Effect of the Heaviness of Smoking Index (HSI) and Duration of Smoking on Central Neural Processing Using Brainstem Auditory Evoked Responses (BAERs).

Purpose of study The goal of this research was to find the correlation of nicotine dependence and duration of smoking with the status of central neuronal processing in chronic smokers. Our primary objective was to record brainstem auditory evoked responses (BAERs) in chronic smokers and further find their correlation to the Heaviness of Smoking Index (HSI) scores and years of non-abstained smoking of the subjects. We postulated that smoking leads to myelination abnormalities which in turn causes decreased impulse conduction velocity. Methods After obtaining informed consent, we conducted BAER on 60 male smokers who were further classified into groups based on their HSI scores (low, moderate, and high nicotine dependency) and 20 age-matched, non-smoking males. The obtained data was examined using the two-way ANOVA test and the Kruskal-Wallis test. Pearson's coefficient of correlation and the median (as a measure of central tendency) were calculated. Results We observed a non-significant negative correlation between wave I BAER latency and the degree of nicotine dependence. Wave II showed minimal correlation, whereas a positive correlation was seen in waves III, IV, and V. Interpeak latencies (IPL) I-III and III-V showed a non-significant positive correlation with the HSI score, whereas IPL I-V showed a significant positive correlation with the same. When correlated with the duration of smoking (years), the latencies (msec) of BAER waves I-V showed a pattern of progressively decreasing negative correlation, out of which waves I, II, and III were significantly affected. The IPL (msec) of waves I-III was non-significantly, yet positively, correlated, while the IPL of waves I-V and III-V showed a significant positive correlation to the duration of smoking. Conclusions The degree of nicotine dependence and duration of tobacco smoking progressively affected the latencies of BAER waves at the pontomedullary level of the brainstem. This indicates slower central neuronal processing at this level and an increased central transmission time, the extent of which is directly dependent on the extent of tobacco smoking. This is attributed to the myelination defects caused by direct and indirect effects of the toxic metabolites of tobacco smoke, chronic hypoxia, hypercapnia, and respiratory acidosis.

Endoscopic Glue Injection vs Glue Plus BRTO or TIPSS for Preventing Gastric Variceal Bleeding: A Randomized Controlled Trial.

BACKGROUND AND AIMS: The study sought to compare the efficacy of endoscopic injection sclerotherapy with cyanoacrylate glue (EIS-CYA) vs EIS-CYA plus a radiologic intervention (RI) (either transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration) for secondary prophylaxis in patients with liver cirrhosis who presented with acute variceal bleeding from cardiofundal varices. Primary outcome measure was gastric varix (GV) rebleed rates at 1 year. METHODS: Consecutive cirrhosis patients with acute variceal bleeding from cardiofundal varices were randomized into 2 arms (45 in each) after primary hemostasis by EIS-CYA. In the endoscopic intervention (EI) arm, EIS-CYA was repeated at regular intervals (1, 3, 6, and 12 months), while in the RI arm, patients underwent transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration followed by endoscopic surveillance. RESULTS: GV rebleed rates at 1 year were higher in the EI arm compared with the RI arm: 11 (24.4%; 95% confidence interval [CI], 12.9%-39.5%) vs 1 (2.2%; 95% CI, 0.1%-11.8%) (P = .004; absolute risk difference: 22.2%; 95% CI, 8.4%-36.6%). GV rebleed-related mortality in the EI arm (8 [17.8%; 95% CI, 8.0%-32.1%]) was significantly higher than in the RI arm (1 [2.2%; 0.1%-11.8%]) (P = .030; absolute risk difference: 15.6; 95% CI, 2.9%-29.2%); however, there was no difference in all-cause mortality between the 2 groups (12 [26.7%; 95% CI, 14.6%-41.9%] vs 7 [15.6%; 95% CI, 6.5%-29.5%]). The number needed to treat to prevent 1 GV-related rebleed at 1 year was 4.5. CONCLUSIONS: RI for secondary prophylaxis reduces rebleeding from GV and GV rebleeding-related mortality in patients with GV hemorrhage. (CTRI/2021/02/031396).

Thromboelastography-Guided versus Standard-of-Care or On-Demand Platelet Transfusion in Patients with Cirrhosis and Thrombocytopenia Undergoing Procedures: A Randomized Controlled Trial.

PURPOSE: To determine the rate of platelet transfusion in patients with cirrhosis and severe thrombocytopenia (platelet counts <50 × 109/L) undergoing high-risk invasive procedures when prescribed by thromboelastography (TEG) compared with empirical and on-demand transfusion strategies. MATERIALS AND METHODS: This was a single-center, single-blinded, randomized controlled trial. Patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures were randomized into 3 groups: TEG group, transfusions based on TEG parameters; standard of care (SOC) group, 3 units of random donor platelets before procedure; and on-demand group, transfusions based on procedural adverse events/clinician's discretion. The primary outcome was periprocedural platelet transfusion in each arm. RESULTS: Eighty-seven patients were randomized (29 in each group) with no significant differences in demographics/coagulation profile/procedures. The median platelet count was 33 × 109/L (interquartile range, 26-43 × 109/L). Percutaneous liver biopsy was the most common procedure (46, 52.9%). Significantly lower number of patients in the TEG group received platelets (4 cases, 13.8%; 95% CI, 3.9-31.7) compared with SOC group (100%; 95% CI, 88.1-100; P < .001). Four patients in the on-demand group received platelets (13.8%; 95% CI, 3.9-31.7). Minor (World Health Organization [WHO] Grade 2) procedure-related bleeding occurred in 3 (10%; 95% CI, 2.2-27.4) patients in the TEG-guided transfusion group compared with 1 (3.4%; 95% CI, 0.1-17.8) patient each in the SOC and on-demand groups (P = .43), although the study was not powered for comparison of bleeding rates. No bleeding-related mortality was observed in any of the 3 groups. CONCLUSIONS: TEG-prescribed transfusion reduced prophylactic transfusions in patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures. The study was not powered for comparison of bleeding rates.

Intravenous albumin infusion does not augment the response rate to a combination of exclusive enteral nutrition and intravenous steroids in acute severe ulcerative colitis: a randomized controlled trial.

INTRODUCTION: 30-40% patients with acute severe ulcerative colitis (ASUC) fail intravenous (IV) steroids requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition (EEN) has been shown to improve steroid response and albumin levels. Albumin infusion due to its anti-inflammatory and anti-oxidant properties might further improve steroid response in ASUC, which was evaluated in present study. METHODS: In this open-label randomized controlled trial, patients with ASUC were randomized in 1:1 ratio to albumin + standard of care (SOC) + EEN vs. SOC + EEN (Jan2021 - Feb2023). Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in albumin arm were administered 5 days of 20% w/v intravenous albumin (100 ml). Primary outcome was 1) steroid failure (need for rescue medical therapy or colectomy) and 2) proportion of patients with adverse events. RESULTS: Sixty-one patients (albumin-30, SOC-31)(mean age-31.6±0.4 years, male-57.4%), were included. Baseline characteristics were comparable. There was no difference in steroid failure between albumin and SOC arm(10/30(33.33 %) vs 13/31(41.94 %), p=0.49). No adverse events were reported with albumin infusions. Colectomy rate(10% vs 9.68%, P=1), response to salvage medical therapy (88.89% vs 76.92%, P=0.62) and median duration of hospitalization (10.5(7-16) vs 10(7-20), P=0.43) were also comparable. Long-term composite outcome of colectomy and re-admission rates was numerically higher in the albumin than SOC arm (37.04% vs 17.86%, p>0.05), although it did not reach statistical significance. CONCLUSION: There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.

Definitions, Etiologies, and Outcomes of Acute on Chronic Liver Failure: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a major public health concern. We aimed to assess the definitions, etiologic spectrum, organ failure (OF), and outcomes of ACLF globally. METHODS: Three databases were searched for studies on ACLF from 1990 until September 2022. Information regarding definitions, acute precipitants, underlying chronic liver disease (CLD), OF, and mortality were extracted. Meta-analyses were performed for pooled prevalence rates (95% confidence interval [CI]) using random-effects model for each definition of ACLF. RESULTS: Of the 11,451 studies identified, 114 articles (142 cohorts encompassing 210,239 patients) met the eligibility criteria. Most studies (53.2%) used the European Association for the Study of the Liver (EASL) definition, followed by Asia-Pacific Association for the Study of the Liver (APASL) (33.3%). Systemic infection was the major acute precipitant, and alcohol use was the major cause of CLD in EASL-defined studies, whereas alcohol was both the major acute precipitant and cause of CLD in APASL-defined studies. Liver failure was the major OF in APASL-based studies, whereas renal failure was predominant in EASL-based studies. Thirty-day mortality varied across definitions: APASL: 38.9%, 95% CI, 31.2%-46.9%; EASL: 47.9%, 95% CI, 42.2%-53.5%; and NACSELD: 52.2%, 95% CI, 51.9%-52.5%. Diagnostic overlap between definitions ranged from 7.7% to 80.2%. Meta-regression suggested that the World Health Organization region influenced 30-day mortality in studies using EASL definition. CONCLUSIONS: Heterogeneity in the definition of ACLF proposed by different expert societies and regional preferences in its use result in differences in clinical phenotype and outcomes. A uniform definition would enhance the comparability and interpretation of global data.

A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn's Disease.

BACKGROUND: Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population. METHODS: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model. RESULTS: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time. CONCLUSIONS: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing. TRIAL REGISTRATION: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .

Combined or High Dose Immunosuppression in Inflammatory Bowel Disease patients who are NUDT15 Homozygous Harbors Risk of Developing Invasive Fungal Infections: A Case Series.

NUDT15 homozygous mutations predispose patients to severe leucopenia, which invites risk of disseminated fungal infections when high doses or a combination of immunosuppressives are administered in this patient population.

Etiological Spectrum of Cirrhosis in India: A Systematic Review and Meta-analysis.

Background: Cirrhosis is a significant cause of morbidity and mortality globally and in India. This systematic review and meta-analysis aimed to ascertain the etiological spectrum and changing trends of cirrhosis in India. Methods: We searched electronic databases, including Pubmed/Medline, Scopus, and Embase. We included original studies that reported the etiology of cirrhosis in the Indian population. Results: We included 158 studies (adults: 147, children: 11). The overall pooled estimate of alcohol as a cause of cirrhosis in adults was 43.2% (95% confidence interval (CI) 39.8-46.6%; I2 = 97.8%), followed by nonalcoholic fatty liver disease (NAFLD)/cryptogenic in 14.4%, 95% CI (11.7-17.3%; I2 = 98.4%), hepatitis B virus (HBV) in 11.5%, 95% CI (9.8-13.3%; I2 = 96.6%), and hepatitis C virus (HCV) in 6.2%, 95% CI (4.8-7.8%; I2 = 97.2%) of the included patients. The most common cause of cirrhosis in all zones was alcohol-related. Comparison of etiologies over time revealed a reduction in the viral hepatitis-related and an increase in the proportion of alcohol-related and NAFLD/cryptogenic-related cirrhosis. The overall pooled estimates of various etiologies in children were: HBV in 10.7%, 95% CI (4.6-18.7%; I2 = 91.0%), NAFLD/Cryptogenic in 22.3%, 95% CI (9.0-39.2%; I2 = 96.7%), and HCV in 2.0%, 95% CI (0.0-8.5%; I2 = 94.6%). Conclusions: Alcohol is the most common etiology of cirrhosis in adults in India. The proportions of alcohol and NAFLD-related cirrhosis are increasing, and those of viral hepatitis-related cirrhosis are reducing. The results of our meta-analysis will help formulate health policies and the allocation of resources.

Comparison of 1-day versus 3-day intravenous terlipressin in cirrhosis patients with variceal bleeding: A pilot randomised controlled trial.

BACKGROUND: In cirrhosis patients with acute variceal bleeding (AVB), the optimal duration of vasoconstrictor therapy after endoscopic haemostasis is unclear. AIMS: We aimed to compare efficacy of 1-day versus 3-day terlipressin therapy in cirrhosis patients with AVB post-endoscopic intervention. The primary objective was to compare rebleeding at 5 days between the two arms. Secondary objectives included rebleeding and mortality rates at 6 weeks. METHODS: In this open-label, randomised controlled trial, cirrhosis patients with AVB were randomised to either 1-day or 3-day terlipressin therapy. RESULTS: A total of 150 cirrhosis patients with AVB were recruited to receive either 1 day (n = 75) or 3 days (n = 75) of terlipressin therapy. One patient from 1-day arm was excluded. Modified intention-to-treat analysis included 149 patients. Baseline characteristics were comparable between the two groups. Rebleeding at 5 days: 3 (4.1%; 95% confidence interval [CI]: 0.4-9.0) versus 4 (5.3%; 95% CI: 2.0-10.0), risk difference (RD) p = 0.726 and 5-day mortality rates: 1 (1.4%; 95% CI: 0-7.3) versus 1 (1.3%; 95% CI: 0.2-7.0), RD p = 0.960 were similar. Rebleeding at 42 days: 9 (12.2%; 95% CI: 7.0-20.0) versus 10 (13.3%; 95% CI: 7.0-20.0), RD p = 0.842 and mortality at 42 days: 5 (6.8%; 95% CI: 3.0-10.0) versus 4 (5.3%; 95% CI: 2.0-10.0), RD p = 0.704 were also similar. Patients in the 1-day terlipressin therapy arm experienced significantly fewer adverse effects compared with those receiving 3 days of terlipressin therapy: 28 (37.8%) versus 42 (56%), p = 0.026. CONCLUSIONS: Our results suggest that 1 day of terlipressin therapy is associated with similar 5-day and 42-day rebleeding rates, 42-day mortality and an overall superior safety profile compared with 3-day of terlipressin therapy. These findings require to be validated in double-blinded, larger, multiethnic and multicentre studies across the various stages of cirrhosis (CTRI/2019/10/021771).

The practice of fecal microbiota transplantation in inflammatory bowel disease.

Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn's disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.

Efficacy of Rifaximin in Patients With Abdominal Bloating or Distension: A Systematic Review and Meta-analysis.

BACKGROUND: Abdominal bloating is a common complaint in patients with functional and organic bowel disease. Rifaximin, a nonabsorbable antibiotic, has been tried for the treatment of this disease. We performed a systematic review and meta-analysis to study the efficacy of rifaximin in abdominal bloating and distension in patients with functional gastrointestinal disorders (FGID). METHODS: We accessed 4 databases (MEDLINE, Embase, SCOPUS, and Web of Science) to identify randomized placebo-controlled trials that utilized rifaximin in FGID. We excluded observational studies, those including patients with organic bowel disorders such as inflammatory bowel diseases, or those in which rifaximin was given for other indications, such as hepatic encephalopathy. RESULTS: A total of 1426 articles were available, of which 813 articles were screened after removing duplicates and 34 articles were selected for full-text review. Finally, 10 trials (3326 patients) were included. Rifaximin was administered in doses ranging from 400 to 1650 mg per day for 1 to 2 weeks. Rifaximin therapy led to a higher likelihood of improvement in symptoms of bloating (44.6% vs. 34.6%, RR 1.22, 95% CI 1.11, 1.35; n=2401 patients) without significant heterogeneity. However, daily doses less than 1200 mg/day were similar to placebo ( P =0.09). Bloating was quantified subjectively in 7 studies, and rifaximin led to a greater reduction in bloating scores compared with placebo (standardized mean difference -0.3, 95% CI -0.51, -0.1, P =0.04) but carried significant heterogeneity ( I2 =61.6%, P =0.01). CONCLUSIONS: Rifaximin therapy is associated with an increased likelihood of improvement in bloating and distension, as well as reduces the subjective severity of these symptoms in patients with FGID.

ABDA Score: A Non-invasive Model to Identify Subjects with Fibrotic Non-alcoholic Steatohepatitis in the Community.

Background: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) are prevalent in the community, especially among those with metabolic syndrome. Patients with fibrotic NASH are at increased risk of liver-related-events. Currently available non-invasive tests have not been utilized for screening for fibrotic NASH among the community. We aimed to develop a screening tool for fibrotic NASH among community members. Methods: We included two large cohorts aimed at assessing cardiovascular disease among community members. Fibrotic NASH was defined using the FibroScan-aspartate aminotransferase score of ≥0.67 that identifies ≥F2 fibrosis and a non-alcoholic fatty liver disease activity score ≥4 with a specificity of 90%. Metabolic parameters, biochemical tests and anthropometry were used to develop a multivariate model. Results: The derivation cohort (n = 1660) included a population with a median age 45 years, 42.5% males, metabolic syndrome in 66% and 2.7% (n = 45) with fibrotic NASH. Multivariate analysis identified the four significant variables (Age, body mass index , Diabetes and alanine aminotransferas levels) used to derive an ABDA score. The score had high diagnostic accuracy (the area under receiver-operating characteristic curve, 0.952) with adequate internal validity. An ABDA score ≥-3.52 identified fibrotic NASH in the derivation cohort with a sensitivity and specificity of 88.9% and 88.3%. The score was validated in a second cohort (n = 357) that included 21 patients (5.9%) with fibrotic NASH, where it demonstrated a high area under receiver-operating characteristic curve (0.948), sensitivity (81%) and specificity (89.3%). Conclusions: ABDA score utilizes four easily available parameters to identify fibrotic NASH with high accuracy in the community.

Poor Performance of Non-invasive Tests for Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: A Multicentric Asian Study.

BACKGROUND: Non-invasive tests (NITs) are useful to assess advanced fibrosis (AF) in nonalcoholic fatty liver disease (NAFLD). Data from Asian countries suggest that these tests have poor performance. We aimed to assess diagnostic accuracy of established thresholds of biomarker-based NITs and Transient Elastography (TE) in identifying AF and evaluated the utility of a two-step test approach. METHODS: Biopsy-proven 641 NAFLD patients (55.2% males, median age 42 years) were included from three different centers of Asia. AF (≥ F3) was identified as per histological staging (24.8%). RESULTS: TE had the highest area under the receiver operating characteristic curve (AUROC) 0.82 (0.79-0.86), and all other biomarker-based NITs had low AUROC (< 0.7). NITs performed poorly at established thresholds. The combination of NITs utilizing liver stiffness measurement (LSM) and biomarkers, Agile 3+ and FAST, demonstrated acceptable diagnostic accuracy (AUROC 0.82 and 0.78, respectively), but none were superior to LSM alone. LSM measured using appropriate M and XL probes remained accurate regardless of body mass index (BMI); NFS and APRI scores were less accurate at higher BMI ranges. A two-step approach using NFS rule-out criteria (< - 2.97 to rule out) followed by LSM (< 7.3 kPa to rule out and ≥ 12.7 kPa to rule in) correctly classified 62.4% of patients, with only 10.2% of patients incorrectly classified. CONCLUSION: NITs have not been validated to identify AF in the Asian NAFLD population, and internationally accepted thresholds yield high false-negative rates. LSM and LSM-based combination tests remain the most accurate.

Hepatic Venous Pressure Gradient Predicts Further Decompensation in Cirrhosis Patients with Acute Esophageal Variceal Bleeding.

BACKGROUND: The role of hepatic venous pressure gradient (HVPG) in predicting further decompensation in cirrhosis patients with acute variceal bleeding (AVB) is not known. We aimed to evaluate the role of HVPG in predicting further decompensation in cirrhosis patients with AVB Methods: In this prospective study, 145 patients with cirrhosis with esophageal or gastric AVB were included. HVPG was measured on the day of the AVB. Decompensating events occurring after 42-days of AVB were considered further decompensation. RESULTS: The median age of the study cohort was 44 years; 88.3% males. The predominant etiology of cirrhosis was alcohol (46.2%). Overall, 40 (27.6%) patients developed further decompensation during median follow-up of 296 days following AVB. Gastro intestinal bleeding n = 27 (18.6%) and new-onset/worsening ascites n = 20 (13.8%) were the most common decompensating events. According to the multivariate model, HVPG was an independent predictor of any further decompensation in esophageal AVB patients but not in gastric variceal bleeding patients. HVPG cut-off of ≥16 mmHg predicted further decompensation in the esophageal AVB. However, HVPG was not an independent predictor of mortality. CONCLUSION: HVPG measured during an episode of acute variceal hemorrhage from esophageal varices predicts further decompensating events in cirrhosis patients.

Th17 overexpression in severe COVID-19: a prospective observational study.

INTRODUCTION: The objective of the study was to determine T-cell subtypes, Natural Killer cell activity and cytokines in COVID-19 patients with mild to moderate disease and compare them between patients who had recovered and those who had progressed to severe disease. METHODS: Peripheral blood samples of COVID-19 patients were collected at the time of hospital admission and after one week. These samples were analysed for interleukins (IL-6, IL-17a) using chemiluminescence ELISA. The T-cell subsets (T naïve, T regulatory, Th17, Th1, Th2, CD8+ T cells] were studied using flow cytometry. Mild, moderate and severe COVID-19 are defined as per CDC guidelines. RESULTS: Nineteen COVID-19-positive patients were enrolled between June 2020 to December 2021. Nine had mild COVID-19 and 10 had moderate COVID-19 at recruitment. All mild cases recovered without progression to severe disease, while five patients from the moderate group progressed to severe disease. Overall, there is a decrease in lymphocyte count in patients with moderate-severe disease, but the ratio of Th17 [5.91 (2.69-12.01)] was higher compared to Th1 [1.12 (0.27-3.13)] and Th2[2.34 (2-3.5)]. The high baseline level of IL-6 observed in patients with moderate disease leads to the proliferation of more Th17 type of CD4+ T-cells(p=0.002) and suppression of Treg cells. A higher Th17 subset leads to neutrophilic inflammation in patients with severe COVID-19. CONCLUSION: Interpretation conclusions: Higher baseline IL-6 leads to depletion of regulatory T-cells, Th1 Th2 CD4 cells. IL-6 leads to the proliferation of Th17 type of CD4+ subsets in moderate COVID-19. Higher Th17 cells in moderate COVID-19 patients lead to the production of IL-17a, which may result in intense neutrophilic inflammatory response and cytokine storm.

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.

Giant aortic arch aneurysm presenting with hoarseness of voice.

A middle-aged male with hypertension and dyslipidaemia presented with hoarseness of voice due to a left vocal palsy. The chest radiograph revealed a saccular opacity silhouetting the left border of the aortic knuckle, suggestive of a large aortic arch aneurysm. Routine investigations, such as a chest radiograph do occasionally identify potentially fatal pathology, even when perhaps not strictly indicated; uncommon presentations do occur!

Neuroleptic malignant syndrome in a case of extra-pontine myelinolysis: On the horns of dilemma.

Osmotic demyelination syndrome (ODS) and neuroleptic malignant syndrome (NMS) lead to severe neurological sequalae. Though currently thought to be different syndromes, literature suggests a relation between the two. We present the case of a 45-year-old male who was found to have chronic severe hyponatremia and underwent rapid correction of sodium and developed parkinsonism features. Magnetic resonance imaging (MRI) confirmed extrapontine myelinolysis (a type of ODS). The patient received haloperidol for agitated behavior and developed new features of rigidity, fever, tachycardia and elevated creatine phosphokinase (CPK) levels and thus neuroleptic malignant syndrome was suspected to overlap with ODS. We report this case highlighting the difficulty in differentiating the between ODS and NMS and their relationship.