from -16.19 mL/min/1.73 m2/year [95% confidence interval (CI): -22.27 to -10.11] 12 months before to -6.16 mL/min/1.73 m2/year (95% CI: -13.37 to 1.05) 12 months after mTOR initiation (P=0.009) showing better outcomes with earlier mTOR inhibitor initiation after lung TPL. Conclusions: This retrospective study suggests stabilization of kidney function after mTOR inhibitor initiation in LTR documented by a slower eGFR decline after mTOR inhibitor introduction with better outcomes early after lung TPL. Intolerance or adverse events of antimetabolites are important indications for the introduction of mTOR inhibitors. A relatively high discontinuation rate (49%) can be explained by planned discontinuation of mTOR inhibitors prior to surgery to avoid impaired wound healing.

Effectiveness of Proton Pump Inhibitor Therapy in the Prevention of Bleeding After Prophylactic Endoscopic Variceal Band Ligation.

Background Endoscopic variceal ligation (EVL) is a surgical intervention that can work well to curb variceal bleeding in people with liver cirrhosis. However, it could make ulcer bleeding worse and be fatal in some cases. The widespread use of proton pump inhibitors (PPI) in cirrhotic individuals with variceal bleeding is empirical rather than based on scientific data. According to many studies, PPIs reduce the size of post-EVL ulcers. This study aimed to see if PPI use could reduce rebleeding after endoscopy therapy in cirrhotic patients with variceal bleeding. Methodology A retrospective cross-sectional study was conducted at a tertiary care hospital from August 2019 to September 2021. Cirrhotic patients with bleeding gastroesophageal varices (GEVs) who had undergone EVL at the same hospital were enrolled in the study. Medical records were organized, and the sample was divided into two groups based on whether or not PPI was given. Both PPI and non-PPI patients had their endoscopic findings, initial hemostasis outcomes, rebleeding rates, bleeding-related mortality rates, and treatment-related comorbidities compared. Results A total of 46 patients were selected for the study and divided into two groups (PPI group n=28 and non-PPI group n=18). The majority of the patients were males. The PPI group had a mean age of 58.6 ±7.8 years, whereas the non-PPI group had a mean age of 53.6 ±4.4 years. Hepatitis B virus (HBV) infection was the most prevalent cause of cirrhosis in both groups. After endoscopic treatment, three patients (16%) in the non-PPI group suffered a variceal hemorrhage. Bleeding-related fatalities and the time it took for the bleeding to stop varied significantly between the two groups. History of variceal bleeding (relative risk (RR)=1.45; 95% confidence interval (CI), 1.60-7.67; p=0.02), presence of gastric varices (RR=2.23; 95% CI, 2.56-9.832; p=0.035), and not administering PPIs (RR =7.542; 95% CI, 3.98-29.13; p=0.008) were linked with rebleeding. The presence of red concurrent esophageal varices (RR=6.37; 95% CI, 0.562-15.342; p=0.002) and failure to provide PPIs (RR=2.3; 95% CI, 1.621-25.64; p=0.04) were linked with post-EVL bleeding in a multivariate analysis. Conclusions Proton pump inhibitors reduce the occurrence of early bleeding and adverse events after EVL in cirrhotic patients. Not prescribing PPIs and the presence of GEVs were substantially related to a higher risk of bleeding during preventative EVL. Not initiating PPI medication immediately was the sole predictor of bleeding complications in patients who had undergone EVL without gastric varix treatment. To lower the risk of post-EVL ulcer bleeding, we recommend PPI use in patients undergoing EVL.

Immunocyte Infiltration Analysis and Immunohistochemistry Identify EVL as a Potential Prognostic Biomarker for Pancreatic Cancer.

Ena-VASP-like (EVL), a member of the Enabled/vasodilator stimulated phosphoprotein family, is functionally expressed in various cancers. This study explored the prognostic value and potential mechanism of EVL in pancreatic cancer (PC). RNA-seq obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to evaluate EVL expression differences, and clinical samples were collected for validation. The prognostic value of EVL was evaluated by survival data obtained from TCGA and clinical samples. The biological pathways involved in EVL were evaluated by functional enrichment analysis such as GO, KEGG, and GSEA. We used immune infiltration analysis to estimate the correlation between EVL and tumor-infiltrating immune cells (TICs). The expression of EVL is down-regulated in PC tissues, which is an independent factor affecting survival time. Survival analysis suggested EVL-high expression was associated with good prognosis in PC patients. The results of the enrichment analysis suggested that the biological function of EVL was closely related to the immune mechanism. Tumor immune infiltration analysis showed that high expression of EVL was accompanied by high levels of immune infiltration. Furthermore, EVL was strongly correlated with the content of immune cells such as CD8+ T cells, B cells, regulatory T cells, CD4+ Tem cells, and follicular Th cells. EVL is a potential independent prognostic marker and immunotherapy target for PC. Mechanistically, EVL may affect the prognosis by extensively promoting immune cell infiltration, including strengthening the anti-tumor immune response of CD8+ T cells.

A case report of a pregnant woman with compensated liver cirrhosis and pancytopenia.

Key Clinical Message: Liver cirrhosis may worsen during pregnancy resulting in adverse maternal and fetal outcomes. Proper antenatal evaluation, staging, and variceal screening will facilitate the management. Elective endoscopic variceal ligation (EVL) during the second trimester can prevent unexpected variceal bleeding. A multidisciplinary approach including the planning of delivery and shared decision-making is recommended for favorable pregnancy outcomes. Abstract: Pregnancy in women with liver cirrhosis is relatively uncommon. During pregnancy, liver cirrhosis and portal hypertension may worsen significantly, placing both the mother and fetus at an increased risk of serious morbidity and life-threatening events. With the use of a wide variety of diagnostic tools and considerably improved treatment strategies, many women with liver disease in pregnancies are being diagnosed with significantly improved obstetric outcomes. We present a case of a 33-year-old lady with a previous medical history of cryptogenic chronic liver disease and schistosomiasis associated with periportal fibrosis, portal hypertension, splenomegaly, and pancytopenia. The mother presented to our tertiary care center at 18 weeks of gestation. She had EVL twice during the second trimester. With multidisciplinary care and follow-up, she labored spontaneously and was discharged home on third postnatal day.

Anticoagulation therapy early is safe in portal vein thrombosis patients with acute variceal bleeding: a multi-centric randomized controlled trial.

Portal vein thrombosis (PVT) and acute variceal bleeding (AVB) are frequent complications of cirrhosis. The efficacy, safety, and timing of anticoagulant treatment in cirrhotic patients with PVT and AVB are contentious issues. We aimed to establish the safety and efficacy of initiating nadroparin calcium-warfarin sequential (NWS) anticoagulation therapy early after esophageal variceal band ligation within PVT patients having cirrhosis and AVB. Cirrhotic patients having AVB and PVT who underwent EVL were included and randomly allocated to either the NWS therapy group (1-month nadroparin calcium by subcutaneous injection following 5-month warfarin through oral administration, n = 43) or the control group (without any anticoagulation therapy, n = 43). The primary endpoint was the rate of PVT recanalization. Secondary endpoints included major bleeding events mainly referring to variceal rebleeding (5-day failure, 14-day, 4-week, 6-week, and 6-month rebleeding rates) and mortality after EVL. The overall recanalization (complete and partial) rate in the NWS therapy group was significantly higher than that in the control group (67.4% vs. 39.5%, P = 0.009). Low Child-Pugh score (P = 0.039, OR: 0.692, 95% CI 0.488-0.982), D-dimer < 2.00 ug/mL (P = 0.030, OR: 3.600, 95% CI 1.134-11.430), and NWS anticoagulation therapy (P = 0.002, OR: 4.189, 95% CI 1.660-10.568) were the predictors of PVT recanalization through univariate analysis of binary logistic regression. NWS anticoagulation therapy (P = 0.003, OR: 4.506, 95% CI 1.687-12.037) was the independent factor of recanalization through multivariate analysis. Nobody bled except for variceal rebleeding. Five-day failure and 14-day rebleeding were zero. There were no significantly different in 4-week (2.3% vs. 4.7%, P = 1.000), 6-week (4.7% vs. 9.3%, P = 0.672) and 6-month rebleeding (18.6% vs. 20.9%, P = 0.787) between the two groups. There was no mortality during six months follow-up. Low serum albumin (P = 0.011, OR: 0.844, 95% CI 0.741-0.962), high MELD score (P = 0.003, OR: 1.564, 95% CI 1.167-2.097) and Child-Pugh score (P = 0.006, OR: 1.950, 95% CI 1.206-3.155) were predictors of rebleeding by univariate analysis of binary logistic regression analysis. The Child-Pugh score (7 [6-8] vs. 6 [5-7], P = 0.003) and albumin levels (33.93 ± 5.30 vs. 37.28 ± 4.32, P = 0.002) were improved in the NWS therapy group at six months. In PVT patients with cirrhosis and AVB, starting NWS anticoagulation therapy early after EVL was safe and effective. It has the potential to raise albumin levels and improve liver function.

Predictors of early bleeding after endoscopic variceal ligation for esophageal varices: a systematic review and meta-analysis.

Aim of the study: Endoscopic variceal ligation (EVL) is important for emergency as well as prophylactic management of esophageal varices. Early bleeding after EVL is associated with significant morbidity and mortality. Assessing the likelihood of early post-EVL bleeding and its determinants can help deciding therapeutic strategies for high-risk patients. The aim of the present meta-analysis was to identify predictors of early bleeding after EVL. Material and methods: A comprehensive search of the literature was conducted from 2000 to November 2021 for studies evaluating the incidence, predictors and outcome of post-EVL bleeding. Pooled odds ratios (OR), mean difference (MD) and their 95% confidence intervals (CI) were calculated for prognostic variables. Results: A total of 16 studies with data on 13,378 patients were included in the meta-analysis. Among 34 parameters, 14 parameters were assessed for association with early bleeding after EVL. Lower hemoglobin at admission (MD = 1.11, 95% CI: -1.91 to -0.31), higher MELD score (MD = 2.00, 95% CI: 0.51-3.50), associated gastric varices (OR = 5.99, 95% CI: 1.06-33.90), higher number of bands (MD = 0.49, 95% CI: 0.02-0.97), and peptic esophagitis (OR = 11.38, 95% CI: 1.21-106.81) were significantly associated with increased risk of bleeding. However, there was significant heterogeneity among the studies with respect to all the analyzed parameters. Conclusions: Major predictors for early post-EVL bleeding in cirrhosis are admission hemoglobin level and MELD score, associated gastric varices, number of bands deployed during EVL, and peptic esophagitis on follow-up endoscopy. These risk factors may be useful for risk stratification after EVL in cirrhotics.

Ena/VASP proteins at the crossroads of actin nucleation pathways in dendritic cell migration.

As sentinels of our immune system dendritic cells (DCs) rely on efficient cell migration for patrolling peripheral tissues and delivering sampled antigens to secondary lymphoid organs for the activation of T-cells. Dynamic actin polymerization is key to their macropinocytic and migratory properties. Both major actin nucleation machineries, formins and the Arp2/3 complex, are critical for different aspects of DC functionality, by driving the generation of linear and branched actin filaments, respectively. However, the importance of a third group of actin nucleators, the Ena/VASP family, has not been addressed yet. Here, we show that the two family members Evl and VASP are expressed in murine DCs and that their loss negatively affects DC macropinocytosis, spreading, and migration. Our interactome analysis reveals Ena/VASP proteins to be ideally positioned for orchestrating the different actin nucleation pathways by binding to the formin mDia1 as well as to the WAVE regulatory complex, a stimulator of Arp2/3. In fact, Evl/VASP deficient murine DCs are more vulnerable to inhibition of Arp2/3 demonstrating that Ena/VASP proteins contribute to the robustness and efficiency of DC migration.

Ena/VASP Protein-Mediated Actin Polymerization Contributes to Naïve CD8+ T Cell Activation and Expansion by Promoting T Cell-APC Interactions In Vivo.

Naïve T cell activation in secondary lymphoid organs such as lymph nodes (LNs) occurs upon recognition of cognate antigen presented by antigen presenting cells (APCs). T cell activation requires cytoskeleton rearrangement and sustained interactions with APCs. Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) proteins are a family of cytoskeletal effector proteins responsible for actin polymerization and are frequently found at the leading edge of motile cells. Ena/VASP proteins have been implicated in motility and adhesion in various cell types, but their role in primary T cell interstitial motility and activation has not been explored. Our goal was to determine the contribution of Ena/VASP proteins to T cell-APC interactions, T cell activation, and T cell expansion in vivo. Our results showed that naïve T cells from Ena/VASP-deficient mice have a significant reduction in antigen-specific T cell accumulation following Listeria monocytogenes infection. The kinetics of T cell expansion impairment were further confirmed in Ena/VASP-deficient T cells stimulated via dendritic cell immunization. To investigate the cause of this T cell expansion defect, we analyzed T cell-APC interactions in vivo by two-photon microscopy and observed fewer Ena/VASP-deficient naïve T cells interacting with APCs in LNs during priming. We also determined that Ena/VASP-deficient T cells formed conjugates with significantly less actin polymerization at the T cell-APC synapse, and that these conjugates were less stable than their WT counterparts. Finally, we found that Ena/VASP-deficient T cells have less LFA-1 polarized to the T cell-APC synapse. Thus, we conclude that Ena/VASP proteins contribute to T cell actin remodeling during T cell-APC interactions, which promotes the initiation of stable T cell conjugates during APC scanning. Therefore, Ena/VASP proteins are required for efficient activation and expansion of T cells in vivo.

Variceal ligation in decompensated cirrhosis before esophageal endoscopic submucosal dissection.

Video 1This video details our case as well as our method for successfully eradicating varices immediately prior to esophageal endoscopic submucosal dissection to minimize risks of variceal hemorrhage.

Management of Refractory Variceal Bleed in Cirrhosis.

Acute variceal bleeding is the major cause of mortality in patients with cirrhosis. The standard medical and endoscopic treatment has reduced the mortality of variceal bleeding from 50% to 10-20%. The refractory variceal bleed is either because of failure to control the bleed or failure of secondary prophylaxis. The patients refractory to standard medical therapy need further interventions. The rescue therapies include balloon tamponade, self-expanding metal stents (SEMS) placement, shunt procedures, including transjugular intrahepatic portosystemic shunt (TIPS), balloon-occluded retrograde transvenous obliteration (BRTO), and endoscopic ultrasound (EUS) guided coiling. In cases where endoscopic variceal ligation (EVL) has failed and the variceal bleeding continues, temporary measures like balloon tamponade can be used to achieve hemostasis and as a bridge to definitive measures. SEMS being in use for refractory bleed is preferred over balloon tamponade due to the reduced complication rate. The shunting procedures are highly effective in reducing portal pressure and represent the gold standard for uncontrolled variceal bleeding. The surgical shunts, as well as nonshunt surgeries such as devascularization have become less popular with the increasing use of minimally invasive techniques like TIPS. TIPS have high success rates in controlling refractory variceal bleeding. The mortality rate is greater in high-risk patients undergoing salvage TIPS, and hence, pre-emptive TIPS should be considered in these patients. BRTO is an interventional radiologic procedure used in the management of bleeding gastric and ectopic varices. The availability of gastrorenal or splenorenal shunts is required for the BRTO procedure, which helps to reach and obliterate the cardiofundal varices through the femoral or jugular vein approach. The EUS guided coiling and glue injection have shown promising results, and further randomized controlled trials are required to establish their efficacy for refractory variceal bleeding.

Unconventional Shunts in Extrahepatic Portal Venous Obstruction-A Retrospective Review.

Background: Proximal splenorenal shunt (PSRS) is one of the most commonly performed portosystemic shunt (PSS) in extrahepatic portal venous obstruction (EHPVO) for portal decompression. Sometimes various anatomical and surgical factors related to the splenic vein and/or left renal vein may make the construction of a PSRS difficult or impossible. Unconventional shunts are required to tide over such conditions. Methods: From January 2008 to December 2018, 189 patients with EHPVO underwent PSS, of which, the 10 patients who underwent unconventional shunts form the study group of this paper. Results: The ten unconventional shunts included 8 proximal splenoadrenal shunts, one collateral-renal shunt, and one inferior mesenteric vein to inferior vena cava (IMV-Caval) shunt. The mean percentage drop in omental pressure was 34.2% post-shunt with a mean anastomotic diameter of 13.7 ± 3.1 mm. Three patients experienced some form of postoperative complication. With a mean follow-up period of 32.3 months (maximum of 111 months) all patients had patent shunts on follow-up Doppler. None of the patients had variceal bleed, or features of biliopathy and hepatic encephalopathy in follow-up. Conclusion: Unconventional shunts can be used safely and effectively with good postoperative outcomes in EHPVO.

Presence of Ascites at Presentation is Associated With Absence of Long-Term Response Amongst Patients With Budd-Chiari Syndrome When Treated With Medical Therapy Alone: A Single Centre Real-Life Experience.

Background: There is lack of data on long-term outcomes of patients with Budd-Chairi Syndrome (BCS) treated with medical therapy including anticoagulation alone. Methods: Consecutive patients (N = 138, mean [standard deviation, SD] age 29.3 [12.9] years; 66 men) with BCS, treated with medical therapy alone including anticoagulation, with minimum follow-up of 12 months were included. Initial response was classified as complete (CR), partial (PR) or nonresponse (NR) and on follow-up as loss of response (LoR) or maintenance of response (MoR). The association of baseline, clinical and biochemical parameters with different responses was evaluated. Results: Seventy-six patients (55.1%) had CR, 26 (18.8%) had PR and 36 (26.1%) had NR. None with PR or NR had CR later. At a median follow-up of 40 (range 12-174) months, LoR was more common in PR group than in CR group (12 [46.2%] vs 18 [23.7%], P = 0.03). LoR was associated with presence of ascites (odds ratio [OR] 1.5; 95% confidence interval [CI] 0.06-0.71), gastrointestinal bleed (OR 1.33; 95% CI 0.09-0.82) or jaundice (OR 1.01; 95% CI 0.11-0.97) at baseline and duration of follow-up (OR 0.018; 95% CI 1.006-1.030). Mortality was higher in NR (28 [77.8%]) compared with CR (15 [19.7%], P = 0.001) and PR (8 [30.8%], P = 0.001). On binary logistic regression analysis, presence of ascites at baseline was associated with LoR (OR 0.303 [0.098-0.931]). Conclusion: Patients with initial CR have better survival than nonresponders. One-third had LoR on follow-up. The presence of ascites at baseline is associated with LoR.

Prevalence, Predictors, and Outcomes of Esophageal Candidiasis in Cirrhosis: An Observational Study With Systematic Review and Meta-Analysis (CANDID-VIEW).

BACKGROUND: Gastrointestinal candidiasis is often neglected and potentially serious infection in cirrhosis patients. Therefore, we evaluated the prevalence, risk factors, and outcomes of esophageal candidiasis (EC) in cirrhotics and did a systematic review to summarize EC's available evidence in cirrhosis. METHODS: Consecutive patients with cirrhosis posted for esophagogastroduodenoscopy (EGD) at a tertiary care institute were screened for EC (cases) between January 2019 and March 2020. EC was diagnosed on EGD findings and/or brush cytology. Controls (without EC) were recruited randomly, and EC's risk factors and outcomes were compared between cases and controls.Four electronic databases were searched for studies describing EC in cirrhosis. Prevalence estimates of EC were pooled on random-effects meta-analysis, and heterogeneity was assessed by I2. A checklist for prevalence studies was used to evaluate the risk of bias in studies. RESULTS: EC was diagnosed in 100 of 2762 patients with cirrhosis (3.6%). Patients with EC had a higher model for end-stage liver disease (MELD) (12.4 vs. 11.2; P = 0.007), acute-on-chronic liver failure (ACLF) (26% vs. 10%; P = 0.003) and concomitant bacterial infections (24% vs. 7%; P = 0.001), as compared with controls. A multivariable model, including recent alcohol binge, hepatocellular carcinoma (HCC), upper gastrointestinal (UGI) bleed, ACLF, diabetes, and MELD, predicted EC's development in cirrhosis with excellent discrimination (C-index: 0.918). Six percent of cases developed the invasive disease and worsened with multiorgan failures, and four patients with EC died on follow-up.Of 236 articles identified, EC's pooled prevalence from 8 studies (all with low-risk of bias) was 2.1% (95% CI: 0.8-5.8). Risk factors and outcomes of EC in cirrhosis were not reported in the literature. CONCLUSIONS: EC is not a rare infection in cirrhosis patients, and it may predispose to invasive candidiasis and untimely deaths. Alcohol binge, HCC, UGI bleed, ACLF, diabetes, and higher MELD are the independent predictors of EC in cirrhosis. At-risk patients with cirrhosis or those with deglutition symptoms should be rapidly screened and treated for EC.

Maternal and neonatal outcomes in extra hepatic portal vein obstruction: Our experience.

BACKGROUND: Women with Extra hepatic portal vein obstruction (EHPVO) are mostly young and belong to Asian countries. In the Indian subcontinent, 20-30% variceal bleeds are caused by EHPVO. Hence pregnancy is a concern in such patients. The objective of this study is to observe the maternal and neonatal outcomes in women with EHPVO. MATERIALS AND METHOD: Extra hepatic portal vein obstruction was studied retrospectively in 28 pregnancies in 20 women from Jan 2011 to July 2018 at a tertiary hospital in South India and the pregnancy outcomes were observed during this period. Institutional Review Board approval obtained. RESULTS: The mean age of the women was 24.3 years and the mean age of diagnosis was 18.5 years. Splenomegaly, thrombocytopenia and anaemia were seen in 22 (78.5%), 17 (60.7%) and 8 (28.5%) of pregnancies, respectively. Rate of abortions and preterm deliveries were 2 (7.1%, n =28) and 10 (35.7%, n =28). There was one stillbirth (3.6%) in the study group. EHPVO was diagnosed in 25 (89.3%) women prenatally in our series. During pregnancy only one woman had variceal bleed, which was managed conservatively. Blood and blood product transfusion was required in 7(25%) of women and there was no maternal mortality. CONCLUSION: Pregnancies in EHPVO have good maternal and neonatal outcomes, provided they are taken care of by a multidisciplinary approach in a tertiary care centre.