BACKGROUND: Pars Plana Vitrectomy (PPV) combined with subretinal injection of low-dose recombinant tissue plasminogen activator (rt-PA) and intravitreal injection of Conbercept as a novel therapy for submacular hemorrhage (SMH) requires evaluation.
METHODS: In a retrospective interventional clinical study, 14 eyes of 14 patients with SMH underwent PPV along with rt-PA (subretinal) and Conbercept (intravitreal) injections. The main outcomes included best-corrected visual acuities (BCVAs), degrees of blood displacement, and adverse events. All patients completed at least 6-month follow-up visits.
RESULTS: Mean BCVAs significantly improved at 7 days (22.29 ± 15.35), 1 month (30.71 ± 16.42), 3 months (38.29 ± 13.72), 4 months (38.86 ± 14.15), and 6 months (41.21 ± 14.91) post-treatment compared to baseline (16.36 ± 13.97) (F = 12.89, P = 0.004). The peak improvement in BCVAs occurred at 6 months postoperatively. The procedure effectively eliminated subfoveal hemorrhages in all eyes, with clots removal and absorption occurring within one month and complete regression by 3-month follow-up visits. Postoperatively, two cases of AMD resulted in discoid scars on the fundus. No instances of rt-PA-related retinal toxicity were observed during the follow-up period.
CONCLUSIONS: The combined approach of PPV with low-dose rt-PA and anti-VEGF shows promise in enhancing both vision and anatomical structure in SMH therapy. Individualized treatment plans tailored to the primary disease should be developed to optimize visual prognoses.
BACKGROUND: Retrospectively registered No.ChiCTR2100053034. Registration date: 10/11/2021.

BACKGROUND: While surgery still remains the gold standard treatment for mechanical prosthetic valve thrombosis (MPVT) by many guidelines, the ultraslow low-dose thrombolytic regimen has been reported as a promising alternative.
METHODS: In this prospective single-center cohort, patients with acute MPVT were treated with an ultraslow low-dose thrombolytic regimen consisting of 25 mg infusion of recombinant tissue-type plasminogen activator (rtPA) over 25 h. The regimen could be repeated in case of failure until resolution/occurrence of adverse events or a maximum cumulative dose of 150 mg. The primary outcome was the complete MPVT resolution rate; other outcomes included first-dose success rate, major bleeding, thromboembolic events, mortality, and total thrombolytic dose/duration.
RESULTS: Between April 2018 to January 2024, 135 episodes of acute MPVT were treated with an ultraslow low-dose thrombolytic regimen in 118 patients. In 118/135 (87.4 %) episodes, right-sided prosthetic valve was involved. Complete success was achieved in 88.1 % of cases, with 39.5 % responding after the first dose. The median total dose was 50 mg over a median of 30 h. Only one fatal intracranial hemorrhage occurred (0.7 %), with no other bleeding or thromboembolic complications.
CONCLUSIONS: The ultraslow low-dose thrombolytic regimen appears to exhibit high efficacy and acceptable safety in treating acute MPVT. Further large clinical trials are essential for validating these preliminary findings.

A 40-year-old patient confirmed on computed tomography of the pulmonary arteries (CT/PAs) a large saddle pulmonary embolus in the main PA extending in both branches. He was managed by ultrasound-supported catheter-directed (EkoSonic, Boston Scientific) intrapulmonary thrombolytic therapy using a recombinant tissue plasminogen activator prolonged infusion over 16 h with a total dose of 50 mg divided in both PAs simultaneously with intravenous unfractionated heparin. He showed clinical improvement with improved arterial oxygen (PaO2) with reduced oxygen therapy with a nasal cannula. Follow-up right heart catheterization showed a significant reduction of PA pressure from 96/32 (mean 64) to 47/27 (mean 39) mmHg. Repeat pulmonary angiography showed significant improvement in PA branch opacification, suggesting increased flow and successful therapy. The patient received oral anticoagulants for months. He had followed with CT/PA and echocardiogram after 4 weeks, both were normalized. He resumed his regular physical activities, including exercises in the gymnasium.

OBJECTIVE: This study aims to evaluate such usage patterns and identify factors that may contribute to the need for repeat imaging in acute ischaemic stroke patients and determine the association between repeat imaging and readmission in Taiwan.
METHODS: We searched and analysed data from the Taiwan National Health Insurance Research Database for patients admitted for acute ischaemic stroke between 2002 and 2017. Cases where repeat brain imaging during the initial hospital admission occurred and where patients were readmitted within 30 days following discharge were documented.
RESULTS: Of a total of 195 016 patients with new onset ischaemic stroke, 51 798 (26.6%) underwent repeat imaging during their initial admission. Factors associated with repeat brain imaging included younger age, longer hospital stay, use of recombinant tissue plasminogen activator (rt-PA) therapy (odds ratio = 2.10 [95% CI, 1.98-2.22]), more recent year of diagnosis, higher National Institutes of Health Stroke Scale (NIHSS) score, and admission to a hospital offering a higher level of care. Repeat imaging was also associated with an increased risk of ischaemic stroke and all types of stroke readmission.
CONCLUSIONS: Repeat brain imaging of patients with stroke has increased in recent years, and it is associated with certain factors including age, length of stay, use of rt-PA, hospital level of care, and NIHSS score. It is also associated with increased readmission.
CONCLUSIONS: Knowledge of the associations of repeat imaging may help clinicians use repeat imaging more carefully and efficaciously.

OBJECTIVE: To determine whether intravitreal injection of recombinant tissue plasminogen activator (rTPA) is effective for the treatment of refractory diabetic macular edema (DME) in patients who already had posterior vitreous detachment (PVD).
METHODS: It is a retrospective chart review of the patients with refractory DME and PVD. The efficacy of intravitreal injection of rTPA was assessed based on the changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA) in these patients.
RESULTS: Nine eyes of nine patients as the study group and 14 eyes of the 14 patients as the control group were examined. Before the injections, the mean CMT was 470.0± 107.6 in the study group, compared to 536.2± 150.5 in the control group, with no statistical significance (p=0.403). The statistical analysis revealed no significant differences in the mean changes in CMT from baseline to one and three months after injections between the study and control groups (p=0.439, p=0.781, respectively). Likewise, no statistically significant disparities were observed in the mean pre-injection BCVA between the study group (0.877± 0.349) and the control group (0.950± 0.300) (p=0.415). Additionally, after three months of injection, there were no significant changes in the mean BCVA of the study group (0.844± 0.304) and the control group (0.864± 0.253) (p=0.512).
CONCLUSIONS: This study showed that rTPA has no effect on changes in CMT and BCVA in patients who had refractory DME and PVD at the same time. This may suggest that the improvement in CMT in previous studies may be due to the induction of PVD.

BACKGROUND: Intrapleural fibrinolytic therapy (IPFT) has been used as an effective agent since 1949 for managing complicated pleural effusion and empyema. Several agents, such as streptokinase, urokinase (UK), and recombinant tissue plasminogen activator (rt-PA), have been found to be effective with variable effectiveness. However, a head-tohead controlled trial comparing the efficacy of the most frequently used agents, i.e., UK and rt-PA (alteplase) for managing complicated pleural effusion has rarely been reported.
METHODS: A total of 50 patients were randomized in two intervention groups, i.e., UK and rt-PA. The dose of rt-PA was 10 mg, and that of UK was 1.0 lac units. UK was given thrice daily for 2 days, followed by clamping to allow the retainment of drugs in the pleural space for 2 hours. rt-PA was instilled into the pleural space twice daily for 2 days, and intercostal drainage was clamped for 1 hour.
RESULTS: A total of 50 patients were enrolled into the study, of which 84% (n=42) were males and 16% (n=8) were females. Among them, 30 (60%) patients received UK, and 20 (40%) patients received alteplase as IPFT agents. The percentage of mean± standard deviation changes in pleural opacity was -33.0%±9.9% in the UK group and -41.0%±14.9% in the alteplase group, respectively (p=0.014). Pain was the most common adverse side effect, occurring in 60% (n=18) of the patients in the UK group and in 40% (n=8) of the patients in the alteplase group (p=0.24), while fever was the second most common side effect. Patients who reported early (within 6 weeks of onset of symptoms) showed a greater response than those who reported late for the intervention.
CONCLUSIONS: IPFT is a safe and effective option for managing complicated pleural effusion or empyema, and newer agents, such as alteplase, have greater efficacy and a similar adverse effect profile when compared with conventional agents, such as UK.

BACKGROUND: Early mobilization (EM) within 24 to 72 hours post-stroke may improve patients\' performance and ability. However, after intravenous thrombolysis (IVT) or mechanical thrombectomy (MT), the increased risk of hemorrhagic complications impacts the implementation of early out-of-bed mobilization. Few studies have investigated EM after IVT or MT for acute ischemic stroke (AIS), and its impact in these patients is unknown.
OBJECTIVE: To investigate the effect of EM on AIS treated with IVT or MT.|.
METHODS: We recruited 122 patients with first AIS; 60 patients were treated with IVT, and 62 patients were treated with MT. For each IVT and MT cohort, the control groups received standard early rehabilitation, and the intervention groups received an EM protocol. The training lasted 30 minutes/day, 5 days/week until discharge.
METHODS: The effectiveness of the interventions was evaluated using the motor domain of the Functional Independence Measure (FIM-motor) and the Postural Assessment Scale for Stroke Patients (PASS) at baseline, 2-week, 4-week, and 3-month post-stroke, the Functional Ambulation Category 2-week post-stroke, and the total length of stay at the stroke center.
RESULTS: Both IVT and MT treatment groups showed improved FIM-motor and PASS scores over time; however, only the IVT EM group had significantly improved FIM-motor performance within 1 month after stroke than the control group. Conclusion. An EM protocol with the same intervention time and session frequency per day as in the standard care protocol was effective in improving the functional ability of stroke patients after IVT.

UNASSIGNED: Glibenclamide alleviates brain edema and improves neurological outcomes in experimental models of stroke. We aimed to assess whether glibenclamide improves functional outcomes in patients with acute ischemic stroke treated with recombinant tissue plasminogen activator (rtPA).
UNASSIGNED: In this randomized, double-blind, placebo-controlled trial, patients with acute ischemic stroke were recruited to eight academic hospitals in China. Patients were eligible if they were aged 18-74 years, presented with a symptomatic anterior circulation occlusion with a deficit on the NIHSS of 4-25, and had been treated with rtPA within 4.5 h of symptom onset. We used web-based randomization (1:1) to allocate eligible participants to the glibenclamide or placebo group, stratified according to endovascular treatment and baseline stroke severity. Glibenclamide or placebo was taken orally or via tube feeding at a loading dose of 1.25 mg within 10 h after symptom onset, followed by 0.625 mg every 8 h for 5 days. The primary outcome was the proportion of patients with good outcomes (modified Rankin Scale of 0-2) at 90 days, assessed in all randomly assigned patients who had been correctly diagnosed and had begun study medication. The study is registered with ClinicalTrials.gov, NCT03284463, and is closed to new participants.
UNASSIGNED: Between January 1, 2018, and May 28, 2022, 305 patients were randomly assigned, of whom 272 (142 received glibenclamide and 130 received placebo) were included in the primary efficacy analysis. 103 (73%) patients in the glibenclamide group and 94 (72%) in the placebo group had a good outcome (adjusted risk difference 0.002, 95% CI -0.098 to 0.103; p = 0.96). 12 (8%) patients allocated to glibenclamide and seven (5%) patients allocated to placebo died from any cause at 90 days (p = 0.35). The number and type of adverse events were similar between the two groups. There were no drug-related adverse events and no drug-related deaths.
UNASSIGNED: The addition of glibenclamide to thrombolytic therapy did not increase the proportion of patients who achieved good outcomes after stroke compared with placebo, but it did not lead to any safety concerns.
UNASSIGNED: Southern Medical University and Nanfang Hospital.

OBJECTIVE: To investigate the 10-year trend in healthcare quality of intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator in acute ischemic stroke (AIS) in China.
METHODS: We analyzed 42,188 AIS within 7 days of onset from the China National Stroke Registry (CNSR) Ⅰ-Ⅲ. Primary outcomes were temporal changes in the proportion of patients arriving at the hospital within 3.5 hours (and 2 hours) of onset and receiving IVT within 4.5 hours (and 3 hours), stratified by region and hospital tier. Secondary outcomes included temporal changes in door-to-needle time (DNT), DNT ≤60 min and favorable outcome defined as a 90-day modified Rankin Scale (mRS) of 0-1.
RESULTS: Among patients arriving at the hospital within 3.5 hours of onset, 13.5%, 7.1% and 33.4% patients received IVT within 4.5 hours in CNSR Ⅰ, Ⅱ and Ⅲ, respectively, including a higher proportion from eastern China (37.0%) and tertiary hospitals (36.5%). The median DNT was shorter in CNSR Ⅲ (60.0 min) than those in Ⅱ (95.0 min) and I (94.0 min). The proportion of patients with DNT ≤60 min was greater in Ⅲ (53.4%) than those in Ⅱ (26.7%) and Ⅰ (13.4%). The proportion of favorable outcomes was higher in CNSR Ⅲ (72.8%) than those in Ⅱ (49.6%) and Ⅰ (49.4%). Similar trends were observed for patients arriving at the hospital within 2 hours and receiving IVT within 3 hours of onset.
CONCLUSIONS: The healthcare quality of IVT has improved remarkably in the past decade, notably in eastern China and tertiary hospitals.

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a <300 mmHg PaO2/FiO2 (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April-30 July 2020 and 21 January-19 February 2021, respectively. Matched historical controls (MHC; n = 18) were used in C1 to explore efficacy. Safety co-primary endpoints were treatment-related bleeds and <1.0-1.5 g/L fibrinogen reduction. A variable dosing strategy with clinical efficacy endpoint and minimal safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40-60 mg rt-PA daily for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeds (one severe, three mild) in three patients were considered treatment related. There were no significant fibrinogen reductions. Greater improvements in mean P/F ratio from baseline to study end were observed in C1 compared with MHC (C1; 154 to 299 vs. MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in the P/F ratio occurred in NIRS patients (NIRS; 126 to 240 vs. IMV; 120 to 188) and fewer treatment days were required (NIRS; 7.86 vs. IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, with a trend towards improved oxygenation, particularly in the NIRS group. Randomized clinical trials are required to demonstrate the clinical effect significance and magnitude.