Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness

Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder. Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013–June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia. We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P < 0.05) (mean ± standard-deviation: IPE: 53 ± 61 pmol/L; DCS: 15 ± 17; controls: 6 ± 3; IPE versus DCS or controls: P < 0.05); (ii) ischemia-modified albumin: 68% of IPE patients had a high level versus 16% of DCS patients (P < 0.05) (IPE: 123 ± 25 arbitrary-units; DCS: 84 ± 25; controls: 94 ± 7; IPE versus DCS or controls: P < 0.05); (iii) BNP: 53% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 383 ± 394 ng/L; DCS: 37 ± 28; controls: 19 ± 15; IPE versus DCS or controls: P < 0.01); (iv) cTnI: 63% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 0.66 ± 1.50 μg/L; DCS: 0.0061 ± 0.0040; controls: 0.0090 ± 0.01; IPE versus DCS or controls: P < 0.01). The combined “BNP-cTnI” levels provided most discrimination: all IPE patients, but none of the DCS patients, had elevated levels of either/both of these markers. We propose that antidiuretic hormone acts together with a myocardial ischemic process to promote IPE. Thus, monitoring of antidiuretic hormone and cardiac biomarkers can help to make a quick and reliable diagnosis of IPE

Dermatite atopique et conseils à l'officine

ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Réintroduction médicamenteuse après toxidermie (impact pour le patient - enquête réalisée dans le service de dermatologie du centre hospitalier du Mans)

Les toxidermies, effets indésirables cutanéo-muqueux d'un médicament, responsables de 10 % des hospitalisations, représentent un problème de santé publique important. Lorsque le corps médical suspecte une allergie médicamenteuse, il détermine l'imputabilité du médicament incriminé, réalise des tests allergologiques cutanés (prick et patch tests, IDR).Lorsque ces tests sont négatifs et que le médicament en cause est indispensable pour le traitement du patient, un test de réintroduction médicamenteuse est réalisé sous surveillance hospitalière. Ce test consiste à réadministrer à dose croissante le médicament testé. Lorsque la réintroduction est positive, elle constitue le "Gold-Standart" pour affirmer l'imputabilité de la molécule. A l'inverse, si elle est négative, le patient peut reprendre le médicament testé. L'enquête rétrospective menée auprès de 62 patients ayant eu un test de réintroduction médicamenteuse, montre l'intérêt et la très bonne acceptabilité de ce test avec 75 % de satisfaction. La valeur prédictive négative des tests cutanés est estimée à 92,6 % et les faux négatifs à 7,4 %. Aucun des patients ayant été autorisé à reprendre le médicament n'a eu de réaction à la reprise de celui-ci ; la valeur prédictive négative des réintroductions médicamenteuses est donc de 100 %. L'enquête montre néanmoins un défaut majeur d'informations concernant ces tests et leurs conclusions auprès des pharmaciens d'officine : les patients ne discutent pas de ces tests avec leur pahrmacien et le compte-rendu d'hospitalisation ne leur est pas envoyé.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Drug survival and postdrug survival of first-line immunosuppressive treatments for atopic dermatitis comparison between methotrexate and cyclosporine

International audienceIntroductionCyclosporine and methotrexate are the two preferred first-line immunosuppressive treatments in atopic dermatitis. The aim of this study was to compare the treatment profiles of methotrexate and cyclosporine in daily practice as the first-line immunosuppressive treatment in atopic dermatitis, using two survival analyses, ‘drug survival’ (time on the drug) and ‘postdrug survival’ (time between two drugs).MethodsRetrospective study including patients with moderate-to-severe atopic dermatitis treated with methotrexate or cyclosporine as the first-line immunosuppressive treatment. The reasons for discontinuation of treatment were collected as follows: controlled disease, treatment failure, side event pregnancy and non-compliance. ‘Drug survival’ and ‘postdrug survival’ analyses were performed using the Kaplan–Meier method and predictive factors were analysed using uni- and multivariate Cox regression analyses.ResultsFifty-six patients, among whom 25 patients treated with cyclosporine and 31 with methotrexate (median age: 34 ± 15 years), were included between 2007 and 2016. Reasons for discontinuation were not significantly different between ‘controlled disease’ and other reasons (P = 0.11). The median ‘drug survival’ was significantly longer for methotrexate (23 months) than for cyclosporine (8 months) (P < 0.0001). Six months from baseline, 93% of patients treated with methotrexate were still being treated vs 63% among patients treated with cyclosporine. The median of ‘postdrug survival’ was significantly longer for methotrexate (12 months) than for cyclosporine (2 months). Only treatment with CYC was a predictive factor for decreased ‘drug survival’ and ‘postdrug survival’.ConclusionThis is the first direct comparison between methotrexate and cyclosporine as first-line immunosuppressive treatments for moderate-to-severe atopic dermatitis in daily practice. We evidenced two different treatment profiles: the duration of methotrexate administration is longer than that of cyclosporine. ‘Postdrug survival’ could be a new tool to assess the maintenance of effect of a drug after withdrawal in atopic dermatitis, and more broadly in chronic skin disease

Efficacy and tolerance of photodynamic therapy for vulvar Paget's disease: a multicentric retrospective study

International audienceBACKGROUND: Extra-mammary Paget's disease is a rare form of intraepithelial adenocarcinoma with a variable pattern of invasion, sometimes associated with distant malignancy. Vulvar Paget's disease (VPD) represents 1% of all vulvar cancers. Standard treatment is surgical excision, however, the recurrence rate is high and surgery leads to anatomical, functional, and sexual morbidity. Some case series suggest efficacy of photodynamic (PDT) as treatment for this indication.OBJECTIVES: Our aim was to assess the efficacy and tolerance of PDT in women suffering from VPD.MATERIALS &amp; METHODS: A retrospective study was conducted on all patients suffering from VPD, treated with PDT at six hospitals in France. Clinical data, histopathological reports at diagnosis, therapeutic history, PDT schedule, tolerance, and clinical response were reported.RESULTS: Thirteen women were included, with a mean age of 70.1 years. Ten women had an in situ disease, two had &lt;1-mm dermal involvement, and one had adnexal involvement. All PDT courses were carried out using the same light source and photosensitizing agent. Complete response was achieved in two patients (15%) and partial response in five patients (38%). Five patients (38%) had stable disease and one (7%) had progressive disease. Ten of the 13 patients underwent pain evaluation; in six cases (60%), pain was described as moderate to intense.CONCLUSION: PDT appears to be a therapeutic option for patients with VPD, with a response rate similar to that of other therapies usually recommended, such as surgery and imiquimod. There is a need to harmonise PDT procedures and pain assessment.</p

A High Neutrophil to Lymphocyte Ratio Prior to BRAF Inhibitor Treatment Is a Predictor of Poor Progression-Free Survival in Patients with Metastatic Melanoma

International audienceSome studies have shown that a high neutrophil/lymphocyte ratio (NLR) ≥q4 before initiating ipilimumab treatment is an independent prognostic indicator of poor survival in patients with metastatic melanoma (MM). To determine whether the NLR before starting BRAF inhibitor (BRAFi) treatment in patients with (MM) is associated with progression-free survival (PFS). This retrospective study included 49 patients consecutively receiving BRAFi for MM between July 2012 and December 2014. Cox proportional hazards regression was used to analyse the relationship between NLR and other factors, such as lactate dehydrogenase (LDH), performance status, BRAFi as first- or second-line therapy, and corticosteroid intake with PFS. The NLR before starting BRAFi was significantly associated with PFS based on univariate analysis and multivariate analysis adjusted for potential confounding factors, such as LDH activity, ulceration, performance status, first-line therapy, and corticosteroid intake. A high NLR (continuous variable) was associated with short PFS (HR: 1.35; 95%~CI: 1.07-1.70; p~=~0.01), and NLR ≥q4 was associated with shorter PFS (HR: 3.24; 95%~CI: 1.30-8.12; p~=~0.01). Corticosteroid intake was not associated with short PFS based on multivariate analysis. An NLR >4, before starting BRAFi treatment, is an independent prognostic indicator of poor progression-free survival

A high neutrophil-to-lymphocyte ratio as a potential marker of mortality in patients with Merkel cell carcinoma: A retrospective study

The prognostic relevance of a high blood neutrophil-to-lymphocyte ratio (NLR) has been reported in many cancers, although, to our knowledge, not investigated in patients with Merkel cell carcinoma (MCC) to date.We assessed whether the NLR at baseline was associated with specific survival and recurrence-free survival in MCC.We retrospectively included MCC cases between 1999 and 2015 and collected clinical data, blood cell count at baseline, and outcome. A Cox model was used to identify factors associated with recurrence and death from MCC.Among the 75 patients included in the study, a high NLR at baseline (NLR ≥4) was associated with death from MCC in univariate (hazard ratio 2.76, 95% confidence interval 1.15-6.62, P = .023) and multivariate (hazard ratio 3.30, 95% confidence interval 1.21-9.01, P = .020) analysis, but not with recurrence.Because of the retrospective design, we excluded patients with missing data and not all confounding factors that may influence the NLR were available.A high NLR at baseline was independently associated with specific mortality in patients with MCC. The NLR seems to constitute an easily available and inexpensive prognostic biomarker at baseline

Impact of Childhood Onset Psoriasis on Addictive Behaviours, Socioeconomic and Educational Data in Adulthood

International audiencePaediatric psoriasis has been associated with school absenteeism, limitation of physical activities, psychiatric disorders and, in the longer term, with sexual dysfunction and addictions. This raises the hypothesis that childhood onset psoriasis may affect patients' educational development, and further social and professional outcomes. This study evaluated the relationship between childhood onset psoriasis and patients' educational and socioeconomic characteristics, and the development of addictions in adulthood. This cross-sectional ancillary study captured patients' characteristics at baseline in the French PSOBIOTEQ registry. Data in adulthood included: educational (baccalaureate) and socioeconomic (working activity) groups, smoking status (self-reporting of being a current smoker vs past smoker or non-smoker), alcohol consumption (defined as at least 1 glass of alcoholic beverage per day), and living conditions (alone/family/social institutions; child at home). A total of 1,960 patients were included, of whom 26.2% had childhood onset psoriasis. In multivariate analyses, childhood onset psoriasis was associated with smoker status (p = 0.02). No association was observed with educational level, working activity, living conditions, or alcohol consumption. This study provides reassuring data overall with regard to the impact of childhood onset psoriasis on major social outcomes. Evidence for some association with addictive behaviours paves the way for larger prospective studies assessing in depth the social and educational impact of this disease

Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No Association with Disease Severity

Merkel cell carcinoma (MCC) is a rare high-grade neuroendocrine tumour of the skin. It has been speculated that MCCs express somatostatin receptors (SSTRs), but this has never been assessed in a large series of MCCs. The main aim of this study was to assess the expression of SSTR2A and SSTR5 in MCC tumours. The secondary aims were to assess whether expression of SSTR was associated with the Ki67 proliferative index, Merkel cell polyomavirus (MCPyV) status, clinical characteristics and outcome.Clinical data and tumours were collected from an ongoing cohort of French patients with MCC. Immunohistochemistry was performed with anti-SSTR2A and anti-SSTR5 monoclonal antibodies, and tumours were classified into 3 groups: 'no expression', 'low expression' and 'moderate expression' using an SSTR staining score.SSTR expression was assessed for 105 MCC tissue samples from 98 patients, and clinical characteristics were available for 87 of them. SSTR expression was consistent between the primary skin tumour and the corresponding metastases for SSTR2A and SSTR5 in 3/7 and 6/7 cases, respectively. SSTR2A and SSTR5 were expressed in 58 cases (59.2%) and in 44 cases (44.9%), respectively. Overall, at least one SSTR was expressed in 75 tumours (76.5%). SSTR expression was not associated with clinical characteristics, Ki67 proliferative index, recurrence-free survival or MCC-specific survival. Expression of SSTR2A was associated with MCPyV status in MCC tumours but not SSTR5.SSTRs were expressed in a high proportion of MCCs, although expression was heterogeneous between tumours and was not associated with disease severit

Myelination induction by a histamine H3 receptor antagonist in a mouse model of preterm white matter injury

International audienc