Synthesis of novel seven-membered carbasugars and evaluation of their glycosidase inhibition potentials

Here, we report the synthesis of five novel seven-membered carbasugar analogs. We adopted a chiral-pool strategy starting from the cheap and readily available d-mannitol to synthesize these ring-expanded carbasugars. Apart from several regioselective protecting group manipulations, these syntheses involved Wittig olefination and ring-closing metathesis as the key steps. We observed an unprecedented deoxygenation reaction of an allylic benzyl ether upon treatment with H₂/Pd during the synthesis. Preliminary biological evaluation of the carbasugars revealed that these ring expanded carbasugars act as inhibitors of various glycosidases. This study highlights the importance of the synthesis of novel ring expanded carbasugars and their biological exploration.

Here, we report the synthesis of five novel seven-membered carbasugar analogs.     

Severity of diabetic retinopathy and its relationship with age at onset of diabetes mellitus in India: A multicentric study

Purpose:To present clinical profile and risk factors of sight-threatening diabetic retinopathy (STDR) among people with age of onset of diabetes (AOD) <25 versus ≥25 years.Methods:A retrospective chart analysis of consecutive patients with diabetic retinopathy (DR) n = 654) treated at 14 eye care centers across India between 2018 and 2019 was performed. Patients were divided into two groups, Group 1: AOD <25 years and Group 2: AOD ≥25 years. DR and diabetic macular edema (DME) were classified using the International Clinical Classification of DR severity scale. STDR included severe nonproliferative DR (NPDR), proliferative DR (PDR), and moderate to severe DME. A multilevel mixed-effects model was used for comparison between two groups: 1) Patients with DR and AOD <25 years and 2) Patients with DR and AOD ≥25 years. Bivariate and multivariate regression analyses were used to evaluate risk factors between the two groups.Results:A total of 654 patients were included, 161 (307 eyes) in AOD <25 and 493 (927 eyes) in AOD >25 group. There was a higher prevalence of PDR with high-risk characteristics in AOD <25 group (24% vs. 12%) at baseline and 12-month follow-up (25% vs. 6%); P < 0.001. Systolic hypertension and poor glycemic control were risk factors in both groups, with no difference in these modifiable risk factors between groups.Conclusion:People with youth-onset DM are likely to present with severer form of STDR despite similar modifiable risk factors. Therefore, strict control of systolic blood pressure, glycemic status, and regular screening for DR are recommended to reduce the risk of STDR irrespective of the age of onset of diabetes.     

Outcomes for Surgery in Large Cell Lung Neuroendocrine Cancer

IntroductionThere are limited small, single-institution observational studies examining the role of surgery in large cell neuroendocrine cancer (LCNEC). We investigated the outcomes of surgery for stage I to IIIA LCNEC by using the National Cancer Database.MethodsPatients with stage I to IIIA LCNEC were identified in the National Cancer Database (2004–2015) and grouped by treatment: definitive chemoradiation versus surgery. Overall survival, by stage, was the primary outcome. Outcomes of surgical patients were also compared with those of patients with SCLC or other non–small cell histotypes.ResultsA total of 6092 patients met the criteria: 96%, 94%, 75%, and 62% of patients received an operation for stage I, II, IIIA, and cN2 disease, respectively. Complete resection was achieved in at least 85% of patients. The 5-year survival rates for patients undergoing an operation for stage I and II LCNEC were 50% and 45%, respectively. Surgical patients with stage IIIA and N2 disease had 36% and 32% 5-year survival rates, respectively. When compared with stereotactic body radiation in stage I disease and chemoradiation in patients with stage II to IIIA disease, surgery was associated with a survival benefit. Patients with LCNEC who underwent an operation generally experienced worse survival by stage than did those with adenocarcinoma but experienced improved survival compared with patients with SCLC. Perioperative chemotherapy was associated with improved survival for pathologic stage II to IIIA disease.ConclusionsSurgery is associated with reasonable outcomes for stage I to IIA LCNEC, although survival is generally worse than for adenocarcinoma. Surgery should be offered to medically fit patients with both early and locally advanced LCNEC, with guideline-concordant induction or adjuvant therapy.