Fabrication of angstrom-scale two-dimensional channels for mass transport.

Fluidic channels at atomic scales regulate cellular trafficking and molecular filtration across membranes, and thus play crucial roles in the functioning of living systems. However, constructing synthetic channels experimentally at these scales has been a significant challenge due to the limitations in nanofabrication techniques and the surface roughness of the commonly used materials. Angstrom (Å)-scale slit-like channels overcome such challenges as these are made with precise control over their dimensions and can be used to study the fluidic properties of gases, ions and water at unprecedented scales. Here we provide a detailed fabrication method of the two-dimensional Å-scale channel devices that can be assembled to contain a desired number of channels, a single channel or up to hundreds of channels, made with atomic-scale precision using layered crystals. The procedure includes the fabrication of the substrate, flake, spacer layer, flake transfers, van der Waals assembly and postprocessing. We further explain how to perform molecular transport measurements with the Å-channels to directly probe the intriguing and anomalous phenomena that help shed light on the physics governing ultra-confined transport. The procedure requires a total of 1-2 weeks for the fabrication of the two-dimensional channel device and is suitable for users with prior experience in clean room working environments and nanofabrication.

Long Term HBsAg Responses to Peg-Interferon Alpha-2b in HBeAg Negative Chronic Hepatitis B Patients Developing Clinical Relapse after Stopping Long-Term Nucleos(t)ide Analogue Therapy.

Background and aims: A high proportion of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients develop clinical relapse after stopping long-term nucleotide analogues (NAs). The aim of this study was to assess the efficacy of pegylated interferon (PEG-IFN) alpha 2b in inducing hepatitis B surface antigen (HBsAg) loss in such patients. Methods: NAs were stopped in 118 HBeAg-negative CHB patients fulfilling the Asian Pacific Association for the Study of Liver (APASL) 2015 criteria for stopping NAs; they had received NAs for a median interquartile range (IQR) of 60 (48-84) months. Results: Overall, 82 of 118 (69.5%) patients developed clinical relapse after stopping NAs; 44 within 12 months (and treated with PEG-IFN alpha 2b 1.5 mcg/kg weekly subcutaneous injections for 48 weeks); and 38 after 12 months [and treated with tenofovir alafenamide fumarate (TAF) 25 mg daily] of follow-up. The decision to treat with either PEG-IFN or TAF was not a time-bound decision but was due to logistical problems.During the median IQR follow-up of 48 (43.5-52.5) months after the start of PEG-IFN, 14 of 44 (31.8%) patients developed clinical relapse after stopping PEG-IFN and were started on TAF. At the last follow-up visit, HBsAg was found to be negative in 7/44 (15.9%) of patients receiving PEG-IFN.Among 38 patients treated with TAF for clinical relapse, during the median IQR follow-up of 18 (12-30) months after start of TAF, no patient became HBsAg negative.36 patients did not develop clinical relapse during the follow-up, and after a median IQR follow-up of 60 (60-60) months after stopping NAs, HBsAg negative was found in 1/36 (2.8%) of patient at the last follow-up. Conclusions: Among patients with HBeAg-negative chronic hepatitis B who developed clinical relapse after stopping long-term NAs therapy and were subsequently treated with PEG-IFN alpha 2b, 15.9% achieved HBsAg loss on long-term follow-up.

COVID-19 - a potential trigger for MOGAD-associated optic neuritis: a case report and literature review.

SARS-CoV-2 affects the nervous system directly by neurotoxic action, by binding to angiotensin-converting enzyme-2 (ACE2) receptors or indirectly by inducing cytokine storm leading to disruption of the blood-brain barrier, immunological mediation, increasing blood coagulation and as a trigger for autoimmune-mediated demyelinating injuries in the central nervous system. In COVID-19 neuro-ophthalmological manifestations are not so common. Optic neuritis is the result of optic nerve inflammation and has varied causes. In many patients, signs of inflammation are not visible on the fundus, and it usually manifests as papillitis-anterior neuritis, retrobulbar neuritis or visible optic nerve oedema. We are reporting a case of a middle-aged adult diagnosed with myelin oligodendrocyte glycoprotein (MOG) antibody-positive optic neuritis of the right eye post-COVID-19 disease. Routine biochemical and haematological investigations, including electrolytes and hepatic and renal functions, were normal. In cerebrospinal fluid (CSF) - glucose 63.8 mg/dL, protein 39.1 mg/dL and ADA - 1 µ/L. No oligoclonal bands of immunoglobulin G (IgG) were seen on high-resolution electrophoresis. Serum Anti-MOG-antibodies were positive. A gadolinium-contrast magnetic resonance imaging (MRI) of the brain and orbits shows post-contrast enhancement in the superior aspect of the right intraconal soft tissue. The right optic nerve appears bulky and heterogeneous with peripheral post-contrast enhancement along its entire length suggestive of neuritis. A diagnosis of MOG antibody-positive optic neuritis was made, and the patient was treated with an injection of Methylprednisolone with intravenous immunoglobulin. Each day, the evaluation of the right eye showed remarkable improvement from finger counting to 6/6 vision. The patient was discharged on the 9th day of admission. We can conclude that early diagnosis was essential for improving the long-term outcome of the patient.

Tolerance of standard dose albumin infused over 6 hrs for treatment of spontaneous bacterial peritonitis-A randomized controlled trial.

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 .

Safety and Efficacy of Endoscopic Retrograde Cholangio-Pancreatography in Patients of Liver Cirrhosis: A Case-Control Study.

Background With the improvement in noninvasive diagnostic imaging modalities, Endoscopic Retrograde Cholangio-Pancreatography (ERCP) has evolved into a primarily therapeutic procedure. Besides being efficacious and one of the most commonly done procedures, ERCP is also associated with a high risk of complications. However, there is a lack of studies analyzing the safety and success of ERCP in patients with liver cirrhosis. We retrospectively evaluated the outcome of ERCP in patients with cirrhosis of the liver compared to non-cirrhotic patients using the database from our institute. Methods Patients with liver cirrhosis who underwent ERCP from January 2010 to March 2020 were analyzed. This was a matched case-control study in which one cirrhotic patient undergoing ERCP was age and gender-matched randomly to one non-cirrhotic patient. We compared adverse events and the success rate of ERCP between cirrhotic patients and non-cirrhotic patients. The primary outcome of the study was analyzing the prevalence of procedure-related adverse events and their independent risk factors in patients of cirrhosis compared to the non-cirrhotic population. Results Two hundred patients were analyzed in both groups. Choledocholithiasis was the most common reason for ERCP in both groups. Mean Child-Turcotte-Pugh (CTP) score and Model for End-stage Liver Disease (MELD) score in the cirrhosis group were 9.16 ±1.78 and 19.09 ±7.06 respectively. Patients in the cirrhosis group had a significantly higher frequency of complications compared to the controls: 41 (20.5 %) versus 15 (7.5%), p < 0.01. Bleeding was the most common adverse event in both groups: 19 (9.5%) vs 6(3%). High International Normalised Ratio (INR), low platelets, and cholangitis at presentation were independently predictive of post-ERCP complications. Despite a similar technical success rate, the clinical success rate was lower in the cirrhotic than in the noncirrhotic group (83.9% versus 97.9%, p=0.006). Conclusion The prevalence of complications following ERCP was nearly three-fold higher in patients with cirrhosis than in non-cirrhotic patients. These events were related primarily to cholangitis, coagulopathy, and the advanced status of chronic liver disease.

Beyond steric selectivity of ions using ångström-scale capillaries.

Ion-selective channels play a key role in physiological processes and are used in many technologies. Although biological channels can efficiently separate same-charge ions with similar hydration shells, it remains a challenge to mimic such exquisite selectivity using artificial solid-state channels. Although there are several nanoporous membranes that show high selectivity with respect to certain ions, the underlying mechanisms are based on the hydrated ion size and/or charge. There is a need to rationalize the design of artificial channels to make them capable of selecting between similar-sized same-charge ions, which, in turn, requires an understanding of why and how such selectivity can occur. Here we study ångström-scale artificial channels made by van der Waals assembly, which are comparable in size with typical ions and carry little residual charge on the channel walls. This allows us to exclude the first-order effects of steric- and Coulomb-based exclusion. We show that the studied two-dimensional ångström-scale capillaries can distinguish between same-charge ions with similar hydrated diameters. The selectivity is attributed to different positions occupied by ions within the layered structure of nanoconfined water, which depend on the ion-core size and differ for anions and cations. The revealed mechanism points at the possibilities of ion separation beyond simple steric sieving.

Tadalafil improves erectile dysfunction and quality of life in men with cirrhosis: a randomized double blind placebo controlled trial.

BACKGROUND AND AIMS: Patients with cirrhosis have high prevalence of erectile dysfunction (ED). The aim of this study was to study the efficacy and safety of tadalafil for ED in patients with cirrhosis. METHODS: 140 cirrhotic males with ED were randomized into tadalafil 10 mg daily (n = 70) or placebo (n = 70) for 12 weeks. ED was diagnosed if erectile function (EF) domain score was < 25 in International Index of Erectile Function (IIEF) questionnaire. The erectile function domain consists of six questions concerning erection frequency, erection firmness, frequency of partner penetration, frequency of maintaining erection after penetration, ability to maintain erection to completion of intercourse and confidence in achieving and maintaining erection. Primary outcome was proportion of patients having an increase in > 5 points in EF domain of the IIEF. Generalized Anxiety Disorder 7 (GAD-7) questionnaire was used for screening and severity measuring of GAD. The presence of depression was screened using the Patient Health Questionnaire (PHQ-9) and the assessment of health related quality of life was done using the Short Form (36) Health Survey. RESULTS: At the end of 12 weeks, more patients in tadalafil group achieved > 5 points increase in the EF domain of the IIEF when compared with the placebo group [44(62.9%) vs. 21(30%), p < 0.001]. At the end of 12 weeks, patients receiving tadalafil had significantly more change in scores on the erectile function domain, orgasmic function domain, intercourse satisfaction domain, overall satisfaction domain, erection vaginal penetration rates and successful intercourse; significantly more decline in the GAD-7 and PHQ-9 scores; significantly more improvement in scores of five of the eight domains of SF-36 (general health perception, vitality score, social functioning, role emotional and mental health) and the mental component summary rates when compared with placebo. The development of side effects and the changes in HVPG were not significantly different between the two groups. CONCLUSIONS: Tadalafil therapy may enhance erectile function, improve anxiety, depression and quality of life; and is well tolerated by men with cirrhosis (CTP score < 10) and ED. However, further larger and long-term studies are needed to confirm these results and look for rarer side effects of using tadalafil in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier number NCT03566914; first posted date: June 25, 2018.

Patency Rates and Outcomes of Renal Access Arteriovenous Fistulas for Hemodialysis in Patients with Chronic Kidney Disease.

Hemodialysis remains the most popular modality of renal replacement therapy for end-stage renal disease patients with chronic kidney disease. Various factors such as a radial artery, cephalic vein diameter, age, hypertension, and diabetes mellitus can affect the fistula maturation. This study was carried out to know the patency rates and factors affecting fistula maturation in the Indian population. This is a prospective observational study which aimed to study the patency rate of arteriovenous (AV) fistulas. On the day of surgery, patients were shifted inside the operation theater. Under all aseptic precautions, an AV fistula was formed using the radial artery and cephalic vein. All patients were followed up for 6 months. The data were analyzed using IBM SPSS version 22. To see the change over a period of time, McNemar test for categorical data and repeated measure for continuous data followed by post hoc comparison by Bonferroni method were used. The mean age of the patients was 46.98 ± 13.33 years. The mean diameter of the cephalic vein, ulnar artery, and radial artery at the wrist was 1.733 ± 0.528, 1.700 ± 0.364, and 1.908 ± 0.420, respectively, whereas the mean diameter of the cephalic vein, ulnar artery, and radial artery at the forearm was 1.952 ± 0.488, 1.910 ± 0.421, and 2.058 ± 0.458, respectively. Immediate thrill after the surgery was present in 36/52 (69.2%) of the patients. The radial artery diameter at the wrist was significantly less in the patients with primary failure in whom immediate thrill was not present (P = 0.016). At 1-month follow-up, 30/49 (61.2%) and, at 6 months, 29/48 (60.4%) fistulas were functional. Radiocephalic AV fistulas have a reasonable success rate and minimal morbidity, and radial artery diameter is a good predictor of the outcome.

Erectile Dysfunction in Cirrhosis: Its Prevalence and Risk Factors.

Background: Erectile dysfunction (ED) is common in men with cirrhosis. The aim of this study was to assess the prevalence of ED and the factors associated with ED in men with cirrhosis. Methods: 400 men with cirrhosis [Child-Turcotte-Pugh (CTP) class A, 44.0%; CTP class B, 41.0%; and CTP class C, 15.0%] having high Karnofsky performance score, and living in a stable monogamous relationship with a female partner were included in the study. International Index of Erectile Function (IIEF) questionnaire, and Short-Form (36) Health Survey (SF-36) were used to assess erectile function and the health-related quality of life (HRQOL), respectively. Results: ED was found in 289 (72.3%) patients. Patients with ED reported significantly lower SF-36 scores across all the eight domains of SF-36 (i.e., physical functioning score, role physical score, bodily pain score, general health perception score, vitality score, social functioning score, role emotional score, and mental health score); physical component summary score, and mental physical component summary score, compared with those without ED. On multivariate analysis, factors associated with ED were older age, longer duration of cirrhosis, CTP-C (vs. CTP-A), higher hepatic venous pressure gradient (HVPG), presence of generalized anxiety disorder (GAD), presence of major depression, and lower appendicular skeletal muscle index measured by dual-energy X-ray absorptiometry (DEXA ASMI). Conclusion: ED is common in men with cirrhosis, and men with ED have poor HRQOL compared with those without ED. Older age, longer duration of cirrhosis, CTP-C (vs. CTP-A), higher HVPG, presence of GAD, presence of major depression, and lower DEXA ASMI are associated with ED.

Comparison of safety and efficacy of convalescent plasma with fresh frozen plasma in severe covid-19 patients.

BACKGROUND: Role of Convalescent plasma (COPLA) to treat severe COVID-19 is under investigation. We compared efficacy and safety of COPLA with fresh frozen plasma (FFP) in severe COVID-19 patients. METHODS: One group received COPLA with standard medical care (n = 14), and another group received random donor FFP, as control with standard medical care (n = 15) in severe COVID-19 disease. RESULTS: The proportion of patients free of ventilation at day seven were 78.5% in COPLA group, and 93.3 % in control group were not significant (p= 0.258). However, improved respiratory rate, O2 saturation, SOFA score, and Ct value were observed in the COPLA group. No serious adverse events were noticed by plasma transfusion in both groups.

Collateral Impact on Patients of Liver Diseases in the Second COVID-19 Wave: A Retrospective Cohort Study.

Background The second wave of the COVID-19 pandemic in India started in April 2021. This necessitated a change in focus from chronic ailments. This wave lasted till May 2021. Its impact on liver disease patients without COVID-19 infection has not been analyzed. Methods Records of liver disease patients from the Institute database admitted from April to May 2021 were compared with that from April to May 2019 i.e., prior to the pandemic. The primary outcome was a comparison of in-hospital mortality rates. Secondary outcomes were a comparison of 30 and 90-day readmission rates and liver transplantation rates. Results Seven hundred and seventy-one patients in April-May 2019 (group 1) and 545 patients in April-May 2021 (group 2) were analyzed. Patients in group 2 were sicker with higher PT (INR), urea, creatinine, CTP, and MELD score and low serum sodium, albumin, and platelet count with a higher prevalence of variceal bleed, hepatic encephalopathy, and acute kidney injury. There was higher mortality in group 2 (128/545; 23.5%) than group 1 (124/ 771;16.1%), OR 1.6, 95% CI 1.2 - 2.1, p<0.01. 30 day readmission rate was numerically higher in group1; 18.3% vs 16.9%, p=0.5. The 31-90 day readmission rate was higher in group 1; 29.4% vs 16.9%, p<0.01. There was no significant difference in the number of patients undergoing liver transplantation in two groups, 19 in group 1 and 14 in group 2 (p=0.90). Conclusion The second wave of the COVID-19 pandemic had a significant collateral impact on liver disease patients even without causing infection in them. Patients were sicker at the time of admission with higher mortality.

Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis.

BACKGROUND & AIMS: Whether non-selective ß-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal hypertension in early cirrhosis. We assessed whether carvedilol may prevent decompensation and improve survival in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH). METHODS: By systematic review we identified randomized-controlled trials (RCTs) comparing carvedilol vs. control therapy (no-active treatment or endoscopic variceal ligation [EVL]) in patients with cirrhosis and CSPH without previous bleeding. We performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (liver transplantation and death were competing events) and death (liver transplantation was a competing event). Models were adjusted using propensity scores for baseline covariates with the inverse probability of treatment weighting (IPTW) approach. RESULTS: Among 125 full-text studies evaluated, 4 RCTs were eligible. The 4 provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo). Baseline characteristics were similar between groups. Standardized differences were <10% by IPTW. The risk of developing decompensation of cirrhosis was lower with carvedilol than in controls (subdistribution hazard ratio [SHR] 0.506; 95% CI 0.289-0.887; p = 0.017; I2 = 0.0%, Q-statistic-p = 0.880), mainly due to a reduced risk of ascites (SHR 0.491; 95% CI 0.247-0.974; p = 0.042; I2 = 0.0%, Q-statistic-p = 0.384). The risk of death was also lower with carvedilol (SHR 0.417; 95% CI 0.194-0.896; p = 0.025; I2 = 0.0%, Q-statistic-p = 0.989). CONCLUSIONS: Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH. This suggests that screening patients with compensated cirrhosis for CSPH to enable the prompt initiation of carvedilol could improve outcomes. PROSPERO REGISTRATION NUMBER: CRD42019144786. LAY SUMMARY: The transition from compensated cirrhosis to decompensated cirrhosis is associated with markedly reduced life expectancy. Therefore, preventing decompensation in patients with compensated cirrhosis would be associated with greatly improved patient outcomes. There has been controversy regarding the use of non-selective ß-blockers (portal pressure-lowering medications) in patients with cirrhosis and elevated portal blood pressure (portal hypertension). Herein, using a competing-risk meta-analysis to optimize sample size and properly investigate cirrhosis as a multistate disease and outcomes as time-dependent events, we show that carvedilol (a non-selective ß-blocker) is associated with a reduced risk of decompensating events and improved survival in patients with cirrhosis and portal hypertension.

Impact of liver disease severity on outcomes of patients undergoing endourological procedures for urolithiasis.

Objectives: This study is aimed to determine the impact of liver disease severity on the outcome of patients undergoing endourological procedures for urolithiasis, and to understand the factors that are helpful in improving the outcome. Materials and methods: We retrospectively analyzed the records of patients with chronic liver disease who underwent endourological procedures between January 2014 and February 2020. Inpatient records and charts were assessed for age, sex, height, weight, body mass index, model for end-stage liver disease (MELD) score, Child-Turcotte-Pugh score, type of procedure and anesthesia, intensive care unit (ICU) stay, duration of hospitalization, number, size, and position of stones, and postoperative complications such as hematuria, sepsis, and secondary procedures. Data are presented as mean ± standard deviation or frequency. The chi-square test was applied to determine the exact association between categorical data and Student t-test or Mann-Whitney U test as appropriate for continuous data. Statistical significance was set at p < 0.05. Results: Hospital and ICU stay as well as administration of different blood products were significantly longer in the Child C than in the Child A and B categories (p < 0.001). Two patients in the Child C category died, while 3 left the hospital against medical advice. The duration of ICU stay and blood products administered increased with augmenting MELD scores. The durations of hospitalization and blood product administration were significantly higher in patients with an MELD score ≥20 than in the group with MELD score <20. Conclusions: Hospital and ICU stay and blood product administration were significantly higher in Child C than in Child A and B class patients. Hospitalization duration and blood product administration were significantly higher in patients with an MELD score ≥20.

Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial).

IMPORTANCE: No proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation. OBJECTIVE: To compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients. DESIGN, SETTING AND PARTICIPANTS: A multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group. INTERVENTION: One group received COPLA with SMT (n=200), and another group received SMT only (n=200). MAIN OUTCOME MEASURES: Primary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O2 therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events. RESULTS: The median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7-13) (p=0.328). The median duration of O2 therapy was 8 days (IQR=6-12) in COPLA and 10 days (IQR=6-12) in SMT group (p=0.64). The PaO2/FiO2 ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80-80)) were higher than SMT group (0 (IQR 0-80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group. CONCLUSION AND RELEVANCE: Convalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes. TRIAL REGISTRATION NUMBER: NCT04425915.

Association of Obstructive Sleep Apnea with Nocturnal Hypoxemia in Metabolic-Associated Fatty Liver Disease Patients: A Cross-sectional Analysis of Record-based Data.

RATIONALE: Obstructive sleep apnea (OSA) is often seen among obese individuals and the obesity has a linear association with MAFLD. The contribution of chronic intermittent nocturnal hypoxia of OSA and association of MAFLD with OSA is an unmet need. The present study aimed to determine the etiology, impact and association of OSA severity and nocturnal hypoxemia among patients ofChronic liver disease (CLD). METHODS: In this study, analysis of the medical records and clinical details of the patients of CLD who had undergone polysomnography were analyzed after appropriate inclusion in study as per inclusion and exclusion criteria. After assessing the eligibility criteria, a total of 78 patients were included in the final analysis. Nocturnal hypoxemia was gauged from the baseline oxygen saturation record of study. Presence and severity of OSA were graded as per American Academy of Sleep Medicine (AASM) criteria. The primary objective of the study was to determine the association between OSA severity and nocturnal hypoxemia to the presence of Non-alcoholic Fatty Liver Disease (NAFLD). Secondary objectives were to assess the association of OSA severity and extent of nocturnal hypoxemia to the BMI and to determine the proportions of NAFLD subjects with OSA. RESULTS: A total of 78 patients were screened, of which only 11 (14.1%) were female. Out of these, 56 (71.8%) were classified to MAFLD group while 22 (28.2%) were to the non-MAFLD group. The patients in MAFLD group with mean age of 56.02 years were older as compared to non-MAFLD with mean age of 51.05 years but that was not statistically different. Patients were categorized into MAFLD (n = 56) and non-MAFLD, representing other etiologies of CLD (n = 22; ethanol, chronic Hepatitis B virus (HBV), chronic Hepatitis C virus (HCV), cryptogenic, Non-cirrhosis portal fibrosis (NCPF), Primary sclerosing cholangitis (PSC), Autoimmune hepatitis (AIH), sarcoidosis, Wilson's disease). The mean BMI was significantly higher in MAFLD in comparison to non-MAFLD (34.51 ± 8.79 vs. 25.47 ± 5.75; P = 0.000) and also the median AHI of MAFLD group was significantly higher than the non-MAFLD 4.95 {(1.85, 25.47) vs. 0.85 (0.30, 2.72) (P value < 0.000)} [Table 1]. Among the desaturation indices, the number of desaturations >3% {median of 122.50 (75.00, 241.25) vs. 63.00 (13.75, 158.00), P value 0.009} and average desaturation {mean of (5.04 ± 2.16) vs. (3.78 ± 1.226)%, P value 0.002} were significantly higher in MAFLD versus non-MAFLD group [Table 2]. The AHI and all desaturation parameters, although not statistically significant, were worst in Child B [Table 3]. CONCLUSION: MAFLD patients have higher prevalence and greater severity of OSA and worse nocturnal desaturation parameters as compared to non-MAFLD patients. OSA is independent of obesity among patients of CLD, but prevalent among NAFLD group. Further prospective studies are needed among MAFLD and OSA patients to elucidate the mechanism linking pathophysiology of OSA-MAFLD and guide therapy.

Prevalence of and Factors Associated with Sleep-Wake Abnormalities in Patients with Cirrhosis.

BACKGROUND & AIMS: Sleep-wake abnormalities [poor nighttime sleep and excessive daytime sleepiness (EDS)] are common in patients with cirrhosis. The aim of this study was to assess the prevalence of sleep-wake abnormalities and clinical factors associated with these abnormalities in a group of patients with cirrhosis. METHODS: 1098 patients with cirrhosis [Child Turcotte Pugh (CTP) class A, 22.2%; CTP class B, 29.2% and CTP class C, 48.6%], with either no ascites or mild ascites controlled on diuretics, and no history of or current overt hepatic encephalopathy were included in the study. RESULTS: Poor nighttime sleep and EDS were found in 569 (51.8%) and 489 (44.5%) patients respectively. On multivariate analysis, factors associated with poor nighttime sleep were CTP class C (vs. class A), presence of minimal hepatic encephalopathy (MHE), intermediate or evening type of diurnal preference category (vs. morning type), high risk for obstructive sleep apnea (OSA), diuretic use, presence of major depression, and presence of generalized anxiety disorder (GAD). Factors associated with EDS on multivariate analysis were CTP class B and C (vs. class A), intermediate or evening type of diurnal preference category (vs. morning type), high risk for OSA, presence of major depression, and presence of GAD. CONCLUSIONS: Sleep-wake abnormalities are common in patients with cirrhosis. CTP status, diurnal preference chronotype, risk of OSA, major depression and GAD are associated with both poor nighttime sleep and EDS. MHE and diuretic use are associated with poor nighttime sleep, but not with EDS.

Comparison of 5% human albumin and normal saline for fluid resuscitation in sepsis induced hypotension among patients with cirrhosis (FRISC study): a randomized controlled trial.

AIMS: Sepsis and septic shock are common causes of hospitalization and mortality in patients with cirrhosis. There is no data on the choice of fluid and resuscitation protocols in sepsis-induced hypotension in cirrhosis. METHODS: In this open-label trial conducted at a single center, we enrolled 308 cirrhotics with sepsis-induced hypotension and randomized them to receive either 5% albumin or normal saline. The primary endpoint was a reversal of hypotension [mean arterial pressure, MAP, ≥ 65 mmHg] at 3 h. Secondary endpoints included serial effects on heart rate, arterial lactate and urine output. RESULTS: 154 patients each received 5% albumin (males, 79.8%, mean MAP 52.9 ± 7.0 mm Hg) or 0.9% saline (85.1%, 53.4 ± 6.3 mm Hg) with comparable baseline parameters and liver disease severity. Reversal of hypotension was higher in patients receiving 5% albumin than saline at the end of one hour [25.3% and 11.7%, p = 0.03, Odds ratio (95% CI)-1.9 (1.08-3.42)] and at the end of three hours [11.7% and 3.2%, p = 0.008, 3.9 (1.42-10.9)]. Sustained reduction in heart rate and hyperlactatemia (p < 0.001) was better in the albumin group. At one week, the proportion of patients surviving was higher in the albumin group than those receiving saline (43.5% vs 38.3%, p = 0.03). Female gender and SOFA ≥ 11 were predictors of non-response to fluid. CONCLUSIONS: 5% human albumin is safe and beneficial in reversing sepsis-induced hypotension compared to normal saline in patients with cirrhosis improving clinically assessable parameters of systemic hemodynamics, tissue perfusion and in-hospital short-term survival of cirrhosis patients with sepsis.

Development of a machine learning model to predict bleed in esophageal varices in compensated advanced chronic liver disease: A proof of concept.

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.

Hydrocarbon contamination in angström-scale channels.

Nonspecific molecular adsorption such as airborne contamination occurs on most surfaces including those of 2D materials and alters their properties. While surface contamination is studied using a plethora of techniques, the effect of contamination on confined systems such as nanochannels/pores leading to their clogging is still lacking. We report a systematic investigation of hydrocarbon adsorption in angstrom (Å) slit channels of varying heights. Hexane is chosen to mimic the hydrocarbon contamination and the clogging of the Å-channels is evaluated via a helium gas flow measurement. The level of hexane adsorption, in other words, the degree of clogging depends on the size difference between the channels and hexane. A dynamic transition of the clogging and revival process is shown in sub-2 nm thin channels. Long-term storage and stability of our Å-channels are demonstrated here for up to three years, alleviating the contamination and unclogging the channels using thermal treatment. This study highlights the importance of the nanochannels' stability and demonstrates the self-cleansing nature of sub-2 nm thin channels enabling a robust platform for molecular transport and separation studies. We provide a method to assess the cleanliness of nanoporous membranes, which is vital for the practical applications of nanofluidics in various fields such as molecular sensing, separation and power generation.