Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Dilatation mitrale percutanée en cours de grossesse

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis

International audienceBACKGROUND: A worldwide increase in the prevalence of obesity has been observed in the past three decades, particularly in women of reproductive age. Female obesity has been clearly associated with impaired spontaneous fertility, as well as adverse pregnancy outcomes. Increasing evidence in the literature shows that obesity also contributes to adverse clinical outcomes following in vitro fertilization (IVF) procedures. However, the heterogeneity of the available studies in terms of populations, group definition and outcomes prevents drawing firm conclusions. A previous meta-analysis published in 2011 identified a marginal but significant negative effect of increased female body mass index (BMI) on IVF results, but numerous studies have been published since then, including large cohort studies from national registries, highlighting the need for an updated review and meta-analysis.OBJECTIVE AND RATIONALE: Our systematic review and meta-analysis of the available literature aims to evaluate the association of female obesity with the probability of live birth following IVF. Subgroup analyses according to ovulatory status, oocyte origin, fresh or frozen-embryo transfer and cycle rank were performed.SEARCH METHODS: A systematic review was performed using the following key words: ('obesity', 'body mass index', 'live birth', 'IVF', 'ICSI'). Searches were conducted in MEDLINE, EMBASE, Cochrane Library, Eudract and clinicaltrial.gov from 01 January 2007 to 30 November 2017. Study selection was based on title and abstract. Full texts of potentially relevant articles were retrieved and assessed for inclusion by two reviewers. Subsequently, quality was assessed using the Newcastle-Ottawa Quality Assessment Scales for patient selection, comparability and assessment of outcomes. Two independent reviewers carried out study selection and data extraction according to Cochrane methods. Random-effect meta-analysis was performed using Review Manager software on all data (overall analysis), followed by subgroup analyses.OUTCOMES: A total of 21 studies were included in the meta-analysis. A decreased probability of live birth following IVF was observed in obese (BMI ≥ 30 kg/m2) women when compared with normal weight (BMI 18.5-24.9 kg/m2) women: risk ratio (RR) (95% CI) 0.85 (0.82-0.87). Subgroups analyses demonstrated that prognosis was poorer when obesity was associated with polycystic ovary syndrome, while the oocyte origin (donor or non-donor) did not modify the overall interpretation.WIDER IMPLICATIONS: Our meta-analysis clearly demonstrates that female obesity negatively and significantly impacts live birth rates following IVF. Whether weight loss can reverse this deleterious effect through lifestyle modifications or bariatric surgery should be further evaluated

Ovarian tissue cryopreservation can be combined simultaneously with oocyte retrieval after controlled ovarian hyperstimulation

International audienceAbstract STUDY QUESTION Can ovarian tissue cryopreservation (OTC) be performed after controlled ovarian hyperstimulation (COH)? SUMMARY ANSWER Unilateral oophorectomy after transvaginal oocyte retrieval is feasible on stimulated ovaries during one surgical step. WHAT IS KNOWN ALREADY In the fertility preservation (FP) field, the timeframe between patient referral and start of curative treatment is limited. Combining oocyte pick-up with ovarian tissue (OT) extraction has been reported to improve FP but COH applied before OT extraction is not currently recommended. STUDY DESIGN, SIZE, DURATION This retrospective cohort-controlled study involved 58 patients who underwent oocyte cryopreservation immediately followed by OTC between September 2009 and November 2021. The exclusion criteria were a delay between oocyte retrieval and OTC of &gt;24 h (n = 5) and IVM of oocytes obtained ex vivo in the ovarian cortex (n = 2). This FP strategy was performed either after COH (stimulated group, n = 18) or after IVM (unstimulated group, n = 33). PARTICIPANTS/MATERIALS, SETTING, METHODS Oocyte retrieval followed by OT extraction on the same day was performed either without previous stimulation or after COH. Adverse effects of surgery and ovarian stimulation, mature oocyte yield and pathology findings of fresh OT were retrospectively analysed. Thawed OTs were analysed prospectively, for vascularization and apoptosis using immunohistochemistry, when patient consent was obtained. MAIN RESULTS AND THE ROLE OF CHANCE No surgical complication occurred after OTC surgery in either group. In particular, no severe bleeding was associated with COH. The number of mature oocytes obtained increased after COH (median = 8.5 (25% = 5.3–75% = 12.0)) compared to the unstimulated group (2.0 (1.0–5.3), P &lt; 0.001). Neither ovarian follicle density nor cell integrity was affected by COH. Fresh OT analysis showed congestion in half of the stimulated OT which was higher than in the unstimulated OT (3.1%, P &lt; 0.001). COH also increased haemorrhagic suffusion (COH + OTC: 66.7%; IVM + OTC: 18.8%, P = 0.002) and oedema (COH + OTC: 55.6%; IVM + OTC: 9.4%, P &lt; 0.001). After thawing, the pathological findings were similar between both groups. No statistical difference in the number of blood vessels was observed between the groups. The oocyte apoptotic rate in thawed OT was not statistically different between the groups (ratio of positive cleaved caspase-3 staining oocytes/total number of oocytes equal to median 0.50 (0.33–0.85) and 0.45 (0.23–0.58) in unstimulated and stimulated groups respectively, P = 0.720). LIMITATIONS, REASONS FOR CAUTION The study reports FP from a small number of women following OTC. Follicle density and other pathology findings are an estimate only. WIDER IMPLICATIONS OF THE FINDINGS Unilateral oophorectomy can be successfully performed after COH with limited bleeding risk and an absence of impact on thawed OT. This approach could be proposed to post pubertal patients when the number of mature oocytes expected is low or when the risk of residual pathology is high. The reduction of surgical steps for cancer patients also has positive implications for introducing this approach into clinical practice. STUDY FUNDING/COMPETING INTEREST(S) This work was made possible through the support of the reproductive department of Antoine-Béclère Hospital and of the pathological department of Bicêtre Hospital (Assistance Publique Hôpitaux de Paris, France). The authors have no conflict of interest to disclose in this study. TRIAL REGISTRATION NUMBER N/A

Pathologies maternelles chroniques et pertes de grossesse. Recommandations françaises

International audienceAim.-To review the available data on maternal chronic diseases and pregnancy losses.Material and Methods-We searched PubMed and the Cochrane library with pregnancy loss,stillbirth, intrauterine fetal demise, intrauterine fetal death, miscarriage and each maternaldiseases of this paper.Results-Antiphospholipid antibodies (anticardiolipin, anti-beta-2-glycoprotein, lupus anti-coagulant) should be measured in case of miscarriage after 10 WG confirmed by ultrasound(grade B) and an antiphospholipid syndrome should be treated by a combination of aspi-rin and low-molecular-weight heparin during a subsequent pregnancy (grade A). We donot recommend testing for genetic thrombophilia in case of first trimester miscarriage(grade B) or stillbirth (grade C). Glycemic control should be a goal before pregnancyfor women with pregestational diabetes to limit the risks of pregnancy loss (grade A)with a goal of prepregnancy HbA1c < 7%. Overt and subclinical hypothyroidisms should betreated by L-thyroxin during pregnancy to reduce the risks of pregnancy loss (grade A).Women who are positive for TPOAb should have TSH concentrations follow-up during pre-gnancy and subsequently treated by L-thyroxin if they develop subclinical hypothyroidism(grade B).Conclusions.-Prepregnancy management of most chronic maternal diseases, ideally throughprepregnancy multidisciplinary counseling, reduces the risks of pregnancy loss

Sirtuin 1 Regulates SREBP-1c Expression in a LXR-Dependent Manner in Skeletal Muscle

International audienceSirtuin 1 (SIRT1), a NAD +-dependent protein deacetylase, has emerged as a main determinant of whole body homeostasis in mammals by regulating a large spectrum of transcriptional regulators in metabolically relevant tissue such as liver, adipose tissue and skeletal muscle. Sterol regulatory element binding protein (SREBP)-1c is a transcription factor that controls the expression of genes related to fatty acid and triglyceride synthesis in tissues with high lipid synthesis rates such as adipose tissue and liver. Previous studies indicate that SIRT1 can regulate the expression and function of SREBP-1c in liver. In the present study, we determined whether SIRT1 regulates SREBP-1c expression in skeletal muscle. SREBP-1c mRNA and protein levels were decreased in the gastrocnemius muscle of mice harboring deletion of the catalytic domain of SIRT1 (SIRT1 Dex4/Dex4 mice). By contrast, adenoviral expression of SIRT1 in human myotubes increased SREBP-1c mRNA and protein levels. Importantly, SREBP-1c promoter transactivation, which was significantly increased in response to SIRT1 overexpression by gene electrotransfer in skeletal muscle, was completely abolished when liver X receptor (LXR) response elements were deleted. Finally, our in vivo data from SIRT1 Dex4/Dex4 mice and in vitro data from human myotubes overexpressing SIRT1 show that SIRT1 regulates LXR acetylation in skeletal muscle cells. This suggests a possible mechanism by which the regulation of SREBP-1c gene expression by SIRT1 may require the deacetylation of LXR transcription factors

Myostatin Gene Inactivation Prevents Skeletal Muscle Wasting in Cancer

Cachexia is a muscle-wasting syndrome that contributes significantly to morbidity and mortality of many patients with advanced cancers. However, little is understood about how the severe loss of skeletal muscle characterizing this condition occurs. In the current study, we tested the hypothesis that the muscle protein myostatin is involved in mediating the pathogenesis of cachexia-induced muscle wasting in tumor-bearing mice. Myostatin gene inactivation prevented the severe loss of skeletal muscle mass induced in mice engrafted with Lewis lung carcinoma (LLC) cells or in Apc(Min/+) mice, an established model of colorectal cancer and cachexia. Mechanistically, myostatin loss attenuated the activation of muscle fiber proteolytic pathways by inhibiting the expression of atrophy-related genes, MuRF1 and MAFbx/Atrogin-1, along with autophagy-related genes. Notably, myostatin loss also impeded the growth of LLC tumors, the number and the size of intestinal polyps in Apc(Min/+) mice, thus strongly increasing survival in both models. Gene expression analysis in the LLC model showed this phenotype to be associated with reduced expression of genes involved in tumor metabolism, activin signaling, and apoptosis. Taken together, our results reveal an essential role for myostatin in the pathogenesis of cancer cachexia and link this condition to tumor growth, with implications for furthering understanding of cancer as a systemic disease. (C)2014 AACR