Combined inhibition of CDK4/6 and AKT is highly effective against the luminal androgen receptor (LAR) subtype of triple negative breast cancer.

Luminal Androgen Receptor (LAR) triple-negative breast cancers (TNBC) express androgen receptors (AR), exhibit high frequency of PIK3CA mutations and intact RB. Herein, we investigated combined blockade of the CDK4/6 and PI3K signaling with palbociclib, alpelisib, and capivasertib, which inhibit CDK4/6, PI3Kα, and AKT1-3, respectively. The combination of palbociclib/capivasertib, but not palbociclib/alpelisib, synergistically inhibited proliferation of MDA-MB-453 and MFM-223 LAR cells [synergy score 7.34 (p = 5.81x10-11) and 4.78 (p = 0.012), respectively]. The AR antagonist enzalutamide was inactive against MDA-MB-453, MFM-223, and CAL148 cells and did not enhance the efficacy of either combination. Palbociclib/capivasertib inhibited growth of LAR patient-derived xenografts more potently than palbociclib/alpelisib. Treatment of LAR cells with palbociclib suppressed phosphorylated-RB and resulted in adaptive phosphorylation/activation of S473 pAKT and AKT substrates GSK3ß, PRAS40, and FoxO3a. Capivasertib blocked palbociclib-induced phosphorylation of AKT substrates more potently than alpelisib. Treatment with PI3Kß inhibitors did not block phosphorylation of AKT substrates, suggesting that PI3Kß did not mediate the adaptive response to CDK4/6 inhibition. Phosphokinase arrays of MDA-MB-453 cells treated with palbociclib showed time-dependent upregulation of PDGFRß, GSK3ß, STAT3, and STAT6. RNA silencing of PDGFRß in palbociclib-treated MDA-MB-453 and MFM-223 cells blocked the upregulation of S473 pAKT, suggesting that the adaptive response to CDK4/6 blockade involves PDGFRß signaling. Finally, treatment with palbociclib and the PDGFR inhibitor CP637451 arrested growth of MDA-MB-453 and MFM-223 cells to the same degree as palbociclib/capivasertib. These findings support testing the combination of CDK4/6 and AKT inhibitors in patients with LAR TNBC, and further investigation of PDGFR antagonists in this breast cancer subtype.

Drug Use Patterns in Wastewater and Socioeconomic and Demographic Indicators.

Importance: Measuring drug use behaviors in individuals and across large communities presents substantial challenges, often complicated by socioeconomic and demographic variables. Objectives: To detect spatial and temporal changes in community drug use by analyzing concentrations of analytes in influent wastewater and exploring their associations with area-based socioeconomic and sociodemographic metrics like the area deprivation index (ADI) and rural-urban commuting area (RUCA) codes. Design, Setting, and Participants: This longitudinal, cross-sectional wastewater study was performed from May 2022 to April 2023 and included biweekly influent wastewater samples of 39 analytes from 8 sampling locations across 6 wastewater treatment plants in southern Nevada. Statistical analyses were conducted in December 2023. Main Outcomes and Measures: It was hypothesized that wastewater monitoring of pharmaceuticals and personal care products (PPCPs) and high-risk substances (HRSs) could reveal true spatial and temporal drug use patterns in near-real time. Data collection of samples for PPCPs and HRSs was performed using mass spectrometry. Both ADI and RUCA scores were utilized to characterize neighborhood contexts in the analysis. The false discovery rate (FDR) method was utilized to correct for multiple comparisons (PFDR). Results: Over the 12-month wastewater monitoring period, 208 samples for PPCPs and HRSs were collected, and analysis revealed an increase in the consumption of HRSs and the seasonal variation in PPCP use in southern Nevada. There was a significant increase in levels of stimulant-associated analytes, such as cocaine (ß = 9.17 × 10-4; SE = 1.29 × 10-4; PFDR = 1.40 × 10-10), and opioids or their metabolites, notably norfentanyl (ß = 1.48 × 10-4; SE = 1.88 × 10-4; PFDR = 1.66 × 10-12). In contrast, DEET, an active ingredient in mosquito and tick repellents, demonstrated a seasonal use pattern (ß = -4.85 × 10-4; SE = 2.09 × 10-4; PFDR = 4.87 × 10-2). Wastewater from more disadvantaged or rural neighborhoods, as assessed through ADI and RUCA scores, was more likely to show a significant positive correlation with HRSs, such as cocaine (ß = 0.075; SE = 0.038; P = .05) and norfentanyl (ß = 0.004; SE = 0.001; P = 1.64 × 10-5). Conclusions and Relevance: These findings suggest that wastewater monitoring of PPCPs and HRSs offers a complementary method to existing public health tools, providing timely data for tracking substance use behaviors and use of PPCPs at a population level.

Assessing Alzheimer's disease via plasma extracellular vesicle-derived mRNA.

INTRODUCTION: Alzheimer's disease (AD), the most prevalent neurodegenerative disorder globally, has emerged as a significant health concern. Recently it has been revealed that extracellular vesicles (EVs) play a critical role in AD pathogenesis and progression. Their stability and presence in various biofluids, such as blood, offer a minimally invasive window for monitoring AD-related changes. METHODS: We analyzed plasma EV-derived messenger RNA (mRNA) from 82 human subjects, including individuals with AD, mild cognitive impairment (MCI), and healthy controls. With next-generation sequencing, we profiled differentially expressed genes (DEGs), identifying those associated with AD. RESULTS: Based on DEGs identified in both the MCI and AD groups, a diagnostic model was established based on machine learning, demonstrating an average diagnostic accuracy of over 98% and showed a strong correlation with different AD stages. DISCUSSION: mRNA derived from plasma EVs shows significant promise as a non-invasive biomarker for the early detection and continuous monitoring of AD. Highlights: The study conducted next-generation sequencing (NGS) of mRNA derived from human plasma extracellular vesicles (EVs) to assess Alzheimer's disease (AD).Profiling of plasma EV-derived mRNA shows a significantly enriched AD pathway, indicating its potential for AD-related studies.The AD-prediction model achieved a receiver-operating characteristic area under the curve (ROC-AUC) of more than 0.98, with strong correlation to the established Clinical Dementia Rating (CDR).

Elevated remnant cholesterol as a potential predictor for cardiovascular events in rheumatoid arthritis patients.

Objective: The risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) remains inadequately defined. Consequently, this study aims to evaluate the predictive value of remnant cholesterol (RC) for assessing CVD risk in RA patients. Methods: Plasma RC levels were measured in 114 RA patients and 41 healthy controls, calculated as total cholesterol minus HDL-C and LDL-C. These levels were further analyzed using 1H-NMR lipid/metabolomics. Meanwhile, the 28-joint Disease Activity Score (DAS28) assessed RA activity. Results: RC levels were significantly elevated in RA patients (19.0 mg/dl, p < 0.001) compared to healthy controls (14.5 mg/dl). Furthermore, RC levels were significantly elevated at 37.4 mg/dl in patients who experienced cardiovascular event (CVE) compared to 17.4 mg/dl in those without CVE (p < 0.001). To enhance the precision and reliability of RC measurements, RC concentrations were further validated using 1H-NMR spectroscopy. Additionally, a positive correlation was observed between RC levels and DAS28. Multivariate analysis identified RC as a significant predictor of CVE (odds ratio = 1.82, p = 0.013). ROC curve analysis revealed superior predictive capability of RC for CVE (AUC = 0.919, p < 0.001) compared to LDL-C (AUC = 0.669, p = 0.018), with a high sensitivity of 94.7% and a specificity of 82.1%. Conclusion: Elevated RC levels demonstrate greater accuracy in predicting CVE occurrence in RA patients compared to traditional measures such as LDL-C. These findings suggest that elevated RC levels may serve as a novel predictor for occurrence of CVE in RA patients, facilitating early intervention strategies based on the risk stratification.

The Association between Percentage of Mean Arterial Pressure and Long-Term Mortality in Acute Myocardial Infarction Patients: An Observational Cohort Study.

Background: Acute myocardial infarction (AMI) is a critical cardiovascular disease with high morbidity and mortality. Identifying practical parameters for predicting long-term mortality is crucial in this patient group. The percentage of mean arterial pressure (%MAP) is a useful parameter used to assess peripheral artery disease. It can be easily calculated from ankle pulse volume recording. Previous studies have shown that %MAP is a useful predictor of all-cause mortality in specific populations, but its relationship with mortality in AMI patients is unclear. Methods: In this observational cohort study, 191 AMI patients were enrolled between November 2003 and September 2004. Ankle-brachial index (ABI) and %MAP were measured using an ABI-form device. All-cause and cardiovascular mortality data were collected from a national registry until December 2018. Cox proportional hazards model and Kaplan-Meier survival plot were used to analyze the association between %MAP and long-term mortality in AMI patients. Results: The median follow-up to mortality was 65 months. There were 130 overall and 36 cardiovascular deaths. High %MAP was associated with increased overall mortality after multivariable analysis (HR = 1.062; 95% CI: 1.017-1.109; p =0.006). However, high % MAP was only associated with cardiovascular mortality in the univariable analysis but became insignificant after the multivariable analysis. Conclusions: In conclusion, this study is the first to evaluate the usefulness of %MAP in predicting long-term mortality in AMI patients. Our study shows that %MAP might be an independent predictor of long-term overall mortality in AMI patients and has better predictive power than ABI.

The American Cancer Society National Lung Cancer Roundtable strategic plan: Lung cancer in women.

Lung cancer in women is a modern epidemic and represents a global health crisis. Cigarette smoking remains the most important risk factor for lung cancer in all patients and, among women globally, rates of smoking continue to increase. Although some data exist supporting sex-based differences across the continuum of lung cancer, there is currently a dearth of research exploring the differences in risk, biology, and treatment outcomes in women. Consequently, the American Cancer Society National Lung Cancer Roundtable recognizes the urgent need to promote awareness and future research that will close the knowledge gaps regarding lung cancer in women. To this end, the American Cancer Society National Lung Cancer Roundtable Task Group on Lung Cancer in Women convened a summit undertaking the following to: (1) summarize existing evidence and identify knowledge gaps surrounding the epidemiology, risk factors, biologic differences, and outcomes of lung cancer in women; (2) develop and prioritize research topics and questions that address research gaps and advance knowledge to improve quality of care of lung cancer in women; and (3) propose strategies for future research. PLAIN LANGUAGE SUMMARY: Lung cancer is the leading cause of cancer mortality in women, and, despite comparatively lower exposures to occupational and environmental carcinogens compared with men, disproportionately higher lung cancer rates in women who ever smoked and women who never smoked call for increased awareness and research that will close the knowledge gaps regarding lung cancer in women.

Metabolic dysregulation in Huntington's disease: Neuronal and glial perspectives.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutant huntingtin protein with an abnormal CAG/polyQ expansion in the N-terminus of HTT exon 1. HD is characterized by progressive neurodegeneration and metabolic abnormalities, particularly in the brain, which accounts for approximately 20 % of the body's resting metabolic rate. Dysregulation of energy homeostasis in HD includes impaired glucose transporters, abnormal functions of glycolytic enzymes, changes in tricarboxylic acid (TCA) cycle activity and enzyme expression in the basal ganglia and cortical regions of both HD mouse models and HD patients. However, current understanding of brain cell behavior during energy dysregulation and its impact on neuron-glia crosstalk in HD remains limited. This review provides a comprehensive summary of the current understanding of the differences in glucose metabolism between neurons and glial cells in HD and how these differences contribute to disease development compared with normal conditions. We also discuss the potential impact of metabolic shifts on neuron-glia communication in HD. A deeper understanding of these metabolic alterations may reveal potential therapeutic targets for future drug development.

Fourier-transform microwave spectroscopy of the ClSS radical.

The ClSS radical is one of the members of the XSS, XSO and XOO (X = H, F, Cl) radicals. It was studied by Fujitake et al. using millimeter- and sub-millimeter wave spectroscopy, where no hyperfine structure was resolved. As the last piece of this series of radicals, it is important to determine the fine and hyperfine constants of the ClSS radical precisely using FTMW spectroscopy. Different from the case of the ClSO radical with the unpaired electron mainly occupying the S atom at the center, the unpaired electron of the ClSS radical mainly occupies the pc orbital of the terminal S atom. Despite this difference, the investigation of the fine and hyperfine structures of the ClSS radical made us confirm that the XSS and XSO radicals share characteristics in common, but they are quite different from the XOO radicals.

Healthcare failure mode and effect analysis combined service blueprint - Mitigating mass casualty triage in emergency units: A qualitative study.

INTRODUCTION: The 24-hour operation of medical emergency units involves crucial first-hand information and medical treatments, which could involve potential complications and disputes if not handled with the utmost professionalism. Effective logistical support and timely activation are crucial in mass casualty triage to prevent systematic treatment issues and chaos. OBJECTIVE: This study explores the integration of Healthcare Failure Mode and Effect Analysis (HFMEA) with a service blueprint to mitigate medical risks and enhance mass casualty triage efficiency in emergency units. METHOD: An expert team analyzed emergency unit standard operating procedure cases using a service blueprint to visually represent mass casualty triage scenarios. The HFMEA identified potential hazards and failure risks in healthcare service delivery during mass casualty triage. RESULTS: Fifteen high-risk hazard indexes exceeding the standard score of eight were identified among three main processes and thirty-one potential failure reasons. The initial operational time for mass casualty triage was approximately 104 min, significantly reduced to 34 min after process revision (p = 0.043, <0.05). CONCLUSIONS: This study demonstrates effective time management in mass casualty triage, potentially saving up to an hour. Improved operational efficiency allows for focused resuscitation efforts, alleviating concerns about timely patient flow initiation.

Utilizing diffusion tensor imaging as an image biomarker in exploring the therapeutic efficacy of forniceal deep brain stimulation in a mice model of Alzheimer's disease.

Objective.With prolonged life expectancy, the incidence of memory deficits, especially in Alzheimer's disease (AD), has increased. Although multiple treatments have been evaluated, no promising treatment has been found to date. Deep brain stimulation (DBS) of the fornix area was explored as a possible treatment because the fornix is intimately connected to memory-related areas that are vulnerable in AD; however, a proper imaging biomarker for assessing the therapeutic efficiency of forniceal DBS in AD has not been established.Approach.This study assessed the efficacy and safety of DBS by estimating the optimal intersection volume between the volume of tissue activated and the fornix. Utilizing a gold-electroplating process, the microelectrode's surface area on the neural probe was increased, enhancing charge transfer performance within potential water window limits. Bilateral fornix implantation was conducted in triple-transgenic AD mice (3 × Tg-AD) and wild-type mice (strain: B6129SF1/J), with forniceal DBS administered exclusively to 3 × Tg-AD mice in the DBS-on group. Behavioral tasks, diffusion tensor imaging (DTI), and immunohistochemistry (IHC) were performed in all mice to assess the therapeutic efficacy of forniceal DBS.Main results.The results illustrated that memory deficits and increased anxiety-like behavior in 3 × Tg-AD mice were rescued by forniceal DBS. Furthermore, forniceal DBS positively altered DTI indices, such as increasing fractional anisotropy (FA) and decreasing mean diffusivity (MD), together with reducing microglial cell and astrocyte counts, suggesting a potential causal relationship between revised FA/MD and reduced cell counts in the anterior cingulate cortex, hippocampus, fornix, amygdala, and entorhinal cortex of 3 × Tg-AD mice following forniceal DBS.Significance.The efficacy of forniceal DBS in AD can be indicated by alterations in DTI-based biomarkers reflecting the decreased activation of glial cells, suggesting reduced neural inflammation as evidenced by improvements in memory and anxiety-like behavior.

Design of a Compact Multiband Monopole Antenna with MIMO Mutual Coupling Reduction.

In this article, the authors present the design of a compact multiband monopole antenna measuring 30 × 10 × 1.6 mm3, which is aimed at optimizing performance across various communication bands, with a particular focus on Wi-Fi and sub-6G bands. These bands include the 2.4 GHz band, the 3.5 GHz band, and the 5-6 GHz band, ensuring versatility in practical applications. Another important point is that this paper demonstrates effective methods for reducing mutual coupling through two meander slits on the common ground, resembling a defected ground structure (DGS) between two antenna elements. This approach achieves mutual coupling suppression from -6.5 dB and -9 dB to -26 dB and -13 dB at 2.46 GHz and 3.47 GHz, respectively. Simulated and measured results are in good agreement, demonstrating significant improvements in isolation and overall multiple-input multiple-output (MIMO) antenna system performance. This research proposes a compact multiband monopole antenna and demonstrates a method to suppress coupling in multiband antennas, making them suitable for internet of things (IoT) sensor devices and Wi-Fi infrastructure systems.

The stony coral Fimbriaphyllia (Euphyllia) ancora's reproductive strategy involves a sex change every year.

A sex change phenomenon was reported in some free-living, non-sessile coral species of the Family Fungiidae. However, there are no reports describing sex change in sessile colonial species. Timing and cellular processes of sex change are also unclear in corals. Here, we report sex change of the colonial coral, Fimbriaphyllia ancora, and its cellular process. Of 26 colonies monitored at Nanwan Bay, southern Taiwan, about 70% changed their sex every year after annual spawning for least 3-4 consecutive years, i.e., colonies that were male two years ago became female last year, and male again this year. The remaining 30% were permanently male or female. Sex-change and non-sex-change colonies grew in close proximity or even side-by-side. No significant differences were found in colony size between sex-change and non-sex-change colonies. Histological analysis showed that, in female-to-male sex change, small oocytes were present up to 3 months in some gonads after spawning and disappeared by 5 months. This suggests that sex change occurred 4-5 months after spawning. In contrast, in male-to-female sex change, oocytes appeared weeks after sperm release and in most gonads by 3 months, suggesting that male-to-female sex change occurred 0-3 months after sperm release.

Prevalent Fast Evolution of Genes Involved in Heterochromatin Functions.

Heterochromatin is a gene-poor and repeat-rich genomic compartment universally found in eukaryotes. Despite its low transcriptional activity, heterochromatin plays important roles in maintaining genome stability, organizing chromosomes, and suppressing transposable elements. Given the importance of these functions, it is expected that genes involved in heterochromatin regulation would be highly conserved. Yet, a handful of these genes were found to evolve rapidly. To investigate whether these previous findings are anecdotal or general to genes modulating heterochromatin, we compile an exhaustive list of 106 candidate genes involved in heterochromatin functions and investigate their evolution over short and long evolutionary time scales in Drosophila. Our analyses find that these genes exhibit significantly more frequent evolutionary changes, both in the forms of amino acid substitutions and gene copy number change, when compared to genes involved in Polycomb-based repressive chromatin. While positive selection drives amino acid changes within both structured domains with diverse functions and intrinsically disordered regions, purifying selection may have maintained the proportions of intrinsically disordered regions of these proteins. Together with the observed negative associations between the evolutionary rate of these genes and the genomic abundance of transposable elements, we propose an evolutionary model where the fast evolution of genes involved in heterochromatin functions is an inevitable outcome of the unique functional roles of heterochromatin, while the rapid evolution of transposable elements may be an effect rather than cause. Our study provides an important global view of the evolution of genes involved in this critical cellular domain and provides insights into the factors driving the distinctive evolution of heterochromatin.

Exploring the key elements for the successful management of primary otolaryngologic clinics in Taiwan.

AIM: This study aims to investigate the key elements for successful operation and management of primary otolaryngologic clinics in Taiwan amidst a declining birth rate and increasing competition among clinics. It employs the Innovation Through Tradition (ITT) theory as a theoretical framework to develop an operational model for effective management strategies. METHODS: This research utilized the triangulation method to identify key elements crucial for the operation and management of primary otolaryngologic clinics. Five key elements were identified, namely service attitude, medication efficacy, diagnostic and treatment procedures, treatment costs, and operating hours. Outpatient satisfaction was analyzed using Donabedian's structure-process-outcomes model to assess the impact of these elements on patient experience. RESULTS: Analysis revealed that service attitude significantly influences outpatient visits, indicating its paramount importance in clinic management. Patient satisfaction was highest in the service outcome dimension, emphasizing the significance of effective treatment outcomes. However, satisfaction was lowest in the service structure dimension, indicating potential areas for improvement in clinic infrastructure and organization. CONCLUSION: Understanding these key elements and enhancing outpatient satisfaction can drive improvements in the quality of medical services, contributing to the overall success of primary otolaryngologic clinics.

Incidence of Subsequent Injuries Associated with a New Diagnosis of Benign Paroxysmal Positional Vertigo and Effects of Treatment: A Nationwide Cohort Study.

Background/Objectives: Benign paroxysmal positional vertigo (BPPV) is the most common cause of recurrent vertigo and the most common peripheral vestibular disorder. It is characterized by intense vertigo triggered by head and position changes. This study investigates the risk of subsequent injury in BPPV patients and the effects of treatment. Methods: A population-based retrospective cohort study was conducted using data from the Longitudinal Health Insurance Database 2005 in Taiwan. Patients with and without BPPV were identified between 2000 and 2017. The study outcomes were diagnoses of all-cause injuries. The Kaplan-Meier method determined the cumulative incidence rates of injury in both cohorts, and a log-rank test analyzed the differences. Cox proportional hazard models calculated each cohort's 18-year hazard ratios (HRs). Results: We enrolled 50,675 patients with newly diagnosed BPPV and 202,700 matched individuals without BPPV. During follow-up, 47,636 patients were diagnosed with injuries (13,215 from the BPPV cohort and 34,421 from the non-BPPV cohort). The adjusted HR for injury in BPPV patients was 2.63 (95% CI, 2.49-2.88). Subgroup analysis showed an increased incidence of unintentional and intentional injuries in BPPV patients (aHR 2.86; 95% CI, 2.70-3.13 and 1.10; 95% CI, 1.04-1.21, respectively). A positive dose-response relationship was observed with increasing BPPV diagnoses. Treatment with canalith repositioning therapy (CRT) or medications reduced the risk of injury slightly but not significantly (aHR, 0.78; 95% CI, 0.37-1.29, 0.88; 95% CI, 0.40-1.40, respectively). Conclusions: BPPV is independently associated with an increased risk of injuries. CRT or medications have limited effects on mitigating this risk. Physicians should advise BPPV patients to take precautions to prevent injuries even after treatment.

Factors influencing nurses' satisfaction to online learning approach: a cross ICU analysis.

BACKGROUND: Given the increasing complexity of illnesses and rapid pace of technological advancements in professional training, it is vital to offer nurses ample opportunities to hone their clinical expertise and skills, particularly in ensuring the delivery of premier medical care. This study aimed to determine the factors and predictors influencing nurses' satisfaction with adopting mobile learning approaches in intensive care unit healthcare settings. Additionally, it sought to investigate the applicability of the technology acceptance model in explaining their inclinations and validating the measurement scales employed in the research. METHODS: The study employed a cross-sectional survey research design, utilizing a technology acceptance questionnaire and a learning satisfaction questionnaire. The survey was conducted in six intensive care unit departments. A total of 212 participants completed the survey as the primary instrument. Rigorous assessments were conducted to establish the content validity and ensure instrument reliability. RESULTS: The findings demonstrated that perceived usefulness was the most influential factor affecting nurses' intentions to embrace mobile learning approaches, with perceived ease of use emerging as the principal determinant of perceived usefulness. CONCLUSIONS: Incorporating mobile learning methodologies is paramount to increasing the calibration of professional nursing education programs. By effectively integrating digital information technology and tools, nursing educators can overcome teaching challenges, deliver innovative clinical nursing education content through mobile learning approaches, and foster optimal development in the field.

Pre-treatment with tocilizumab reduces lipopolysaccharide-induced acute lung injury in biliary cirrhotic rats.

Infection-related lipopolysaccharide (LPS) release causes cytokine storm and acute lung injury. Emerging data show that the interleukin 6 (IL-6) inhibitor tocilizumab can improve lung damage in patients with sepsis. This study aimed to investigate the therapeutic effect of tocilizumab on acute lung injury in cirrhotic rats. Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Tocilizumab was administered on post-operative day 21, and LPS was injected intraperitoneally on day 29. Three hours after LPS injection, hemodynamic parameters, biochemistry data, and arterial blood gas analysis were evaluated, along with measurements of IL-6 and tumor necrosis factor-α (TNF-α). Liver and lung histology was examined, and protein levels were analyzed. LPS administration reduced portal pressure, portal venous flow and cardiac index in the BDL rats. In addition, LPS administration induced acute lung injury, hypoxia and elevated TNF-α and IL-6 levels. Pre-treatment with tocilizumab did not affect hemodynamic and biochemistry data, but it ameliorated lung injury and decreased TNF-α, IL-6, and CD68-positive macrophage infiltration. Moreover, tocilizumab administration improved hypoxia and gas exchange in the BDL rats, and downregulated hepatic and pulmonary inflammatory protein expression. In conclusion, LPS administration induced acute lung injury in biliary cirrhotic rats. Pre-treatment with tocilizumab reduces lung damage and hypoxia, possibly by downregulating inflammatory proteins and reducing IL-6, TNF-α and CD68-positive macrophage recruitment in the lung.

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

BACKGROUND: 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. MATERIALS AND METHODS: 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 (0.9 mg/kg) or reduced (<0.9 mg/kg) dose. Standard window (SW) cohort was defined as MT performed within 6 h of acute ischemic stroke onset, while those beyond 6 h as the extended window (EW) cohort. 90 days Modified Rankin Scale (mRS) score, technical treatment success, in-hospital mortality, and post-treatment hemorrhage were analyzed. RESULTS: 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 90 days (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). CONCLUSION: 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.