RESUMO
Heterozygous activin receptor-like kinase 1 (ALK1) mutations are associated with two vascular diseases: hereditary hemorrhagic telangiectasia (HHT) and more rarely pulmonary arterial hypertension (PAH). Here, we aimed to understand the impact of ALK1 mutations on BMP9 and BMP10 transcriptomic responses in endothelial cells. Endothelial colony-forming cells (ECFCs) and microvascular endothelial cells (HMVECs) carrying loss of function ALK1 mutations were isolated from newborn HHT and adult PAH donors, respectively. RNA-sequencing was performed on each type of cells compared to controls following an 18 h stimulation with BMP9 or BMP10. In control ECFCs, BMP9 and BMP10 stimulations induced similar transcriptomic responses with around 800 differentially expressed genes (DEGs). ALK1-mutated ECFCs unexpectedly revealed highly similar transcriptomic profiles to controls, both at the baseline and upon stimulation, and normal activation of Smad1/5 that could not be explained by a compensation in cell-surface ALK1 level. Conversely, PAH HMVECs revealed strong transcriptional dysregulations compared to controls with > 1200 DEGs at the baseline. Consequently, because our study involved two variables, ALK1 genotype and BMP stimulation, we performed two-factor differential expression analysis and identified 44 BMP9-dysregulated genes in mutated HMVECs, but none in ECFCs. Yet, the impaired regulation of at least one hit, namely lunatic fringe (LFNG), was validated by RT-qPCR in three different ALK1-mutated endothelial models. In conclusion, ALK1 heterozygosity only modified the BMP9/BMP10 regulation of few genes, including LFNG involved in NOTCH signaling. Future studies will uncover whether dysregulations in such hits are enough to promote HHT/PAH pathogenesis, making them potential therapeutic targets, or if second hits are necessary.
Assuntos
Hipertensão Arterial Pulmonar , Telangiectasia Hemorrágica Hereditária , Adulto , Recém-Nascido , Humanos , Células Endoteliais/metabolismo , Fator 2 de Diferenciação de Crescimento/genética , Fator 2 de Diferenciação de Crescimento/metabolismo , Hipertensão Arterial Pulmonar/metabolismo , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/metabolismo , Proteínas Morfogenéticas Ósseas/genética , Mutação/genética , Perfilação da Expressão Gênica , Receptores de Activinas Tipo II/genética , Receptores de Activinas Tipo II/metabolismoRESUMO
In May 2019, a measles outbreak occurred in the French subregion of Loire-Atlantique, particularly affecting Roma settlements. Various obstacles hindered the implementation of postexposure measures among Roma population, resulting in the spread of the cases to other settlements. Suspected cases of measles were immediately investigated and concerned settlements were visited for measles-mumps-rubella (MMR) vaccination. From July 1 to September 3, 2019, a first and then a second Health Reserve team helped for vaccination on the affected and then also the measles-free settlements. Vaccination uptake was monitored with the use of the department's vaccination center immunization registry. Genotyping of selected samples was performed for comparison with viruses circulating at the same time in France and Romania. As of September 16 2019, 109 cases of measles were confirmed among Roma population, including 99 (91%) children under 15 years. Of the 85 people eligible for vaccination, 60 (71%) had not been vaccinated and 23 (27%) had an unknown vaccination status. Sequence comparison revealed that 28/29 sequenced D8 strains were 100% identical to the strain responsible for a large number of cases throughout France in 2019, and to two sequences reported in Romania among sporadic cases. The vaccination campaign resulted in 1136 people on 35 settlements receiving at least one dose of MMR vaccine and in the increase of one-dose MMR vaccine coverage at 24 months from 43% (23/53) to 91% (48/53). With measles transmission continuing in Europe, efforts must be made to meet immunization coverage targets, particularly in hard-to-reach communities where outbreaks may be difficult to control.
Assuntos
Sarampo , Caxumba , Roma (Grupo Étnico) , Rubéola (Sarampo Alemão) , Criança , Humanos , Surtos de Doenças , França/epidemiologia , Sarampo/epidemiologia , Sarampo/prevenção & controle , Vacina contra Sarampo-Caxumba-Rubéola , Caxumba/epidemiologia , Rubéola (Sarampo Alemão)/epidemiologia , VacinaçãoRESUMO
Pulmonary arterial hypertension (PAH) is a rare and severe disorder characterized by progressive pulmonary vasculopathy. Growth differentiation factor (GDF)2 encodes the pro-protein bone morphogenetic protein (BMP) 9, activated after cleavage by endoproteases into an active mature form. BMP9, together with BMP10, are high-affinity ligands of activin receptor-like kinase 1 (ALK1) and BMP receptor type II (BMPR2). GDF2 mutations have been reported in idiopathic PAH with most patients being heterozygous carriers although rare homozygous cases have been described. The link between PAH occurrence and BMP9 or 10 expression level is still unclear. In this study, we describe a pediatric case of PAH also presenting with telangiectasias and epistaxis. The patient carries the novel homozygous GDF2 c.946A > G mutation, replacing the first arginine of BMP9's cleavage site (R316) by a glycine. We show that this mutation leads to an absence of circulating mature BMP9 and mature BMP9-10 heterodimers in the patient's plasma although pro-BMP9 is still detected at a similar level as controls. In vitro functional studies further demonstrated that the mutation R316G hampers the correct processing of BMP9, leading to the secretion of inactive pro-BMP9. The heterozygous carriers of the variant were asymptomatic, similarly to previous reports, reinforcing the hypothesis of modifiers preventing/driving PAH development in heterozygous carriers.
Assuntos
Hipertensão Arterial Pulmonar , Criança , Humanos , Proteínas Morfogenéticas Ósseas/genética , Fator 2 de Diferenciação de Crescimento/genética , Mutação , Mutação de Sentido Incorreto/genética , Hipertensão Arterial Pulmonar/genéticaRESUMO
BACKGROUND: We aimed to describe and discuss the algorithms used to identify chronic inflammatory rheumatisms and psoriasis in medico-administrative databases. METHODS: We performed a literature review on the Medline database of articles published up to 31 January 2018. Our inclusion criteria were: original articles using medico-administrative databases in accordance with the International Classification of Diseases, version 10 (ICD-10) and concerning rheumatoid arthritis (RA) or ankylosing spondylitis (AS) or psoriatic arthritis (PsoA) or Psoriasis (Pso). Our exclusion criteria were: letters to the editor, commentaries on published articles, studies using codes other than those of the ICD or a previous version. RESULTS: Out of the 590 articles identified, 37 studies were included. Concerning RA (n=10), all studies used the M05 code, associated with the M06 code in six studies. The remaining four studies specifically targeted codes M06.0, M06.2, M06.3, M06.8, M06.9, and two of them also used code M12.3. For AS (n=8), 7 studies used the M45 code, while only one study used M45.9, M46.1 or M46.8. For Pso (n=17), all studies used the L40 code and/or at least two dispensations of vitamin D. Concerning PsoA (n=13), all studies used the same codes: M07.0, M07.1, M07.2, M07.3. CONCLUSION: We recommend using codes M05 and M06 rather than M06.1 and M06.4 for RA, M45 for AS, the algorithm L40 and/or two dispensations of topical vitamin D for psoriasis, and codes M070 to M073 to identify PsoA patients in medico-administrative databases.
Assuntos
Artrite Reumatoide , Psoríase , Febre Reumática , Algoritmos , Bases de Dados Factuais , Humanos , Classificação Internacional de Doenças , Psoríase/diagnóstico , Psoríase/epidemiologiaRESUMO
PURPOSE: In children, the usual indications for continuous positive airway pressure (CPAP) are residual OSA after adenotonsillectomy and/or persistent OSA due to obesity. Data concerning adherence (hours/night) following ambulatory CPAP initiation are scarce. METHODS: An observational cohort of 78 children was followed over 2 years. All exhibited sleep-disordered breathing (SDB) symptoms, were assessed by polysomnography, and prescribed CPAP. CPAP was initiated at hospital for 10 children. RESULTS: OSA children, mean age 10.4 ± 3.2 years, were mostly males (75.6%), with a mean body mass index of 21.2 ± 7.3 kg/m2, and mean apnea+hypopnea index of 12.2 ± 10.6 events/hour. Seventy-two children were still on CPAP at 3 months, 63 at 6 months, 55 at 1 year, and 34 at 2 years. CPAP was discontinued thanks to rehabilitation programs, dento-facial orthopedics, and/or weight loss. Mean CPAP adherence at 1, 3, 6, 12, and 24 months was respectively 6.1 ± 2.8, 6.2 ± 2.6, 6.2 ± 2.8, 6.3 ± 2.8, and 7.0 ± 2.7 h/night. There was a trend towards higher CPAP adherence and younger age, primary versus middle/high school attendance, higher baseline apnea+hypopnea index, and neurocognitive disorders. CONCLUSION: In our population, mean CPAP adherence defined in hours per night was high and did not decrease during the 24-month follow-up. These findings support the feasibility of ambulatory CPAP initiation in non-syndromic OSA. The high CPAP adherence is expected to be associated with improvements in neurocognition, and in metabolic and cardiovascular parameters.
Assuntos
Assistência Ambulatorial/psicologia , Pressão Positiva Contínua nas Vias Aéreas/psicologia , Assistência de Longa Duração/psicologia , Cooperação do Paciente/psicologia , Apneia Obstrutiva do Sono/psicologia , Apneia Obstrutiva do Sono/terapia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , PolissonografiaRESUMO
Background: Peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem-cell transplantation (ASCT) is, therefore, still intensely debated. Patients and methods: In the absence of randomized trials addressing the role of ASCT, we performed a large multicentric retrospective study and used both a multivariate proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not to ASCT in intention-to-treat (ITT). Results: Among 527 patients screened from 14 centers in France, Belgium and Portugal, a final cohort of 269 patients ≤65 years old with PTCL-not otherwise specified (NOS) (N = 78, 29%), angioimmunoblastic T-cell lymphoma (AITL) (N = 123, 46%) and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-ALCL) (N = 68, 25%) with partial (N = 52, 19%) or complete responses (N = 217, 81%) after induction was identified and information about treatment allocation was carefully collected before therapy initiation from medical records. One hundred and thirty-four patients were allocated to ASCT in ITT and 135 were not. Neither the Cox multivariate model (HR = 1.02; 95% CI: 0.69-1.50 for PFS and HR = 1.08; 95% CI: 0.68-1.69 for OS) nor the propensity score analysis after stringent matching for potential confounding factors (logrank P = 0.90 and 0.66 for PFS and OS, respectively) found a survival advantage in favor of ASCT as a consolidation procedure for patients in response after induction. Subgroup analyses did not reveal any further difference for patients according to response status, stage disease or risk category. Conclusions: The present data do not support the use of ASCT for up-front consolidation for all patients with PTCL-NOS, AITL, or ALK-ALCL with partial or complete response after induction.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Células T Periférico/terapia , Adulto , Idoso , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Quimioterapia de Indução , Linfoma de Células T Periférico/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transplante Autólogo , Adulto JovemRESUMO
Initial results with the Elecsys Toxo IgG Avidity assay showed some potential for interpretation of a very low or very high index result. We aimed to examine these new insights into interpretation using a large panel of serum samples and to define the optimal thresholds. A total of 741 patient serum samples with known date of infection (from a few weeks to more than 9 months after infection), were analysed with the Elecsys Toxo IgG Avidity assay. Values ≥80% (threshold defined by the manufacturer) were reported in 289 sera; 288 sera were sampled more than 4 months after infection. Thus, avidity values ≥80% excluded an infection less than 4 months. Avidity values ≥90% were reported in 112 sera sampled more than 9 months after infection. Thus, avidity values ≥90% excluded infection less than 9 months. Moreover avidity values ≤15% were reported in the 62 sera sampled less than 3 months after infection. Thus avidity values ≤15% excluded infection more than 3 months.
Assuntos
Anticorpos Antiprotozoários/sangue , Afinidade de Anticorpos , Imunoensaio/métodos , Imunoglobulina G/sangue , Toxoplasmose/diagnóstico , Toxoplasmose/imunologia , Feminino , Humanos , Gravidez , Fatores de TempoRESUMO
Anti-Aspergillus IgG antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We compared the performance of a new commercial enzyme immunoassay (EIA) (Bordier Affinity Products) with that of the Bio-Rad and Virion\Serion EIAs. This assay is novel in its association of two recombinant antigens with somatic and metabolic antigens of Aspergillus fumigatus In a prospective multicenter study, 436 serum samples from 147 patients diagnosed with CPA (136 samples/104 patients) or ABPA (94 samples/43 patients) and from 205 controls (206 samples) were tested. We obtained sensitivities of 97%, 91.7%, and 86.1%, and specificities of 90.3%, 91.3%, and 81.5% for the Bordier, Bio-Rad, and Virion\Serion tests, respectively. The Bordier kit was more sensitive than the Bio-Rad kit (P < 0.01), which was itself more sensitive than the Virion\Serion kit (P = 0.04). The Bordier and Bio-Rad kits had similar specificity (P = 0.8), both higher than that of the Virion\Serion kit (P = 0.02). The area under the receiver operating characteristic (ROC) curves confirmed the superiority of the Bordier kit over the Bio-Rad and the Virion\Serion kits (0.977, 0.951, and 0.897, respectively; P < 0.01 for each comparison). In a subset analysis of 279 serum samples tested with the Bordier and Bio-Rad kits and an in-house immunoprecipitin assay (IPD), the Bordier kit had the highest sensitivity (97.7%), but the IPD tended to be more specific (71.2 and 84.7%, respectively; P = 0.10). The use of recombinant, somatic, and metabolic antigens in a single EIA improved the balance of sensitivity and specificity, resulting in an assay highly suitable for use in the diagnosis of chronic and allergic aspergillosis.
Assuntos
Anticorpos Antifúngicos/sangue , Aspergillus fumigatus/imunologia , Técnicas Imunoenzimáticas/métodos , Imunoglobulina G/sangue , Aspergilose Pulmonar/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Adulto JovemRESUMO
The diagnosis and follow-up of candidemia still rely on blood cultures (BCs). In vitro studies show that antifungals can significantly modify the result of blood culture not containing adsorbing agents. We aimed to evaluate, under clinical conditions, the impact on BC yeast detection of systemic antifungal therapy (SAT). Patients (n = 125) experiencing candidemia at Grenoble University Hospital (France) were included in a 4-year retrospective study. The Plus Aerobic/F (Aerobic) and Plus Anaerobic/F (Anaerobic) bottles, which both contain adsorbing resins and the non-resin selective Mycosis IC/F (Mycosis) bottles, were compared using multivariate hierarchical models adjusted for clinical characteristics. The positivity rate (PR) is decreased in patients with SAT (p < 0.01), abdominal surgery (p = 0.01), and hemodialysis (p = 0.02). In all bottles, SAT reduces PR by a factor of 0.16 (95 % CI: [0.08; 0.32]) and increases the time to positivity (TTP) by a factor of 1.76 ([1.30; 2.40]; p < 0.01). In the presence of SAT, TTP is higher in non-resin bottles (Mycosis) than in resin bottles (RR = 1.76, [1.30; 2.40]); however, the TTP in nonresin and resin bottles remains comparable. Although discordant results are observed with and without SAT (37 and 58 % respectively), we showed that the presence of SAT decreases significantly the agreement rate by a factor of 0.29 (CI: [0.12; 0.68]). The combination of Anaerobic and Mycosis bottles allowed a 100 % positivity rate for C. glabrata. SAT significantly affects BC results. Because they provide additional and complementary results, this study supports the concomitant use of resin and selective bottles, especially in patients receiving SAT.
Assuntos
Antifúngicos/uso terapêutico , Candida , Candidemia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Idoso , Candida/isolamento & purificação , Candidíase/diagnóstico , Feminino , Humanos , Masculino , Técnicas Microbiológicas , Pessoa de Meia-Idade , Razão de Chances , Estudos RetrospectivosRESUMO
BACKGROUND: Whether women are more or equally susceptible to the carcinogenic effects of cigarette smoke on the lungs compared with men is a matter of controversy. Using a large French population-based case-control study, we compared the lung cancer risk associated with cigarette smoking by gender. METHODS: The study included 2276 male and 650 female cases and 2780 male and 775 female controls. Lifetime smoking exposure was represented by the comprehensive smoking index (CSI), which combines the duration, intensity and time since cessation of smoking habits. The analysis was conducted among the ever smokers. All of the models were adjusted for age, department (a regional administrative unit), education and occupational exposures. RESULTS: Overall, we found that the lung cancer risk was similar among men and women. However, we found that women had a two-fold greater risk associated with a one-unit increase in CSI than men of developing either small cell carcinoma (OR=15.9, 95% confidence interval (95% CI) 7.6, 33.3 and 6.6, 95% CI 5.1, 8.5, respectively; P<0.05) or squamous cell carcinoma (OR=13.1, 95% CI 6.3, 27.3 and 6.1, 95% CI 5.0, 7.3, respectively; P<0.05). The association was similar between men and women for adenocarcinoma. CONCLUSION: Our findings suggest that heavy smoking might confer to women a higher risk of lung cancer as compared with men.
Assuntos
Neoplasias Pulmonares/epidemiologia , Fumar/epidemiologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/etiologia , Idoso , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Pequenas/etiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Feminino , França/epidemiologia , Humanos , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Risco , Fatores Sexuais , Fumar/efeitos adversosRESUMO
Aflatoxin B1 (AFB1) is a carcinogenic mycotoxin produced by Aspergilli of the section Flavi that may contaminate food, in the field or during storage. Cassava represents an important staple food in sub-Saharan Africa. The analysis of aflatoxigenic fungi in 36 cassava samples obtained from producers in Benin indicated that 40% were contaminated by Aspergilli of the section Flavi. Upon morphological and molecular characterization of the 20 isolates, 16 belonged to Aspergillus flavus, 2 to Aspergillus parvisclerotigenus and 2 to Aspergillus novoparasiticus. This is the first time that this latter species is isolated from food. Although most of these isolates were toxigenic on synthetic media, no AFB1 contamination was observed in these cassava samples. In order to determine the action of cassava on AFB1 synthesis, a highly toxigenic strain of A. flavus, was inoculated onto fresh cassava and despite a rapid development, no AFB1 was produced. The anti-aflatoxin property was observed with cassava from different geographical origins and on other aflatoxigenic strains of the section Flavi, but it was lost after heating, sun drying and freezing. Our data suggest that fresh cassava is safe regarding AFB1 contamination, however, processing may alter its ability to block toxinogenesis leading to secondary contamination.
Assuntos
Aflatoxina B1/metabolismo , Aspergillus flavus/isolamento & purificação , Manihot/microbiologia , Verduras/microbiologia , Aspergillus/classificação , Aspergillus/isolamento & purificação , Aspergillus/metabolismo , Aspergillus flavus/classificação , Aspergillus flavus/metabolismo , Contaminação de Alimentos/análiseRESUMO
BACKGROUND: Nivolumab is the first immune checkpoint inhibitor approved in Europe for the treatment of advanced renal cell carcinoma (aRCC) in patients resistant to prior antiangiogenic therapy. WITNESS is an ongoing, prospective, observational study designed to evaluate the effectiveness and safety of nivolumab in patients with aRCC treated in real life (or routine practice) in France (ClinicalTrials.gov identifier: NCT03455452). PATIENTS AND METHODS: This study includes adult patients with a confirmed diagnosis of aRCC who have initiated nivolumab after 1-2 prior lines of antiangiogenic therapy. Endpoints include overall survival (OS), progression-free survival (PFS), duration of treatment (DOT), duration of response (DOR), overall response rate (ORR), subgroup analyses, and treatment-related adverse events (TRAEs). Results after a median follow-up of 12.3 months are presented here. RESULTS: A total of 325 patients with aRCC were included, of whom 38.2% had a Karnofsky score <80, 77.8% received nivolumab as second-line therapy, and 69.5% had undergone a previous nephrectomy. In the overall population, median OS was 20.5 [95% confidence interval (CI) 17.6-25.0] months and median PFS was 5.2 (95% CI 4.5-5.9) months. ORR was 34.5%, median DOT was 3.8 months, and median DOR was 16.5 months. Nivolumab was effective in different subgroups including patients with bone or glandular metastases and those receiving baseline corticosteroids. Moreover, effectiveness was observed irrespective of prior nephrectomy and line of treatment. No new safety signals were identified; TRAEs of any grade were reported in 32.0% of patients, grade ≥3 and serious TRAEs in 11.1% each, and TRAEs leading to discontinuation in 8.9%. CONCLUSIONS: Preliminary results of the ongoing WITNESS study confirm the real-world effectiveness and safety of nivolumab monotherapy in previously treated patients with aRCC. Treatment benefits were similar to those observed in the pivotal phase III CheckMate 025 randomized clinical trial, despite a broader, real-life study population.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Nivolumabe , Humanos , Nivolumabe/uso terapêutico , Nivolumabe/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Feminino , Masculino , França , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Intervalo Livre de ProgressãoRESUMO
The signaling pathway of the bone morphogenetic protein (BMP)-9 binding to the endothelial receptor BMP receptor type II (BMPR-II), activin receptor-like kinase-1 (ALK1) and the coreceptor endoglin is essential to maintain the pulmonary vascular integrity. Dysregulation of this pathway is implicated in numerous vascular diseases, such as pulmonary arterial hypertension (PAH), hereditary hemorrhagic telangiectasia (HHT) and hepatopulmonary syndrome (HPS). This article aims to provide a comprehensive review of the implication of the BMP-9/BMPR-II/ALK1/endoglin pathway in the pathophysiology of these diseases.
Assuntos
Fator 2 de Diferenciação de Crescimento , Telangiectasia Hemorrágica Hereditária , Humanos , Endoglina , Transdução de Sinais/fisiologia , Pulmão , Telangiectasia Hemorrágica Hereditária/complicaçõesRESUMO
INTRODUCTION: Investigation for obstructive sleep apnea syndrome (OSAS) is mandatory before bariatric surgery. Data regarding chronic insomnia and chronic sleep deprivation are scarce in this population. METHODS: A cross-sectional study assessing the prevalence of chronic insomnia, OSAS and chronic sleep privation in an obese population referred for bariatric surgery. RESULTS: In all, 88 patients (74% women, median age 41 [33.5-50] years and median body mass index 42 [39.2-45.7] kg/m2) were included. The prevalence of chronic insomnia was 31% in the 87% suffering from OSAS that required continuous positive airway pressure therapy. Comorbid insomnia and sleep apnoea (COMISA) were found in 27% of our population. Chronic insomnia was associated with a lower quality of life (median EQ5D analogue visual scale: 60 [50-70] P=0.04) and a poor sleep quality (median Pittsburgh sleep quality index (PSQI): 8 (6-11 P<0.01) The deleterious combination of sleep privation and insomnia had a higher impact in terms of impairment of quality of life and sleep quality (median EQ5D analogue visual scale: 50 [40-65] P=0.02 et median PSQI: 11 [9-14, P<0.01) CONCLUSION: Chronic insomnia and sleep privation have synergistic deleterious effects in candidates for bariatric surgery. Further studies need to be conducted to evaluate the evolution after surgery.
Assuntos
Cirurgia Bariátrica , Qualidade de Vida , Adulto , Pressão Positiva Contínua nas Vias Aéreas , Estudos Transversais , Feminino , Humanos , Masculino , SonoRESUMO
BACKGROUND: Colonization pressure is a risk factor for intensive care unit (ICU)-acquired multi-drug-resistant organisms (MDROs). AIM: To measure the long-term respective impact of colonization pressure on ICU-acquired extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) and meticillin-resistant Staphylococcus aureus (MRSA). METHODS: All patients admitted to two ICUs (medical and surgical) between January 1997 and December 2015 were included in this retrospective observational study. Rectal and nasal surveillance cultures were obtained at admission and weekly thereafter. Contact precautions were applied for colonized or infected patients. Colonization pressure was defined as the ratio of the number of MDRO-positive patient-days (PDs) of each MDRO to the total number of PDs. Single-level negative binomial regression models were used to evaluate the incidence of weekly MDRO acquisition. FINDINGS: Among the 23,423 patients included, 2327 (10.0%) and 1422 (6.1%) were colonized with ESBL-PE and MRSA, respectively, including 660 (2.8%) and 351 (1.5%) acquisitions. ESBL-PE acquisition increased from 0.51/1000 patient-exposed days (PEDs) in 1997 to 6.06/1000 PEDs in 2015 (P<0.001). In contrast, MRSA acquisition decreased steadily from 3.75 to 0.08/1000 PEDs (P<0.001). Controlling for period-level covariates, colonization pressure in the previous week was associated with MDRO acquisition for ESBL-PE (P<0.001 and P=0.04 for medical and surgical ICU, respectively), but not for MRSA (P=0.34 and P=0.37 for medical and surgical ICU, respectively). The increase in colonization pressure was significant above 100/1000 PDs for ESBL-PE. CONCLUSION: Colonization pressure contributed to the increasing incidence of ESBL-PE but not MRSA. This study suggests that preventive control measures should be customized to MDROs.
Assuntos
Infecção Hospitalar/diagnóstico , Enterobacteriaceae , Monitoramento Ambiental/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Staphylococcus aureus Resistente à Meticilina , Adulto , Idoso , Antibacterianos/farmacologia , Portador Sadio , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Incidência , Controle de Infecções , Masculino , Meticilina/farmacologia , Pessoa de Meia-Idade , Paris , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo , beta-LactamasesRESUMO
To evaluate the value of apnoea + hypopnoea index versus self-reported sleepiness at the wheel in anticipating the risk of sleepiness-related accidents in patients referred for obstructive sleep apnoea. A cross-sectional analysis of the French national obstructive sleep apnoea registry. 58,815 subjects referred for a suspicion of obstructive sleep apnoea were investigated by specific items addressing sleepiness at the wheel and sleepiness-related accidents. Apnoea + hypopnoea index was evaluated with a respiratory polygraphy or full polysomnography. Subjects had a median age of 55.6 years [45.3; 64.6], 65% were men, with a median apnoea + hypopnoea index of 22 [8; 39] events/h. Median Epworth sleepiness scale score was 9 [6; 13], 35% of the patients reported sleepiness at the wheel (n = 20,310), 8% (n = 4,588) reported a near-miss accident and 2% (n = 1,313) reported a sleepiness-related accident. Patients reporting sleepiness at the wheel whatever their obstructive sleep apnoea status and severity exhibited a tenfold higher risk of sleepiness-related accidents. In multivariate analysis, other predictors for sleepiness-related accidents were: male gender, ESS, history of previous near-miss accidents, restless leg syndrome/periodic leg movements, complaints of memory dysfunction and nocturnal sweating. Sleep apnoea per se was not an independent contributor. Self-reported sleepiness at the wheel is a better predictor of sleepiness-related traffic accidents than apnoea + hypopnoea index.
Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Apneia Obstrutiva do Sono/complicações , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Fatores de Risco , Autorrelato , Apneia Obstrutiva do Sono/diagnóstico , SonolênciaRESUMO
BACKGROUND: Transient and persistent acute kidney injury (AKI) could share similar physiopathological mechanisms. The objective of our study was to assess prognostic impact of AKI duration on ICU mortality. DESIGN: Retrospective analysis of a prospective database via cause-specific model, with 28-day ICU mortality as primary end point, considering discharge alive as a competing event and taking into account time-dependent nature of renal recovery. Renal recovery was defined as a decrease of at least one KDIGO class compared to the previous day. SETTING: 23 French ICUs. PATIENTS: Patients of a French multicentric observational cohort were included if they suffered from AKI at ICU admission between 1996 and 2015. INTERVENTION: None. RESULTS: A total of 5242 patients were included. Initial severity according to KDIGO creatinine definition was AKI stage 1 for 2458 patients (46.89%), AKI stage 2 for 1181 (22.53%) and AKI stage 3 for 1603 (30.58%). Crude 28-day ICU mortality according to AKI severity was 22.74% (n = 559), 27.69% (n = 327) and 26.26% (n = 421), respectively. Renal recovery was experienced by 3085 patients (58.85%), and its rate was significantly different between AKI severity stages (P < 0.01). Twenty-eight-day ICU mortality was independently lower in patients experiencing renal recovery [CSHR 0.54 (95% CI 0.46-0.63), P < 0.01]. Lastly, RRT requirement was strongly associated with persistent AKI whichever threshold was chosen between day 2 and 7 to delineate transient from persistent AKI. CONCLUSIONS: Short-term renal recovery, according to several definitions, was independently associated with higher mortality and RRT requirement. Moreover, distinction between transient and persistent AKI is consequently a clinically relevant surrogate outcome variable for diagnostic testing in critically ill patients.
RESUMO
BACKGROUND: Serological investigation of Toxoplasma gondii can answer many questions about toxoplasmosis in human pathology. Along these lines, studies on serum storage in biobanks need to be performed especially in terms of determining the impact of storage on relevance of sera analysis after freezing. This study assessed the impact of long-term sera storage on the stability of anti-Toxoplasma immunoglobulins. MATERIAL AND METHODS: The stability of anti-Toxoplasma IgG and IgM was studied in 244 and 242 sera respectively, stored at -20°C from one month to ten years. ELISA-immunoassay (Vidas®, bioMérieux) was used for initial and post-storage analyses. Linear models for repeated measures and subgroup analyses were performed to assess the effect of storage duration and sample characteristics on immunoglobulins stability. RESULTS: Until ten years, the variability attributed to storage (maximum 8.07% for IgG, 13.17% for IgM) was below the variations inherent to the serological technique and allowed by quality assurance systems (15%). Subgroup analysis reported no variation attributed to sera storage. Serological interpretation was modified for 3 sera (1.2%) tested for IgM, all stored more than seven years. CONCLUSION: Anti-Toxoplasma immunoglobulins can reliably be measured for at least up to six years of storage with no modification of interpretation of toxoplasmosis serologies.