The association between breast cancer diagnosis and treatment and the risk of incident ischemic stroke remains unclear. We investigated ischemic stroke risk among breast cancer survivors and evaluated associations by age, follow-up duration, and type of cancer treatment. We conducted a nationwide, retrospective, matched cohort study using the Korean National Health Insurance Service database. Women aged 18 years and older with newly diagnosed breast cancer who underwent breast cancer surgery between January 2010 and December 2016 and had no prior stroke were identified. Each was matched 1:3 by birth year to cancer-free women. The primary outcome was first ischemic stroke, defined as hospitalization with International Classification of Disease, Tenth Revision codes I63/I64 plus inpatient brain CT or MRI. Subdistribution hazard ratios (sHRs) and 95% CIs were estimated using Fine-Gray models that accounted for death as a competing risk and adjusted for sociodemographic factors and cardiovascular and non-CV comorbidities. We analyzed 107,606 breast cancer surgery survivors (mean age, 50.0 years) and 322,818 matched cancer-free women. Over a mean 7.2-year follow-up, ischemic stroke occurred in 1,155 survivors (1.07%). Stroke risk was elevated shortly after breast cancer diagnosis (1-year sHR 1.59; 95% CI 1.34-1.89; 3-year sHR 1.17; 95% CI 1.05-1.30) compared with cancer-free women, with stronger associations at 3 and 6 months after diagnosis across all age groups. Over the long term, survivors had a slightly lower risk of stroke (sHR 0.94; 95% CI 0.88-1.00), and in a 1-year landmark analysis including only event-free individuals, the risk was lower (sHR 0.87, 95% CI 0.81-0.93). Among survivors, anthracycline use (sHR 1.25) and combined tamoxifen-aromatase inhibitor therapy (sHR 1.49) were associated with increased risk of stroke, whereas radiation therapy was associated with decreased risk (sHR 0.84). These associations attenuated and became nonsignificant beyond 1 year. Stroke risk was also higher among survivors with low income, hypertension, diabetes, or current smoking. The association between breast cancer and ischemic stroke risk is time dependent, with a short-term increase after diagnosis and treatment followed by a gradual decline over time. These findings highlight the need for proactive stroke risk management, including early CV assessment and ongoing monitoring for thromboembolic events during survivorship.

Elective repair for an abdominal aortic aneurysm (AAA) is performed to prevent rupture and subsequent death. The risk of early mortality is higher after open repair than after endovascular repair and needs to be reduced. Registries lack granular individual data to investigate this increased mortality. An independent, detailed, patient-level analysis of the international randomized controlled ACTION-1 trial was performed to investigate the relation between thromboembolic, hemorrhagic, or other events with mortality after open AAA repair, thereby exploring the cascade of pathological events leading to death. An adjudication committee was installed to assess the following domains: attributability of thromboembolic or bleeding event, whether the event occurred intraoperative or postoperative, cascade of pathological events, and cause of death. An intraoperative bleeding score was calculated to stratify the severity of bleeding. In 16 out of 20 deceased patients (80%), death was attributable to a thromboembolic or bleeding event. Four patients (20%) succumbed to causes unrelated to a thromboembolic or bleeding event. Intraoperative bleeding was the primary cause of death in 4 patients, all of whom underwent activated clotting time-guided heparinization. In contrast, an intraoperative thromboembolic event was the primary cause of death in one patient who had received 5,000 IU of heparin. In a randomized controlled trial on 297 patients with open AAA repair, 16 out of 20 (80%) deaths were due to bleeding or thromboembolic events. In most deceased patients, increased perioperative bleeding resulted in a pathological cascade of hypoperfusion, organ failure, and shock. Bleeding and thromboembolic complications must be addressed to reduce mortality after elective open AAA repair.

Modified antiplatelet therapies in patients with high on-treatment platelet reactivity (HTPR) remains unknown in neurointerventional treatment. We aimed to compare the safety and effectiveness of two different modified antiplatelet therapies in patients with HTPR undergoing stent-assisted coil embolization for an unruptured intracranial aneurysm. We conducted a prospective, randomized clinical trial. Participants with HTPR were randomly assigned (1:1) to the triple antiplatelet therapy (TAT, addition of cilostazol) or modified dual antiplatelet therapy (MDAT, switched from clopidogrel to low-dose prasugrel) group. The primary outcome was all-bleeding-events during the 90-day follow-up period. The secondary outcomes were thromboembolic events and changes in the P2Y12 reaction unit (PRU) value throughout the follow-up period. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed. In total, 172 of the 198 participants maintained initial antiplatelet therapy for 90 days. There was no significant difference in the all-bleeding-event rate between the two groups, both in the ITT population (hazard ratio [HR], 0.77 [95% CI, 0.49-1.20]; P = .26) and the PP population (HR, 0.79 [95% CI, 0.50-1.30]; P = .34). The thromboembolic event rate did not differ between the 2 groups in either the ITT population (HR, 0.33 [95% CI, 0.03-3.20]; P = .34) or the PP population (HR, 0.42 [95% CI, 0.04-4.70]; P = .48). Compared with those in the TAT group, the PRU values in the MDAT group greatly decreased over time, particularly for PRU after loading. Among patients with HTPR who underwent stent-assisted coil embolization for an unruptured intracranial aneurysm, there was no significant difference between the TAT and MDAT groups regarding the risk of all bleeding events and thromboembolic events during the 90 days of follow-up.

Thrombotic and thromboembolic events are a common and potentially preventable complication in multitrauma patients, and substantial quality improvement efforts are directed at prevention. The results of several randomized controlled trials (RCTs) related to the association between tranexamic acid (TXA) and thrombotic/thromboembolic events have demonstrated conflicting results. We aimed to address this by examining whether prehospital TXA was associated with higher rates of thrombotic/thromboembolic events in a harmonized data set from three large multicenter RCTs. We analyzed data using a harmonized data set from three RCTs examining the effects of prehospital TXA: The Pre-Hospital Anti-fibrinolytics for Traumatic Coagulopathy and Hemorrhage Study (PATCH trial), Study of Tranexamic Acid During Air and Ground Medical Prehospital Transport Trial (STAAMP trial) and the Prehospital TXA for TBI trial, part of the Resuscitation Outcomes Consortium (ROC trial). Outcomes included deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, stroke, combined venous thrombotic/thromboembolic events (VTE), and combined arterial thrombotic/thromboembolic events. Multivariable regression was used to adjust for TXA administration, sex, age, injury severity score, Glasgow Coma Scale, shock index, and 24-hour red cell transfusion. There were no differences in myocardial infarction, stroke, arterial thrombotic/thromboembolic events, DVT, PE, or VTE in patients who were randomized to TXA compared with those who were not. On univariate analysis, rates of PE, DVT and VTE were significantly higher in the PATCH cohort compared with STAAMP and ROC cohorts, but patients in PATCH had significantly higher injury severity scores and chest trauma when compared with those in ROC and STAAMP. This multicenter database combining three large RCTs showed that randomization to TXA was not associated with higher rates of arterial and VTE. The higher rates of thrombotic/thromboembolic events observed in the PATCH trial may be explained by higher injury severity as well as protocolized screening. ( J Trauma Acute Care Surg. 2026;101: 48-56. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). Sub-analysis of randomized controlled trials; Level II.

This guideline summarizes diagnostic and therapeutic approaches based on a systematic literature review and evidence evaluation using the GRADE methodology. Given the limited high-quality data, expert consensus was additionally obtained through a modified Delphi process. Remethylation disorders are rare inherited conditions that disrupt the methionine-homocysteine cycle and consecutively impair essential methylation dependent metabolic pathways. Remethylation disorders are caused by defects in the cobalamin or folate metabolism. The disorders typically result in elevated homocysteine and often low methionine; combined cobalamin-related defects also affect mitochondrial methylmalonic acid clearance. The cblC-MMACHC defect is the most common cobalamin-related remethylation disorder. Early-onset patients usually present with severe neurological and eye symptoms. Late-onset cases show variable symptoms (e.g., psychiatric, renal, thromboembolic events). Plasma total homocysteine, methionine, methylmalonic acid, serum vitamin B12 (and folates) should be assessed in suspected cases. Early detection through newborn screening is associated with improved clinical outcomes. Betaine as first-line therapy for methylenetetrahydrofolate reductase deficiency and parenteral hydroxocobalamin for cobalamin-related defects have reduced mortality and morbidity. Total homocysteine, methionine (and methylmalonic acid) should be kept as close to normal values as achievable. Emerging evidence suggests that early use of high-dose hydroxocobalamin (> 0.35 mg/kg/day) may improve neurocognitive impairment and may ameliorate eye disease in severe cobalamin-related defects. A major limitation in current practice is the lack of availability of high concentration hydroxocobalamin formulations for parenteral administration.

Impact of intraoperative intravenous heparin bolus on clinical outcomes during radical nephrectomy and IVC tumor thrombectomy in renal cell carcinoma with level I-IV IVC thrombus: A multi-institutional study.

This systematic review and meta-analysis aimed to evaluate the risk of thromboembolic events and assess the overall safety and effectiveness of avatrombopag in adult patients with immune thrombocytopenia using real-world evidence. A systematic search was conducted following the PRISMA 2020 guidelines. Observational studies (2020-2024) on adults with primary immune thrombocytopenia treated with avatrombopag were included. Primary outcomes were thromboembolic complications and treatment response; secondary outcomes included time to response, treatment discontinuation, and adverse events. Random-effects meta-analyses were performed to synthesise pooled proportions and rates. Risk of bias was assessed using the ROBINS-Version 2 tool. Fifteen studies were included. The pooled proportion of patients with thromboembolic events was 2.82% (95% confidence interval: 1.61%-4.27%), with an incidence rate of 3.29 per 100 patient-years (95% CI: 1.81-5.08). Response and complete response were achieved by 80.0% and 92.0% of patients, respectively. The median time to response was 11 days, and the discontinuation rate was 18.9%. Adverse events occurred in 4.1% of patients. In real-world practice, avatrombopag demonstrated high platelet response rates and a low pooled incidence of thrombotic events. These findings add real-world evidence on avatrombopag outcomes in adult immune thrombocytopenia.

Tranexamic acid (TXA) is widely used in total joint arthroplasty (TJA) to reduce perioperative blood loss and transfusion requirements. There is a growing body of literature on the use of extended postoperative TXA following total knee arthroplasty (TKA). This study evaluated the impact of an extended postoperative oral TXA regimen following total hip arthroplasty (THA) and TKA. After obtaining Institutional Review Board approval, a retrospective chart review was conducted to identify patients who underwent THA/TKA at a single institution. All patients received a standard 1-gram intravenous TXA dose prior to incision and at the time of closure. Those who underwent TJA after formal adoption of an institutional protocol implementing an extended postoperative oral TXA regimen received an additional 1.95-gram dose of oral TXA starting on the day of surgery and continued for three days postoperatively. Patient-reported outcome measures, hospital lengths of stay (LOSs), postoperative complications, 90-day readmissions, and primary TJA-related emergency department visits were compared between the oral TXA group and a historical cohort. All patients included in the analysis had a minimum follow-up of three months. A total of 312 patients were included (153 in the oral TXA group and 159 historical controls). Baseline demographics and preoperative Hip Disability and Osteoarthritis Outcome/Knee Injury and Osteoarthritis Outcome scores were comparable between groups. Extended TXA use was associated with significantly greater improvement in patient-reported outcome measures (change of 27.7 versus a change of 18.1; P < 0.001) and a significant reduction in TJA-related emergency department visits (odds ratio 0.11; 95% confidence interval 0.02 to 0.49; P = 0.007). There were no significant differences in LOS, 90-day readmissions, or postoperative complications, including infection or thromboembolic events (all P > 0.05). In this retrospective cohort of primary THA and TKA patients, the use of oral TXA for three days postoperatively was associated with improved early patient-reported function without an increase in complications or LOSs.

Acute stroke is frequently complicated by new-onset cardiac or thromboembolic events, referred to as Stroke-Heart Syndrome (SHS). The role of stroke subtype and lesion location in determining SHS risk remains underexplored. We conducted a retrospective analysis of data from the hospital-based Perugia Stroke Registry (March 2005-September 2019). Patients with acute neurological symptoms were classified as ischaemic stroke (IS) or haemorrhagic stroke (HS) based on neuroimaging. Logistic regression identified predictors of stroke subtype and in-hospital complications. Subgroup analyses compared first-ever versus recurrent strokes, and lesion location (lacunar, non-lacunar anterior, or non-lacunar posterior for IS; typical versus atypical for HS). The primary outcome was a composite of all-cause death, cardiac events and venous thromboembolic events during Stroke Unit stay. Secondary outcomes were each component. Among 2080 patients (mean age 72.8 ± 12.5 years; 57% male), 1788 (86%) had IS and 292 (14%) HS. During Stroke Unit stay (median 8 days, IQR 5-14), HS patients had higher rates of the composite outcome (26% vs 14%) and all-cause death (21.2% vs 8.8%) than IS. In IS, non-lacunar posterior and anterior strokes were associated with increased risk of composite outcome (OR 1.97, 95%CI 1.10-3.63; OR 1.61, 95%CI 0.96-2.81) and all-cause death (OR 3.35, 95%CI 1.35-9.51; OR 2.90, 95%CI 1.28-7.79) versus lacunar strokes. Among HS, atypical lesions increased risk of composite outcome (OR 2.51, 95%CI 1.24-5.22) and all-cause death (OR 2.80, 95%CI 1.31-6.17). Lesion location is a key determinant of SHS. Non-lacunar posterior stroke and atypical HS predict higher mortality and cardiovascular complications.

Perioperative systemic therapy versus surgery alone for resectable colorectal peritoneal-only metastases (CAIRO6): a randomised, open-label, phase 3 trial.

Pregnancy, delivery, and neonatal outcomes in women with uterine fibroids carrying singleton vs. multiple gestations: A retrospective population database cohort study.

Are Patients Who Have Sarcoidosis at Increased Risk of Adverse Postoperative Outcomes Following Total Knee Arthroplasty?

BackgroundLigament and tendon pathology of the ankle is frequently complicated by chronic instability, poor tissue quality, and prior failed repairs. Augmentation devices have been introduced to reinforce primary repair and protect healing tissues during the early postoperative period. A novel synthetic augmentation device was used as an adjunct in primary ankle ligament repair across a range of clinical presentations.MethodsThis retrospective case series evaluates early clinical outcomes in 5 patients who underwent ankle ligament repair augmented with TEKBRACE (Theramicro, Cordova, Tennessee). The cohort included 3 males and 2 females with a mean age of 52 years (range, 37-65) and mean body mass index of 29.9 (range, 22.7-39.1). Diagnoses included acute lateral instability (n = 3), acute-on-chronic instability (n = 1), and chronic instability with concomitant tendinopathy (n = 1). All diagnoses were confirmed by clinical examination and magnetic resonance imaging. Mean follow-up was 18 weeks (range, 16-24 weeks). All patients followed a standardized postoperative immobilization and rehabilitation protocol.ResultsAt early follow-up, all patients demonstrated stable clinical courses without device-related complications. There were no postoperative infections, wound complications, thromboembolic events, skin reactions, or mechanical failures. Visual Analog Scale pain scores improved from a mean of 4.8/10 preoperatively to a mean of 0.6/10 at final follow-up. Range of motion was within normal limits compared to preoperative baseline in all patients. Four of 5 patients returned to full unrestricted activity. No gross instability was detected on clinical examination at any postoperative visit.ConclusionEarly outcomes following TEKBRACE augmented ankle ligament repair were encouraging in this small preliminary series, with no device-related complications observed. These findings support the feasibility of the technique and provide rationale for prospective investigation with standardized outcome collection and longer follow-up.

Anticoagulation in Heart Transplantation Patients: Increased Bleeding without Reducing Thromboembolic Events?

Venous thromboembolism (VTE) is a preventable condition associated with an increased risk of morbidity and mortality in hospitalized patients. Pharmacological and/or mechanical prophylaxis can prevent thromboembolism events. Guidelines recommend the use of scores for risk assessment in hospitalized patients. These scores are based on a variety of risk factors, including age, reduced mobility, and type of surgery. They help determine the most appropriate prophylaxis method for each patient. However, VTE prophylaxis is still a challenge, and there are limitations associated with it. In this scenario, clinical pharmacists may play a key role in improving VTE prophylaxis. The main aim of this real-life study was to evaluate the contribution of the clinical pharmacist to thromboembolism prophylaxis in a large sample of clinical and surgical patients. This is an observational and retrospective study using hospital-based data. The study included 4031 patients, and we evaluated how pharmacist interventions contributed to the appropriate indication and correct use of VTE prophylaxis in clinical and surgical patients. We included 1093 clinical patients and 2938 surgical patients. Following clinical pharmacist involvement (262 pharmacist interventions), there were improvements in the adequacy rate: 62.0% for clinical patients and 55.0% for surgical patients. The intervention of the clinical pharmacist can contribute to improved rates of adherence to VTE protocols.

Anticoagulation after total knee arthroplasty (TKA) remains a balance between clot prevention and postoperative bleeding. This study aimed to analyze anticoagulant choice for deep vein thrombosis prophylaxis on rates of stiffness requiring manipulation under anesthesia (MUA) and hematoma formation after TKA. A large national database was queried for all primary TKAs. We included patients who filled a prescription for an anticoagulant within three days before or five days after surgery. We excluded those who filled prescriptions for multiple or no anticoagulants. Logistic regression was used to compare potent anticoagulants (warfarin, Xa inhibitors, and low molecular weight heparin (LMWH)) to our control group receiving aspirin. The primary outcomes of interest were MUA or hematoma formation within 90 days postoperatively. After applying the exclusion criteria, 462,869 patients were available to review. Of those, 148,159 (32.05%) received aspirin, followed by factor Xa inhibitors (123,909 [26.80%]), warfarin (96,338 [20.84%]), and LMWH (84,962 [18.38%]). Using logistic regression analyses, patients receiving factor Xa inhibitors (odds ratio [OR] 1.38 [95% confidence interval (CI) 1.32 to 1.43]), indirect factor Xa inhibitors (OR 1.33, [95% CI 1.19 to 1.48]), warfarin (OR 1.29 [95% CI 1.23 to 1.35]), and LMWH (OR 1.26, [95% CI 1.20 to 1.32]) had higher rates of MUA than the aspirin cohort. Additionally, when compared to aspirin, those receiving LMWH (OR 1.69 [95% CI 1.46 to 1.96]), indirect factor Xa inhibitors (OR 1.62 [95% CI 1.13 to 2.26]), direct factor Xa inhibitors (OR 1.55 [95% CI 1.35 to 1.78]), and warfarin (OR 1.33 [95% CI 1.14 to 1.55]) were at a significantly higher risk of hematoma formation. The use of aspirin for deep vein thrombosis prophylaxis after TKA is associated with a significantly lower risk of undergoing MUA and hematoma formation, without increasing the clotting risk profile, than more potent anticoagulants.

While DOACs - Direct Oral Anticoagulants are the current standard for stroke prevention, nearly 30-50% of eligible patients remain untreated or undertreated due to perceived or actual bleeding risk. Therefore, evaluating agents that potentially uncouple antithrombotic efficacy from hemostasis is a clinical priority. Factor XI/XIa (FXI/XIa) inhibitors are proposed to reduce bleeding while maintaining antithrombotic efficacy. We aimed to compare the efficacy and safety of FXI/XIa inhibitors versus DOACs in patients with AF. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing FXI/XIa inhibitors with DOACs in adults with AF. Databases including MEDLINE, Embase, and Scopus were searched until February 28, 2025. The study protocol was prospectively registered in PROSPERO (CRD420251045353). The primary outcome was ISTH major bleeding. Secondary outcomes included ischemic stroke, clinically relevant non-major (CRNM) bleeding, and all-cause mortality. Random-effects models were used to pool odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity was assessed using I². Four RCTs (OCEANIC-AF, AZALEA-TIMI 71, PACIFIC-AF, and LIBREXIA-AF [design protocol]) involving 16,852 patients were included in the qualitative synthesis, with data from three trials contributing to quantitative meta-analyses. Compared to DOACs, FXI/XIa inhibitors were associated with a significant reduction in ISTH major bleeding (0.40% vs. 1.32%; OR 0.30, 95% CI 0.20-0.43; P < 0.001; I²=0%) and CRNM bleeding (1.53% vs. 3.94%; OR 0.38, 95% CI 0.30-0.47; P < 0.001; I²=0%). However, FXI/XIa inhibitors were associated with a significantly increased risk of ischemic stroke (1.12% vs. 0.35%; OR 3.20, 95% CI 1.85-5.55; P = 0.004; I²=0%). A modest but statistically significant reduction in all-cause mortality was observed (1.37% vs. 1.68%; OR 0.81, 95% CI 0.69-0.95; P = 0.021; I²=0%). In patients with atrial fibrillation, Factor XI/XIa inhibitors significantly reduce major and clinically relevant non-major bleeding compared to DOACs but are associated with an increased risk of ischemic stroke. While a modest reduction in all-cause mortality was noted, the unfavorable efficacy profile for stroke prevention raises concerns about the net clinical benefit of the currently evaluated FXI/XIa inhibitors in this population. Further data from ongoing large-scale trials are needed to define their ultimate clinical role.

Approaches to treating tricuspid valve disease are at the forefront of current clinical investigation. Utilization of an established large animal model to evaluate novel valves is required for regulatory approval prior to clinical investigation. Here we present a sheep model of surgical tricuspid valve replacement using a clinically approved surgical prosthesis. Five adult sheep underwent surgical tricuspid valve replacement (STVR) using a Medtronic Mosaic™ prosthesis and were survived for 140days per regulatory guidance. Serial clinical pathology and echocardiography data was collected. At the study endpoint, echocardiography and cardiac catheterization was performed, followed by a comprehensive necropsy. Four animals successfully underwent STVR. Epicardial echocardiography at the time of implantation and terminal procedure confirmed preserved cardiac output and effective orifice area. Serial transthoracic echocardiography showed no sign of valvular regurgitation and comparable functional parameter throughout the postoperative study period. Intracardiac catheterization at the study endpoint confirmed absence of regurgitant flow across the device at rest and under dobutamine induced stress. Gross pathology revealed a well-seated valve with preserved functional integrity and no signs of downstream thromboembolic events. Using a relevant sheep model of STVR, this study demonstrates how detailed follow-up using echocardiography, intracardiac catheterization as well as clinical and gross pathology can yield valuable long-term in vivo data on tricuspid device safety and function.

Background Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and remains a leading cause of cancer-related mortality. Surgical resection remains the cornerstone of curative treatment for CRC; however, postoperative complications, including anastomotic leakage, infections, and thromboembolic events, continue to substantially affect patient prognosis. These complications are associated with prolonged hospitalization, increased healthcare expenditures, delayed postoperative recovery, and elevated mortality risk. Therefore, the accurate identification of patients at high risk for postoperative complications is of considerable clinical importance for optimizing perioperative management and improving surgical outcomes. Methods A total of 154 patients were retrospectively enrolled, including 99 patients in the training cohort and 55 patients in the external validation cohort. Abdominal CT images at the L1-L5 levels were automatically segmented using a pretrained DeepLabv3-ResNet101 model implemented on the Onekey platform, followed by manual correction to ensure segmentation accuracy. Visceral adipose tissue, subcutaneous adipose tissue, skeletal muscle, and intramuscular adipose tissue were segmented, and body composition indices (VAT_h, SAT_h, SMA_h, and IMAT_h) were subsequently calculated after normalization by patient height. Deep learning features were extracted from CT images using a pretrained 3D ResNet-18 model. Feature selection and model development were conducted independently. Random forest, logistic regression, and extremely randomized trees combined with recursive feature elimination were applied for feature selection. Subsequently, logistic regression, random forest, support vector machine (SVM), k-nearest neighbors (KNN), XGBoost, and LightGBM algorithms were constructed and compared for predictive performance. Results Univariate and multivariate analyses identified BMI, SMA_h, SAT_h, and VAT_h as independent risk factors for postoperative complications. Among all predictive models, the combined model incorporating the deep learning score (DL-score) achieved the best performance, with AUC values of 0.944 and 0.855 in the training and validation cohorts, respectively. DeLong test results further demonstrated that both the deep learning model and the combined model significantly outperformed the clinical and body composition models, whereas the combined model provided superior discrimination in identifying high-risk patients.

Eight-year clinical and radiographic outcomes after meniscal repair augmented with autologous synovial mesenchymal stem cell transplantation: A long-term follow-up case series.