OBJECTIVE: Previous randomized prospective trials have demonstrated the effectiveness of transcatheter tissue plasminogen activator (tPA) thrombolysis in treating acute limb ischemia (ALI) compared to conventional surgery. These pivotal trials have also highlighted contraindications for these procedures. Given recent advancements in techniques and technology, our aim is to reassess the relevance of these contraindications in contemporary practice.
METHODS: A retrospective chart analysis was performed utilizing the inpatient medical records of consecutive individuals who underwent tPA treatment for acute limb ischemia (ALI) from September 2016 to April 2022. Inclusion criteria encompassed patients aged 18 and above displaying clinical symptoms and imaging evidence of ALI within 14 days. All patients received tPA with suction thrombectomy following the fast-track thrombolysis protocol. In cases where a persistent thrombus or stenosis was detected, catheter-directed thrombolysis was considered overnight, and patients underwent angiography and reassessment in the operating room subsequently.
RESULTS: Patients were classified into two groups based on the STILE trial\'s established contraindications for endovascular treatment in acute limb ischemia (ALI). If a patient had any of these contraindications, they were placed in the contraindicated group. This resulted in 24 patients (32%) in the contraindicated group and 52 patients (68%) in the non-contraindicated group. No statistically significant demographic variations were observed between these groups. Contraindications in our study included uncontrolled hypertension (12/24, 50%), recent invasive procedures (7/27, 29%), history of cerebrovascular accident (CVA) within 6 months (3/24, 12%), and intracranial malformation/neoplasms (2/24, 8%). Three patients within the non-contraindicated group experienced bleeding complications: two with puncture site bleeds and one with nasal bleeding. In contrast, one patient in the contraindicated group had transient postoperative hematuria. There were no significant differences in bleeding complications observed between the two groups (p = .771). Additionally, no amputations were observed within our population.
CONCLUSIONS: In light of our study results and advancements in endovascular therapies, we can now safely and efficiently treat patients who were previously considered contraindicated for such treatments. It is essential to individualize treatments and carefully balance the risks and benefits of endovascular versus open surgical revascularization for these patients. Additionally, we believe that the nearly 30-year-old guidelines for endovascular therapies need to be revisited and updated to align with modern technology.

Determination of indications for acute reperfusion therapy (intravenous recombinant tissue plasminogen activator administration and mechanical thrombectomy) and identification of stroke mimics and chameleons are essential components of effective stroke treatment. Moreover, neurologists select the appropriate medications and manage the patient\'s general condition. Therefore, a neurologist\'s solid diagnostic skills based on neurological symptomatology and an internist\'s broad knowledge and insight play key roles clinically.

OBJECTIVE: To compare the effectiveness and safety of the use of non-immunogenic staphylokinase (NS) and alteplase (AP) for intravenous thrombolysis (IT) for ischemic stroke (IS) in real clinical practice at a regional vascular center.
METHODS: Data from 100 patients with IS who received IT with NS and 100 patients who received IT with AP for the period 2022-2023 were analyzed. The groups were comparable on sociodemographic parameters, cardiovascular risk factors and diseases, and stroke characteristics.
RESULTS: Door-to-needle time was 17 (13-22) min in the NS group and 38 (33-42) min in the AP group (p<0.001). During control neuroimaging, a cerebral infarction was detected in 46% of patients in the NS group and 61% of patients in the AP group (OR 0.479 [0.263; 0.875], p=0.035). When performing IT with NS, an NIHSS score of 0 points (no neurological deficit) was observed twice as often (OR 2.202 [1.079; 4.504], p=0.023). The incidence of hemorrhagic transformation, including symptomatic, as well as hospital mortality did not differ.
CONCLUSIONS: IT with NS is associated with a lower probability of cerebral infarction and greater positive dynamics of the neurological status in comparison with the use of AP already within the first stage of treatment and rehabilitation.
UNASSIGNED: Сравнить эффективность и безопасность применения неиммуногенной стафилокиназы (НС) и алтеплазы (АП) для внутривенной тромболитической терапии (ВТТ) при ишемическом инсульте (ИИ) в реальной клинической практике регионального сосудистого центра.
UNASSIGNED: Проанализированы данные 100 пациентов с ИИ, получивших ВТТ НС, и 100 пациентов, получивших ВТТ АП за период 2022—2023 гг. Группы сопоставимы по социально-демографическим параметрам, сердечно-сосудистым факторам риска и заболеваниям, а также характеристикам ИИ.
UNASSIGNED: Время «от двери до иглы» составило 17 (13—22) мин в группе НС и 38 (33—42) мин в группе АП (p<0,001). При контрольной нейровизуализации сформированный очаг инфаркта головного мозга обнаружен у 46% пациентов в группе НС и у 61% — АП (ОШ 0,479 [0,263; 0,875], p=0,035). При проведении ВТТ НС в 2 раза чаще наблюдался результат в виде отсутствия неврологического дефицита при завершении первого этапа лечения и реабилитации (ОШ 2,202 [1,079; 4,504], p=0,023). Частота развития геморрагической трансформации, в том числе симптомной, а также госпитальная летальность не отличались.
UNASSIGNED: Проведение ВТТ НС сопряжено с меньшей вероятностью формирования инфаркта головного мозга и более выраженной положительной динамикой неврологического статуса в сравнении с применением АП уже в рамках первого этапа лечения и реабилитации.

OBJECTIVE: In patients with a need for frequent but intermittent apheresis, vascular access can prove challenging. We describe the migration of the use of a Vortex LP dual lumen port (Angiodynamics, Latham, NY) to one Powerflow and one ClearVUE power injectable port (Becton Dickinson, Franklin Lakes, NJ) in a series of patients undergoing intermittent apheresis.
METHODS: All patients had a need for long-term intermittent apheresis. Eight had double lumen Vortex port (pre) and were exchanged for one Powerflow port and one conventional subcutaneous venous port with 90° needle entry (post) while 12 did not have any port in place and received the same configuration. IRB approval was granted. We recorded the treatment time, flow rate, and tissue plasminogen activator (tPA) use for five treatment sessions after placement. When available, we compared five treatments with the Vortex port and the new configuration.
RESULTS: The mean treatment time is reduced with the new configuration (P = 0.0033). The predicted mean treatment time, adjusting for gender, race, BMI and age and accounting for correlations within a patient is 91.18 min pre and 77.96 min post. The flow rate is higher with the new configuration (P < 0.0001). The predicted mean flow rate in mL/min is 61.59 for the Vortex port and 71.89 for the new configuration. tPA use was eliminated in the population converted from Vortex ports and had a 48% reduction when compared to all other configurations in the study.
CONCLUSIONS: The introduction of a novel device configuration of venous access ports for intermittent apheresis resulted in higher flow rates and less total time for treatment. Use of tPA was greatly reduced. These results suggest that the new configuration could result in less expense for the hospital and better throughput in a busy pheresis practice. Clinical trial registration with ClinicalTrials.gov: NCT04846374.

There is no effective and noninvasive solution for thrombolysis because the mechanism by which certain thrombi become tissue plasminogen activator (tPA)-resistant remains obscure. Endovascular thrombectomy is the last option for these tPA-resistant thrombi, thus a new noninvasive strategy is urgently needed. Through an examination of thrombi retrieved from stroke patients, we found that neutrophil extracellular traps (NETs), ε-(γ-glutamyl) lysine isopeptide bonds and fibrin scaffolds jointly comprise the key chain in tPA resistance. A theranostic platform is designed to combine sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Breakdown of the key chain leads to a recanalization rate of more than 90% in male rat tPA-resistant occlusion model. Vascular reconstruction is observed one month after recanalization, during which there was no thrombosis recurrence. The system also demonstrates noninvasive theranostic capabilities in managing pigs\' long thrombi (>8 mm) and in revascularizing thrombosis-susceptible tissue-engineered vascular grafts, indicating its potential for clinical application. Overall, this noninvasive theranostic platform provides a new strategy for treating tPA-resistant thrombi.

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OBJECTIVE: This study is to establish a nomination graph model for individualised early prediction of the 3-month prognosis of patients who had an acute ischaemic stroke (AIS) receiving intravenous thrombolysis with recombinant tissue plasminogen activator.
METHODS: For the period from January 2016 through August 2022, 991 patients who had an acute stroke eligible for intravenous thrombolysis were included in the retrospective analysis study. The study was based on multifactor logistic regression.
METHODS: Patients who received treatment from January 2016 to February 2021 were included in the training cohort, and those who received treatment from March 2021 to August 2022 were included in the testing cohort.
METHODS: Each patient received intravenous thrombolysis within 4.5 hours of onset, with treatment doses divided into standard doses (0.9 mg/kg).
METHODS: The primary outcome measure was a 3-month adverse outcome (modified Rankin Scale 3-6).
RESULTS: The National Institutes of Health Stroke Scale Score after thrombolysis (OR=1.18; 95% CI: 1.04 to 1.36; p = 0.015), door-to-needle time (OR=1.01; 95% CI: 1.00 to 1.02; p = 0.003), baseline blood glucose (OR=1.08; 95% CI: 1.00 to 1.16; p=0.042), blood homocysteine (OR=7.14; 95% CI: 4.12 to 12.71; p<0.001), monocytes (OR=0.05; 95% CI: 0.01 to 0.043; p=0.005) and monocytes/high-density lipoprotein (OR=62.93; 95% CI: 16.51 to 283.08; p<0.001) were independent predictors of adverse outcomes 3 months after intravenous thrombolysis, and the above six factors were included in the nominated DGHM2N nomogram. The area under the receiver operating characteristic curve value of the training cohort was 0.870 (95% CI: 0.841 to 0.899) and in the testing cohort was 0.822 (95% CI: 0.769 to 0.875).
CONCLUSIONS: A reliable nomogram model (DGHM2N model) was developed and validated in this study. This nomogram could individually predict the adverse outcome of patients who had an AIS receiving intravenous thrombolysis with alteplase for 3 months.

Background: Bacterial aggregation has been well described to occur in synovial fluid, but it is unknown if bacteria form aggregates in body fluids beyond the synovial fluid. Consequently, this translational study evaluated the ability to form bacterial aggregates in different pleural fluids. Methods: Four of the most common causes of thoracic empyema-Streptococcus mitis, Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa-were used here. The different pleural fluids included one transudative and two exudative pleural fluids. Twenty-four-well microwell plates were used to form the aggregates with the aid of an incubating shaker at different dynamic conditions (120 RPM, 30 RPM, and static). The aggregates were then visualized with SEM and evaluated for antibiotic resistance and the ability of tissue plasminogen activator (TPA) to dissolve the aggregates. Statistical comparisons were made between the different groups. Results: Bacterial aggregates formed at high shaking speeds in all pleural fluid types, but no aggregates were seen in TSB. When a low shaking speed (30 RPM) was used, only exudative pleural fluid with a high protein content formed aggregates. No aggregates formed under static conditions. Furthermore, there was a statistical difference in the CFU/mL of bacteria present after antibiotics were administered compared to bacteria with no antibiotics (p < 0.005) and when TPA plus antibiotics were administered compared to antibiotics alone (p < 0.005). Conclusions: This study shows that bacteria can form aggregates in pleural fluid and at dynamic conditions similar to those seen in vivo with thoracic empyema. Importantly, this study provides a pathophysiological underpinning for the reason why antibiotics alone have a limited utility in treating empyema.

Patients undergoing transurethral resection of the prostate (TURP) surgery can develop TURP syndrome and post-TURP bleeding. Post-TURP bleeding can be surgical, from arteries or venous sinuses, or non-surgical, due to coagulopathy preventing clot formation. Non-surgical post-TURP bleeding may be due to high concentrations of urokinase and tissue plasminogen activator (tPA) in the urine that cause fibrinolytic changes and increase bleeding risk. Urine urokinase and tPA may have both local and systemic fibrinolytic effects that may prevent blood clot formation locally at the site of surgery, and cause fibrinolytic changes systemically through leaking into the blood stream. Another post-TURP complication that may happen is TURP syndrome, due to absorption of hypotonic glycine fluid through the prostatic venous plexus. TURP syndrome may present with hyponatremia, bradycardia, and hypotension, which may be preceded by hypertension. In this case report, we had a patient with benign prostatic hyperplasia (BPH) who developed both TURP syndrome and non-surgical post-TURP bleeding. These complications were transient for one day after surgery. The local effect of urine urokinase and tPA explains the non-surgical bleeding after TURP by preventing clot formation and inducing bleeding. Coagulation studies showed fibrinolytic changes that may be explained by urokinase and tPA leakage into the blood stream. In conclusion, non-surgical bleeding after TURP can be explained by the presence of fibrinolytic agents in the urine, including urokinase and tPA. There is a deficiency in existing studies explaining the pathophysiology of the fibrinolytic changes and risk of bleeding after TURP. Herein, we discuss the possible pathophysiology of developing fibrinolytic changes after TURP. More research effort should be directed to explore this area to investigate the appropriate medications to treat and prevent post-TURP bleeding. We suggest monitoring patients\' coagulation profiles and electrolytes after TURP because of the risk of developing severe acute hyponatremia, TURP syndrome, fibrinolytic changes, and non-surgical bleeding. In our review of the literature, we discuss current clinical trials testing the use of an antifibrinolytic agent, Tranexamic acid, locally in the irrigation fluid or systemically to prevent post-TURP bleeding by antagonizing the fibrinolytic activity of urine urokinase and tPA.