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Bleeding risk and thrombosis in cirrhosis:a paradox with a need to address them

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Hepatobiliary Surgery and Nutrition 2023年第3期12卷 410-412页

作者： anand v.kulkarni K.Rajender Reddy Department of Hepatology Asian Institute of GastroenterologyHyderabadIndia Division of Gastroenterology and Hepatology University of PennsylvaniaPhiladelphiaPAUSA

Patients with cirrhosis have a state of“rebalanced hemostasis”where there is a simultaneous reduction in both qualitative and quantitative properties of procoagulants and anticoagulants,i.e.,platelets,fibrinogen,coagulation factors,protein C,S,and antithrombin and conversely,there is an increase in the levels of von Willebrand factor,endothelial factor vIII,tissue plasminogen activator(t-PA),and plasminogen activator inhibitor type 1(PAI-1)(1).Laboratory tests,such as INR,involving these coagulation proteins have been used for the prognostication of patients with cirrhosis/liver failure and have historically been part of several severity scores(2,3).Spontaneous bleeding due to clotting factor deficiencies is less frequent in the absence of mechanical trauma,while thrombosis is not uncommon and may merit anticoagulation therapy(4).However,the management of patients with cirrhosis with abnormalities in the hemostasis system is *** meet this unmet need,the European Association for the Study of the Liver(EASL)developed new guidelines for the prevention and management of bleeding and thrombosis in patients with cirrhosis(5).The bleeding here is referred to mucocutaneous and visceral bleeding events.

关键词： viscoelastic tests international normalized ratio(INR) coagulation liver disease

Drugs for Non-alcoholic Steatohepatitis (NASH): Quest for the Holy Grail

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 40-50页

作者： Mithun Sharma Madhumita Premkumar anand v kulkarni Pramod Kumar D Nageshwar Reddy Nagaraja Padaki Rao Department of Hepatology Asian Institute of GastroenterologyHyderabadIndia Department of Hepatology PGIMERChandigarhIndia Department of Gastroenterology Asian Institute of GastroenterologyHyderabadIndia

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic that is likely to become the most common cause of chronic liver disease in the next decade, worldwide. Though numerous drugs have been evaluated in clinical trials, most of them have returned inconclusive results and shown poorly-tolerated adverse effects. None of the drugs have been approved by the Food and Drug Administration for treating biopsy-proven non-alcoholic steatohepatitis (NASH). vitamin E and pioglitazone have been extensively used in treatment of biopsy-proven nondiabetic NASH patients. Although some amelioration of inflammation has been seen, these drugs did not improve the fibrosis component of NASH. Therefore, dietary modification and weight reduction have remained the cornerstone of treatment of NASH;moreover, they have shown to improve histological activity as well as fibrosis. The search for an ideal drug or ‘Holy Grail’ within this landscape of possible agents continues, as weight reduction is achieved only in less than 10% of patients. In this current review, we summarize the drugs for NASH which are under investigation, and we provide a critical analysis of their up-to-date results and outcomes.

关键词： Fatty liver NAFLD NASH Obeticholic acid Saroglitazar

Pathophysiology and Prevention of Paracentesis-induced Circulatory Dysfunction:A Concise Review

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Journal of Clinical and Translational Hepatology 2020年第1期8卷 42-48页

作者： anand v kulkarni Pramod Kumar Mithun Sharma T R Sowmya Rupjyoti Talukdar Padaki Nagaraj Rao D Nageshwar Reddy Department of Hepatology Asian Institute of GastroenterologyHyderabadIndia Department of Gastroenterology Asian Institute of GastroenterologyHyderabadIndia

Annually,10%of cirrhotic patients with ascites develop refractory ascites for which large-volume paracentesis(LvP)is a frequently used therapeutic ***,although a safe method,is associated with circulatory dysfunction in a significant percentage of patients,which is termed para-centesis-induced circulatory dysfunction(PICD).PICD results in faster reaccumulation of ascites,hyponatremia,renal impairment,and shorter *** is diagnosed through laboratory results,with increases of>50%of baseline plasma renin activity to a value≥4 ng/mL/h on the fifth to sixth day after *** this review,we discuss the pathophysi-ology and prevention of PICD.

关键词： Refractory ascites Plasma renin activity Large-volume paracentesis Cirrhosis Portal hypertension

Clinical validation of Global Coagulation Tests to Guide Blood Component Transfusions in Cirrhosis and ACLF

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 210-219页

作者： Madhumita Premkumar Rohit Mehtani Smita Divyaveer Kamal Kajal anand vkulkarni Syed Ahmed Harmanpreet Kaur Harpreet Kaur Radhakrishna Dhiman Ajay Duseja Arka De Departments of Hepatology Postgraduate Institute of Medical Education and ResearchChandigarhIndia Nephrology Postgraduate Institute of Medical Education and ResearchChandigarhIndia Anesthesia and Intensive CarePostgraduate Institute of Medical Education and ResearchChandigarhIndia Department of Hepatology Asian Institute of GastroenterologyHyderabadIndia Medicine Postgraduate Institute of Medical Education and ResearchChandigarhIndia

Background and Aims:Patients with cirrhosis and acuteon-chronic liver failure(ACLF)may have bleeding complications and need for invasive ***-of-care(POC)coagulation tests like thromboelastography(TEG)and Sonoclot may be better for guiding patient management than the standard coagulation tests(SCTs),like prothrombin time,platelet count and international normalized ***:We prospectively compared and validated the POC tests and SCTs in 70 persons with ACLF and 72 persons with decompensated cirrhosis who had clinical bleeding and checked for episodes of re-bleeding and transfusion *** assessed pre-procedure requirement of blood components when correction was done based on an SCT or POC ***:Episodes of bleeding were seen in 45%and 28%of ACLF and cirrhosis patient,respectively(p=0.036),with the major site of bleeding being gastrointestinal(31%and 16%,respectively).Platelet counts correlated with TEG-maximum amplitude in cirrhosis(p=0.045)and prothrombin time correlated positively with TEG-reaction(R)time(p=0.032),TEG-Clot kinetics(K)time(p=0.042),Son-activated clotting time(p=0.038)and negatively with clot rate(p=0.043)in ACLF,making these correctable target variables in POC transfusion *** 223 procedures,transfusion of fresh frozen plasma and platelet concentrate was reduced by 25%(p=0.035)and 20.8%(p=0.045)by using a POC strategy in 76 *** of deranged Son-activated clotting time and TEG-reaction time was noted in 68%and 72%after 24 h of fresh frozen plasma transfusion in ACLF and 85%and 80%in cirrhosis,***:Our study clinically validates that POC tests can better detect coagulation defects and transfusion thresholds in ACLF and cirrhosis,whereas use of conventional tests appear to be less suitable in patients with clinical *** Registration:NCT04332484.

关键词： Coagulation Cirrhosis ACLF validation Sonoclot Thromboelastography

Nonselective beta‐blockers reduce mortality in patients with acute‐on‐chronic liver failure

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Portal Hypertension & Cirrhosis 2022年第1期1卷 15-22页

作者： anand v.kulkarni Madhumita Premkumar Karan Kumar Juned A.Khan Baqar A.Gora Sowmya Tirumalle Sameer Shaik Mithun Sharma Rajesh Gupta Nageshwar D.Reddy Padaki N.Rao Department of Hepatology AIG HospitalsHyderabadIndia Department of Hepatology PGIMERChandigarhIndia Department of Hepatology Mahatma Gandhi HospitalsJaipurIndia Department of Hepatology Hopewell HospitalLucknowIndia

Aim:Nonselective beta‐blockers(NSBBs)can reduce the incidence of complications in patients with cirrhosis and prolong *** safety and efficacy of NSBBs in real‐world settings in patients with acute‐on‐chronic liver failure(ACLF)identified by the Asian Pacific Association for the Study of Liver criteria are *** study aimed to assess the safety and efficacy of NSBBs in patients with Asian Pacific Association for the Study of Liver(APASL)‐defined ACLF Methods:In this retrospective,multicenter study,patients with ACLF with complete 30 days follow‐up from January 2019 to December 2021 were *** primary objective was to compare 30‐day mortality among standard of care(SOC)and NSBB(+SOC)*** secondary objectives were to compare the incidence of infection,variceal bleed,and recompensation among both the ***:A total of 346 patients were *** 26%(n=89)of them received NSBBs,while 74%(n=257)received only *** Kaplan-Meier analysis,the incidence of mortality was 21%(95%confidence interval[CI]:16.20-26.50)in SOC group compared to only 8%(95%CI:3.22-15.53)in NSBB group at Day 30(p=0.005).Similarly,mortality in SOC group was 63%(95%CI:56.81-69.00)compared to 46%(95%CI:35.44-57.00)in NSBB group at 1 year(p=0.001).NSBB therapy could not reduce the incidence of infections or variceal ***‐seven percent of patients in the SOC group and 73%of patients in the NSBB group(pvariceal bleed in patients with ***,only one in four ACLF patients are suitable for NSBB therapy.

关键词： ACLF infection portal hypertension variceal bleed

Higher Grain-Filling Rate in Inferior Spikelets of Tolerant Rice Genotype Offset Grain Yield Loss under Post-Anthesis High Night Temperatures

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Rice science 2024年第5期31卷 572-586,I0059-I0061页

作者： Nitin SHARMA Bhupinder SINGH Subbaiyan Gopala KRISHNAN Haritha BOLLINEDI Pranab Kumar MANDAL Milan Kumar LAL Prakash Kumar JHA P.v.vara PRASAD Anjali anand Division of Plant Physiology Indian Council of Agricultural Research(ICAR)-Indian Agricultural Research Institute(IARI)New Delhi 110012India Division of Environment Science ICAR-IARINew Delhi 110012India Division of Genetics ICAR-IARINew Delhi 110012India ICAR-National Institute for Plant Biotechnology New Delhi 110012India Division of Crop Physiology and Biochemistry ICAR-National Rice Research InstituteCuttack 753006India Department of Plant and Soil Sciences Mississippi State UniversityStarkvilleMS 39762USA Feed the Future Innovation Lab for Collaborative Research on Sustainable Intensification Kansas State UniversityManhattanKS 66506USA Department of Agronomy Kansas State UniversityManhattanKS 66506USA

Increased nighttime respiratory losses decrease the amount of photoassimilates available for plant growth and yield. We hypothesized that the increased respiratory carbon loss under high night temperatures(HNT) could be compensated for by increased photosynthesis during the day following HNT exposure. Two rice genotypes, vandana(HNT-sensitive) and Nagina 22(HNT-tolerant), were exposed to HNT(4 ℃ above the control) from flowering to physiological maturity. They were assessed for alterations in the carbon balance of the source(flag leaf) and its subsequent impact on grain filling dynamics and the quality of spatially differentiated sinks(superior and inferior spikelets). Both genotypes exhibited significantly higher night respiration rates. However, only Nagina 22 compensated for the high respiration rates with an increased photosynthetic rate, resulting in a steady production of total dry matter under HNT. Nagina 22 also recorded a higher grain-filling rate, particularly at 5 and 10 d after flowering, with 1.5- and 4.0-fold increases in the translocation of ^(14)C sugars to the superior and inferior spikelets, respectively. The ratio of photosynthetic rate to respiratory rate on a leaf area basis was negatively correlated with spikelet sterility, resulting in a higher filled spikelet number and grain weight per plant, particularly for inferior grains in Nagina 22. Grain quality parameters such as head rice recovery, high-density grains, and gelatinization temperature were maintained in Nagina 22. An increase in the rheological properties of rice flour starch in Nagina 22 under HNT indicated the stability of starch and its ability to reorganize during the cooling process of product formation. Thus, our study showed that sink adjustments between superior and inferior spikelets favored the growth of inferior spikelets, which helped to offset the reduction in grain weight under HNT in the tolerant genotype Nagina 22.

关键词： high night temperature inferior grain pasting property radiolabeled sugar superior grain

Faster Region Convolutional Neural Network(FRCNN)Based Facial Emotion Recognition

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Computers, Materials & Continua 2024年第5期79卷 2427-2448页

作者： J.Sheril Angel A.Diana Andrushia TMary Neebha Oussama Accouche Louai Saker N.anand Department of Electronics and Communication Engineering Karunya Institute of Technology and SciencesCoimbatore641114India College of Engineering and Technology American University of the Middle EastEgaila54200Kuwait Department of Civil Engineering Karunya Institute of Technology and SciencesCoimbatore641114India

Facial emotion recognition(FER)has become a focal point of research due to its widespread applications,ranging from human-computer interaction to affective *** traditional FER techniques have relied on handcrafted features and classification models trained on image or video datasets,recent strides in artificial intelligence and deep learning(DL)have ushered in more sophisticated *** research aims to develop a FER system using a Faster Region Convolutional Neural Network(FRCNN)and design a specialized FRCNN architecture tailored for facial emotion recognition,leveraging its ability to capture spatial hierarchies within localized regions of facial *** proposed work enhances the accuracy and efficiency of facial emotion *** proposed work comprises twomajor key components:Inception v3-based feature extraction and FRCNN-based emotion *** experimentation on Kaggle datasets validates the effectiveness of the proposed strategy,showcasing the FRCNN approach’s resilience and accuracy in identifying and categorizing facial *** model’s overall performance metrics are compelling,with an accuracy of 98.4%,precision of 97.2%,and recall of 96.31%.This work introduces a perceptive deep learning-based FER method,contributing to the evolving landscape of emotion recognition *** high accuracy and resilience demonstrated by the FRCNN approach underscore its potential for real-world *** research advances the field of FER and presents a compelling case for the practicality and efficacy of deep learning models in automating the understanding of facial emotions.

关键词： Facial emotions FRCNN deep learning emotion recognition face CNN

Alternative models of cancer stem cells: The stemness phenotype model, 10 years later

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World Journal of Stem Cells 2021年第7期13卷 934-943页

作者： vivek Kaushik Yogesh kulkarni Kumar Felix Neelam Azad anand Krishnan v Iyer Juan Sebastian Yakisich School of Pharmacy Department of Pharmaceutical SciencesHampton UniversityHamptonVA 23668United States

The classical cancer stem cell(CSCs)theory proposed the existence of a rare but constant subpopulation of *** this model cancer cells are organized hierarchically and are responsible for tumor resistance and tumor ***,eliminating CSCs will eventually lead to cure of *** simplistic model has been challenged by experimental *** 2010 we proposed a novel and controversial alternative model of CSC biology(the Stemness Phenotype Model,SPM).The SPM proposed a non-hierarchical model of cancer biology in which there is no specific subpopulation of CSCs in ***,cancer cells are highly plastic in term of stemness and CSCs and non-CSCs can interconvert into each other depending on the *** model predicts the existence of cancer cells ranging from a pure CSC phenotype to pure non-CSC phenotype and that survival of a single cell can originate a new *** the past 10 years,a plethora of experimental evidence in a variety of cancer types has shown that cancer cells are indeed extremely plastic and able to interconvert into cells with different stemness *** this review we will(1)briefly describe the cumulative evidence from our laboratory and others supporting the SPM;(2)the implications of the SPM in translational oncology;and(3)discuss potential strategies to develop more effective therapeutic regimens for cancer treatment.

关键词： Cancer Stem cells Stemness Plasticity Chemotherapy Interconversion

Effectiveness of m-health technology-enabled physical activity program on physical activity adoption and adherence in people with hypertension in India:A randomized controlled trial protocol

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Chronic Diseases and Translational Medicine 2024年第2期10卷 92-101页

作者： vidhi Thakar Sureshkumar Kamalakannan v.Prakash Ashok&Rita Patel Institute of Physiotherapy Charotar University of Science and TechnologyChangaAnandGujaratIndia Department of Social Work Education and Community-WellbeingNorthumbria UniversityNewcastle upon TyneUK

Background Exercise and medication have similar benefits in reducing blood pressure(BP);however,hypertension management initiatives primarily focus on *** is due to scarce research on the effectiveness of implementation strategies for optimal exercise adoption and *** were found to be effective in delivering hypertension care and increase exercise *** this,only a small number of research projects in India have used smartphones as a strategy for managing *** We hypothesized that smartphone application-based care would lead to higher exercise adherence among adults(30–79 years)with hypertension compared to those who receive usual *** will be a multicentric,randomized controlled,parallel-design,superiority clinical *** outcome assessor and data analyst will be blinded to group *** in the intervention group will receive mobile application-based care for 6 *** in the usual care group will receive a standard *** groups will receive the same number of *** The primary outcome is the difference in the proportion of people adherent to the recommended level of physical activity evaluated using an exercise adherence rating scale in the intervention group and the control *** adoption will be measured as the percentage of eligible participants in each study setting willing to initiate the exercise *** secondary outcome includes differences in systolic and diastolic BP and self-management(evaluated using the Hypertension Self-Care Profile).The trial outcome will be accompanied by a process *** This research will inform about the comparative effectiveness of conventional and m-health interventions for exercise adoption and adherence in people with hypertension in resource-constrained settings.

关键词： hypertension low-and middle-income countries m-health physical activity adherence