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BackgroundSubphenotypes were recently reported within clinical acute respiratory distress syndrome (ARDS), with distinct outcomes and therapeutic responses. Experimental models have long been used to mimic features of ARDS pathophysiology, but the presence of distinct subphenotypes among preclinical ARDS remains unknown. This review will investigate whether: 1) subphenotypes can be identified among preclinical ARDS models; 2) such subphenotypes can identify some responsive traits.MethodsWe will include comparative preclinical (in vivo and ex vivo) ARDS studies published between 2009 and 2019 in which pre-specified therapies were assessed (interleukin (IL)-10, IL-2, stem cells, beta-agonists, corticosteroids, fibroblast growth factors, modulators of the receptor for advanced glycation end-products pathway, anticoagulants, and halogenated agents) and outcomes compared to a control condition. The primary outcome will be a composite of the four key features of preclinical ARDS as per the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar-capillary barrier, lung inflammatory response, and physiological dysfunction). Secondary outcomes will include the single components of the primary composite outcome, net alveolar fluid clearance, and death. MEDLINE, Embase, and Cochrane databases will be searched electronically and data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments guidelines. Meta-regressions will be performed to identify subphenotypes prior to comparing outcomes across subphenotypes and treatment effects.DiscussionThis study will inform on the presence and underlying pathophysiological features of subphenotypes among preclinical models of ARDS and should help to determine whether sufficient evidence exists to perform preclinical trials of subphenotype-targeted therapies, prior to potential clinical translation.Systematic review registrationPROSPERO (ID: CRD42019157236).

Introduction: The COVID-19 pandemic has been associated with significant variability in acute kidney injury (AKI) incidence, leading to concerns regarding patient heterogeneity. The study's primary objective was a cluster analysis, to identify homogeneous subgroups of patients (clusters) using baseline characteristics, including inflammatory biomarkers. The secondary objectives were the comparisons of MAKE-90 and mortality between the different clusters at three months. Methods: This retrospective single-center study was conducted in the Medical Intensive Care Unit of the University Hospital of Clermont-Ferrand, France. Baseline data, clinical and biological characteristics on ICU admission, and outcomes at day 90 were recorded. The primary outcome was the risk of major adverse kidney events at 90 days (MAKE-90). Clusters were determined using hierarchical clustering on principal components approach based on admission characteristics, biomarkers and serum values of immune dysfunction and kidney function. Results: It included consecutive adult patients admitted between March 20, 2020 and February 28, 2021 for severe COVID-19. A total of 149 patients were included in the study. Three clusters were identified of which two were fully described (cluster 3 comprising 2 patients). Cluster 1 comprised 122 patients with fewer organ dysfunctions, moderate immune dysfunction, and was associated with reduced mortality and a lower incidence of MAKE-90. Cluster 2 comprised 25 patients with greater disease severity, immune dysfunction, higher levels of suPAR and L-FABP/U Creat, and greater organ support requirement, incidence of AKI, day-90 mortality and MAKE-90. Conclusions: This study identified two clusters of severe COVID-19 patients with distinct biological characteristics and renal event risks. Such clusters may help facilitate the identification of targeted populations for future clinical trials. Also, it may help to understand the significant variability in AKI incidence observed in COVID-19 patients. [ABSTRACT FROM AUTHOR]

The objective of our study was to evaluate serum CX3CL1/Fractalkine, a monocyte/macrophage chemoattractant expressed in cytotrophoblasts and decidual cells, as a predictive biomarker for the occurrence of preterm premature rupture of membranes (PPROM). A case-control study of 438 pregnancies including 82 PPROM cases and 64 preterm labor with intact membranes cases with blood samples collected at first trimester, second trimester and delivery was conducted. The predictive ability of CX3CL1 and maternal risk factors for the occurrence of PPROM was assessed by receiver operating characteristic curve analysis. A second, independent cohort was prospectively constituted to confirm the case-control study results. First trimester CX3CL1 was significantly increased in PPROM cases when compared to matched controls. Multivariate regression analysis highlighted a significant difference for CX3CL1 measured during the first trimester (p<0.001). Alone, CX3CL1 predicts PPROM with a 90 % sensitivity and a specificity around 40 %. The area under the receiver operating characteristic curve for PPROM prediction were 0.64 (95% confidence interval: 0.57–0.71) for first trimester CX3CL1, and 0.61 (95% confidence interval: 0.54–0.68) for maternal risk factors (body mass index<18.5 kg/m2, nulliparity, tobacco use and the absence of high school diploma). The combination of CX3CL1 and maternal risk factors significantly improved the area under the curve: 0.72 (95% confidence interval: 0.66–0.79) (p<0.001). The results were confirmed on a second independent cohort. CX3CL1 is a promising blood biomarker in the early (first trimester) prediction of PPROM. [ABSTRACT FROM AUTHOR]

The measurement of blood glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) may assist in the management of mild traumatic brain injury (mTBI). This study aims to compare GFAP and UCH-L1 values measured using a handheld device with those measured using a core laboratory platform. We enrolled 230 mTBI patients at intermediate risk of complications. Following French guidelines, a negative S100B value permits the patient to be discharged without a computed tomography scan. Plasma GFAP and UCH-L1 levels were retrospectively measured using i-STAT® and Alinity® i analyzers in patients managed within 12 h post-trauma. Our analysis indicates a strong correlation of biomarker measurements between the two analyzers. Cohen's kappa coefficients and Lin's concordance coefficients were both ≥0.7, while Spearman's correlation coefficient was 0.94 for GFAP and 0.90 for UCH-L1. Additionally, the diagnostic performance in identifying an intracranial lesion was not significantly different between the two analyzers, with a sensitivity of 100% and specificity of approximately 30%. GFAP and UCH-L1 levels measured using Abbott's i-STAT® and Alinity® i platform assays are highly correlated both analytically and clinically in a cohort of 230 patients managed for mTBI according to French guidelines. [ABSTRACT FROM AUTHOR]

To compare for the first time the performance of "GFAP and UCH-L1" vs. S100B in a cohort of patients managed for mild traumatic brain injury (mTBI) according to actualized French guidelines. A prospective study was recently carried at the Emergency Department of Clermont-Ferrand University Hospital in France. Patients with mTBI presenting a medium risk of complications were enrolled. Blood S100B and "GFAP and UCHL-1" were sampled and measured according to French guidelines. S100B was measured in patients with samples within 3 h of trauma (Cobas®, Roche Diagnostics), while GFAP and UCHL-1 were measured in all patients (samples <3 h and 3–12 h) using another automated assay (i-STAT® Alinity, Abbott). For sampling <3 h, serum S100B correctly identifies intracranial lesions with a specificity of 25.7 % (95 % CI; 19.5–32.6 %), a sensitivity of 100 % (95 % CI; 66.4–100 %), and a negative predictive value of 100 % (95 % CI; 92.5–100 %). For sampling <12 h, plasma "GFAP and UCH-L1" levels correctly identify intracranial lesions with a specificity of 31.7 % (95 % CI; 25.7–38.2 %), a sensitivity of 100 % (95 % CI; 73.5–100 %), and a negative predictive value of 100 % (95 % CI; 95–100 %). Comparison of specificities (25.7 vs. 31.7 %) did not reveal a statistically significant difference (p=0.16). We highlight the usefulness of measuring plasma "GFAP and UCH-L1" levels to target mTBI patients (sampling within 12 h post-injury) and optimize the reduction of CT scans. [ABSTRACT FROM AUTHOR]

We conducted a prospective double-blind study to compare two vaginal diagnostic methods in singleton pregnancies with threatened preterm labor (TPL) at the University Hospital of Clermont-Ferrand (France) from August 2018 to December 2020. Our main objective was to compare the diagnostic capacity at admission, in terms of positive predictive value (PPV) and negative predictive value (NPV), of Premaquick® (combined detection of IL-6/total IGFBP-1/native IGFBP-1) and QuikCheck fFN™ (fetal fibronectin) for delivery within 7 days in cases of TPL. We included 193 patients. Premaquick® had a sensitivity close to 89%, equivalent to QuikCheck fFN™, but a higher statistical specificity of 49.5% against 38.6% for QuikCheck fFN™. We found no superiority of Premaquick® over QuickCheck fFN™ in terms of PPV (6.6% vs. 7.9%), with NPV being equivalent in predicting childbirth within 7 days in cases of TPL (98.6% vs. 98.9%). Nevertheless, the combination of positive native and total IGFBP-1 and the combination of all three positive markers were associated with a higher PPV. Our results, though non-significant, support this combined multiple-biomarker approach to improve testing in terms of predictive values. [ABSTRACT FROM AUTHOR]

The objective of our study is to evaluate the effect of storage temperature and time to analysis on arterial blood gas parameters in order to extend the CLSI recommendations. Stability of 12 parameters (pH, pCO₂, pO₂, Na+, K+, Ca2+, glucose, lactate, hemoglobin, oxyhemoglobin, carboxyhemoglobin, methemoglobin) measured by GEM PREMIER™ 5000 blood gas analyzer was studied at room temperature and at +4 °C (52 patients). The storage times were 30, 45, 60, 90 and 120 min. Stability was evaluated on the difference from baseline, the difference from the analyte-specific measurement uncertainty applied to the baseline value, and the impact of the variation on the clinical interpretation. At room temperature, all parameters except the lactate remained stable for at least 60 min. A statistically significant difference was observed for pH at T45 and T60 and for pCO2 at T60 without modification of clinical interpretation. For lactate, clinical interpretation was modified from T45 and values were outside the range of acceptability defined by the measurement uncertainty. All parameters except pO2 remained stable for at least 120 min at +4 °C. A one-hour transport at room temperature is compatible with the performance of all the analyses studied except lactate. If the delay exceeds 30 min, the sample should be placed at +4 °C for lactate measurement. If the samples are stored in ice, it is important to note that the pO2 cannot be interpreted. [ABSTRACT FROM AUTHOR]