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BACKGROUND: Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA).METHODS: MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220.FINDINGS: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]).INTERPRETATION: In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow.FUNDING: Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.

Introduction: Acute pulmonary embolism (PE) is a disease with a broad spectrum of clinical presentations. While some patients can be treated at home or may even be left untreated, other patients require an aggressive approach with reperfusion treatment. Areas covered: (1) Advanced reperfusion treatment in hemodynamically stable acute PE patients considered to be at high risk of decompensation and death, (2) the treatment of subsegmental pulmonary embolism, (3) outpatient treatment for hemodynamically stable PE patients with signs of right ventricle (RV) dysfunction, and (4) the optimal approach to identify and treatpost-PE syndrome. Expert opinion: Outside clinical trials, hemodynamically stable acute PE patients should not be treated with primary reperfusion therapy. Thrombolysis and/or catheter-directed therapy are only to be considered as rescue treatment. Subsegmental PE can be left untreated in selected low-risk patients, after proximal deep vein thrombosis has been ruled out. Patients with an sPESI or Hestia score of 0 criteria can be treated at home, independent of the presence of RV overload. Finally, health-care providers should be aware of post-PE syndrome and diagnose chronic thromboembolic pulmonary disease (CTEPD) as early as possible. Persistently symptomatic patients without CTEPD benefit from exercise training and cardiopulmonary rehabilitation.

The gut microbiome affects the development and progress of various types of disease such as obesity, diabetes, atherosclerosis and arterial thrombosis. Gut microbiome derived metabolites have been established to be predictive of arterial thrombosis in epidemiological studies. In these studies atherosclerosis and prothrombotic effect cannot be distinguished but preclinical studies show gut derived metabolites can induce platelet hyperreactivity and increase thrombotic potential. Gut commensals can also influence platelets through serotonin synthesis and may enhance Von Willebrand factor production. The effects on secondary haemostasis are less studied. In antiphospholipid syndrome, a thrombotic auto-immune disorder, autoreactive T cells and antibodies cross-react with auto-antigen mimicking peptides from gut commensals which appears to contribute to the pathophysiology. This review focusses on the prothrombotic effect of the gut microbiome and aims to provide insight into its influence on thromboembolic disease and the haemostatic system.

Objective: To investigate the impact of stimulus duration on motor unit (MU) thresholds and alternation within compound muscle action potential (CMAP) scans. Methods: The stimulus duration (0.1, 0.2, 0.6, and 1.0 ms) in thenar CMAP scans and individual MUs of 14 healthy subjects was systematically varied. We quantified variability of individual MU's thresholds by relative spread (RS), MU thresholds by stimulus currents required to elicit target CMAPs of 5% (S5), 50% (S50) and 95% (S95) of the maximum CMAP, and relative range (RR) by 100*[S95-S5]/S50. We further assessed the strength-duration time constant (SDTC). Experimental observations were subsequently simulated to quantify alternation. Results: RS, unaffected by stimulus duration, was 1.65% averaged over all recordings. RR increased for longer stimulus duration (11.4% per ms, p < 0.001). SDTC shortened with higher target CMAPs (0.007 ms per 10% CMAP, p < 0.001). Experiments and simulations supported that this may underlie the increased RR. A short compared to long stimulus duration recruited relative more MUs at S50 (more alternation) than at the tails (less alternation). Conclusions: The stimulus duration significantly affects MU threshold distribution and alternation within CMAP scans. Significance: Stimulation settings can be further optimized and their standardization is preferred when using CMAP scans for monitoring neuromuscular diseases.

Objectives: This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows:. To determine and compare the diagnostic accuracy of the clinically used tests for pregnancy-related DVT. This is a generic protocol that covers two separate reviews. The primary objectives of each review will be the following. Review one:. To determine the diagnostic accuracy of CDRs and D-dimer as triage tests for diagnosis of lower-extremity DVT during pregnancy and the postpartum period. CDR and D-dimer are analyzed as triage tests and will not be directly compared to each other since they are not alternatives but potentially complimentary. Review two:. To determine and compare the accuracy of US and MRI for diagnosis of lower-extremity DVT during pregnancy and the postpartum period. US and MRI are alternatives for the diagnosis of lower-extremity DVT in pregnancy and the postpartum period and will, therefore, be compared for diagnostic superiority if sufficient data are available, as will alternative CDRs. Secondary objectives Secondary objectives will be the following. To investigate the effects of different technological aspects of D-dimer assays, US, and MRI on test accuracy. These will include D-dimer assay types; use of Doppler flow measurement in US; MRI scanner type and scanning technique. To investigate the effect of different thrombus locations on US and MRI accuracy: distal (distal from popliteal vein), proximal (including and proximal from popliteal vein, but below the groin), and pelvic (above the groin). To investigate the effects of varying D-dimer cut-off values on test accuracy. To investigate the effect of trimester on test accuracy. To determine the number of inconclusive test results for US and MRI, defined as neither showing nor excluding DVT.

Background The intestinal microbiome plays a versatile role in the etiology of arterial thrombosis. In venous thrombosis, driven chiefly by plasma coagulation, no such role has yet been established. We hypothesized that the intestinal microbiome composition affects coagulation in humans. Methods We used healthy donor fecal microbiota transplant (FMT) to experimentally change the microbiome composition in metabolic syndrome patients. Thirty‐five subjects were randomized in a blinded fashion to healthy donor FMT or autologous FMT as a control in a 2:1 ratio. We measured thrombin generation at baseline and after 6 weeks using automated calibrated thrombinography, and we determined plasma abundance of 32 coagulation related proteins using a targeted mass spectrometry‐based quantitative proteomics assay with heavy labeled internal standards. Results Healthy donor FMT prolonged the thrombinography lag time (median delta 0.0 versus 0.25 minutes, P = .039). The other thrombinography parameters showed no significant difference. Unsupervised cluster analysis suggested overall downregulation of coagulation related plasma proteins in subject clusters containing predominantly subjects that had a metabolic response to healthy donor FMT. FMT treatment status itself showed no clear clustering pattern with up‐ or downregulation, however, and proteins did not cluster according to an apparent biological grouping. Discussion A single healthy donor FMT tends to modestly suppress the onset thrombin generation in metabolic syndrome patients, representing initial proof‐of‐principle that the intestinal microbiota composition might affect the coagulation system in humans. The findings merit external validation as a role for intestinal microbiota in coagulation can have clinically important implications.

Summary The rate of identified isolated subsegmental pulmonary embolism (ssPE) has doubled with advances in computed tomography pulmonary angiography (CTPA) technology, but its clinical relevance is debated. The YEARS diagnostic algorithm was shown to safely reduce the number of required CTPAs in the diagnostic management of PE. We hypothesized that the higher threshold for performing CTPA in YEARS was associated with a lower prevalence of ssPE compared to the conventional diagnostic algorithm. We compared 2291 consecutive patients with suspected PE managed according to YEARS to 3306 consecutive control patients managed according to the Wells score for the prevalence of isolated ssPE. In the YEARS cohort, 52% were managed without CTPA, 12% had pulmonary embolism (PE) of which 10% were isolated ssPE, and the 3‐month diagnostic failure rate was 0·35%. In the control cohort, 32% were managed without CTPA, 20% had PE of which 16% were isolated ssPE, and the 3‐month failure rate was 0·73%. The isolated ssPE prevalence was significantly lower in YEARS (absolute difference 6·2% (95% confidence interval [CI] 1·4–10), Odds Ratio 0·58 (95% CI 0·37–0·90). In conclusion, YEARS is associated with a lower prevalence of isolated ssPE, due to reduction in CTPAs by the higher D‐dimer threshold. This was however not associated with a higher risk of recurrent VTE during follow‐up.

Pulmonary embolism, although rare, is a leading cause of maternal mortality. There is no strong evidence base for the diagnosis and management of pregnancy-related pulmonary embolism, hampering firm recommendations. In women with a suspicion of pulmonary embolism, the diagnosis is confirmed in 1 in 25–30 women only. However, imaging is always necessary to exclude pulmonary embolism, as no clinical decision rules or D-dimer-based strategies have been validated in pregnancy. Computed tomography pulmonary angiography and pulmonary scintigraphy are both suitable modalities, unless deep vein thrombosis is confirmed by compression ultrasonography of lower limb veins. Low-molecular-weight heparin (LMWH) in therapeutic doses is the treatment of choice during pregnancy, and anticoagulation should be continued until 6 weeks after delivery with a minimum total duration of 3 months. Use of LMWH or vitamin K antagonists does not preclude breastfeeding. Whether dosing should be based on weight or anti-Xa levels is unknown, and practices differ between centres. Management of delivery, including the type of anaesthesia if deemed necessary, requires a multidisciplinary approach, and several options are possible, depending on local preferences and patient-specific conditions. Prevention of pulmonary embolism with LMWH is indicated in all postpartum women with a history of venous thromboembolism, and in most women also during pregnancy.