Specific niche requirements underpin multidecadal range edge stability, but may introduce barriers for climate change adaptation

Aim: To investigate some of the environmental variables underpinning the past and present distribution of an ecosystem engineer near its poleward range edge. Location: >500 locations spanning >7,400 km around Ireland. Methods: We collated past and present distribution records on a known climate change indicator, the reef-forming worm Sabellaria alveolata (Linnaeus, 1767) in a biogeographic boundary region over 182 years (1836–2018). This included repeat sampling of 60 locations in the cooler 1950s and again in the warmer 2000s and 2010s. Using species distribution modelling, we identified some of the environmental drivers that likely underpin S. alveolata distribution towards the leading edge of its biogeographical range in Ireland. Results: Through plotting 981 records of presence and absence, we revealed a discontinuous distribution with discretely bounded sub-populations, and edges that coincide with the locations of tidal fronts. Repeat surveys of 60 locations across three time periods showed evidence of population increases, declines, local extirpation and recolonization events within the range, but no evidence of extensions beyond the previously identified distribution limits, despite decades of warming. At a regional scale, populations were relatively stable through time, but local populations in the cold Irish Sea appear highly dynamic and vulnerable to local extirpation risk. Contemporary distribution data (2013–2018) computed with modelled environmental data identified specific niche requirements which can explain the many distribution gaps, namely wave height, tidal amplitude, stratification index, then substrate type. Main conclusions: In the face of climate warming, such specific niche requirements can create environmental barriers that may prevent species from extending beyond their leading edges. These boundaries may limit a species’ capacity to redistribute in response to global environmental change

Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: towards recommendation for molecular testing and management

International audienceSHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had 4 or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included IUGR \textless 10(th) percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended

Polyneuropathie diabétique et pressions plantaires (une évolution parallèle ?)

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Pasireotide-LAR in acromegaly patients treated with a combination therapy: a real-life study

Purpose Little data are available regarding the safety and efficacy of switching to Pasireotide-LAR monotherapy in acromegaly patients with partial resistance to first-generation somatostatin agonists (1gSRL) who require combination treatment with cabergoline or pegvisomant. Method In this monocentric prospective study within a tertiary university hospital, 15 consecutive acromegalic adults partially resistant to 1gSRL treated with octreotide LAR or lanreotide SR, and cabergoline ( n = 4, 3.5 mg/week) or pegvisomant ( n = 11, median dose 100 mg/week), were switched to Pasireotide-LAR (8 with 40 mg/month; 7 with 60 mg/month). Immunohistochemical expression level of SSTR5 and the granulation pattern of nine somatotroph adenomas were retrospectively determined to test for a correlation with the therapeutic efficacy of Pasireotide-LAR. Results Median IGF-1 concentration at the first evaluation (median 3 months) was similar to baseline (1.0 vs 1.1 ULN). 11/15 patients had IGF-1 levels ≤1.3 ULN before and after the switch but individual changes were variable. Hyperglycemia was frequent and greater in diabetic patients. 7/15 patients stopped Pasireotide-LAR due to lack of control of IGF-1 or intolerance. 8/15 patients received Pasireotide-LAR for a median of 29 months with IGF-1 levels ≤1.3 ULN and acceptable glucose tolerance (median HbA1c 6.1%). Two patients required initiation of oral antidiabetic treatment. The intensity of SSTR5 expression and the granulation pattern of adenomas were of limited value for the prediction of Pasireotide-LAR effectiveness. Conclusion Pasireotide-LAR may represent a suitable therapeutic alternative in a subset of acromegalic patients requiring combination therapy involving a 1gSR

Impact of emotional competence on physicians’ clinical reasoning: a scoping review protocol

Introduction Clinical reasoning (CR) is a key competence for physicians and a major source of damaging medical errors. Many strategies have been explored to improve CR quality, most of them based on knowledge enhancement, cognitive debiasing and the use of analytical reasoning. If increasing knowledge and fostering analytical reasoning have shown some positive results, the impact of debiasing is however mixed. Debiasing and promoting analytical reasoning have also been criticised for their lack of pragmatism. Alternative means of increasing CR quality are therefore still needed. Because emotions are known to influence the quality of reasoning in general, we hypothesised that emotional competence (EC) could improve physicians’ CR. EC refers to the ability to identify, understand, express, regulate and use emotions. The influence of EC on CR remains unclear. This article presents a scoping review protocol, the aim of which will be to describe the current state of knowledge concerning the influence of EC on physicians’ CR, the type of available literature and finally the different methods used to examine the link between EC and CR.Method and analysis The population of interest is physicians and medical students. EC will be explored according to the model of Mikolajczak et al, describing five major components of EC (identify, understand, express, regulate and use emotions). The concept of CR will include terms related to its processes and outcomes. Context will include real or simulated clinical situations. The search for primary sources and reviews will be conducted in MEDLINE (via Ovid), Scopus and PsycINFO. The grey literature will be searched in the references of included articles and in OpenGrey. Study selection and data extraction will be conducted using the Covidence software. Search and inclusion results will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review model (PRISMA-ScR).Ethics and dissemination There are no ethical or safety concerns regarding this review.Registration details OSF Registration DOI: https://doi.org/10.17605/OSF.IO/GM7YD

Genetic analysis in young patients with sporadic pituitary macroadenomas:Beside AIP don't forget MEN1 genetic analysis.

CONTEXT: germline mutations in the AIP gene have been identified in young patients (age </= 30 years old) with sporadic pituitary macroadenomas. Otherwise, there are few data concerning the prevalence of MEN1 mutations in such population. OBJECTIVE: We assessed the prevalence of both AIP and MEN1 genetic abnormalities (mutations and large gene deletions) in young patients (age </= 30 years old) diagnosed with sporadic and isolated macroadenoma, without hypercalcemia and/or MEN1-associated lesions. DESIGN: The entire coding sequences of AIP and MEN1 were screened for mutations. In cases of negative sequencing screening, multiplex ligation-dependent probe amplification was performed for the detection of large genetic deletions. PATIENTS AND SETTINGS: 174 patients from Endocrinology Departments of 15 French University Hospital Centers were eligible for this study. RESULTS: 21/174(12%) patients had AIP (n=15, 8.6%) or MEN1 (n=6, 3.4%) mutations. In pediatric patients (age </= 18 years old), AIP/MEN1 mutation frequency reached nearly 22% (n=10/46). AIPmut and MEN1mut were respectively identified in 8/79 (10.1%) and 1/79 (1.2%) somatotropinoma patients; they each accounted for 4/74 (5.4%) prolactinoma patients with mutations. Half of patients (n=3/6) with gigantism displayed mutations in AIP. Interestingly, 4/12 (33%) patients with non-secreting adenomas bore either AIP or MEN1 mutations, whereas none of the 8 corticotroph-adenomas and a single thyrotropinoma case had mutations. No large gene deletions were observed in sequencing-negative patients. CONCLUSION: mutations in MEN1 can be of significance in young patients with sporadic isolated pituitary macroadenomas, particularly prolactinomas, and together with AIP, we suggest genetic analysis of MEN1 in such population

Normotensive Incidentally Discovered Pheochromocytomas Display Specific Biochemical, Cellular, and Molecular Characteristics

International audienceDesign: This was a retrospective cohort recruited from 2001 to 2011 in 2 tertiary care medical departments.Patients and Methods: Clinical, biological, and radiological investigations performed in 96 consecutive patients with sporadic unilateral pheochromocytomas were examined; 47 patients had overt pheochromocytomas responsible for hypertension. Among the patients with incidental pheochromocytomas, 28 had hypertension and 21 were normotensive (NIPs). A total of 62 tumors were examined to determine the Pheochromocytoma of the Adrenal Gland Scale Score, and 29 were studied for the expression of 16 genes involved in chromaffin cell function.Context: A number of incidentally discovered pheochromocytomas are not associated with hypertension. The characteristics of normotensive incidentally discovered pheochromocytomas (NIPs) are poory known.Objective: The purpose of this work was to assess the clinical, hormonal, histological, and molecular features of NIPs.Results: Tumor size and metaiodobenzylguanidine (MIBG) scintigraphy results were similar for hypertensive pheochromocytomas (HPs) and NIPs. Patients with NIPs displayed reduced summed levels of urinary catecholamines and metanephrines and, more specifically, reduced levels of adrenaline and metadrenaline compared with those of patients with HPs (P < .001). Urinary metanephrines had 98% diagnostic sensitivity in patients with HPs and only 75% in patients with NIPs (P < .01). Tumor diameter positively correlated with the total amount of urinary concentrations of metanephrines in patients with HPs (P < .001) but not in patients with NIPs. NIPs displayed global decreased chromaffin gene expression (reaching significance for 5 of them) and 2 corresponding proteins (phenylethanolamine N-methyltransferase and secretogranin II) and a significant increase in the cellularity, mitotic activity, and presence of atypical mitosis (P < .05).Conclusions: NIPs differ from pheochromocytomas responsible for hypertension and display features of altered chromaffin differentiation. These tumors may be misdiagnosed with the use of the usual biological diagnostic tools

Rituximab and Cyclophosphamide in Antisynthetase Syndrome–related Interstitial Lung Disease: An Observational Retrospective Study

International audienceObjective Antisynthetase syndrome (AS)-related interstitial lung disease (ILD) has a poor prognosis. Intravenous cyclophosphamide (IV CYC) and rituximab (RTX) are the main treatments currently used for moderate to severe ILD. Here, we compare the efficacy of CYC followed by standard immunosuppressive treatment (IST) versus RTX in AS-related ILD. Methods This observational retrospective study was conducted between 2003 and 2016 in 3 tertiary care centers. All patients with AS-related ILD and treated with CYC or RTX with at least 6 months of follow-up were included. Pulmonary progression-free survival (PFS), defined according to the American Thoracic Society guidelines, was assessed at 6 months and 2 years. All severe adverse events (AE) were recorded. Results Sixty-two patients were included. Thirty-four patients received 2–12 monthly IV CYC pulses, followed by standard IST in 30 cases (88%). The RTX group included 28 patients. Following the initial Day 1 to Day 15 infusions, RTX was repeated every 6 months in 26 cases (93%) and 15 patients (54%) concomitantly received another IST. The median steroid dose was similar between both groups. Although RTX and CYC demonstrated similar PFS at 6 months (92% vs 85%, respectively), RTX was superior at 2 years (HR 0.263, 95% CI 0.094–0.732, P = 0.011). Interestingly, lower diffusing lung capacity for carbon monoxide (DLCO) at baseline was independently predictive of poor 2-year PFS [0.965 (0.936–0.995), P = 0.023]. Forced vital capacity and DLCO improved in both groups without significant differences. Serious AE were similar in both groups. Conclusion Despite similar PFS at 6 months, RTX was associated with a better 2-year PFS compared to CYC in patients with AS-related ILD