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Toward Standardized Massive Transfusion Protocols: A Multicenter Evaluation of Practice Variability Within a National Trauma System
No full textBackground/Objectives: Hemorrhage remains a leading cause of early mortality in trauma patients, and timely transfusion guided by a structured massive transfusion protocol (MTP) is critical for improving outcomes. Although regional trauma centers have been established, standardized MTPs remain insufficiently developed in many settings. This study aimed to evaluate current MTP practices across five major trauma centers within a national trauma care system. Methods: Participating institutions provided written protocols and completed a structured survey addressing key domains, including activation criteria, transfusion strategies, laboratory monitoring, adjunct therapies, termination processes, and performance improvement measures. Findings were analyzed and compared against established international recommendations. Results: All centers had implemented MTPs and were capable of delivering initial blood products within 15 min. However, considerable variation was observed in activation triggers, transfusion ratios, and laboratory monitoring protocols. None of these centers maintained thawed plasma or whole blood in immediate readiness. Only one of five centers had a formal performance improvement monitoring system. Tranexamic acid was included in all institutional protocols. Conclusions: This review highlights significant variability and critical gaps in MTP implementation across trauma centers. Inconsistent activation criteria, the absence of essential components, and limited quality monitoring may compromise the efficacy of current practices. To improve patient outcomes, a standardized, evidence-based MTP framework should be developed and implemented nationwide
Optimizing systolic blood pressure targets for elderly hypertensive patients: a meta-analysis of mortality, cardiovascular outcomes, and adverse events
No full textBACKGROUND: Hypertension is a common health issue among elderly populations, substantially increasing morbidity and mortality risks. This meta-analysis aimed to determine optimal systolic blood pressure (SBP) targets in elderly hypertensive patients and their effects on clinical outcomes. METHODS: We conducted a systematic search of PubMed, Embase, and the Cochrane Library to identify randomized controlled trials involving antihypertensive therapy in participants aged 60 years and older. Mortality, cardiovascular events, and significant adverse events data were extracted and analyzed using random-effects models. RESULTS: The analysis included 24 studies, with 9 specifically examining elderly participants aged 60 and older. Targeting a lower SBP of less than 140 mmHg was associated with significant reductions in primary outcome events (relative risk [RR], 0.69; 95% confidence interval [CI], 0.56-0.86), all-cause mortality (RR, 0.64; 95% CI, 0.49-0.83), cardiovascular mortality (RR, 0.59; 95% CI, 0.39-0.87), and stroke (RR, 0.68; 95% CI, 0.47-0.98; I(2) = 0%). Achieving an intensive SBP target in the pooled range less than 130 mmHg reduced the risks of primary outcome events (RR, 0.73; 95% CI, 0.62-0.85), heart failure (RR, 0.57; 95% CI, 0.38-0.84), and stroke (RR, 0.72; 95% CI, 0.53-0.96), though it also led to an elevated risk of hypotension (RR, 1.43; 95% CI, 1.18-1.73). CONCLUSIONS: In elderly hypertensive patients, lower SBP targets correlate with improved clinical outcomes, including reduced mortality and cardiovascular events. Nonetheless, the heightened risk of adverse effects underscores the need for careful, individualized treatment strategies. Additional research is warranted to refine these targets and achieve a balance between therapeutic efficacy and safety
Comparisons of clinical outcomes between hypertensive and normotensive living kidney donors: a prospective, multicenter nationwide cohort study
No full textBACKGROUND: Living kidney donors with hypertension are potential candidates for solving the donor shortages in renal transplantation. However, the safety of donors with hypertension after nephrectomy has not been sufficiently confirmed. METHODS: A total of 642 hypertensive and 4,848 normotensive living kidney donors who were enrolled in the Korean Organ Transplantation Registry between May 2014 and December 2020 were included in this study. The study endpoints were a decreased estimated glomerular filtration rate (eGFR) and proteinuria. RESULTS: In the entire cohort, donors with hypertension had a lower eGFR before nephrectomy in comparison to normotensive donors which remained lower after kidney transplantation. The incidence of proteinuria in hypertensive donors increased during follow-up. In propensity score-matched analysis, the risk of eGFR being <60 mL/min/1.73 m2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.50-1.19) or <45 mL/min/1.73 m2 (HR, 0.50; 95% CI, 0.06-4.03) was not significantly increased in donors with hypertension. However, hypertensive donors were found to have a significantly higher risk of proteinuria than normotensive donors (HR, 2.28; 95% CI, 1.05-4.94). Similar findings were also observed in the analysis of the entire cohort, indicating that hypertensive donors had a significantly higher risk of proteinuria (adjusted HR, 1.77; 95% CI, 1.10-2.85), without a substantial increase in the risk of decreased renal function. CONCLUSION: The risk of proteinuria after donation was substantially increased in donors with hypertension. These findings underscore the need for careful monitoring of proteinuria in hypertensive donors following donation
Human Pluripotent Stem Cell-Derived Skeletal Muscle Organoid Model of Aging-Induced Sarcopenia
No full textBACKGROUND: Sarcopenia is defined by the age-related loss of muscle mass and function, with an impaired regenerative capacity of satellite cells (SCs). Despite their recognized importance in muscle regeneration, human model-based studies on SCs in sarcopenia are still lacking, limiting our understanding of their role in age-related muscle loss. Here, we aimed to develop a sarcopenia model using human pluripotent stem cells (hPSCs)-derived skeletal muscle organoids (hSkMOs) and prevent the sarcopenia progression by testosterone treatment. METHODS: The 3D hSkMOs were generated from hPSC and exhibited structurally and functionally mature muscle fibres and spinal-derived neurons including motor neurons and interneurons. The proportion of muscle and the diameter of muscle fibres were assessed. To investigate the acute pro-inflammatory response and intrinsic regenerative capacity of hSkMOs, we induced sarcopenia-like conditions by TNF-alpha treatment for 2 days and analysed. To model aging-induced sarcopenia and investigate the preventive effect of testosterone, chronic TNF-alpha treatment was applied, followed by testosterone administration. Histological, biochemical, molecular and electrophysiological analyses were conducted in various experiments. RESULT: We employed a stepwise differentiation protocol from 2D paraxial mesodermal induction to 3D myogenic specification, concluding with a maturation culture system. We observed that the majority of cells were T/BRA- and TBX6-positive ((+)) paraxial mesodermal progenitors (T/BRA(+), 82.04%; TBX6(+), 78.18%), whereas the neuromesodermal progenitors demonstrated a relatively low proportion (T/BRA(+)/SOX2(+), 15.91%; TBX6(+)/SOX2(+), 11.45%). Single-nucleus RNA-sequencing and extensive immunohistochemistry confirmed the presence of the myogenic lineage cell types (myogenic progenitors/SCs, myocytes, muscle fibres) and the neural lineage cell types (spinal-derived interneurons, motor neurons, glial cells, Schwann cells). Additionally, the growth of MyHC(+) muscle fibres reached twice the thickness on Day 100 compared to that on Day 50 (p < 0.0001). We subjected them to TNF-alpha treatment and analysed. Western blot analysis confirmed that TNF-alpha/NF-kappaB pathway associated factors such as NF-kappaB p65, IkappaB-alpha and AKT were highly phosphorylated (p < 0.05, p < 0.001). The administration of testosterone increased the proportion of activated SCs (PAX7(+)/MYOD(+), 7.97%; PAX7(+)/Ki67(+), 7.03%) compared to the TNF-alpha group (PAX7(+)/MYOD(+), 2.29%; PAX7(+)/Ki67(+), 2.07%, p < 0.001). The administration of testosterone increased the Cross-Sectional-Area (987.1 mum(2)) compared to the TNF-alpha group (644.7 mum(2), p < 0.01). CONCLUSIONS: We successfully developed a hSkMOs to demonstrate the structural maturity of the skeletal muscle and its functional interaction with spinal-derived interneurons and motor neurons. Furthermore, we demonstrated that our hSkMOs are useful for modelling aging-induced sarcopenia and providing a valuable platform for testing therapeutic interventions
Apixaban outcomes in atrial fibrillation patients with a single-dose reduction criterion: ASPIRE 1-year results
No full textAIMS: This study, using a prospective cohort, evaluated the effectiveness and safety of off-label reduced-dose apixaban vs. the on-label dose in atrial fibrillation (AF) patients meeting a single-dose reduction criterion. METHODS AND RESULTS: The efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE) study is a multicentre, prospective observational cohort involving AF patients who met a single-dose reduction criterion of apixaban. Patients were divided into two groups: an on-label standard dose (5 mg twice daily) and an off-label reduced dose (2.5 mg twice daily). The primary effectiveness outcome was stroke/systemic embolism (SSE), and the primary safety outcome was major bleeding. Of 1944 patients (mean age 74.3 +/- 7.9 years, 56% women), 997 (51%) were receiving off-label reduced-dose apixaban. The off-label reduced-dose group was older, had more comorbidities, higher concomitant antiplatelet use, and higher CHA2DS2-VASc and HAS-BLED scores. During follow-up (1.0 +/- 0.2 year), crude incidence rates were 0.9 vs. 0.7 per 100 person-years for SSE and 0.5 vs. 1.0 for major bleeding in the on-label vs. off-label groups. After inverse probability of treatment weighting, the off-label reduced-dose group showed no significant differences in the risk of SSE [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.28-1.59, P = 0.370] and major bleeding (HR 1.38, 95% CI 0.44-4.35, P = 0.578) compared with the on-label standard dose group. CONCLUSION: In Korean patients with AF meeting a single-dose reduction criterion of apixaban, off-label reduced-dose apixaban showed no significant differences in SSE and major bleeding compared with the on-label standard dose. These findings suggest that individualized anticoagulation strategies, such as reduced-dose apixaban, may be beneficial for patients with a high risk of bleeding
Machine learning-based prediction of amyloid positivity using early-phase F-18 flutemetamol PET
No full textBackgroundPrevious studies have suggested that early-phase imaging of amyloid positron emission tomography (PET) may offer information for predicting amyloid positivity.ObjectiveThis study aimed to evaluate whether early-phase fluorine-18 flutemetamol (eFMM) PET images provide valuable information for predicting amyloid positivity using machine learning (ML) models and whether incorporating clinical and neuropsychological features improves predictive performance.MethodsIn total, 454 patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) were enrolled and randomly divided into training (n = 354) and test (n = 100) groups. We developed ML models using logistic regression (LR) and linear discriminant analyses (LDA) for predicting amyloid positivity: eFMM features alone (eFMM model), eFMM features combined with clinical features (eFMM + C model), eFMM features combined with neuropsychological features (eFMM + N model), eFMM features combined with both clinical and neuropsychological features (eFMM + C + N model), clinical and neuropsychological features combined (C + N model), and dFMM features alone (dFMM model).ResultsIn the test group, the eFMM models achieved areas under the receiver operating characteristic curves (AUROCs) of 0.791 (LR) and 0.779 (LDA). The eFMM + C + N models significantly improved predictive performance, with AUROCs of 0.902 for both LR and LDA, outperforming the eFMM models.ConclusionsML predictive models using eFMM PET data demonstrated fair performance in predicting amyloid positivity in patients with MCI and AD. The addition of relevant clinical and neuropsychological features further enhanced the predictive performance of the eFMM models, achieving excellent performance
A Novel Liver-Specific Pseudogene Biomarker, BMS1P8, for Diagnosis and Prognosis in Hepatocellular Carcinoma
No full textBackground: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. Despite advances in therapeutic approaches, the lack of effective biomarkers continues to limit early detection and prognostic evaluation. Pseudogenes, once considered nonfunctional, have emerged as regulators of biological processes in tumors and as potential biomarkers. This study aimed to identify and validate BMS1 Pseudogene 8 (BMS1P8) as a liver-specific, clinically relevant diagnostic and prognostic biomarker in HCC.
Methods: A comprehensive survey of pseudogene expression across different stages of liver disease was performed and validated using clinical HCC samples. Correlation, enrichment, and competing endogenous RNA (ceRNA) analyses integrating matched microRNA (miRNA)-seq and mRNA-seq were used to explore the functional networks surrounding BMS1P8. Public RNA-seq datasets (GSE114564, The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA_LIHC)) were used to delineate differentially expressed pseudogenes, and 98 paired tumor and non-tumor tissues were assessed using quantitative reverse transcription polymerase chain reaction. Diagnostic and prognostic performances were evaluated using receiver operating characteristic curves and Kaplan-Meier statistics.
Results: BMS1P8 was markedly upregulated in HCC and was overexpressed in 25 other cancer types. Receiver operating characteristics analysis yielded an area under the curve of 0.81, underscoring the diagnostic utility. High BMS1P8 expression and enrichment of cell cycle pathways were associated with poor survival. ceRNA screening revealed an inverse BMS1P8-miR-30c-2-3p correlation and concordant NME/NM23 nucleoside diphosphate kinase 6 (NME6) upregulation, with the BMS1P8/miR-30c-2-3p/NME6 triad further stratifying patient outcomes.
Conclusion: Our findings highlight BMS1P8 as a novel liver-specific biomarker with substantial diagnostic and prognostic value in HCC. Its diagnostic utility suggests its potential application in early detection and personalized treatment strategies, contributing to improved patient outcomes
Public perception and changing attitudes toward antidepressants over a decade in social media: Lessons learned from online discussion using artificial intelligence
No full textBACKGROUND: Antidepressants play a crucial role in treating mental health disorders such as depression and anxiety. Understanding of patients' perspective on antidepressants is essential for improving treatment outcomes; however, year-to-year change in the public's perception of antidepressants remains unclear. We aimed to analyze changes in public sentiments and predominant perceptions regarding antidepressants using artificial intelligence pipeline. METHODS: This study analyzed online discussions related to antidepressants on Reddit from January 1, 2009, to December 31, 2022. Antidepressant-associated communities were explored to collect a list of discussions relevant to antidepressant therapy. Discussion topics on antidepressants were identified using BERTopic, and the sentiments were analyzed using a RoBERTa model. Trends were assessed using the Mann-Kendall test to evaluate shifts in sentiments over time. RESULTS: We analyzed 429,510 antidepressant-related discourse over 14 years and found a predominance in negative sentiments. Key discussion topics include the benefits and side effects of antidepressants, experiences with drug switching, and specific concerns regarding bupropion therapy. In trend analyses, negative sentiments decreased, while neutral sentiments increased over time. This aligns with a decline in the annual proportion of topics associated with side effects within each cluster. CONCLUSIONS: Negative perceptions toward antidepressants are prevalent on social media, mainly focusing on efficacy and side effects. However, a decade-long analysis shows a decline in negative sentiments, with an increase in neutral sentiments with a downturn in yearly proportion of side-effected related topics within each cluster. These trends and information may help improve strategies to address barriers to antidepressant use and adherence
Periventricular diffusivity reflects APOE ε4–modulated amyloid accumulation and cognitive impairment in the Alzheimer's disease continuum
No full textINTRODUCTION: Altered glymphatic-related fluid dynamics are increasingly recognized as a feature of Alzheimer's disease (AD). We generalized an established diffusion imaging framework to quantify periventricular diffusivity (PVeD), hypothesizing that fast diffusion signals in the periventricular region can reflect amyloid beta (Abeta) deposition across the AD continuum. METHODS: Participants from two multi-site cohorts (n = 440 and 414), comprising cognitively unimpaired individuals, those with mild cognitive impairment, and patients with AD, were included. We tested and validated the association of PVeD with Abeta burden and core AD characteristics. RESULTS: Lower PVeD was extensively associated with greater Abeta burden, neurodegeneration, cognitive impairment, and clinical severity in the clinical cohort. Importantly, the relationship between PVeD and Abeta burden was significantly modulated by apolipoprotein E (APOE) epsilon4 status; APOE epsilon4 carriers exhibited a replicable stronger negative association. Baseline PVeD also predicted longitudinal cognitive decline. DISCUSSION: These findings suggest that periventricular diffusion signals reflect APOE epsilon4-modulated Abeta burden and cognitive decline in AD. HIGHLIGHTS: An automated method for quantifying periventricular diffusivity (PVeD) is developed. Lower PVeD is associated with higher amyloid load only in a mild cognitive impairment-dominant cohort. Higher amyloid burden may mediate the link between lower PVeD and poorer cognitive outcomes in the clinical cohort. Apolipoprotein E epsilon4 carriers show a reproducibly stronger inverse PVeD-amyloid association than non-carriers. Baseline PVeD can predict longitudinal Mini-Mental State Examination decline in two independent cohorts