Evolution of treated obstructive sleep apneas syndrome after bariatric surgery: an observational retrospective study.

BACKGROUND: The resolution of obstructive sleep apneas syndrome (OSAS) following bariatric surgery appears to be promising for the majority of patients although this resolution does not necessarily exhibit a linear correlation with weight loss. Previous small-scale studies have pinpointed a younger age and preoperative weight under 100kg as predictive factors of OSAS improvement OBJECTIVES: The primary objective was to evaluate the evolution of OSAS in patients treated with continuous positive airway pressure (CPAP). Additionally, we tried to identify potential predictive factors for OSAS improvement postsurgery. SETTING: Brest Hospital, France, University Hospital. METHODS: In this retrospective, observational study we analyzed a cohort of 44 patients who underwent bariatric surgery, between January 2015 and December 2021. Each patient underwent respiratory polygraphy (RP) or polysomnography (PSG) before and after the surgical procedure. We collected CPAP data (including effective pressure and adherence) before and during the 6 months following the intervention. RESULTS: Within the study population, 68.18% of patients exhibited improved OSAS, as defined as an apnea-hypopnea index of less than 15 per hour. A higher mean oxygen saturation prior to surgery emerged as the sole predictive factor for OSAS improvement. CPAP adherence and therapeutic pressure value, 2 rarely studied parameters, did not show significant difference between improved and nonimproved patients. CONCLUSIONS: The rate of OSAS resolution after surgery is 68.18%, with only a higher mean oxygen saturation before surgery identified as a predictive factor for OSAS resolution.

Predictors of pulmonary embolism in chronic obstructive pulmonary diseases patients admitted for worsening respiratory symptoms: An individual participant data meta-analyses.

BACKGROUND: Pulmonary embolism (PE) and acute exacerbation of chronic obstructive pulmonary disease (COPD) have similar clinical symptoms, making PE diagnosis challenging. Previous studies have shown that the prevalence of PE among COPD patients admitted with worsening respiratory symptoms was not negligible, but that systematic search for PE did not provide a clinical benefit. Predictive factors for PE remain unknown. OBJECTIVE: to identify predictive factors for PE among COPD patients with worsening respiratory symptoms. METHODS: We conducted an individual participant data meta-analysis which included the patients from the prospective PEP cohort and those randomized to the intervention arm in the SLICE trial which included a systematic search for PE in COPD patients admitted for worsening respiratory symptoms. Univariable and multivariable analysis were used to assess factors associated with the diagnosis of PE during the initial management. RESULTS: Among 1110 COPD patients, PE was diagnosed in 61 (5.49 %; 95 %CI 4.15 %-6.84 %). In univariable analysis, BNP (Brain natriuretic peptide) (odds ratio [OR] 1.02 per 100 ng/L increase, 95 %CI 1.01-1.04), prothrombin time (OR 0.78, 95 %CI 0.65-0.94), fibrinogen (OR 0.80, 95 %CI 0.64-0.98), atrial fibrillation (OR 4.74, 95 %CI 1.84-10.80), respiratory rate ≥30 min (OR 2.34, 95 %CI 1.13-4.6) and recent medical immobilization (OR 1.79, 95 %CI 0.99-3.13]) were associated with the risk of PE diagnosed during the initial management. In multivariable analysis, respiratory rate ≥30 (OR 2.77, 95 %CI 1.08-6.71) was a predictive factor for PE, as well as BNP (OR 1.02, 95 %CI 1.00-1.05) with an area under the curve =0.64, negative predictive value =0.15 (95 %CI 0.09-0.23), sensitivity =0.78 (95 %CI 0.74-0.82) and specificity =0.46 (95 %CI 0.29-0.63). CONCLUSION: Among patients with COPD admitted for worsening respiratory symptoms, respiratory rate and BNP levels are predictor of PE, but with limited discriminatory power.

Duration of anticoagulation of venous thromboembolism.

Venous thromboembolism (VTE) is a common, serious condition that requires anticoagulation for at least three months to prevent recurrence and long-term complications. After this initial period, the decision to continue or stop anticoagulation depends on the balance between the risk of recurrent VTE and the risk of bleeding. Established guidelines suggest short-term anticoagulation for VTE caused by transient factors and indefinite anticoagulation for recurrent or cancer-associated VTE. However, for a first unprovoked VTE, decision-making remains challenging. Current predictive scores for recurrence and bleeding are not sufficiently reliable, and the safety and efficacy of reduced-dose anticoagulation remain unclear. In the future, precision and patient-centred medicine may improve treatment decisions in this area.

Impact of thrombophilia on venous thromboembolism management.

Hypercoagulable states, also called thrombophilia, can either be congenital or acquired. Congenital thrombophilia, associated mainly with venous thrombosis, is either secondary to coagulation-inhibitor deficiencies, i.e., antithrombin, protein C and Protein S, or gain of function mutations, i.e., factor V Leiden and prothrombin G20210A mutations. Despite the relative frequency of these two mutations, they have not been associated with venous thrombosis recurrence. Most prevalent thrombophilia have a limited impact and usually does not change indications for duration of antithrombotic treatment or prophylaxis compared to decisions based on clinical factors. However, rare inherited thrombophilia such as antithrombin deficiency could justify a long-term anticoagulation. The main acquired thrombophilia, the Antiphospholipid syndrome (APS), is associated with both arterial and venous thrombosis. Its impact on patient management is significant: choice of the anticoagulant (DOAC vs. warfarin), duration of anticoagulation, screening of any organ involvement and systemic autoimmune disease, introduction of immunosuppressive therapy.

Characteristics of Young Women Presenting With Acute Myocardial Infarction: The Prospective, Multicenter, Observational Young Women Presenting Acute Myocardial Infarction in France Study.

BACKGROUND: The percentage of women <50 years of age hospitalized with myocardial infarction is increasing. We describe the clinical, morphological, and biological characteristics, as well as the clinical outcomes of this population. METHODS AND RESULTS: This prospective, observational study included consecutive women <50 years of age admitted for myocardial infarction at 30 centers in France (May 2017-June 2019). The primary outcome was the composite of net adverse clinical events: all-cause death, cardiovascular death, recurrent myocardial infarction, stent thrombosis, any stroke, or major bleeding occurring during hospitalization with a 12-month follow up. Three hundred fourteen women were included. The mean age was 43.0 (±5.7) years, 60.8% presented with ST-segment-elevation myocardial infarction, 75.5% were current smokers, 31.2% had a history of complicated pregnancy, and 55.1% reported recent emotional stress. Most (91.6%) women presented with typical chest pain. Of patients on an estrogen-containing contraceptive, 86.0% had at least 1 contraindication. Of patients with ST-segment-elevation myocardial infarction, 17.8% had myocardial infarction with nonobstructive coronary arteries and 14.6% had spontaneous coronary artery dissection, whereas 29.3% presented with multivessel vessel disease. During hospitalization, 11 net adverse clinical events occurred in 9 (2.8%) women, but no deaths or stent thromboses occurred. By 12 months, 14 net adverse clinical events occurred in 10 (3.2%) women; 2 (0.6%) died (from progressive cancer) and 25 (7.9%) had an ischemia-driven repeat percutaneous coronary intervention. CONCLUSIONS: Most young women with myocardial infarction reported typical chest pain and had modifiable cardiovascular risk factors. History of adverse pregnancy outcomes and prescription of combined oral contraceptive despite a contraindication were prevalent, emphasizing the need for comprehensive cardiological and gynecological evaluation and follow-up. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03073447.

Predelivery Haemostatic Biomarkers in Women with Non-Severe Postpartum Haemorrhage.

Background: Postpartum haemorrhage (PPH) is a frequent complication of childbirth that is difficult to predict. Predelivery coagulation biomarkers may help to guide preventive strategies. Our objective was to evaluate the association of predelivery haemostatic biomarkers with non-severe PPH. Methods: A nested case-control study was conducted within the « Study of Biological Determinants of Bleeding Postpartum ¼ in order to compare different haemostatic biomarkers in plasma from pregnant women with non-severe PPH (cases) and controls without PPH matched for age, body mass index, term, and mode of delivery. Blood was collected at entry in the delivery room. Global haemostatic assays (thrombin generation assay (TGA) and plasmin generation assay (PGA)) were then performed on freshly thawed aliquots of platelet-poor plasma. Results: A total of 370 pregnant women (185 cases and 185 controls) were included. Median [interquartile range] predelivery platelet count was lower in PPH cases than in controls (217 [181-259] versus 242 [196-280] G/L). TGA and PGA parameters were similar between cases and controls. In a subset analysis of vaginal deliveries (n = 144), median predelivery TGA thrombin peak was lower, and median predelivery PGA lag phase was longer in cases compared to controls. In multivariable analysis, only predelivery platelet count was independently associated with non-severe PPH. Conclusions: Predelivery platelet count is associated with non-severe PPH. Differences in other haemostatic parameters are tenuous, questioning their usefulness in predicting non-severe PPH.

Safety of treating acute pulmonary embolism at home: an individual patient data meta-analysis.

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

Extracellular RNA Induces Neutrophil Recruitment Via Toll-Like Receptor 3 During Venous Thrombosis After Vascular Injury.

BACKGROUND: Venous thromboembolism is associated with endothelial cell activation that contributes to the inflammation-dependent activation of the coagulation system. Cellular damage is associated with the release of different species of extracellular RNA (eRNA) involved in inflammation and coagulation. TLR3 (toll-like receptor 3), which recognizes (viral) single-stranded or double-stranded RNAs and self-RNA fragments, might be the receptor of these species of eRNA during venous thromboembolism. Here, we investigate how the TLR3/eRNA axis contributes to venous thromboembolism. METHODS AND RESULTS: Thrombus formation and size in wild-type and TLR3 deficient (-/-) mice were monitored by ultrasonography after venous thrombosis induction using the ferric chloride and stasis models. Mice were treated with RNase I, with polyinosinic-polycytidylic acid, a TLR3 agonist, or with RNA extracted from murine endothelial cells. Gene expression and signaling pathway activation were analyzed in HEK293T cells overexpressing TLR3 in response to eRNA or in human umbilical vein endothelial cells transfected with a small interference RNA against TLR3. Plasma clot formation on treated human umbilical vein endothelial cells was analyzed. Thrombosis exacerbated eRNA release in vivo and increased eRNA content within the thrombus. RNase I treatment reduced thrombus size compared with vehicle-treated mice (P<0.05). Polyinosinic-polycytidylic acid and eRNA treatments increased thrombus size in wild-type mice (P<0.01 and P<0.05), but not in TLR3-/- mice, by reinforcing neutrophil recruitment (P<0.05). Mechanistically, TLR3 activation in endothelial cells promotes CXCL5 (C-X-C motif chemokine 5) secretion (P<0.001) and NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation (P<0.05). Finally, eRNA triggered plasma clot formation in vitro (P<0.01). CONCLUSIONS: We show that eRNA and TLR3 activation enhance venous thromboembolism through neutrophil recruitment possibly through secretion of CXCL5, a potent neutrophil chemoattractant.

Full-dose rivaroxaban in patients with a history of bariatric surgery: bridging the knowledge gap through a phase 1 study.

BACKGROUND: Bariatric surgery (BS) induces significant changes in gastrointestinal anatomy, potentially influencing the pharmacokinetics of orally administered drugs such as rivaroxaban. OBJECTIVES: This phase 1 study aimed to assess the pharmacokinetics and safety of full-dose rivaroxaban in post-BS patients. METHODS: The ABSORB (Rivaroxaban Pharmacokinetics and Pharmacodynamics After Bariatric Surgery and in Morbid Obesity) study was a single-center, nonrandomized, multiple-dose, parallel-design bioequivalence trial. Adult patients with stable weight after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were compared with subjects with class III obesity and healthy controls. Participants received 20 mg of rivaroxaban daily for 8 days. RESULTS: Post-BS patients exhibited altered rivaroxaban pharmacokinetics, suggesting reduced absorption. Mean area under the concentration-time curve from time 0 to 24 hours after the first dose (RYGB, 1806.8 ng.h/mL; SG, 1648.9 ng.h/mL) was lower compared with that in controls (1893.5 ng.h/mL). At steady state, the area under the concentration-time curve values remained lower in BS groups (RYGB, 2129.9 ng.h/mL; SG, 1946.4 ng.h/mL) than in controls (2224.8 ng.h/mL). The maximum concentration after the first dose was lower in post-RYGB subjects (214.9 ng/mL) than in controls (264.1 ng/mL). This difference was less pronounced at steady state (RYGB, 256.9 ng/mL vs controls, 288.8 ng/mL). Neither BS group met bioequivalence criteria compared with controls, whereas the group with class III obesity met bioequivalence criteria compared with controls at steady state. CONCLUSION: Rivaroxaban displayed minor pharmacokinetic variations in post-BS patients. Given reported interindividual variability in the general population, these variations are unlikely to be of clinical significance. Our findings support rivaroxaban use in BS patients, emphasizing the need for further research in this area.

Chronic obstructive pulmonary disease exacerbation purulence status and its association with pulmonary embolism: protocol for a systematic review with meta-analysis.

INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) increases the risk of pulmonary embolism (PE). AECOPD and PE have similar symptoms which results in a high proportion of patients with AECOPD undergoing imaging to rule out PE. Finding predictors and explanatory factors of PE in AECOPD, such as purulence status, could help reduce the need for imaging. This systematic review with meta-analysis aims to evaluate if there is an association between purulence status in AECOPD and PE diagnosis. METHODS AND ANALYSIS: MEDLINE, EMBASE and CENTRAL will be searched from database inception to April 2024. Randomised trials, cohort studies and cross-sectional studies on the prevalence of PE in patients with AECOPD will be included if the prevalence of PE based on the AECOPD purulence status is available. There will be no restriction on language. The primary outcome will be PE at the initial assessment and secondary outcomes will be all venous thromboembolism (deep venous thrombosis (DVT) and PE) and DVT, respectively, diagnosed at the initial assessment. Relative risks with their 95% CI will be calculated by using a Mantel-Haenszel random-effect model to compare the association between the risk of PE and the AECOPD purulence status (purulent vs non-purulent/unknown). Subgroup analyses will be performed based on the type of study, systematic search of PE versus no systematic search of PE and localisation of PE. Risk of bias will be evaluated by the ROBINS-E tool, publication bias will be evaluated with the funnel plot. The manuscript will be drafted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. ETHICS AND DISSEMINATION: This study does not require ethics approval. This work will be submitted for presentation at an international conference and for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023459429.

Comparison of three diagnostic strategies for suspicion of pulmonary embolism: planar ventilation-perfusion scan (V/Q), CT pulmonary angiography (CTPA) and single photon emission CT ventilation-perfusion scan (SPECT V/Q): a protocol of a randomised controlled trial.

INTRODUCTION: Pulmonary embolism (PE) is a challenge to diagnose and when missed, exposes patients to potentially fatal recurrent events. Beyond CT pulmonary angiography (CTPA) and planar ventilation/perfusion (V/Q) scan, single photon emission CT (SPECT) V/Q emerged a new diagnostic modality of scintigraphic acquisition that has been reported to improve diagnostic performances. To date, no management outcome study or randomised trial evaluated an algorithm based on SPECT V/Q for PE diagnosis. We present the design of a randomised multicentre, international management study comparing SPECT V/Q with validated strategies. MATERIAL AND METHODS: We will include a total of 3672 patients with suspected PE requiring chest imaging, randomised into three different groups, each using a different diagnostic strategy based on SPECT V/Q, CTPA and planar V/Q scan. Randomisation will be unbalanced (2:1:1), with twice as many patients in SPECT V/Q arm (n=1836) as in CTPA and planar V/Q arms (n=918 in each). Our primary objective will be to determine whether a diagnostic strategy based on SPECT V/Q is non-inferior to previously validated strategies in terms of diagnostic exclusion safety as assessed by the 3-month risk of thromboembolism in patients with a negative diagnostic workup. Secondary outcomes will be the proportion of patients diagnosed with PE in each arm, patients requiring additional tests, the incidence of major and clinically relevant non-major bleeding and the incidence and cause of death in each arm. ETHICS AND DISSEMINATION: This trial is funded by a grant from Brest University Hospital and by INVENT. The study protocol was approved by Biomedical Research Ethics Committee. The investigator or delegate will obtain signed informed consent from all patients prior to inclusion in the trial. Our results will inform future clinical practice guidelines and solve the current discrepancy between nuclear medicine guidelines and clinical scientific society guidelines. TRIAL REGISTRATION NUMBER: NCT02983760.

[Translation into French and republication of: "Home treatment for patients with cancer-associated venous thromboembolism"]. / Traduction et republication de : « Traitement à domicile des patients atteints de maladie veineuse thromboembolique associée au cancer ¼.

Patients hospitalised with acute venous thromboembolism (VTE), and notably patients with pulmonary embolism, often remain in hospital for extended periods due to the perceived risk of complications. However, several studies have shown that home treatment of selected patients is feasible and safe, with a low incidence of adverse events. This may offer clear benefits for patients' quality of life, hospital planning and cost to the health service. Nonetheless, there is a need for a VTE risk-stratification tool specifically addressing prognosis in patients with cancer. This may aid in the selection of low-risk patients with cancer and VTE who are suitable for outpatient treatment. Although several prognostic scores have been proposed, we suggest using a pragmatic clinical decision-making tool such as the Hestia criteria for selecting patients for home care in everyday clinical practice. Once patients have been discharged, it is mandatory to monitor patients regularly (we suggest after 3 days, 10 days, 1 month and 3 months, or more frequently if needed) with the involvement of a multidisciplinary team, so that appropriate and timely remedial action can be taken in case of warning signs of complications. If patients are selected carefully and monitored effectively, many patients who experience acute VTE can be cared for safely at home.

Nationwide Audit of Postoperative Mortality and Complications After Digestive Cancer Surgery: Will New Legal Thresholds be Sufficient?

BACKGROUND: French policymakers recently chose to regulate high-risk digestive cancer surgery (DCS). A minimum of five cases per year should be performed for each of the following types of curative cancer surgery: esophagus/esogastric junction (ECS), stomach (GCS), liver (LCS, metastasis included), pancreas (PCS), and rectum (RCS). This study aimed to evaluate the hypothetical beneficial effects of the new legal minimal volume thresholds on the rates of 90-day postoperative mortality (90POM) for each high-risk DCS. METHODS: This nationwide observational population-based cohort study used data extracted from the French National Health Insurance Database from 1 January 2015-31 December 2017. Mixed-effects logistic regression models were performed to estimate the independent effect of hospital volume. RESULTS: During the study period, 61,169 patients (57.1 % male, age 69.7 ±12.2 years) underwent high-risk DCS including ECS (n = 4060), GCS (n = 5572), PCS (n = 8598), LCS (n = 10,988), and RCS (n = 31,951), with 90POM of 6.6 %, 6.9 %, 6.0 %, 5.2 %, and 2.9 %, respectively. For hospitals fulfilling the new criteria, 90POM was lower after adjustment only for LCS (odds ratio [OR],15.2; 95 % confidence interval [CI], 9.5-23.2) vs OR, 7.6; 95 % CI, 5.2-11.0; p < 0.0001) and PCS (OR, 3.6; 95 % CI, 1.7-7.6 vs OR, 2.1; 95 % CI, 1.0-4.4; p<0.0001). With higher thresholds, all DCSs showed a lower adjusted risk of 90POM (e.g., OR, 0.38; 95 % CI, 0.28-0.51) for PCS of 40 or higher. CONCLUSION: Based on retrospective data, thresholds higher than those promulgated would better improve the safety of high-risk DCS. New policies aiming to further centralize high-risk DCS should be considered, associated with a clear clinical pathway of care for patients to improve accessibility to complex health care in France.

CT Imaging Assessment of Response to Treatment in Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma.

BACKGROUND: One of the major challenges in managing allergic bronchopulmonary aspergillosis remains consistent and reproducible assessment of response to treatment. RESEARCH QUESTION: What are the most relevant changes in CT scan parameters over time for assessing response to treatment? STUDY DESIGN AND METHODS: In this ancillary study of a randomized clinical trial (NebuLamB), patients with asthma with available CT scan and without exacerbation during a 4-month allergic bronchopulmonary aspergillosis exacerbation treatment period (corticosteroids and itraconazole) were included. Changed CT scan parameters were assessed by systematic analyses of CT scan findings at initiation and end of treatment. CT scans were assessed by two radiologists anonymized to the clinical data. Radiologic parameters were determined by selecting those showing significant changes over time. Improvement of at least one, without worsening of the others, defined the radiologic response. Agreement between radiologic changes and clinical and immunologic responses was likewise investigated. RESULTS: Among the 139 originally randomized patients, 132 were included. We identified five CT scan parameters showing significant changes at end of treatment: mucoid impaction extent, mucoid impaction density, centrilobular micronodules, consolidation/ground-glass opacities, and bronchial wall thickening (P < .05). These changes were only weakly associated with one another, except for mucoid impaction extent and density. No agreement was observed between clinical, immunologic, and radiologic responses, assessed as an overall response, or considering each of the parameters (Cohen κ, -0.01 to 0.24). INTERPRETATION: Changes in extent and density of mucoid impaction, centrilobular micronodules, consolidation/ground-glass opacities, and thickening of the bronchial walls were found to be the most relevant CT scan parameters to assess radiologic response to treatment. A clinical, immunologic, and radiologic multidimensional approach should be adopted to assess outcomes, probably with a composite definition of response to treatment. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02273661; URL: www. CLINICALTRIALS: gov).

Outpatient management of cancer-associated pulmonary embolism: A post-hoc analysis from the HOME-PE trial.

INTRODUCTION: Cancer-related pulmonary embolism (PE) is associated with poor prognosis. Some decision rules identifying patients eligible for home treatment categorize cancer patients at high risk of complications, precluding home treatment. We sought to assess the effectiveness and the safety of outpatient management of patients with low-risk cancer-associated PE. METHODS: In the HOME-PE trial, hemodynamically stable patients with symptomatic PE were randomized to either triaging with Hestia criteria or sPESI score. We analyzed 3 groups of low-risk PE patients: 47 with active cancer treated at home (group 1), 691 without active cancer treated at home (group 2), and 33 with active cancer as the only sPESI criterion qualifying them for hospitalization (group 3). The main outcome was the composite of recurrent venous thromboembolism, major bleeding, and all-cause death within 30 days after randomization. RESULTS: Patients treated at home had composite outcome rates of 4.3 % (2/47) for those with cancer vs. 1.0 % (7/691) for those without (odds ratio (OR) 4.98, 95%CI 1.15-21.49). Patients with cancer had rates of complications of 4.3 % when treated at home vs. 3.0 % (1/33) when hospitalized (OR 1.19, 95%CI 0.15-9.47). In multivariable analysis, active cancer was associated with an increased risk of complications for patients treated at home (OR 7.95; 95%CI 1.48-42.82). For patients with active cancer, home treatment was not associated with the primary outcome (OR 1.19, 95%CI 0.15-9.74). CONCLUSIONS: Among patients treated at home, active cancer was a risk factor for complications, but among patients with active cancer, home treatment was not associated with adverse outcomes.

Venous thromboembolism and amyotrophic lateral sclerosis: the Venous Thrombo-Embolism and Sclerosis Lateral Amyotrophic study.

Background: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease. Given the inflammatory nature of ALS and the high number of ALS-related clinical circumstances (eg, prolonged immobilization and infections), patients with ALS may have a high risk of venous thromboembolism (VTE). Objectives: To determine the annual incidence rate of VTE and the predictors of VTE in patients with ALS. Methods: We analyzed a prospective cohort of patients with ALS diagnosed between 2009 and 2019 followed in the Brest University Hospital ALS Centre. Results: Among 227 patients with ALS, VTE occurred in 19 patients during a median follow-up period of 717 days (IQR, 488-1308), yielding an annual incidence rate of 2.93% (95% CI, 1.88%-4.53%). Predictors for VTE were a family history of VTE (hazard ratio [HR], 15.24; 95% CI, 1.72-134.84; P = .01), the presence of noninvasive ventilation at ALS diagnosis (HR, 6.98; 95% CI, 1.09-44.59; P = .04) and a short time (ie, <213 days) between first symptoms and ALS diagnosis (HR, 5.48; 95% CI, 1.57-19.11; P = .01). Recurrent VTE occurred within 3 months after stopping anticoagulation in 5 patients (26.3%). Conclusion: The annual incidence of VTE in patients with ALS is high. Predictive factors of VTE were a VTE history, noninvasive ventilation, and a short time between first symptoms of ALS and ALS diagnosis.

Recurrent venous thromboembolism in anticoagulated cancer patients: Diagnosis and treatment.

Patients with cancer are at significantly increased risk of venous thromboembolism (VTE), due both to the impact of malignant disease itself and to the impact of certain anticancer drugs on haemostasis. This is true both for first episode venous thromboembolism and recurrence. The diagnosis and management of VTE recurrence in patients with cancer poses particular challenges, and these are reviewed in the present article, based on a systematic review of the relevant scientific literature published over the last decade. Furthermore, it is uncertain whether diagnostic algorithms for venous thromboembolism, validated principally in untreated non-cancer patients, are also valid in anticoagulated cancer patients: the available data suggests that clinical decision rules and D-dimer testing perform less well in this clinical setting. In patients with cancer, computed tomography pulmonary angiography and venous ultrasound appear to be the most reliable diagnostic tools for diagnosis of pulmonary embolism and deep vein thrombosis respectively. Options for treatment of venous thromboembolism include low molecular weight heparins (at a therapeutic dose or an increased dose), fondaparinux or oral direct factor Xa inhibitors. The choice of treatment should take into account the nature (pulmonary embolism or VTE) and severity of the recurrent event, the associated bleeding risk, the current anticoagulant treatment (type, dose, adherence and possible drug-drug interactions) and cancer progression.

Management of cancer-associated thromboembolism in vulnerable population.

Although all patients with cancer-associated thrombosis (CAT) have a high morbidity and mortality risk, certain groups of patients are particularly vulnerable. This may expose the patient to an increased risk of thrombotic recurrence or bleeding (or both), as the benefit-risk ratio of anticoagulant treatment may be modified. Treatment thus needs to be chosen with care. Such vulnerable groups include older patients, patients with renal impairment or thrombocytopenia, and underweight and obese patients. However, these patient groups are poorly represented in clinical trials, limiting the available data, on which treatment decisions can be based. Meta-analysis of data from randomised clinical trials suggests that the relative treatment effect of direct oral factor Xa inhibitors (DXIs) and low molecular weight heparin (LMWH) with respect to major bleeding could be affected by advanced age. No evidence was obtained for a change in the relative risk-benefit profile of DXIs compared to LMWH in patients with renal impairment or of low body weight. The available, albeit limited, data do not support restricting the use of DXIs in patients with CAT on the basis of renal impairment or low body weight. In older patients, age is not itself a critical factor for choice of treatment, but frailty is such a factor. Patients over 70 years of age with CAT should undergo a systematic frailty evaluation before choosing treatment and modifiable bleeding risk factors should be addressed. In patients with renal impairment, creatine clearance should be assessed and monitored regularly thereafter. In patients with an eGFR<30mL/min/1.72m2, the anticoagulant treatment may need to be adapted. Similarly, platelet count should be assessed prior to treatment and monitored regularly. In patients with grade 3-4, thrombocytopenia (<50,000 platelets/µL) treatment with a LMWH at a reduced dose should be considered. For patients with CAT and low body weight, standard anticoagulant treatment recommendations are appropriate, whereas in obese patients, apixaban may be preferred.

From early risk to 1-year mortality: a comprehensive assessment of postoperative venous thromboembolism in upper gastrointestinal cancer patients - a nationwide cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a well-recognized complication following gastrointestinal cancer surgery, particularly early postoperatively. The incidence and risk factors of VTE within 1-year after esophageal (including esophago-gastric junction) (ECS) and gastric (GCS) cancer surgeries, and especially its impact on 1-year global mortality, are yet under-explored. METHODS: This nationwide observational population-based cohort study used data extracted from all patients undergoing ECS and GCS in France between 1 January 2015 and 31 December 2017. Multivariate logistic regression was used to identify risk factors for 90 postoperative days (POD) VTE (OR 95% CI). Cox proportional hazards models investigated the impact of 1-year postoperative VTE on 1-year global mortality [HR (95% CI)]. RESULTS: During the study period, 8005 patients underwent ECS ( N =3429) or GCS ( N =4576) (31.8% female; 66.7±12.1 years old). Majority ( N =4951) of patients had preoperative treatment (chemotherapy or radiochemotherapy). Ninety POD incidence of VTE were 4.7% (ECS=6.2%) (GCS=3.6%) (44.7% during first hospitalization, 19.0% needing readmission, and 36.3% ambulatory management). Main risk factors were three and two field esophagectomy [3.6 (2.20-5.83) and 2.2 (1.68-3.0)], obesity [1.9 (1.40-2.58)] and history of VTE [5.1 (2.72-9.45)]. Late-onset VTE rates (occurring between the 6th and 12th month) represented 1.80 and 1.46% of the overall ECS and GCS groups. Patients with VTE within 1-year had higher risks of 1-year global mortality: (2.04 1.52; 2.73) and 2.71 (2.09; 3.51), respectively. CONCLUSION: Our extensive analysis of a nationwide database highlights the significant risk of postoperative VTE after ECS and GCS, persisting within 90 POD and up to 1-year. Crucially, a higher risk of global mortality within 1-year for patients experiencing early or late VTE was found. These findings could advocate for further research into extended prophylactic regimens, particularly for those most at risk.