French Endocrine Society Guidance on endocrine side-effects of immunotherapy

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPI). However, the use of ICPI has a risk of side-effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, we will then outline expert opinion focusing primarily on methods for screening, management and monitoring for endocrine side-effects in patients treated by ICPI. We will then look in turn at endocrinopathies that are induced by ICPI including dysthyroidism, hypophysitis, primary adrenal insufficiency and fulminant diabetes. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. These expert opinions will also discuss the methodology for categorizing these side-effects in oncology using \u27Common terminology criteria for adverse events\u27 (CTCAE) and the difficulties in applying this to endocrine side-effects in the case of these anti-cancer therapies. This is shown in particular by certain recommendations that are used for other side-effects (high-dose corticosteroids, contra-indicated in ICPI for example), and that cannot be considered as appropriate in the management of endocrine toxicity, as it usually does not require ICPI withdrawal or high dose glucocorticoid intake

Fenofibrate Reduces Mortality and Precludes Neurological Deficits in Survivors in Murine Model of Japanese Encephalitis Viral Infection

Background: Japanese encephalitis (JE), the most common form of viral encephalitis occurs periodically in endemic areas leading to high mortality and neurological deficits in survivors. It is caused by a flavivirus, Japanese encephalitis virus (JEV), which is transmitted to humans through mosquitoes. No effective cure exists for reducing mortality and morbidity caused by JEV infection, which is primarily due to excessive inflammatory response. Fenofibrate, a peroxisome proliferator-activated receptor-a (PPARa) agonist is known to resolve inflammation by repressing nuclear factor-kB (NF-kB) and enhancing transcription of anti-oxidant and anti-inflammatory genes. In addition, fenofibrate also up-regulates a class of proteins, cytochrome P4504Fs (Cyp4fs), which are involved in detoxification of the potent pro-inflammatory eicosanoid, leukotriene B4 (LTB4) to 20-hydroxy LTB4. Methodology/Principal Findings: The neuroprotective effect of fenofibrate was examined using in vitro (BV-2 microglial cell line) and in vivo (BALB/c mice) models of JEV infection. Mice were treated with fenofibrate for 2 or 4 days prior to JEV exposure. Pretreatment with fenofibrate for 4 but not 2 days reduced mortality by 80 % and brain LTB4 levels decreased concomitantly with the induction of Cyp4f15 and 4f18, which catalyze detoxification of LTB4 through hydroxylation. Expression of cytokines and chemokine decreased significantly as did microglial activation and replication of the JEV virus. Conclusions/Significance: Fenofibrate confers neuroprotection against Japanese encephalitis, in vivo, in mouse model o

The Poor Prognosis of Diabetic Patients with High Ankle-Brachial Index. Depends on the Presence of masked Peripheral Arterial Disease

ERMAInternational audienc

Type-2 diabetes and carotid stenosis: a proposal for a screening strategy in asymptomatic patients.

International audienceThe objective of this prospective observational study was to establish the prevalence of carotid atherosclerosis in an asymptomatic diabetic population and to determine predictive factors for a screening optimization. A total of 300 consecutive type-2 diabetic subjects (166 males, 134 females) underwent a physical examination and duplex carotid scanning. Patients with a recent cerebrovascular event ( or = 60% or occlusion was 4.7%; the prevalence of carotid atherosclerosis was 68.3%. Risk factors for stenosis > or = 60% or occlusion were the presence of diabetic retinopathy (OR: 3.62; 95% CI: 1.12-11.73), ankle-brachial index (ABI) 60% stenosis is highest among men with a history of coronary heart disease or an ABI <0.85

Description prospective des manifestations du complexe de Carney : première analyse du PHRC national EVA-Carney

International audiencePOP-015Description prospective des manifestations du complexe de Carney : première analyse du PHRC national EVA-CarneyLe complexe de Carney (CNC), souvent lié à une mutation de PRKAR1A, est une néoplasie multiple endocrine et non endocrine rare.ObjectifDescription des manifestations de la maladie à partir d’explorations prospectives standardisées.MéthodePHRC national Eva-carney avec explorations standardisées annuelles prospectives sur 3 ans de 69 patients CNC ou apparentés mutés pour PRKAR1A.RésultatsLa fréquence, la nature des anomalies observées dans la maladie et leur cinétique d’apparition sont décrites : lentigines (57 % des patients), myxome cutané (17 %), atteinte nerveuse (8,7 %), hypophysaire (15 %), thyroïdienne (20 %), testiculaire (35 %), osteochondromyxomes (3 %) (étude préliminaire). Dix-neuf pour cent des patients avaient un antécédent de myxome cardiaque. Au cours du suivi, un premier myxome et une récidive ont été diagnostiqués chez 4 % et 6 % des patients respectivement. Une dysplasie micronodulaire pigmentée des surrénales était connue pour la moitié des patients. Un quart des autres patients ont présenté une anomalie surrénalienne. Au total, 57 % des patients ont eu une surrénalectomie à la fin du suivi. La réalisation systématique d’IRM rachidienne a permis de décrire pour la première fois des anomalies nodulaires vertébrales asymptomatiques d’allure non évolutive chez 45 % des patients. Les patients porteurs de mutations exoniques de PRKAR1A avaient plus volontiers ces lésions osseuses ou un phénotype sévère que ceux porteurs de mutations introniques.ConclusionLe phénotype du CNC s’étend de formes pauci-symptomatiques à des formes sévères caractérisées par un grand nombre d’atteintes et/ou de manifestations graves. Les lésions rachidiennes décrites ici sont très probablement une nouvelle manifestation du CNC