Deciphering the Substrate Specificity Reveals that CRISPR-Cas12a Is a Bifunctional Enzyme with Both Endo- and Exonuclease Activities.

The class 2 CRISPR-Cas9 and CRISPR-Cas12a systems, originally described as adaptive immune systems of bacteria and archaea, have emerged as versatile tools for genome-editing, with applications in biotechnology and medicine. However, significantly less is known about their substrate specificity, but such knowledge may provide instructive insights into their off-target cleavage and previously unrecognized mechanism of action. Here, we document that the Acidaminococcus sp. Cas12a (AsCas12a) binds preferentially, and independently of crRNA, to a suite of branched DNA structures, such as the Holliday junction (HJ), replication fork and D-loops, compared with single- or double-stranded DNA, and promotes their degradation. Further, our study revealed that AsCas12a binds to the HJ, specifically at the crossover region, protects it from DNase I cleavage and renders a pair of thymine residues in the HJ homologous core hypersensitive to KMnO4 oxidation, suggesting DNA melting and/or distortion. Notably, these structural changes enabled AsCas12a to resolve HJ into nonligatable intermediates, and subsequently their complete degradation. We further demonstrate that crRNA impedes HJ cleavage by AsCas12a, and that of Lachnospiraceae bacterium Cas12a, without affecting their DNA-binding ability. We identified a separation-of-function variant, which uncouples DNA-binding and DNA cleavage activities of AsCas12a. Importantly, we found robust evidence that AsCas12a endonuclease also has 3'-to-5' and 5'-to-3' exonuclease activity, and that these two activities synergistically promote degradation of DNA, yielding di- and mononucleotides. Collectively, this study significantly advances knowledge about the substrate specificity of AsCas12a and provides important insights into the degradation of different types of DNA substrates.

Randomized, Double-Blind, Placebo-Controlled, Clinical Study of Passiflora incarnata in Participants With Stress and Sleep Problems.

Background and objectives SIVI is a standardized extract prepared using the aerial parts of Passiflora incarnata developed to enhance the quality of sleep. ​​​​​​The objective of the present study was to the evaluate efficacy and safety of SIVI (Passiflora incarnata extract) in the management of stress and sleep problems in Indian participants in a randomized, double-blind, placebo-controlled, clinical study. Materials and methods A total of 65 participants with stress and insomnia were randomized to two groups with 32 in the SIVI (Passiflora incarnata extract) group and 33 in the placebo group. Subjects were asked to take the test substance along with water at bedtime for 30 days. The Perceived Stress Scale, quality of life using the General Health Questionnaire (GHQ-12) scale, and Insomnia Severity Index were assessed on day 1, day 15, and day 30. Results Passiflora incarnata extract showed a statistically significant reduction in the mean score of stress on the Perceived Stress Scale and significantly increased the mean score of total sleep time compared to placebo. The general psychological health was found to be significantly improved in the SIVI (Passiflora incarnata extract) group compared to the placebo group on day 15 and day 30. SIVI (Passiflora incarnata extract) did not show any adverse effects. Conclusions The results of the current study indicate that Passiflora incarnata extract is beneficial in the management of stress and helps to improve sleep quality in subjects with stress and insomnia.

Centre-level variation in the survival of patients receiving haemodialysis in India: findings from a nationwide private haemodialysis network.

Background: There are no large studies examining survival in patients receiving haemodialysis in India or considering centre-level effects on survival. We measured survival variation between dialysis centres across India and evaluated the extent to which differences are explained by measured centre characteristics. Methods: This is a multilevel analysis of patient survival in centres of the NephroPlus dialysis network consisting of 193 centres across India. Patients receiving haemodialysis at a centre for ≥90 days between April 2014 and June 2019 were included, with analyses restricted to centres with ≥10 such patients. The primary outcome was all-cause mortality, measured from 90 days after joining a centre. Proportional hazards models with shared frailty were used to model centre- and patient-level effects on survival. Findings: Amongst 23,601 patients (median age 53 years; 29% female), the unadjusted centre-specific 180-day Kaplan-Meier survival estimates ranged between 55% (95% confidence interval [CI] 38-80%) and 100%, with a median of 88% (interquartile interval 83%-92%). After accounting for multilevel factors, estimated 180-day survival ranged between 83% (73-89%) and 97% (95-98%), with 90% 180-day survival in the average centre. The mortality rate in patients attending rural centres was 32% (Hazard Ratio 1.32; 95% CI 1.06-1.65) higher than those at urban centres in adjusted analyses. Multiple patient characteristics were associated with mortality. Interpretation: This is the first national benchmark for survival amongst dialysis patients in India. Centre- and patient-level characteristics are associated with survival but there remains unexplained variation between centres. As India continues to widen dialysis access, ongoing quality improvement programs will be an important part of ensuring that patients experience the best possible outcomes at the point of care. Funding: This project received no external funding.

Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome.

BACKGROUND: There is scant literature on hepatocellular carcinoma (HCC) in patients with Budd-Chiari syndrome (BCS). AIM: To assess the magnitude, clinical characteristics, feasibility, and outcomes of treatment in BCS-HCC. METHODS: A total of 904 BCS patients from New Delhi, India and 1140 from Mumbai, India were included. The prevalence and incidence of HCC were determined, and among patients with BCS-HCC, the viability and outcomes of interventional therapy were evaluated. RESULTS: In the New Delhi cohort of 35 BCS-HCC patients, 18 had HCC at index presentation (prevalence 1.99%), and 17 developed HCC over a follow-up of 4601 person-years, [incidence 0.36 (0.22-0.57) per 100 person-years]. BCS-HCC patients were older when compared to patients with BCS alone (P = 0.001) and had a higher proportion of inferior vena cava block, cirrhosis, and long-segment vascular obstruction. The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up (13029 ng/mL vs 500 ng/mL, P = 0.01). Of the 35 BCS-HCC, 26 (74.3%) underwent radiological interventions for BCS, and 22 (62.8%) patients underwent treatment for HCC [transarterial chemoembolization in 18 (81.8%), oral tyrosine kinase inhibitor in 3 (13.6%), and transarterial radioembolization in 1 (4.5%)]. The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo (P = 0.0001). In contrast to the New Delhi cohort, the Mumbai cohort of BCS-HCC patients were predominantly males, presented with a more advanced HCC [Barcelona Clinic Liver Cancer C and D], and 2 patients underwent liver transplantation. CONCLUSION: HCC is not uncommon in patients with BCS. Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.

Paving the way to environment-friendly greener anesthesia.

Health-care settings have an important responsibility toward environmental health and safety. The operating room is a major source of environmental pollution within a hospital. Inhalational agents and nitrous oxide are the commonly used gases during general anesthesia for surgeries, especially in the developing world. These greenhouse gases contribute adversely to the environmental health both inside the operating room and in the outside atmosphere. Impact of these anesthetic agents depends on the total consumption, characteristics of individual agents, and gas flows, with higher levels increasing the environmental adverse effects. The inimical impact of nitrous oxide is higher due to its longer atmospheric half-life and potential for destruction of the ozone layer. Anesthesiologist of today has a choice in the selection of anesthetic agents. Prudent decisions will help in mitigating environmental pollution and contributing positively to a greener planet. Therefore, a shift from inhalational to intravenous-based technique will reduce the carbon footprint of anesthetic agents and their impact on global climate. Propofol forms the mainstay of intravenous anesthesia technique and is a proven drug for anesthetic induction and maintenance. Anesthesiologists should appreciate growing concerns about the role of inhalational anesthetics on the environment and join the cause of environmental responsibility. In this narrative review, we revisit the pharmacological and pharmacokinetic considerations, clinical uses, and discuss the merits of propofol-based intravenous anesthesia over inhalational anesthesia in terms of environmental effects. Increased awareness about the environmental impact and adoption of newer, versatile, and user-friendly modalities of intravenous anesthesia administration will pave the way for greener anesthesia practice.

Comparative Evaluation of Three Different Techniques of Radial Artery Cannulation: A Prospective Randomised Study.

OBJECTIVE: We planned this study to compare three approaches to arterial cannulation, i.e., catheter over the needle, catheter over the guidewire, and ultrasound-guided cannulation, in terms of overall success rate, first pass success rate, time for cannulation and incidence of complications. METHODS: After obtaining informed written consent from the patient, they were randomized into three groups, based on chits in the box technique, to undergo radial artery cannulation as follows: group N (using catheter over needle technique), group W (using catheter over guidewire technique), group U (radial artery cannulations under ultrasound guidance). We calculated a sample size of 50 patients in each group based on the primary endpoint of the overall success rate. The data was analyzed using one-way ANOVA and post hoc Tukey's test. RESULTS: There was a non-statistically significant trend towards a higher overall success rate in groups W and U compared to group N (47 and 46, respectively, compared to 43, p-value 0.35). Similarly, no significant differences were observed concerning any of the characteristics of radial artery cannulation, except the first pass success rate, where the success rate was highest in group W (33, 70.21%), followed by group U (34, 68%) with a p-value of 0.04. CONCLUSION: Though catheter over guidewire and ultrasound-based techniques offer advantages in terms of higher first-pass success rate, they do not significantly increase the overall success rate or reduce the total incidence of complications.

Infections and Their Outcomes in Cancer Patients With and Without Neutropenia: A Single-Center Experience.

Background Patients with cancer are at a high risk of developing infections due to immunosuppression resulting from cancer treatment. Infections may occur both during neutropenic and non-neutropenic episodes and negatively impact outcomes both in terms of hospital stay and mortality. In this study, we aimed to determine the infection types, microbiological picture of infections, their outcomes, and associated factors in cancer patients during neutropenic and non-neutropenic episodes. Methods This is a retrospective cross-sectional study conducted at the Department of Medical Oncology, Geetanjali Medical College & Hospital, a tertiary care hospital in northern India. A total of 82 cancer patients with infections between August 2021 and July 2022 were included in this study. Results A total of 82 patients had 96 episodes of infections. Out of 82 patients, 24 (29.3%) had hematological malignancies, and 58 (70.7%) had solid malignancies. The majority of episodes (n = 60; 62.5%) were seen in patients with solid malignancies, and the rest (n = 36; 37.5%) of them were seen in patients with hematological malignancies. Among all the episodes of infection, 28 (29.2%) were encountered during neutropenic episodes, while the rest (n = 68; 70.8%) of the incidences were encountered during non-neutropenic episodes. Out of 28 neutropenic episodes of infection, the majority (n = 23; 82.1%) occurred in patients with hematological malignancies. An absolute neutrophil count (ANC) of <500 cells/mm3 (severe neutropenia) was present in 26 (92.8%) patients in the neutropenic group. There was no major difference in causative microbiology among both groups. Gram-negative organisms were the predominant pathogens in both groups. Escherichia coli was the most commonly isolated, followed by Klebsiella pneumoniae and Candida spp. The mortality rate was 12.5%, with a significantly higher mortality in the neutropenic group (odds ratio (OR) 3.4, 95% confidence interval (CI) 1.178-9.813; p = 0.042). Neutropenic patients also had a longer median length of stay (LOS, 10 days) as compared to non-neutropenic patients (seven days). Conclusion This study revealed a high frequency of neutropenia in patients with hematological malignancies. Gram-negative pathogens were the major causative organisms of infection in both patient groups. E. coli infection rates were high in both groups. Neutropenic patients had significantly higher mortality rates and a longer LOS compared to non neutropenic patients.

Validation of no-biopsy pathway for the diagnosis of celiac disease in Asian adults: a multicenter retrospective study.

BACKGROUND AND AIM: While European Society of Pediatric Gastroenterology Hepatology and Nutrition advocates a no-biopsy pathway for the diagnosis of celiac disease (CeD) in children if IgA anti-tissue transglutaminase antibody (anti-tTG ab) titer is ≥10-fold upper limit of normal (ULN) and have a positive IgA anti-endomysial antibody (EMA); the data for anti-tTG Ab titer-based diagnosis of CeD in adults is still emerging. We planned to validate if IgA anti-tTG Ab titer ≥10-fold predicts villous abnormalities of modified Marsh grade ≥2 in Asian adult patients with CeD. METHODS: We recruited 937 adult patients with positive anti-tTG Ab from two databases, including AIIMS Celiac Clinic and Indian National Biorepository. The diagnosis of definite CeD was made on the basis of a positive anti-tTG Ab and the presence of villous abnormalities of modified Marsh grade ≥2. RESULTS: Of 937 adult patients with positive anti-tTG Ab, 889 (91.2%) showed villous abnormalities of modified Marsh grade ≥2. Only 47.6% of 889 adults with CeD had anti- tTG Ab titers of ≥10-fold. The positive predictive value (PPV) and specificity of anti tTG Ab titer ≥10-fold for predicting modified Marsh grade ≥2 were 99.8% and 98%, respectively. At anti-tTG Ab titer ≥11-fold, specificity and PPV were 100% for predicting villous abnormalities of modified Marsh grade ≥2. CONCLUSIONS: Approximately 50% of adults with CeD may benefit from the no biopsy pathway, reducing the health burden and risks of gastroscopy/anesthesia.

Impact of delay in the diagnosis on the severity of celiac disease.

BACKGROUND AND AIM: Celiac disease (CeD) has now become a global disease with a worldwide prevalence of 0.67%. Despite being a common disease, CeD is often not diagnosed and there is a significant delay in its diagnosis. We reviewed the impact of the delay in the diagnosis on the severity of manifestations of CeD. METHODS: We reviewed clinical records of 726 consecutive patients with CeD from the Celiac Clinic database and the National Celiac Disease Consortium database. We extracted specific data including the demographics, symptoms at presentation, time of onset of symptoms, time to diagnosis from the onset of the symptoms, and relevant clinical data including fold-rise in anti-tissue transglutaminase antibody (IgA anti-tTG Ab) and severity of villous and crypt abnormalities as assessed using modified Marsh classification. RESULTS: The median duration between the onset of symptoms and the diagnosis of CeD was 27 months (interquartile range 12-60 months). A longer delay in the diagnosis of CeD from the onset of symptoms was associated with lower height for age, lower hemoglobin, higher fold rise in IgA Anti tTG titers, and higher severity of villous and crypt abnormalities. About 18% of patients presented with predominantly non-gastrointestinal complaints and had a longer delay in the diagnosis of CeD. CONCLUSIONS: There is a significant delay in the diagnosis of CeD since the onset of its symptoms. The severity of celiac disease increases with increasing delay in its diagnosis. There is a need to keep a low threshold for the diagnosis of CeD in appropriate clinical settings.

Sieving out non-celiac gluten sensitivity amongst patients with irritable bowel syndrome.

OBJECTIVES: It is challenging to make diagnosis of non-celiac gluten sensitivity/non-celiac wheat sensitivity (NCGS/NCWS) in clinical practice, since there is no biomarker and diagnosis is based on response to gluten-free-diet (GFD). We used anti-gliadin antibody (AGA) for screening patients with IBS for gluten-sensitivity. METHODS: 492 Adult-patients with IBS underwent screening for celiac disease and gluten-sensitivity using IgA anti-tissue transglutaminase antibody and IgA-AGA and IgG-AGA, respectively. Patients with positive AGA (IgA and/or IgG) were invited to follow GFD, those willing were put on GFD for 6-weeks. Responsive patients were given gluten re-challenge. Diagnosis of NCGS was confirmed if they had recurrence of symptoms. RESULTS: Of 492 patients with IBS, AGA was positive in 61(12.4 %), hence suspected to have gluten-sensitivity. Of 31 who agreed to participate and followed GFD for 6-weeks, 17 (54.8 %) had complete (>30 % improvement) and 10(32.2 %) had partial (>20 % improvement) response. All 17 complete-responders were given gluten re-challenge for 6-weeks, symptoms recurred in all and hence were confirmed to have NCGS/NCWS. Significant decrease in AGA levels occurred almost in all GFD-responders. CONCLUSIONS: 12.4 % IBS patients have biological evidence of gluten/wheat-sensitivity. Almost 87 % patients with IBS having AGA responded to GFD. The value of AGA may further be explored as a biomarker for screening for the presence of NCGS, before recommending this test for the clinical practice.

An unexpected intraoperative airway obstruction due to betadine solution.

Intraoperative airway obstruction is a nightmare for anesthesiologists, especially in head and neck surgeries. Due to the proximity of airway and surgical area, it will be difficult for anesthesiologists for the airway access. There are many causes of intraoperative airway obstruction. To the best of our literature search, there is no case report of airway obstruction due to betadine solution. Here we present a case of airway obstruction due to endotracheal tube blockade by the use of betadine solution in the surgery of cervical region in a child posted for posterior C1-C2 fusion in prone position on skull pins.

Mapping fluid structuration to flow enhancement in nanofluidic channels.

Fluid flow in miniature devices is often characterized by a boundary "slip" at the wall, as opposed to the classical paradigm of a "no-slip" boundary condition. While the traditional mathematical description of fluid flow as expressed by the differential forms of mass and momentum conservation equations may still suffice in explaining the resulting flow physics, one inevitable challenge against a correct quantitative depiction of the flow velocities from such considerations remains in ascertaining the correct slip velocity at the wall in accordance with the complex and convoluted interplay of exclusive interfacial phenomena over molecular scales. Here, we report an analytic engine that applies combined physics-based and data-driven modeling to arrive at a quantitative depiction of the interfacial slip via a molecular-dynamics-trained machine learning algorithm premised on fluid structuration at the wall. The resulting mapping of the system parameters to a single signature data that bridges the molecular and continuum descriptions is envisaged to be a preferred computationally inexpensive route as opposed to expensive multi-scale or molecular simulations that may otherwise be inadequate to resolve the flow features over experimentally tractable physical scales.

A prospective observational multicentric clinical trial to evaluate microscopic examination of acid-fast bacilli in sputum by artificial intelligence-based microscopy system.

Microscopy-based tuberculosis (TB) diagnosis i.e., Ziehl-Neelsen (ZN) stained smear screening still remains the primary diagnostic method in resource poor and high TB burden countries, however itrequires considerable experience and is bound to human errors. In remote areas, wherever expert microscopist is not available, timely diagnosis at initial level is not possible. Artificial intelligence (AI)-based microscopy may be a solution to this problem. A prospective observational multi-centric clinical trial to evaluate microscopic examination of acid-fast bacilli (AFB) in sputum by the AI based system was done in three hospitals in Northern India. Sputum samples from 400 clinically suspected cases of pulmonary tuberculosis were collected from three centres. Ziehl-Neelsen staining of smears was done. All the smears were observed by 3 microscopist and the AI based microscopy system. AI based microscopy was found to have a sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of 89.25%, 92.15%, 75.45%, 96.94%, 91.53% respectively. AI based sputum microscopy has an acceptable degree of accuracy, PPV, NPV, specificity and sensitivity and thus may be used as a screening tool for the diagnosis of pulmonary tuberculosis.

Blastic plasmacytoid dendritic cell neoplasm in an adolescent female: a rare entity with challenging diagnosis and management.

Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive haematopoietic neoplasm with poor prognosis. It usually presents with cutaneous lesions and symptoms secondary to bone marrow involvement. Due to rarity and lack of standard treatment protocols, these cases are difficult to diagnose and treat. We report a case of a female in early adolescence who presented with skin nodules on the leg. The diagnosis was established by immunophenotypic studies. We discuss the investigations and treatment options available to diagnose and treat this malignancy.

GPU-based, interactive exploration of large spatiotemporal climate networks.

This paper introduces the Graphics Processing Unit (GPU)-based tool Geo-Temporal eXplorer (GTX), integrating a set of highly interactive techniques for visual analytics of large geo-referenced complex networks from the climate research domain. The visual exploration of these networks faces a multitude of challenges related to the geo-reference and the size of these networks with up to several million edges and the manifold types of such networks. In this paper, solutions for the interactive visual analysis for several distinct types of large complex networks will be discussed, in particular, time-dependent, multi-scale, and multi-layered ensemble networks. Custom-tailored for climate researchers, the GTX tool supports heterogeneous tasks based on interactive, GPU-based solutions for on-the-fly large network data processing, analysis, and visualization. These solutions are illustrated for two use cases: multi-scale climatic process and climate infection risk networks. This tool helps one to reduce the complexity of the highly interrelated climate information and unveils hidden and temporal links in the climate system, not available using standard and linear tools (such as empirical orthogonal function analysis).

Post COVID-19 syndrome and new onset diseases: A prospective observational study.

Introduction: The National Institute of Health and Care Excellence (NICE) has defined the terms, 'acute coronavirus disease 2019' (COVID-19), 'ongoing symptomatic COVID-19' and 'post-COVID-19 syndrome', with the latter two described as having persistent symptoms after the onset of COVID-19 symptoms for 4-12 weeks and >12 weeks, respectively. Persistent symptoms can either be due to the after-effects of COVID-19 or new-onset diseases after acute COVID-19. All symptoms observed beyond 4 weeks after the onset of COVID-19 need not be present at the time of onset. Previous studies on persistent post-COVID-19 symptoms have not mentioned new-onset diseases after acute COVID-19, and only a select few studies have discussed such new-onset symptoms. Methods: Ninety-five patients who attended the post-COVID-19 clinic completed the requisite follow-up till 16 weeks after COVID-19 symptom onset. Data was recorded on a predesigned proforma. Necessary investigations were conducted to rule out any other cause of persistent symptoms. Results: Fatigue (62.1%), breathlessness (50.5%) and cough (27.4%) were the most common symptoms present beyond 4 weeks after the onset of COVID-19 symptoms. Forty-nine (51.57%) patients developed post-COVID-19 syndrome - their severity of symptoms (odds ratio [OR] 17.77) and longer duration of hospital stay (OR 1.095) during acute disease were significantly associated with the development of post-COVID-19 syndrome. During follow-up, 25 patients developed new-onset symptoms, such as diabetes mellitus, hypertension and idiopathic tachycardia. Conclusion: Patients can have persistent symptoms, new-onset symptoms and new-onset diseases after recovery from acute COVID-19.

Predictors of Mortality among Patients Hospitalized with COVID-19 during the First Wave in India: A Multisite Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused more than 6 million deaths globally. Understanding predictors of mortality will help in prioritizing patient care and preventive approaches. This was a multicentric, unmatched, hospital-based case-control study conducted in nine teaching hospitals in India. Cases were microbiologically confirmed COVID-19 patients who died in the hospital during the period of study and controls were microbiologically confirmed COVID-19 patients who were discharged from the same hospital after recovery. Cases were recruited sequentially from March 2020 until December-March 2021. All information regarding cases and controls was extracted retrospectively from the medical records of patients by trained physicians. Univariable and multivariable logistic regression was done to assess the association between various predictor variables and deaths due to COVID-19. A total of 2,431 patients (1,137 cases and 1,294 controls) were included in the study. The mean age of patients was 52.8 years (SD: 16.5 years), and 32.1% were females. Breathlessness was the most common symptom at the time of admission (53.2%). Increasing age (adjusted odds ratio [aOR]: 46-59 years, 3.4 [95% CI: 1.5-7.7]; 60-74 years, 4.1 [95% CI: 1.7-9.5]; and ≥ 75 years, 11.0 [95% CI: 4.0-30.6]); preexisting diabetes mellitus (aOR: 1.9 [95% CI: 1.2-2.9]); malignancy (aOR: 3.1 [95% CI: 1.3-7.8]); pulmonary tuberculosis (aOR: 3.3 [95% CI: 1.2-8.8]); breathlessness at the time of admission (aOR: 2.2 [95% CI: 1.4-3.5]); high quick Sequential Organ Failure Assessment score at the time of admission (aOR: 5.6 [95% CI: 2.7-11.4]); and oxygen saturation < 94% at the time of admission (aOR: 2.5 [95% CI: 1.6-3.9]) were associated with mortality due to COVID-19. These results can be used to prioritize patients who are at increased risk of death and to rationalize therapy to reduce mortality due to COVID-19.

Incidence and Predictors of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is the commonest type of liver disease worldwide. We aimed to assess the incidence and predictors of liver-related events (LREs) and mortality in NAFLD patients. Methods: NAFLD patients (n = 957) evaluated between January 2000 and November 2021 were included. Patients were categorised as noncirrhosis (NC), compensated cirrhosis (CC) and decompensated cirrhosis (DC), and the incidence of LRE and mortality were estimated and compared. Results: The proportions of NC, CC and DC were 87.8% (n = 840), 8.8% (n = 84) and 3.4% (n = 33), respectively. The median follow-up duration was 3.9 (3.0-5.7) years, and the total cumulative duration was 4633 person-years. The incidence of LRE per 100 person-years was 0.14, 2.72 and 10.24 in patients with NC, CC and DC, respectively. The incidence of mortality was 0.12, 1.05 and 4.24 per 100 person-years, respectively, in the 3 groups. The causes of mortality in the 3 groups were liver related in 1/5 (20%), 3/4 (75%) and 6/9 (66.7%), respectively. Overall, the mortality rate was higher in those with diabetes than those without diabetes (log-rank P value = 0.005). On further analysis, diabetes was associated with poor outcomes only in NC group (log-rank P value = 0.036), and not in CC (log-rank P value = 0.353) or DC groups (log-rank P value = 0.771). On multivariate Cox proportional hazard analysis, age (hazard ratio [HR] 1.070), hypertension (HR 4.361) and DC (HR 15.036) were independent predictors of poor outcomes. Liver stiffness measurement, bilirubin, CC and DC were independent predictors of LRE. Conclusion: In our study of NAFLD from India, the incidence of LRE was found to be similar to that seen in Western studies. In NC NAFLD, diabetes was associated with poor outcomes.

Therapeutic plasma-exchange improves short-term, but not long-term, outcomes in patients with acute-on-chronic liver failure: A propensity score-matched analysis.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is associated with a high short-term mortality rate in the absence of liver transplantation. The role of therapeutic plasma exchange (TPE) in improving the outcomes of ACLF and acute decompensation (AD) is unclear. In this retrospective analysis, we aimed to determine the impact of TPE on mortality in patients with ACLF. METHODS: ACLF patients receiving TPE with standard medical treatment (SMT) were propensity score matched (PSM) with those receiving SMT alone (1:1) for sex, grades of ACLF, CLIF C ACLF scores, and the presence of hepatic encephalopathy. The primary outcomes assessed were mortality at 30 and 90 days. Survival analysis was performed using Kaplan Meier survival curves. RESULTS: A total of 1151 patients (ACLF n = 864 [75%], AD [without organ failure] n = 287 [25%]) were included. Of the patients with ACLF (n = 864), grade 1, 2, and 3 ACLF was present in 167 (19.3%), 325 (37.6%), and 372 (43.0%) patients, respectively. Thirty-nine patients received TPE and SMT, and 1112 patients received only SMT. On PSM analysis, there were 38 patients in each group (SMT plus TPE vs SMT alone). In the matched cohort, the 30-days mortality was lower in the TPE arm compared to SMT (21% vs 50%, P = .008), however, the 90-day mortality was not significantly different between the two groups (36.8% vs 52.6%, P = .166); HR, 0.82 (0.44-1.52), P = .549. CONCLUSION: TPE improves short-term survival in patients with ACLF, but has no significant impact on long-term outcomes. Randomized control trials are needed to obtain a robust conclusion in this regard.