Exploratory analysis of obsessive compulsive symptom dimensions in children and adolescents: a Prospective follow-up study

BACKGROUND: Recent statistical approaches based on factor analysis of obsessive compulsive (OC) symptoms in adult patients have identified dimensions that seem more effective in symptom-based taxonomies and appear to be more stable over time. Although a phenotypic continuum from childhood to adulthood has been hypothesized, no factor analytic studies have been performed in juvenile patients, and the stability of OC dimensions in children and adolescents has not been assessed. METHODS: This study was designed to perform an exploratory factor analysis of OC symptoms in a sample of children and adolescents with OC disorder (OCD) and to investigate the course of factors over time (mean follow-up period: four years). RESULTS: We report for the first time that four symptom dimensions, remarkably similar to those previously described in adults, underlined the heterogeneity of OC symptoms in children and adolescents. Moreover, after follow-up, the symptom dimensions identified remained essentially unmodified. The changes observed concerned the intensity of dimensions rather than shifts from one dimension to another. CONCLUSION: These findings reinforce the hypothesis of a phenotypic continuum of OC symptoms from childhood to adulthood. They also strengthen the interest for investigating the clinical, neurobiological and genetic heterogeneity of OCD using a dimension-based approach

ERS/EACTS statement on the management of malignant pleural effusions

Malignant pleural effusions (MPE) are a common pathology, treated by respiratory physicians and thoracic surgeons alike. In recent years, several well-designed randomized clinical trials have been published that have changed the landscape of MPE management. The European Respiratory Society (ERS) and the European Association for Cardio-Thoracic Surgery (EACTS) established a multidisciplinary collaboration of clinicians with expertise in the management of MPE with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified, including the optimum management of symptomatic MPE, management of trapped lung in MPE, management of loculated MPE, prognostic factors in MPE, whether there is a role for oncological therapies prior to intervention for MPE and whether a histological diagnosis is always required in MPE. The literature revealed that talc pleurodesis and indwelling pleural catheters effectively manage the symptoms of MPE. There was limited evidence regarding the management of trapped lung or loculated MPE. The LENT score was identified as a validated tool for predicting survival in MPE, with Brims' prognostic score demonstrating utility in mesothelioma prognostication. There was no evidence to support the use of oncological therapies as an alternative to MPE drainage, and the literature supported the use of tissue biopsy as the gold standard for diagnosis and treatment planning.Management options for malignant pleural effusions have advanced over the past decade, with high-quality randomized trial evidence informing practice in many areas. However, uncertainties remain and further research is required http://ow.ly/rNt730jOxOS

Dimensions obsessionnelles et compulsives chez l'enfant et l'adolescent (structure et stabilité temporelle)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

ITGBL1 is a new immunomodulator that favors development of melanoma tumors by inhibiting natural killer cells cytotoxicity

Resistances to immunotherapies remains a major hurdle towards a cure for melanoma in numerous patients. An increase in the mesenchymal phenotype and a loss of differentiation have been clearly associated with resistance to targeted therapies. Similar phenotypes have been more recently also linked to resistance to immune checkpoint therapies. We demonstrated here that the loss of MIcrophthalmia associated Transcription Factor (MITF), a pivotal player in melanocyte differentiation, favors the escape of melanoma cells from the immune system. We identified Integrin beta-like protein 1 (ITGBL1), a secreted protein, upregulated in anti-PD1 resistant patients and in MITFlow melanoma cells, as the key immunomodulator. ITGBL1 inhibited immune cell cytotoxicity against melanoma cells by inhibiting NK cells cytotoxicity and counteracting beneficial effects of anti-PD1 treatment, both in vitro and in vivo. Mechanistically, MITF inhibited RUNX2, an activator of ITGBL1 transcription. Interestingly, VitaminD3, an inhibitor of RUNX2, improved melanoma cells to death by immune cells. In conclusion, our data suggest that inhibition of ITGBL1 might improve melanoma response to immunotherapies

Epidemiology and clinical characteristics of Klebsiella spp. meningitis in France

International audienceObjectives: To describe the epidemiology of Klebsiella spp. meningitis in France with respect to clinical and bacteriological data.Methods: We performed a four-year multicenter, retrospective, observational study. The primary objective was to provide a clinical description of patients with Klebsiella spp. meningitis. Secondary objectives were to compare community-acquired meningitis and healthcare-associated meningitis and to analyze factors associated with mortality.Results: We enrolled 131 patients with Klebsiella spp. meningitis. Eighty-two (62.6%) infections were reported following neurosurgery. Twenty-eight strains (21.4%) were resistant to third-generation cephalosporins (3GC). The median [IQR] cellularity was 980/mm3 [116-5550], the median protein level was 5.67 [1.62-9] g/L and the median CSF glucose level was 2.5 [0-3.4] mmol/L. The in-hospital mortality rate was 23.6%. Community-acquired meningitis isolates were more frequently susceptible to 3GC than isolates from healthcare-associated meningitis (89.2% versus 72%; P=0.04). Comorbidities reported for patients with community-acquired meningitis were mainly diabetes mellitus and liver cirrhosis. In multivariate analysis, focal neurological disorder at the time of diagnosis was the only factor associated with in-hospital mortality (P=0.01).Conclusions: Purulent meningitis caused by Klebsiella spp. needs to be considered in patients with community-acquired meningitis and preexisting conditions, as well as in case of meningitis following neurosurgical procedures

Capnocytophaga zoonotic infections: a 10-year retrospective study (the French CANCAN study)

International audienceZoonotic species of Capnocytophaga genus belong to the oral microbiota of dogs and cats. They may be responsible for serious human infections, mainly after animal bites, with a high mortality rate. In France, only few cases have been reported and no multicenter study has been conducted. Our aim was to describe the French epidemiology of Capnocytophaga zoonosis. We conducted a multicenter (21 centers) retrospective non-interventional, observational study in France describing the epidemiology of Capnocytophaga zoonosis (C. canimorsus, C. cynodegmi, C. canis) over 10 years with regard to clinical and bacteriological data. From 2009 to 2018, 44 cases of Capnocytophaga zoonotic infections were described (C. canimorsus, n = 41; C. cynodegmi, n = 3). We observed an increase (2.5 times) in the number of cases over the study period (from the first to the last 5 years of the study). The most frequent clinical presentations were sepsis (n = 37), skin and soft tissue infections (n = 12), meningitis (n = 8), osteoarticular infections (n = 6), and endocarditis (n = 2). About one-third of patients with sepsis went into septic shock. Mortality rate was 11%. Mortality and meningitis rates were significantly higher for alcoholic patients (p = 0.044 and p = 0.006, respectively). Other comorbidities included smoking, splenectomy, diabetes mellitus, and immunosuppressive therapy are associated to zoonotic Capnocytophaga infection. Eighty-two percent of cases involved contact with dogs, mostly included bites (63%). Despite all isolates were susceptible to the amoxicillin-clavulanic acid combination, three of them were resistant to amoxicillin

Antimicrobial resistance in enterobacterales recovered from urinary tract infections in France

International audienceIn the context of increasing antimicrobial resistance in Enterobacterales, the management of these UTIs has become challenging. We retrospectively assess the prevalence of antimicrobial resistance in Enterobacterales isolates recovered from urinary tract samples in France, between 1 September 2017, to 31 August 2018. Twenty-six French clinical laboratories provided the susceptibility of 134,162 Enterobacterales isolates to 17 antimicrobials. The most frequent species were $E.\ coli$ (72.0%), $Klebsiella\ pneumoniae$ (9.7%), $Proteus\ mirabilis$ (5.8%), and $Enterobacter\ cloacae$ complex (2.9%). The overall rate of ESBL-producing Enterobacterales was 6.7%, and ranged from 1.0% in $P.\ mirabilis$ to 19.5% in $K.\ pneumoniae$, and from 3.1% in outpatients to 13.6% in long-term care facilities. Overall, 4.1%, 9.3% and 10.5% of the isolates were resistant to cefoxitin, temocillin and pivmecillinam. Cotrimoxazole was the less active compound with 23.4% resistance. Conversely, 4.4%, 12.9%, and 14.3% of the strains were resistant to fosfomycin, nitrofurantoin, and ciprofloxacin. However, less than 1% of E. coli was resistant to fosfomycin and nitrofurantoin. We identified several trends in antibiotics resistances among Enterobacterales isolates recovered from the urinary tract samples in France. Carbapenem-sparing drugs, such as temocillin, mecillinam, fosfomycin, cefoxitin, and nitrofurantoin, remained highly active, including towards ESBL-E

Retrospective multicentric study on Campylobacter spp. bacteremia in France: the Campylobacteremia study

International audienceAbstract Background Campylobacter spp. bacteremia is a severe infection. A nationwide 5-year retrospective study was conducted to characterize its clinical features and prognostic factors. Methods Patients diagnosed with Campylobacter spp. bacteremia in 37 French hospitals participating in the surveillance network of the National Reference Center for Campylobacter and Helicobacter were included from January 1, 2015, to December 31, 2019. The goal was to analyze the effects of a delay of appropriate antibiotic therapy and other risk factors on 30-day mortality, antibiotic resistance, patient characteristics and prognosis according to the Campylobacter species. Findings Among the 592 patients, Campylobacter jejuni and Campylobacter fetus were the most commonly identified species (42.9 and 42.6%, respectively). The patients were elderly (median age 68 years), and most had underlying conditions, mainly immunodepression (43.4%), hematologic malignancies (25.9%), solid neoplasms (23%) and diabetes (22.3%). C. jejuni and Campylobacter coli were associated with gastrointestinal signs, and C. fetus was associated with secondary localizations. Among the 80 patients (13.5%) with secondary localizations, 12 had endocarditis, 38 vascular, 24 osteo-articular and 9 ascitic fluid infections. The thirty-day mortality rate was 11.7%, and an appropriate antibiotic treatment was independently associated with 30-day survival (odds ratio [OR]=0.47, 95% CI [0.24–0.93], p=0.03). The median efficient therapy initiation delay was quite short (2 days, IQR [0–4]) but it had no significant impact on 30-day mortality (p=0.78). Interpretation Campylobacter spp. bacteremia mainly occurred in elderly immunocompromised individuals with variable clinical presentations according to the species involved. Appropriate antimicrobial therapy was associated with improved 30-day survival

Multicenter Retrospective Study of Vascular Infections and Endocarditis Caused by Campylobacter spp., France

The incidence of campylobacteriosis has substantially increased over the past decade, notably in France. Secondary localizations complicating invasive infections are poorly described. We aimed to describe vascular infection or endocarditis caused by Campylobacter spp. We included 57 patients from a nationwide 5-year retrospective study on Campylobacter spp. bacteremia conducted in France; 44 patients had vascular infections, 12 had endocarditis, and 1 had both conditions. Campylobacter fetus was the most frequently involved species (83%). Antibiotic treatment involved a β-lactam monotherapy (54%) or was combined with a fluoroquinolone or an aminoglycoside (44%). The mortality rate was 25%. Relapse occurred in 8% of cases and was associated with delayed initiation of an efficient antimicrobial therapy after the first symptoms, diabetes, and coexistence of an osteoarticular location. Cardiovascular Campylobacter spp. infections are associated with a high mortality rate. Systematically searching for those localizations in cases of C. fetus bacteremia may be warranted

Femoral Versus Nonfemoral Peripheral Access for Transcatheter Aortic Valve Replacement

International audienceBACKGROUND:Femoral access is the gold standard for transcatheter aortic valve replacement (TAVR). Guidelines recommend reconsidering surgery when this access is not feasible. However, alternative peripheral accesses exist, although they have not been accurately compared with femoral access.OBJECTIVES:This study compared nonfemoral peripheral (n-FP) TAVR with femoral TAVR.METHODS:Using the data from the national prospective French registry (FRANCE TAVI [French Transcatheter Aortic Valve Implantation]), this study compared the characteristics and outcomes of TAVR procedures according to whether they were performed through a femoral or a n-FP access, using a pre-specified propensity score-based matching between groups. Subanalysis during 2 study periods (2013 to 2015 and 2016 to 2017) and among low/intermediate-low and intermediate-high/high volume centers were performed. RESULTS:Among 21,611 patients, 19,995 (92.5%) underwent femoral TAVR and 1,616 (7.5%) underwent n-FP TAVR (transcarotid, n = 914 or trans-subclavian, n = 702). Patients in the n-FP access group had more severe disease (mean logistic EuroSCORE 19.95 vs. 16.95; p < 0.001), with a higher rate of peripheral vascular disease, known coronary artery disease, chronic pulmonary disease, and renal failure. After matching, there was no difference in the rate of post-procedural death and complications according to access site, except for a 2-fold lower rate of major vascular complications (odds ratio: 0.45; 95% confidence interval: 0.21 to 0.93; p = 0.032) and unplanned vascular repairs (odds ratio: 0.41; 95% confidence interval: 0.29 to 0.59; p < 0.001) in those who underwent n-FP access. The comparison of outcomes provided similar results during the second study period and in intermediate-high/high volume centers.CONCLUSIONS:n-FP TAVR is associated with similar outcomes compared with femoral peripheral TAVR, except for a 2-fold lower rate of major vascular complications and unplanned vascular repairs. n-FP TAVR may be favored over surgery in patients who are deemed ineligible for femoral TAVR and may be a safe alternative when femoral access risk is considered too high