Mitra shunt (spleen preserving, side to side lieno-renal shunt) for portal hypertension with hypersplenism in early infancy

Extrahepatic portal vein obstruction (EHPVO) is the commonest cause of portal hypertension presenting with gastrointestinal bleeding and splenomegaly. Medical management of this condition may provide relief, but involves repeated hospital visits and endoscopic procedures. Surgery is an effective curative solution by lowering portal venous pressure with effective shunting of venous blood from splanchnic to systemic circulation. Shunt surgery for such a small baby has not been previously reported and splenectomy has its own problems. Similarly, banding or sclerotherapy in such babies is not without risk. Among the various shunt options, Mitra shunt (spleen preserving, side-to-side lienorenal shunt), developed and standardized in our own country, stands out as the most optimum surgical treatment for EHPVO in early infancy. We report a 4-month-old baby, youngest recipient of Mitra shunt reported in literature with successful outcome

Discovery and Development of 1‑[(2-Bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]‑1<i>H</i>‑indole Dimesylate Monohydrate (SUVN-502): A Novel, Potent, Selective and Orally Active Serotonin 6 (5-HT₆) Receptor Antagonist for Potential Treatment of Alzheimer’s Disease

Optimization of a novel series of 3-(piperazinylmethyl) indole derivatives as 5-hydroxytryptamine-6 receptor (5-HT₆R) antagonists resulted in identification of 1-[(2-bromophenyl)­sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)­methyl]-1<i>H</i>-indole dimesylate monohydrate (<b>5al</b>, SUVN-502) as a clinical candidate for potential treatment of cognitive disorders. It has high affinity at human 5-HT₆R (<i>K</i>_i = 2.04 nM) and selectivity over 100 target sites which include receptors, enzymes, peptides, growth factors, ion channels, steroids, immunological factors, second messengers, and prostaglandins. It has high selectivity over 5-HT_2A receptor. It is orally bioavailable and brain penetrant with robust preclinical efficacy. The combination of <b>5al</b>, donepezil, and memantine (triple combination) produces synergistic effects in extracellular levels of acetylcholine in the ventral hippocampus. Preclinical efficacy in triple combination and high selectivity over 5-HT_2A receptors are the differentiating features which culminated in selection of <b>5al</b> for further development. The Phase-1 evaluation of safety and pharmacokinetics has been completed, allowing for the initiation of a Phase-2 proof of concept study