Normative values of skeletal muscle mass, strength and performance in the Indian population.

BACKGROUND AND OBJECTIVES: Skeletal muscle is characterized by its mass, strength and performance. These normative values are pivotal in defining sarcopenia. Sarcopenia is associated with poor outcome of numerous medical and surgical conditions. This study aimed to establish normative benchmarks for skeletal muscle mass, strength and performance within the context of the Asian (Indian) population. METHODS: Our investigation utilized the computed tomography (CT) skeletal muscle index (SMI), handgrip strength (HGS), gait velocity and chair-stand test to construct reference values for muscle characteristics in the Indian population. RESULTS: The SMI analysis incorporated 1485 cases of acute abdomen (54.7%) males). The calculated SMI (kg/m2) was 38.50 (35.05-42.30) in males and 36.30 (32.20-41.20) in females (p = 0.510). The study also involved 3083 healthy individuals (67.6% males) evaluated for muscle strength and performance between August 2017 and August 2018. Notably, HGS (kg force) was recorded at 34.95 (26.50-43.30) in males and 25.50 (18.60-31.20) in females (p < 0.001). Gait velocity (metres/second) exhibited values of 1.25 (1.04-1.56) in males and 1.24 (1.03-1.56) in females (p = 0.851). Additionally, chair-stand test (seconds) results were 10.00 (9.00-13.00) in males and 12.00 (10.00-14.00) in females (p < 0.001). CONCLUSIONS: The investigation determined that males had greater muscle strength and performance than females. But gender wise, there was no significant difference in muscle mass. Interestingly, our population's muscle parameters were consistently lower compared to western literature benchmarks. These normative values will help to define sarcopenia parameters in our population, which have prognostic value in multiple ailments.

Wide Local Excision of Complex or Infected Pilonidal Sinus Followed by Negative Pressure Wound Therapy: Does It Enhance Wound Healing?

Background Pilonidal sinus disease (PSD) is a chronic skin condition caused by hair retention that affects the sacrococcygeal cleft. The purpose of this study is to compare the efficacy of negative pressure wound therapy (NPWT) to routine daily dressings (DDs) in wound healing after complex or infected pilonidal sinus tract excision. Materials and methods The study included 81 individuals who had extensive local excisions for pilonidal sinuses that were complex or infected. Randomly selected participants were given either NPWT or the usual dressing. Between the two groups, the length of hospitalization, the amount of time needed to resume daily activities, and the amount of time needed for full wound closure were compared. Results Forty-two patients received NPWT, while 39 patients received DDs as usual. There was no discernible difference between the two groups in terms of operating time or hospital stay. However, patients who underwent NPWT experienced a quicker final wound closure (59.24 ± 10.21 days compared to routine DD with a mean time of 75.31 ± 14.68 days, P = 0.001) and returned to normal activities earlier (17.36 versus 21.75 days in NPWT and routine DD, respectively). Conclusion Compared to patients who received standard DDs, those who were postoperatively managed with NPWT showed faster wound healing and return to normal activities. Whenever feasible, this strategy may be employed to improve patient recovery.

Quality of life in Indian patients with functional dyspepsia: Translation and validation of the Hindi version of Short-Form Nepean Dyspepsia Index.

BACKGROUND/PURPOSE: Patients with functional dyspepsia (FD) have poor health-related quality of life (HRQOL), but Indian data are  lacking. Also, there is non-availability of validated disease-specific questionnaire to assess HRQOL in Hindi-speaking patients with dyspepsia. We aimed to develop and validate a reliable translation of Short-Form Nepean Dyspepsia Index (SF-NDI) in Hindi, and assess the impact of FD on HRQOL in Indian patients. METHODS: Cross-cultural adaptation of English version of SF-NDI, translation to Hindi, and adaptation of Hindi version were performed using standard procedures. English and Hindi versions were assessed against Short Form-36 (SF-36), examining for internal consistency, test-retest reliability, and validity. RESULTS: Total 211 FD patients (144 Hindi speaking, 67 English speaking) were enrolled (mean age 40.8 ± 11.7 years; male:female = 115:96). Median total SF-NDI scores for both languages were 38.75 and 40.0, respectively. Test-retest reliability intraclass correlation coefficients were 0.85 (Hindi) and 0.89 (English). Internal consistency evaluation revealed Cronbach's α coefficient of 0.79-0.86 (Hindi) and 0.78-0.89 (English). SF-NDI sub-scales showed moderate to good correlation with various domains of SF-36 (content validity). There was significant (p < 0.001) decline of HRQOL in patients with severe dyspepsia relative to those with mild dyspepsia (construct validity). On multivariate analysis, factors independently associated with HRQOL were duration of symptoms and dyspepsia severity. CONCLUSION: Both English and Hindi versions of SF-NDI are reliable and valid for HRQOL assessment in Indian FD patients, and will be useful in future epidemiological and clinical studies. Indian FD patients have poor HRQOL, being worse in those with severe dyspepsia and longer duration of symptoms.

Low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet in patients with diarrhea-predominant irritable bowel syndrome: A prospective, randomized trial.

BACKGROUND AND AIM: Low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet improves irritable bowel syndrome (IBS) symptoms. Data on long-term "modified" FODMAP diet are emerging. We aimed to assess efficacy and acceptability of short-term "strict" low FODMAP diet (LFD) and long-term "modified" FODMAP diet in patients with diarrhea-predominant IBS (IBS-D). METHODS: This prospective randomized trial included patients with IBS-D (Rome IV) and IBS severity scoring system (IBS-SSS) ≥ 175. In phase I (4 weeks), patients were randomized to strict LFD and traditional dietary advice (TDA) groups. From 4 to 16 weeks, LFD group was advised systematic reintroduction of FODMAPs ("modified" FODMAP diet). Response was defined as > 50-point reduction in IBS-SSS. RESULTS: Of the total 166 patients with IBS-D screened, 101 (mean age 41.9 ± 17.1 years, 58% male) were randomized to LFD (n = 52) and TDA (n = 49) groups. Both at 4 and 16 weeks, total IBS-SSS and IBS quality of life score reduced significantly in both groups, but there was significantly greater reduction in LFD group. By intention-to-treat analysis, responders in LFD group were significantly higher than TDA group (4 weeks-62.7% [32/51] vs 40.8% [20/49], respectively, P = 0.0448; 16 weeks-52.9% [27/51] vs 30.6% [15/49], respectively; P = 0.0274). Compliance to LFD was 93% at 4 weeks and 64% at 16 weeks. Energy, carbohydrate, fat, and fiber intake showed reduction in LFD group at 4 weeks, which improved till 16 weeks. CONCLUSIONS: Strict LFD for short-term and "modified" LFD for long term in IBS-D patients is acceptable and leads to significant improvement in symptoms and quality of life.

Muscle strength and physical performance, rather than muscle mass, correlate with mortality in end-stage liver disease.

OBJECTIVES: Sarcopenia is characterized by the loss of skeletal muscle mass, strength and performance. The study aimed to provide cut off values of various Sarcopenia parameters [computerized tomography skeletal muscle index (SMI), handgrip strength (HGS), gait velocity and chair stand] to predict mortality in end-stage liver disease (ESLD). METHODS: The inclusion criteria were age 18-75 years, model for end-stage liver disease > 15. All patients with advanced heart, lung, kidney diseases, active malignancy were excluded from the study. Sarcopenia indices were compared between survivors and non-survivors to find cut off value for prediction of mortality in ESLD patients. RESULTS: One hundred sixty-one subjects suffering from ESLD were enrolled. The cutoff value of the SMI to identify high risk of mortality in sarcopenia patients is ≤21.2 cm2/m2, area under the curve (AUC) 0.537 [95% confidence interval (CI) 0.456-0.616]. The cutoff value of the hand grip strength to identify high-risk mortality is ≤25.3 kilogram-force, AUC 0.682 (95% CI 0.604-0.753). The cutoff value of the gait velocity for the same is as ≤0.84 m/s, AUC 0.551 (95% CI 0.459-0.641). The cutoff value of the chair stand is ≥20.9 seconds, AUC 0.956 (95% CI 0.910-0.983). In the multivariate analysis, HGS, gait velocity and chair stand correlated with mortality. CONCLUSION: The current study is a comprehensive Asian study that gives the cut off values of Sarcopenia: muscle mass, strength and performance which identify high risk of mortality in ESLD patients. Muscle strength and performance correlated with mortality.

Early feeding after esophageal variceal band ligation in cirrhotics is safe: Randomized controlled trial.

BACKGROUND AND AIM: Oral feeding following variceal ligation in cirrhotics is usually delayed due to fear of rebleeding. Solid diet is usually further delayed (until 72 h) despite lack of evidence. We aimed to compare the impact of early versus delayed feeding on rebleeding following variceal ligation. METHODS: This was a prospective randomized controlled trial including patients undergoing variceal ligation for active esophageal variceal bleeding. Patients were randomized into two groups. In the early-feeding group, liquid diet was given after 1 h following variceal ligation and a regular solid diet was resumed after 4 h. In the delayed-feeding group, patients fasted for the first 4 h after variceal ligation, liquid diet was given until 24 h, soft diet for the next 48 h and a regular solid diet after 72 h. RESULTS: There were 52 and 49 patients in the early and delayed feeding groups, respectively. Very early rebleeding rates [2 (3.84%) vs 1 (2.04%); P ≥ 0.99] and delayed rebleeding rates [2 (3.84%) vs 4 (8.16%); P = 0.75] were similar in both groups. Protein and calorie intake in the early-feeding group was significantly better and early infections in active bleeders were significantly lower compared to the delayed-feeding group. One-month mortality was similar in both groups [3 (5.76%) vs 4 (8.16%); P = 0.75]. CONCLUSION: Early feeding with a regular solid diet in conscious patients after successful variceal ligation for esophageal varices is safe, provides better nutrition and results in lower incidence of infections in bleeders compared to delayed feeding.

L-ornithine L-aspartate in bouts of overt hepatic encephalopathy.

High-quality data on the efficacy of L-ornithine L-aspartate (LOLA) in patients with cirrhosis and bouts of overt hepatic encephalopathy (OHE) are missing. We evaluated the efficacy of intravenous LOLA in the reversal of bouts of OHE in patients with cirrhosis. In this prospective, double-blind, randomized, placebo-controlled trial conducted at two tertiary care institutes in India, 370 patients with cirrhosis and bouts of OHE were screened. After exclusion, 193 (52.16%) patients were randomized to receive either intravenous infusions of LOLA (n = 98), 30 g daily, or placebo (n = 95) for 5 days. Standard of care treatment (including lactulose and ceftriaxone) was given in both groups. Randomization was done centrally (http://www.sealedenvelope.com/). All study personnel were blinded to the treatment assignment. Fasting venous ammonia levels were estimated daily from 0 to 5 days. Serum tumor necrosis factor-alpha, interleukins, hemogram, and liver and renal function tests were performed at days 0 and 5. Primary outcome was mental state grade at day 5 of treatment. The grade of OHE was significantly lower in the LOLA group (compared to placebo) on days 1-4 but not on day 5. The mean time taken for recovery was lower in the LOLA group compared to the placebo group (1.92 ± 0.93 versus 2.50 ± 1.03 days, P = 0.002; 95% confidence interval -0.852 to -0.202). Venous ammonia at day 5 and length of hospital stay were significantly lower in the LOLA group. No significant difference in interleukins was seen between the groups. Conclusion: In patients with bouts of OHE, intravenous LOLA (as an add-on therapy to lactulose and ceftriaxone) significantly improves the grade of OHE over days 1-4, but not on day 5, and decreases venous ammonia, time of recovery, and length of hospital stay. (Hepatology 2018;67:700-710).

Treatment of chronic hepatitis C genotype 3 with Sofosbuvir-based therpy: a real-life study.

BACKGROUND AND AIMS: Recently, Sofosbuvir was launched in India at affordable cost. We conducted a real-life study to determine the efficacy and safety of Sofosbuvir plus Ribavirin, with and without peginterferon-alfa 2a, in patients with chronic hepatitis C (CHC) genotype 3, the commonest genotype in South Asia. METHODS: This study included data of CHC patients from 11 sites in northern India between March 2015 and December 2015 (n = 1203). Patients with CHC genotype 3 (n = 931), who were treated with either Sofosbuvir 400 mg plus weight-based Ribavirin, daily ×24 weeks (n = 432) (dual therapy), or Peginterferon-α2a 180 mcg weekly, Sofosbuvir 400 mg plus weight-based Ribavirin, daily ×12 weeks (n = 499) (triple therapy) were included for analysis. Primary outcome was the proportion of patients achieving sustained viral response at 12 weeks post-therapy. RESULTS: The overall SVR rates were 91 and 92% in the dual and triple therapy arms, respectively. The SVR rates in treatment experienced were 67 and 74% versus 93 and 96% in naïve patients, on the dual and triple therapy arms, respectively. The SVR rates of cirrhotics were 73 and 75% on the dual and triple treatment arms, respectively. The SVR rates were low in the experienced cirrhotic patients: 44% (dual therapy) and 58% (triple therapy). Common adverse events were fatigue, headache, and myalgia. CONCLUSION: Both dual and triple therapy regimes resulted in SVR rates of >95% in CHC genotype 3 who were naive non-cirrhotics. However, the SVR rates were low in treatment-experienced cirrhotics.

New paradigms in management of alcoholic hepatitis: a review.

Severe alcoholic hepatitis (SAH) is defined by modified Maddrey discriminant function ≥32 or Model for End-Stage Liver Disease (MELD) >21 and/or hepatic encephalopathy. It has a 3-month mortality rate ≥30-70 %. Patients with severe alcoholic hepatitis need combined, i.e., static (MELD score) and dynamic (Lille's score), prognostication. Systemic inflammation and poor regeneration are hallmarks of SAH, rather than intrahepatic inflammation. SAH is characterized by dysregulated and uncontrolled systemic inflammatory response followed by weak compensatory antiinflammatory response that leads to increased susceptibility to infection and multiple organ failure. Massive necrosis of hepatocytes exceeds the proliferative capacity of hepatocytes. Liver progenitor cells proliferate to form narrow ductules which radiate out into the damaged liver parenchyma. Corticosteroids have been the standard-of-care therapy, albeit controversial. However, the recent Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial revealed that prednisolone was not associated with a significant reduction in 28-day mortality, with no improvement in outcomes at 90 days or 1 year. A paradigm shift from antiinflammatory therapy such as corticosteroids to liver regeneration treatment, e.g., granulocyte-colony stimulating factor, molecular targeted treatments, and fecal microbiota transplantation, for severe alcoholic hepatitis is taking place. Liver transplantation should be offered to select patients with severe alcoholic hepatitis who are nonresponsive to medical treatment.

Minimal Hepatic Encephalopathy in Cirrhosis- How Long to Treat?

Abstract: Introduction. Minimal hepatic encephalopathy (MHE) can reverse after short-term treatment. However, relapse rate of MHE after stopping treatment has not been studied so far. We aimed to evaluate long-term (9 months) efficacy of a short-term (3 months) treatment of MHE with lactulose/rifaximin, for maintenance of remission from MHE. Material and methods. In this prospective study, consecutive patients with cirrhosis and MHE were treated with lactulose/rifaximin for 3 months. After treatment, they were followed up for 6 months. Psychometric testing for diagnosis of MHE was performed at baseline, 3 months and 9 months. Results. Of the 527 patients screened, 351 were found eligible and tested for MHE. Out of these, 112 (31.9%) patients had MHE (mean age 55.3 years; 75% males). They were randomized to receive Rifaximin (n = 57; 1,200 mg/day) or Lactulose (n = 55; 30-120 mL/day) for three months. At 3 months, 73.7% (42/57) patients in Rifaximin group experienced MHE reversal compared to 69.1% (38/55) in Lactulose group (p = 0.677). Six months after stopping treatment, 47.6% (20/42) in rifaximin group and 42.1% (16/38) patients in lactulose group experienced MHE relapse (p = 0.274). The overt hepatic encephalopathy development rate (7.1% vs. 7.9%) and mortality rate (0.23% vs. 0%) were similar in both groups. The Child-Turcotte-Pugh score and model for end stage liver disease (MELD) scores of patients who had MHE relapse were higher compared to those who didn’t. On multivariate regression analysis, MELD score was an independent predictor of MHE relapse. Conclusion. Of the patients who became MHE negative after short-term (3 months) treatment with rifaximin/lactulose, almost 50% had a relapse of MHE at 6 months follow-up.

Minimal hepatic encephalopathy in cirrhosis- how long to treat?

INTRODUCTION: Minimal hepatic encephalopathy (MHE) can reverse after short-term treatment. However, relapse rate of MHE after stopping treatment has not been studied so far. We aimed to evaluate long-term (9 months) efficacy of a short-term (3 months) treatment of MHE with lactulose/rifaximin, for maintenance of remission from MHE. MATERIAL AND METHODS: In this prospective study, consecutive patients with cirrhosis and MHE were treated with lactulose/rifaximin for 3 months. After treatment, they were followed up for 6 months. Psychometric testing for diagnosis of MHE was performed at baseline, 3 months and 9 months. RESULTS: Of the 527 patients screened, 351 were found eligible and tested for MHE. Out of these, 112 (31.9%) patients had MHE (mean age 55.3 years; 75% males). They were randomized to receive Rifaximin (n = 57; 1,200 mg/day) or Lactulose (n = 55; 30-120 mL/day) for three months. At 3 months, 73.7% (42/57) patients in Rifaximin group experienced MHE reversal compared to 69.1% (38/55) in Lactulose group (p = 0.677). Six months after stopping treatment, 47.6% (20/42) in rifaximin group and 42.1% (16/38) patients in lactulose group experienced MHE relapse (p = 0.274). The overt hepatic encephalopathy development rate (7.1% vs. 7.9%) and mortality rate (0.23% vs. 0%) were similar in both groups. The Child-Turcotte-Pugh score and model for end stage liver disease (MELD) scores of patients who had MHE relapse were higher compared to those who didn't. On multivariate regression analysis, MELD score was an independent predictor of MHE relapse. CONCLUSION: Of the patients who became MHE negative after short-term (3 months) treatment with rifaximin/lactulose, almost 50% had a relapse of MHE at 6 months follow-up.

Rifaximin vs. lactulose in treatment of minimal hepatic encephalopathy.

BACKGROUND & AIMS: Lactulose and rifaximin have already been shown to improve both cognitive functions and health related quality of life (HRQOL) in MHE patients. We aimed to compare the efficacy of rifaximin with lactulose in reversal of MHE and improvement in HRQOL in cirrhotic patients with MHE. METHOD: This prospective, randomized, open label, non-inferiority trial, was conducted at the Gastroenterology department of a tertiary care institute in Northern India. MHE was diagnosed if any two of the five neuro-psychometric (NP) tests were positive. HRQOL was assessed using the sickness impact profile (SIP) questionnaire (John Hopkins University, USA). RESULTS: Of 527 cirrhotics screened, 351 were found eligible and tested for MHE. A total of 112 (31.9%) patients were found to have MHE and then randomized into two groups group A (lactulose; 30-120 ml/day) and B (Tablet. rifaximin; 400 mg thrice a day). Based on the intention-to-treat population, the proportion of patients with MHE reversal at 3 months was 73.7% (42/57) in the rifaximin arm and 69.1% (38/55) in the lactulose arm [4.6% difference (90% CI -9.3% to 18.4%)]. However, non-inferiority of rifaximin over lactulose could not be established as the pre-specified non-inferiority margin (-5%) lies within the two-sided 90% confidence interval of the difference. HRQOL was significantly improved in both groups (P = 0.20). However, the proportion of patients with flatulence (P = 0.004) and diarrhoea (P = 0.0002) was significantly higher in patients who took lactulose. CONCLUSION: Non-inferiority of rifaximin over lactulose for MHE reversal was not established.