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Wide inter-individual variation of expression of compound metabolic enzymes is determined by polymorphism and may predispose the development of diseases provoked by environmental factors. The combined analysis of phase II detoxification system genes: arylamine N-acetyltransferase 2 (NAT2), and glutathione S-transferases (GST) M1 and T1 was carried out in patients with minimal/mild (group I; n = 36) and moderate/severe endometriosis (group II; n = 29) and controls (n = 72) of French origin, using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The results show a significant difference between patients and controls with regard to NAT2 gene polymorphism (P < 0.05). This is mainly due to the high percentage of slow acetylator genotypes (SA) in patients compared with controls (60.0 versus 38.9%; P < 0.02) with a distinct preponderance in subjects with minimal/mild endometriosis (69.4%, P < 0.005) where there is a significantly elevated frequency of slow allele S1 (NAT2*5) (P = 0.05). Significantly increased proportions of GSTM1-deficient genotypes were found in both groups of patients, in comparison with the controls (75.0 and 79.3% versus 45.8%; P < 0.0001). A preponderance of GSTT1-negative subjects among patients was also detected, but did not appear significant. We suggest the involvement of both NAT2 and GSTM1 detoxification system genes in the pathogenesis of endometriosis and the possible impact of NAT2 gene polymorphism in the development of different forms of this disease. [ABSTRACT FROM AUTHOR]

Purpose: The primary objective was to evaluate bone fragility on dual X-ray absorptiometry (DXA) in patients with obesity before and 2 years after bariatric surgery. The secondary objective was to identify risk factors for the development of a bone mineral density ≤ -2 SD at 2 years., Methods: This descriptive study included patients with obesity who underwent DXA before and 2 years (±6 months) after bariatric surgery. The BMD and the T-score were assessed at the lumbar spine, femoral neck and total hip. Data on body composition on DXA were also collected. The diagnosis of osteoporosis was retained for a T-score ≤ - 2.5 SD at any measured location. Osteopenia, or low bone mass, was defined by -2.5 SD < T-score ≤ -1 SD., Results: Among the 675 included patients, 77.8 % were women, with a mean age of 49.5 years (±11.1). After bariatric surgery, there were significantly more patients with osteoporosis: 3.6 % vs. 0.9 % ( p  = 0.0001). Multivariate analysis revealed that the risk factors for developing a bone mineral density ≤ -2 SD 2 years after bariatric surgery in patients with normal BMD before surgery were age and lower lean and fat mass before the surgery (OR = 1.07, 95%CI = [1.03-1.12], OR = 0.83, 95%CI = [0.77-0.91], OR = 1.08, 95%CI = [1.02-1.15], respectively)., Conclusion: There was a significantly higher prevalence of osteoporosis and low bone mass 2 years after bariatric surgery. Older age and lower lean and fat mass at baseline were risk factors for the development of a BMD ≤ -2SD at 2 years., Competing Interests: Marine Fauny, Marion Halin, Edem Allado, Laurent Brunaud, Claire Nomine-Criqui, Eliane Albuisson, Isabelle Chary-Valckenaere, Didier Quilliot, and Damien Loeuille declare that they have no conflict of interest., (© 2024 The Authors.)

The impact of regular cannabis use on retinal function has already been studied using flash (fERG) and pattern (PERG) electroretinogram. Delayed ganglion and bipolar cells responses were observed as showed by increased peak time of PERG N95 and fERG b-wave recorded in photopic condition. Hypoactivity of amacrine cells was also showed by decreased amplitudes of oscillatory potentials (OPs). However, it is unknown how these retinal anomalies evolve according to the level of cannabis use in cannabis users. The aim of this study was to longitudinally assess the retinal function during a treatment aiming to reduce cannabis use. We recorded PERG and fERG in 40 regular cannabis users receiving either an 8 weeks mindfulness-based relapse prevention program or an 8 weeks treatment-as-usual therapy. ERGs were recorded before treatment, at the end of it, and 4 weeks afterward. We found reduced peak times in PERG N95 and fERG b-wave ( p = 0.032 and p = 0.024: Dunn's post-hoc test) recorded at week 8 and increased amplitudes in OP2 and OP3 ( p = 0.012 and p = 0.030: Dunn's post-hoc test) recorded at week 12 in users with decreased cannabis use. These results support variations of retinal anomalies with the level of cannabis use, implying that reduction of cannabis use could restore retinal function in regular users., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schwitzer, Moreno-Zaragoza, Dramé, Schwan, Angioi-Duprez, Albuisson and Laprévote.)

Following COVID-19 infection, many patients suffer from long-lasting symptoms that may greatly impair their quality of life. Persisting dyspnea and other functional respiratory complaints can evoke hyperventilation syndrome (HVS) as a putative contributor to long-COVID presentation in COVID-19 survivors. We aimed to assess the possible relationship between HVS and previous acute COVID-19 infection. We designed a cross-sectional, single-center study, including all patients consecutively referred to our Lung Function and Exercise Testing Department between January and June 2021. Participants completed a systematic Nijmegen Questionnaire, a modified Medical Research Council dyspnea scale assessment, a post-COVID screening questionnaire, and performed a standardized lung function test. The population was divided according to HVS diagnosis, defined as a Nijmegen score of > 23/64. The occurrence of previous COVID-19 infection was compared according to the Nijmegen score after adjustment for potential confounders by multivariate logistic regression. In total, 2846 patients were included: 1472 men (51.7%) with a mean age of 56 (±16.6) years. A total of 455 patients (16%) declared a previous SARS-CoV-2 infection, and 590 patients presented a positive score (>23/64) in the Nijmegen Questionnaire (20.7%). Compared with COVID-19-free patients, there was an increased occurrence of HVS+ in cases of COVID-19 infection that did not require hospitalization (aOR = 1.93 [1.17−3.18]). The results of this large-scale, cross-sectional study suggest an association between HVS diagnosis and a history of COVID-19 disease in patients who were not hospitalized.

The primary objective was to evaluate bone fragility prevalence on dual X-ray absorptiometry (DXA) and computed tomography (CT) in patients with severe obesity. The secondary objective was to evaluate the risk factors for bone fragility. This monocentric study was conducted in patients with grade 2 and 3 obesity. Bone mineral density (BMD) and T-score were studied on DXA, and the scanographic bone attenuation coefficient of L1 (SBAC-L1) was measured on CT. Among the 1386 patients included, 1013 had undergone both DXA and CT within less than 2 years. The mean age was 48.4 (±11.4) years, 77.6% were women, and the mean BMI was 45.6 (±6.7) kg/m². Eight patients (0.8%) had osteoporosis in at least one site. The mean SBAC-L1 was 192.3 (±52.4) HU; 163 patients (16.1%) were under the threshold of 145 HU. Older age (OR[CI95] = 1.1 [1.08-1.16]), lower BMD on the femoral neck and spine (OR[CI95] = 0.04[0.005-0.33] and OR[CI95] = 0.001[0.0001-0.008], respectively), and higher lean mass (OR[CI95] = 1.1 [1.03-1.13]) were significantly associated with an SBAC-L1 ≤ 145 HU in multivariate analysis. Approximately 16% of patients with severe obesity were under the SBAC-L1 threshold, while less than 1% were classified as osteoporotic on DXA.

Remote photoplethysmography imaging (rPPGc) is a new method measuring essential parameters, such as heart rate (HR), which uses a video camera during teleconsultation. Our work aimed to evaluate the accuracy of such remote measurements compared with existing contact point measurement methods in real-life clinical settings. The prospective hospital-based study recruited 1045 patients who required a pulmonary function test. For each patient, measurements of HR using a standard electrocardiogram acquisition system (gold standard) were carried out concomitantly with the measurements made by the rPPGc system (Caducy v1.0.0) taken within a 60 s timeframe. Age, gender, and skin phototype were collected. We performed an intraclass coefficient correlation (ICC) and Bland-Altman plotting to determine the accuracy and precision of the rPPGc algorithm readings. We achieved measurement of HR using the two methods in 963 patients. The ICC measured at a 60 s timeframe, and when we compared the rPPGc with the gold standard, it had a 95% confidence interval (CI95) value of 0.886 [0.871:0.899]. In all, 94.6% ( n = 911) patients showed promising results with a CI95 in Bland-Altman plotting. Fifty-two measurements were discordant, and further analysis established the method's accuracy at 96.2%. Our results described a good accuracy and correlation between the rPPGc system and the gold standard, thus paving the way for more precise care via telemedicine.

Background: A higher risk of osteoporotic fracture was described in systemic sclerosis patients than in healthy patients., Objective: To evaluate the relation between osteoporotic fracture risk measured by the scanographic bone attenuation coefficient of the first lumbar vertebra (SBAC-L1) on computed tomography (CT) scan and the presence of ectopic calcifications: vascular, valvular and spinal., Methods: This monocentric retrospective study was performed on patients followed between 2000 and 2014 at Nancy University Hospital. Systemic sclerosis patients, according to ACR/EULAR 2013 criteria, followed from 2000 to 2014 and who underwent, during their follow-up, a CT including the first lumbar vertebra were included. The SBAC-L1 was measured with a threshold set at 145 Hounsfield units (HU). Vascular and spinal calcifications were studied on CT. For vascular calcifications, the Agatston score was used. Valvular calcifications were studied on echocardiography., Results: A total of 70 patients were included (mean age: 62.3 (±15.6) years, women 88.5%). The mean SBAC-L1 was 157.26 (±52.1) HU, and 35 patients (50%) presented an SBAC-L1 ⩽ 145 HU. The reproducibility of the calcification evaluation was good, with kappa coefficients varying between 0.63 and 1. In univariate analysis, spinal and vascular calcifications were associated with an SBAC-L1 ⩽ 145 HU, with ORs of 13.6 (1.6-113.3) and 8 (95%CI: 2.5-25.5), respectively. In multivariate analysis, the SBAC-L1 was not associated with the presence of any ectopic calcifications. The SBAC-L1 decreased with age (p = 0.0001)., Conclusion: Patients with systemic sclerosis with an SBAC-L1 ⩽ 145 HU were older, but they did not have more ectopic calcification., Trial Registration: The ethics committee of Nancy Hospital agreed with this study (referral file number 166). This study was designed in accordance with the general ethical principles outlined in the Declaration of Helsinki., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2022.)

Background: Bipolar disorders (BD) is a common, chronic and disabling psychiatric condition. In addition to being characterized by significant clinical heterogeneity, notable disturbances of sleep and cognitive function are frequently observed in all phases of the disease. Currently, there is no readily available biomarker in current clinical practice to help diagnose or predict the disease course. Thus, identification of biomarkers in BD is today a major challenge. In this context, the study of electrophysiological biomarkers based on electroretinogram (ERG) measurements in BD seems highly promising. The BiMAR study aims to compare electrophysiological data measured with ERG between a group of euthymic patients with BD and a group of healthy control subjects. Secondarily, we will also describe the existing potential relationship between clinical, sleep and neuropsychological phenotypes of patients and electrophysiological data., Methods: The BiMAR study is a comparative and monocentric study carried out at the Expert Center for BD in Nancy, France. In total, 70 euthymic adult patients with BD and 70 healthy control subjects will be recruited. Electrophysiological recordings with ERG and electroencephalogram (EEG) will be performed with a virtual reality headset after a standardized clinical evaluation to all participants. Then, an actigraphic monitoring of 21 consecutive days will be carried out. At the end of this period a neuropsychological evaluation will be performed during a second visit. The primary outcome will be electrophysiological measurements with ERG flash and pattern. Secondary outcomes will be EEG data, sleep settings, clinical and neuropsychological assessments. For patients only, a complementary ancillary study, carried out at the University Hospital of Nancy, will be proposed to assess the retinal structure and microvascularization using Optical Coherence Tomography. Recruitment started in January 2022 and will continue until the end of July 2023., Discussion: The BiMAR study will contribute to identifying candidate ERG electrophysiological markers for helping the diagnosis of BD and identify subgroups of patients with different clinical profiles. Eventually, this would allow earlier diagnosis and personalized therapeutic interventions., Clinical Trial Registration: The study is registered at Clinicaltrials.gov, NCT05161546, on 17 December 2021 (https://clinicaltrials.gov/ct2/show/NCT05161546)., Competing Interests: The authors declare that they have a scientific collaboration with BioSerenity in this study using the Retinaute® (BioSerenity)., (Copyright © 2022 Gross, Tursini, Albuisson, Angioi-Duprez, Conart, Louis Dorr, Schwan and Schwitzer.)

One of the biggest tasks for health professionals is to address the needs of persons with chronic illnesses like type 1 diabetes (T1D) and to support the acquisition of all necessary self-management behaviors. Functional insulin therapy (FIT) enables patients to adapt insulin doses according to everyday situations and reduces the risk of complications of diabetes. The aim was to describe the co-development, with patient as partners, of an eHealth tool for the acquisition of skills in FIT, to evaluate the user's acceptability and learning effectiveness on a sample of T1D patients followed in the University Hospital of Nancy. Subjects were invited to participate between July and August 2020. A total of 35 participants from different professional categories, median age of 41 years (IQR 27; 60) were included. In 22 subjects having access to all learning activities, there were positive relationships between the success score and the task (Spearman's rank correlation coefficient r s  = 0.5), between the intent to use and following parameters: perceived utility (r s  = 0.694), educational adequacy (r s  = 0.786), tasks r s  = (0.664), technology (r s  = 0.520) and ease of use (r s  = 0.659). This pilot study describes a user-centered approach to development of an eHealth tool for the acquisition of self-management skills in FIT. The online tool was well accepted and showed a positive impact on learning. The concept presented here will be useful to prompt future eHealth interventions in T1D or other chronic conditions aiming to increase patients' autonomy to prevent disease-related complications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The aim of this study was to evaluate the real intensity level of exercise in a sample of patients with chronic disease from obesity, rheumatology, hematology and other departments involved in a hospital-based program of adapted physical activity (APA). For this cross-sectional study, we studied seventy-five patients with chronic disease and no beta-blocker treatment. They systematically performed a cardiopulmonary exercise test before participating in a supervised APA practice using a telemetry wireless system to monitor heart rate (HR) during the first session. Based upon the results of the functional evaluation of exercise performance, we studied two groups of patients: (1) No limitation in exercise performance (maximal oxygen uptake greater than or equal to 80% of the theoretical reference) and (2) limited exercise performance (maximal oxygen uptake less than 80% of the theoretical value). Fifty-two patients (69.3%) were women, mean age was 42.6 (± 13.8), and mean BMI was 36.7 (± 10.6). Most patients had been referred for obesity (57.3%). We found 39 patients with normal exercise capacities and 36 patients with limited exercise performance. There were no significant differences in demographic and clinical characteristics between the two groups. For all populations, the mean and median real intensity levels of exercise in a sample of patients were moderate (55-70% HR max) and were the same for both groups. During the most intensive 15-min bout of the APA session, the HR for patients in both groups was greater than 70% of the actual maximum HR. This study observed a moderate level of APA exercise intensity in patients suffering from various chronic diseases. We found no significant difference in intensity level of exercise between patients' capacities, i.e., with and without limitation of their maximal performance., (© 2022. The Author(s).)

Remote photoplethysmography imaging (rPPG) is a new solution proposed to measure vital signs, such as respiratory rate (RR) in teleconsultation, by using a webcam. The results, presented here, aim at evaluating the accuracy of such remote measurement methods, compared with existing measurement methods, in a real-life clinical setting. For each patient, measurement of RR, using the standard system (control), has been carried out concomitantly with the experimental system. A 60-s time frame was used for the measurements made by our rPPG system. Age, gender, BMI, and skin phototype were collected. We performed the intraclass correlation coefficient and Bland-Altman plot to analyze the accuracy and precision of the rPPG algorithm readings. Measurements of RR, using the two methods, have been realized on 963 patients. Comparison of the two techniques showed excellent agreement (96.0%), with most of the patients (n = 924-standard patients) being in the confidence interval of 95% in Bland-Altman plotting. There were no significant differences between standard patients and outlier patients for demographic and clinical characteristics. This study indicates a good agreement between the rPPG system and the control, thus allowing clinical use of this remote assessment of the respiratory rate.

Background: Refractory cardiac arrest management relies on extracorporeal cardiopulmonary resuscitation (ECPR), requiring the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Circulatory flow recovery can be associated with an ischemia-reperfusion injury, leading to vasoplegia and vasopressor requirement. The aim of this work was to evaluate the impact on hemodynamics of a methylene blue bolus infusion in a porcine model of ischemic refractory cardiac arrest., Methods: Ischemic refractory cardiac arrest was induced in 20 pigs. After a low flow period of 30 min, VA-ECMO was initiated and the pigs were randomly assigned to the standard care group (norepinephrine + crystalloids) or methylene blue group (IV 2 mg·kg -1 bolus of methylene blue over 30 min + norepinephrine and crystalloids). Macrocirculatory parameters and lactate clearance were measured. Sublingual microcirculation was evaluated with sidestream dark field (SDF) imaging. The severity of the ischemic digestive lesions was assessed according to the histologic Chiu/Park scale., Results: Eighteen pigs were included. The total crystalloid load (5000 (6000-8000) mL vs. 17,000 (10,000-19,000) mL, p = 0.007, methylene blue vs. standard care group) and catecholamine requirements (0.31 (0.14-0.44) μg·kg -1 ·min -1 vs. 2.32 (1.17-5.55) μg·kg -1 ·min -1 , methylene blue vs. standard care group, p = 0.004) were significantly reduced in the methylene blue group. There were no significant between-group differences in lactate clearance, sublingual capillary microvascular parameters assessed by SDF or histologic Chiu/Park scale., Conclusions: In our refractory cardiac arrest porcine model treated with ECPR, methylene blue markedly reduced fluid loading and norepinephrine requirements in comparison to standard care during the first 6 h of VA-ECMO.

Background: This study aimed to assess the prevalence of alexithymia in a sample of university students and to determine its association with specific sports practice characteristics (competition and training)., Methods: In this cross-sectional study, anthropometric data and characteristics of sport practice were collected, as well as level of alexithymia (Toronto Alexithymia Scale, (TAS-20))., Results: The study included 253 French university students who completed a questionnaire specifying their regular sports practice and level of alexithymia (TAS-20). We found 76 subjects (30%) who had proven alexithymia and 92 (36.4%) who were borderline alexithymic. A significant positive relationship between alexithymia and the weekly amount of training practice was observed. It should be noted that students who engage in more than 5 h of physical activity are more prone to be borderline or alexithymic (respectively, 19.6 and 19.7% versus 7.1% for non-alexithymics; p = 0.03)., Conclusion: With a 30% frequency, alexithymia is more prevalent in this context than in the general population. Furthermore, alexithymia and borderline alexithymia are most favorably associated with higher physical activity (over 5 h per week).

Background: This study aimed to evaluate the efficacy of the Six-Minute Walk Test (6MWT) to determine the physical activity capacities of patients with chronic disease. Methods: For this cross-sectional study, we investigated 156 patients with chronic disease and no beta-blocker treatment. They systematically performed a maximal cardiopulmonary exercise test to determine their heart rate peak (HRPeak) and maximal oxygen uptake (V’O2max). We considered two groups of patients based upon the results of the functional evaluation of exercise performance: (1) No limitation in exercise performance (V’O2max greater or equal to 80% of the theoretical reference) and (2) limited exercise performance (V’O2max less than 80% of the theoretical value). All patients also received a 6MWT on the same day as the exercise test. Results: We found 68 (43.6%) patients with normal exercise capacities and 88 (56.4%) patients with limited exercise performance. In this sample, 6MWT mean distances were 510 (87) and 506 (86) m, respectively. There were no significant differences between the two groups for distance and end-test heart rate. The correlation between matrix V’O2max measured during the maximal incremental exercise test and the 6MWT distance displayed a positive slope (r = 0.549 CI95 [0.431−0.656]—p < 0.001). Conclusion: Our results showed a moderate relationship between 6MWT and physical activity capacity for patients with chronic disease.

Background: The early detection of patients at risk of developing schizophrenia and bipolar disorder, and more broadly mood spectrum disorder, is a public health concern. The phenotypical overlap between the prodromes in these disorders calls for a simultaneous investigation into both illness trajectories., Method: This is an epidemiological, retrospective, multicentre, descriptive study conducted in the Grand-Est region of France in order to describe and compare early symptoms in 205 patients: 123 of which were diagnosed with schizophrenia and 82 with bipolar disorder or mood spectrum disorder. Data corresponding to the pre-morbid and prodromal phases, including a timeline of their onset, were studied in child and adolescent psychiatric records via a data grid based on the literature review conducted from birth to 17 years of age., Results: Two distinct trajectories were highlighted. Patients with schizophrenia tended to present more difficulties at each developmental stage, with the emergence of negative and positive behavioural symptoms during adolescence. Patients with mood spectrum disorder, however, were more likely to exhibit anxiety and then mood-related symptoms. Overall, our results corroborate current literature findings and are consistent with the neurodevelopmental process. We succeeded in extracting a decision tree with good predictability based on variables relating to one diagnosis: 77.6% of patients received a well-indexed diagnosis. An atypical profile was observed in future mood spectrum disorder patients as some exhibited numerous positive symptoms alongside more conventional mood-related symptoms., Conclusion: The combination of all these data could help promote the early identification of high-risk patients thereby facilitating early prevention and appropriate intervention in order to improve outcomes., (© 2022. The Author(s).)

Objective: This study aimed to evaluate the efficacy of the 1-minute Sit to Stand test (1MSTS) to determine physical activity capacities for patients with chronic disease., Methods: For this cross-sectional study, we studied fifty patients with chronic disease and no beta-blocker treatment. They systematically performed a cardiopulmonary exercise test to determine maximal oxygen uptake (V'O 2 max). We considered two groups of patients based on the results of the functional evaluation of exercise performance: (1) No limitation in exercise performance (V'O 2 max greater or equal to 80% of the theoretical reference) and (2) limited exercise performance (V'O 2 max <80% of the theoretical value). All patients also received an 1MSTS on the same day., Results: We found 22 (44.0%) patients with normal exercise capacity and 28 (56.0%) patients with limited exercise performance. In this sample, mean 1MSTS repetitions were 27.1 (7.1) and 25.2 (8.7), respectively. There were no significant differences between the two groups for repetition and Borg Scale end test. The correlation between V'O 2 max measured during the exercise test and 1MSTS repetitions displayed a positive slope [ r = 0.401 (95% CI 0.114-625)]., Conclusion: This study demonstrated a moderate relationship between 1MSTS and V'O 2 max for patients with chronic disease. 1MSTS did not permit the precise determination of physical activity capacities in this sample., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Allado, Poussel, Albuisson, Paysant, Temperelli, Hily, Moussu, Benhajji, Gauchard and Chenuel.)

Background: This was a multicenter, cross-sectional study which aimed to investigate the relationship between the characteristics of sport practice (weekly training duration, level of practice) and alexithymia in adults who were officially licensed at a sports club., Methods: From a sample of sports club licensed adults, 188 participants were included. The participants completed computerized questionnaires on anthropometric data and characteristics of sport practice (level and weekly time spent on sport practice) as well as alexithymia (TAS 20), depression (BDI-13) and anxiety traits (STAI-Y form B)., Results: In this sample, 91 (48.4%) and 97 (51.6%) athletes engaged in recreational and competitive sport practice, respectively. We observed a prevalence of 31.9% for alexithymia. Moreover, alexithymics were more involved in competitive than recreational practice (40.2% versus 23.1%, respectively; p = 0.019) and they were less anxious (63.9% versus 80.2%, respectively; p = 0.010). Finally, alexithymia was significantly more pronounced than non-alexithymia among sports competition practitioners (OR: 3.57 (95 CI [1.26-10.08]; p = 0.016) and we observed less alexithymia in team sports practice than confrontation sports (OR: 0.20 (95 CI [0.05-0.78]; p = 0.020)., Conclusions: Alexithymic athletes were more involved in competition than recreational sports compared to non-alexithymic subjects, whilst there were more alexithymic athletes in confrontation sports than in team sports.

Background: The choice of the best vasopressor after ExtraCorporeal Membrane Oxygenation (ECMO) implantation after cardiac arrest is not well defined. Circulatory flow recovery with ECMO is associated with vasoplegia and vasopressor need. The present study aimed to compare the effects of norepinephrine and vasopressin in the first 6 h after ECMO initiation., Methods: Cardiac arrest was induced in 20 pigs by coronary surgical ligature and veno-arterial-ECMO was started after a 30-min period of cardio-pulmonary resuscitation. Pigs were randomized into two groups, arginine vasopressin (AVP) or norepinephrine (NE), with the drugs titrated to maintain a mean arterial pressure (MAP) at 65 mm Hg. Macrocirculatory and metabolic parameters were assessed by lactate clearance. Microcirculatory parameters were assessed by sublingual microcirculation with Sidestream Dark Field imaging and peripheral Near InfraRed Spectroscopy. Pulmonary edema was evaluated by measuring lung wet/dry weight ratio., Results: No difference was found between groups regarding ECMO flow and MAP. Fluid resuscitation volume was higher in the NE group (14,000 [11,250-15,250] mL vs. 3,500 [1,750-4,000] mL in the AVP group, P < 0.05). Lung wet/dry weight ratio was higher in the Norepinephrine group. Lactate clearance between H0 and H6 was higher in the AVP group (47.84 [13.42-82.73]% vs. the NE group 25.66 [-7.31 to 35.34)% vs. P < 0.05). No significant difference was observed for sublingual microcirculation values. Baseline tissue oxygen saturation was comparable and higher at both H3 and H6 in the Vasopressin group comparatively to the Norepinephrine group (P < 0.05). Renal and liver function evolution also remained similar in the two groups throughout the study., Conclusions: AVP administration in refractory cardiac arrest resuscitated by veno-arterial-ECMO is associated with a faster lactate clearance, less fluid resuscitation, and less pulmonary edema when compared with NE for similar global and regional hemodynamic effects., Competing Interests: The other authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Introduction: Physiological signals are essential for assessing human health. The absence of a medical device to carry out these measurements remotely is one of the main limitations of telemedicine. Remote photoplethysmography imaging (rPPG) makes it possible to use a camera video to measure some of the most valuable physiological variables: heart rate (HR), respiratory rate (RR) and oxygen saturation (SpO 2 ). Our objective was to evaluate the value of such remote measurements compared with existing contact point measurements techniques in real-life clinical settings., Methods and Analysis: Prospective hospital-based study that will recruit 1045 patients who require a pulmonary function test. For each patient, measurements of HR, RR and SpO 2 , using a standard acquisition system, will be carried out concomitantly with the measurements made by the rPPG system. 30, 60 and 120 s time frames will be used to take measurements. Age, gender and skin phototype will also be collected. The intraclass coefficient correlation will be performed to determine the accuracy and precision of the rPPG algorithm readings., Ethics and Dissemination: The study protocol has been approved by the French Agency for the Safety of Health Products (ANSM registration no. ID RCB 2020-A02428-31) and by a French ethics committee (CPP OUEST I-TOURS-2020T1-30 DM at 30 October 2020). Results will be published in peer-reviewed journals, at scientific conferences and through press releases., Trial Registration Number: NCT04660318., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Intra-articular (IA) and peri-articular glucocorticoid (GC) injections are common in sports medicine. However, from 1 January 2022, all injectable GC routes (including IA administration) will be prohibited in-competition by World Anti-Doping Agency (WADA). Owing to these rules, an IA GC treatment out-of-competition could result in an adverse analytical finding in-competition if the washout period is not clearly defined. The aim of this study is to determine the urinary excretion profile of triamcinolone acetonide following IA injection to strengthen the definition of the washout periods., Methods and Analysis: This is a prospective multicentre trial to include 20 subjects who practice sports for at least 4 hours/week and present a knee disorder requiring IA injection of triamcinolone acetonide for therapeutic purposes. To determine the excretion profile of triamcinolone acetonide in both urine and blood following IA injection of the drug, We will perform 20 urinary tests and 20 dried blood spot tests, two prior to GC injection (baseline) and the last one at 35 days. Analyses will be performed by the French antidoping agency laboratory in accordance with WADA standards and regulations., Ethics and Dissemination: The study protocol was approved by the French ethics committee (CPP Sud Est III-Lyon-2020-070B on 06 October 2020). All subjects will provide written informed consent. The results of this study will be accessible in peer-reviewed publication and be presented at academic conference., Trial Registration Number: NCT04574232., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Infants presenting respiratory distress syndrome (RDS) not responding to surfactant often receive a second instillation. Few studies evaluated the consequences of this second administration. This study aimed at determining the outcome of infants presenting persistent RDS and receiving an early second dose of surfactant. Methods: Infants below 32 weeks' gestation who received a second dose of 100mg/kg of surfactant within the first 72 h of life, were retrospectively involved in this 42 months' study. They were matched to two controls receiving a single dose of 200mg/Kg based upon gender and gestational age. Results: 52/156 infants receiving two doses (Group 2-doses) were significantly more often SGA [22 (42%) vs. 21 (20%) p = 0.04] and outborn [29 (56%) vs. 13 (12%) p = 0.001]. They had received antenatal corticos teroid therapy less often [26 (50%) vs. 89 (86%) p = 0.001] and presented more severe RDS based upon FiO2 level, oxygenation index and radiography. Group 2-doses survival was lower (65.4% vs. 79.6 % p < 0.1) but surviving infants did not have different morbidity than controls. Discussion: Premature newborn receiving a second dose of surfactant had adverse antenatal characteristics, presented more severe RDS and only partially responded to the first dose. Outcomes of surviving infants who received 2 doses of surfactant were comparable to others., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Greiner, Wittwer, Albuisson and Hascoët.)

To evaluate whether the risk of bone fragility on computed tomography (CT) (scanographic bone attenuation coefficient of the first lumbar vertebra (SBAC-L1)) is associated with the severity of spine structural involvement (mSASSS) in patients with ankylosing spondylitis (AS). This retrospective study included AS patients, followed from 2009 to 2017, who fulfilled the New York criteria and who underwent thoraco-abdomino-pelvic CT and radiography (spine, pelvis). The structural involvement was retained for mSASSS ≥ 2. The SBAC-L1 was measured in Hounsfield units (HU). A SBAC-L1 ≤ 145 HU was used to define patients at risk of vertebral fracture (VF). A total of 73 AS patients were included (mean age: 60.3 (± 10.7) years, 8 women (11%), mean disease duration: 24.6 years (± 13.9)). Sixty patients (82.2%) had a mSASSS ≥ 2 (mean score 20.7 (± 21.2)). The mean SBAC-L1 was 141.1 HU (± 45), 138.1 HU (± 44.8) and 154.8 HU (± 44.9) in the total, mSASSS ≥ 2 and mSASSS < 2 populations, respectively. Patients with bone bridges had lower SBAC-L1 than mSASSS ≥ 2 patients without ankylosis (p = 0.02) and more often SBAC-L1 ≤ 145 HU (73% vs 41.9%, p = 0.006). A SBAC-L1 ≤ 145 HU was not associated with structural spine involvement, but patients with bone bridges had significantly decreased SBAC-L1 and an increased probability of being under the fracture threshold.

Online learning is a method for analyzing very large datasets ('big data') as well as data streams. In this article, we consider the case of constrained binary logistic regression and show the interest of using processes with an online standardization of the data, in particular to avoid numerical explosions or to allow the use of shrinkage methods. We prove the almost sure convergence of such a process and propose using a piecewise constant step-size such that the latter does not decrease too quickly and does not reduce the speed of convergence. We compare twenty-four stochastic approximation processes with raw or online standardized data on five real or simulated data sets. Results show that, unlike processes with raw data, processes with online standardized data can prevent numerical explosions and yield the best results., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 Informa UK Limited, trading as Taylor & Francis Group.)

The objectives of this study were to describe the prevalence and characteristics of radiographic lesions of the hands, and calcifications of the spine on computer tomography scans (CT-scans), and to investigate the relationships between radiographic and CT-scan abnormalities and clinical features in a population of patients with systemic sclerosis (SSc).Subjects underwent X-ray examination of the hands, and thoracic or thoraco-abdominal and pelvic CT scan or lumbar CT scan in the year. Structural lesions on hand X ray was scored and spinal calcifications were evaluated in the anterior, intracanal and posterior segments. Intra and inter-reliability was tested for radiography and CT- scan. Prognostic factors considered were interstitial pulmonary lesions on the CT scan, pulmonary arterial hypertension (PAH) and death.This study involved 77 SSc patients, 58 (75%) with limited cutaneous SSc (lcSSc) and 19 (25%) with diffuse SSc (dSSc). The prevalences of radiographic lesions of the hand were 28.6% for periarticular calcifications and 26% for calcinosis. On CT scan, 64 (83%) patients exhibited at least 1 calcification. Spine calcifications were depicted in 80.5%, 27.3%, and 35.1% at the anterior, intracanal and posterior segments respectively. Calcifications were mainly localized on thoracic spine. Inter reader reliabilities were good for hands and moderate for spine respectively. Spine calcifications and periarticular calcifications in the hands were associated (P = .012). Calcinosis in the hands was related to PAH (P = .02). Posterior calcification segment and foraminal calcifications were associated with interstitial lung disease (ILD) (P = .029) and death (P = .001).More than 80% of systemic sclerosis patients presented spine calcifications. A significant association between hands and spinal calcifications were confirmed and some localization in the posterior segment considered as a bad prognostic factor.

Objective: To evaluate prevalence of structural lesions, synovitis and bone marrow lesions (BMLs) on MRI performed with a 0.3T imaging system in patients with erosive hand osteoarthritis (EHOA) and to compare them to the anatomic radiographic Verbruggen-Veys score (VV)., Design: For this Cross-sectional study, fifty-five EHOA patients were studied with 0.3T contrast-enhanced MRI and radiography (RX) of their dominant hand. Structural lesions were scored according to the OMERACT Hand Osteoarthritis MRI Scoring System as follows: osteophytes and erosions were graded from 0 to 3. On joint destruction lesion synovitis and BMLs were graded from 0 to 1. And on MRI, we evaluated the presence of several structural features: N: normal, O: osteophytic lesions, E: erosive lesions, E/O: osteophytic and erosive lesions and D: joint destruction. RX was scored according to the VV system. Relations between MRI features and VV stages were analysed., Results: MRI identified more structural lesions than RX (77.3% versus 74.8%) and particularly more erosive lesions (E or E/O) than VV Phase E (33.5% versus 20.2%). E/O and D were mostly found on MRI. Synovitis and BMLs were significantly associated with E/O and D with the following odds ratios (ORs): 8.4 (95% CI 1.8-13.6); OR: 13.7 (95% CI 2.9-21.0); OR: 15.7 (95% CI 3.2-23.5); OR: 38.5 (95% CI 9.5-57.0), respectively., Conclusion: MRI 0.3T appears completely relevant for EHOA lesion analysis. First, MRI shows more erosive lesions than RX in EHOA; second, it allows for the analysis of synovitis and BMLs to be associated with more specific structural MRI features (E/O and D)., Competing Interests: The authors have declared that no competing interests exist.

The objective of this study was to describe the normal variation of bone marrow fat content in the proximal femur considering the influence of side, age, sex and body mass index using fat fraction MRI. From September 2012 to July 2016, the MRI of 131 patients (258 hips) considered to have a normal MRI appearance were retrospectively evaluated. Patient records were searched to allow calculation of the body mass index (BMI). Water-fat based chemical shift MRI was available for all patients included. Proton density fat fraction maps were calculated, and measurements were performed in the femoral epiphysis, intertrochanteric region, and greater trochanter. The influence of patient age, sex, hip side and BMI on fat fraction values was assessed. Fat fraction was significantly different in the different locations evaluated (P = 0.0001). Patient sex and age significantly influenced fat fraction values in all regions evaluated (P < 0.02) with the exception of the epiphysis for sex (p = 0.07). In all locations, PDFF values were higher in men compared to women (3.3%, 4.4% and 13.1% higher in the epiphysis, greater trochanter and intertrochanteric region respectively). The intertrochanteric region presented the lowest fat fraction values with the highest variation compared to the greater trochanter and the epiphysis. BMI only influenced fat fraction values in the intertrochanteric region of females over 42 years old (P = 0.014). The interobserver variability of the measurements performed was considered to be excellent (ICC = 0.968). In conclusion, patient sex, age, and measurement location significantly influenced fat fraction values indicating that specific standards of reference are needed depending on these factors.

The objective of this study is to identify the prevalence of vertebral fractures (VFs) and to measure the scanographic bone attenuation coefficient of the first lumbar vertebra (SBAC-L1) based CT-scan, a biomarker of bone fragility in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and in a control group. This monocentric and retrospective study included patients with RA and AS, based on ACR/EULAR or New-York criteria, respectively. A control group was constituted. All of the patients received a CT-scan. VFs were determined via CT-scans according to the Genant classification, and the SBAC-L1 was measured in Hounsfield units (HU). SBAC-L1 ≤145 HU (fracture threshold) defined patients at risk of VFs. 244 patients were included (105 RA, 83 AS, 56 controls). Of the 4.365 vertebrae studied, 66 osteoporotic VFs were found in 36 patients: 18 (17.1%) RA, 13 (15.7%) AS and 5 (8.9%) controls. The mean SBAC-L1 was 142.2 (±48.4) HU for RA, 142.8 (±48.2) for AS, both of which were significantly lower than that of the control group (161.8 (±42.7) HU). Of the 36 patients with VFs and rheumatism, 28% had a T-score ≤-2.5 SD and 71.4% a SBAC-L1 ≤145 HU. A T-score ≤-2.5 SD and a SBAC-L1 ≤145 HU were associated with VF (OR = 3.07 (CI 95%: 1.07; 8.81), and 2.31 (CI 95%: 1.06; 5.06)), respectively. The SBAC-L1 was significantly lower in the RA and AS groups than in the control group. Furthermore, SBAC-L1 ≤145 HU was associated with a higher risk of VFs, with an odds ratio similar to that of a DXA.

Mean telomere length in human leukocyte DNA samples reflects the different lengths of telomeres at the ends of the 23 chromosomes and in an admixture of cells. However, only rudimentary information is available regarding the distribution of telomere lengths in all chromosomes and the different cell types in leukocyte samples. Understanding the configuration of leukocyte telomere length distribution (LTLD) could be helpful in capturing intrinsic elements that are not provided by the mean leukocyte telomere length (mLTL). The objective of this study was to analyse LTLD and its temporal variation in adults. Leukocyte samples were donated on two occasions (8 years apart) by 72 participants in the ADELAHYDE study. Telomere length was measured by Southern blotting of the terminal restriction fragments. Individuals with comparable mLTLs displayed different shapes of LTLDs. Inter-individual variation in LTLD shape was much larger than intra-individual variation in LTLD shape between baseline and follow-up leukocyte samples. These results show an important individual stability of LTLD shape over time indicating that each individual has a characteristic LTLD signature.

The present study addresses the problem of sequential least square multidimensional linear regression, particularly in the case of a data stream, using a stochastic approximation process. To avoid the phenomenon of numerical explosion which can be encountered and to reduce the computing time in order to take into account a maximum of arriving data, we propose using a process with online standardized data instead of raw data and the use of several observations per step or all observations until the current step. Herein, we define and study the almost sure convergence of three processes with online standardized data: a classical process with a variable step-size and use of a varying number of observations per step, an averaged process with a constant step-size and use of a varying number of observations per step, and a process with a variable or constant step-size and use of all observations until the current step. Their convergence is obtained under more general assumptions than classical ones. These processes are compared to classical processes on 11 datasets for a fixed total number of observations used and thereafter for a fixed processing time. Analyses indicate that the third-defined process typically yields the best results.

Background: There is currently no recommendation for the mean arterial pressure target in the particular setting of Extracorporeal Cardiopulmonary Resuscitation (ECPR) in the first hours following cardiogenic shock complicated by cardiac arrest. This study aimed to assess the effects of two different levels of mean arterial pressure on macrocirculatory, microcirculatory, and metabolic functions., Design: Randomized animal study., Setting: University research laboratory., Intervention: Ventricular fibrillation was induced in 14 male pigs by surgical ligature of the interventricular coronary artery. After 20 min of cardiopulmonary resuscitation, Extracorporeal Life Support (ECLS) was initiated to restore circulatory flow. Thereafter, animals were randomly allocated to a high mean arterial pressure group (High-MAP, 80-85 mm Hg) or to a standard mean arterial pressure group (Standard-MAP, 65-70 mm Hg). Assessments conducted at baseline, immediately following and 6 h after ECLS initiation were focused on lactate evolution, amount of infused fluid, and microcirculatory parameters., Results: There was no significant difference between the two groups at the time of ECLS initiation and at 6 h with regard to lactate levels (High-MAP vs. Standard-MAP: 8.8 [6.7-12.9] vs. 9.6 [9.1-9.8] mmol·l, P = 0.779 and 8.9 [4.3-11.1] vs. 3.3 [2.4-11] mmol·l, P = 0.603). Infused fluid volume did not significantly differ between the two groups (4,000 [3,500-12,000] vs. 5,000 [2,500-18,000] mL, P = 0.977). There was also no significant difference between the two groups regarding renal and liver functions, and sublingual capillary microvascular flow index assessed by Sidestream Dark Field imaging., Conclusion: Compared with a standard mean arterial pressure regimen, targeting a high mean arterial pressure in the first hours of an experimental ECPR model did not result in any hemodynamic improvement nor in a decrease in the amount of infused fluid.

Background: Administration of a selective β1-blocker, such as esmolol, in human septic shock has demonstrated cardiovascular protective effects related to heart rate reduction. Certain experimental data also indicate that esmolol exerts systemic anti-inflammatory and beneficial effects on vascular tone. Thus, the present study aimed to determine whether a non-chronotropic dose of esmolol maintains its protective cardiovascular and anti-inflammatory effects in experimental septic shock., Methods: Four hours after cecal ligation and puncture (CLP), Wistar male rats were randomly allocated to the following groups (n = 8): CLP, CLP + E-1 (esmolol: 1 mg.kg -1 .h -1 ), CLP + E-5 (esmolol: 5 mg.kg -1 .h -1 ), CLP + E-18 (esmolol: 18 mg.kg -1 .h -1 ). An additional eight rats underwent sham operation. All rats received a continuous infusion of saline, analgesic and antibiotics 4 hours after the surgery. Assessment at 18 hours included in vivo cardiac function assessed by echocardiography and ex vivo vasoreactivity assessed by myography. Circulating cytokine levels (IL-6 and IL-10) were measured by ELISA. Cardiac and vascular protein expressions of p-NF-κB, IκBα, iNOS, p-AKT/AKT and p-eNOS/eNOS were assessed by western blotting., Results: CLP induced tachycardia, hypotension, cardiac output reduction, hyperlactatemia and vascular hypo-responsiveness to vasopressors. Compared to CLP animals, heart rate was unchanged in CLP + E-1 and CLP + E-5 but was reduced in CLP + E-18. Stroke volume, cardiac output, mean arterial pressure and lactatemia were improved in CLP + E-1 and CLP + E-5, while vascular responsiveness to phenylephrine was only improved in CLP + E-5 and CLP + E-18. Plasma IL-6 levels were decreased in all esmolol groups. p-NF-κB was decreased in both cardiac and vascular tissues in CLP + E-5 and CLP + E-18., Conclusion: In experimental septic shock, low doses of esmolol still improved cardiac function and vasoreactivity. These benefits appear to be associated with a modulation of inflammatory pathways.