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Low intrinsic noise, high bandwidth, and high accuracy vector magnetometers are key components for many ground or space geophysical applications. Here, we report the design and the test of a 4He vector optically pumped magnetometer specifically dedicated to these needs. It is based on a parametric resonance magnetometer architecture operated in the Earth magnetic field with closed-loop compensation of the three components of the magnetic field. It provides offset-free vector measurements in a ±70 μT range with a DC to 1 kHz bandwidth. We demonstrate a vector sensitivity up to 130 fT/√Hz, which is about ten times better than the best available fluxgate magnetometers currently available for the same targeted applications. [ABSTRACT FROM AUTHOR]

Background: Any surgical procedure carries a risk for venous thromboembolism (VTE), albeit variable. Improvements in medical and surgical practices and the shortening of care pathways due to the development of day surgery and enhanced recovery after surgery, have reduced the perioperative risk for VTE., Objective: A collaborative working group of experts in perioperative haemostasis updated in 2024 the recommendations for the Prevention of perioperative venous thromboembolism published in 2011., Methods: The addressed questions were defined by 40 experts (GIHP, SFAR, SFTH and SFMV) and formulated in a PICO format. They performed the literature review and formulated recommendations according to the Grading of GRADE system. Recommendations were then validated by a vote determining the strength of each recommendation. Of note, these recommendations do not cover all surgical specialties. Especially, thromboprophylaxis in cardiac surgery, neurosurgery and obstetrics is not addressed., Results: 78 recommendations were formalized into 17 sections, including patient-related VTE risk factors, types of surgery, extreme body weight, renal impairment, mechanical prophylaxis, distal deep vein thrombosis; 27 were found to have a high level of evidence (GRADE 1) and 41 a low level of evidence (GRADE 2) and 10 were expert opinion. All had strong agreement among the experts., Conclusions: These guidelines help to weigh the perioperative risk for VTE (which includes the risk associated to surgery and the patient-related risk) against the adverse effects of thromboprophylaxis, either pharmacological or mechanical. This includes particularly the bleeding risk induced by antithrombotic drugs as well as costs., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Limited language proficiency is an established barrier to research participation among racialized populations. While prior studies have highlighted the under-representation of racialized populations in venous thromboembolism (VTE) research, the impact of limited language proficiency as a reason for non-consent among eligible patients is unknown., Methods: We reviewed all prospective VTE studies conducted at a research-intensive academic thrombosis research program in Canada between 2014 and 2024. Studies with screening logs that systematically and consecutively captured eligibility assessment and reasons for non-consent were included. Primary outcome was non-consent of a screen-eligible patient due to limited language proficiency as the reported reason. We derived pooled estimates of non-consents due to limited language proficiency as a proportion of consented participants, and determined subgroup rates by phase of VTE management, associated medical conditions, and recruitment settings., Results: Screening logs of 28 studies with 22,057 screening events, 8,317 screen-eligible patients and 3,320 consented participants were included. For every 100 consented participants, 3.2 (95% CI 2.0 - 5.3) screen-eligible individuals were unable to be consented due to limited language proficiency. Rates of non-consent were highest in studies involving cancer (5.6 per 100 participants, 95% CI 2.9 - 10.4) and in studies recruiting patients from ambulatory settings outside of the thrombosis clinic (10.8 per 100 participants, 95% CI 4.8 - 22.6)., Conclusions: Language proficiency is a key barrier to VTE research participation. Urgent implementation of targeted interventions aimed at mitigating linguistic barriers is essential to ensure equitable opportunities for VTE research participation for racialized patients disproportionately affected by language proficiency., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Head and neck squamous cell carcinoma (HNSCC) remains a malignancy with high rates of locoregional recurrence and poor prognosis for recurrent cases. Early detection of subclinical lesions is challenging but critical for effective patient management. Imaging surveillance after treatment, particularly 18 F-FDG PET/CT, has shown promise in the diagnosis of HNSCC recurrence. The aim was to evaluate the diagnostic performance of 18 F-FDG PET/CT according to delay after treatment in detecting subclinical recurrence (SCR) in HNSCC patients. Methods: In this retrospective study, all 18 F-FDG PET/CT scans were performed at a single center. All adults with histologically proven HNSCC who were treated with curative intent between January 1, 2006, and December 31, 2021, were included. They had a normal clinical examination before each scan. Patients who underwent an intensive follow-up strategy after treatment had 18 F-FDG PET/CT with an intravenous contrast agent at 3-6 mo and annually thereafter for 5 y. The primary endpoint was diagnostic performance (positive and negative predictive values, sensitivity, specificity, and accuracy). Results: In total, 2,566 18 F-FDG PET/CT scans were performed among 852 patients, with an average of 3 scans per patient. The overall diagnostic performance measures were as follows: positive predictive value (88%), negative predictive value (98%), sensitivity (98%), specificity (89%), and accuracy (93%). There were no significant differences in diagnostic performance over time. The scans detected 126 cases of SCR (14.8%) and 118 cases of metachronous cancer (13.8%). The incidence of SCR decreased over time, with the highest detection rate in the first 2 y after treatment. Positive predictive value improved over time, reaching 90% for the digital Vision 600 system (third period) compared with 76% for the analog Gemini GXLi system (first period, P < 0.001). Multivariate analysis identified advanced stage, high body mass index, and initial PET/CT upstaging as predictive factors for detection of SCR. Conclusion: Our study demonstrates that 18 F-FDG PET/CT has high diagnostic performance in detecting SCR during follow-up after treatment of HNSCC, especially in the first 2 y. Advanced tumor stage, initial PET/CT upstaging, and high body mass index were associated with a higher likelihood of SCR detection. The routine use of 18 F-FDG PET/CT during follow-up seems justified for patients with HNSCC., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Introduction: Approximately 10 % of all diagnosed pulmonary embolism are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE) managed with or without anticoagulant therapy remains poorly understood., Methods: This is an observational cohort study including consecutive adult patients diagnosed with acute isolated SSPE between June 01, 2019, and August 31, 2022. We excluded patients with a concomitant diagnosis of deep vein thrombosis and those who had an indication for long-term anticoagulation. The primary outcome was objectively confirmed recurrent VTE., Results: Overall, 118 patients with acute SSPE were included in the analysis. The mean (± standard deviation [SD]) age of the participants was 59 ± 17 years and 44 % of them had active cancer. Mean (±SD) duration of follow-up was 438 ± 426 days. Seventy-seven patients (65 %) were initially treated with anticoagulation, whereas 41 patients (35 %) were not. Of the 77 patients receiving anticoagulant therapy, 23 (30 %) received extended-duration anticoagulation (beyond 3 months) for secondary prevention. Overall, recurrent VTE events occurred in 6/118 (5 %, 95 % CI 2.4 to 10.7) patients. Four events (4/77 = 5.2 %, 95 % CI 2.0 to 12.6) occurred in initially treated patients. Two recurrent VTE occurred in patients initially left untreated (2/41 = 4.9 %, 95 % CI 1.4 to 16.1). Half of the recurrent VTE occurred in patients with active cancer., Conclusions: Most patients diagnosed with an acute SSPE received anticoagulation. The incidence of recurrent VTE detected over time was relatively high, especially in patients with cancer., Competing Interests: Declaration of competing interest L. Girardi, L. A. Ciuffini, V. Mai, D. Santagata and TF. Wang report no conflicts of interests. W. Ageno reports advisory board honoraria from Bayer, Boehringer Inghelheim, Daiichi Sankyo, BMS/Pfizer, Sanofi, and Portola, and reports research funding and personal fees from Bayer, and personal fees from BMS/Pfizer, Daiichi Sankyo, Sanofi, Aspen, Janssen, and Portola, outside the submitted work. M. Carrier has received research funding from BMS, Pfizer, and Leo Pharma, and honoraria from Bayer, Pfizer, BMS, Servier, and Leo Pharma. G. Le Gal reports advisory board honoraria from Inari, Pfizer, Sanofi. G. Le Gal holds a Chair on Diagnosis of Venous Thromboembolism at the Faculty of Medicine, University of Ottawa., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Competing interests: VM, LG, KdW, SA, FC and DAF do not have conflicts of interest. LC’s research institution has received honoraria from Bayer, BMS-Pfizer Alliance, The Academy for Continued Advancement in Healthcare Education, Amag Pharmaceutical, LEO Pharma, Sanofi, Valeo Pharma and Servier. GLG is a coinvestigator for a clinical trial from Pfizer and one from Bristol-Myers Squibb and GLG received honoraria from Pfizer, Sanofi and Aspen Pharma., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Diagnosis of pulmonary embolism remains a challenge for clinicians as its differential diagnosis is wide. The use of sequential diagnostic strategies based on the assessment of clinical probability, D-dimer measurement, and computed tomography pulmonary angiography have been validated in large prospective outcome studies. D-dimer measurement at a standard cutoff of 500 μg/L has gained wide acceptance to rule out pulmonary embolism in around 20 to 30% of patients with a clinically suspected pulmonary embolism. To improve the efficiency of D-dimer measurement, different ways of selecting a higher, albeit safe cutoff were explored: the age-adjusted D-dimer cutoff and the clinical adapted D-dimer cutoff. While both have been prospectively validated in large studies, some differences do exist. In particular, the prevalence of pulmonary embolism in these different validation studies was very different. Overall, the age-adjusted cutoff seems to be safer and less efficient, while the clinical probability adapted cutoff seems more efficient and less safe. Here, we report the available data regarding these two different ways to increase the diagnostic yield of D-dimer. Also, well beyond the accuracy of these adjusted/adapted cutoffs, some external factors, such as the prevalence of pulmonary embolism in the tested population and the clinical setting, have an important impact of the negative predictive value and on the overall efficiency of these cutoffs. Therefore, we also discuss which cutoff should be used according to the expected prevalence of the disease and according to the clinical setting.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The risk of venous thromboembolism (VTE) is increased postpartum and contributes to important morbidity and mortality. While there have been advances in evaluating diagnostic algorithms for suspected VTE during pregnancy, there is limited data for postpartum individuals., Objective: We conducted a scoping review to describe and evaluate diagnostic strategies used to investigate suspected VTE in postpartum individuals., Methods: A comprehensive search strategy was conducted in Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (January 1, 2000-September 30, 2022) to identify original articles that reported on diagnostic strategies in postpartum individuals with suspected VTE. We extracted demographics, clinical decision rules used, D-dimer and imaging completed, including test performance and VTE outcomes., Results: A total of 13 studies conducted across 11 countries with separate postpartum data were included for 759 individuals with suspected PE (n = 634) or DVT (n = 125), including unpublished data (n = 251). Among those with suspected PE, computed tomography pulmonary angiography was conducted more commonly (n = 522) than ventilation-perfusion scans (n = 69), with PE positivity rates that ranged from 4 %-27.6 % and 0-50 % across studies, respectively. Among 131 postpartum individuals with suspected PE who had a D-dimer measured, only 4.6 % (6/131) had a negative D-dimer test. For postpartum individuals with suspected DVT, the most common diagnostic test was compression ultrasonography (positivity rate 12.2 %-18.6 %). There were limited retrospective data evaluating the clinical decision rules., Conclusions: There are heterogeneous approaches globally in the diagnosis of suspected postpartum VTE. Limited high-quality data available underscores the need for more robust evidence to inform clinical practice., Competing Interests: Declaration of competing interest Dr. Skeith holds unrelated research funding from CSL Behring and honoraria from Leo Pharma and Sanofi. The remaining authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The aim of this work was to compare anatomic and functional dose-volume parameters as predictors of acute radiation-induced lung toxicity (RILT) in patients with lung tumors treated with stereotactic body radiation therapy., Methods and Materials: Fifty-nine patients treated with stereotactic body radiation therapy were prospectively included. All patients underwent gallium 68 lung perfusion positron emission tomography (PET)/computed tomography (CT) imaging before treatment. Mean lung dose (MLD) and volumes receiving x Gy (VxGy, 5-30 Gy) were calculated in 5 lung volumes: the conventional anatomic volume (AV) delineated on CT images, 3 lung functional volumes (FVs) defined on lung perfusion PET imaging (FV50%, FV70%, and FV90%; ie, the minimal volume containing 50%, 70%, and 90% of the total activity within the AV), and a low FV (LFV; LFV = AV - FV90%). The primary endpoint of this analysis was grade ≥2 acute RILT at 3 months as assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Dose-volume parameters in patients with and without acute RILT were compared. Receiver operating characteristic curves assessing the ability of dose-volume parameters to discriminate between patients with and without acute RILT were generated, and area under the curve (AUC) values were calculated., Results: Of the 59 patients, 10 (17%) had grade ≥2 acute RILT. The MLD and the VxGy in the AV and LFV were not statistically different between patients with and without acute RILT (P > .05). All functional parameters were significantly higher in acute RILT patients (P < .05). AUC values (95% CI) for MLD AV, LFV, FV50%, FV70%, and FV90% were 0.66 (0.46-0.85), 0.60 (0.39-0.80), 0.77 (0.63-0.91), 0.77 (0.64-0.91), and 0.75 (0.58-0.91), respectively. AUC values for V20Gy AV, LFV, FV50%, FV70%, and FV90% were 0.65 (0.44-0.87), 0.64 (0.46-0.83), 0.82 (0.69-0.95), 0.81 (0.67-0.96), and 0.75 (0.57-0.94), respectively., Conclusions: The predictive value of PET perfusion-based functional parameters outperforms the standard CT-based dose-volume parameters for the risk of grade ≥2 acute RILT. Functional parameters could be useful for guiding radiation therapy planning and reducing the risk of acute RILT., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The 4-level clinical pretest probability score (4PEPS) was recently introduced as a clinical decision rule for the diagnosis of pulmonary embolism (PE). Based on the score, patients are classified into clinical pretest probability categories (c-PTP). The "very low" category aims at excluding PE without further testing; "low" and "moderate" categories require D-dimer testing with specific thresholds, while patients with a "high" pretest directly proceed to imaging., Objectives: To provide further external validation of the 4PEPS model., Methods: The 4PEPS was applied to a previously collected prospective database of 756 patients with clinically suspected PE enrolled from European emergency departments in 2002 to 2003. The safety threshold for the failure rate in our study was calculated at 1.95% based on a 26% prevalence of PE in our study, as per the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee guidance., Results: Patients were classified as follows: 90 (12%) in the very low c-PTP group, of whom 5 (5.6%; 95% CI, 2.4%-12.4%) had PE; 363 (49%) in the low c-PTP group, of whom 34 had PE (9.4%); 246 (34%) in the moderate c-PTP group, of whom 124 (50%) had PE; and 35 (5%) in the high c-PTP group of whom 30 (86%) had PE. Overall, the failure rate of the 4PEPS was 9/734 (1.2%; 95% CI, 0.59%-2.23%) Overall, 9 out of 734 patients (1.2%; 95% CI, 0.59%-2.23%) were diagnosed with PE despite a negative 4PEPS rule; 5 (5.6%) from the very low c-PTP group, 3 (1.4%) in the low c-PTP group, and 1 (3.2%) in the moderate c-PTP group., Conclusion: We provide external validation data of the 4PEPS. In this high-prevalence cohort (26% prevalence), PE prevalence in the very low-risk group was higher than expected. A prospective validation study is needed before implementing the 4PEPS model in routine clinical practice., (© 2024 The Author(s).)

Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation., Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin., Methods: Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21., Results: Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low., Conclusions: Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis., Competing Interests: The ACTIV-4a platform was sponsored by the 10.13039/100000050National Heart, Lung, and Blood Institute, 10.13039/100000002National Institutes of Health, Bethesda and administered through OTA-20 to 011. The research was, in part, funded by the 10.13039/100000002National Institutes of Health (NIH) Agreement 1OT2HL156812 through the 10.13039/100000050National Heart, Lung, and Blood Institute (NHLBI) CONNECTS program. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the NIH. The ATTACC platform was supported by grants from the 10.13039/501100000024Canadian Institutes of Health Research, 10.13039/100012357LifeArc, Thistledown Foundation, Peter Munk Cardiac Centre, 10.13039/100008794Research Manitoba, 10.13039/100009395CancerCare Manitoba Foundation, 10.13039/501100023238Victoria General Hospital Foundation, and the 10.13039/501100000226Ontario Ministry of Health. The REMAP-CAP platform was supported by the European Union—through FP7-HEALTH-2013-INNOVATION: the Platform for European Preparedness Against (Re)emerging Epidemics (PREPARE) consortium (602525), and 10.13039/100010661Horizon 2020 research and innovation program: the Rapid European Covid-19 Emergency Research response (RECOVER) consortium (101003589)—and by the Australian 10.13039/501100000925National Health and Medical Research Council (APP1101719), the 10.13039/501100001505Health Research Council of New Zealand (16/631), the 10.13039/501100000024Canadian Institutes of Health Research (Strategy for Patient-Oriented Research Innovative Clinical Trials Program Grant - 158584, and COVID-19 Rapid Research Operating Grant - 447335), the U.K. NIHR and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (CTN 2014-012), the UPMC Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (PHRC-20-0147), the Minderoo Foundation, Amgen, Eisai, the Global Coalition for Adaptive Research, and the Wellcome Trust Innovations Project (215522). Dr Godoy is supported by the Frederick Banting and Charles Best Canada Graduate Scholarship (Doctoral Research Award) from the 10.13039/501100000024Canadian Institutes of Health Research. Dr Neal has received grants from the 10.13039/100000002National Institutes of Health and 10.13039/100000005United States Department of Defense; has received research support from Haemonetics, Janssen and Instrumentation Laboratories; has received honoraria from Haemonetics, 10.13039/100005565Janssen, and 10.13039/501100014255CSL Behring; and serves on the Scientific Advisory Board of Haima Therapeutics. Dr Goligher has received personal fees and nonfinancial support from Getinge, nonfinancial support from Timpel, outside the submitted work. Dr Cushman has received personal fees from the 10.13039/100000002National Institutes of Health, during the conduct of the study. Dr Bradbury has received personal fees from BMS Pfizer; nonfinancial support from 10.13039/100002429Amgen; personal fees and nonfinancial support from Bayer; personal fees and nonfinancial support from 10.13039/100004336Novartis; personal fees from Janssen; personal fees from Portola; and personal fees from Ablynx, outside the submitted work. Dr Tritschler is a member of the Canadian Venous Thromboembolism Research Network (CanVECTOR); the network receives grant funding from the 10.13039/501100000024Canadian Institutes of Health Research (CDT-142654). Dr Kahn is supported by a Tier 1 10.13039/501100001804Canada Research Chair. Dr L. Berry has received grants from PREPARE Network, 10.13039/501100000780European Commission through University Antwerp, grants from OPTIMISE CAP. She reports Australia funding through Monash University; grants from REMAP-CAP; New Zealand funding through Medical Research Institute of New Zealand; grants from Global Coalition for Adaptive Research (GCAR); United States funding through grants from ATTACC; Canada funding through 10.13039/100009663University Health Network, grants from ACTIV-4; and reports IP funding, 10.13039/100007921University of Pittsburgh, during the conduct of the study. Dr Lorenzi has received grants from PREPARE in EU (University Antwerp), grants from OPTIMISE-CAP in Australia (Monash University), grants from REMAP-CAP in New Zealand (Medical Research Institute of New Zealand (MRINZ)), grants from REMAP-COVID in the US (GCAR), grants from ATTACC in Canada (10.13039/100009663University Health Network), grants from ACTIV-4 IP in the U.S. (10.13039/100007125University of Pittsburgh), during the conduct of the study. Dr Higgins has received grants from 10.13039/501100000925National Health and Medical Research Council, grants from 10.13039/501100016056Minderoo Foundation, during the conduct of the study. Dr Berger has received grants from 10.13039/100000002National Institutes of Health - 10.13039/100000050NHLBI, during the conduct of the study; personal fees from Astra Zeneca, personal fees from Janssen, personal fees from Amgen, outside the submitted work. Dr Gong has received grants from 10.13039/100000050NHLBI, during the conduct of the study. Dr Castellucci has received unrelated honoraria received from Bayer, BMS-Pfizer Alliance, The Academy, LEO Pharma, Sanofi, Servier, and Valeo; and holds a Heart and Stroke Foundation of Canada National New Investigator Award, and a Tier 2 research Chair in Thrombosis and Anticoagulation Safety from the University of Ottawa. Dr Le Gal holds a Heart and Stroke Foundation of Canada National Clinician-Scientist Award, and the Chair on Diagnosis of Venous Thromboembolism from the University of Ottawa. Dr Rosenson has a patent EFSID 40934007 pending. Dr Derde has received grants from EU FP7-HEALTH-2013-INNOVATION-1, grant number 602525, grants from H2020 RECOVER grant agreement No 101003589, during the conduct of the study; COVID-19 guideline committee SCCM/ESICM/ SSC, ESICM COVID-19 taskforce, Dutch intensivists (NVIC) taskforce infectious threats, outside the submitted work. Dr Kumar has received grants from Merck, outside the submitted work. Dr McVerry has received grants from 10.13039/100000002NIH - National Heart, Lung and Blood Institute, during the conduct of the study; grants from Bayer Pharmaceuticals, Inc, outside the submitted work. Dr Nicolau has received personal fees from AMGEN, grants from 10.13039/100004325AstraZeneca, grants and personal fees from Bayer, grants from 10.13039/501100022336Esperion, grants from CLS Behring, personal fees from Daiichi-Sankyo, grants from Dalcor, grants from Janssen, grants and personal fees from Novartis, grants from NovoNordisk, grants and personal fees from Sanofi, personal fees from Servier, grants from Vifor, outside the submitted work. Dr Huang has received grants from the 10.13039/100000002NIH, during the conduct of the study. Dr Reynolds has received grants from 10.13039/100000050National Heart, Lung and Blood Institute, during the conduct of the study; nonfinancial support from 10.13039/100011949Abbott Vascular, nonfinancial support from BioTelemetry Inc, nonfinancial support from 10.13039/100004340Siemens, outside the submitted work. Dr Carrier has received grants from 10.13039/100004319Pfizer, grants from 10.13039/501100000024Canadian Institutes of Health Research, grants from 10.13039/100002491BMS, during the conduct of the study; grants and personal fees from Leo Pharma, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Bayer, personal fees from Sanofi Aventis, personal fees from Pfizer, outside the submitted work. Dr S. Berry reports grants from PREPARE Network, grants from Optimise-CAP, grants from REMAP-CAP, grants from GCAR, grants from 10.13039/100009663University Health Network, grants from 10.13039/100007125University of Pittsburgh, during the conduct of the study. Dr Webb reports grants from 10.13039/501100000925National Health and Medical Research Council, grants from 10.13039/501100016056Minderoo Foundation, during the conduct of the study. Dr Turgeon reports grants from 10.13039/100022992Canadian Institutes of Health Research, during the conduct of the study. Dr McArthur has received grants from 10.13039/501100001505Health Research Council of New Zealand, during the conduct of the study. Dr Farkouh has received grants from 10.13039/100002429Amgen, grants from Novo Nordisk, grants from 10.13039/100004336Novartis, outside the submitted work. Dr Hochman is a principal investigator for the ISCHEMIA trial which, in addition to funding by 10.13039/100000002NIH, received support in the form of devices and medications provided by: Medtronic, Inc; Abbott Vascular, Inc (formerly St. Jude Medical, Inc); Royal Philips NV (formerly Volcano Corporation); Arbor Pharmaceuticals, LLC; AstraZeneca Pharmaceuticals, LP; Merck Sharp & Dohme Corp; Omron Healthcare, Inc; Sunovion Pharmaceuticals, Inc; Espero BioPharma; and Amgen Inc; and financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr Zarychanski has received unrelated grant funding from the 10.13039/501100000024Canadian Institutes of Health Research, 10.13039/100009395CancerCare Manitoba Foundation, and 10.13039/100008794Research Manitoba and receives operating support as the Lyonel G. Israels Research Chair in Hematology at the 10.13039/100010318University of Manitoba. Dr Lawler has received unrelated consulting fees from Novartis, CorEvitas, and Brigham and Women’s Hospital, and unrelated royalties from McGraw-Hill Publishing; and is supported by a Heart and Stroke Foundation of Canada National New Investigator career award. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Introduction:  Obesity is a risk factor for venous thromboembolism, but studies evaluating its association with pulmonary embolism (PE) in patients with suspected PE are lacking., Objectives:  To evaluate whether body mass index (BMI) and obesity (i.e., BMI ≥30 kg/m 2 ) are associated with confirmed PE in patients with suspected PE and to assess the efficiency and safety of the age-adjusted D-dimer strategy in obese patients., Methods:  We conducted a secondary analysis of a multinational, prospective study, in which patients with suspected PE were managed according to the age-adjusted D-dimer strategy and followed for 3 months. Outcomes were objectively confirmed PE at initial presentation, and efficiency and failure rate of the diagnostic strategy. Associations between BMI and obesity, and PE were examined using a log-binomial model that was adjusted for clinical probability and hypoxia., Results:  We included 1,593 patients (median age: 59 years; 56% women; 22% obese). BMI and obesity were not associated with confirmed PE. The use of the age-adjusted instead of the conventional D-dimer cut-off increased the proportion of obese patients in whom PE was considered ruled out without imaging from 28 to 38%. The 3-month failure rate in obese patients who were left untreated based on a negative age-adjusted D-dimer cut-off test was 0.0% (95% confidence interval: 0.0-2.9%)., Conclusion:  BMI on a continuous linear scale and obesity were not predictors of confirmed PE among patients presenting with a clinical suspicion of PE. The age-adjusted D-dimer strategy appeared safe in ruling out PE in obese patients with suspected PE., Competing Interests: None declared., (Thieme. All rights reserved.)

Importance: Intensive interventions are provided to young children with unilateral cerebral palsy (UCP), classically focused on the upper extremity despite the frequent impairment of gross motor function. Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) effectively improves manual dexterity and gross motor function in school-aged children., Objective: To verify if HABIT-ILE would improve manual abilities in young children with UCP more than usual motor activity., Design, Setting, and Participants: This prospective randomized clinical trial (November 2018 to December 2021), including 2 parallel groups and a 1:1 allocation, recruitment took place at European university hospitals, cerebral palsy specialized centers, and spontaneous applications at 3 sites: Brussels, Belgium; Brest, France; and Pisa, Italy. Matched (age at inclusion, lesion type, cause of cerebral palsy, and affected side) pairs randomization was performed. Young children were assessed at baseline (T0), 2 weeks after baseline (T1), and 3 months after baseline (T2). Health care professionals and assessors of main outcomes were blinded to group allocation. At least 23 young children (in each group) aged 12 to 59 months with spastic/dyskinetic UCP and able to follow instructions were needed. Exclusion criteria included uncontrolled seizures, scheduled botulinum toxin injections, orthopedic surgery scheduled during the 6 months before or during the study period, severe visual/cognitive impairments, or contraindications to magnetic resonance imaging., Interventions: Two weeks of usual motor activity including usual rehabilitation (control group) vs 2 weeks (50 hours) of HABIT-ILE (HABIT-ILE group)., Main Outcomes and Measures: Primary outcome: Assisting Hand Assessment (AHA); secondary outcomes: Gross Motor Function Measure-66 (GMFM-66), Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT), and Canadian Occupational Performance Measure (COPM)., Results: Of 50 recruited young children (26 girls [52%], median age; 35.3 months for HABIT-ILE group; median age, 32.8 months for control group), 49 were included in the final analyses. Change in AHA score from T0 to T2 was significantly greater in the HABIT-ILE group (adjusted mean score difference [MD], 5.19; 95% CI, 2.84-7.55; P < .001). Changes in GMFM-66 (MD, 4.72; 95% CI, 2.66-6.78), PEDI-CAT daily activities (MD, 1.40; 95% CI, 0.29-2.51), COPM performance (MD, 3.62; 95% CI, 2.91-4.32), and satisfaction (MD, 3.53; 95% CI, 2.70-4.36) scores were greater in the HABIT ILE group., Conclusions and Relevance: In this clinical trial, early HABIT-ILE was shown to be an effective treatment to improve motor performance in young children with UCP. Moreover, the improvements had an impact on daily life activities of these children., Trial Registration: ClinicalTrials.gov Identifier: NCT04020354.

Background: Guidelines suggest but cannot recommend the optimal management of superficial vein thrombosis (SVT)., Objectives: To identify the prevalence of asymptomatic deep vein thrombosis (DVT) at the time of SVT diagnosis, and to report the treatment and 3-month complications of patients with only SVT more than 3 cm from deep vein junction (or unknown distance)., Methods: We performed a single-center retrospective review of patients referred to the Ottawa Hospital thrombosis unit with ultrasound (US)-diagnosed SVT, and followed patients with only SVT for 3 months., Results: Three hundred sixteen patients with SVT were included. Of the 218 patients without DVT symptoms at presentation, 19 (8.7%; 95% CI, 5.7%-13.2%) were found to have asymptomatic concomitant DVT (11 proximal and 8 distal), and 45 (20.6%) had SVT within 3 cm of the saphenofemoral or saphenopopliteal junctions. Among the 192 patients diagnosed with SVT only, we observed 3-month thrombotic complications in 56 (29.2%; 95% CI, 23.2%-36.0%) patients, with a total of 69 events: 11 (5.7%) DVTs, 2 (1.0%) pulmonary embolisms, 37 (19.2%) SVT extensions, and 19 (9.8%) SVT recurrences. Eighty-two percent (9/11) of the 3-month DVT and pulmonary embolism events occurred in patients who initially received conservative management. Therapeutic treatment doses were most effective., Conclusion: At the time of SVT diagnosis, many patients had asymptomatic DVT and SVT near the deep venous system, supporting the systematic use of initial US in patients clinically diagnosed with SVT. The observed differences in 3-month complication rates, according to the treatment provided, highlight the need for large-scale randomized controlled trials to establish optimal management., (© 2023 The Authors.)

Ventilation-perfusion (V/Q) lung scans constitute one of the oldest nuclear medicine procedures, remain one of the few studies performed in the acute setting, and are amongst the few performed in the emergency setting. V/Q studies have witnessed a long fluctuation in adoption rates in parallel to continuous advances in image processing and computer vision techniques. This review provides an overview on the status of artificial intelligence (AI) in V/Q scintigraphy. To clearly assess the past, current, and future role of AI in V/Q scans, we conducted a systematic Ovid MEDLINE(R) literature search from 1946 to August 5, 2022 in addition to a manual search. The literature was reviewed and summarized in terms of methodologies and results for the various applications of AI to V/Q scans. The PRISMA guidelines were followed. Thirty-one publications fulfilled our search criteria and were grouped into two distinct categories: (1) disease diagnosis/detection (N = 22, 71.0%) and (2) cross-modality image translation into V/Q images (N = 9, 29.0%). Studies on disease diagnosis and detection relied heavily on shallow artificial neural networks for acute pulmonary embolism (PE) diagnosis and were primarily published between the mid-1990s and early 2000s. Recent applications almost exclusively regard image translation tasks from CT to ventilation or perfusion images with modern algorithms, such as convolutional neural networks, and were published between 2019 and 2022. AI research in V/Q scintigraphy for acute PE diagnosis in the mid-90s to early 2000s yielded promising results but has since been largely neglected and thus have yet to benefit from today's state-of-the art machine-learning techniques, such as deep neural networks. Recently, the main application of AI for V/Q has shifted towards generating synthetic ventilation and perfusion images from CT. There is therefore considerable potential to expand and modernize the use of real V/Q studies with state-of-the-art deep learning approaches, especially for workflow optimization and PE detection at both acute and chronic stages. We discuss future challenges and potential directions to compensate for the lag in this domain and enhance the value of this traditional nuclear medicine scan., Competing Interests: Declaration of Competing Interest Eric Moulton reports a relationship with Jubilant DraxImage Inc that includes: employment. Ran Klein reports a relationship with Jubilant DraxImage Inc that includes: consulting or advisory. Ran Klein received revenue shares from Jubilant DraxImage, Inc and Invia Medical Solutions for myocardial blood flow quantification., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: While several risk stratification tools have been developed to predict the risk of recurrence in patients with an unprovoked venous thromboembolism (VTE), only 1 in 4 patients are categorized as low-risk. Rather than a one-time measure, serial D-dimer assessment holds promise to enhance the prediction of VTE recurrence after oral anticoagulant (OAC) cessation., Methods: Using the REVERSE cohort, we compared VTE recurrence among patients with normal D-dimer levels (<490 ng/mL among males under age 70, <500 ng/mL in others) at OAC cessation and 1-month follow-up, to those with an elevated D-dimer level at either timepoint. We also evaluated VTE recurrence based on absolute increase in D-dimer levels between the two timepoints (e.g., ∆D-dimer) according to quartiles., Results: Among 214 patients with serial D-dimer levels measured at OAC cessation and 1-month follow-up, an elevated D-dimer level at either timepoint was associated with a numerically higher risk of recurrent VTE than patients with normal D-dimer levels at both timepoints (6.9 % vs. 4.2 % per year, hazard ratio 1.6; 95 % CI 0.9-2.7). Among women with <2 HERDOO2 criteria, a normal D-dimer level at both timepoints predicted a very low risk of recurrent VTE during follow-up (0.8 % per year, 95 % CI 0.1-2.8). Irrespective of baseline value, recurrent VTE risk was only 3 % per year (95 % CI 1.4-5.6) among patients in the lowest ∆D-dimer quartile., Conclusion: Serial normal D-dimer levels have the potential to identify patients at a low risk of recurrent VTE. In addition, ∆D-dimer, irrespective of its elevation above cutoff threshold, may predict recurrent VTE., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Xu, Khan, Kovacs, Sabri, Righini, Kahn, Anderson, Chagnon, White, Rodger and Le Gal have no conflicts of interest to report. Dr. Carrier reports research funding from BMS, Leo Pharma, and Pfizer; and honoraria from Bayer, Pfizer, BMS, Leo Pharma, Servier, and Sanofi. Dr. Wells reports speaker honoraria from BMS and Bayer Healthcare and prior grant funding from BMS/Pfizer. Dr. Crowther reports honoraria from Pfizer, CSL Behring, and Diagnostica Stago; consultation services to/served on advisory boards for Servier Canada, Asahi Kasei, and Precision Biologics; serving on the data safety monitoring board for Bayer; stock ownership in Alnylam; and holds the Leo Pharma Chair in Thromboembolism research, the funding for which is held in perpetuity at McMaster University (the interest is used to support M.A.C.'s research activities)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The prevalence of pulmonary embolism (PE) is approximately 11-17 % in patients with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The optimal diagnostic strategy for PE in these patients remains undetermined., Aims: To evaluate the safety and efficacy of standard (revised Geneva and Wells PE scores combined with fixed D-dimer cut-off) and computed tomography pulmonary angiogram (CTPA)-sparing diagnostic strategies (ADJUST-PE, YEARS, PEGeD, 4PEPS) in patients with AE-COPD., Method: Post-hoc analyses of data from the multicenter prospective PEP study were performed. The primary outcome was the diagnostic failure rate of venous thromboembolism (VTE) during the entire study period. Secondary outcomes included diagnostic failure rate of PE and deep venous thrombosis (DVT), respectively, during the entire study period and the number of CTPA needed per diagnostic strategy., Results: 740 patients were included. The revised Geneva and Wells PE scores combined with fixed D-dimer cut-off had a diagnostic failure rate of VTE of 0.7 % (95%CI 0.3 %-1.7 %), but >70.0 % of the patients needed imaging. All CTPA-sparing diagnostic algorithms reduced the need for CTPAs (-10.1 % to -32.4 %, depending on the algorithm), at the cost of an increased VTE diagnosis failure rate of up to 2.1 % (95%CI 1.2 %-3.4 %)., Conclusion: Revised Geneva and Wells PE scores combined with fixed D-dimer cut-off were safe, but a high number of CTPA remained needed. CTPA-sparing algorithms would reduce imaging, at the cost of an increased VTE diagnosis failure rate that exceeds the safety threshold. Further studies are needed to improve diagnostic management in this population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Couturaud reports having received research grant support from Bristol-Myers Squibb/Pfizer and Bayer and fees for board memberships or symposia from Bayer, Bristol-Myers Squibb/Pfizer, Merck Sharp and Dohme, Merck Sharp and Dohme, Sanofi, Leo Pharma, Janssen and Astra Zeneca and having received travel support from Bayer, Bristol-Myers Squibb/Pfizer, Leo Pharma, Pfizer. Dr. Bertoletti reports having received research grant support from Bayer and fees for board memberships or symposia from Actelion, Aspen, Bayer, Bristol-Myers Squibb/Pfizer and MSD, and having received travel support from Aspen, Bayer, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Leo Pharma, MSD and Actelion. Dr. Pastre declares he has no conflict of interest related to this research. Dr. Roy declares he has no conflict of interest related to this research. Dr. Rambaud declares he has no conflict of interest related to this research. Dr. Mai declares she has no conflict of interest related to this research. Dr. Motreff declares she has no conflict of interest related to this research. Dr. Auffret declares he has no conflict of interest related to this research. Dr. Le Mao declares he has no conflict of interest related to this research. Dr. Gagnadoux declares he has no conflict of interest related to this research. Dr. Paleiron declares he has no conflict of interest related to this research. Dr. Schmidt declares he has no conflict of interest related to this research. Dr. Schmidt declares he has no conflict of interest related to this research. Dr. Sanchez reports having received research grant support from Bayer, Daiichi-Sankyo and Portola Pharmaceuticals, and fees or non-financial support for consultancy activities from Actelion, GlaxoSmithKline, Boehringer Ingelheim and Chiesi. Dr. Bressollette declares he has no conflict of interest related to this research. Dr. Nonent declares he has no conflict of interest related to this research. Dr. Tromeur declares she has no conflict of interest related to this research. Dr. Salaun declares he has no conflict of interest related to this research. Dr. Mismetti reports having received research grants from Bayer, fees for board memberships from Bayer, Bristol-Myers Squibb/Pfizer and Daiichi Sankyo, for lectures from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo and Sanofi, and for development of educational presentations from Bayer and Bristol-Myers Squibb/Pfizer. Dr. Girard reports having received personal fees and non-financial support from Bayer and Leo Pharma. Dr. Lacut reports having received personal fees from Bayer-Health Care, Bristol-Myers Squibb and Boehringer Ingelheim. Dr. Lemarie declares she has no conflict of interest related to this research. Dr. Meyer reports having received research grant support from Bayer, Boehringer Ingelheim, LEO Pharma Research Foundation and Sanofi, having been an uncompensated board member and a consultant for Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Leo Pharma and Pfizer, and having received travel support from Bayer, Boehringer Ingelheim, Daiichi Sankyo, Leo Pharma and Sanofi. Dr. Leroyer reports having received research grant support from Pfizer and fees for board memberships or symposia from Bayer and Astra Zeneca and having received travel support from Bayer, Leo Pharma. No other potential conflict of interest relevant to this article was reported., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: We previously determined good agreement and high specificity of the International Society on Thrombosis and Haemostasis (ISTH) definition of pulmonary embolism (PE)-related death among an expert central adjudication committee (CAC). CACs are often composed of experts in the corresponding research field. Involving physician trainees in CACs would allow investigators to divide the workload and foster trainees' research experience., Objective: To evaluate the accuracy of the ISTH definition of PE-related death for PE- versus non-PE-related deaths as confirmed by autopsy and its interrater agreement among physician trainees., Methods: This retrospective autopsy cohort included all patients with PE-related deaths between January 2010 and July 2019 as well as patients who died in 2018 from a cause other than PE at the New York-Presbyterian Hospital. Based on premortem clinical summaries, two physician trainees independently determined the cause of death using the ISTH definition of PE-related death. We calculated the sensitivity and specificity of the ISTH definition to identify autopsy-confirmed PE-related death and its interrater agreement., Results: Overall, 126 death events were adjudicated (median age, 68 years; 60 [48%] women), of which 29 (23%) were due to PE, as confirmed by autopsy. Sensitivity and specificity of the ISTH definition for autopsy-confirmed PE-related death was 48% (95% CI, 29-67) and 100% (95% CI, 96-100), respectively. Interrater reliability for PE-related death was good (percentage agreement, 93%; 95% CI, 87-96, Cohen's Kappa, 0.67; 95% CI, 44-85)., Conclusion: Our findings are consistent with our previous validation study. They further support the use of the ISTH definition of PE-related death and revealed high agreement between adjudicators with varied experience., Competing Interests: Declaration of competing interests There are no competing interests to disclose. Funding information S.R. Kahn, A. Delluc, N. Langlois, G. Le Gal, and T. Tritschler are members of the Canadian Venous Thromboembolism Research Network (CanVECTOR); the Network received grant funding from the Canadian Institutes of Health Research (Funding Reference: CDT-142654). S.R. Kahn holds a Tier 1 Canada Research Chair in venous thromboembolism. A. Delluc is recipient of a University of Ottawa Department of Medicine Research Salary Award. G. Le Gal holds a mid-career clinician scientist award from the Heart and Stroke Foundation of Ontario, and the Chair on the Diagnosis of Venous Thromboembolism, Department of Medicine, University of Ottawa., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)