CHRU de Strasbourg
  • Strasbourg, France
Recent publications
Although chronic kidney disease is characterized by low glomerular filtration rate (GFR) or albuminuria, estimated GFR (eGFR) is more widely utilized as a marker of risk profile in cardiovascular diseases, including heart failure (HF). The presence and magnitude of albuminuria confers a strong prognostic association in forecasting risk of incident HF as well as its progression, irrespective of eGFR. Despite the high prevalence of albuminuria in HF, whether it adds incremental prognostic information in clinical practice and serves as an independent risk marker, and whether there are any therapeutic implications of assessing albuminuria in patients with HF is less well-established. In this narrative review, we assess the potential role of albuminuria in risk profiling for development and progression of HF, strengths and limitations of utilizing albuminuria as a risk marker, its ability to serve in HF risk prediction models, and the implications of adopting albuminuria as an effective parameter in cardiovascular trials and practice.
Advances in the techniques for assessing human cerebral white matter have recently contributed to greater attention to structural connectivity. Yet, little is known about the vascularization of most white matter fasciculi and the fascicular composition of the vascular territories. This paper presents an original method to label the arterial supply of macroscopic white matter fasciculi based on a standardized protocol for post-mortem injection of colored material into main cerebral arteries combined with a novel fiber dissection technique. Twelve whole human cerebral hemispheres obtained post-mortem were included. A detailed description of every step, from obtaining the specimen to image acquisition of its dissection, is provided. Injection and dissection were reproducible and manageable without any sophisticated equipment. They successfully showed the arterial supply of the dissected fasciculi. In addition, we discuss the challenges we faced and overcame during the development of the presented method, highlight its originality. Henceforth, this innovative method serves as a tool to provide a precise anatomical description of the vascularization of the main white matter tracts.
Background: The network approach has emerged as a useful framework for conceptualizing and investigating psychopathology, including eating disorders. Network connectivity, that is, the density of the connections among network nodes, has been somewhat neglected despite its theoretical relevance. As predicted by network theory, symptom connectivity would be distinct but related to symptom severity and may be a useful clinical indicator of psychopathology as stronger and/or more diffuse connections among symptoms offer more avenues for symptom activation. This study aimed to investigate the relationship between moment-by-moment individual-level symptom connectivity and global levels of symptom severity in the context of eating disorder symptoms and experiences. Methods: A sample of 58 female undergraduate college students, mean (SD) age = 20.5 (3.1) provided data on eating disorder symptoms eight times a day over the course of 10 days. Network analyses were used to calculate the eating disorder symptoms network connectivity for each participant. In addition, participants completed survey of self-report measures of eating disorder symptom severity and trait mindfulness and body image flexibility. Results: Analyses revealed a moderate, positive relationship between individual network connectivity and eating disorder symptom severity. In addition, symptom connectivity predicted unique variance of symptom severity even after controlling for other clinically-relevant variables. Conclusions: Individual-level network connectivity may be an important dimension of psychopathology and further work exploring the role of network connectivity is warranted. Public significance: These findings suggest that symptom severity and the extent to which different eating disorder symptoms are connected are related but different dimensions. Investigating how these different dimensions play a role in eating disorder pathology could help to better understand and treat these disorders.
Objective COVID-19 outcome may be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases (RMD) receiving immunosuppressive therapy. We aimed to investigate whether RMD patients on anti-IL6 therapy prior to SARS-CoV-2 infection have less severe disease and better outcomes of COVID-19. Methods We conducted a retrospective national, multicentre cohort study using data from the French RMD COVID-19 cohort. We compared the severity and outcome of highly suspected or confirmed COVID-19 infection in RMD patients previously treated with tocilizumab or sarilumab (anti-IL6 group) with patients who did not receive anti-IL6 therapy (no anti-IL6 group). Results Data were collected for 1883 patients with mean age of 55.2 years [SD 16.7] and 1256 (66.7%) female. Two hundred ten (11.1%) developed severe COVID-19 and 115 (6.4%) died. After adjusting for potential confounding factors, severe COVID-19 was less frequent in the anti-IL6 group compared with the no anti-IL6 group (aOR for moderate vs. mild severity, 0.23 [95% CI, 0.10 to 0.54], p ≤ 0.01 and aOR for severe vs. mild, 0.29 [95% CI, 0.10 to 0.81], p ≤ 0.01). No significant differences were found for the evolution of COVID-19 between the anti-IL6 group and the no anti-IL6 group (aOR for recovery with sequelae vs recovery without sequelae, 0.78 [95% CI, 0.41 to 1.48] and aOR for death vs recovery without sequelae, 0.29 [95% CI, 0.07 to 1.30]). Conclusion RMD patients receiving anti-IL6 therapy prior to SARS-CoV-2 infection have less severe forms of COVID-19. No difference was observed in COVID-19 evolution, i.e., sequelae or death, between the groups.
Allogeneic haematopoietic cell transplant (allo-HCT) provides the only potential route to long-term remission in patients diagnosed with blast phase transformation of myeloproliferative neoplasm (BP-MPN). We report on a large, retrospective EBMT registry-based study of BP-MPN patients undergoing allo-HCT. BP-MPN patients undergoing first allo-HCT between 2005-2019 were included. A total of 663 patients were included. With a median follow-up of 62 months, the estimated 3-year OS was 36% (95% CI, 32-36). Factors associated with lower OS were Karnofsky Performance Status (KPS) <90 (HR 1.65, p<0.001) and active disease at allo-HCT (HR 1.45, p<0.001), whereas patients undergoing allo-HCT more recently associated with a higher OS (HR 0.96, p=0.008). In a selected patients population, the 3-year OS of patients undergoing allo-HCT in complete response (CR) and with a KPS ≥90 was 60%. KPS<90 (HR 1.4, p=0.001) and active disease (HR 1.44, p=0.0004) were associated with a lower PFS. Conversely, most recent allo-HCT associated with a higher PFS (HR 0.96, p=0.008). Active disease at allo-HCT (HR 1.34, p=0.03) was associated with a higher cumulative incidence of relapse (RI) and allo-HCT in earlier calendar years (HR 0.96, p=0.02) associated with a lower RI. Lastly, KPS<90 (HR 1.91, p<0.001), active disease (HR 1.74, p=0.003) and allo-HCT from mismatched related donors were associated with a higher NRM (HR 2.66, p=0.003). In this large series of BP-MPN patients, about one third were alive at 3 years after transplantation. Patients undergoing allo-HCT in the more recent era, with a KPS≥90 and in CR at transplant had a better prognosis. This article is protected by copyright. All rights reserved.
Aims: Few reports have examined the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) or their relationship with mortality in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF). Methods and results: Data from the PARAGON-HF, TOPCAT, I-Preserve, and CHARM-Preserved trials were merged. VT/VF, reported as adverse events, were identified. Patients who experienced VT/VF were compared with patients who did not. The relationship between VT/VF and mortality was examined in time-updated Cox proportional hazard regression models. Variables associated with VT/VF were examined in Cox proportional hazard regression models. The rate of VT/VF in patients with HFmrEF compared with patients with HFpEF was examined in a Cox proportional hazards regression model. Of 13 609 patients, over a median follow-up of 1170 days (interquartile range: 966-1451), 146 (1.1%) experienced an investigator-reported VT/VF (incidence rate 0.3 per 100 person-years). Patients who experienced VT/VF were more likely to be male, have had a myocardial infarction, poorer renal function, more adverse left ventricular remodelling, and higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) than patients who did not. Occurrence of VT/VF was associated with NT-proBNP, history of atrial fibrillation/flutter, male sex, lower ejection fraction, and history of hypertension. VT/VF was associated with all-cause death [adjusted hazard ratio (HR): 3.95, 95% confidence interval (CI): 2.80-5.57; P < 0.001] and cardiovascular death, driven by death from heart failure and not sudden death. Patients with HFmrEF had a higher rate of VT/VF than patients with HFpEF (adjusted HR: 2.19, 95% CI: 1.77-2.71). Conclusion: VT/VF was uncommon in patients with HFmrEF and HFpEF. However, such events were strongly associated with mortality and appear to be a marker of disease severity rather than risk of sudden death. Clinical trial registration: unique identifier: NCT01920711(PARAGON-HF); NCT00094302 (TOPCAT); NCT00095238 (I-Preserve); NCT00634712 (CHARM-Preserved).
Meningiomas are the most common primary tumors of the central nervous system. Based on the 2021 WHO classification, they are classified into three grades reflecting recurrence risk and aggressiveness. However, the WHO’s histopathological criteria defining these grades are somewhat subjective. Together with reliable immunohistochemical proliferation indices, other molecular markers such as those studied with genome-wide epigenetics promise to revamp the current prognostic classification. In this study, 48 meningiomas of various grades were randomly included and explored for DNA methylation with the Infinium MethylationEPIC microarray over 850k CpG sites. We conducted differential and correlative analyses on grade and several proliferation indices and markers, such as mitotic index and Ki-67 or MCM6 immunohistochemistry. We also set up Cox proportional hazard models for extensive associations between CpG methylation and survival. We identified loci highly correlated with cell growth and a targeted methylation signature of regulatory regions persistently associated with proliferation, grade, and survival. Candidate genes under the control of these regions include SMC4, ESRRG, PAX6, DOK7, VAV2, OTX1, and PCDHA-PCDHB-PCDHG, i.e., the protocadherin gene clusters. This study highlights the crucial role played by epigenetic mechanisms in shaping dysregulated cellular proliferation and provides potential biomarkers bearing prognostic and therapeutic value for the clinical management of meningioma.
Purpose To assess the most efficient biopsy method to improve International Society of Urological Pathology (ISUP) grade group accuracy with final pathology of the radical prostatectomy (RP) specimen in the era of magnetic resonance imaging (MRI)-driven pathway. Methods A total of 753 patients diagnosed by transrectal MRI-targeted and systematic biopsies (namely “standard method”), treated by RP, between 2016 and 2021 were evaluated. Biopsy methods included MRI-targeted biopsy, side-specific systematic biopsies relative to index MRI lesion and combination of both. Number of MRI-targeted biopsy cores and positive cores needed per index MRI lesion were assessed. Multivariable analysis was performed to analyze predictive factors of upgrading using MRI targeted and ipsilateral systematic biopsies method. Results Overall, ISUP grade group accuracy varied among biopsy methods with upgrading rate of 35%, 49%, 27%, and 24% for MRI targeted, systematic, MRI targeted and ipsilateral systematic biopsies and standard methods, respectively (p < 0.001). A minimum of two positive MRI-targeted biopsies cores per index MRI lesion were required when testing MRI targeted and ipsilateral systematic biopsies method to reach equivalent accuracy compared to standard method. Omitting contralateral systematic biopsies spared an average of 5.9 cores per patient. At multivariable analysis, only the number of positive MRI-targeted biopsy cores per index MRI lesion was predictive of upgrading. Conclusion MRI targeted and ipsilateral systematic biopsies allowed an accurate definition of ISUP grade group and appears to be an interesting alternative when compared with standard method, reducing total number of biopsy cores needed.
The EMPEROR-Preserved trial showed that the sodium–glucose co-transporter 2 inhibitor empagliflozin significantly reduces the risk of cardiovascular death or hospitalization for heart failure (HHF) in heart failure patients with left ventricular ejection fraction (LVEF) > 40%. Here, we report the results of a pre-specified analysis that separately evaluates these patients stratified by LVEF: preserved (≥ 50%) (n = 4,005; 66.9%) or mid-range (41–49%). In patients with LVEF ≥ 50%, empagliflozin reduced the risk of cardiovascular death or HHF (the primary endpoint) by 17% versus placebo (hazard ratio (HR) 0.83; 95% confidence interval (CI): 0.71–0.98, P = 0.024). For the key secondary endpoint, the HR for total HHF was 0.83 (95%CI: 0.66–1.04, P = 0.11). For patients with an LVEF of 41–49%, the HR for empagliflozin versus placebo was 0.71 (95%CI: 0.57–0.88, P = 0.002) for the primary outcome (Pinteraction = 0.27), and 0.57 (95%CI: 0.42–0.79, P < 0.001) for total HHF (Pinteraction = 0.06). These results, together with those from the EMPEROR-Reduced trial in patients with LVEF < 40%, support the use of empagliflozin across the full spectrum of LVEF in heart failure.
Research suggests that the risk of body image concerns among sexual minority men is high. Recent work has increasingly examined body image in relation to psychological, interpersonal, and behavioral constructs, but these findings have yet to be consolidated and critically examined to identify potential risk and protective factors. The present study sought to systematically review and synthesize published findings on body image among sexual minority men. A total of 136 articles published between January 2011 and March 2022 were included. Sexual minority men were generally reported to have more negative body image compared to heterosexual men, yet findings varied across body image constructs. In correlational work, body image was often examined in relation to disordered eating, mental health, internalization of appearance ideals, objectification, sexual behavior and relationships, gay community identification and discrimination, and health concerns (e.g., HIV, AIDS). Robust relationships emerged among body image and stigma variables, including internalized homophobia and harassment related to LGBTQ+ presentation and intersecting minority identities. Sociocultural, objectification, and minority stress theories were employed to interpret findings and to delineate future directions grounded in intersectional approaches. Additional work focused on the role of stigma and discrimination in the development of these concerns across the lifespan is needed.
Riassunto La chirurgia polmonare è un intervento chirurgico non privo di rischi. Infatti, la mortalità ospedaliera varia dall’1% al 10% a seconda dei diversi tipi di exeresi, che vanno dalla semplice resezione atipica alla pneumonectomia. Tuttavia, la mortalità può aggirarsi intorno al 12% nelle pneumonectomie destre più o meno allargate e al 18% nelle lobectomie di totalizzazione a destra. Pertanto, la tendenza attuale è quella di limitare l’estensione dell’exeresi parenchimale. Ciò può essere spiegato da diversi fattori: un’alterazione meno significativa della funzionalità respiratoria postoperatoria, il contributo della radiochemioterapia neoadiuvante che talvolta consente resezioni meno significative riducendo la massa tumorale e la mortalità ospedaliera tre volte inferiore dopo lobectomia. La definizione di migliori programmi riabilitativi dopo l’intervento chirurgico ha permesso di ottimizzare il follow-up postoperatorio dopo exeresi polmonari. In questo articolo affrontiamo successivamente la valutazione preoperatoria, i principi generali di anestesia e di chirurgia e infine le complicanze postoperatorie.
Background PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition. Methods We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction. Results We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52–0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77–0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression. Conclusions The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection.
Introduction Les cryoglobulinémies de type 1 (CG1) sont souvent associées à une hémopathie lymphoïde B dont le traitement dépend du type de l’hémopathie sous-jacente (clone lymphocytaire ou plasmocytaire) et de la sévérité de l’atteinte. Environ la moitié des patients présentent des rechutes conduisant à une escalade thérapeutique avec un risque considérable d’effets indésirables. L’objectif de ce travail était d’étudier les facteurs pronostiques et l’évolution à long terme des CG 1 et selon son type (IgM vs IgG). Patients et méthodes Nous avons analysé rétrospectivement les données d’une cohorte nationale de patients avec une CG 1 entre 2001 et 2018. Les patients ayant une infection au VHB, VHC et au VIH ont été exclus. Les caractéristiques clinicobiologiques, le traitement ainsi que la réponse à six mois ont été comparés selon le type de CG1. Une régression logistique a été réalisée pour évaluer la survie sans événements (SRE) et les facteurs associés à une réponse complète à six mois. Résultats Notre cohorte incluait 168 patients, dont 43 % de femmes, avec un âge médian au diagnostic de 65 ans (56–73) et un suivi médian de 50 mois (1–267). Le MGUS était l’étiologie la plus fréquente (31 %), suivi par la maladie de Waldenstrom (27 %), les lymphomes B (20 %), le myélome multiple (15 %) et la leucémie lymphoïde chronique (7 %). Les patients avec une CG 1 de type IgG avaient significativement plus d’atteinte cutanée nécrosante (45 % versus 15 %, p < 0,0001), plus de neuropathie (22 % versus 11 %, p = 0,05), et plus d’atteinte rénale (54 % versus 19 %, p < 0,0001) que les patients avec un isotype IgM. La SRE à un et à cinq ans était de 64 % et 26,5 %, respectivement. En analyse multivariée, l’isotype IgM (hazard ratio [HR] 0,51 [0,30–0,88], p = 0,01) était significativement associée à une meilleure SSE, alors que l’atteinte rénale (hazard ratio [HR] 2,42 [1,41–4,17], p = 0,001) était le seul facteur associé à une mauvaise SSE. Les rechutes de vascularite étaient plus fréquentes chez les patients avec un isotype IgG (65 %) que ceux avec un isotype IgM (34 %), p = 0,0001. La rémission complète à six mois, était de 29,6 % dont 36 % avec IgG et 43 % avec IgM. La survie globale à 10 ans était de 52,5 %, les principales causes de décès étaient l’insuffisance cardiaque (21 %) et les infections (7 %). Conclusion Les patients avec une CG1 de type IgG présentent plus de neuropathie, plus d’atteinte rénale et plus d’atteinte cutanée nécrosante que ceux avec un isotype IgM. La survie sans évènements est défavorable en cas d’atteinte rénale ou de CG1 de type IgG.
Introduction Le risque thrombotique et/ou hémorragique sévère au cours de la grossesse et du post-partum est autour de 1 % dans la population générale. Ce risque n’a pas été évalué de façon prospective chez les femmes suivies pour un syndrome des antiphospholipides (SAPL). Notre objectif est de décrire ces complications et les facteurs associés à ces évènements, à partir de la cohorte Groupe de Recherche sur la Grossesses et les maladies Rares (GR2). Patients et méthodes À partir de la cohorte prospective multicentrique française EGR2, nous avons inclus avant 18 semaines d’aménorrhées (SA), des femmes suivies pour SAPL, avec une grossesse évolutive à 12 SA. Les patientes étaient exclues en cas de néphropathie active (définie par une protéinurie > 1000 mg/jour ou une créatinine > 100 μmol/L), ou de grossesse multiple. Les évènements thrombotiques incluaient les thromboses artérielles, veineuses et le syndrome catastrophique des antiphospholipides (CAPS). Les évènements hémorragiques sévères étaient définis par la nécessité d’une transfusion, d’un transfert en réanimation de la mère ou d’un traitement invasif comme une chirurgie. L’insuffisance placentaire était définie par la survenue d’une préeclampsie, d’un syndrome hemolysis, elevated liver enzymes low platelet (HELLP), d’un retard de croissance in utero ou d’un hématome retro placentaire. Les patientes étaient suivies depuis l’inclusion jusqu’à au moins 3 mois post-partum. Le traitement et le suivi étaient laissés à l’appréciation du clinicien référent. Résultats Cent soixante-huit femmes ont été incluses avec une médiane d’inclusion de 8 SA [IQR : 6–11]. La moitié (53 %) avait un antécédent thrombotique. L’anticoagulant circulant (ACC) était positif au cours de la grossesse dans 53 % des cas (n = 84/158), avec une triple positivité dans 28 % des cas (n = 44/159). Toutes les patientes sauf 6 recevaient de l’aspirine (165/168) et de l’héparine (165/168) avec 80 % des patientes recevant un traitement adapté aux recommandations et 8 % un traitement en accord avec nos connaissances actuelles (antécédents de complications malgré un traitement adapté, négativation de biologie APL) [1]. Un événement est survenu chez seize femmes (9,5 %) : 6 ont présenté une thrombose (3,6 %, dont deux CAPS) et 12 une hémorragie sévère (7,1 %, dont 10 en post-partum). Les grossesses des 2 patientes ayant développé un CAPS ont également été compliquées d’un syndrome HELLP et d’une hémorragie sévère. Aucun décès maternel n’est survenu. Toutes sauf une recevaient un traitement en accord avec les recommandations actuelles. Les principaux facteurs associés aux thromboses étaient la présence d’un ACC au cours de la grossesse (100 % versus 51 %, p = 0,03) ou une complication de l’insuffisance placentaire (66,7 % versus 17 %, p = 0,01). Les principaux facteurs associés aux hémorragies sévères étaient une hypertension artérielle maternelle pré-existante (33 % versus 7 %, p = 0,01), la présence d’un ACC au cours de la grossesse (100 % versus 49 %, p < 0,0001) ou dans l’histoire du SAPL, une triple positivité (67 % versus 24 %, p = 0,004), une complication de l’insuffisance placentaire (42 % versus 17 %, p = 0,04), et une naissance prématurée avant 34 SA (45 % versus 8 %, p = 0,003). Toutes les patientes avec complications avaient un ACC. Dix-neuf pour cent des patientes avec ACC ont eu une complication maternelle thrombotique et/ou hémorragique sévère versus aucune chez celles sans ACC. Conclusion Malgré un traitement en accord avec les recommandations internationales et/ou l’état actuel de nos connaissances, une femme sur 10 suivie pour un SAPL présentait une complication thrombotique et/ou hémorragique sévère au cours de la grossesse, le plus souvent dans la période post-partum. La présence d’un ACC et d’une complication de l’insuffisance placentaire étaient associées à ces complications sévères. En l’absence d’ACC aucun évènement ne survenait.
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790 members
Carole Mathelin
  • Unité de sénologie
Emanuele Boatta
  • Imagerie Interventionnelle
David Rey
  • HIV Infection Center
Michel Hasselmann
  • Pôle Urgences / réanimations médicales / CAP
Cécile Sonntag
  • Pôle Onco-hématologie
Strasbourg, France