Machine and Deep Learning Approaches Applied to Classify Gougerot-Sjögren Syndrome and Jointly Segment Salivary Glands.

To diagnose Gougerot-Sjögren syndrome (GSS), ultrasound imaging (US) is a promising tool for helping physicians and experts. Our project focuses on the automatic detection of the presence of GSS using US. Ultrasound imaging suffers from a weak signal-to-noise ratio. Therefore, any classification or segmentation task based on these images becomes a difficult challenge. To address these two tasks, we evaluate different approaches: a classification using a machine learning method along with feature extraction based on a set of measurements following the radiomics guidance and a deep-learning-based classification. We propose, therefore, an innovative method to enhance the training of a deep neural network with a two phases: multiple supervision using joint classification and a segmentation implemented as pretraining. We highlight the fact that our learning methods provide segmentation results similar to those performed by human experts. We obtain proficient segmentation results for salivary glands and promising detection results for Gougerot-Sjögren syndrome; we observe maximal accuracy with the model trained in two phases. Our experimental results corroborate the fact that deep learning and radiomics combined with ultrasound imaging can be a promising tool for the above-mentioned problems.

Pulmonary embolism detection on venous thrombosis ultrasound images with bi-dimensional entropy measures: Preliminary results.

BACKGROUND: Venous thromboembolism (VTE) is a common health issue. A clinical expression of VTE is a deep vein thrombosis (DVT) that may lead to pulmonary embolism (PE), a critical illness. When DVT is suspected, an ultrasound exam is performed. However, the characteristics of the clot observed on ultrasound images cannot be linked with the presence of PE. Computed tomography angiography is the gold standard to diagnose PE. Nevertheless, the latter technique is expensive and requires the use of contrast agents. PURPOSE: In this article, we present an image processing method based on ultrasound images to determine whether PE is associated or not with lower limb DVT. In terms of medical equipment, this new approach (Doppler ultrasound image processing) is inexpensive and quite easy. METHODS: With the aim to help medical doctors in detecting PE, we herein propose to process ultrasound images of patients with DVT. After a first step based on histogram equalization, the analysis procedure is based on the use of bi-dimensional entropy measures. Two different algorithms are tested: the bi-dimensional dispersion entropy ( D i s p E n 2 D $DispEn_{2D}$ ) mesure and the bi-dimensional fuzzy entropy ( F u z E n 2 D $FuzEn_{2D}$ ) mesure. Thirty-two patients (12 women and 20 men, 67.63 ± 16.19 years old), split into two groups (16 with and 16 without PE), compose our database of around 1490 ultrasound images (split into seven different sizes from 32× 32 px to 128 × 128 px). p-values, computed with the Mann-Whitney test, are used to determine if entropy values of the two groups are statistically significantly different. Receiver operating characteristic (ROC) curves are plotted and analyzed for the most significant cases to define if entropy values are able to discriminate the two groups. RESULTS: p-values show that there are statistical differences between F u z E n 2 D $FuzEn_{2D}$  of patients with PE and patients without PE for 112× 112 px and 128× 128 px images. Area under the ROC curve (AUC) is higher than 0.7 (threshold for a fair test) for 112× 112 and 128× 128 images. The best value of AUC (0.72) is obtained for 112× 112 px images. CONCLUSIONS: Bi-dimensional entropy measures applied to ultrasound images seem to offer encouraging perspectives for PE detection: our first experiment, on a small dataset, shows that F u z E n 2 D $FuzEn_{2D}$  on 112× 112 px images is able to detect PE. The next step of our work will consist in testing this approach on a larger dataset and in integrating F u z E n 2 D $FuzEn_{2D}$  in a machine learning algorithm. Furthermore, this study could also contribute to PE risk prediction for patients with VTE.

Prevalence and risk factors of significant persistent pain symptoms after critical care illness: a prospective multicentric study.

BACKGROUND: Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated. METHODS: We performed a prospective multicentric study in patients with an intensive care unit (ICU) length of stay ≥ 48 h. The primary outcome was the prevalence of significant persistent pain, defined as a numeric rating scale (NRS) ≥ 3, 3 months after admission. Secondary outcomes were the prevalence of symptoms compatible with neuropathic pain (ID-pain score > 3) and the risk factors of persistent pain. RESULTS: Eight hundred fourteen patients were included over a 10-month period in 26 centers. Patients had a mean age of 57 (± 17) years with a SAPS 2 score of 32 (± 16) (mean ± SD). The median ICU length of stay was 6 [4-12] days (median [interquartile]). At 3 months, the median intensity of pain symptoms was 2 [1-5] in the entire population, and 388 (47.7%) patients had significant pain. In this group, 34 (8.7%) patients had symptoms compatible with neuropathic pain. Female (Odds Ratio 1.5 95% CI [1.1-2.1]), prior use of anti-depressive agents (OR 2.2 95% CI [1.3-4]), prone positioning (OR 3 95% CI [1.4-6.4]) and the presence of pain symptoms on ICU discharge (NRS ≥ 3) (OR 2.4 95% CI [1.7-3.4]) were risk factors of persistent pain. Compared with sepsis, patients admitted for trauma (non neuro) (OR 3.5 95% CI [2.1-6]) were particularly at risk of persistent pain. Only 35 (11.3%) patients had specialist pain management by 3 months. CONCLUSIONS: Persistent pain symptoms were frequent in critical illness survivors and specialized management remained infrequent. Innovative approaches must be developed in the ICU to minimize the consequences of pain. TRIAL REGISTRATION: NCT04817696. Registered March 26, 2021.

Validation of a pre-established triage protocol for critically ill patients in a COVID-19 outbreak under resource scarcity: A retrospective multicenter cohort study.

INTRODUCTION: In case of COVID-19 related scarcity of critical care resources, an early French triage algorithm categorized critically ill patients by probability of survival based on medical history and severity, with four priority levels for initiation or continuation of critical care: P1 -high priority, P2 -intermediate priority, P3 -not needed, P4 -not appropriate. This retrospective multi-center study aimed to assess its classification performance and its ability to help saving lives under capacity saturation. METHODS: ICU patients admitted for severe COVID-19 without triage in spring 2020 were retrospectively included from three hospitals. Demographic data, medical history and severity items were collected. Priority levels were retrospectively allocated at ICU admission and on ICU day 7-10. Mortality rate, cumulative incidence of death and of alive ICU discharge, length of ICU stay and of mechanical ventilation were compared between priority levels. Calculated mortality and survival were compared between full simulated triage and no triage. RESULTS: 225 patients were included, aged 63.1±11.9 years. Median SAPS2 was 40 (IQR 29-49). At the end of follow-up, 61 (27%) had died, 26 were still in ICU, and 138 had been discharged. Following retrospective initial priority allocation, mortality rate was 53% among P4 patients (95CI 34-72%) versus 23% among all P1 to P3 patients (95CI 17-30%, chi-squared p = 5.2e-4). The cumulative incidence of death consistently increased in the order P3, P1, P2 and P4 both at admission (Gray's test p = 3.1e-5) and at reassessment (p = 8e-5), and conversely for that of alive ICU discharge. Reassessment strengthened consistency. Simulation under saturation showed that this two-step triage protocol could have saved 28 to 40 more lives than no triage. CONCLUSION: Although it cannot eliminate potentially avoidable deaths, this triage protocol proved able to adequately prioritize critical care for patients with highest probability of survival, hence to save more lives if applied.

Atrial fibrillation and peripheral arterial disease define MPN patients with very high risk of thrombosis.

Myeloproliferative neoplasms (MPNs) are associated with a high risk of thrombotic and hemorrhagic complications, especially in elderly patients. Atrial fibrillation (AF) and peripheral arterial disease (PAD), also frequently discovered in aging patients, are associated with similar complications. We analysed the incidence and complication rates of AF and PAD in a large cohort of MPN patients. In total, 289/1113 patients (26 %) suffered at least one of these diseases as follows: 179 (16.1 %) with AF alone, 81 with PAD alone (7.3 %) and 29 (2.6 %) with both conditions. Postdiagnosis thrombotic events were observed in 31.3 % of AF patients (p = 0.002, OR = 1.80 [1.23;2.61]), 35.8 % of PAD patients (p = 0.002, OR = 2.21[1.31;3.67]) and 62.1 % of AF/PAD patients (p < 0.0001, OR = 6.47 [2.83;15.46]) compared to 20.1 % of no-AF/no-PAD patients. Postdiagnosis hemorrhagic events were also identified in 17.9 %, 16 %, 24.1 % and 10.1 % of AF, PAD, AF/PAD, and no-AF/no-PAD patients, respectively (p = 0.003). This significantly higher risk of thrombosis/bleeding was also observed in patients <60 years old. AF and PAD were significant risk factors for both thrombotic and hemorrhagic risks in multivariate analysis. We identified AF and PAD as criteria for high risk of thrombosis, hemorrhage, and death, emphasizing the interest in early detection and efficient treatment of these conditions.

Venous Thromboembolism Associated with Assisted Reproductive Technology: A Systematic Review and Meta-analysis.

BACKGROUND: Hormonal exposure leads to an increased risk of venous thromboembolism (VTE) but the risk of VTE associated with assisted reproductive technology (ART) is not clearly determined. METHODS: We searched in PubMed, EMBASE, Web of Science, and the Cochrane Library databases and identified all relevant articles published up to February 1, 2021. The primary objective was to determine the frequency of VTE associated with ART. Secondary objectives were to determine (1) the risk of VTE associated with ART as compared to pregnancy without ART; (2) the risk of VTE associated with ovarian hyperstimulation syndrome (OHSS); and (3) to determine potential risk factors of VTE related to ART. RESULTS: Fourteen studies were included. The overall frequency of VTE associated with ART was 0.23% (95% confidence interval [CI]: 0.07-0.46). Women undergoing ART had a two- to threefold increased risk of VTE as compared to spontaneous pregnancy (relative risk [RR]: 2.66; 95% CI: 1.60-4.43). The overall frequency of VTE specifically related to OHSS was <0.001%. The risk of VTE after ART complicated by OHSS, as compared to ART without OHSS, was higher but not statistically significant (RR: 14.83; 95% CI: 0.86-255.62). Risk factors of VTE associated with ART were in vitro fertilization procedure (RR, odds ratio [OR], and hazard ratio varying from 1.77, 95% CI: 1.41-2.23 to 4.99, 95% CI: 1.24-20.05), hyperhomocysteinemia (OR: 15.2; 95% CI: 2.0-115.0), polycystic ovarian syndrome (PCOS) (RR: 4.8; 95% CI: 1.7-13.4), successful ART leading to pregnancy (OR: 13.94; 95% CI: 1.41-137.45). CONCLUSION: Further large prospective studies on risk factors of VTE in women undergoing ART are needed in order to optimize thromboprophylaxis in this context.

In-hospital cardiac arrest rhythm analysis by anesthesiologists: a diagnostic performance study.

PURPOSE: In-hospital cardiac arrest is associated with high morbidity and mortality, with an overall survival rate at one year of approximately 13%. The first cardiac rhythm is often analyzed by anesthesiologist-intensivists. We aimed to determine the diagnostic performance of anesthesiologist-intensivists when distinguishing between shockable and nonshockable rhythms. METHODS: We conducted a simulation-based, multicentre, prospective, observational study between May 2019 and March 2020. The responses of the participants were used to calculate individual sensitivity (defined as the proportion of decisions to shock for shockable rhythms) and individual specificity (defined as the proportion of decisions not to shock for nonshockable rhythms). The main outcome measure was the overall diagnostic performance, defined as the overall sensitivity and specificity. Secondary outcome measures were the sensitivity and specificity of participants' decisions for each type of cardiac arrest rhythm and their decision-making times. RESULTS: Among the 267 physicians contacted, 179 (67%) completed the test. The median [interquartile range (IQR)] overall sensitivity was 88 [79-95]% and the median overall specificity was 86 [77-92]%. Among shockable rhythms, the median [IQR] sensitivity was 100 [100-100]% for ventricular tachycardia (VT), 100 [100-100]% for coarse ventricular fibrillation (VF), and 60 [20-100]% for fine VF. The median [IQR] specificities for nonshockable rhythms were 93 [86-100]% for asystole and 83 [72-86]% for pulseless electrical activity. The median decision times ranged from 2.0 to 3.5 sec. CONCLUSION: Anesthesiologist-intensivists were quickly and effectively able to analyze rhythms in this simulation-based study. Participants' sensitivity in deciding to deliver shocks for VT and coarse VF was excellent, while specificity of their decisions for pulseless electrical activity was insufficient.

RéSUMé: OBJECTIF: L'arrêt cardiaque intra-hospitalier est associé à une morbidité et mortalité élevées, associées à un taux de survie global à un an d'environ 13 %. Le premier rythme cardiaque est souvent analysé par des anesthésiologistes-intensivistes. Nous avons cherché à déterminer la performance diagnostique des anesthésiologistes-intensivistes à distinguer un rythme choquable d'un rythme non choquable. MéTHODE: Nous avons effectué une étude observationnelle prospective, multicentrique basée sur la simulation entre mai 2019 et mars 2020. Les réponses des participants ont été utilisées pour calculer la sensibilité individuelle (définie comme étant la proportion de décisions de choquer pour les rythmes choquables) et la spécificité individuelle (définie comme la proportion de décisions de ne pas choquer pour les rythmes non choquables). Le critère d'évaluation principal était la performance diagnostique globale, définie comme étant la sensibilité et la spécificité globales. Les critères d'évaluation secondaires étaient la sensibilité et la spécificité des décisions des participants pour chaque type de rythme d'arrêt cardiaque, ainsi que le temps de prise de décision. RéSULTATS: Parmi les 267 médecins contactés, 179 (67 %) ont complété le test. La sensibilité globale médiane [écart interquartile (ÉIQ)] était de 88 [79-95] % et la spécificité globale médiane était de 86 [77-92] %. Parmi les rythmes choquables, la sensibilité médiane [ÉIQ] était de 100 [100-100] % pour la tachycardie ventriculaire (TV), de 100 [100-100] % pour la fibrillation ventriculaire (FV) large et de 60 [20-100] % pour la FV fine. Les spécificités médianes [ÉIQ] pour les rythmes non choquables étaient de 93 [86-100] % pour l'asystolie et de 83 [72-86] % pour l'activité électrique sans pouls. Les temps de décision médians variaient de 2,0 à 3,5 secondes. CONCLUSION: Les anesthésiologistes-intensivistes ont été rapidement et efficacement en mesure d'analyser les rythmes dans cette étude basée sur la simulation. La sensibilité de prendre la décision d'administrer un choc pour une TV ou une FV était excellente pour les participants, tandis que la spécificité de cette décision pour l'activité électrique sans pouls était insuffisante.

Predictors of Recurrent Venous Thromboembolism or Arterial Thrombotic Events during and after Anticoagulation for a First Venous Thromboembolism.

After first episodes of venous thromboembolism (VTE), patients are at increased risk of recurrent VTE and arterial thrombotic events (ATE) compared with the general population, two disorders that are influenced by anticoagulation. However, risk factors of these conditions occurring during and after anticoagulation are little described. Using cause-specific hazard regression models, we aimed to determine risk factors of the composite outcome recurrent VTE/ATE, and separately recurrent VTE or ATE, during and after anticoagulation in patients with first episodes of VTE from a prospective cohort. Hazard ratios (HRs) are given with 95% confidence intervals (CIs). A total of 2,011 patients treated for at least 3 months were included. A total of 647 patients had recurrent VTE/ATE (incidence: 4.69% per patient-years) during overall follow-up (median: 92 months). Of these events, 173 occurred during anticoagulation (incidence: 3.67% per patient-years). Among patients free of events at the end of anticoagulation, 801 had a post-anticoagulation follow-up ≥3 months; and 95 had recurrent VTE/ATE (incidence: 1.27% per patient-years). After adjustment for confounders, cancer-associated VTE (HR: 2.64, 95% CI: 1.70-4.11) and unprovoked VTE (HR: 1.95, 95% CI: 1.35-2.81) were the identified risk factors of recurrent VTE/ATE during anticoagulation (vs. transient risk factor-related VTE). Risk factors of recurrent VTE/ATE after anticoagulation included 50 to 65 years of age (vs. < 50, HR: 1.99, 95% CI: 1.04-3.81), older than 65 years (vs. < 50, HR: 5.28, 95% CI: 3.03-9.21), and unprovoked VTE (vs. transient risk factor-related VTE, HR: 2.06, 95% CI: 1.27-3.34). Cancer-associated VTE and unprovoked VTE are the main risk factors of recurrent VTE/ATE during anticoagulation, while older age and unprovoked VTE mainly predict the risk of these events after anticoagulation.

A Multicenter, Investigator-Blinded, Randomized Controlled Trial to Assess the Efficacy of Calf Neuromuscular Electrical Stimulation Program on Walking Performance in Peripheral Artery Disease: The ELECTRO-PAD Study Protocol.

This paper describes a currently on-going multicenter, randomized controlled trial designed to assess the efficacy of calf neuromuscular electrical stimulation (NMES) on changes in maximal walking distance in people with lower extremity peripheral artery disease (PAD), compared with a non-intervention control-group. This study (NCT03795103) encompasses five participating centers in France. PAD participants with a predominant claudication at the calf level and a maximal treadmill walking distance ≤300 m are randomized into one of the two groups: NMES group or Control group. The NMES program consists of a 12-week program of electrical stimulations at the calf-muscle level. The primary outcome of the study is the change in maximal treadmill walking distance at 12 weeks. Main secondary outcomes include changes in the pain-free treadmill walking distance; 6 min total walking distance; global positioning system (GPS)-measured outdoor walking capacity; daily physical activity level by accelerometry; self-reported walking impairment; self-reported quality of life; ankle-brachial index; and skin microvascular function, both at the forearm and calf levels. Recruitment started in September 2019 and data collection is expected to end in November 2022.

Anticoagulation for VTE: Impact on the Risk of Major Adverse Cardiovascular Events.

BACKGROUND: It was recently established that patients who developed VTE are at increased risk of major adverse cardiovascular events (MACE) compared with the general population. However, whether the anticoagulation used for VTE influences the risk of MACE remains undescribed. RESEARCH QUESTION: Does the anticoagulant treatment for VTE affect the risk of subsequent MACE? STUDY DESIGN AND METHODS: This study included patients from a large prospective cohort who received only one family of anticoagulant treatment after the acute phase of VTE, including vitamin K antagonist (VKAs) and direct oral anticoagulants (DOACs). MACE included nonfatal acute coronary syndrome, nonfatal stroke, and all-cause death. The secondary outcome, MACE-2, included cardiovascular death instead of all-cause death. Cox proportional and Fine-Gray models served to study the relationship between anticoagulation characteristics and the risk of outcomes. RESULTS: A total of 3,790 patients (47.2% male; mean age, 60.48 years) were included. A total of 1,228 patients (32.4%) were treated for 0 to 3 months (median in overall population, 6 months). Compared with these patients, those treated for 3 to 12 months (hazard ratio [HR], 0.64; 95% CI, 0.54-0.76) or > 12 months (HR, 0.47, 95% CI, 0.39-0.56) had a significant reduced risk of MACE following adjustment for confounders. Findings were similar for MACE-2 (sub-HR for 3-12 months, 0.61 [95% CI, 0.47-0.79]; sub-HR > 12 months, 0.52 [95% CI, 0.39-0.68]). After adjustment for confounders, there was a reduced risk of MACE (HR, 0.53; 95% CI, 0.39-0.71) and MACE-2 (sub-HR, 0.48; 95% CI, 0.29-0.77) in patients treated with DOACs (vs VKAs). INTERPRETATION: Treatment of VTE for > 3 months is associated with a reduced risk of MACE, as is treatment with DOACs vs VKAs. These findings, which may influence the choice of anticoagulation strategies for VTE, need confirmation by randomized clinical trials.

Risk Factors of Cardiovascular Death after Venous Thromboembolism: Results from a Prospective Cohort Study.

BACKGROUND: Cardiovascular deaths (CVDTs) are more frequent in patients with venous thromboembolism (VTE) than in the general population; however, risk factors associated with this increased risk of CVDT in patients with VTE are not described. METHODS: To determine the risk factors of CVDT in patients with VTE from a multicenter prospective cohort study, Fine and Gray subdistribution hazard models were conducted. RESULTS: Of the 3,988 included patients, 426 (10.7%) died of CVDT during a median follow-up of 5 years. The risk factors of CVDT after multivariate analyses were: age of 50 to 65 years (vs. <50 years, hazard ratio [HR]: 3.22, 95% confidence interval [CI]: 1.67-6.62), age >65 years (vs. <50 years, HR: 7.60, 95% CI: 3.73-15.52), cancer-associated VTE (vs. transient risk factor-related VTE, HR: 1.73, 95% CI: 1.15-2.61), unprovoked VTE (vs. transient risk factor-related VTE, HR: 1.42, 95% CI: 1.02-2.00), past tobacco use (vs. never, HR: 1.43, 95% CI: 1.06-1.94), current tobacco use (vs. never, HR: 1.87, 95% CI: 1.15-3.01), hypertension (HR: 2.11, 95% CI: 1.51-2.96), chronic heart failure (HR: 2.28, 95% CI: 1.37-3.79), chronic respiratory failure (HR: 1.72, 95% CI: 1.02-2.89), and atrial fibrillation (HR: 1.67, 95% CI: 1.06-2.60). The risk of CVDT was significantly reduced with direct oral anticoagulants (vs. vitamin-K antagonists) and with longer duration of treatment (>3 months). CONCLUSION: Risk factors of CVDT after VTE include some traditional cardiovascular risk factors and other risk factors that are related to characteristics of VTE, and patients' comorbidities.

The conundrum of the definition of haemorrhagic shock: a pragmatic exploration based on a scoping review, experts' survey and a cohort analysis.

PURPOSE: Traumatic hemorrhagic shock (THS) is a complex, dynamic process and, no consensual definition of THS is available. This study aims (1) to explore existing definitions of traumatic hemorrhagic shock (THS), (2) to identify essential components of these definitions and (3) to illustrate in a pragmatic way the consequences of applying five of these definitions to a trauma registry. METHODS: We conducted (1) a scoping review to identify the definitions used for traumatic hemorrhagic shock (THS); (2) an international experts survey to rank by relevance a selection of components extracted from these definitions and (3) a registry-based analysis where several candidate definitions were tested in a large trauma registry to evaluate how the use of different definitions affected baseline characteristics, resources use and patient outcome. RESULTS: Sixty-eight studies were included revealing 52 distinct definitions. The most frequently used was "a systolic blood pressure (SBP) less than or equal to 70 mmHg or between 71 and 90 mmHg if the heart rate is greater than or equal to 108 beats per min". The expert panel identified base excess, blood lactate concentration, SBP and shock index as the most relevant physiological components to define THS. Five definitions of THS were tested and highlighted significant differences across groups on important outcomes such as the proportion of massive transfusion, the need for surgery, in-hospital length of stay or in-hospital mortality. CONCLUSIONS: This study demonstrates a large heterogeneity in the definitions of THS suggesting a need for standardization. Five candidate definitions were identified in a three-step process to illustrate how each shapes study cohort composition and impacts outcome. The results inform research stakeholders in the choice of a consensual definition.

Risk Factors for Major Adverse Cardiovascular Events and Major Adverse Limb Events after Venous Thromboembolism: A Large Prospective Cohort Study.

BACKGROUND: There is an increased risk of arterial events including major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after venous thromboembolism (VTE). However, their risk factors remain little explored. METHODS: We aimed to determine the risk factors for MACE (acute coronary syndrome/stroke/cardiovascular death) and MALE (limb ischemia/critical limb ischemia/non-traumatic amputation/any limb revascularization) after VTE. Competing risk models (Fine-Gray) were used in a multicenter prospective cohort of 4,940 patients (mean age: 64.6 years and median follow-up: 64 months). RESULTS: MACE occurred in 17.3% of participants (2.35% per patient-years) and MALE in 1.7% (0.27% per patient-years). In multivariable analysis, the identified risk factors for MACE were the age of 50 to 65 years (vs. <50 years, hazard ratio [HR]: 2.00, 95% confidence interval [CI]: 1.38-2.91), age >65 years (vs. <50 years, HR 4.85, 95% CI: 3.35-7.02), pulmonary embolism + deep vein thrombosis (DVT) (vs. isolated-DVT, HR: 1.25, 95% CI: 1.02-1.55), unprovoked-VTE (vs. transient risk factor associated-VTE, HR: 1.29, 95% CI: 1.04-1.59), current tobacco use (vs. never, HR: 1.45, 95% CI: 1.07-1.98), hypertension (HR: 1.61, 95% CI: 1.30-1.98), past history of symptomatic atherosclerosis (HR: 1.52, 95% CI: 1.17-1.98), heart failure (HR: 1.71, 95% CI: 1.21-2.42), atrial fibrillation (HR: 1.55, 95% CI: 1.15-2.08), and vena cava filter insertion (HR: 1.46, 95% CI: 1.03-2.08). The identified risk factors for MALE were the age of 50-65 years (vs. <50 years, HR: 3.49, 95% CI: 1.26-9.65) and atrial fibrillation (HR: 2.37, 95% CI: 1.15-4.89). CONCLUSIONS: Risk factors for MACE and MALE after VTE included some traditional cardiovascular risk factors, patient's comorbidities, and some characteristics of VTE.

Risk factors of arterial thrombotic events after unprovoked venous thromboembolism, and after cancer associated venous thromboembolism: A prospective cohort study.

INTRODUCTION: The increased risk of arterial thrombotic (ATE) after VTE, particularly when they are unprovoked or cancer-associated has been established. However, the risk factors of ATE after these VTE remain unclear. MATERIAL AND METHODS: Using cause-specific hazard regression models, we determined risk factors of ATE (myocardial infarction, ischemic stroke, acute limb ischemia, digestive tract ischemia, or renal ischemia) in 2242 patients with unprovoked VTE and in 914 patients with cancer-associated VTE from a multi-center prospective cohort. RESULTS: Of patients with unprovoked-VTE, 174 developed ATE (7.8%, incidence: 1.26 per 100 patient-years) during follow-up (median: 68 months). Among patients with cancer-associated VTE, 57 developed ATE (6.2%, incidence: 1.98 per 100 patient-years) during follow-up (median: 30 months). After multivariable analysis, the identified risk factors of ATE in patients with unprovoked-VTE were age > 65 years (vs. <50 years, HR 2.59, 95% CI: 1.56-4.29), past history of symptomatic atherosclerosis (HR 2.11, 95% CI: 1.40-3.19), and treatment with low molecule weight heparin (vs. vitamin K antagonists, HR: 2.26, 95% CI: 1.13-4.52). In patients with cancer-associated VTE, the identified risk factors of ATE were: past history of symptomatic atherosclerosis (HR: 3.13, 95% CI: 1.72-5.67), and ongoing anticoagulation at the diagnosis of VTE (HR: 2.77, 95% CI: 1.07-7.22). CONCLUSIONS: The risk of ATE after unprovoked VTE and after cancer-associated VTE, is determined by some classic cardiovascular risk factors and appears to be influenced by anticoagulant treatment introduced for VTE, as well as the presence or absence of ongoing anticoagulation at the diagnosis of VTE.

Comparison of halo and compression signs assessed by a high frequency ultrasound probe for the diagnosis of Giant Cell Arteritis.

OBJECTIVE: To evaluate the diagnosis performances of halo and compression signs alone and combined, assessed by a high frequency 22-MHz probe, and test their agreement in giant cell arteritis (GCA). METHODS: In this cross-sectional study on patients suspected with GCA, halo sign was defined as hypo or iso-echogenic circumferential aspect of the vessel wall in transverse or longitudinal view; and compression sign was defined as visibility of the vessel wall upon transducer-imposed compression of the artery. Agreement of the two signs was tested using the Cohen's kappa statistic. RESULTS: A total of 80 patients (50% women) were included with a mean age of 74.4 years. Twenty participants (25%) were ultimately treated for GCA. Halo and compression signs have respective prevalences of 35% and 48%, with respective sensitivity and specificity of 80% and 80% for the halo sign; and 85% and 65% for the compression sign. The kappa coefficient for the global agreement of the two signs was 0.67 (95% confident interval: 0.54-0.85). Combination of the two signs give a sensitivity of 80% and a specificity of 81.7%. CONCLUSION: Halo and compression signs assessed by a high frequency probe, show a good level of agreement for the diagnosis of GCA and improve ultrasound specificity when combined together.

Risk stratification for predicting recurrent venous thromboembolism after discontinuation of anticoagulation: a post hoc analysis of a French prospective multicentre study.

BACKGROUND: We aimed to validate and to refine current recurrent venous thromboembolism (VTE) risk classification. METHODS: We performed a post hoc analysis of a multicentre cohort including 1881 patients with a first symptomatic VTE prospectively followed after anticoagulation discontinuation. The primary objective was to validate the International Society of Thrombosis and Haemostasis (ISTH) risk classification in predicting recurrence risk. The secondary objective was to evaluate a refined ISTH classification based on the recurrence risk estimate for each individual risk factor. RESULTS: During a 4.8-year median follow-up after anticoagulation discontinuation, symptomatic recurrent VTE occurred in 230 patients (12.2%). Based on the ISTH classification, patients with unprovoked VTE or VTE with minor or major persistent risk factors had a 2-fold increased recurrence risk compared with those with VTE and major transient risk factors. Recurrence risk was not increased in patients with minor transient factors (hazard ratio (HR) 1.31, 95% CI 0.84-2.06). Individual risk factors analysis identified hormone-related VTE (pregnancy: HR 0.26, 95% CI 0.08-0.82; oestrogens: HR 0.25, 95% CI 0.14-0.47) and amyotrophic lateral sclerosis (HR 5.84, 95% CI 1.82-18.70). After reclassification of these factors as major transient for the former and major persistent for the latter, the modified ISTH classification allowed us to accurately discriminate between patients at low risk of recurrence (i.e. with major transient risk factors) and those at high risk of recurrence (i.e. without major transient risk factors). CONCLUSIONS: Among patients who stopped anticoagulation after a first VTE, a refined ISTH classification based on recurrence risk intensity of individual factors allowed discrimination between patients at low recurrence risk, including hormonal exposure in women, and patients at high recurrence risk.

Cardiovascular Mortality after Venous Thromboembolism: A Meta-Analysis of Prospective Cohort Studies.

Many studies from current literature show that cardiovascular diseases in patients with venous thromboembolism (VTE) are more frequent than in the general population without VTE. However, data summarizing the impact of cardiovascular diseases on mortality of patients with VTE are lacking. In this systematic review and meta-analysis, we aimed to determine the frequency and incidence rate of cardiovascular death in patients with VTE. MEDLINE and EMBASE were searched from January 1, 2000 to February 28, 2021. Eligible studies were observational prospective cohort studies including patients with VTE and reporting all causes of death. Cardiovascular death was defined as deaths that result from new or recurrent pulmonary embolism, death due to acute myocardial infarction, sudden cardiac death or heart failure, death due to stroke, death due to cardiovascular procedures or hemorrhage, death due to ruptured aortic aneurysm or aortic dissection and death due to other cardiovascular causes. Random-effect models meta-analysis served to determine all pooled effect size of interest with their 95% confidence interval (CI). Thirteen observational studies enrolling 22,251 patients were identified and included. The mean/median age varied between 49 and 75 years. The proportion of men ranged from 38.3 to 53.2%. The overall pooled frequency of cardiovascular death in patients with VTE was 3.9% (95% CI: 2.5-5.6%), while the overall pooled frequency of all-cause mortality was 12.0% (95% CI: 9.1-15.4%). The pooled proportion of cardiovascular death among all causes of deaths in patients with VTE was 35.2% (95% CI: 22.2-49.3%). The pooled incidence rate of cardiovascular death was 1.92 per 100 patient-years (95% CI: 0-4.1). The frequency of cardiovascular death in patients with VTE was significantly higher than in patients without VTE (risk ratio: 3.85, 95% CI: 2.75-5.39). Based on this updated meta-analysis from 13 prospective cohort studies, cardiovascular death in patients with VTE is more frequent than in the general population without VTE.

Risk Factors of Arterial Events in Patients with Venous Thromboembolism: A Systematic Review and Meta-Analysis.

BACKGROUND: If recent studies suggested that arterial ischemic events in patients with venous thromboembolism (VTE) are more frequent than in the general population without VTE, whether patients with VTE have different risk factors of arterial events than classic known cardiovascular risk factors remain undefined. Through this systematic review and meta-analysis, we aimed to identify risk factors of arterial ischemic events in patients with VTE. METHODS: We searched PubMed, EMBASE, and Cochrane databases to identify cohort studies published between January 1, 2000, and December 31, 2020, reporting risk factors of arterials ischemic events in patients with VTE. Random-effect models meta-analysis served to get the pooled hazard ratio (HR) and 95% confidence interval (CI) of each risk factor identified. RESULTS: We screened 1,467 records of which 18 were finally included in systematic review and 10 in meta-analyses. Adjusted HR for 9 factors were included in meta-analysis. Male gender (HR: 1.38; 95% CI: 1.28-1.49), diabetes (HR: 1.65; 95% CI: 1.28-2.12), hypertension (HR: 1.38; 95% CI: 1.04-1.84), previous atherothrombotic event (HR: 3.22; 95% CI: 1.12-9.23), chronic kidney disease (HR: 1.41; 95% CI: 1.05-1.88), cancer (HR: 1.72; 95% CI: 1.41-2.09), and unprovoked VTE (HR: 1.88; 95% CI: 1.37-2.57) were the identified risk factors of arterial events in VTE population after meta-analysis. CONCLUSION: Risk factors of arterial events in patients with VTE include usual cardiovascular risk factors and other risk factors that are related to VTE such as cancer and unprovoked VTE.

French multicentre observational study on SARS-CoV-2 infections intensive care initial management: the FRENCH CORONA study.

AIM: Describing acute respiratory distress syndrome patterns, therapeutics management, and outcomes of ICU COVID-19 patients and indentifying risk factors of 28-day mortality. METHODS: Prospective multicentre, cohort study conducted in 29 French ICUs. Baseline characteristics, comorbidities, adjunctive therapies, ventilatory support at ICU admission and survival data were collected. RESULTS: From March to July 2020, 966 patients were enrolled with a median age of 66 (interquartile range 58-73) years and a median SAPS II of 37 (29-48). During the first 24 h of ICU admission, COVID-19 patients received one of the following respiratory supports: mechanical ventilation for 559 (58%), standard oxygen therapy for 228 (24%) and high-flow nasal cannula (HFNC) for 179 (19%) patients. Overall, 721 (75%) patients were mechanically ventilated during their ICU stay. Prone positioning and neuromuscular blocking agents were used in 494 (51%) and 460 (48%) patients, respectively. Bacterial co-infections and ventilator-associated pneumonia were diagnosed in 79 (3%) and 411 (43%) patients, respectively. The overall 28-day mortality was 18%. Age, pre-existing comorbidities, severity of respiratory failure and the absence of antiviral therapy on admission were identified as independent predictors of 28-day outcome. CONCLUSION: Severity of hypoxaemia on admission, older age (> 70 years), cardiovascular and renal comorbidities were associated with worse outcome in COVID-19 patients. Antiviral treatment on admission was identified as a protective factor for 28-day mortality. Ascertaining the outcomes of critically ill COVID-19 patients is crucial to optimise hospital and ICU resources and provide the appropriate intensity level of care.

Frequency and incidence of arterial events in patients with venous thromboembolism compared to the general population: A systematic review and meta-analysis of cohort studies.

BACKGROUND: Recent literature hypothesized that patients with venous thromboembolism (VTE) are at increased risk of developing arterial ischemic events than general population without VTE. However, data summarizing the epidemiology of arterial events among VTE population compared to the general population are lacking. METHODS: We conducted a systematic review and meta-analysis from current literature. PubMed, EMBASE, and Cochrane databases were searched between Jan 1, 2000, and December 31, 2020. Eligible studies were observational cohort studies published in English on arterial ischemic events in patients with VTE. Pooled effect size estimates and their 95% confidence intervals were obtained through random-effect models meta-analysis. RESULTS: Twenty-eight observational studies enrolling 352,014 patients were identified and included. The pooled frequency of all arterial events was 6.1% (95% CI: 3.7-9.1) in patients with VTE and was significantly higher than the pooled frequency of 5.0% (95% CI: 3.1-7.2) found in controls, with a pooled risk ratio (RR) of 1.20 (95% CI: 1.01-1.44; p = 0.0422). The pooled incidence of all arterial events in patients with VTE was 11.3‰ per patient-year (95% CI: 4.6-18.0), and was significantly higher than the 9.2‰ per patient-year (95% CI: 2.0-16.4) obtained in controls (Incidence rate ratio, IRR: 1.32; 95% CI: 1.08-1.61; p = 0.0103). The pooled frequency and pooled incidence of arterial events were also higher in patients with unprovoked VTE than in patients with provoked VTE (RR: 2.12; 95% CI: 1.38-3.24; p = 0.0042; and IRR: 2.26, 95% CI: 1.45-3.49; p = 0.0032). CONCLUSION: The frequency and incidence of arterial events in patients with VTE are considerably higher than in the general population, without VTE. Further studies are urgently needed to understand these differences and reduce the burden related to these diseases. FUNDING: None.