Ana Isabel Casanegra

Background: Left ventricular thrombus (LVT) is a serious thromboembolic complication of cardiac dysfunction. Vitamin K antagonists (VKAs) are the historical standard therapy, but have limitations. While direct oral anticoagulants (DOACs) offer practical advantages, their efficacy and safety in LVT remain uncertain. This meta-analysis aimed to compare the efficacy and safety of DOACs versus VKAs for the treatment of LVT. Methods: We conducted a meta-analysis by systematically searching electronic databases from inception to December 2025. A random-effects model was used for all analyses. The primary outcome was LVT resolution. Secondary outcomes included ischemic stroke, non-cerebral systemic embolism (SE), the composite of stroke and SE, any bleeding, major bleeding, and mortality. Results: A total of 35 studies (7 RCTs and 28 retrospective cohort studies), with 6,437 patients (DOACs n = 2,421, VKAs n = 4,016), were included in the analysis. DOACs showed a non-significant trend toward higher LVT resolution than VKAs (odds ratio [OR] 1.17; 95% confidence interval [CI] 0.99–1.39). DOACs were associated with a lower risk of stroke (OR 0.77, 95% CI 0.65–0.92), while SE rates remained comparable (OR 0.79, 95% CI 0.54–1.15). DOACs were associated with a significantly lower risk of major bleeding compared to VKAs (OR 0.62, 95% CI 0.48–0.79; p < 0.001). When analyses were limited to only randomized trials or post–acute coronary syndrome, efficacy and safety were similar across anticoagulants. Trial sequential analysis indicated indecisive results, highlighting the need for further clinical trials. Conclusions: DOACs showed overall efficacy similar to VKAs for the treatment of LVT, with lower rates of major bleeding. Despite the large number of included studies, the current evidence base remains inconclusive due to the predominance of observational studies, underscoring the need for additional large, well-designed clinical trials.

Background: Chronic venous insufficiency (CVI) can be evaluated using Duplex ultrasonography (US) and air plethysmography (PG), yet comparative performance remains unclear. Methods: We retrospectively identified patients who underwent venous insufficiency US and PG within a 90-day interval from March 1, 2015 through July 31, 2024. CVI severity was classified by the clinical (C) component of the Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) classification system and categorized as mild (C0–2), moderate (C3), or severe (C4–6). PG and insufficiency US findings were compared across categories and machine learning models were trained to predict severe CVI. Results: We analyzed 1478 limbs from 839 patients who were predominantly women (62%) with a mean age of 61 years (± 14 years). Severe CVI was present in 32.3% of limbs. US detected venous incompetence in 67.4% of limbs overall and in 75.3% of severe CVI limbs. Abnormal PG findings occurred in 72.9% of limbs overall and in 88.5% of severe CVI limbs. PG parameters in machine learning models outperformed US parameters in predicting severe CVI (area under the receiver operating characteristic curve [AUROC] 0.82 vs 0.65). The top PG model (multilayer perceptron [MLP]) achieved an AUROC of 0.82, versus the best US model (gradient boosting) with an AUROC of 0.65. Limiting PG data to incompetence and obstruction parameters modestly reduced performance but remained higher than US (logistic regression AUROC 0.72). Conclusion: Our findings indicate that PG assessment in CVI offers superior performance compared to US. Overall, these results validate the quantitative whole-limb hemodynamic approach using PG, which provides a more complete understanding of the pathology behind CVI.

Post-pulmonary embolism syndrome (PPES) encompasses a diverse spectrum of long-term complications that are associated with persistent dyspnea, exercise intolerance, and a decrease in quality of life. The PPES constellation ranges from life-threatening conditions such as chronic thromboembolic pulmonary hypertension (CTEPH) to nonlife-threatening but still debilitating conditions such as chronic thromboembolic pulmonary disease (CTED) or post-PE deconditioning. The safety and efficacy of exercise and cardiopulmonary rehabilitation programs to prevent and manage these symptoms in PPES has not been well established. Herein, we review contributors to PPES and synthesize the evidence for exercise training after PE to treat and prevent PPES.

Guidelines recommend placement of inferior vena cava filters (IVCFs) in patients with acute proximal lower extremity deep vein thrombosis (DVT) and a contraindication to anticoagulation. IVCF placement during pregnancy or immediately postpartum presents technical challenges and is not extensively described in the existing literature. This study aimed to describe the use of IVCFs in the obstetric population along with outcomes related to filter placement. Retrospective chart review of all patients at Mayo Clinic from 2001 to 2020 with an IVCF at the time of conception or who underwent placement during pregnancy/postpartum. About 24 pregnancies in 23 women (mean age 26.3 years, range 18–41) were included: 5 (21%) with IVCF placement prior to pregnancy, 7 (29%) during pregnancy, and 12 (50%) during postpartum. IVCFs placed during pregnancy were frequently in the suprarenal position, in 5 (71%) cases. Meanwhile, 16 (94%) were deployed in an infrarenal position prior to pregnancy and postpartum. Complications included multiple attempts to remove the IVCF (n = 2), severe angulation (n = 4), embedded struts (n = 3), fracture (n = 1), and one case of cardiac tamponade (n = 1). Complications were more common when placement was performed prior to pregnancy or during pregnancy (2, 40% and 4, 57% respectively) versus postpartum (2, 17%). IVCF placement prior or during pregnancy/postpartum is uncommon and is associated with a high incidence of complications, although most did not fundamentally impact clinical outcomes. While IVCFs remain an option for clinicians treating pregnant and postpartum patients, these should be considered a last resource.

Antiphospholipid antibody (aPL) testing is fundamental for diagnosing and classifying antiphospholipid syndrome (APS) under the Sydney criteria, which recommend the detection of lupus anticoagulant (LA), anticardiolipin antibody (aCL), and anti-β2-glycoprotein I (ab2GPI) antibodies in both IgG and IgM isotypes.[1] However, the clinical significance of IgM has remained uncertain. Comparative studies consistently show that IgG isotypes have stronger and more reproducible associations with thrombotic or obstetric events than IgM.[2] Reflecting this, the International Society on Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee (SSC) emphasized that while IgM testing is formally included, its interpretation is often complex, particularly in the absence of IgG or LA positivity, due to assay variability and limited outcome correlations.[3] This evolving evidence was incorporated into the 2023 American College of Rheumatology and the European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria, where isolated IgM positivity is assigned minimal laboratory weight due to its reduced specificity and frequent low-risk or false-positive profiles. Importantly, this weighting applies to classification only and does not alter the recommended diagnostic workup.[4] While some reports find little correlation between isolated IgM and morbidity,[5] others note possible phenotype-specific links, such as obstetric events, retinal vein thrombosis, or cerebrovascular events in younger patients.[6] [7] [8] Large-scale work, such as Egiziano et al's analysis of over 33,000 patients, demonstrates the value of big-data approaches in uncovering real-world testing patterns, showing that many IgM-positive results were not reproducible on repeat testing and underscoring the limited reliability of isolated IgM positivity.[9] Our study expands this evidence by describing real-world aPL ordering patterns and testing results of LA, aCL, and anti-β2-glycoprotein, both IgG and IgM. We reviewed all aPL results across Mayo Clinic sites in the United States from January 2006 to July 2025, aligning with the release of the revised Sapporo (Sydney) criteria. This was a laboratory-based analysis without incorporation of clinical events, and positive aPL laboratories should not be interpreted as a diagnosis of antiphospholipid syndrome. For each patient, we identified the earliest occasion on which any aPL test was performed. We extracted available results for LA, aCL IgG and IgM, and β2-glycoprotein I (b2GPI) IgG and IgM. Positivity was defined according to international criteria and internal standards: ≥40 units for aCL and b2GPI, and for LA, ISTH SSC guideline-based demonstration of a phospholipid-dependent inhibitor in Dilute Russell's viper venom time (DRVVT) or activated partial thromboplastin time (aPTT)-based platelet neutralization procedure, Staclot LA delta, and HEX LA delta assays, with specific cutoffs applied for each. Given the laboratory-based nature of this study, potential false positives could not be excluded. Positivity rates were calculated for individual markers, and a subset of patients who underwent complete testing for all three categories at initial workup were analyzed for single-, double-, and triple-positivity distributions, defined as positivity for one, two, or all three aPL categories (LA, aCL, or b2GPI, in either IgG or IgM isotype), respectively. We also identified patients positivity only for IgM isotypes (aCL or b2GPI) in the absence of IgG or LA. We identified 99,814 patients tested for at least one aPL marker, with LA being the most frequently ordered test (n = 75,085; positivity rate = 10.3%), followed by aCL IgG (n = 69,539; positivity rate = 1.2%), aCL IgM (n = 69,640; positivity rate = 1.7%), b2GPI IgG (n = 37,791; positivity rate =1.9%), and b2GPI IgM (n = 37,601; positivity rate = 2.0%; [Table 1]). LA was the predominant laboratory investigation, while ordering of IgM isotypes was less frequent. The ordering patterns and overlaps between the five markers are shown in [Fig. 1]. Among the 30,274 patients who were fully tested for all three marker categories (LA, aCL, and b2GPI), 1.3% (n = 407) were triple-positive, 1.4% (n = 427) were double-positive, and 9.9% (n = 3,009) were single-positive; the remaining 87.3% (n = 26,431) were negative for all markers ([Table 1]). Within the single-positive group, most patients had isolated LA (73.1%), while 9.9% (n = 296) had aCL IgM only and 7.5% (n = 224) had b2GPI IgM only ([Fig. 2]). Omitting IgM from the panels would have resulted in missing 17% (668/3,843) of patients with at least one positive aPL marker and in the reclassification of 34% (140/407) of those initially classified as triple positive, reflecting classification effects. These findings apply to initial laboratory profiles only and cannot be interpreted as missed APS diagnoses, as repeat testing and clinical data were not available for this study. In this real-world analysis of the largest to date laboratory cohort of patients undergoing initial aPL testing over a 20-year timeframe, we found that LA was the most frequently ordered assay, followed by aCL IgG, aCL IgM, b2GPI IgG, and b2GPI IgM. This pattern aligns with previous studies in which LA was also the most frequently tested.[10] In contrast, Egiziano et al found that aCL was the most frequently ordered test, followed by LA and b2GPI, with only 19% of patients receiving simultaneous testing for all three criteria antibodies.[9] These comparisons suggest considerable variability in aPL ordering practices across regions, driven by institutional protocols and health care system factors. In our institution, LA may have resulted as part of the protocol for prolonged aPTT, without a clinical suspicion of APS, and additionally, its higher frequency is explained by the fact that LA is included in the thrombophilia panel, whereas aCL and b2GPI antibodies are not....

Background: Plantar vein thrombosis is a rare vascular condition typically presenting with unilateral plantar foot pain and edema. Of interest to the musculoskeletal clinician, mechanical trauma to the plantar foot has been cited as a risk factor for development of these thrombi. Objective: To assess the demographics, presenting history, risk factors, treatment protocols, and long‐term sequelae of patients with plantar vein thrombosis secondary to increased mechanical trauma. Design: Retrospective chart review. Setting: Tertiary care center. Participants: Adult patients with mention of plantar vein thrombosis in imaging impressions. Main Outcome Measures: Primary outcome measure was determination of the demographic and clinical characteristics of plantar vein thrombosis in patients with mechanical trauma as a preceding risk factor. Secondary outcome was evaluation of treatment options in this patient population. Results: Between 2005 and 2023, nine patients at a single institution were diagnosed with plantar vein thrombosis through imaging and were determined to have developed the thrombus due at least in part to mechanical trauma. Patients typically presented with localized plantar foot pain and foot edema. Diagnosis was made via magnetic resonance imaging or ultrasound. The most frequent treatment was therapeutic anticoagulation but initial conservative treatment with serial ultrasound resulted in conversion to anticoagulation in only one patient. Among those patients with mechanical trauma as an inciting factor, the only noted complication was propagation of the thrombosis in one patient. Conclusions: Although rare, plantar vein thrombosis should be considered by the musculoskeletal clinician in the differential diagnosis of unilateral plantar foot pain. Treatment of these thrombi is most commonly therapeutic anticoagulation, but in the absence of additional high‐risk factors serial ultrasound evaluations may be an adequate first line treatment due to the overall minimal risk of thrombosis propagation.

Warfarin is a commonly prescribed anticoagulant with a narrow therapeutic window, requiring frequent and specialized monitoring. This work aims to develop standardized optimal warfarin dose decision support using a machine learning model based on time series anticoagulation data and patient demographic characteristics. We propose an offline reinforcement learning model (RL) using a Batch-Constrained Q-Learning algorithm (BCQ) in the discrete action setting to predict the cumulative warfarin dose for the days until the next INR (International Normalized Ratio) test. Prior approaches utilized time-series supervised learning methods such as regression or Long Short Term Memory (LSTM) neural networks. The key advantage of reinforcement learning is its capacity to learn optimal dosing strategies from suboptimal clinical states in the data. To evaluate the model we compared the predicted warfarin doses with the physician-prescribed doses. Our BCQ model with a prediction accuracy of 98.6% significantly outperformed our baseline Long Short Term Memory (LSTM) model with a prediction accuracy of 71.09%. Further qualitative evaluation for explainability indicated that the model correctly adjusted the warfarin dose at time steps when patients had out-of-range INRs.

Ankle brachial index (ABI) can be unreliable in patients with non-compressible vessels. Our aim is to determine the feasibility of toe brachial index (TBI) and reporting criteria in a large population. We evaluated Doppler waveforms and segmental pressures in 26,719 limbs. TBI was obtained in 92.7%, mean TBI = 0.61 ± 0.25. TBI was obtained in 82%of limbs with unobtainable ABI. In hemodynamically normal subgroup (defined as those with normal ankle-brachial indices at rest and after exercise) the mean TBI was 0.84 ± 0.14. In severe PAD subgroup (defined as ABI < 0.5 and monophasic waveforms) the mean TBI was 0.16 ± 0.12. Limbs with a diagnosis of a PAD (ABI ≤ 0.9) had a TBI <0.8 in 99.5% of the cases, and <0.6 in 90% of the cases. A TBI of 0.8 had a negative predictive value for PAD of 0.99. A TBI cutoff of 0.6 had a positive predictive value for PAD of 0.95. Based on these results we propose defining normal TBI above 0.8, borderline between 0.8 and 0.61, abnormal TBI ≤ 0.6 and severe PAD as TBI ≤ 0.2. In conclusion TBI can be reliably measured in patients with PAD and offer valuable information when diagnosing PAD. We present our diagnostic criteria based on clinical data.