Diagnostic Accuracy of Posterior/Anterior Periventricular WMH Ratio to Differentiate CAA From Hypertensive Arteriopathy.

BACKGROUND: Periventricular white matter hyperintensities (PVWMHs) in cerebral amyloid angiopathy (CAA) have been reported posterior predominant using semiautomated segmentation method and logarithmic transformation. We aimed to compare PVWMH extent and posterior/anterior distribution between patients with CAA and patients with hypertensive arteriopathy with radiological tools available in daily practice. METHODS: We retrospectively analyzed confluent PVWMH directly adjacent to lateral ventricles on axial FLAIR (fluid-attenuated inversion recovery) from 108 patients with CAA and 99 patients with hypertensive arteriopathy presenting with hemorrhage-related symptoms consecutively recruited in our stroke database (Nîmes University Hospital, France) between January 2015 and March 2022. For each of the left (L), right (R), anterior (A), and posterior (P) horns of lateral ventricles, the maximal distance between the outer PVWMH border and ventricle border was measured. The sum of anterior left PVWMH and anterior right PVWMH, and posterior left PVWMH and posterior right PVWMH resulted in anterior and posterior extent, respectively. RESULTS: Compared with hypertensive arteriopathy, patients with CAA were older (median, 77 versus 71; P=0.0010) and less frequently male (46% versus 64%; P=0.012) and had less frequent hypertension (45% versus 63%; P=0.013) and more chronic hemorrhages (P<0.0001). CAA showed slightly more extensive anterior right PVWMH (median, 6.50 versus 5.90 mm; P=0.034), far more extensive (all P<0.0001) posterior left PVWMH (median, 13.95 versus 6.95 mm), posterior right PVWMH (median, 14.15 versus 5.45 mm), posterior (median, 27.95 versus 13.00 mm), and total (median, 39.60 versus 24.65 mm) PVWMH, and higher posterior/anterior ratios (median, 1.82 versus 1.01). Age-/sex-adjusted model predicting CAA incorporating total PVWMH extent and posterior/anterior ratios for the given score (-4.3683+0.0268×PVWMH-T+0.3749×posterior/anterior PVWMH ratio+0.0394×age+0.3046 when female) showed highest area under the curve (0.76 [0.70-0.83]), with a 72% [62.50-80.99] sensitivity and 76% [67.18-84.12] specificity. Values above the optimal threshold of 0.22 for the score showed a crude relative risk of 2.75 (2.26-2.37; P<0.0001). CONCLUSIONS: Severe posterior PVWMH and high posterior/anterior PVWMH ratio assessed by radiological tools used in daily practice are associated with probable CAA versus hypertensive arteriopathy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05486897.

Dementia and glaucoma: Results from a Nationwide French Study between 2006 and 2018.

PURPOSE: Glaucoma is the leading cause of irreversible blindness worldwide. The brain and eye share many characteristics, so the eye may provide an easy-access window on brain processes. The aim of the study was to evaluate the link between glaucoma as well as intraocular pressure (IOP)-lowering drops load and all-cause dementia. METHODS: This was a nested case-control study based on the French national healthcare database from 1 January 2006 to 31 December 2018in individuals aged ≥60 years. We compared cases of incident all-cause dementia with 1:5 controls matched by date of case diagnosis (index date), age, sex, and income. We set a 5-year exposure to glaucoma period ending 2 years before the index date (lag-time period to avoid protopathic bias). The main outcome was glaucoma defined with hospitalization related to POAG and/or dispensations of IOP-lowering drops. The secondary outcome was the IOP-lowering drops load. RESULTS: In total, 4810 incident all-cause dementia and 24 050 matched controls were analysed (median [IQR] age 82 [10] years; 66.6% women). The prevalence of glaucoma was 14.0% in controls and cases. Risk of all-cause dementia was not associated with glaucoma (crude OR, 1.02; 95% CI [0.93-1.11]; p = 0.7; adjusted OR, 0.99; 95% CI [0.91-1.09]; p = 0.9) or IOP-lowering drops load (p = 0.2). CONCLUSION: The present study in general population ≥60 years old in France did not find any association between glaucoma and incident all-cause dementia.

Addressing unmeasured confounders in cohort studies: Instrumental variable method for a time-fixed exposure on an outcome trajectory.

Instrumental variable methods, which handle unmeasured confounding by targeting the part of the exposure explained by an exogenous variable not subject to confounding, have gained much interest in observational studies. We consider the very frequent setting of estimating the unconfounded effect of an exposure measured at baseline on the subsequent trajectory of an outcome repeatedly measured over time. We didactically explain how to apply the instrumental variable method in such setting by adapting the two-stage classical methodology with (1) the prediction of the exposure according to the instrumental variable, (2) its inclusion into a mixed model to quantify the exposure association with the subsequent outcome trajectory, and (3) the computation of the estimated total variance. A simulation study illustrates the consequences of unmeasured confounding in classical analyses and the usefulness of the instrumental variable approach. The methodology is then applied to 6224 participants of the 3C cohort to estimate the association of type-2 diabetes with subsequent cognitive trajectory, using 42 genetic polymorphisms as instrumental variables. This contribution shows how to handle endogeneity when interested in repeated outcomes, along with a R implementation. However, it should still be used with caution as it relies on instrumental variable assumptions hardly testable in practice.

Relationship between Lean Tissue Mass and Muscle Function in Women with Obesity.

It is well documented that lean tissue mass (LTM) decreases with aging in patients with obesity, but there is no information available regarding muscle strength changes, a parameter that may be better associated with sarcopenic obesity (SO). The objectives of this study were to analyze the changes in LTM and fat mass (FM), muscle strength and muscle function with aging in women with obesity and to determine the prevalence of SO. LTM and FM were determined by DXA, muscle strength with the hand-grip test and muscle function with the 6 min walk test (6MWT) in 383 women with obesity. A redistribution of the LTM and FM occurred with age, characterized by a gain at the trunk to the detriment of the lower limbs, thus reducting in appendicular LTM indices. The physical performances evaluated by the muscle strength and muscle function decreased concomitantly, and the prevalence of low values for both these parameters was 22.8% and 13.4%, respectively, in the older patients. In summary, although a reduction in appendicular LTM and muscle performances occurred with age and resulted in an increase in the prevalence of SO, the number of women with obesity affected by SO remained low (n ≤ 15), even in those older than 60 years.

Cross-Calibration Study of The Stratos And Hologic QDR 4500A Dual-Energy X-Ray Absorptiometers to Assess Bone Mineral Density And Body Composition.

The objective of the study was to assess the agreement between the Stratos (DMS) and QDR 4500A (Hologic) DXAs in determining whole body and regional aBMD, as well as whole body composition. Fifty-five individuals (46 women: 84%) with a mean age of 41 ± 13.0 years (range: 20 to 64) and a mean BMI of 31.9 ± 10 kg/m² (range: 12.2 to 49.5) were consecutively scanned on the same day using the two devices. Predictive equations for areal bone mineral density (aBMD) and whole body composition (WBC) were derived from linear regression of the data. The two DXAs were highly correlated (p<0.001 for all parameters) with a correlation coefficient (r) ranging from 0.89 to 0.99 for aBMD (r=0.89 for whole body, r=0.92 for radius, r=0.95 for femoral neck, r=0.96 for total hip, and r=0.99 for L1-L4). For WBC, the r value was 0.98 for lean tissue mass (LTM) and 1.0 for fat mass (FM). Paired t-tests indicated a statistically significant bias between the two DXAs for the majority of measurements, requiring the determination of specific cross-calibration equations. Compared to QDR 4500A, Stratos underestimated whole body aBMD and LTM and overestimated neck and hip aBMD and whole body FM. Conversely, no significant bias was demonstrated for mean aBMD at L1-L4 and radius. For whole body aBMD and FM, the concordance between the two DXAs was influenced by BMI. Despite a high concordance between the two DXAs, the systematic bias for aBMD and WBC measurements illustrates the need to define cross-calibration equations to compare data across systems.

Whole-body vibration may not affect bone mineral density and bone turnover in persons with chronic spinal cord injury: A preliminary study.

CONTEXT: Spinal-cord injury (SCI) induces bone loss and dramatically increases the risk of fracture. OBJECTIVES: Determine the effects of whole-body vibration (WBV) on areal bone mineral density (aBMD), whole body composition and bone biological parameters in individuals with chronic-state SCI. DESIGN: Randomized study. SETTING: Centre Neurologique PROPARA. PARTICIPANTS: Fourteen subjects were randomly assigned to a WBV or a control group. INTERVENTIONS: WBV (20-45 min, 30-45 Hz, 0.5 g) was performed in verticalized persons twice weekly for 6 months. OUTCOME MEASURES: aBMD was measured by DXA at baseline and 6 months and bone biological parameters at baseline, 1, 3 and 6 months. RESULTS: No significant aBMD change was found in either the WBV or control group after 6 months of follow-up. Similarly, periostin, sclerostin and bone turnover markers remained relatively stable throughout follow-up and no difference in variation was observed within-group and between groups. Except for whole-body fat mass, which showed a significant decrease in the WBV group compared to controls, no difference in changes was observed, whatever the localization for fat and lean body mass. CONCLUSIONS: During the chronic phase, aBMD and bone remodeling reach a new steady state. However, the DXA technique and the bone markers, including sclerostin and periostin, both of which reflect bone cell activity influenced by mechanical strain, showed that the bone tissue of individuals with SCI was insensitive to 6 months of WBV training at the study dose. Nevertheless, results of this preliminary study that was underpowered need to be confirmed and other modalities of WBV may be more effective in improving aBMD of this population. TRIALS REGISTRATION: N°IDRCB:2011-A00224-37.

Surgery in rare bleeding disorders: the prospective MARACHI study.

Background: Despite the wide use of bleeding scores and the reliability of clotting factor level measurement, bleeding risk stratification before surgery remains challenging in patients with rare inherited bleeding disorders. Objectives: This multicenter observational prospective study assessed in patients with rare coagulation factor deficiency, the perioperative hemostatic management choices by hemostasis experts and the bleeding outcomes after surgery. Methods: One hundred seventy-eight patients with low coagulation activity level (factor [F] II, FV, combined FV-FVIII, FVII, FX, or FXI <50%) underwent 207 surgical procedures. The bleeding outcome, Tosetto's bleeding score, and perioperative hemostatic protocols were collected. Results: Among the 81 procedures performed in patients with severe factor deficiency (level ≤10%), 27 were done without factor replacement (including 6 in patients at high bleeding risk), without any bleeding event. Factor replacement therapy was used mainly for orthopedic procedures. In patients with mild deficiency, 100/126 surgical procedures were carried out without perioperative hemostatic treatment. In patients with FVII or FXI deficiency, factor replacement therapy was in function of the procedure, bleeding risk, and to a lesser extent previous bleeding history. Tranexamic acid was used in almost half of the procedures, particularly in case of surgery in tissues with high fibrinolytic activity (76.8%). Conclusions: The current perioperative hemostatic management of patients with rare bleeding disorders appears to be adapted. Among the 207 procedures, only 6 were associated with excessive bleeding. Our findings suggest that rather than the bleeding score, factor level and surgery type are the most relevant criteria for perioperative factor replacement therapy.

How valid are proxy assessment of mental health and sleep comorbidities of patients with epilepsy using standardized questionnaires?

BACKGROUND: The study aimed to determine the level of agreement between patients with epilepsy and their proxies when assessing psychiatric comorbidities, sleep disorders, and medication adherence using standardized questionnaires. METHODS: This agreement study is an ancillary analysis of the PRERIES study, a matched case-control study exploring SUDEP risk factors. Controls aged 15 years and older, with active epilepsy or in remission for less than 5 years were recruited between 01/01/2011 and 03/31/2019. An interview was carried out by a trained psychologist on both the patient and a proxy-respondent. During these independent interviews, the following comorbidities were explored: psychiatric comorbidities using the MINI, the STAI- Y2 and NDDI-E scales, sleep disorders with the SDQ-SA and Epworth scales and medication adherence. Level of agreement between patient and their proxy was estimated using Gwet's AC1&2. RESULTS: Among the 107 patient-proxy dyads recruited, proxy respondents were mainly family members (65.4%) or spouses (30.8%). Exploration of present major depression showed excellent agreement at 0.81 [0.65;0.97], as well as exploration of dysthymia at 0.96 [0.61;1]. Suicidal risk evaluation had a lesser agreement at 0.77 [0.60;0.94]. Agreement on anxiety was moderate 0.5 [0.38;0.62]. For sleep disorder, SDQ-SA presented a better agreement than the Epworth questionnaire with respectively 0.73 [0.51;0.95] and 0.45 [0.26;0.63]. For medication adherence, the overall agreement rate was excellent (0.90 [0.78;1]). CONCLUSION: Exploration of potential risk factors through families can give valuable and relatively robust information, especially if the respondent lives with the patient, and should be retrieved, when possible, in usual clinical setting.

Reference Values of Cardiopulmonary Exercise Test Parameters in the Contemporary Paediatric Population.

BACKGROUND: The evaluation of health status by cardiopulmonary exercise test (CPET) has shown increasing interest in the paediatric population. Our group recently established reference Z-score values for paediatric cycle ergometer VO2max, applicable to normal and extreme weights, from a cohort of 1141 healthy children. There are currently no validated reference values for the other CPET parameters in the paediatric population. This study aimed to establish, from the same cohort, reference Z-score values for the main paediatric cycle ergometer CPET parameters, apart from VO2max. RESULTS: In this cross-sectional study, 909 healthy children aged 5-18 years old underwent a CPET. Linear, quadratic, and polynomial mathematical regression equations were applied to identify the best CPET parameters Z-scores, according to anthropometric parameters (sex, age, height, weight, and BMI). This study provided Z-scores for maximal CPET parameters (heart rate, respiratory exchange ratio, workload, and oxygen pulse), submaximal CPET parameters (ventilatory anaerobic threshold, VE/VCO2 slope, and oxygen uptake efficiency slope), and maximum ventilatory CPET parameters (tidal volume, respiratory rate, breathing reserve, and ventilatory equivalent for CO2 and O2). CONCLUSIONS: This study defined paediatric reference Z-score values for the main cycle ergometer CPET parameters, in addition to the existing reference values for VO2max, applicable to children of normal and extreme weights. Providing Z-scores for CPET parameters in the paediatric population should be useful in the follow-up of children with various chronic diseases. Thus, new paediatric research fields are opening up, such as prognostic studies and clinical trials using cardiopulmonary fitness outcomes. Trial registration NCT04876209-Registered 6 May 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04876209 .

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study.

BACKGROUND: Omalizumab (OMA) dramatically improves disease control and quality of life in patients with chronic urticaria (CU). OBJECTIVE: We aimed to evaluate the discontinuation patterns of OMA and their determinants in a cohort of French patients with CU. METHODS: We conducted a retrospective multicenter study in 9 French tertiary referral hospitals. All patients diagnosed with either spontaneous (CSU) and/or inducible (CIndU) CU who received at least 1 injection of OMA between 2009 and 2021 were included. We analyzed OMA drug survival and investigated possible determinants using Kaplan-Meier curves and log-rank tests. RESULTS: A total of 878 patients were included in this study; 48.8% had CSU, 10.1% CIndU, and 41.1% a combination of both. OMA was discontinued in 408 patients, but the drug was later reintroduced in 50% of them. The main reason for discontinuing treatment was the achievement of a well-controlled disease in 50% of patients. Half of the patients were still being treated with OMA 2.4 years after the initiation of treatment. Drug survival was shorter in patients with CIndU and in those with an autoimmune background. In atopic patients, OMA was discontinued earlier in patients achieving a well-controlled disease. A longer OMA drug survival was observed in patients with a longer disease duration at initiation. CONCLUSION: In French patients with CU, the drug survival of OMA appears to be longer than that observed in previous studies conducted elsewhere, highlighting discrepancies in prescription and reimbursement possibilities. Further studies are warranted to develop customized OMA treatment schemes based on individual patterns.

Use of new paediatric VO2max reference equations to evaluate aerobic fitness in overweight or obese children with congenital heart disease.

AIMS: Overweight and obesity in children with congenital heart disease (CHD) represent an alarming cardiovascular risk. Promotion of physical activity and cardiac rehabilitation in this population requires assessing the level of aerobic fitness (VO2max) by a cardiopulmonary exercise test (CPET). Nevertheless, the interpretation of CPET in overweight/obese children with CHD remains challenging as VO2max is affected by both the cardiac condition and the body mass index (BMI). The new paediatric VO2max  Z-score reference equations, based on a logarithmic function of VO2max, height and BMI, were applied to overweight/obese children with a CHD and compared with overweight/obese children without any other chronic condition. METHODS AND RESULTS: In this cross-sectional controlled study, 344 children with a BMI > 85th percentile underwent a CPET (54% boys; mean age 11.5 ± 3.1 years; 100 CHD; 244 controls). Using the VO2max  Z-score equations, aerobic fitness was significantly lower in obese/overweight CHD children than that in matched obese/overweight control children (-0.43 ± 1.27 vs. -0.01 ± 1.09; P = 0.02, respectively), and the proportion of children with impaired aerobic fitness was significantly more important in obese/overweight CHD children than in matched controls (17% vs.6%, P = 0.02, respectively). The paediatric VO2max  Z-score reference equations also identified specific complex CHD at risk of aerobic fitness impairment (univentricular heart and right outflow tract anomalies). Using Cooper's weight- and height-based linear equations, similar matched-comparisons analyses found no significant group differences. CONCLUSIONS: As opposed to the existing linear models, the new paediatric VO2max  Z-score equations can discriminate the aerobic fitness of obese/overweight children with CHD from that of obese/overweight children without any chronic disease. REGISTRATION: ClinicalTrials.gov NCT04815577.

The new paediatric VO2max  Z-score reference equations found a lower aerobic fitness in obese or overweight children with CHD than that in matched obese or overweight control children and a high proportion of children with impaired aerobic fitness in obese or overweight children with CHD and identified specific complex CHD at risk of aerobic fitness impairment. As opposed to Cooper's weight-based or height-based linear equations, the new paediatric VO2max  Z-score equations can discriminate the aerobic fitness of obese or overweight children with CHD from that of obese or overweight children without any chronic disease.

Alteration of Volumetric Bone Mineral Density Parameters in Men with Spinal Cord Injury.

Spinal cord injury (SCI) induces severe losses of trabecular and cortical volumetric bone mineral density (vBMD), which cannot be discriminated with conventional dual-energy X-ray absorptiometry (DXA) analysis. The objectives were to: (i) determine the effects of SCI on areal BMD (aBMD) and vBMD determined by advanced 3D-DXA-based methods at various femoral regions and (ii) model the profiles of 3D-DXA-derived parameters with the time since injury. Eighty adult males with SCI and 25 age-matched able-bodied (AB) controls were enrolled in this study. Trabecular and cortical vBMD, cortical thickness and derived strength parameters were assessed by 3D-SHAPER® software at various femoral subregions. Individuals with SCI had significantly lower integral vBMD, trabecular vBMD, cortical vBMD, cortical thickness and derived bone strength parameters (p < 0.001 for all) in total proximal femur compared with AB controls. These alterations were approximately to the same degree for all three femoral subregions, and the difference between the two groups tended to be greater for cortical vBMD than trabecular vBMD. There were minor differences according to the lesion level (paraplegics vs tetraplegics) for all 3D-DXA-derived parameters. For total proximal femur, the decreasing bone parameters tended to reach a new steady state after 5.1 years for integral vBMD, 7.4 years for trabecular vBMD and 9.2 years for cortical vBMD following SCI. At proximal femur, lower vBMD (integral, cortical and trabecular) and cortical thickness resulted in low estimated bone strength in individuals with SCI. It remains to be demonstrated whether these new parameters are more closely associated with fragility fracture than aBMD.

Comparison of the Discovery A and Stratos DR densitometers for assessing whole-body and regional bone mineral density and body composition.

PURPOSE: The agreement between the Stratos DR and Discovery A densitometers was assessed for measurements of whole-body (WB) and regional fat mass (FM), fat-free soft tissue (FFST) and bone mineral density (BMD). Moreover, the precision of the Stratos DR was also evaluated. METHODS: Fifty participants (35 women, 70%) were measured consecutively, once on the Discovery A and once on the Stratos DR. In a subgroup of participants (n = 29), two successive measurements with the Stratos DR were also performed. RESULTS: FM, FFST and BMD measured with the two devices were highly correlated, with a coefficient of correlation ranging from 0.80 to 0.99. Bland-Altman analyses indicated significant bias between the two devices for all measurements. Thus, compared to the Discovery A, the Stratos DR underestimated WB BMD and WB and regional FM and FFST, with the exception of trunk FM and visceral adipose tissue (VAT), which were overestimated. Precision error for the Stratos DR, when expressed as root mean square-coefficient of variation (RMS-CV%) for FM, was 1.4% for WB, 3.0% for the gynoid and android regions, and 15.9% for VAT. The RMS-CV% for FFST was 1.0% for WB. The root mean square of standard deviation for WB BMD was 0.018 g/cm², corresponding to a 1.4% CV. The least significant change was 0.050 g/cm² (SD), and 4.0% was considered to be a significant biological change. CONCLUSIONS: Differences between the Stratos DR and Discovery A measurements are significant and require the use of translational cross-calibration equations. For most of the BMD and body composition parameters, our results demonstrated good Stratos DR precision.

Intensive Care Unit activity in France from the national database between 2013 and 2019: More critically ill patients, shorter stay and lower mortality rate.

BACKGROUND: Knowledge of the occurrence and outcome of admissions to Intensive Care Units (ICU) over time is important to inform healthcare services planning. This observational study aims at describing the activity of French ICUs between 2013 and 2019. METHODS: Patient admission characteristics, organ dysfunction scores, therapies, ICU and hospital lengths of stay and case fatality were collected from the French National Hospital Database (population-based cohort). Logistic regression models were developed to investigate the association between age, sex, SAPS II, organ failure, and year of care on in-ICU case fatality. FINDINGS: Among 1,594,801 ICU admissions, the yearly ICU admission increased from 3.3 to 3.5 per year per 1000 inhabitants (bed occupancy rate between 83.4 and 84.3%). The mean admission SAPS II was 42 ± 22, with a gradual annual increase. The median lengths of stay in ICU and in hospital were 3 (interquartile range (IQR) = [1-7]) and 11 days (IQR = [6-21]), respectively, with a progressive decrease over time. The in-ICU and hospital mortality case fatalities decreased from 18.0% to 17.1% and from 21.1% to 19.9% between 2013 and 2019, respectively. Male sex, age, SAPS II score, and the occurrence of any organ failure were associated with a higher case fatality rate. After adjustment on age, sex, SAPS II and organ failure, in-ICU case fatality decreased in 2019 as compared to 2013 (adjusted Odds Ratio = 0.87 [95% confidence interval, 0.85-0.89]). INTERPRETATION: During the study, an increasing incidence of ICU admission was associated with higher severity of illness but lower in-ICU case fatality.

Reference values of aerobic fitness in the contemporary paediatric population.

AIMS: There has been a growing interest in the use of markers of aerobic physical fitness (VO2max assessed by cardiopulmonary exercise test (CPET)) in the follow-up of paediatric chronic diseases. The dissemination of CPET in paediatrics requires valid paediatric VO2max reference values to define the upper and lower normal limits. This study aimed to establish VO2max reference Z-score values, from a large cohort of children representative of the contemporary paediatric population, including those with extreme weights. METHODS AND RESULTS: In this cross-sectional study, 909 children aged 5 to 18 years old from the general French population (development cohort) and 232 children from the general German and US populations (validation cohort) underwent a CPET, following the guidelines on high-quality CPET assessment. Linear, quadratic, and polynomial mathematical regression equations were applied to identify the best VO2max Z-score model. Predicted and observed VO2max values using the VO2max Z-score model, and the existing linear equations were compared, in both development and validation cohorts. For both sexes, the mathematical model using natural logarithms of VO2max, height, and BMI was the best fit for the data. This Z-score model could be applied to normal and extreme weights and was more reliable than the existing linear equations, in both internal and external validity analyses (https://play.google.com/store/apps/details?id=com.d2l.zscore). CONCLUSION: This study established reference Z-score values for paediatric cycloergometer VO2max using a logarithmic function of VO2max, height, and BMI, applicable to normal and extreme weights. Providing Z-scores to assess aerobic fitness in the paediatric population should be useful in the follow-up of children with chronic diseases. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04876209.

Prognostic value of an automated thrombin generation assay in COVID-19 patients entering hospital: A multicentric, prospective observational study.

INTRODUCTION: The prognostic significance of the thrombin generation assay (TGA) with a thrombomodulin (TM) challenge in patients entering hospital with severe COVID-19 is uncertain. METHODS: We prospectively evaluated an automated TGA (aTGA) using the ST-ThromboScreen® assay and ST-Genesia® analyser in 179 patients with severe COVID-19 during their admission to 2 university hospitals. The primary outcome was early survival at Day 28 (D28). Secondary outcomes were late survival at Day 90 (D90), later transfer to an intensive care unit (ICU), and occurrence of any thrombotic complications during hospitalisation. RESULTS: Among the 174 patients, 50 were initially admitted to ICUs. Forty-two were transferred to ICUs before D28. Fourteen patients, all in ICUs, died before D28, and 20 before D90, all but 1 in ICUs. None of the aTGA-derived results were associated with vital status either at D28 or D90. Nine patients had a thrombotic event with no association with the aTGA results. Later transfer to the ICU was associated with higher velocity index, thrombin peak height and endogenous thrombin potential (ETP) values of the aTGA performed with TM, and mainly with a lower TM-induced decrease in ETP (odds ratio 15.5 (2.15-132), p = 0.009). CONCLUSIONS: aTGA, a global assay supposed to evidence coagulopathy, could predict neither early or late survival, nor thrombotic events, in hospitalised COVID-19 patients. Its clinical justification in that setting is thus unlikely. A relative resistance of the ETP to TM was associated with later transfer to the ICU and deserves further investigation.

[ECRIN standard requirements for good clinical practices-compliant data management in multinational clinical trials]. / Référentiel ECRIN pour la conformité aux bonnes pratiques de gestion des données des essais cliniques multinationaux.

CONTEXT: Clinical studies involve an increasing amount of data collection and management. However, there is no specific quality standard sufficiently practical, in free access, and open for data management and the underlying IT-infrastructure in academic units. European Clinical Research Infrastructures Network (ECRIN) published standard requirements for certified data management units. We present a French version of these standards. METHODS: A group of experts produced the standards, by consensus. The first version was revised after two pilot audits for data centre certification were performed. RESULTS: The revised version includes 21 lists of five to ten standards, in three groups: information technologies, data management (DM) and "general". CONCLUSIONS: These standards offer a clear description of DM and IT requirements for clinical studies. Initially created for ECRIN certification purposes, they offer a very useful reference for academic DM structures.

Balloon dilation for persistent unilateral chronic obstructive Eustachian tube dysfunction is effective: a prospective multicentre study.

PURPOSE: Balloon dilatation of the Eustachian tube (BDET) is an option for treating chronic obstructive Eustachian tube dysfunction (COETD). In this prospective multicentric study, the main objective was to evaluate the results of BDET in unilateral COETD refractory to medical treatment. METHODS: Adults with unilateral COETD whose Eustachian Tube Score (ETS) was less than 5 despite medical pressure therapy were included. The primary endpoint was the change in ETS measured at 2, 6, and 12 months after BDET. Secondary objectives were the evolution of clinical symptoms assessed by the Eustachian Tube Questionnaire (ETDQ-7), audiometry, tympanometry, and otoscopy changes after BDET. RESULTS: Twenty-eight patients were included between May 2014 and December 2017 and were treated with BDET without adverse effects in three different referral centers. Population's median age was 52 (Q25; Q75: 24, 82) years. The median follow-up time was 381 (Q25; Q75: 364; 418) days. The median ETS was 2 (Q25; Q75: 1; 4) before BDET. There was a significant improvement in ETS at 2 and 6 months and 1 year after BDET (score at 1 year: 6 (Q25; Q75: 2; 8) (p < 0.0001)). There was a significant, sustained improvement in the ETDQ-7 with a score of 4.21 (Q25; Q75-3.50; 4.79) before BDET and 3.43 (Q25; Q75-2.43; 4.14) (p = 0.0012) at 1 year. There was a suggestive improvement in tympanometry results at 1 year (p = 0.025). CONCLUSION: BDET provides an improvement in symptoms and objective measures assessed at 1 year in patients with COETD who have failed medical treatment. TRIAL REGISTRATION: NCT02123277 (April 25, 2014).

Neurofilament Light Chain Levels Are Predictive of Clinical Conversion in Radiologically Isolated Syndrome.

BACKGROUND AND OBJECTIVES: To evaluate the predictive value of serum neurofilament light chain (sNfL) and CSF NfL (cNfL) in patients with radiologically isolated syndrome (RIS) for evidence of disease activity (EDA) and clinical conversion (CC). METHODS: sNfL and cNfL were measured at RIS diagnosis by single-molecule array (Simoa). The risk of EDA and CC according to sNfL and cNfL was evaluated using the Kaplan-Meier analysis and multivariate Cox regression models including age, spinal cord (SC) or infratentorial lesions, oligoclonal bands, CSF chitinase 3-like protein 1, and CSF white blood cells. RESULTS: Sixty-one patients with RIS were included. At diagnosis, sNfL and cNfL were correlated (Spearman r = 0.78, p < 0.001). During follow-up, 47 patients with RIS showed EDA and 36 patients showed CC (median time 12.6 months, 1-86). When compared with low levels, medium and high cNfL (>260 pg/mL) and sNfL (>5.0 pg/mL) levels were predictive of EDA (log rank, p < 0.01 and p = 0.02, respectively). Medium-high cNfL levels were predictive of CC (log rank, p < 0.01). In Cox regression models, cNfL and sNfL were independent factors of EDA, while SC lesions, cNfL, and sNfL were independent factors of CC. DISCUSSION: cNfL >260 pg/mL and sNfL >5.0 pg/mL at diagnosis are independent predictive factors of EDA and CC in RIS. Although cNfL predicts disease activity better, sNfL is more accessible than cNfL and can be considered when a lumbar puncture is not performed. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in people with radiologic isolated syndrome (RIS), initial serum and CSF NfL levels are associated with subsequent evidence of disease activity or clinical conversion.

Primary acute convexity subarachnoid hemorrhage in older patients: analysis of baseline, clinical and MRI characteristics including quantitative surface study and topographical probabilistic mapping of convexity subarachnoid hemorrhage.

OBJECTIVES: Primary acute convexity subarachnoid hemorrhage (cSAH) in older patients can be observed in cerebral amyloid angiopathy (CAA) or idiopathic (with cSAH as potential initial manifestation of suspected CAA). We aimed to analyze baseline, clinical and MRI (including quantitative cSAH surface analysis and topographical probabilistic cSAH mapping) characteristics in elderly cSAH patients with CAA. MATERIALS AND METHODS: Baseline/clinical/MRI characteristics of 50 consecutive primary acute cSAH patients ≥ 55 years with suspected/possible/probable CAA were retrospectively analyzed. RESULTS: Median age was 74, with 26% of patients showing suspected, 22% possible and 52% probable CAA. Transient focal neurological episode (TFNE) was observed in 78%, with spreading symptoms in 79% (median spreading speed five minutes), a median of two episodes before cSAH diagnosis, and similar symptoms in 91% when multiple TFNE, with a median duration of 15 min. Motor/sensory/speech/visual symptoms were observed in 85%/69%/46%/8%, respectively, and brachiofacial/brachial was the most frequent distribution for sensory-motor symptoms. Positive clinical-radiological correlation was observed in 84%, headache in 22%, and antiepileptics started in 78%. MRI showed chronic intracerebral hemorrhage in 10%, cortical superficial siderosis in 68%, cerebral microbleeds in 48%, median total Fazekas score of 3, lacunes in 6% and DWI lesion (all unique/cortical/ < 10 mm) in 6%. cSAH involved a median of 1 sulcus, with central sulcus as most frequently (47.5%) involved followed by precentral sulcus (17%). Median cSAH surface was 2170 mm2. No baseline, clinical or MRI characteristics were associated with cSAH surface extent in multivariate analysis. CONCLUSIONS: Baseline, clinical, or MRI features seem not to influence CAA-related cSAH extent. CLINICAL TRIAL REGISTRATION-URL: http://www. CLINICALTRIALS: gov . Unique identifier: NCT04825808.