Discovery of BMS-986308: A Renal Outer Medullary Potassium Channel Inhibitor for the Treatment of Heart Failure.

Recent literature reports highlight the importance of the renal outer medullary potassium (ROMK) channel in renal sodium and potassium homeostasis and emphasize the potential impact that ROMK inhibitors could have as a novel mechanism diuretic in heart failure patients. A series of piperazine-based ROMK inhibitors were designed and optimized to achieve excellent ROMK potency, hERG selectivity, and ADME properties, which led to the identification of compound (BMS-986308). BMS-986308 demonstrated efficacy in the volume-loaded rat diuresis model as well as promising in vitro and in vivo profiles and was therefore advanced to clinical development.

Resectable Distal Duodenal Gastrointestinal Stromal Tumour Presenting with Features of Anaemia.

Although gastrointestinal stromal tumours (GISTs) are encountered all along the gastrointestinal tract, duodenal GISTs are uncommon and account for <5% of the cases. A 45-year-old woman presented chiefly with anaemia and associated symptoms, whom on further evaluation was found to have a non-metastatic GIST in the distal duodenum sparing the pancreas and major vasculature. Patient was undertaken for segmental duodenectomy with the help of advanced bipolar energy device (tumour occupying D3-D4 with 1 cm proximal margin and 15 cm jejunum) preserving the pancreas and ampulla with end-to-end duodenojejunostomy with an uneventful postoperative course and clear margins on histopathology.

Comparison of Perioperative Complication Rates of Total Extraperitoneal and Transabdominal Preperitoneal Repairs in Primary Inguinal Hernia.

Background: Hernia may be defined as a protrusion of viscus through layers anatomically designed to contain that viscus. Most abdominal hernias occur at well-described sites of potential weakness. Repair of inguinal hernia is one of the most common operations in general surgery.

Discovery of ()-1-((2',6-Bis(difluoromethyl)-[2,4'-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine (BMS-986176/LX-9211): A Highly Selective, CNS Penetrable, and Orally Active Adaptor Protein-2 Associated Kinase 1 Inhibitor in Clinical Trials for the Treatment of Neuropathic Pain.

Recent mouse knockout studies identified adapter protein-2 associated kinase 1 (AAK1) as a viable target for treating neuropathic pain. Potent small-molecule inhibitors of AAK1 have been identified and show efficacy in various rodent pain models. ()-1-((2',6-Bis(difluoromethyl)-[2,4'-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine (BMS-986176/LX-9211) () was identified as a highly selective, CNS penetrant, potent AAK1 inhibitor from a novel class of bi(hetero)aryl ethers.

Can renal transplant improve the quality of life of caregiver donors? A prospective study from India.

Live-related renal transplantation in India by "caregiver donors" provides huge financial, emotional, and physical support. Their psychological and mental health has not been addressed. We performed a prospective study using the World Health Organization Quality of Life (WHOQoL) BREF Scores and the Hospital Anxiety and Depression Scales preoperatively, at two weeks and three months after transplant.

Significant Liver Atrophy Due to Vascular Compromise Associated With Adult Congenital Diaphragmatic Hernia.

Diaphragmatic hernia in adults is mostly post-traumatic in origin, and rarely congenital. In both situations, the right side is less commonly involved due to the protection offered by the liver and earlier closure of the right pleuroperitoneal canal. A congenital diaphragmatic hernia may present in adulthood with multi-visceral contents, of which the liver is an extremely rare content, mentioned only in a few previous reports.

Predictors of Lymphatic Complications Following Renal Transplant: A Prospective Study Involving Predominantly Living Donor Transplants From India.

Introduction Lymphatic complications (LC) are common (up to 33%) and troublesome after renal transplantation. Different studies have established varying medical and surgical risk factors, mostly by retrospective analysis on deceased donor renal transplants (DDRTs). The end-point is mostly lymphocele, with few reports documenting the equally important lymphorrhea.

Successful Transplant of Two Kidneys Harvested from a Young Brain-Dead Liver Transplant Recipient.

Efforts to increase the dismal deceased renal transplantation (DRT): live renal transplantation (LRT) ratio in our country have gathered momentum recently, with governmental and non-governmental projects focussing on building public awareness and capacity-building, and appropriate legislation. Worldwide, efforts at increasing the number of organs from the deceased pool have focussed on the use of 'expanded criteria donors', including deceased cardiac donors (DCD). 'Reuse' transplant, where an organ is transplanted after removal from the first recipient, is a rare strategy, used more commonly in liver than in kidney transplantation.

Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain.

To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL).