Real-life implementation of guidelines on the hospital-to-home transition for older patients: a cohort study in general practice

International audienceAbstract Background hospital discharge is a critical event for older patients. The French guidelines recommended the swift transmission of a discharge summary to the general practitioner (GP) and a primary care consultation within 7 days. The relevance and feasibility of these guidelines have not previously been assessed. Objective to perform a real-life assessment of compliance with French guidelines on the transmission of discharge summaries and post-discharge medical reviews and to examine these factors’ association with 30-day readmissions. Design a prospective multicentre cohort study. Setting primary care (general practice) in France. Subjects a sample of GPs and the same number of patients aged 75 or over having consulted within 30 days of hospital discharge. Methods the main endpoints were the proportion of discharge summaries available and the proportion of patients consulting their GP within 7 days. The 30-day readmission rate was also measured. Factors associated with these endpoints were assessed in univariate and multivariate analyses. Results seventy-one GPs (mean ± standard deviation age: 49 ± 11; males: 62%) and 71 patients (mean age: 84 ± 5; males: 52%; living at home: 94%; cognitive disorders: 22%) were included. Forty-six patients (65%, [95% confidence interval [CI]]: 53–76) consulted their GP within 7 days of hospital discharge. At the time of the consultation, 27 GPs (38% [95% CI]: 27–50) had not received the corresponding hospital discharge summary. Discharge summary availability was associated with a lower risk of 30-day readmission (adjusted odds ratio [95% CI] = 0.25 [0.07–0.91]). Conclusions compliance with the French guidelines on hospital-to-home transitions is insufficient

From azoospermia to macrozoospermia, a phenotypic continuum due to mutations in the ZMYND15 gene

International audienceThanks to tremendous advances in sequencing technologies and in particular to whole exome sequencing (WES), many genes have now been linked to severe sperm defects. A precise genetic diagnosis is obtained for a minority of patients and only for the most severe defects like azoospermia or macrozoospermia which is very often due to defects in the aurora kinase C (AURKC) gene. Here, we studied a subject with a severe oligozoospermia and a phenotypic diagnosis of macrozoospermia. AURKC analysis did not reveal any deleterious variant. WES was then initiated which permitted to identify a homozygous loss of function variant in the zinc finger MYND-type containing 15 (ZMYND15) gene. ZMYND15 has been described to serve as a switch for haploid gene expression, and mice devoid of ZMYND15 were shown to be sterile due to nonobstructive azoospermia (NOA). In man, ZMYND15 has been associated with NOA and severe oligozoospermia. We confirm here that the presence of a bi-allelic ZMYND15 variant induces a severe oligozoospermia. In addition, we show that severe oligozoospermia can be associated macrozoospermia, and that a phenotypic misdiagnosis is possible, potentially delaying the genetic diagnosis. In conclusion, genetic defects in ZMYND15 can induce complete NOA or severe oligozoospermia associated with a very severe teratozoospermia. In our experience, severe oligozoospermia is often associated with severe teratozoospermia and can sometimes be misinterpreted as macrozoospermia or globozoospermia. In these instances, specific AURKC or dpy-19 like 2 (DPY19L2) diagnosis is usually negative and we recommend the direct use of a pan-genomic techniques such as WES

Aortic Event Rate in the Marfan Population: A Cohort Study

International audienceOptimal management, including timing of surgery, remains debated in Marfan syndrome because of a lack of data on aortic risk associated with this disease

Poliovirus Induces Bax-Dependent Cell Death Mediated by c-Jun NH2-Terminal Kinase▿

Poliovirus (PV) is the causal agent of paralytic poliomyelitis, a disease that involves the destruction of motor neurons associated with PV replication. In PV-infected mice, motor neurons die through an apoptotic process. However, mechanisms by which PV induces cell death in neuronal cells remain unclear. Here, we demonstrate that PV infection of neuronal IMR5 cells induces cytochrome c release from mitochondria and loss of mitochondrial transmembrane potential, both of which are evidence of mitochondrial outer membrane permeabilization. PV infection also activates Bax, a proapoptotic member of the Bcl-2 family; this activation involves its conformational change and its redistribution from the cytosol to mitochondria. Neutralization of Bax by vMIA protein expression prevents cytochrome c release, consistent with a contribution of PV-induced Bax activation to mitochondrial outer membrane permeabilization. Interestingly, we also found that c-Jun NH2-terminal kinase (JNK) is activated soon after PV infection and that the PV-cell receptor interaction alone is sufficient to induce JNK activation. Moreover, the pharmacological inhibition of JNK by SP600125 inhibits Bax activation and cytochrome c release. This is, to our knowledge, the first demonstration of JNK-mediated Bax-dependent apoptosis in PV-infected cells. Our findings contribute to our understanding of poliomyelitis pathogenesis at the cellular level

Proteomic analysis of the autoantibody response following immunization with a single autoantigen

International audienceIn most autoimmune diseases, the autoantibody response is directed against several antigens of the target organ whose identification is crucial for understanding the physiopathological process. Thus, technologies allowing a characterization of the whole autoantibody pattern of both human and experimental autoimmune diseases are required. Here we have used immunoproteomic analysis of human epidermal extracts to characterize the diversity of the anti-desmosome antibody response induced in normal mice immunized with desmoglein 1, the major autoantigen of pemphigus foliaceus, an autoimmune blistering skin disease. In particular, this analysis enables us to characterize the binding properties of anti-desmosome mAbs derived from these mice and to show that the autoantibody response induced upon immunization with a single autoantigen targets different epidermal autoantigens with a pattern similar to that observed in certain variety of human pemphigus

Surgical management of patients with Marfan syndrome: Evolution throughout the years

International audienceTo evaluate the evolution of surgical management in a large population of patients with Marfan syndrome

Clinical Significance of Aortic Root Modification Associated With Bicuspid Aortic Valve in Marfan Syndrome.

International audienceBACKGROUND:Both bicuspid aortic valve (BAV) and Marfan syndrome have been associated with aortic dissection risk, but it is unknown whether the presence of BAV is associated with an increased aortic risk in patients with an FBN1 gene mutation. We evaluated aortic diameters, aortic valve function, and aortic shape in Marfan syndrome patients with and without BAV and reported aortic events during follow-up.METHODS:All patients with an FBN1 gene mutation evaluated in our clinic were included. Aortic root diameters were measured, and the aortic valve was studied using echocardiography at each visit.RESULTS:Of the 1437 patients with an FBN1 gene mutation, 26 patients (1.8%) had a BAV. Both aortic root maximal diameter and normalized Z score were larger at all ages, in patients with BAV when compared with patients with tricuspid aortic valve. Prophylactic aortic root surgery tended to be performed in younger patients when BAV was present, although aortic diameter threshold was similar in the 2 populations. No aortic dissection was observed in Marfan syndrome patients with BAV.CONCLUSIONS:In patients with a FBN1 mutation, BAV is associated with larger aortic root diameter, with no difference in evolution of Z score with age. We found a trend towards prophylactic aortic root surgery at younger ages but similar aortic diameter thresholds without occurrence of aortic dissection. We did not find any evidence for lowering aortic diameter thresholds used to propose preventive aortic root surgery in the presence of BAV in patients with FBN1 mutations

Rationale and design of a randomized clinical trial (Marfan Sartan) of angiotensin II receptor blocker therapy versus placebo in individuals with Marfan syndrome.

International audienceBACKGROUND: Recent studies have demonstrated that blockade of the angiotensin II type 1 receptor with losartan decreases aortic damage in an animal model of Marfan syndrome (a KI mouse model with a pathogenic mutation in the gene coding for fibrillin-1). AIMS: To demonstrate a beneficial effect of losartan on aortic dilatation when added to optimal therapy in patients with Marfan syndrome. METHODS: This is a multicentre, randomized, placebo-controlled, double-blind, clinical trial with a 2-year inclusion period and a 3-year follow-up period. Aortic root diameter will be measured using two-dimensional echocardiography. Secondary endpoints will include incidence of aortic dissection, aortic root surgery, death, quality of life, tolerance and compliance with treatments. We aim to enroll a total of 300 patients aged > or =10 years who fulfil the Ghent criteria for Marfan syndrome. Analyses will be based on intention to treat. CONCLUSION: The results of this clinical trial could lead to profound modification of the management of aortic risk and complications in patients with Marfan syndrome and possibly in patients with thoracic aortic aneurysms of other aetiologies

Hyperventilation as one of the mechanisms of persistent dyspnoea in SARS-CoV-2 survivors

Conflict of interest statementConflict of interest: E. Vidal-Petiot reports personal fees and non-financial support from Servier, outside the submitted work. A. Cohen-Solal has received grants or honoraria from Novartis, Servier, Daiichi Sankyo, Vifor, Menarini and Cardiorentis, outside of the submitted work. J. Frija-Masson reports non-financial support from Vitalaire, Boehringer Ingelheim, Oxyvie and LVL Medical, outside the submitted work. All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.International audienceInadequate exercise hyperventilation should not be overlooked while exploring the causes of exertional dyspnoea in SARS-CoV-2 survivors https://bit.ly/3AxOiD