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.

Imaging modalities for non-acute pathologies of the foot and ankle.

Chronic foot and ankle pain, in contrast to acute traumatic injuries, presents a diagnostic challenge due to its diverse underlying causes. Accurate diagnosis often necessitates the utilization of various imaging modalities, emphasizing the importance of selecting the most appropriate one. The intricate structure of the foot, composed of multiple bones and supported by soft tissues like ligaments and plantar fascia, gives rise to a spectrum of mechanical disorders, including stress fractures, plantar fasciitis, Morton's neuroma, and more. In addition to mechanical issues, non-acute abnormalities encompass inflammatory diseases affecting tendons and joints, benign tumors, tumor-like lesions, vascular abnormalities, and others. This article reviews the indispensable role of imaging in the assessment of these conditions, with a focus on plain radiography, computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine studies, tailored to the specific clinical presentation. By providing insights into the selection and interpretation of imaging modalities, this article aims to assist clinicians in achieving accurate diagnoses and optimizing patient care for nonacute foot and ankle pathologies.

Arterial embolization during percutaneous vertebroplasty resulting in bilateral renal infarcts and ischemic colitis.

This case report documents an arterial embolic event that occurred during vertebroplasty for a pathological compression fracture of T12 in a 54-year-old female with known metastatic breast carcinoma. A CT angiogram performed after the procedure demonstrated cement migration into the aorta, both kidneys, and the inferior mesenteric artery and its branches, with ischemic colitis involving the descending colon and sigmoid colon. A CT scan 4 months post-procedure demonstrated resolution of the colitis. Neovascularity and cortical destruction in malignant bone lesions are thought to contribute to arterial cement leak.

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.

Corticosteroids Reduce Risk of Death Within 28 Days for Patients With Severe Alcoholic Hepatitis, Compared With Pentoxifylline or Placebo-a Meta-analysis of Individual Data From Controlled Trials.

BACKGROUND & AIMS: We performed a meta-analysis of individual patient data from 11 randomized controlled trials comparing corticosteroids, pentoxifylline, or their combination in patients with severe alcoholic hepatitis. We compared the effects of the treatments on survival for 28 days or 6 months, and response to treatment based on the Lille model. METHODS: We searched PubMed for randomized controlled trials of pharmacologic therapy for severe alcoholic hepatitis. Our final analysis comprised 11 studies, of 2111 patients. We performed 4 meta-analyses of the effects of corticosteroids vs placebo or control, corticosteroids vs pentoxifylline, corticosteroids and pentoxifylline vs corticosteroids and placebo or control, and pentoxifylline vs placebo. In each meta-analysis, the effect of treatment on the primary outcome (overall survival at 28 days, defined as the period from the first day of assigned treatment to 28 days) was estimated using a Cox proportional hazards regression model, including trials as random effect. RESULTS: Corticosteroid treatment significantly decreased risk of death within 28 days compared with controls (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.48-0.86) or to pentoxifylline (HR 0.64; 95% CI 0.43-0.95). In multiple-imputation and complete case analyses, the effect of corticosteroids compared with controls remained significant. When we compared corticosteroids vs pentoxifylline, the corticosteroid effect remained significant in the complete case analysis (HR 0.66; P = .04) but not in multiple-imputation analysis (HR 0.71; P = .08). There was no difference in 28-day mortality when patients were given a combination of corticosteroids and pentoxifylline vs corticosteroids alone or between patients given pentoxifylline vs control. In our analysis of secondary outcomes, we found no significant differences in 6-month mortality when any treatments or controls were compared. Corticosteroids were significantly associated with increased response to therapy compared with controls (relative risk 1.24; 95% CI 1.10-1.41) or pentoxifylline (relative risk 1.43; 95% CI 1.20-1.68). We found no difference in response to therapy between patients given a combination of corticosteroids and pentoxifylline vs corticosteroids alone or pentoxifylline vs controls. CONCLUSIONS: In a meta-analysis of 4 controlled trials, we found corticosteroid use to reduce risk of death within 28 days of treatment, but not in the following 6 months. This loss of efficacy over time indicates a need for new therapeutic strategies to improve medium-term outcomes.

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.

Noradrenaline is as Effective as Terlipressin in Hepatorenal Syndrome Type 1: A Prospective, Randomized Trial.

OBJECTIVES: Hepatorenal syndrome (HRS) is a functional renal failure occurring in end stage liver disease, which is associated with poor prognosis. Terlipressin has been shown to be effective in treatment of HRS. More recently, it was suggested that noradrenaline, an alpha-adrenergic drug may be also effective in HRS. We aimed to compare the efficacy of noradrenaline versus terlipressin in treatment of HRS type 1. METHODS: Consecutive patients with cirrhosis and HRS type 1 were enrolled and randomised into 2 groups- Group A received intravenous noradrenaline infusion (0.5-3 mg/h) and group B received intravenous terlipressin (0.5-2 mg/6h) for 2 weeks. Intravenous albumin (20 g/day) was given to both groups. RESULTS: Out of 55 cirrhotics screened, 41 were randomised into group A (n=21) or group B (n=20). Baseline characteristics of the two groups were similar. HRS reversal was seen in 47.6%(10/21) patients in group A, and 45% (9/20) patients in group B (p=1.00). In both groups, there was a significant decrease in serum creatinine from baseline (group A- 3.1±1.4 mg/dl to 2.2±1.3 mg/dl, p=0.028; group B- 3.4±1.6 mg/dl to 2.3±1.3 mg/dl, p=0.035). Both the groups showed a significant increase in mean arterial pressure (group A- 77.3±8.6 mmHg to 103.4±8.3 mmHg, p=0.0001; group B- 76.8±11.6 mmHg to 100±9.4 mmHg, p=0.0001). Noradrenaline was associated with fewer adverse events and was significantly cheaper than terlipressin. Lower baseline MELD score was an independent predictor of response to treatment. CONCLUSIONS: Noradrenaline is as effective and safe as terlipressin in the treatment of HRS type 1.

Pentoxifylline in severe alcoholic hepatitis: a prospective, randomised trial.

BACKGROUND: Role of corticosteroids in treatment of severe alcoholic hepatitis (SAH) is controversial. Pentoxifylline (PTX), an inhibitor of TNF, has also been shown to decrease short term mortality in SAH. Aim of this study was to evaluate the effect of PTX on short term mortality, renal and hepatic functions in patients with SAH. METHODS: Fifty patients with SAH {Maddrey's Discriminant Function (DF) > or = 32} were prospectively enrolled. Twenty five patients received PTX (400 mg orally, three times a day), and 25 received placebo for 4 weeks. Serum tumor necrosis factor (TNF) was measured in both groups. RESULTS: Baseline characteristics of the two groups were similar. At 4 weeks, mortality in PTX group was lower than that in controls {20% (5/25) versus 40% (10/25) respectively; p = 0.216; RR 0.5; 95% CI 0.19-1.25}. Renal failure was the cause of mortality in 20% (1/5) patients in PTX group, and 70% (7/10) in controls (p = 0.11). Significant reduction in urea, creatinine, DF and TNF was noted in PTX group. Reduction in TNF did not correlate with reduction in creatinine or DF. CONCLUSIONS: In patients with SAH, PTX leads to a significant improvement in renal and hepatic functions, and a trend towards decreased short term mortality.

Corticosteroid plus pentoxifylline is not better than corticosteroid alone for improving survival in severe alcoholic hepatitis (COPE trial).

BACKGROUND: Corticosteroids and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis (SAH), but not to the extent desired. Combining both drugs may lead to better survival, but has not yet been studied. AIM: To compare the efficacy of corticosteroids plus pentoxifylline with that of corticosteroids alone in improving survival of SAH patients. METHODS: Of the 111 patients screened, 70 patients with SAH (Maddrey discriminant function (MDF) ≥ 32) were enrolled. Patients with active infection, bleeding, renal failure, or pancreatitis were excluded. Treatment was given for four weeks to group A (n = 36; prednisolone 40 mg/day plus pentoxifylline 400 mg thrice/day) and group B (n = 34; prednisolone 40 mg/day). Patients were followed up for 6 months. Data are expressed as median (range) or percentage. RESULTS: Baseline characteristics of the two groups were similar (MDF group A 78.5 (36.8-140.9), group B 74.9 (45.6-140.2)). Four-week and six-month survival in groups A and B were not significantly different (four-week 72.2 and 73.5%, respectively, p = 1.00; six-month 30.6 and 23.5%, respectively, p = 0.417). At seven days, 55.6% of patients in group A and 64.7% in group B had a Lille score <0.45 (p = 0.473). Six-month survival was significantly higher for patients with a Lille Score <0.45 than for those with a Lille score ≥0.45 (group A 55.5 vs. 0%, p = 0.0006; group B 36 vs. 0%, p = 0.0304). Biological improvement at 28 days was significant for both groups; however, the difference between the groups was not significant. CONCLUSIONS: For patients with severe alcoholic hepatitis, a combination of corticosteroids and pentoxifylline has no additional survival advantage compared with corticosteroids alone.

Rifaximin improves psychometric performance and health-related quality of life in patients with minimal hepatic encephalopathy (the RIME Trial).

OBJECTIVES: Cirrhotics with minimal hepatic encephalopathy (MHE) have a poor health-related quality of life (HRQOL). Treatment of MHE is still evolving. The aim of this double-blind randomized pilot study was to assess the efficacy of rifaximin in improving neuropsychometric (NP) test performance and HRQOL in patients with MHE. METHODS: MHE was diagnosed if any two NP tests (number and figure connection tests, picture completion, digit symbol, and block design tests) were deranged beyond 2 s.d. of normal. HRQOL was assessed using the sickness impact profile (SIP) questionnaire. RESULTS: A total of 486 patients with cirrhosis were screened and 284 were found eligible. Out of these 115 (40.9%) had MHE, of which 21 refused consent and 94 were randomized to receive placebo (n=45) and rifaximin (n=49; 1200 mg/day) for 8 weeks. At the end of treatment, significantly more number of patients in rifaximin group showed reversal of MHE (75.5% (37/49) vs. 20% (9/45) in placebo group; P<0.0001). Rifaximin group also showed significant reduction in mean number of abnormal NP tests (baseline, 2.35 (95% confidence interval (CI), 2.17-2.53); 2 weeks, 1.29 (95% CI, 1.02-1.56), P=0.002; 8 weeks, 0.81 (95% CI, 0.61-1.02), P=0.000), compared with placebo group (baseline, 2.31 (95% CI, 2.03-2.59); 2 weeks, 2.03 (95% CI, 1.74-2.31); 8 weeks, 1.97 (95% CI, 1.69-2.25), P>0.05). The mean total SIP score also improved significantly in rifaximin group (baseline, 11.67 (95% CI, 10.31-13.03); 8 weeks, 6.45 (95% CI, 5.59-7.30); P=0.000) compared with placebo group (baseline, 9.86 (95% CI, 8.66-11.06); 8 weeks, 8.51 (95% CI, 7.35-9.67); P=0.82). Improvement in HRQOL correlated with improvement in NP tests. Rifaximin was well tolerated. CONCLUSIONS: Rifaximin significantly improves both cognitive functions and HRQOL in patients with MHE.

Embolotherapy in massive post sphincterotomy bleed.

A 38-year-old female with obstructive jaundice underwent therapeutic ERCP. Minor self limiting bleed was observed from the ampulla during the procedure. Later she had massive bleed for which endoscopic therapy was not possible due to obscured vision of the ampulla. So immediate angiographic embolisation of the bleeding vessel using the available coronary hardware was performed and bleed was controlled. Embolotherapy is an attractive and safe therapeutic option for control of massive post-sphincterotomy bleed.