Opportunistic screening for osteopathy with routine abdominal computed tomography scan in chronic pancreatitis.

BACKGROUND AND AIMS: Lumbar vertebral bone attenuation, measured in Hounsfield units (HU) can indirectly indicate the bone mineral density (BMD). The aim of this study is to determine the optimal HU threshold on abdominal computed tomography (CT) scans to detect osteopathy in patients with chronic pancreatitis (CP). METHODS: This cross-sectional study included patients with CP who underwent CT scans to measure HU at L1 to L4 vertebrae. The mean lumbar vertebral attenuation of female renal transplant donors, aged 20-30 years was utilized to calculate the T-scoreHU of all patients at each vertebral level. Receiver operator characteristic analysis was used to determine the HU and T-scoreHU for diagnosis of osteopathy in patients with CP. Dual-energy X-ray absorptiometry value was used to categorize osteopenia and osteoporosis. RESULTS: A total of 175 patients (mean age, 34.5 ± 10.9 years; 72 % males) and 33 female renal transplant donors (mean age, 28 ± 2.4 years) were included. A threshold HU value 212 or T scoreHU of -1.80 at L1 vertebra was found to have a 78 % sensitivity and 70 % specificity for differentiating between osteoporosis and non-osteoporosis (osteopenia and normal BMD). Similarly, a threshold HU value of 254 or a T-scoreHU of -0.46 at L1 vertebra had 78 % sensitivity and 71 % specificity for distinguishing between normal and low BMD (osteoporosis and osteopenia). CONCLUSION: Abdominal CT images, which are routinely performed in chronic pancreatitis, can be used for opportunistic screening of osteoporosis and osteopenia without additional cost or radiation exposure.

Clinical significance of Notch pathway-associated microRNA-107 in pancreatic ductal adenocarcinoma.

Background & aim: MicroRNAs associated with the Notch pathway play a critical role in the progression of pancreatic carcinoma. Our aim was to study the clinical significance of miR-107 and NOTCH2 in pancreatic ductal adenocarcinoma (PDAC). Methods: The circulating miR-107 levels in PDAC and controls were determined by qPCR. NOTCH2 protein (target) expression in tissue of PDAC, periampullary carcinoma, chronic pancreatitis and normal pancreatic tissue was assessed by immunohistochemistry. Results: The circulating miR-107 levels were found to be significantly reduced in PDAC as compared with controls. Additionally, NOTCH2 protein expression was higher in PDAC tissue as compared with controls and was clinically associated with metastasis. Conclusion: Our findings demonstrate the utility of circulating miR-107 as a potential differentiating marker in PDAC.

Vitamin D status & bone health in patients with liver cirrhosis.

Background & objectives: Vitamin D plays an important role in bone metabolism, and liver is the intermediary site of vitamin D metabolism. The purpose of this study was to study the prevalence of vitamin D deficiency and bone health in patients with cirrhosis. Methods: Prospectively, serum 25-hydroxy vitamin D [25(OH)D] level were assessed in cirrhotics by chemiluminescence method. Endocrine Society Clinical practice guideline was used to define deficiency and insufficiency of vitamin D. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry and the World Health Organization criteria was used to define osteoporosis and osteopenia. The lowest T score at the left hip neck or lumbar spine was taken as osteoporosis or osteopenia. The Child-Turcotte-Pugh score was used to assess the severity of cirrhosis. Results: Cirrhotics (n=350, male: 278, compensated: 210) were included. Mean serum 25(OH)D level was 8.75 ng/ml. The prevalence of vitamin D deficiency (VDD) and low-BMD (osteopenia and osteoporosis) was 89.4 and 86 per cent, respectively. VDD, insufficiency and osteoporosis was found in 86.7, 11.9 and 33.8 per cent, respectively, in patients with compensated cirrhosis; and 93.6, 3.6 and 40 per cent, respectively, in patients with decompensated cirrhosis. Body mass index of >25 kg/m2 was protective for bone health. Interpretation & conclusions: VDD and low-BMD is prevalent in Indian patients with cirrhosis and should be looked for in patients with cirrhosis for its prevention.

Association of vitamin D status with disease severity and outcome in Indian patients with IgA nephropathy.

BACKGROUND: Vitamin D deficiency has been examined as a risk factor for severity and progression of kidney disease due to its immunomodulatory effects. There is paucity of data about its impact in IgA nephropathy (IgAN). METHODS: In a retrospective cohort study, 25 (OH) vitamin D assay was performed in bio-banked baseline serum samples collected during kidney biopsy of 105 adult patients with primary IgAN diagnosed between 2015 and 2019. A level of < 10 ng/mL was defined as Vitamin D deficiency. RESULTS: Mean age of patients was 34 ± 10.6 years, 69.5% were males. Mean baseline 25(OH) Vitamin D levels was 15.9 ± 11.9 ng/mL and 41(39%) patients had vitamin D deficiency. Serum albumin level was lower in vitamin D deficient patients compared to those who had higher vitamin D levels (3.7 ± 0.9 vs 4.1 ± 0.7 g/dl, p = 0.018)but there was no significant difference in baseline proteinuria and eGFR. Crescentic lesions were more frequent in vitamin D deficient group (19.5% vs 6.3%, p = 0.022). At median follow up of 21.5 months (6 - 56 months), there was no difference in remission (68.3% vs 65.6%, p = 0.777) and disease progression (12.5% vs 9.4%, p = 0.614) in those with and without Vitamin D deficiency respectively. On multivariate cox proportional hazard analysis, vitamin D deficiency was not a significant risk factor for renal survival (HR-1.79, 95% confidence interval:0.50-6.34, p = 0.368). CONCLUSION: There was no association between vitamin D deficiency and disease profile as well as renal outcome in Indian patients with IgAN.

Evaluation of the GCS-Pupils Score for PrOgnosis in trauMatic brAin injury- The COMA Study.

OBJECTIVES: Glasgow Coma Scale-Pupils (GCS-P) score has been found to be strongly related to in-hospital mortality in retrospective studies. We hypothesized that GCS-P would be better prognosticator than Glasgow Coma Scale (GCS) in patients with traumatic brain injury (TBI). METHODS: In this prospective, multicentric, observational study, GCS and GCS-P scores were noted in adult TBI patients at ICU admission. Demographic variables, relevant clinical history, clinical/radiological findings and ICU complications were also noted. Extended Glasgow Outcome scale was noted at hospital discharge and at 6 months post-injury. Logistic regression analysis was carried out to estimate the odds for poor outcome adjusted for covariates. Sensitivity, specificity, area under curve (AUC) and odds ratio are reported for poor outcome at estimated cutoff point. RESULTS: A total of 573 patients were included in this study. The predictive power for mortality, shown by the AUC, was 0.81 [95% CI: 0.77-0.85] for GCS and 0.81 [95% CI: 0.77-0.86] for GCS-P score, both being comparable. Similarly, the predictive ability for outcome at discharge and 6 months, the AUC-ROC for both GCS and GCS-P were comparable. CONCLUSIONS: GCS-P is a good predictor of mortality and poor outcome. However, the predictive performance of GCS and GCS-P for in-hospital mortality and functional outcome at discharge and at 6 months remains comparable.

Characterisation of anaemia amongst school going adolescent girls in rural Haryana, India.

OBJECTIVE: High burden of anaemia exists amongst rural adolescent girls in India. The objective of this study was to characterise anaemia in school going adolescent girls in rural Haryana, India. DESIGN: Linear and multiple logistic regression analysis of data collected prior to an intervention trial was conducted. Participants were classified into anaemic (haemoglobin <12 g/dl) and non-anaemic group and were further classified into deficiencies of Fe, folate or vitamin B12, mixed, anaemia of other causes and inflammation. SETTING: Three schools in Ballabgarh block of Faridabad District, Haryana, India. PARTICIPANTS: One hundered and ninety-eight non-anaemic and 202 anaemic adolescent girls (12-19 years). RESULTS: Anaemic girls had 29·6 % Fe deficiency, 28·1 % folate or vitamin B12 deficiency, 15·8 % mixed deficiency and 9·7 % acute inflammation. Anaemia of other causes was found in 16·8 % of the anaemic participants. Girls with Fe and isolated folate deficiency had 2·5 times and four times higher odds of developing anaemia, respectively, as compared with non-anaemic girls. Fe deficiency with no anaemia was found amongst 11 % non-anaemic girls. Non-anaemic girls had a high prevalence of combined deficiency of folate or vitamin B12 (29·5 %) and acute inflammation (14·4 %). CONCLUSIONS: The current strategy of Fe and folic acid supplementation alone will not suffice for achieving the desired reduction in the prevalence of anaemia as unknown causes and anaemia of inflammation contribute to a substantial proportion of anaemia. Integrating other nutrition-specific components like improving water, sanitation and hygiene practices with the ongoing micronutrient supplementation program will comprehensively tackle anaemia. Unknown causes of anaemia warrant further research.

Evaluation of delays during diagnosis and management of lung cancer in India: A prospective observational study.

OBJECTIVE: The majority of lung cancers are diagnosed at an advanced stage; the reasons for which are variable and unclear. METHODS: Lung cancer patients were evaluated prospectively to quantify various timelines and establish reasons for delays. Timelines were defined as time intervals between symptom onset, first physician visit, first specialist visit, date of diagnosis and treatment. RESULTS: A total 410 patients were included, majority having advanced disease. The median period for a first visit to a physician was 30 days (interquartile range [IQR] 20-90), 50 days (IQR 20-110) for referral to our centre, 23 days (IQR 14-33) to reach diagnosis, and 24 days (IQR 14.5-34) to initiate treatment. Administration ofanti-tuberculosis treatment further delayed referral to specialist centre. Treatment delays were related to performance status, disease stage and treatment type. On multivariate analysis, education and histology affected diagnosis delay and treatment delay. Treatment delay was less in those who received targeted therapy compared to chemotherapy. Various time delays did not affect the overall survival. CONCLUSION: Poor education status and inappropriate anti-tubercular treatment were primary factors associated with longer diagnostic delays. Creating disease awareness and high clinical suspicion are essential to overcome these lacunae in lung cancer care.

Effect of Vitamin D Supplementation on Vitamin D Level and Bone Mineral Density in Patients With Cirrhosis: A Randomized Clinical Trial.

INTRODUCTION: In patients with cirrhosis, highly prevalent vitamin D deficiency and low bone mineral density (BMD) increase the burden of disease, and role of vitamin D supplementation is not clear. So, our aim was to determine the effect of vitamin D supplementation on vitamin D level and BMD in patients with cirrhosis. METHODS: Patients with cirrhosis (18-60 years) of any etiology were enrolled. We measured serum 25(OH)D, parathyroid hormone, thyroid-stimulating hormone, free T4, bone-specific alkaline phosphatase, insulin-like growth factor (IGF)-1, and health-related quality of life at entry and at 1 year; however, serum calcium was measured at 3-month interval. BMD was measured by dual-energy x-ray absorptiometry at lumbar spine and left hip neck at entry and after 1 year. Statistical analysis was performed according to intention-to-treat analysis. RESULTS: Of 390 screened patients with cirrhosis, 164 participants (82 in each group) were randomized. There was significant increase in 25(OH)D levels in intervention group after 1 year (33.7 [24.3-45.7] ng/mL vs 23.1 [17-28.2] ng/mL; P < 0.001) when compared with placebo. The mean difference in BMD at lumbar spine and left hip neck was not significantly changed after 1 year of intervention with vitamin D between both groups. There was no significant change in both the groups in levels of calcium, thyroid-stimulating hormone, parathyroid hormone, free T4, IGF-1, and bone-specific alkaline phosphatase and quality of life. DISCUSSION: Supplementation with vitamin D for 1 year improves vitamin D levels but did not result in improvement in BMD at lumbar spine and left hip neck in patients with cirrhosis.

To study heterogeneity in SARS-CoV-2 IgG response titre in patients recovered from COVID-19.

The COVID-19 pandemic caused a serious health challenge to the entire mankind. The association between clinical characteristics of disease and formation of neutralizing antibodies have not well studied. A prospective study was conducted for patients recovered from confirmed SARS-CoV-2 infections from 1st August 2020 to 28th February 2021, to study the association between SARS-CoV-2 IgG antibody response titres and clinical characteristics of the disease. A total 92 patients were included in the study. Median age was 52 years; majority were male and middle or old aged.  About 48% patients required hospitalization and 38.3% had moderate CT severity score. Positive SARS-CoV-2-IgG was detected in all patients except one. On comparing the antibody titres among various sub-groups of COVID-19 recovered patients, old age was the only factor associated with statistically significant higher antibody response (28 AU/ml for age<35 years, 53 AU/ml for age group 35-60, and 71 AU/ml for age group >60 years, p=0.01). Severity of infection, worse CT severity scores, need of hospitalization, oxygen or ventilatory support were associated with higher antibody titres but were not statistically significant. There was a strong correlation of antibody titres when analysed for age of study population (Spearman correlation=0.39, p<0.001); whereas a weak correlation (Spearman correlation=0.03, p=0.753) was seen when analysed for CT severity score. Elderly patients had higher antibody titre after recovery from Covid-19 infection. Severity of disease, need of hospitalisation or oxygen/mechanical ventilation did not influence the antibody titre.

Kitchen-based diet versus commercial polymeric formulation in acute pancreatitis: a pilot randomized comparative study.

INTRODUCTION: Nutrition plays an important role in management of acute pancreatitis (AP) and decreases its severity and infectious complications. Various formulations of enteral nutrition (EN) are available and are costly. For developing countries, cost and availability is a major issue and kitchen-based diet should be explored in patients with AP. AIM: Comparison of kitchen-based diet with a commercially available polymeric formulation in terms of various outcomes in patients with AP within 14 days after the onset of pain. METHODS: Sixty patients (39 male, mean age 36.1 ± 12.7 years) of moderately severe and severe AP of any etiology were randomized (30 in each group) to either kitchen-based diet or commercial polymeric formulation group. Outcome measures were refeeding pain, tolerability, infectious complications, mortality, total hospital/intensive care unit stay; and change in serum C-reactive protein (CRP), transferrin and pre albumin. RESULTS: There was no significant difference in baseline demographic and biochemical parameters in both groups. No difference was observed in refeeding pain (7.1% vs 8%, p = 0.99), tolerability (28.6% vs 12%, p = 0.17), infectious complications (57.14% vs 36%, p = 0.12), mortality (31.7% vs 20%, p = 0.69), hospital stay (19.5 vs 23.5 days, p = 0.86), CRP (74.4 vs 59 mg/L, p = 0.97), transferrin levels (23.6 vs 25.6 mg/dL, p = 0.75) and pre albumin (9.45 vs 13.09 mg/dL, p = 0.68) in both groups. CONCLUSION: Kitchen-based diet is comparable to commercial polymeric formulation for the early initiation of enteral nutrition in patients with severe or moderately severe acute pancreatitis. CLINICAL TRIAL REGISTRATION: Trial registered with the Clinical Trials registry-India (CTRI/2018/01/011188).

Outcome predictors of patients who underwent limb amputation/s following trauma at a level I trauma center in North India.

PURPOSE: Limb amputation is one of the oldest medical operations, dating back over 2500 years to Hippocrates' time. In developing countries like India, most of the patients are young, and trauma is the primary cause of limb amputation. The objectives of this study were to investigate the factors that can predict the outcome of patients who underwent upper or lower limb amputations. MATERIALS AND METHODS: This was a retrospective analysis of the prospectively collected data of patients who underwent limb amputations from January 2015 to December 2019. RESULTS: From January 2015 to December 2019, 547 patients underwent limb amputations. Males predominated (86%). Road traffic injuries (RTI) were the most common (323, 59%) mechanism of injury. Hemorrhagic shock was present in 125 (22.9%) patients. Above-knee amputation was the most common (33%) amputation procedure performed. The correlation of hemodynamic status at presentation with the outcome was statistically significant (p-0.001). Outcome measures like delayed presentation, hemorrhagic shock, Injury severity scores (ISS), and the new injury severity scores (NISS) were statistically significant (p-0.001) when compared to the outcome. There were 47 (8.6%) mortalities during the study period. CONCLUSION: Factors that affected the outcome were delayed presentation, hemorrhagic shock, higher ISS, NISS, MESS scores, surgical-site infection, and associated injuries. Overall mortality during the study was 8.6%.

Clinical Significance of MUC4 and Associated Proteins in Pancreatic and Periampullary Cancers.

OBJECTIVE: This study primarily aimed to assess the expression of MUC4 in patients with pancreatic ductal adenocarcinoma (PDAC) as compared with controls and assess its clinical relevance. MATERIALS AND METHODS: Serum MUC4 levels and MUC4 gene expression in snap-frozen tissue were analyzed through surface plasmon resonance and quantitative polymerase chain reaction, respectively. Tumor tissues and control tissues were analyzed for MUC4 and other mucins through immunohistochemistry. RESULT: MUC4 expression in tumor tissue was found to be significantly elevated in PDAC patients as compared with chronic pancreatitis tissues and normal pancreatic tissues. Periampullary carcinoma and cholangiocarcinoma tissue also showed increased expression of MUC4 and other mucins. CONCLUSIONS: Differential expression of MUC4 in pancreatic tumor tissues can help to differentiate PDAC from benign conditions.

Genetic polymorphisms in phase II metabolizing enzymes in alcoholic and idiopathic chronic pancreatitis: Indian scenario.

AIM: To study polymorphisms in glutathione-S-transferases (GST-T1, GST-M1, GST-P1) and uridine-5'-diphosphate-glucuronosyl-transferases (UGT1A7) genes and the risk of developing chronic pancreatitis (CP) associated with these polymorphisms. METHODS: This study included 49 alcoholic and 51 idiopathic chronic pancreatitis patients, 50 alcohol addicts and 50 healthy controls. Polymorphism(s) in GST-T1 and GST-M1 genes were assessed by multiplex polymerase chain reaction (PCR), while PCR-radiofrequency lesioning (RFLP) was employed to assess the same in GST-P1 and UGT1A7 genes. The differences in polymorphism frequency between groups and the risk of developing pancreatitis were assessed by the odds ratio. RESULTS: Strong association of the null genotype of GST-T1 with CP susceptibility was observed. Alcoholics with the Val allele of GST-P1 have higher chances of having pancreatitis. Idiopathic pancreatitis patients with higher age at the onset of pain were found to have the null genotype of GST-M1. CONCLUSION: Alcoholics with the null genotype of the GST-T1 gene and the Valine allele of the GST-P1 gene are at a higher risk of developing CP. Thus, genotyping of these genes may serve as an important screening tool for the identification of high-risk groups among alcoholics.

Beneficial effects of premeal almond load on glucose profile on oral glucose tolerance and continuous glucose monitoring: randomized crossover trials in Asian Indians with prediabetes.

BACKGROUND: Rapid conversion from prediabetes to diabetes and frequent postprandial hyperglycemia (PPHG) is seen in Asian Indians. These should be the target of dietary strategies. OBJECTIVES: We hypothesized that dietary intervention of preloading major meals with almonds in participants with prediabetes will decrease overall glycemia and PPHG. DESIGN: The study included two phases: (1) an oral glucose tolerance test (OGTT)-based crossover randomized control study, the effect of a single premeal almond load (20 g) given before OGTT was evaluated (n = 60, 30 each period). (2) The continuous glucose monitoring system (CGMS)-based study for 3 days including premeal almond load before three major meals was a free-living, open-labeled, crossover randomized control trial, where control and premeal almond load diets were compared for glycaemic control (n = 60, 30 in each period). The study was registered at clinicaltrials.gov (registration no. NCT04769726). RESULTS: In the OGTT-based study phase, the overall AUC for blood glucose, serum insulin, C-peptide, and plasma glucagon post-75 g oral glucose load was significantly lower for treatment vs. control diet (p < 0.001). Specifically, with the former diet, PPHG was significantly lower (18.05% in AUC on OGTT, 24.8% at 1-h, 28.9% at 2-h post OGTT, and 10.07% during CGMS). The CGMS data showed that premeal almond load significantly improved 24-glucose variability; SD of mean glucose concentration and mean of daily differences. Daily glycaemic control improved significantly as per the following: mean 24-h blood glucose concentration (M), time spent above 7.8 mmol/L of blood glucose, together with the corresponding AUC values. Premeal almond load significantly decreased following: overall hyperglycemia (glucose AUC), PPHG, peak 24-h glycaemia, and minimum glucose level during night. CONCLUSION: Incorporation of 20 g of almonds, 30 min before each major meal led to a significant decrease in PPHG (as revealed in OGTT-based study phase) and also improved insulin, C-peptide, glucagon levels, and improved glucose variability and glycemic parameters on CGMS in participants with prediabetes. CLINICAL TRIAL REGISTRY: The study was registered at clinicaltrials.gov (registration no. NCT04769726).

Premeal almond load decreases postprandial glycaemia, adiposity and reversed prediabetes to normoglycemia: A randomized controlled trial.

BACKGROUND: Asian Indians show rapid conversion from prediabetes to type 2 diabetes (T2D). Novel dietary strategies are needed to arrest this progression, by targeting postprandial hyperglycaemia (PPHG). DESIGN: We conducted a free-living randomized controlled open-label parallel arm study to evaluate the effect of a premeal load of almonds (20 g) 30 min before major meals on anthropometric, glycaemic, and metabolic parameters over 3 months. Sixty-six participants with prediabetes in the age range of 18-60 yrs were recruited. The study was registered at clinicaltrials.gov (registration no. NCT04769726). RESULTS: Thirty participants in each arm completed the study. As per 'intention-to-treat' analysis, overall additional mean reductions were statistically significant for body weight, BMI, waist circumference (WC), subscapular and suprailiac skinfolds, and improved handgrip strength (Kg) (p < 0·001 for all) in the treatment arm vs. the control arm (after multiple adjustments). In the blood parameters, the additional mean reduction in the treatment arm vs. control arm was statistically significant for fasting and post-75 g oral glucose-load blood glucose, postprandial insulin, HOMA-IR, HbA1c, proinsulin, total cholesterol, and very low-density lipoprotein cholesterol (p < 0·001 for all). Most importantly, we observed a reversal to normoglycemic state (fasting blood glucose and 2 h post-OGTT glucose levels) in 23.3% (7 out of 30) of participants in the treatment arm which is comparable to that seen with Acarbose treatment (25%). CONCLUSION: Incorporation of 20 g of almonds, 30 min before each major meal leads to significant improvement in body weight, WC, glycemia (particularly PPHG), and insulin resistance and shows potential for reversal of prediabetes to normal glucose regulation over 3 months.

Smoothened percentiles for height, weight and body mass index of urban school going adolescents aged 11-17 years in national capital territory region of Delhi, India.

Purpose: The aim of the study was to estimate centiles by using improved statistical smoothing procedure, the Box-Cox power-exponential (BCPE) method, in urban northern Indian adolescents aged 11-17 years. Materials and Methods: Data were collected cross-sectionally by measuring specific anthropometric features such as height, weight, and mid-upper arm circumference in school-based adolescents aged 11-17 years including both boys (n = 838) and girls (n = 788) enrolled in government educational institutions in urban Delhi. We used a state-of-the-art statistical methodology (BCPE method) to establish centile curves. Results: The model fitted before smoothing revealed that weight, height, and BMI did not follow a normal distribution; both skewness and kurtosis were observed in all three variables. After correcting both skewness and kurtosis, estimated empirical percentile values showed a gradual increase in weight, height, and BMI in both boys and girls. Girls had higher weight and height than boys in initial ages and observed a steep increase in boys in both weight and height in later ages. BMI was higher in girls than boys and visibly higher during 14-16 years of age. The 50th percentile value of BMI was smaller in all the ages in our study than that in other studies. Conclusions: Smoothened percentile values derived for BMI by using the state-of-the-art statistical methodology may help policymakers to promote better growth in urban adolescents.

Comparison of Anthropometry, Bioelectrical Impedance, and Dual-energy X-ray Absorptiometry for Body Composition in Cirrhosis.

Background & aims: This study was planned to evaluate triceps skinfold thickness (TSFT), mid-arm muscle circumference (MAMC) and bioelectrical impedance analysis (BIA) for assessing body composition using dual-energy X-ray absorptiometry (DEXA) (reference) and to predict fat mass (FM) and fat-free mass (FFM) in patients with cirrhosis. Methods: FM and FFM were assessed by using DEXA and BIA. Skin-fold calliper was used for measuring TSFT, and MAMC was calculated. Bland-Altman plot was used to determine agreement and linear regression analysis for obtaining equations to predict FM and FFM. Results: Patients with cirrhosis (n = 302, 241 male, age 43.7 ± 12.0 years) were included. Bland-Altman plot showed very good agreement between BIA and DEXA for the estimation of FM and FFM. Majority of patients were within the limit of agreement: FM (98%) and FFM (96.4%). BIA shows a positive correlation with DEXA:FM (r = 0.73, P ≤ 0.001) and FFM (r = 0.86, P ≤ 0.001). DEXA (FM and FFM) shows a positive correlation with TSFT (r = 0.69, P ≤ 0.01) and MAMC (r = 0.61, P ≤ 0.01). The mean difference between the observed and predicted value of FM and FFM by BIA in the developmental set was 0.01 and 0.05, respectively; whereas in the validation set, it was -0.13 and 0.86, respectively. The mean difference between the observed and predicted value of TSFT and MAMC in the developmental set was 0.43 and 0.07; whereas, in the validation set, it was 0.16 and 0.48, respectively. Conclusion: Anthropometry (TSFT and MAMC) and BIA are simple and easy to use and can be a substitute of DEXA for FM and FFM assessment in routine clinical settings in patients with cirrhosis.

Quantitative plasma proteomics identifies metallothioneins as a marker of acute-on-chronic liver failure associated acute kidney injury.

Background: Acute kidney injury (AKI) considerably increases the risk of short-term mortality in acute-on-chronic liver failure (ACLF) but predicting AKI is not possible with existing tools. Our study aimed at de novo discovery of AKI biomarkers in ACLF. Methods: This observational study had two phases- (A) Discovery phase in which quantitative proteomics was carried-out with day-of-admission plasma from ACLF patients who initially had no-AKI but either progressed to AKI (n=10) or did not (n=9) within 7 days of admission and, (B) Validation phase in which selected biomarkers from the discovery phase were validated by ELISA in a larger set of ACLF plasma samples (n=93) followed by sub-group analyses. Results: Plasma proteomics revealed 56 differentially expressed proteins in ACLF patients who progressed to AKI vs those who did not. The metallothionein protein-family was upregulated in patients who progressed to AKI and was validated by ELISA as significantly elevated in both- (i) ACLF-AKI vs no-AKI (p-value ≤ 0.0001) and (ii) progression to AKI vs no-progression to AKI (p-value ≤ 0.001). AUROC for AKI vs no-AKI was 0.786 (p-value ≤0.001) and for progression to AKI vs no-progression to AKI was 0.7888 (p-value ≤0.001). Kaplan-Meier analysis revealed that ACLF patients with plasma MT concentration >5.83 ng/mL had a high probability of developing AKI by day 7 (p-value ≤0.0001). High expression of metallothionein genes was found in post-mortem liver biopsies of ACLF patients. Conclusion: Day-of-admission measurements of plasma metallothionein can act as predictive biomarkers of AKI in ACLF.