Determine the outcome of patients treated with catheter-directed interventions as per published recommendations for management escalation by the Pulmonary Embolism Response Team (PERT) Consortium. Retrospective, observational cohort study. Retrospective review of patient records managed with catheter-directed intervention between April 2012 and March 2022. Risk stratification was performed as per European Society of Cardiology (ESC) guidelines. Patient demographics, clinical status, and imaging on presentation, procedural details, and outcomes with a minimum follow-up period of 1year were analysed. Seventy-nine cases were performed in 76 patients (n = 76; mean age 52years, range 7-86; male:female = 37:39). Fifty-four patients were high-risk, 16 intermediate-high and 7 intermediate-low risk (n = 77 cases). 39% of high-risk and 22% of intermediate-risk cases had an absolute or relative contraindication to thrombolytic therapy. Seventeen percent of high-risk and 4% of intermediate-risk cases had a failed trial of systemic thrombolysis. 54% of high-risk and 78% of intermediate-risk cases had a failed trial of anticoagulation. There was a statistically significant reduction in the RV:LV ratio (p = 0.05) and clot burden (p < 0.0001) following catheter intervention. Available echocardiographic data demonstrated a trend towards improving right heart strain. Bleeding events occurred in 18% of cases, with 79% being high-risk. There was a significant improvement in functional outcomes as per WHO functional status (p < 0.001). Catheter-directed thrombolysis under the guidance of a PERT is a safe and effective therapy and provides a valuable management option for patients who have a contraindication to systemic thrombolysis or have failed a trial of systemic therapy.

Children with empyema thoracis often respond to medical management, but some do not, and require surgical intervention. Prediction of failure of medical management will help to guide further management and plan surgical intervention. To systematically review literature for clinical, radiological, laboratory, or microbiological predictors, associated with failure of medical management or the need for surgery in children with empyema thoracis. A systematic search was conducted in seven databases (PubMed, Embase, Cochrane Library, Scopus, Web of Science, ProQuest, and Open Grey) and four trial registries. Observational studies exploring predictors of treatment failure in empyema thoracis were eligible. Two reviewers independently screened the studies, extracted the data, and assessed the risk of bias. Data were analyzed in accordance with the review protocol. Amongst 12,311 citations identified, seven studies were included. One study identified three statistically significant predictors of medical treatment failure, viz. immediate ICU admission: OR (95%CI) 1.95 (1.18, 3.22); absence of complex septations on ultrasonography: 1.72 (1.21, 2.47); and positive blood culture: 2.8 (1.54, 5.07). Another study reported that "continuing pus discharge for ≥ 10days after chest tube insertion" and "persistence of loculations on ultrasonography or CT scan despite fibrinolytic therapy" prompted surgical intervention. The presence of fever was identified as a significant predictor, although its duration and grade were not reported. The evidence had very low overall certainty, being limited by small, single-center, retrospective studies with heterogeneous designs, population, and outcome definitions, limiting generalizability. Current evidence did not identify any clinically meaningful predictors of the failure of medical management (or need for surgery) in children with empyema thoracis.

Ischemic stroke, induced by the occlusion of cerebral blood vessels, represents a leading cause of global morbidity and mortality. Although thrombolytic therapy and mechanical thrombectomy are cornerstone treatments for restoring cerebral perfusion, their clinical effectiveness is severely constrained by a narrow therapeutic window. This study presents a reactive oxygen species (ROS) - responsive hydrogel platform loaded with engineered apoptotic vesicles (apoVs) designed to simultaneously target multiple post-stroke pathological processes. Proteomic analyses reveal that apoV isolated from apoptotic neural stem cells are enriched in proteins associated with angiogenesis and neuroprotection. In vitro investigations and in vivo animal experiment further demonstrate that the hydrogel can alleviate oxidative stress, promote angiogenesis and protect nerve injury by releasing hydrogen sulfide (H2S) - functionalized apoV in the infarct area. In summary, this hydrogel platform holds considerable therapeutic promise by transforming the hostile post-stroke microenvironment into a regeneration-permissive niche, thereby fostering endogenous tissue repair.

Evidence of Improvement: A Two-Decade Decline in Pulmonary Embolism Procedural Mortality.

Deep vein thrombosis (DVT) is a serious complication in acute ischemic stroke (AIS) patients undergoing revascularization therapy, but prediction tools remain limited. To develop and validate machine learning models for predicting DVT risk in AIS patients after revascularization therapy, and to enhance clinical decision-making through model interpretability. A retrospective cohort study was conducted using data from the Shenzhen Stroke Database, including AIS patients who underwent endovascular thrombectomy and/or thrombolytic therapy. Various machine learning models, including random forest (RF), support vector machine, gradient boosting machine, decision tree, and Gaussian naive Bayes, were trained and validated using a 70:30 train-validation split. The synthetic minority over-sampling technique was applied to address class imbalance. Among 362 AIS patients undergoing revascularization therapy, DVT incidence was 8.84%. The RF model achieved the highest prediction accuracy with an area under the curve of 0.87. Key predictors included D-dimer levels, aspirin use, National Institutes of Health Stroke Scale score during hospitalization, international normalized ratio, and anti-infective treatments. SHapley Additive exPlanations analysis enhanced model interpretability, providing clear insights into individual predictor contributions. The RF model significantly improved DVT risk prediction in AIS patients post-revascularization, offering a more accurate and interpretable tool for clinical practice.

Twelve benzohydrazide Schiff base derivatives (3a–3l) with systematic variations in the aromatic aldehyde moiety were designed and synthesized to evaluate their anti-inflammatory, antiplatelet, and in vitro antithrombotic activities. Among them, compound 3d (the condensation product of 4-chlorobenzohydrazide and furan-2-carbaldehyde) was identified as the most promising lead, displaying moderately selective COX-1 inhibition (IC50 = 1.63 µM, selectivity index = 8.87) together with moderate 5-LOX inhibition (IC50 = 10.63 µM). In LPS-stimulated macrophages, 3d concentration-dependently suppressed the release of TNF-α, IL-6, IL-1β, and PGE2. It inhibited ADP- and collagen-induced platelet aggregation (IC50 = 5.48 µM and 4.52 µM, respectively), reduced the expression of platelet activation markers CD62P and PAC-1, and prolonged clotting time while decreasing clot strength in thromboelastography. Under arterial shear conditions in a parallel-plate flow chamber, 3d significantly attenuated thrombus formation in a concentration-dependent manner. Importantly, in an in vitro clot lysis model, 3d (50 µM) enhanced the thrombolytic rate of low-dose urokinase (100 IU per mL) from 35.0% to 45.2%, highlighting its potential to augment thrombolysis. Preliminary ADME profiling revealed moderate plasma protein binding (89.3%) and a metabolic half-life of 0.75 h in liver microsomes. This study provides the first systematic structure–activity relationship analysis of aromatic aldehyde substituents on benzohydrazide Schiff bases and identifies 3d as a lead compound possessing combined anti-inflammatory, antiplatelet, and thrombolysis-enhancing activities. These findings support the potential of 3d as an adjunctive agent for catheter-directed thrombolysis in in-stent thrombosis, pending further in vivo efficacy and safety investigations.

The purpose of this study is to evaluate the effectiveness of monotherapeutic High-Intensity Focused Ultrasound (HIFU) for thrombolysis in highly occluded vessels using an in vitro model, with emphasis on thermal safety. &#xD;Methods: HIFU was applied to vessel phantom with various occlusion ratios (60%, 70%, 80%, 90%, and 100%) of the lumen cross-sectional area, each with an equal clot length of 15 mm, under a pulsatile flow of 5 mL/min generated by a peristaltic pump operated at 70 rpm. The insonation was conducted at a frequency of 1.1 MHz, power (Pelect) of 180 W, duty cycle (DC) of 0.4%, pulse repetition frequency (PRF) of 1 Hz and total exposure time of 30 minutes. A step-by-step exposure technique was employed, where the focus of the HIFU beam was progressively moved from one end of the clot to the other. A multi-layer simulation model was used to estimate the acoustic pressure and temperature at the focal point, with temperature distribution monitored throughout the exposure to ensure thermal safety. Thrombolysis efficiency was assessed by measuring the pre- and post-treatment clot weights.&#xD;Results: HIFU achieved a thrombolysis efficiency (defined as fractional reduction in clot weight) of 65.99% at 100% occlusion when high power and step-by-step exposure were used. This efficiency increased to 78.6% at 60% occlusion. These results were achieved while ensuring thermal safety by maintaining the temperature below 43°C.&#xD;Conclusions: This study further confirms that HIFU is a promising non-invasive method for thrombolysis in highly occluded vessels while ensuring thermal safety by using high power and a step-by-step exposure method.

Stroke remains a leading cause of mortality and long-term disability worldwide, with an increasing burden in low- and middle-income countries. This retrospective cross-sectional study aimed to evaluate the prevalence, clinical profile, stroke severity, and pharmacological management patterns among patients admitted with stroke in a tertiary care hospital. A total of 120 consecutive patients were included over a six-month period, and data were obtained from anonymized medical records, including demographics, stroke subtype, presenting symptoms, comorbidities, and prescribed medications. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS), and statistical analyses were performed using descriptive and inferential methods. Stroke accounted for 25% of neurology admissions during the study period. The most prevalent age group was 51-60years (33.3%), followed by 61-70years (29.2%), with a male predominance (60%). Ischemic stroke constituted 75% of cases. The most common presenting symptom was hemiparesis (66.7%), followed by speech disturbances and visual impairment. Hypertension (58.3%) and diabetes mellitus (41.7%) were the most frequent comorbidities. The majority of patients presented with moderate stroke severity. Stroke severity increased significantly with age, whereas no significant difference was observed between sexes. Antiplatelet therapy was the most commonly prescribed treatment, and dual antiplatelet therapy was administered in 33.3% of patients. Thrombolytic therapy was used in a limited proportion of patients. Stroke in this cohort predominantly affected middle-aged and elderly individuals and was largely ischemic in nature. The high prevalence of modifiable risk factors highlights the need for improved preventive strategies, while the limited use of thrombolysis underscores gaps in acute stroke care.

Intrapleural Fibrinolytic Therapy for Pediatric Empyema: What Is the Proper Regimen?

Catheter-directed thrombolysis (CDT) is a first-line therapy for Rutherford IIa acute limb ischemia (ALI). However, 20% to 30% of patients exhibits suboptimal response. Balloon-assisted CDT (BA-CDT), which combines mechanical thrombus disruption with continued thrombolysis, offers a potential escalation strategy. A multi-center, retrospective cohort study was conducted across 3 tertiary vascular centers from January 2022 to June 2025. Consecutive patients with Rutherford IIa ALI who demonstrated suboptimal clinical and/or angiographic response to initial CDT, based on predefined criteria (eg, lack of clinical improvement, >50% residual thrombus, and poor tibial runoff) were escalated to BA-CDT. The primary endpoint was limb salvage at 30 days. Secondary endpoints included technical success clinical improvement (≥0.15 ankle-brachial index [ABI] increase), target lesion primary patency (TLPP) at 6 months, and procedure-related complications. Propensity score adjustment was used to account for baseline differences between the BA-CDT cohort and patients who responded to CDT alone. Among 124 patients undergoing CDT, 34 patients (27.4%) were escalated to BA-CDT. Technical success was achieved in all cases. The median ABI improved significantly from 0.06 at baseline to 0.77 post-BA-CDT (p<0.001). Limb salvage was achieved in 94.1% of the patients. Target lesion primary patency rates were 94.1%, 82.4%, and 64.7% at 1, 3, and 6 months, respectively. Complications included access-site hematoma (17.6%) and distal embolization (14.7%). Cox regression identified an escalation time exceeding 12 hours (hazard ratio [HR] 8.87, p=0.04) and occurrence of distal embolization (HR 3.79, p=0.05) as independent predictors of TLPP loss. After propensity score adjustment, outcomes for the BA-CDT group (which had more complex baseline anatomy) were comparable with those of the CDT-only group in terms of limb salvage, patency, and major complications. For patients with ALI who do not respond adequately to initial conventional deep vein thrombosis treatment (CDT), escalating to BA-CDT is a safe and effective strategy. This approach improves blood flow, achieves high limb salvage rates, and is a resource-efficient alternative to advanced thrombectomy devices or surgical interventions within a standardized treatment algorithm.Clinical ImpactThis study establishes balloon-assisted catheter-directed thrombolysis (BA-CDT) as an effective, stepwise approach for treating Rutherford IIa acute limb ischemia patients who do not respond adequately to initial thrombolysis. By utilizing standard balloons instead of expensive mechanical thrombectomy devices, clinicians can disrupt thrombus mechanically, improve drug penetration, and address underlying lesions. The protocol outlines specific angiographic and clinical criteria for timely escalation (within 12 hours), achieving a limb salvage rate of 94% even in complex, multilevel occlusions. In resource-limited settings, BA-CDT provides an accessible and effective rescue option before surgical intervention, potentially lowering amputation rates and healthcare costs while ensuring patient safety.

Thrombosis at the crossroads of inflammation, coagulation, and vascular biology: Recent advances and emerging therapeutic strategies.

Cardioembolic stroke accounts for more than 20% of all acute ischemic strokes (AIS) and is mainly caused by cardiac arrhythmias, particularly atrial fibrillation (AF). The presence of specific or multiple additional vascular risk factors indicates the need for oral anticoagulant (OAC) therapy in AF patients (according to the CHA2DS2-VASc classification). While OAC treatment significantly reduces the risk of AIS by over 80% in this population, the risk remains higher compared to the general population. Approximately half of AF patients on OAC therapy who experience AIS do not meet the criteria for thrombolytic (high blood activity of OAC) or mechanical thrombectomy (non-large vessel occlusion stroke) treatment. This study aims to assess the efficacy and safety of recombinant tissue plasminogen activator (rtPA) in AIS patients who have been on chronic non-vitamin K antagonist oral anticoagulant (DOAC) therapy after receiving a specific reversal agent. Patients with acute ischemic stroke (AIS) who are treated with specific oral anticoagulants (OACs) with anti-Xa activity have been on chronic non-vitamin K antagonist oral anticoagulant e included in the study. The protocol involves administering a fast-acting antidote (andexanet alfa for rivaroxaban or apixaban) or a placebo, followed by intravenous thrombolytic therapy with rtPA or a placebo. The study arms for rivaroxaban and apixaban are designed as prospective, randomized, placebo-controlled interventional trials that meet phase II trial criteria. The STRoke on Oral AntiCoagulants for Thrombolysis (STROACT) trial is, to our knowledge, the first randomized phase II study designed to explore the feasibility, efficacy, and safety of reversal-enabled intravenous thrombolysis in a highly selected population of acute ischemic stroke patients on factor Xa inhibitors. The results are expected to be hypothesis-generating and may inform the design of future confirmatory trials. www.clinicaltrialsregister.eu; EudraCT Nr: 2020-004898-41; March 31, 2021.

Abstract Background and aims Rescue stenting (RS) as a salvage method for reperfusion in mechanical thrombectomy (MT) for acute ischemic stroke (AIS) has improved clinical outcomes with comparable periprocedural complications despite concurrent IV thrombolysis and aggressive antiplatelet therapy during and after stenting. This retrospective review compared periprocedural complications and clinical outcomes in AIS patients who underwent MT with and without rescue stenting. Methods Using logistic regression, we retrospectively analyzed data for 325 patients with AIS who underwent MT between January 2022-October 2024. Degree of recanalization was evaluated using the Modified Thrombolysis in Cerebral Infarction (mTICI) score; clinical outcomes at 90 days were assessed using modified Rankin score (mRS) at discharge or 90 days dichotomized for desirable (mRS 0-2) and undesirable (mRS 3-6) functional outcomes. Bleeding events included intracranial hemorrhage (ICH) at 48 hours and systemic bleeding requiring transfusion. Results 80 of 325 patients (19-99 years old, 54% female with NIHSS 1-34) underwent rescue stenting; these patients did not have more bleeding complications or worse functional outcomes than those without rescue stents (p=0.747 and p=0.882, respectively). Bleeding complications were not affected by IV thrombolysis (p=0.675) and functional status was not modified by stent location (intracranial vs. Carotid) (p=0.242). Conclusions In this sample, rescue stenting did not significantly affect clinical outcomes, likelihood of ICH or severe systemic bleeding in patients undergoing MT for AIS, nor did stent location or IV thrombolytics increase complication risk. In contrast to prior studies, despite no increase in complication risk, rescue stenting failed to provide significant long-term clinical benefits in this sample. Conflict of interest Suzan Farris: nothing to disclose. Patrick Reynolds: nothing to disclose. Cheryl Bushnell: nothing to disclose. Mathieu Norcross: nothing to disclose.

Background: To note patient characteristics, risk factors, use of streptokinase, complications, and mortality in subjects presenting with acute myocardial infarction. Methods: This prospective, observational, case study was conducted at DHQ Teaching Hospital, Rawalpindi, from January 2001 to January 2002. All 95 patients who were admitted with a diagnosis of acute myocardial infarction during this period were included. Patients were managed in the standard way, initially in CCU and then in the medical ward. Data obtained was statistically examined using Epi Info 2000. Results: Of the 95 patients, 70 (73.7%) were male and 25 (26.3%) female. Mean patient age was $57\pm12.54$ years. Anterior wall was involved commonly (38.9% patients). Forty-nine (51.6%) patients received thrombolysis with streptokinase. Arrythmias (57.9% patients) and cardiac failure (53.6% patients) were the commonest complications of acute myocardial infarction. Mean hospital stay was 8 days. 11.5% $(n=11)$ patients died during hospital stay, of these 27.2% $(n=3)$ received streptokinase. Age, sex, smoking, and sedentary life styles were common (&gt;50%) risk factors for myocardial infarction. Conclusion: Acute myocardial infarction is common in males and over the age of 50 years. Majority of these patients are candidates for thrombolytic therapy with streptokinase. Myocardial infarction related in-hospital mortality, even in a tertiary care setting, may be 11.5%

Real-world practices in the management of pediatric iliofemoral deep vein thrombosis: Results of the ELITE-Kids survey.

BackgroundIntravenous thrombolytic (IVT) and mechanical thrombectomy (MT) therapies are the current standard of care for large vessel occlusion (LVO) stroke. Multiple studies emphasized the impact of time metrics on patient outcomes, particularly door-to-needle (DTN) and door-to-puncture (DTP) times. Tenecteplase (TNK) offers potential advantages over alteplase (ALT), including a simplified one-time bolus administration, which may reduce DTP time. Results suggest TNK is non-inferior to ALT in terms of clinical outcomes, but few large cohort studies have compared DTP time for patients receiving TNK vs. ALT prior to thrombectomy. This real-world study aimed to compare DTP times and discharge outcomes in patients treated with TNK vs. ALT before thrombectomy.MethodsRetrospective data were collected from three comprehensive stroke centers (CSCs) in Texas from October 2019 to November 2024 and included subjects that received both IVT and MT. Data were analyzed for DTP times and other time metrics.ResultsAmong 50 ALT and 89 TNK patients in our study cohort, the TNK group had significantly shorter DTP times of 80 min (62–96) compared to ALT times of 101.5 min (80–121), P < 0.001. No significant differences were found for door-to-imaging and imaging-to-needle times; however, needle-to-puncture times were significantly shorter with TNK 39 min (29–51) compared to ALT 55 min (43–77), P < 0.001. Both groups had similar favorable outcomes at discharge.ConclusionsOur Lone Star Stroke (LSS) TNK registry represents the real-world experience of academic CSCs in Texas. We demonstrated that transitioning to TNK is associated with shorter DTP times compared to ALT. These results are primarily due to shorter needle-to-puncture times and may be attributable to TNK's simplified single-bolus administration. Both TNK and ALT groups demonstrated high rates of favorable outcomes at discharge, but given its faster DTP time, TNK is likely a preferable option for LVO stroke patients requiring both IVT and MT.

ObjectiveCurrent treatment strategies for acute lower extremity deep vein thrombosis (DVT) have shifted from merely preventing pulmonary embolism to actively removing thrombus and preserving valve function. However, there is limited evidence comparing the indications and perioperative outcomes of different endovascular strategies. This study aims to investigate the differences in indications, perioperative characteristics, and efficacy trends among three strategies: Angiojet mechanical thrombectomy alone, other thrombus removal devices alone, and a combination of Angiojet with other devices.MethodsA retrospective analysis was conducted on the clinical data of 232 DVT patients who underwent endovascular treatment in the Vascular Surgery Department of our hospital between January 2022 and April 2025. Based on the core thrombus removal method, patients were divided into three groups: Group A (Angiojet alone, n = 22), Group B (other devices alone, including manual aspiration and catheter-directed thrombolysis CDT, n = 35), and Group C (Angiojet combined with other devices, n = 175). Baseline characteristics, thrombus anatomical extent, and perioperative parameters were compared across the groups. Chi-square test, analysis of variance, or Kruskal–Wallis test were used for intergroup comparisons.ResultsThere were fundamental differences in thrombus burden among the three groups (P < 0.001). Groups A and B primarily treated limited (femoral/popliteal) thrombosis (50.0% and 51.4%, respectively), while Group C was the predominant approach for extensive thrombosis (iliofemoral-popliteal, 50.9%) and thrombosis involving the inferior vena cava (22.3%). The operative time for Group C (134 ± 48 min) was significantly longer than for Group A (98 ± 36 min) and Group B (115 ± 45 min) (P < 0.001), and blood loss (66 ± 39 mL) was also higher compared to the other two groups (P = 0.008). In terms of treatment intensity, the balloon angioplasty rate (96.0%) and stent implantation rate (58.9%) in Group C were significantly higher than in Groups A and B (P < 0.001). Group B showed the highest trend for documented “partial thrombus residue” (22.9%).ConclusionCurrent endovascular DVT treatment has formed a clear risk-stratified decision-making pathway. Angiojet alone is an efficient and streamlined option for limited acute DVT; for extensive and complex DVT, the intensified strategy of Angiojet combined with other thrombus removal devices has become the standard choice, with its longer operative time and higher rate of vascular interventions reflecting disease complexity. This study provides real-world evidence for individualized endovascular DVT treatment.

Breaking the Blockage by Advancing Treatment Strategies for Upper Extremity Deep Vein Thrombosis.

Hereditary antithrombin III (AT III) deficiency is a rare thrombophilic disorder that may cause resistance to systemic thrombolytic therapy. We report a case of massive iliofemoral deep-vein thrombosis (DVT) with high-risk pulmonary thromboembolism (PTE) refractory to systemic thrombolysis, successfully treated with catheter-directed thrombolysis (CDT). A previously healthy 33-year-old man presented with dyspnoea and left-leg swelling. Imaging revealed bilateral pulmonary-artery thrombi with acute right-ventricular failure and extensive iliofemoral DVT. Despite systemic alteplase infusion, thrombus resolution was incomplete, and hereditary AT III deficiency (53% activity) was diagnosed. CDT via the right femoral vein was performed using alteplase (0.02 mg/kg/h for 48 h), achieving near-complete thrombus resolution and restoration of venous flow without bleeding complications. This case highlights systemic thrombolysis failure associated with AT III deficiency and demonstrates that CDT can serve as an effective, low-bleeding-risk rescue therapy for extensive DVT when systemic treatment is inadequate. These findings underscore the importance of early recognition of AT III deficiency and consideration of catheter-based intervention in similar high-risk settings.

Self-sacrificing templated-derived chitosan microcapsules for targeted drug delivery in thrombolytic therapy.