Novel predictors of response to therapy with terlipressin and albumin in hepatorenal syndrome-acute kidney injury.

Background: A combination of terlipressin and albumin is the first-line pharmacologic treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI). We assessed the response rates to terlipressin-albumin therapy in patients with HRS-AKI and determined early predictors of treatment response and survival. Methods: A total of 84 patients with HRS-AKI (International Club of Ascites definition 2015) treated with terlipressin-albumin were included. Predictors of HRS reversal were identified by logistic regression analysis. Survival analysis was performed using the Kaplan-Meier method, and Cox regression models were used to determine independent predictors of mortality. Results: Complete response to therapy was observed in 54.8%, partial response in 14.3%, and no response in 31% of patients. The factors associated with complete treatment response were the presence of systemic inflammatory response syndrome (SIRS), baseline serum creatinine, a rise in mean arterial pressure by day 3, and a reduction in the renal resistive index (ΔRRI) by day 3 of treatment. Independent predictors of HRS reversal were the presence of SIRS at baseline (P=0.022; odds ratio [OR] 15.74, 95% confidence interval [CI] 1.47-167.82) and ΔRRI ≥5% by day 3 of treatment (P=0.048; OR 6.67, 95%CI 1.021-43.62). Mean transplant-free survival at 6 months was significantly better in treatment responders (148 vs. 90 days, P<0.001). Independent predictors of 6-month mortality were response to treatment (P=0.004) and model for end-stage liver disease-sodium >23 (P=0.018). Conclusions: SIRS and ΔRRI are simple parameters to predict treatment response in HRS-AKI. Non-responders have higher mortality and should be identified early to expedite liver transplantation.

A case-cohort study of left ventricular diastolic dysfunction in patients with cirrhosis: the liver-heart axis.

Background: Left ventricular diastolic dysfunction (LVDD) is an early manifestation of cirrhotic cardiomyopathy. Few studies have addressed its clinical significance in cirrhosis. We assessed the association of LVDD with the factors affecting cirrhosis patients' severity, complications, and survival. Methods: A total of 203 cirrhosis patients were enrolled and underwent investigations, including 2-dimensional echocardiography with tissue Doppler imaging, and 139 patients with LVDD (cases) were compared with 64 patients without LVDD (controls). Logistic regression and Kaplan-Meier analysis were applied. Results: Mean age was 52.76±10 years. Among LVDD patients, 56% had grade-1, and 44% had grade-2 LVDD. Cirrhosis related to NASH had a more significant association with LVDD (P<0.001) than other etiologies. LVDD was significantly associated with a greater incidence of Child-Turcotte-Pugh (CTP) class C (P<0.001), higher model for end-stage liver disease scores (P=0.001), duration of cirrhosis >2 years since diagnosis (P=0.028), ascites (P<0.001), hepatic encephalopathy (P<0.010), hepatorenal syndrome (P<0.001), and a history of obesity (P=0.004). Multivariate analysis showed that higher CTP score, ascitic fluid protein and prolonged QTc interval were independently associated with LVDD (P=0.009; P=0.018; P=0.016, respectively). Kaplan-Meier survival analysis showed significantly poorer survival status in patients with higher grades of LVDD (P<0.001). The area under the receiver operating characteristic curve (0.78) was greatest for ascitic fluid protein in predicting LVDD, with a cutoff of >1 g/dL. Conclusions: Higher CTP score, prolonged QTc, higher ascitic fluid protein levels, and poor survival are significantly associated with LVDD. Ascitic fluid protein >1 g/dL could be an indicator for evaluating LVDD.

Hardware-aware training for large-scale and diverse deep learning inference workloads using in-memory computing-based accelerators.

Analog in-memory computing-a promising approach for energy-efficient acceleration of deep learning workloads-computes matrix-vector multiplications but only approximately, due to nonidealities that often are non-deterministic or nonlinear. This can adversely impact the achievable inference accuracy. Here, we develop an hardware-aware retraining approach to systematically examine the accuracy of analog in-memory computing across multiple network topologies, and investigate sensitivity and robustness to a broad set of nonidealities. By introducing a realistic crossbar model, we improve significantly on earlier retraining approaches. We show that many larger-scale deep neural networks-including convnets, recurrent networks, and transformers-can in fact be successfully retrained to show iso-accuracy with the floating point implementation. Our results further suggest that nonidealities that add noise to the inputs or outputs, not the weights, have the largest impact on accuracy, and that recurrent networks are particularly robust to all nonidealities.

Assessment of Visceral Fat Volume and Its Correlation with the Severity of Hepatic Fibrosis in Patients with NAFLD.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease. The spectrum of NAFLD includes simple steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. Our study aimed to calculate visceral fat volume at the L3-L4 vertebral level and its association with hepatic fibrosis assessed by transient elastography. METHODS: All patients above 18 years undergoing computed tomography (CT) abdomen in the Department of Radiodiagnosis of Medical College Thiruvananthapuram during the study period with NAFLD were included. Transient elastography was done. Patients were categorized to advanced fibrosis (>10 kPa) and without advanced fibrosis (<10 kPa). The area under the receiver operating characteristic (AUROC) curve was plotted. RESULTS: Sixty-four patients comprised 36 males and 28 females. Thirty-one (46%) were having advanced fibrosis (transient elastography>10 kPa) and 34 (54%) patients were without advanced fibrosis. About 0.733 was the AUROC for visceral fat in predicting advanced fibrosis. The cutoff was 167.5cm3 (sensitivity was 77.4% and specificity was 51.5% in predicting advanced fibrosis). CONCLUSION: About 0.733 was the AUROC for visceral fat in predicting advanced fibrosis. The cutoff was 167.5cm3 (sensitivity was 77.4% and specificity was 51.5% in predicting advanced fibrosis).

Barrett's Esophagus: A Comparison Study between Two Cohorts of Gastroesophageal Reflux Disease.

INTRODUCTION: Barrett's esophagus (BE) is a complication of gastroesophageal reflux disease (GERD). It is seen among 15% of GERD patients as per a population-based study by Ronkainen et  al. Barrett's has malignant potential and annual progression to carcinoma depends on the presence or absence of dysplasia. There are various risk factors for the development of BE. We compared two symptomatic cohorts of GERD patients from the same geographical area who were evaluated for the presence of Barrett's and various factors that can contribute to Barrett's Materials and methods: Cross-sectional study. Two GERD cohorts, one from Kottayam and the other from Trivandrum were taken. The presence of Barrett's and the factors contributing to the development of Barrett's were analyzed between the two groups. Since biopsy data of all patients were not available, endoscopically suspected esophageal metaplasia (ESEM) was taken as Barrett's Results: 415 patients were enrolled for the study (203 from Trivandrum and 212 from Kottayam). 192 females (99 from Trivandrum and 93 from Kottayam), and 223 males (104 from Trivandrum and 119 from Kottayam). Barrett's esophagus and especially long-segment Barrett's were significantly more common in Kottayam than Trivandrum (68 vs 22 and 36 vs 9) (p-value <0.001). Among the factors that were traditionally thought to contribute to the development of Barrett's esophagus, age (>50 years) was not statistically significant among the two cohorts (mean age of Trivandrum was 48 years and Kottayam was 49 years). Duration of GERD symptoms was significantly more in the Trivandrum cohort compared to Kottayam (p-value <0.001). Hiatus hernia and body mass index (BMI) were more common in Kottayam. There were no statistically significant differences in erosive esophagitis and antral gastritis (%age?) between the two cohorts. CONCLUSION: Both Trivandrum and Kottayam belong to the same geographical area and are separated by a distance of only 150 km. The Kottayam cohort is more prone to develop distal esophageal carcinoma as the BE is more in Kottayam. This data also suggests the need for GERD registries so that high-risk population can be targeted and early intervention can lead to a decrease in the incidence of distal esophageal carcinomas.

Validation of Spleen Shear Wave Elastography for the Screening of High-risk Varices in Patients with Compensated Advanced Chronic Liver Disease.

OBJECTIVES: Total number of avoided endoscopies using Baveno VI criteria is relatively low. Spleen elastography is an attractive tool and when compared with liver stiffness, it better represents the dynamic changes occurring in portal hypertension. The aim of the study was to evaluate spleen shear wave elastography (SWE) in compensated advanced chronic liver disease (cACLD) patients for ruling out the presence of esophageal high-risk varices (HRV). METHODS: A total of 401 patients with cACLD were included in this cross-sectional study. The total sample was split into training set (200 patients) and validation set (201 patients). Spleen stiffness was measured with two-dimensional shear wave elastography (2D SWE). Esophageal HRV were defined as large varices (diameter >5 mm) or small varices with red color signs. In the training set, the receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) of spleen SWE was assessed. A cutoff value was chosen (highest sensitivity and negative predictive value). In the validation set, the spleen SWE cutoff score and Baveno VI criteria were validated. RESULTS: The prevalence of HRV was 12% in the training set and 13% in the validation set. Spleen SWE had an AUC of 0.89 in ruling out the presence of high-risk esophageal varices (cutoff value of 48.7 kPa, sensitivity of 100%, and specificity of 53%). Validating spleen SWE ≤48.7 kPa in a different cohort of 201 cACLD patients, 55% of screening endoscopies could be avoided without missing any HRV, whereas using Baveno VI criteria only 30% of screening endoscopies could be spared. CONCLUSION: Spleen SWE ≤48.7 kPa was able to identify cACLD patients who could safely avoid screening endoscopy with good accuracy. Spleen SWE could avoid an additional 25% of screening endoscopies compared to the Baveno VI criteria and no HRV were missed.

Switching of ferroelectric polarization in epitaxial BaTiO3 films on silicon without a conducting bottom electrode.

Epitaxial growth of SrTiO3 on silicon by molecular beam epitaxy has opened up the route to the integration of functional complex oxides on a silicon platform. Chief among them is ferroelectric functionality using perovskite oxides such as BaTiO3. However, it has remained a challenge to achieve ferroelectricity in epitaxial BaTiO3 films with a polarization pointing perpendicular to the silicon substrate without a conducting bottom electrode. Here, we demonstrate ferroelectricity in such stacks. Synchrotron X-ray diffraction and high-resolution scanning transmission electron microscopy reveal the presence of crystalline domains with the long axis of the tetragonal structure oriented perpendicular to the substrate. Using piezoforce microscopy, polar domains can be written and read and are reversibly switched with a phase change of 180°. Open, saturated hysteresis loops are recorded. Thus, ferroelectric switching of 8- to 40-nm-thick BaTiO3 films in metal-ferroelectric-semiconductor structures is realized, and field-effect devices using this epitaxial oxide stack can be envisaged.

Oxygen vacancies in high dielectric constant oxide-semiconductor films.

We provide evidence that the oxygen vacancy is a dominant intrinsic electronic defect in nanometer scaled hafnium oxide dielectric films on silicon, relevant to microelectronics technology. We demonstrate this by developing a general model for the kinetics of oxygen vacancy formation in metal-ultrathin oxide-semiconductor heterostructures, calculating its effect upon the band bending and interfacial oxidation rates and showing good experimental agreement with the predictions.