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

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(pd in 77.5%and propranolol in 22.5%of ***:NSBBs reduce mortality without any effect on infection or variceal bleed in patients with ***,only one in four ACLF patients are suitable for NSBB therapy.

关键词： ACLF infection portal hypertension variceal bleed

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Small molecule inhibitor ddQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi Pradeepkiran Priyanka Rawat Arubala P.reddy Erika Orlov PHemachandra reddy department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA department of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA department of Pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA department of Speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA department of Public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(ddQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of ddQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate ddQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cdNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed ddQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with ddQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,ddQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(ddQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

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Pain in chronic pancreatitis: Managing beyond the pancreatic duct

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World Journal of Gastroenterology 2013年第38期19卷 6319-6328页

作者： Rupjyoti Talukdar d nageshwar reddy department of Medical Gastroenterology Asian Institute of GastroenterologySomajigudaHyderabad 500082India Asian Healthcare Foundation SomajigudaHyderabad 500082India

Chronic pancreatitis(CP)continues to be a clinical *** or recurrent abdominal pain is the most compelling symptom that drives patients to seek medical ***,in spite of using several treatment approaches in the clinical setting,there is no single specific treatment modality that can be earmarked as a cure for this ***,ductal hypertension has been associated with causation of pain in CP;and patients are often subjected to endotherapy and surgery with a goal to decompress the pancreatic *** studies on humans(clinical and laboratory based)and experimental models have put forward several mechanisms,including neuroimmune alterations,which could be responsible for *** might explain the partial or no response to single modality treatment in a significant proportion of *** current review discusses the recent concepts of pain generation in CP and evidence based therapeutic approaches(other than ductal decompression)to handle persistent or recurrent *** focus primarily on parenchymal and neural components;and discuss the role of antioxidants and the existing controversies,drugs that interfere with neural transmission,pancreatic enzyme supplementation,celiac neurolysis,and pancreatic resection *** review concludes with the treatment approach that we follow at our institute.

关键词： Pain Chronic pancreatitis Nociception Neuroplasticity Antioxidant micronutrients Pregabalin Pancreatic enzymes

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Endotherapy in chronic pancreatitis

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World Journal of Gastroenterology 2013年第37期19卷 6156-6164页

作者： Manu Tandan d nageshwar reddy department of Medical Gastroenterology Asian Institute of Gastroenterology

Chronic pancreatitis(CP)is a progressive disease with irreversible changes in the *** commonly present with pain and with exocrine or endocrine *** therapeutic efforts in CP are directed towards relief of pain as well as the management of associated *** therapy offers many advantages in patients with CP who present with ductal calculi,strictures,ductal leaks,pseudocyst or associated biliary *** offers a high rate of success with low morbidity in properly selected *** procedure can be repeated and failed endotherapy is not a hindrance to subsequent *** pancreatic sphincterotomy is helpful in patients with CP with minimal ductal changes while minor papilla sphincterotomy provides relief in patients with pancreas divisum and chronic *** shock wave lithotripsy is the standard of care in patients with large pancreatic ductal *** term follow up has shown pain relief in over 60%of patients.A transpapillary stent placed across the disruption provides relief in over 90%of patients with ductal *** ductal strictures are managed by single large bore *** stents are placed for *** associated benign biliary strictures(BBS)are best treated with multiple plastic stents,as the response to a single plastic stent is *** self expanding metal stents are increasingly being used in the management of BBS though further long term studies are *** are best drained endoscopically with a success rate of 80%-95%at most ***(EUS)has added to the therapeutic armamentarium in the management of patients with *** of pseudcysts,cannulation of inaccessible pancreatic ducts and celiac ganglion block in patients with intractable pain are all performed using *** should be offered as the first line of therapy in properly selected patients with CP who have failed to respond to med

关键词： Chronic pancreatitis Endoscopic retrograde cholangiopancreatography Pancreatic sphincterotomy Extracorporeal shockwave lithotripsy Endosonography

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Endoscopic management of pancreatic fluid collectionsrevisited

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World Journal of Gastroenterology 2017年第15期23卷 2660-2672页

作者： Zaheer Nabi Jahangeer Basha d nageshwar reddy department of Gastroenterology Asian Institute of Gastro-enterology

The development of pancreatic fluid collections(PFC) is one of the most common complications of acute severe pancreatitis. Most of the acute pancreatic fluid collections resolve and do not require endoscopic drainage. However, a substantial proportion of acute necrotic collections get walled off and may require drainage. Endoscopic drainage of PFC is now the preferred mode of drainage due to reduced morbidity and mortality as compared to surgical or percutaneous drainage. With the introduction of new metal stents, the efficiency of endoscopic drainage has improved and the task of direct endoscopic necrosectomy has be-come easier. The requirement of re-intervention is less with new metal stents as compared to plastic stents. However, endoscopic drainage is not free of adverse events. Severe complications including bleeding, perforation, sepsis and embolism have been described with endoscopic approach to PFC. Therefore, the endoscopic management of PFC is a multidisciplinary affair and involves interventional radiologists as well as GI surgeons to deal with unplanned adverse events and failures. In this review we discuss the recent advances and controversies in the endoscopic management of PFC.

关键词： Endotherapy Pseudocyst Pancreatic necrosis Necrosectomy

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Thinking outside the liver: Induced pluripotent stem cells for hepatic applications

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World Journal of Gastroenterology 2013年第22期19卷 3385-3396页

作者： Mekala Subba Rao Mitnala Sasikala d nageshwar reddy Institute of Basic Sciences and Translational Research Asian Healthcare Foundation Asian Institute of Gastroenterology Hyderabad 500082 India Asian Healthcare Foundation Asian Institute of Gastroenterology Hyderabad 500082 India

The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos. This breakthrough in generating iPSCs from somatic cells has overcome the ethical issues and immune rejection involved in the use of human embryonic stem cells. Hence, iPSCs form a great potential source for developing disease models, drug toxicity screening and cell-based therapies. These cells have the potential to differentiate into desired cell types, including hepatocytes, under in vitro as well as under in vivo conditions given the proper microenvironment. iPSC-derived hepatocytes could be useful as an unlimited source, which can be utilized in disease modeling, drug toxicity testing and producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. In this review, we discuss the induction methods, role of reprogramming factors, and characterization of iPSCs, along with hepatocyte differentiation from iPSCs and potential applications. Further, we discuss the location and detection of liver stem cells and their role in liver regeneration. Although tumor formation and genetic mutations are a cause of concern, iPSCs still form a promising source for clinical applications.

关键词： Liver stem cells Hepatocytes disease modeling drug toxicity Clinical applications Patient-specific induced pluripotent stem cell-derived hepatocytes

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Management of hepatitis B and C in special population

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World Journal of Gastroenterology 2021年第40期27卷 6861-6873页

作者： Anand V Kulkarni nageshwar reddy duvvuru department of Hepatology Asian Institute of GastroenterologyHyderabad 500032TelanganaIndia department of Gastroenterology Asian Institute of GastroenterologyHyderabad 500032TelanaganaIndia

Chronic viral hepatitis is one of the leading causes of cirrhosis *** hepatitis B is more common in the Asia-Pacific region due to the larger population and lower screening *** C predominates in the west due to injection drug *** discovery of(oral)direct-acting antiviral agents(dAAs)has changed the landscape of chronic hepatitis C(CHC)***(t)ide analogs(NUCs)have also changed the approach to the treatment of chronic hepatitis B(CHB).Oral NUCs and dAAs have excellent efficacy and patient acceptance as well as a lower risk of ***,certain populations have no robust data and safety and efficacy of such oral drugs is still *** this review,we provide an overview of the management of CHB and CHC in special populations,such as those with chronic kidney disease,pregnant women,healthcare workers,and those undergoing chemo-or immunosuppressive therapy.

关键词： Chronic kidney disease Pregnancy Hepatitis B Hepatitis C Health care professionals Tenofovir

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Prediction,prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy:An update

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World Journal of Gastroenterology 2024年第9期30卷 1096-1107页

作者： Zaheer Nabi Pradev Inavolu nageshwar reddy duvvuru department of Gastroenterology Asian Institute of GastroenterologyHyderabad 500082TelanganaIndia department of Medical Gastroenterology Asian Institute of GastroenterologyHyderabad 500032TelanganaIndia

Achalasia cardia,the most prevalent primary esophageal motility disorder,is predominantly characterized by symptoms of dysphagia and *** principal therapeutic approaches for achalasia encompass pneumatic dilatation(Pd),Heller's myotomy,and the more recent per-oral endoscopic myotomy(POEM).POEM has been substantiated as a safe and efficacious modality for the management of *** POEM demonstrates superior efficacy compared to Pd and an efficacy parallel to Heller's myotomy,the incidence of gastroesophageal reflux disease(GERd)following POEM is notably higher than with the aforementioned *** symptomatic reflux post-POEM is relatively infrequent,the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERd-related *** advancements in the field have enhanced our comprehension of the risk factors,diagnostic methodologies,preventative strategies,and therapeutic management of GERd subsequent to *** review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux,potential modifications in the POEM technique to mitigate GERd risk,and the strategies for managing reflux following POEM.

关键词： Achalasia cardia Per-oral endoscopic myotomy Gastroesophageal reflux Esophagitis Gastroesophageal reflux disease

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Extracorporeal shock wave lithotripsy for pancreatic and large common bile duct stones

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World Journal of Gastroenterology 2011年第39期17卷 4365-4371页

作者： Manu Tandan d nageshwar reddy reddy Asian Institute of Gastroenterology 6-3-652 SomajigudaHyderabad 500 082India

Extraction of large pancreatic and common bile duct(CBd)calculi has always challenged the therapeutic *** shockwave lithotripsy(ESWL)is an excellent tool for patients with large pancreatic and CBd calculi that are not amenable to routine *** calculi in the head and body are targeted by ESWL,with an aim to fragment them todiameter so that they can be extracted by subsequent endoscopic retrograde cholangio-pancreatography(ERCP).In our experience,complete clearance of the pancreatic duct was achieved in 76% and partial clearance in 17%of 1006 ***-term pain relief with reduction in the number of analgesics ingested was seen in 84%of these *** large CBd calculi,a nasobiliary tube is placed to help target the calculi,as well as bathe the calculi in salinea simple maneuver which helps to facilitate *** aim is to fragment calculi tod clear the same during *** clearance of the CBd was achieved in 84.4%of and partial clearance in 12.3%of 283 *** than 90%of the patients with pancreatic and biliary calculi needed three or fewer sessions of ESWL with 5000 shocks being de-livered at each *** use of epidural anesthesia helped in reducing patient ***,together with the better focus achieved with newer third-gen-eration lithotripters,prevents collateral tissue damage and minimizes the *** in our experience with nearly 1300 patients were minimal,and no extension of hospital stay was *** rates of clearance of pancreatic and biliary calculi with minimal adverse effects have been reported from the centers where ESWL is performed *** view of its high efficiency,non-invasive nature and low complication rates,ESWL can be offered as the first-line therapy for selected patients with large pancreatic and CBd calculi.

关键词： Pancreatic calculi Extracorporeal shock-wave lithotripsy Common bile duct calculi

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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

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