Acquired lipodystrophy associated with immune checkpoint inhibitors.

Immune checkpoint inhibitors have become the mainstay of treatment for metastatic melanoma. This article presents a new case of acquired generalised lipodystrophy (AGL) during anti-programmed cell death-1 (anti-PD-1) therapy and a systematic review of the literature with an aim to further understand the pathogenesis. A comprehensive search was conducted using PubMed, Embase, MEDLINE and Cochrane Central databases. We identified four cases of lipodystrophy associated with anti-PD-1 immunotherapy, including our own. Of these, three were associated with nivolumab, and one with pembrolizumab. Body composition changes occurred at a median of 7 months after anti-PD-1 initiation. All cases reported AGL, with subcutaneous fat loss affecting majority of the body. There were three reported cases of insulin resistance associated with AGL. AGL should be a recognised adverse event associated with anti-PD-1 therapy.

The Indian type 2 diabetes risk score also helps identify those at risk of macrovasvular disease and neuropathy (CURES-77).

AIMS: To see whether the diabetic individuals identified by the Indian Diabetes Risk Score (IDRS) also have a higher prevalence of diabetes related complications. METHODS: Type 2 diabetic subjects were selected from the Chennai Urban Rural Epidemiology Study in south India. Four field stereo retinal colour photography was done and diabetic retinopathy [DR] was classified according to Early Treatment Diabetic Retinopathy Study grading system. Coronary artery disease was diagnosed using Minnesota coding of 12-lead electrocardiograms. Diabetic peripheral neuropathy (DPN) was diagnosed if vibratory perception threshold [VPT] of the right great toe measured by biothesiometry was > or =20. The criterion for diagnosis of peripheral vascular disease (PVD) was an ankle-brachial index < 0.9. Macroalbuminuria was diagnosed if urinary albumin excretion was > or =300 microg/mg creatinine. A total of 1476 individuals who had information on all test parameters were included for analysis. RESULTS: Subjects with IDRS score > or =60 had significantly higher prevalence of coronary artery disease (CAD) [9.2% vs. 5.4%, p = 0.043], DPN [29.2% vs. 8.8%, p < 0.001] and PVD [4.8% vs. 1.9%, p = 0.038] compared to subjects with IDRS score <60. However, the prevalence of DR and macroalbuminuria did not differ between the two IDRS subgroups. Age explained much of the observed differences in prevalence of CAD, PVD and DPN between the two IDRS subgroups. CONCLUSIONS: This study further extends the clinical usefulness of IDRS to predicting diabetic complications like CAD, PVD and DPN as well.

Is moderation of protease production an adaptation of well-defined anthropization in dermatophytes?

The protease activity of different isolates of dermatophytes representing different ecological groups namely geophilic, zoopahilic and anthropophilic, in their vegetative and sporulation growth phases were compared. Unlike their geophilic and zoophilic counterparts, all the isolates of anthropophilic dermatophytes viz. Trichophyton rubrum, T. mentagrophytes, T. tonsurans, T. violaceum and Epidermophyton floccosum recorded reduced protease activity during artificially induced sporulation phase in comparison to their vegetative growth phase. Even among the anthropophilic group, a classical moderation of protease activity was recorded in Trichyphyton rubrum which also correlates to its clinical manifestation. This enzyme moderation could also be an evolutionary adaptation of the anthropization of these species.