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Serotonin (5-hydroxytryptamine (5-HT)) is one of the important neurotransmitters which is released from the endocrine system. An abnormal level of this biomarker leads to several neurological diseases. The accurate assessment of serotonin is the utmost option to start treatment in the early stages of the disease. The current work is focused on the development of a disposable, screen-printed electrochemical sensor for the depression biomarker, serotonin in the physiological pH medium (pH 7.4) with the aid of a hexagonal, Ni(OH)2-nanoplate (NH-HNP)-embedded chitosan (Chit) and modified, screen-printed carbon electrode (SPCE). Initially, hexagonal nanoplates of Ni(OH)2 were synthesized by an eco-friendly and simple hydrothermal method. The prepared materials were well characterized by advanced analytical techniques to examine the physicochemical properties of the synthesized Ni(OH)2 hexagonal nanoplates. From the cyclic voltametric (CV) analysis, it was found that the oxidative current response of 5-HT at a NH-HNP-modified SPCE has about fivefold higher current values than over bare SPCE. The scan rate studies of NH-HNP-Chit/SPCE electrodes revealed that the oxidation mechanism of 5-HT is controlled by the diffusion behavior of the analyte. Differential pulse voltammetric tests of the NH-HNP-Chit/SPCE electrode exhibited a linear response in the dynamic concentration range of 0.1 to 30 µM, with a detection limit of about 60 nM. The sensor response is very reproducible from electrode to electrode, and the deactivation or surface-fouling of the sensor was not observed within the several experimental measurements. The sensor exhibited excellent storage stability over a period of twenty days. Finally, the fabricated, disposable SPCE sensor has shown respectable activity for the detection of depression biomarker 5-HT from synthetic urine and saliva samples.

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies., (© 2025. The Author(s).)

Background and Aims: Acute liver failure (ALF) is a medical emergency and liver transplantation (LT) may be required as definitive therapy. The etiology varies across geographical locations and is mostly viral dominant in India. We aimed at evaluating the spectrum, impact of interventions (plasma exchange [PLEx], continuous renal replacement therapy [CRRT]) and outcomes of ALF in India in recent times., Methods: A multicentre retrospective study across four major tertiary care centres., Results: As many as 183 ALF patients (median age, 23 years; females, 43.1%; model for end-stage liver disease [MELD], 32.7) from January 2021 to December 2023 were included. Nineteen per cent had infection and 40.4% of patients satisfied King's College criteria (KCC) at admission. Most common cause for ALF was hepatitis A virus (HAV) (44.2%) followed by rodenticide poisoning (10.3%). Approximately 35% of patients each received either PLEx or CRRT. The 7, 14 and 21-day transplant-free survival probability was 65.5%, 60.1%, and 57.3%, respectively. Only 3.8% of patients underwent liver transplantation. On multivariable Cox regression analysis, hemoglobin (HR, 0.74 [0.63-0.87]), lactate (HR, 1.14 [1.03-1.26]), advanced hepatic encephalopathy (HE) (HR, 4.87 [1.89-12.5]) and fulfilling KCC [HR, 10.04 [4.57-22.06]) at admission were the independent predictors of mortality. A model including KCC + lactate + HE ≥ 3 with or without hemoglobin had an AUROC of 0.81-0.84 to predict mortality. In those who underwent PLEx, advanced HE (HR, 4.13 [1.75-9.7]), procalcitonin (HR, 1.18 [1.07-1.30]) and KCC (HR, 4.6 [1.6-13.1), while for those who received CRRT, lactate (HR, 1.37 [1.22-1.54]) and KCC (HR, 6.4 [2.5-15.8]) independently predicted mortality., Conclusions: Hepatitis A virus is currently the most common cause for ALF in India, emphasizing the need for universal vaccination programmes. Spontaneous survival in tertiary care centres is 57%. LT rates were low., Competing Interests: Declarations. Conflict of interest: AR, KK, MP, AS, AG, MS, MA, SI, SV, UCG, MG, PNR, VAS, NDR AVK and RKR declare no competing interests. Ethics statement: The study was performed conforming to the Helsinki Declaration of 1975, as revised in 2000 and 2008 concerning human and animal rights, and the authors followed the policy concerning informed consent as shown on Springer.com. Ethics approval and consent to participate: Not applicable. Consent for publication: Yes. Human ethics: Not violated. Disclaimer: The authors are solely responsible for the data and the contents of the paper. In no way, the Honorary Editor-in-Chief, Editorial Board Members, the Indian Society of Gastroenterology or the printer/publishers are responsible for the results/findings and content of this article., (© 2024. Indian Society of Gastroenterology.)

Background and Aims: Severity scores, including the model for end-stage liver disease (MELD) and discriminant function score, guide the treatment of patients with severe alcohol-associated hepatitis (AH). We aimed to investigate the impact of functional status on outcomes of patients with AH., Methods: Medically managed patients (n = 133) with AH from 1 January 2019 to 31 December 2022 were included in this prospective study. The objectives were to compare the long-term survival, recompensation rates, corticosteroid response, incidence of infections, hepatic encephalopathy (HE) and acute kidney injury (AKI) among propensity score-matched patients with good Karnofsky performance status (KPS) (score ≥50) and poor KPS (score <50) using Kaplan-Meier analysis., Results: Twenty-five patients with good KPS were matched with 25 patients with poor KPS and followed up for a median duration of 10 (0.5-33) months. Survival was 76% (19/25; 95% confidence interval (CI), 54.9-90.6) in patients with good KPS compared to 42.3% (11/25; 95% CI, 23.4-63.1) patients with poor KPS (P = 0.001) at 10 months. The recompensation rate was higher in the good KPS group than in the poor KPS group (68% vs 44%; P = 0.04). A higher proportion of patients in the good KPS group (78.9%) than in the poor KPS group (42.8%; P = 0.03) responded to corticosteroids. Survival was lower among non-responders in the poor KPS group (0% vs 75%; P = 0.01). The proportion of patients who developed infection (36% vs 28%; P = 0.051), HE (36% vs 12%; P = 0.01) and AKI (60% vs 16%; P < 0.001) was higher in patients with poor KPS than in good KPS., Conclusions: KPS is an important determinant of outcomes in patients with AH, including survival, recompensation, response to corticosteroids and complications., (© 2024 Royal Australasian College of Physicians.)

Competing Interests: The authors have no conflicts of interest to declare.

Aim and Background: A combination of terlipressin and albumin is the standard of care for patients with hepatorenal syndrome-acute kidney injury (HRS-AKI). The study aimed to compare the venous congestion using lung ultrasound score (LUS) and radiographic assessment of lung edema (RALE) scores among terlipressin responders and nonresponders and survivors and non-survivors., Materials and Methods: In this single-center, prospective, observational study, we included adult patients with HRS-AKI who had received terlipressin and albumin from 28th April 2022 to 16th October 2022., Results: Of the 102 patients included, 74.5% (95%CI: 58.7-93.2) responded to terlipressin. The median dose of terlipressin and albumin was 2 (1-8) mg/day and 100 (40-200) g for a duration of 5 (2-10) days. On Kaplan-Meier analysis, survival was 26.9% of patients in the nonresponder group compared to 61.4% in the responder group ( p = 0.001). Day 3 LUS score worsened in 76.9% of patients in nonresponders group compared to 52.6% in responder group ( p = 0.03). There was a significant increase in RALE score in those who died [6 (-6-48) vs alive: 0 (-4- 30); p < 0.001]. Lung ultrasound score had improved or been maintained in 63.6% of patients who were alive, compared to 14.9% in those who had died ( p < 0.001). On multivariable Cox regression analysis, age [HR, 1.02 (1.002-1.05)], terlipressin non-response [HR, 2.8 (1.47-5.34)], APACHE score [HR, 1.07 (1.03-1.12)], duration of terlipressin therapy [HR, 0.37 (0.27-0.5)] and worsening of LUS [HR, 2.9 (1.81-7)] predicted mortality., Conclusion: Lung ultrasound score and chest X-ray can accurately identify venous congestion in the lungs, which is common in patients with advanced liver disease who receive terlipressin and albumin in the intensive care unit (ICU)., How to Cite This Article: Amara V, Kulkarni AV, Gupta A, Venishetty S, Sripathi SR, Reddy LSK, et al. Point-of-care Ultrasonography in Patients with Hepatorenal Syndrome: A Single Center Observational Study. Indian J Crit Care Med 2024;28(11):1015-1022., Competing Interests: Source of support: Nil Conflict of interest: NoneConflict of interest: None, (Copyright © 2024; The Author(s).)

Backgrounds/aims: Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezo-bev remains unknown., Methods: In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging., Results: Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age, 58.5 years; women, 17%; Barcelona Clinic Liver Cancer stage system B/C, 5/7) had received 3-12 cycles of atezo- bev, and four of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 days (range, 54-114) following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 months (range, 4-30), none of the alive patients developed HCC recurrence or graft rejection., Conclusions: Surgical therapy, including LT, is possible after atezo-bev therapy in well-selected patients after downstaging.

Background and Aims: Patients with Child-Turcotte-Pugh class B and C cirrhosis with upper gastrointestinal bleeding (UGIB) have systemic as well as localized (in the mucosa of the esophagus and stomach) fibrinolysis. The aim of this study was to evaluate the efficacy and safety of tranexamic acid in the treatment of acute UGIB in patients with cirrhosis., Approach and Results: A total of 600 patients with advanced liver cirrhosis (Child-Turcotte-Pugh class B or C) presenting with UGIB were randomly allocated to either the tranexamic acid (n=300) or the placebo group (n=300). The primary outcome measure was the proportion of patients developing 5-day treatment failure. Failure to control bleeding by day 5 was seen in 19/300 (6.3%) patients in the tranexamic acid group and 40/300 (13.3%) patients in the placebo group ( p =0.006). Esophageal endoscopic variceal ligation (EVL) site as a source of failure to control bleeding by day 5 among patients undergoing first-time esophageal EVL (excluding patients with a previous post-EVL ulcer as a source of bleed) was seen in 11/222 (4.9%) patients in the tranexamic acid group and 27/225 (1212.0%) patients in the placebo group ( p =0.005). However, 5-day and 6-week mortality was similar in the tranexamic acid and placebo groups., Conclusions: Tranexamic acid significantly reduces the failure to control bleeding by day 5 and failure to prevent rebleeding after day 5 to 6 weeks in patients with advanced liver cirrhosis (Child-Turcotte-Pugh class B or C) presenting with UGIB, by preventing bleeding from the EVL site., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background/aims: Acute liver failure (ALF) is associated with fatal outcomes without liver transplantation. Two randomized studies reported standard volume (SV) and high volume (HV) plasma exchange (PLEX) as effective therapeutic modalities for patients with ALF. However, no studies have compared the safety and efficacy of SV with HV PLEX, which we aimed to assess., Methods: This retrospective study included patients with ALF admitted between March 2021 and March 2023 who underwent PLEX. All patients underwent HV PLEX until May 2022, and then thereafter, SV PLEX was performed. The objectives of the study were to compare transplant-free survival (TFS) at 30 days, efficacy in reducing severity scores, biochemical variables, and adverse events between SV (total plasma volume x 1) and HV (total plasma volume x 1.5-2) PLEX., Results: Forty two ALF patients (median age: 23.5 years; females: 57.1%; MELD Na: 34.67 ± 6.07; SOFA score- 5.24 ± 1.42) underwent PLEX. Of these, 22 patients underwent SV-PLEX, and 20 underwent HV-PLEX. The mean age, sex, etiology distribution, and severity scores were similar between the groups. The median number of PLEX sessions (2) was similar in both groups. On Kaplan-Meier analysis, TFS was 45.5% in SV group and 45% in HV group ( P  = 0.76). A comparable decline in total bilirubin, PT/INR, ammonia, and MELD Na scores was noted in both groups. The cumulative number of adverse events was similar between the HV group (77.3%) and SV group (54.5%; P  = 0.12)., Conclusions: SV PLEX is safe and as effective as HV PLEX in patients with ALF. Further randomized controlled trials with a larger sample size are needed to validate these findings., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: Critically ill patients with cirrhosis admitted to the intensive care unit (ICU) are usually on broad-spectrum antibiotics because of suspected infection or as a hospital protocol. It is unclear if additional rifaximin has any synergistic effect with broad-spectrum antibiotics in ICU patients with acute overt hepatic encephalopathy (HE)., Methods: In this double-blind trial, patients with overt HE admitted to ICU were randomized to receive antibiotics (ab) alone or antibiotics with rifaximin (ab + r). Resolution (or 2 grade reduction) of HE, time to resolution of HE, in-hospital mortality, nosocomial infection, and changes in endotoxin levels were compared between the 2 groups. A subgroup analysis of patients with decompensated cirrhosis and acute-on-chronic liver failure was performed., Results: Baseline characteristics and severity scores were similar among both groups (92 in each group). Carbapenems and cephalosporin with beta-lactamase inhibitors were the most commonly used ab. On Kaplan-Meier analysis, 44.6% (41/92; 95% confidence interval [CI], 32-70.5) in ab-only arm and 46.7% (43/92; 95% CI, 33.8-63) in ab + r arm achieved the primary objective ( P = 0.84).Time to achieve the primary objective (3.65 ± 1.82 days and 4.11 ± 2.01 days; P = 0.27) and in-hospital mortality were similar among both groups (62% vs 50%; P = 0.13). Seven percent and 13% in the ab and ab + r groups developed nosocomial infections ( P = 0.21). Endotoxin levels were unaffected by rifaximin. Rifaximin led to lower in-hospital mortality (hazard ratio: 0.39 [95% CI, 0.2-0.76]) in patients with decompensated cirrhosis but not in patients with acute-on-chronic liver failure (hazard ratio: 0.99 [95% CI, 0.6-1.63]) because of reduced nosocomial infections., Discussion: Reversal of overt HE in those on ab was comparable with those on ab + r., (Copyright © 2023 by The American College of Gastroenterology.)

Background and Aims: Twenty per cent albumin (1.5 g/kg at diagnosis and 1 g/kg on day three, infused over six-hour duration) is recommended particularly in high-risk spontaneous bacterial peritonitis (SBP). Whether reduced dose albumin infusion is as effective as the standard dose albumin infusion is not clear. The aim of this study was to compare standard dose albumin infusion with reduced dose albumin infusion in acute kidney injury (AKI) development or progression in patients with cirrhosis and high-risk SBP., Methods: Sixty-three patients were randomized to the standard dose albumin arm (n = 31) and reduced dose albumin arm (n = 32, 0.75 g/kg at diagnosis and 0.5 g/kg 48 h later). The albumin was infused over six-hour duration in both groups. When the patient developed respiratory distress, the albumin infusion was stopped and that dose (i.e. of day one or day three) was not restarted and no attempt was made to finish the whole dose of that day. However, the next dose was started at the pre-calculated infusion rate if there was no evidence of respiratory distress at the start of next infusion., Results: All 31 patients in standard dose and two (6.25%) in the reduced dose group developed symptomatic circulatory overload (p < 0.001), with infusions being stopped prematurely. The actual albumin dose received on day one was similar in both groups and only slightly higher in the standard dose group on day three. Resolution of SBP, progression of AKI to higher stage, in-hospital mortality and 28 days' mortality were similar in both groups., Conclusions: For treatment of SBP, standard dose albumin infusion (1.5 g/kg at diagnosis and 1 g/kg 48 hours later) infused over six hours is not tolerated by Indian patients. The effectiveness of standard dose albumin infused over more prolonged periods, as compared to reduced dose albumin, should be evaluated in further studies., Trial Registration: Clinical Trials.gov Identifier: NCT04273373 ., (© 2023. Indian Society of Gastroenterology.)

Background and Aim: Risk stratification beyond the endoscopic classification of esophageal varices (EVs) to predict first episode of variceal bleeding (VB) is currently limited in patients with compensated advanced chronic liver disease (cACLD). We aimed to assess if machine learning (ML) could be used for predicting future VB more accurately., Methods: In this retrospective analysis, data from patients of cACLD with EVs, laboratory parameters and liver stiffness measurement (LSM) were used to generate an extreme-gradient boosting (XGBoost) algorithm to predict the risk of VB. The performance characteristics of ML and endoscopic classification were compared in internal and external validation cohorts. Bleeding rates were estimated in subgroups identified upon risk stratification with combination of model and endoscopic classification., Results: Eight hundred twenty-eight patients of cACLD with EVs, predominantly related to non-alcoholic fatty liver disease (28.6%), alcohol (23.7%) and hepatitis B (23.1%) were included, with 455 (55%) having the high-risk varices. Over a median follow-up of 24 (12-43) months, 163 patients developed VB. The accuracy of machine learning (ML) based model to predict future VB was 98.7 (97.4-99.5)%, 93.7 (88.8-97.2)%, and 85.7 (82.1-90.5)% in derivation (n = 497), internal validation (n = 149), and external validation (n = 182) cohorts, respectively, which was better than endoscopic classification [58.9 (55.5-62.3)%] alone. Patients stratified high risk on both endoscopy and model had 1-year and 3-year bleeding rates of 31-43% and 64-85%, respectively, whereas those stratified as low risk on both had 1-year and 3-year bleeding rates of 0-1.6% and 0-3.4%, respectively. Endoscopic classification and LSM were the major determinants of model's performance., Conclusion: Application of ML model improved the performance of endoscopic stratification to predict VB in patients with cACLD with EVs., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The severe acute respiratory syndrome corona virus-2 (referred to as SARS CoV2) pandemic had a great impact on public life in general as well as on populations with pre-existing disease and co-morbidities. Liver transplant and immunosuppressant medication predisposes to more severe disease and is often associated with poor outcome. The clinical features, disease course, treatment and process of modulating the immunosuppression is challenging. Here, we describe the clinical presentation, treatment and outcomes in six liver transplant recipients. Out of those six patients, three had mild, one had moderate and one had severe COVID-19, and one was asymptomatic. The immunosuppression minimization or withdrawal was done based upon the clinical severity. Consideration of tocilizumab and/o convalescent plasma as well as antivirals i.e. remdesvir done in severe cases. The routine practice of prophylactic anticoagulation, consideration of repurposed drugs (i.e. teicoplanin and doxycycline), and watchful monitoring of asymptomatic recipients helped to achieve an uneventful recovery., Competing Interests: The authors have no conflict of interests related to this publication., (© 2020 Authors.)

Aims: The aim of this study was to correlate serum uric acid (SUA) levels and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (DM)., Settings and Design: This study was a cross-sectional observational study on 103 diabetic patients conducted from September 2015 to May 2017., Subjects and Methods: We screened 103 patients with type 2 DM between the ages of 30-65 years. SUA levels and the CIMT were measured. The patients were divided into quartiles based on uric acid level. The CIMT of the quartiles is compared and analyzed., Statistical Analysis Used: Chi-squared test, Analysis of Variance, and Pearson's correlation., Results: Uric acid levels were positively associated with CIMT ( P = 0.001). The association remained significant after further adjustment for potential confounders. Strong correlation was found among them as depicted by correlation coefficient (r = 0.779)., Conclusions: Carotid atherosclerosis as measured by IMT is associated with SUA levels in patients with type 2 DM., Competing Interests: There are no conflicts of interest.

Infective endocarditis by Methicillin Resistant Staphylococcus aureus (MRSA) bacteraemia is a common association and carries a high mortality. However, rising Minimum Inhibitory Concentrations (MICs) for vancomycin amongst MRSA strains is an emerging threat which carries poor prognosis and higher mortality. Here, we report a case of 41-year-old young non-addict gentleman presenting with fever of 3 days duration following recovery from an acute kidney injury necessitating haemodialysis. Systemic examination revealed signs of mitral regurgitation and left sided cerebellar signs. Laboratory investigations revealed anaemia, MRSA bacteraemia and transthoracic echocardiogram showed a mitral valve vegetation. He was diagnosed with MRSA mitral valve endocarditis with acute left cerebellar infarct. He was initially treated with intravenous vancomycin based on MIC at the dose of one gram every twelfth hourly. As the MRSA strain was shown to demonstrate a vancomycin creep phenomemon along with worsening clinical condition of the patient, treatment was changed to intravenous daptomycin at dose of 9mg/kg as per blood culture and sensitivity pattern which was administered for 6 weeks. Following initiation of daptomycin patient became afebrile and vegetations reduced in size and finally disappeared.