tPA Group Research Articles

Effects of intracameral tissue plasminogen activator injection on posterior capsular opacification, fibrin formation, and intraocular pressure in dogs after phacoemulsification.

To evaluate whether intracameral tissue plasminogen activator (tPA) injection is effective in regulating posterior capsular opacification (PCO), fibrin formation and intraocular pressure (IOP) after cataract surgery. Prospective study involving 30 eyes of 21 dogs that underwent phacoemulsification. Thirty eyes were randomly divided into two groups of 15 eyes (control and tPA groups). Intracameral tPA (25 μg/0.1 mL) was injected into tPA group eyes before corneal incision closure but not into the eyes of the control group. The grades of anterior fibrin formation and PCO were compared based on slit lamp biomicroscope examination at 1 and 2 weeks, 1 month, and 2-3 months postoperatively. IOP was measured using applanation tonometry every 30 min for 4 h immediately after operation and on the following morning. The IOP of the two groups at each time was compared. The grade of anterior fibrin formation and that of PCO were not significantly different between the two groups at any time point (p > .05). However, the IOP of the tPA group was significantly lower than that of the control group at each point on the day of surgery (p < .05). No complications were observed with tPA injection, except for temporary hyphema (for 3 days) in one eye. Although the intracameral tPA injection did not affect anterior fibrin formation and PCO, it effectively maintained normal IOP immediately after phacoemulsification. Thus, our findings provide valuable insights into the potential benefits of intracameral tPA injection in achieving immediate IOP control after phacoemulsification.

Treatment outcome of bridge mechanical thrombectomy with different IV-tPA dosages in the standard and extended time window in real-world practice.

Differences of treatment outcome between full or reduced dose of tissue plasminogen activator (tPA) for bridge mechanical thrombectomy (MT) in the extended time window have not been clearly established. We aimed to present real-world results of bridge MT with different tPA dosages in the standard and extended windows. Patients with anterior circulation stroke treated with MT between 2017 and 2021 at two stroke referral centers were retrospectively reviewed. Bridge MT with tPA were categorized as full (0.9mg/kg) or reduced (<0.9mg/kg) dose. Standard window (SW) cohort was defined as MT performed within 6h of acute ischemic stroke onset, while those beyond 6h as the extended window (EW) cohort. 90days Modified Rankin Scale (mRS) score, technical treatment success, in-hospital mortality, and post-treatment hemorrhage were analyzed. A total of 423 patients met the inclusion criteria, 218 of which treated in the SW, while 205 treated in the EW. Within the SW cohort, the full-dose tPA group demonstrated a higher proportion of good functional outcome (GFO) at 90days (mRS0-3) versus reduced (49% vs 21%, p = 0.0358). The overall GFO of SW was higher than that of the EW cohort (33% vs 20%, p = 0.0480). Within the EW cohort, GFO was similar between full and reduced dose groups. Successful reperfusion rate was lower in SW versus EW cohorts (39% vs 58%, p = 0.0199). In real-world practice, the GFO of bridge MT is better than MT alone. The tPA dosage is not a determining factor of GFO in EW MT.

Endovascular Thrombectomy Versus Intravenous Alteplase For Distal Medium Vessel Occlusions: A Propensity Score‐Matched Analysis

Background The benefits of endovascular thrombectomy (EVT) for distal medium vessel occlusions (DMVOs) are not well established. This study aimed to determine the superiority of EVT over intravenous tissue‐type plasminogen activator (IV tPA) in the treatment of DMVOs. Methods This study analyzed data from the Kanagawa Intravenous and Endovascular Treatment of Acute Ischemic Stroke Registry, a prospective, multicenter, observational registry of acute ischemic stroke patients treated with EVT or IV tPA. The study evaluated patients with acute DMVOs who were treated with EVT and/or IV tPA. DMVOs was defined as occlusions in M2–M3 segment of the middle cerebral artery, anterior cerebral artery, or posterior cerebral artery. The analysis included primary DMVOs and excluded secondary DMVOs, such as distal embolism after recanalization of proximal vessel occlusion. Propensity score‐matched analysis was conducted to compare the outcomes between EVT and IV tPA alone. A good outcome was defined as a modified Rankin Scale score 0–2 or no worsening at 90 days. An excellent outcome was defined as an modified Rankin Scale score 0–1. Results The study included 1148 patients with DMVOs, of whom 816 were treated with EVT and 332 were IV tPA alone. Before propensity score matching, the incidence of good and excellent outcomes was significantly lower in EVT group (good outcomes: EVT 50.3% versus IV tPA 68.0%; P &lt; 0.01; excellent outcomes: 39.8% versus 59.8%; P &lt; 0.001). After propensity score matching, there were no significant differences between EVT and IV tPA groups in good outcomes (EVT 57.8% versus IV tPA 61.3%; P = 0.51), excellent outcomes (46.6% versus 55.0%; P = 0.17), all cerebral hemorrhage (11.6% versus 12.7%; P = 0.74), and symptomatic hemorrhage (2.9% versus 0.6%; P = 0.13). Subarachnoid hemorrhage was more frequent in EVT group (14.5% versus IV tPA 0%). Conclusion The benefits of EVT for acute DMVOs were similar to IV tPA alone. Randomized multicenter trials are warranted to establish the superiority of EVT over IV tPA alone for DMVOs.

Relative Improvement in Language vs Motor Functions with Reperfusion Therapies for Acute Stroke due to Large Vessel Occlusion.

When weighing potential risks versus benefits of reperfusion therapy, the functions likely to recover if blood flow can be restored should be considered. Because deep and motor areas of the brain often infarct relatively early in acute stroke, we hypothesized that reperfusion therapies are more likely to improve language function and neglect (cortical functions) more than motor function. In this retrospective review of a prospectively collected database, patients with acute stroke due to large vessel occlusion), we evaluated percent improvement (mean change in score/maximum score) for different items of the National Institutes of Health Score Scale with and without endovascular thrombectomy, and/or intravenous thrombolysis. In total, 290 patients (mean age 61.8; SD 14.0; 47.9% female) met the inclusion criteria. For all outcome measures (percent change in language, total language, motor, and neglect) there were significant effects of treatment group (p<0.0001 for all), with the greatest change in the EVT +tPA group, then EVT only group, followed by tPA only, followed by no intervention. Differences between EVT + tPA and EVT only were not significant (p=.30 to 0.79 across outcomes). For patients with aphasia and/or right sided weakness before treatment, the percent change in language was significantly greater than the percent change in weakness (29.8% vs. 12.7%; t(93)=5.3;p<0.0001). Greater percent improvement in language was observed in all treatment groups (p=0.0003 to 0.03 across treatment groups). In patients with acute ischemic stroke due to LVO, improvements in all neurological functions occur with tPA, and even more with EVT (with and without IV tPA). However, gains in language are even greater than gains in motor function with both interventions. Few patients had neglect before treatment, but of those who did, the majority improved, and most (92.8%) improved with EVT.

Abstract PO1-01-03: Pathological response according to early metabolic remission in an interim FDG-PET scan and to tumor infiltrating lymphocytes - A secondary analysis of the phase II trial ABCSG 52/ATHENE investigating atezolizumab in early HER2+ BC

Abstract Background: ABCSG-52/ATHENE investigated a neoadjuvant chemotherapy de-escalation/immunotherapy escalation approach with trastuzumab, pertuzumab, atezolizumab and epirubicin for early-stage HER2-positive breast cancer. The pathological complete response rate (pCR; ypT0/Tis, ypN0) - the primary endpoint of the trial - was 60.3% (95% CI 47.5% - 71.9%), and was higher than the predefined threshold for positivity (≥ 40%). Interestingly, higher pCR rates were observed in PD-L1 immune cell (IC) negative tumors (pCR 69.2%) as compared to PD-L1 IC positive tumors (pCR 55.2%). No new safety concerns were observed. Primary outcome data were reported at the ESMO Breast Cancer Conference 2023. Here, we present the correlation of pathological outcome according to early metabolic response in an interim fluorodeoxyglucose F18 positron emission tomography (FDG-PET) scan, and according to stromal tumor infiltrating lymphocytes (TILs) at baseline. Methods: Patients (pts) with previously untreated, histologically confirmed HER2-positive early breast cancer (EBC; clinical prognostic stage cT1c-4a-d, N0–3, M0) were randomized 1:1 to two 3-weekly cycles of a chemotherapy-free induction phase (Part 1) with trastuzumab and pertuzumab (TP) plus 1200 mg atezolizumab (TP+A), or TP alone. Subsequently, all pts received 4 cycles of TP+A in combination with epirubicin 90 mg/m² (Part 2). Randomization was stratified according to baseline TILs (&amp;lt; 5% vs ≥ 5%), hormone receptor status (positive vs. negative), and prognostic stage (≤ IIA vs. ≥ IIB; AJCC v.8.0). An FDG-PET assessment was performed at baseline and after 2 cycles of study treatment. According to PERCIST, early metabolic responses were classified as metabolic complete response (mCR) and metabolic partial response (mPR) and association with outcome was tested with Fisher’s exact test. TIL assessment in pretreatment biopsy specimen were performed according to the recommendations from the International TILs Working Group. Lymphocytic predominant phenotype was defined as a TIL proportion of ≥ 50%. Correlation of TILs and pCR was modeled with logistic regression. Results: Overall, 58 pts were randomized to TP-A (n=29) or TP (n=29) at 9 sites. In 45 patients, a protocol predefined PERCIST assessment was available. An early mCR was achieved in 14 pts (n=14/45, 31.1%): 5 pts (n=5/21, 23.8%) in the TP group and 9 pts (n=9/24, 37.5%) in the TP-A group. Pts with and without an early mCR achieved a pCR in 92.9% (n=13/14) and 54.8% (n=17/31) of cases (p=0.016), respectively. An early mCR/mPR was achieved in 37 pts (n=37/45, 82.2%). Pts with and without an early mCR/mPR achieved a Residual Cancer Burden (RCB) class 0 or I in 89.2% (n=33/37) and 50.0% (n=4/8) of cases (p=0.024), respectively. The mean stromal TIL proportion was 23.9% in the overall population, with 22.8% in TP group and 25.0% in TP-A group. A lymphocytic predominant phenotype was seen in 10.3% of pts treated in the TP group, and 17.2% of pts treated in the TP-A group. No association between TIL proportion at baseline and pCR could be detected (OR for a 10%-point increase = 1.02, 95% CI 0.78-1.34). A moderate positive correlation between numeric values of TILs and PD-L1 ICs was observed (spearman r=0.57, P&amp;lt; 0.0001). Exploratory correlation analyses of PD-L1 status, TIL proportion and metabolic responses in interim FDG-PET scans will be presented at the meeting. Conclusions: In ABCSG-52, chemotherapy de-escalation with intensified immunotherapy was effective and safe. Early metabolic response assessment was feasible and predicted pathologic response; therefore, incorporation of interim FDG-PET results into de-escalation trials merits further investigation. In contrast to regimens without immune-checkpoint inhibitors, TIL proportion at baseline did not correlate with pathological outcome. Funding: Provision of IMP and financial support by Roche Austria GmbH Citation Format: Gabriel Rinnerthaler, Daniel Egle, Rupert Bartsch, Clemens Schmitt, Andreas Petzer, Marija Balic, Edgar Petru, Ursula Denison, Christian F. Singer, Vesna Bjelic-Radisic, Simon Gampenrieder, Michael Knauer, Karl Sotlar, Christine Brunner, Florian Posch, Dominik Hlauschek, Lidija Sölkner, Zsuzsanna Bago-Horvath, Martin Filipits, Manuela Gili, Michael Gnant, Richard Greil. Pathological response according to early metabolic remission in an interim FDG-PET scan and to tumor infiltrating lymphocytes - A secondary analysis of the phase II trial ABCSG 52/ATHENE investigating atezolizumab in early HER2+ BC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-03.

Variability of fibrinolytic activity in pregnant patients exposed to tissue plasminogen activator: an in vitro study utilizing rotational thromboelastometry

BackgroundThe investigation into the variability of fibrinolysis in obstetric patients is notably limited despite its relevance to postpartum hemorrhage. We investigate an in vitro model of fibrinolysis measured by rotational thromboelastrometry (ROTEM) in maternal blood samples with lysis stimulated by tissue plasminogen activator (tPA). MethodsWritten informed consent was obtained from 19 patients at term pregnancy during admission to the labor and delivery unit. Patients who were taking medication affecting coagulation were excluded. Tissue plasminogen activator was added to whole blood samples to a final concentration of 100 or 220 ng/mL prior to ROTEM testing. ResultsThe addition of tPA produced high intra-individual fibrinolytic variability for clot firmness and lysis parameters. Patients responded differently to each tPA dose ranging from clot lysis within the range of 0 ng/mL tPA group to complete clot lysis. The coefficient of variation (CV) values for the 220 ng/mL tPA group were: EXTEM MCF 0.510, EXTEM LI30 1.601, FIBTEM MCF 0.349, FIBTEM LI30 2.097. CV values for the 100 ng/mL tPA group were: EXTEM MCF 0.144, EXTEM LI30 1.038, FIBTEM MCF 0.096, FIBTEM LI30 1.238. ConclusionWe demonstrate a wide range of fibrinolytic response in the obstetric population to exogeneous tPA. We found subgroups of patients that were very responsive to tPA and insensitive to tPA. This study represents a preliminary exploration into classifying the obstetric fibrinolytic phenotypes. Further research will integrate relevant coagulation factors to establish a predictive model for testing susceptibility to lysis that can be applied at the point of care.

Abstract WP202: Thrombectomy versus Combined Thrombolysis and Thrombectomy for Primary Medium and Distal Intracranial Occlusions: A Propensity-Score Matched Multicenter Analysis

Background: Mechanical thrombectomy (MT) has demonstrated superiority over medical therapy for acute ischemic stroke (AIS) with large vessel occlusion (LVO). The role of adjunctive intravenous thrombolysis, such as intravenous tissue plasminogen activator (IVtPA), with MT remains unclear, especially for medium vessel occlusion (MeVO). This multicenter study aimed to compare outcomes between MT alone and MT+IVtPA in patients with MeVO. Methods: Data from 827 patients treated at 37 academic centers in North America, Asia, and Europe were collected between September 2017 and July 2021. Propensity score matching was performed to create two well-balanced groups: MT alone and MT+IVtPA. Baseline characteristics, procedural details, and clinical outcomes were analyzed. Results: After propensity score matching, 577 patients (315 in the MT alone group and 262 in the MT+IVtPA group) were included in the analysis. The two groups had comparable baseline characteristics, except for longer onset-to-puncture and onset-to-recanalization times in the MT alone group. In univariable regression, all outcomes were comparable between the two groups, except for higher mRS 0-2 rates in the MT+IVtPA group. Multivariable regression analysis showed no significant differences in first pass effect (FPE), number of passes, Thrombolysis in Cerebral Infarction (TICI) scores, rates of mRS 0-1, mRS 0-2, mortality, or intracranial hemorrhage between the groups. Conclusion: In patients with primary medium and distal intracranial occlusions, MT alone and MT+IVtPA yielded similar clinical outcomes. These findings suggest that adding IVtPA to MT may not confer additional benefit in this population. Further research is needed to determine the optimal treatment approach for MeVO.

Abstract WP26: Effectiveness of Tenecteplase versus Alteplase in Acute Ischemic Stroke Selected Subgroups of a Real-World-Data Set

Introduction: Tenecteplase is increasingly utilized as an alternative acute ischemic stroke (AIS) thrombolytic to Alteplase (tPA). Although many larger AIS trials have demonstrated the non-inferiority of TNK, Real World Data in many specific subgroups continue to be lacking. We studied the comparative effectiveness of AIS thrombolysis with TNK to tPA at our institution, focusing on currently understudied cohorts. Methods: We conducted a retrospective cohort analysis of AIS patients treated with thrombolysis within our health system. We utilized the Get With the Guidelines (GWTG) database to obtain basic demographic data. Additional variables and key outcomes (functional and radiographic) were abstracted independently by two authors from the electronic record. Disagreements were resolved by mutual consensus or a third investigator. An ordinal logistic regression model was used to assess the interventions' effectiveness, with the outcome being the modified Rankin Scale (mRS) score 90 days post-stroke. Subgroups included Age (&lt;60, 61-80, &gt;80), location of vessel occlusion (Large or Medium vessel), thrombolysis in the extended time window (beyond 4.5 hours), treatment via telestroke, and thrombectomy. Results: There were 500 consecutive AIS patients with complete outcome data. The mean age of the participants was 70.1 years, with 52.7% of patients being male. In the adjusted ordinal logistic regression analysis, the TNK group presented with 1.00 odds of a worse mRS score than the tPA group (95% CI 0.57-1.74). Subgroup regression analysis demonstrated no heterogeneity in effect size. Figure 1 is a Forest Plot demonstrating the Odds Ratio for each subgroup. Conclusions: It’s well-published that TNK is a comparable treatment for AIS and has demonstrated advantages. This analysis compared specific subgroups of real-world patients and showed no heterogeneity. This real-world subgroup analysis adds to the literature supporting the use of TNK for the treatment of AIS.

Abstract WP24: Safety of Tenecteplase vs Alteplase in Telestroke: A Large Multistate Experience (STAT)

Background: Prompt treatment with IV thrombolytics (IVT) in acute ischemic stroke (AIS) patients is critical for improved recovery and survival. Recently, hospital systems are switching to the IVT tenecteplase (TNK) instead of the FDA approved alteplase (tPA) for treatment. Multiple studies and meta-analyses evaluating the efficacy and safety of TNK demonstrate similar or superior outcomes when compared to tPA. TNK is not FDA approved for treatment leading to hesitation and attention on the complications profile including intracranial hemorrhage (ICH) rates. Methods: AIS consults seen in the ED by TeleSpecialists, LLC at 220 facilities (26 states) from January 1, 2022 to May 31, 2023 were extracted from the TeleCare by TeleSpecialists TM database. The encounters were reviewed for IVT candidate, door to needle (DTN) time, IVT used, advanced imaging, LVO, complication occurrence, complication type, symptomatic ICH, and ECASS II ICH score. Comparison of complications was performed between the two groups by IVT: TNK or tPA. Comparison of continuous variables was performed by student’s t-test for normally distributed data, and the Mann-Whitney test for nonnormally distributed data. Pearson's Chi-square test was employed for comparisons of categorical variables. Results: A total of 2305 TNK patients and 3337 tPA patients were extracted. DTN times were faster (37 min vs 42 min, p &lt; 0.0001) and more total complications were seen in the TNK group (87 vs 80, p =0.0035). In nonLVO IVT patients, TNK group had more complications (57 vs 47, p 0.0078), specifically ICH (48 vs 35, p= 0.0036). In LVO IVT patients, TNK group did not have a statistically significant difference in ICH (21 vs 18, p =0.07). In IVT patients not accepted for NIR, TNK group had more complications (77 vs 69, p=0.005), specifically ICH (63 vs 51, p=0.0026). In IVT patients accepted for NIR, no significant differences were observed. There were no statistically significant differences in symptomatic ICH between groups. Conclusions: TNK group was found to have significantly more complications including ICH compared to tPA group driven by non-LVO patients. Closer analysis of potential for increased risk to non-LOV patients is warranted based on this data from the largest simultaneously collected data.

A difluoroboron compound with latent fingerprint detection and inkless writing based on aggregation-induced emission enhancement and mechanofluorochromic behavior

A pyridine-based difluoroboron compound with the TPA group displayed excellent AIEE activity and MFC behavior, which was applied for latent fingerprint detection and inkless writing.

Abstract 13017: National Characteristics and Outcomes of Adults With Pulmonary Embolism Undergoing Catheter Directed Thrombolysis Compared to Systemic Tissue Plasminogen Activator

Introduction: Catheter Directed Thrombolysis (CDT) and systemic tissue plasminogen activator (tPA) are commonly used interventions for pulmonary embolism (PE). We aim to compare these two procedures. Methods: Cases of pulmonary embolism in adults were used for our study from the National Inpatient Sample (2016-2020). We compared the characteristics and outcomes of patients undergoing CDT vs. systemic tPA &lt;24 hours after hospitalization. Results: We found 16675 cases of PE, with 9130 (54.8%) patients undergoing tPA and 7545 (45.2%) needing CDT. Compared to tPA cases, a lower rate of weekend admission was seen in patients undergoing CDT. Both groups consisted of Whites and were covered primarily by Medicare. Most admissions took place in urban teaching centers, with large bed sizes and in the southern regions of the US. Furthermore, CDT patients were older (mean age 56.2 vs. 52.1 years), involving more patients with hypertension and obesity. However, CDT cases had fewer patients with diabetes, peripheral vascular disease, chronic kidney disease, prior stroke, and drug abuse and reported a lower mean Charlson Comorbidity Index(CCI) score(table 1). tPA patients also had higher rates of atrial fibrillation, ventricular fibrillation, and atrial flutter. Overall, 5.9% of patients undergoing tPA died, while 1.8% died in the CDT cohort (aOR death in tPA 2.604 vs. CDT, 95% CI 2.033-3.335, p&lt;0.01). A higher mortality rate within the first week of hospitalization was also seen in the tPA group (figure 1). tPA cohort also reported higher odds of acute kidney injury(AKI) (aOR 1.484, 95% CI 1.364-1.615, p&lt;0.01) and cardiogenic shock (aOR 3.588, 95% CI 2.990-4.304, p&lt;0.01). Finally, tPa patients had a lengthier stay. Conclusions: CDT cases showed lower mortality during the first week of the procedure. Differences in comorbidities exist between the two groups. Further research exploring additional factors may help address current protocols to improve long-term outcomes.

Abstract 040: Hemorrhagic Conversion Patterns After Transition of Stroke Thrombolysis from Alteplase to Tenecteplase; Real‐World Experience

Introduction Importance:Tenecteplase (TNK) use is more prevalent as the thrombolytic drug of choice for acute ischemic stroke (AIS), given its ease of use with results from randomized trials showing non‐ inferiority and comparable safety to Alteplase (tPA). However, there is conflicting data in terms of intracranial hemorrhage risk. Objective: We are reporting the rate of symptomatic intracranial hemorrhage(sICH) in TNK and tPA treated stroke populations across two large hospital systems. Methods Design: Retrospective cohort observational study. Data was collected from April 1, 2022 through March 29, 2023. Setting: Data was collected from 15 stroke centers: 10 primary and 5 comprehensive stroke centers in Texas. Participants: Inclusion criteria: 18 years or older, suspected to have an AIS were eligible to receive thrombolytic therapy, and received either IV TNK or tPA at the standard dose. A total of 431 patients were included. 216 patients received alteplase and 215 patients received tenecteplase. Exposure: Data was collected 90 days before and 90 days after the stroke center changed from tPA to TNK. Main Outcomes: The primary endpoint was to compare the incidence of sICH according to SITS‐MOST/ECASS‐3 criteria in the tPA and TNK groups. Secondary endpoints included the radiographic pattern of hemorrhagic conversion according to the Heidelberg bleeding classification (HBc). Results A total of 431 patients; half of them had been administered Alteplase (n=216) and the other half had Tenecteplase (n=215). Approximately half of them were females 110 (51%) for alteplase and 117 (54%) for Tenecteplase. Almost 2/3 of the study population never smoked; 66% for alteplase 64% for Tenecteplase. Majority of the patient population got thrombolytic therapy within 3 hours 174 (81%) for alteplase versus 176 (82%) for Tenecteplase. 34 patients (15%) in the alteplase group as compared to 26 patients (12%) in the Tenecteplase group had endovascular thrombectomy attempted. 7 patients in the tPA group (3.2%) and 14 patients (6.5%) in the TNK group had sICH. An increase in the NIHSS on arrival (p=0.048) was a statistically significant predictor of sICH. A two sample proportion test on TNK produced a statistically significant increase in Heidelberg Bleed class 3 (HBc3) (p=0.040) over tPA. Conclusion We observed increased cases of bleeding associated with TNK administration with statistically significant increase in the HBc3 when compared to patients who received tPA. Suggested mechanisms of bleeding are hemorrhagic conversion in clinically silent infarcts, and contusions underlying the lesions. These findings suggest a potential need to reevaluate the criteria for administering TNK to patients. Larger studies are required to confirm this data.

Dehydroabietic acid and triphenylamine combined BioAIEgens with an imine linker and RIM: mechanochromism and acidichromism

The petrochemical-based multi-stimuli responsive materials have been widely explored as advanced functional materials in the past several decades, but they inevitably face problems like complicated synthesis, non-renewability, and non-sustainability. On this basis, the bio-based materials used to construct multi-stimuli responsive due to the unique natural structures have come to the fore. In this work, three novel triphenylamine-based salicylideneanilines have been simply designed with aggregation-induced emission (AIE) properties. Among all, DAMB-TPAOH and DAMB-TPA possessing the natural structure of dehydroabietic acid from rosin are bioproduct-inspired AIE luminogens (BioAIEgens). Derived from the excited-state intramolecular proton transfer (ESIPT) and restriction of intramolecular motion (RIM) dual-mechanism caused by the hydroxyl group and rigidification of alicyclic moiety, respectively, the solid-state DAMB-TPAOH exhibits red-shifted (compared to DAMB-TPA) and stronger (compared to BA-TPAOH) emission, endowing this BioAIEgen with the best fluorescence behavior. Further, the introduction of the natural skeleton, propeller TPA, and imine group results in the high-contrast mechanochromic and acidichromic properties of DAMB-TPAOH. The multi-stimuli responsive properties endow DAMB-TPAOH with potential utilization in the manufacture of rewritable paper and multi-color ink. The current work contributes greatly to the development of BioAIEgens with both mechanochromism and acidichromism.

Growth and anemia among children with tuberculosis infection at different sites in Southwest China.

To explore the effects of tuberculosis (TB) infection at different sites on anthropometric indicators, malnutrition and anemia incidence in children in Southwest China. From January 2012 to December 2021, a total of 368 children aged 1 month to 16 years were enrolled. According to the sites of TB infection, they were divided into three groups: tuberculous meningitis (T group), tuberculous meningitis complicated withpulmonary tuberculosis (TP group), and tuberculous meningitis complicated with pulmonary tuberculosis and abdominal tuberculosis (TPA group). Data on weight, height, nutritional risk, blood biochemical indicators and basic descriptions were collected within 48 h after admission. The body mass index-for-age z score (BAZ), height-for-age z score (HAZ), and concentrations of hemoglobin (Hb) and albumin (ALB) decreased in the following order: T group, TP group, and TPA group. The prevalence of malnutrition was the highest in the TPA group (69.5%, 82/118) and 10-to 16-year-old group (72.4%, 63/87). Children aged 0.5-2 years exhibited the highest anemia prevalence of 70.6% (48/68) among the four age groups.The TPA group had the highest incidence of anemia (70.5%, 67/95) compared to T group and TP group.Compared with the treatment group, the abandonment group had a lower BAZ, HAZ and levels of HB and ALB, a higher rate of severe malnutrition, and higher nutritional risk scores. Children who had a low BAZ [odds ratio (OR) = 1.98], nutritional risk (OR = 0.56) and anemia (OR = 1.02) were less likely to obtain treatment with their guardians' support. Children with tuberculous meningitis were at risk for growth disorders and anemia, especially when complicated with pulmonary tuberculosis and abdominal tuberculosis. The prevalence of anemia and malnutrition was the highest among patients aged 1 month to 2 years and 10-16 years, respectively. Nutritional status was one of the causes of abandoning treatment.

Effect of intra-arterial thrombolysis following successful endovascular thrombectomy on functional outcomes in patients with large vessel occlusion acute ischemic stroke: A post-CHOICE meta-analysis

IntroductionEndovascular thrombectomy (EVT) is the standard treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Although > 70% of patients in the trials assessing EVT for AIS-LVO had successful recanalization, only a third ultimately achieved favorable outcomes. A “no-reflow” phenomenon due to distal microcirculation disruption might contribute to such suboptimal outcomes. Combining intra-arterial (IA) tissue plasminogen activator (tPA) and EVT to reduce the distal microthrombi burden was investigated in a few studies. We present a pooled-data meta-analysis of the existing evidence of this combinatorial treatment. MethodsWe followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) recommendations. We aimed to include all original studies investigating EVT plus IA tPA in AIS-LVO patients. Using R software, we calculated pooled odds ratios (ORs) with corresponding 95% confidence intervals (CI). A fixed-effects model was adopted to evaluate pooled data. ResultsFive studies satisfied the inclusion criteria. Successful recanalization was comparable between the IA tPA and control groups at 82.9% and 82.32% respectively. The 90-day functional independence was similar between both groups (OR= 1.25; 95% CI= 0.92-1.70; P= 0.154). Symptomatic intracranial hemorrhage (sICH) was also comparable between both groups (OR= 0.66; 95% CI= 0.34-1.26; P= 0.304). ConclusionOur current meta-analysis does not show significant differences between EVT alone and EVT plus IA tPA in terms of functional independence or sICH. However, with the limited number of studies and included patients, more randomized controlled trials (RCTs) are needed to further investigate the benefits and safety of combined EVT and IA tPA.

123O Randomized phase II trial of neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in early HER2-positive breast cancer (ABCSG-52/ATHENE)

For most HER2-positive early breast cancer (EBC) patients (pts), neoadjuvant dual HER2 blockade with trastuzumab (T) and pertuzumab (P) plus poly-chemotherapy is standard of care. To improve the balance between toxicity burden and treatment outcomes, chemotherapy de-escalation has been a major focus in recent years. Among other immunogenic properties, anthracyclines can trigger an immunogenic cell death that engages the adaptive immune system. Within the ABCSG-52 trial we investigated a chemotherapy de-escalation immunotherapy regimen in HER2-positive EBC. Pts with previously untreated, histologically confirmed HER2-positive EBC (clinical prognostic stage cT1c-4a-d, N0–3,M0) were randomized 1:1 to two 3-weekly cycles of a chemotherapy-free induction phase (part 1) with TP plus 1200mg atezolizumab (TP+A) or TP alone. Afterwards, all pts received 4 cycles of TP+A in combination with epirubicin (part 2). The primary endpoint was pathological complete response (pCR; ypT0/Tis ypN0) in the overall study population. A pCR rate of ≥ 40% was considered as a positive trial result. Overall, 58 pts were randomized to TP-A (n=29) or TP (n=29) in 9 Austrian study centers. Median age was 57 (range 33-82), 16 pts (27.6%) had hormone-receptor (HR)-negative and 42 (72.4%) had HR-positive tumors. 45 pts (77.6%) had stage ≤ IIA and 13 (22.4%) ≥ IIB. In 35 pts a pCR was observed (60.3%; 95%CI 47.5% - 71.9%), 19 (65.5%) in the TP-A group and 16 (55.2%) in TP group (Δ 10.3%; 95%CI -14.7% - 35.4%). Residual cancer burden (RCB) class 0 or I was seen in 44 out of 55 pts (80%) with valid RCB assessment. Treatment emergent adverse events (AEs) grade ≥ 3 were reported in 17 pts (29.3%), 9 in TP-A group (31.0%) and 8 (27.6%) in TP group. No AEs of special interest (immune-related AEs, cardiac disorders grade ≥ 2, or infusion-related reactions) grade ≥ 3 were detected. Outcome according to PD-L1 expression status is currently analyzed and will also be presented at the meeting. For HER2-positive EBC, a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab and epirubicin is highly effective and safe and merits further investigation.

Intra-Arterial Thrombolysis Associated with Symptomatic Intracranial Hemorrhage in Acute Basilar Artery Thrombectomy, PC-SEARCH Registry Analysis (P8-5.008)

Intra-Arterial Thrombolysis Associated with Symptomatic Intracranial Hemorrhage in Acute Basilar Artery Thrombectomy, PC-SEARCH Registry Analysis (P8-5.008)

307 Clinical Efficacy of Thrombolytic Therapies in Mothership Versus Drip and Ship Model: A Systematic Review and Meta-Analysis

INTRODUCTION: There exist substantial uncertainty in understanding the benefit of organizational paradigms in stroke centers. METHODS: Studies between 1990 and 2021 were analyzed from electronic databases. Critical time measurements, functional independence, and mortality were all compared. IBM SPSS 23 and Rev Manager were used for statistical analysis. RESULTS: 7,232 patients’ data were collected from 24 studies. MT+IVtPA vs. IVtPA only did not show significant difference between both cohorts when analyzing NIHSS (p = 0.461). When conducting a subgroup analysis to interpret differences between MS and DS patients in each treatment method, no significant difference (p &gt; 0.05) was noted for the mean time of symptoms to onset and the mean stroke onset to successful recanalization time for the Mt+IVtPA (p = 0.267) and IVtPA cohorts (p = 0.461). The MT+/-IVtPA reported significant differences between MS and DS patients in both these times (p &lt; 0.001 and p = 0.011, respectively). Moreover, no significant difference was noted for mortality at 90-days and symptomatic intracranial hemorrhage (sICH) among these different thrombolytic groups for the DS and MS model patients in all three treatment method cohorts (p = 0.941 for the MT+IVtPA group, p = 0.993 for the MT+/-ItPA and N/A for IVtPA only). The MT+/-IVtPA cohort was the only one to show a significantly larger percentage of patients in the DS group, compared to the MS, to have a mRS score of 3-6 (bad functional outcome) (p = 0.034). CONCLUSIONS: Our results showed that there is no sufficient significant difference in clinical efficacy based on MS or DS models in each treatment type.

Effects of Self-Administered Acupressure on Fatigue Following Traumatic Brain Injury: A Randomized Controlled Trial.

Fatigue is a common symptom after a traumatic brain injury (TBI) and may persist for weeks or years. However, nonpharmacological management strategies for fatigue alleviations are almost nonexistent; thus, effective fatigue management programs are needed urgently. We aimed to evaluate the effects of self-administered acupressure programs on post-TBI fatigue and heart rate variability and identify the possible correlation between the improvements in fatigue symptoms and the changes in heart rate variability. This randomized controlled trial included 2-point acupressure (TPA; n = 27), 5-point acupressure (FPA; n = 27), and usual care (UC, control; n = 27) groups who underwent several assessments before and after the study intervention. Heart rate variability was evaluated at baseline, weeks 2 and 3, and treatment completion. The TPA and FPA groups self-administered acupressure (3 minutes per acupoint; bilateral), thrice daily for 4 weeks, whereas the UC group received routine treatment without acupressure. Both the TPA and FPA groups exhibited substantial improvements in fatigue symptoms compared with the baseline findings in the UC group. In addition, the TPA and FPA groups exhibited increased high-frequency power and mean number of times per hour in which the changes in successive normal sinus intervals (RR) gradually exceeded 50 ms (pNN50). Changes in high-frequency power and pNN50 were correlated with improvements in post-TBI fatigue symptoms. Acupressure may alleviate chronic fatigue and enhance parasympathetic activity in TBI survivors. The enhancement of parasympathetic activity may be correlated with improvements in post-TBI fatigue symptoms. Healthcare providers should incorporate self-administered acupressure into the care plans for TBI survivors to improve their fatigue symptoms.

Outcome of Medial Parapatellar Versus Transpatellar Tendon Approach of Intramedullary Nail Insertion Techniques in Tibial Shaft Fractures

Background: Fractures of the tibia are among the most serious long bone fractures. Materials and method: This is a retrospective study conducted in Aden. We reviewed records of patients who were admitted and treated for tibial fractures by intramedullary nail. We gathered data from 48 patients, underwent MPA and TPA approach for surgery. SPSS version 17 was used to analyze the data. The Fisher test was used to compare the two groups, MPA and TPA group. The significance level was set at P&lt;0.05. Results: Males were (72.9%) and females were (27.1%). Their mean age was 37 ± 11.9 years. Stair ascending impairment were found in MPA approach (20.8%) and (29.2%) after TPA (p &gt; 0.05). Limping was found in MPA group (22.9%) and (20.8%) in TPA group (p &gt; 0.05). Inability squaring found in MPA group (27.1%) and (29.2%) in TPA group, (p &gt; 0.05). Anterior knee pain was found in (27.1%) of MPA approach and (35.4%) in TPA approach, (p &gt; 0.05). In the MPA insertion approach, (29.2%) patients showed a full flexion after two days of the surgical insertion while in TPA approach there were (16.6%) patients showed a full flexion (p &gt; 0.05). Full extraction found in MPA approach (33.3%) after 2 days of surgery and (29.2%) in TPA approach, (p &gt; 0.05). After 2 days (31.3%) patients whom treated with MPA approach and (22.9%) whom treated with TPA approach. Conclusion: The study showed us the advantage of medial parapatellar tendon approach of treating the tibial shaft fractures. Keywords: Outcome, intramedullary nail, tibia, fracture.