COVID-19 increased the risk of ICU-acquired bloodstream infections: a case-cohort study from the multicentric OUTCOMEREA network.
- 作者列表："Buetti N","Ruckly S","de Montmollin E","Reignier J","Terzi N","Cohen Y","Siami S","Dupuis C","Timsit JF
PURPOSE:The primary objective of this study was to investigate the risk of ICU bloodstream infection (BSI) in critically ill COVID-19 patients compared to non-COVID-19 patients. Subsequently, we performed secondary analyses in order to explain the observed results. METHODS:We conducted a matched case-cohort study, based on prospectively collected data from a large ICU cohort in France. Critically ill COVID-19 patients were matched with similar non-COVID-19 patients. ICU-BSI was defined by an infection onset occurring > 48 h after ICU admission. We estimated the effect of COVID-19 on the probability to develop an ICU-BSI using proportional subdistribution hazards models. RESULTS:We identified 321 COVID-19 patients and 1029 eligible controls in 6 ICUs. Finally, 235 COVID-19 patients were matched with 235 non-COVID-19 patients. We observed 43 ICU-BSIs, 35 (14.9%) in the COVID-19 group and 8 (3.4%) in the non-COVID-19 group (p ≤ 0.0001), respectively. ICU-BSIs of COVID-19 patients were more frequently of unknown source (47.4%). COVID-19 patients had an increased probability to develop ICU-BSI, especially after 7 days of ICU admission. Using proportional subdistribution hazards models, COVID-19 increased the daily risk to develop ICU-BSI (sHR 4.50, 95% CI 1.82-11.16, p = 0.0012). Among COVID-19 patients (n = 235), a significantly increased risk for ICU-BSI was detected in patients who received tocilizumab or anakinra (sHR 3.20, 95% CI 1.31-7.81, p = 0.011) but not corticosteroids. CONCLUSIONS:Using prospectively collected multicentric data, we showed that the ICU-BSI risk was higher for COVID-19 than non-COVID-19 critically ill patients after seven days of ICU stay. Clinicians should be particularly careful on late ICU-BSIs in COVID-19 patients. Tocilizumab or anakinra may increase the ICU-BSI risk.
目的: 本研究的主要目的是调查新型冠状病毒肺炎例危重患者与非新型冠状病毒肺炎例患者相比，ICU血流感染 (BSI) 的风险。随后，我们进行了二次分析以解释观察到的结果。 方法: 我们进行了一项匹配的病例队列研究，该研究基于前瞻性收集的来自法国大型ICU队列的数据。危重症新型冠状病毒肺炎例患者与相似的非新型冠状病毒肺炎例患者相匹配。ICU-BSI定义为ICU入院后> 48 h发生感染。我们使用比例分布风险模型估计了新型冠状病毒肺炎对发生ICU-BSI概率的影响。 结果: 我们在6个icu中确定了321例新型冠状病毒肺炎患者和1029例合格对照。最后，235名新型冠状病毒肺炎患者与235名非新型冠状病毒肺炎患者匹配。我们观察到43例ICU-BSIs，新型冠状病毒肺炎组35例 (14.9%)，非新型冠状病毒肺炎组8例 (3.4%) (p ≤≤ 0.0001)。新型冠状病毒肺炎例患者的ICU-bsi更常见 (47.4%)。新型冠状病毒肺炎的患者发生ICU-BSI的概率增加，特别是在ICU入院7天后。使用比例子分布风险模型，新型冠状病毒肺炎增加了发生ICU-BSI的每日风险 (sHR 4.50，95% CI 1.82-11.16，p = 0.0012)。在新型冠状病毒肺炎例患者 (n = 235) 中，在接受托珠单抗或anakinra (sHR 3.20，95% CI 1.31-7.81，p = 0.011) 但未接受皮质类固醇的患者中检测到ICU-BSI风险显著增加。 结论: 使用前瞻性收集的多中心数据，我们显示ICU住院7天后，新型冠状病毒肺炎的ICU-BSI风险高于非新型冠状病毒肺炎重症患者。临床医生应特别小心新型冠状病毒肺炎例患者的晚期ICU-BSIs。托珠单抗或anakinra可能会增加ICU-BSI风险。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.