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Background: Spontaneous intracerebral hemorrhage (sICH) is a critical and disabling form of stroke and accounts for an obvious number of stroke-related deaths and disabilities globally. Hematoma growth is a key target for therapeutic intervention because of its association with poor outcomes. Recently, the STOP-MSU trial showed that intravenous tranexamic acid (TA) did not reduce hematoma growth or improve clinical outcomes when administered within 2 h of intracerebral hemorrhage symptom onset. This study aims to evaluate the efficacy of TA in reducing hematoma growth and improving clinical outcomes in patients with spontaneous sICH by incorporating the findings from the latest STOP-MSU trial and consolidating past research to clarify the overall efficacy and safety of TA on sICH., Methods: A systematic review and meta-analysis were conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA guidelines. We included randomized controlled trials (RCTs) comparing TA to placebo in adult patients with sICH. Databases such as PubMed, Medline, and Cochrane were searched up to May 2024. Key outcomes analyzed included hematoma expansion, mortality within 90 days, thromboembolic events, and favorable functional outcomes. Data were pooled using a random-effects model and analyzed using the "metafor" package in RStudio., Results: Five RCTs involving 1419 patients were included. The meta-analysis showed no significant difference in hematoma expansion (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.74-1.03), mortality within 90 days (OR 1.03, 95% CI 0.86-1.24), thromboembolic events (OR 1.07, 95% CI 0.69-1.64), and favorable functional outcomes (modified Rankin Scale of 0-2 at 90 days; OR 1.04, 95% CI 0.88-1.22) between the TA and placebo groups., Conclusions: TA does not significantly reduce hematoma growth or improve clinical outcomes in patients with sICH. Despite its affordability and availability, the routine use of TA in sICH is not supported by current evidence., Competing Interests: Declarations. Ethical approval and consent to participate: Not applicable for systematic review/meta-analysis., (© 2025. The Author(s).)

Ethnopharmacological Relevance: Endometriosis is a common gynecological disorder that manifests as chronic pelvic pain and subfertility. Guizhi Fuling Wan (GFW), which contains five herbs, was first described in Chinese canonical medicine to treat qi stagnation and circulation. Although the inhibition of endometriosis by GFW has been previously demonstrated, its efficacy could potentially be improved by adjusting the dose of each component., Aim: This study aimed to examine the relative importance of herbs in endometriosis treatment., Materials and Methods: Endometriosis was induced in C57BL/6NCrlBltw mice, followed by treatment with H 2 O, GFW, all individual herbs of GFW, and GFW with sequential deletion of a single herb for 28 days. Immunohistochemistry and western blotting were performed to examine the expression of inflammatory and apoptotic markers., Results: The endometriosis-inhibiting effect of GFW was reduced by deletion of either Guizhi or Fuling. Guizhi, Fuling, or Taoren alone also inhibit the development of endometriosis. The reduction in intercellular adhesion molecule 1 (ICAM-1) by GFW was attenuated by deletion of Guizhi, Fuling, or Taoren, whereas either Guizhi or Fuling alone decreased ICAM-1 expression. The deletion of either Guizhi or Fuling diminished the enhancement of caspase-3 by GFW, whereas caspase-3 expression was elevated by either Guizhi or Fuling alone., Conclusion: Deletion of either Guizhi or Fuling attenuated the inhibition of endometriosis development, while either Guizhi or Fuling alone maintained the endometriosis-inhibiting effect of GFW. Consistent with the description in the canonical literature of traditional Chinese medicine, this study revealed that Guizhi and Fuling are the most crucial components of GFW in treating endometriosis, as they are the emperor drugs of this formula, whereas Taoren is a minister drug., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The IL-17B/IL-17RB oncogenic signaling axis promotes pancreatic cancer progression through interaction with mixed-lineage kinase 4 (MLK4). Here, we improved the effectiveness of a therapeutic peptide (TAT-IL17RB 403-416 , loop peptide) that disrupted IL-17RB/MLK4 interaction by converting its linear structure into a cyclic form. The modified cyclic peptide with higher uptake efficiency inhibited pancreatic cancer cell growth and metastasis, outperforming the original linear peptide both in vitro and in an orthotopic mouse model. At the molecular level, cysteine 408 in IL-17RB was important for mediating interactions with arginine 216 within MLK4 kinase domain. This interaction was fundamental to the efficacy of the cyclic peptide. Additionally, lysine 410 in IL-17RB was essential for maintaining the structural integrity of the cyclic peptide as a protein-protein disruptor These findings provide a deeper understanding of the IL-17RB-MLK4 interaction, offering insights for developing therapeutic agents targeting this pathway in pancreatic cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Kidney transplant recipients have an increased risk of cytomegalovirus (CMV) infection and disease. A strategy for mitigating the risk of CMV infection in kidney transplant recipients has not yet been established in Taiwan. The Transplantation Society of Taiwan aimed to develop a consensus by expert opinion on the prevention and management of CMV infection. Based on the results of Consensus Conference, we suggested low-dose valganciclovir prophylaxis (450 mg once daily) for kidney transplant recipients. The prophylaxis duration was ≥6 months for high-risk (D+/R-) patients and 3 months for moderate-risk (R+) patients. Even for low-risk (D-/R-) patients, prophylaxis for at least 3 months is recommended because of the high seroprevalence of CMV in Taiwan. CMV prophylaxis was suggested after anti-thymocyte globulin treatment but not after methylprednisolone pulse therapy. Routine surveillance after prophylaxis, secondary prophylaxis after CMV disease treatment, and mTOR inhibitors for primary CMV prophylaxis were not recommended. Letermovir and marabavir are emerging CMV agents used for prophylaxis and refractory CMV disease. CMV immunoglobulins have been used to treat refractory CMV disease in Taiwan. We hope this consensus will help professionals manage patients with CMV in Taiwan to improve the quality of care., Competing Interests: Declaration of competing interest All authors declared no conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation of p38 mitogen-activated protein kinase (MAPK) is implicated in ALS. However, it is unclear how p38 MAPK affects TDP-43 proteinopathy. Here, we show that p38α MAPK inhibition reduces pathological TDP-43 phosphorylation, aggregation, cytoplasmic mislocalization, and neurotoxicity. Remarkably, p38α MAPK inhibition mitigates aberrant TDP-43 phenotypes in diverse ALS patient-derived motor neurons. p38α MAPK phosphorylates TDP-43 at pathological S409/S410 and S292, which reduces TDP-43 liquid-liquid phase separation (LLPS) but allows pathological TDP-43 aggregation. Moreover, we establish that PRMT1 methylates TDP-43 at R293. Importantly, S292 phosphorylation reduces R293 methylation, and R293 methylation reduces S409/S410 phosphorylation. Notably, R293 methylation permits TDP-43 LLPS and reduces pathological TDP-43 aggregation. Thus, strategies to reduce p38α-mediated TDP-43 phosphorylation and promote PRMT1-mediated R293 methylation could have therapeutic utility for ALS and related TDP-43 proteinopathies., Competing Interests: Declaration of interests H.J.W., D.G.B., and N.J.B. were full-time employees and shareholders of AstraZeneca at the time these studies were conducted. S.J.M. is a consultant for SAGE Therapeutics and AstraZeneca, relationships that are regulated by Tufts University., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Microplastic pollution significantly threatens marine ecosystems, including those with unique adaptations. This study evaluates the implications of polyethylene microplastics (PE-MPs) on the hydrothermal vent crab, Xenograpsus testudinatus. Crabs were exposed to varying fluorescent green polyethylene microspheres (FGPE) concentrations for 7 days. Histological analysis revealed severe damage to the hepatopancreas and gills at higher FGPE concentrations. Antioxidant enzyme activities (SOD, CAT, GR, GST, GPx, LPO) and gene expression (sod, cat) were assessed to evaluate oxidative stress responses. Results indicated significant upregulation of SOD and CAT activities at lower FGPE concentrations, suggesting an initial antioxidant response. However, GR and GST activities were inhibited at higher concentrations, and oxidative stress markers increased. These findings proved that PE-MPs induce molecular oxidative damage and lead to possible oxidative responses. Despite their resilience to extreme environments, HV crabs are vulnerable to pollutant-induced stressors, which pose ecological risks to species interactions and population dynamics within vent ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Purpose: This study presents a novel technique for intraocular lens (IOL) fixation. The technique can be used on single-piece acrylic IOLs and can manage patients who are either with aphakia or with a dislocated IOL., Methods: One end of the Gore-Tex suture is tied into the optic-haptic junction of the IOL. Another end is fixated on the scleral wall. The single-sclerotomy and double-sclerotomy settings can be applied to different situations., Results: Twelve eyes received this procedure. After a follow-up period of up to 20 months, the IOLs were well centered., Conclusion: The technique is a reliable method for scleral fixation of IOLs, which can be applied to the widely used single-piece acrylic IOLs. In the authors' experience, it is reproducible and rarely causes complications.

Background: Entamoeba histolytica, a protozoan parasite, is responsible for intestinal amebiasis and can cause severe complications. It is prevalent in tropical and subtropical regions and is a significant health concern in developing countries. Traditional diagnostic methods often delay the diagnosis, leading to prolonged patient suffering and increased risk of complications., Methods: We report the case of a 59-year-old HIV-positive man on Odefsey, who presented with a week-long history of abdominal pain and diarrhea. Initial stool analysis suggested bacterial colitis, and empirical treatment with levofloxacin was initiated. However, the patient's condition worsened, resulting in hospitalization. Laboratory findings included elevated white blood cell count and high-sensitivity C-reactive protein, with low plasma sodium and potassium levels. Stool bacterial cultures were negative for common pathogens., Results: Rapid diagnosis was achieved using the FilmArray GI Panel, which detected E. histolytica within an hour. Subsequent stool microscopy suggested the presence of E. histolytica/E. dispar cysts. Prompt antiamoebic therapy with metronidazole and paromomycin resulted in significant clinical improvement. The case was reported to the Centers for Disease Control (CDC) as a Category II notifiable disease., Conclusions: This case underscores the critical role of the FilmArray GI Panel in the rapid detection of E. his-tolytica, facilitating timely and effective treatment. Early diagnosis using advanced molecular diagnostics significantly improves patient outcomes and should be incorporated into routine clinical practice for managing gastrointestinal infections.

Polymyxin B is a viable option for treating antibiotic-resistant infections; however, current data on its pharmacokinetics, particularly in patients with renal insufficiency, remain inconclusive and necessitates further investigation. To address this gap, we conducted an open-label, single-center, single-dose, parallel-group pharmacokinetic study. Participants received an intravenous dose of 0.75 mg/kg of polymyxin B and were categorized based on their renal function: those with normal function (creatinine clearance [CLcr] ≥ 90 mL/min), mild renal insufficiency (CLcr 60-89 mL/min), and end-stage kidney disease patients on intermittent hemodialysis (IHD) (CLcr < 10 mL/min). The pharmacokinetic parameters assessed included the area under the curve (AUC), maximum concentration (C max ), clearance rate (CL), volume of distribution (Vz), and half-life (t 1/2 ). Results indicated that subjects with mild renal insufficiency exhibited pharmacokinetic profiles similar to healthy individuals. Nevertheless, in patients undergoing long-term IHD, we observed significant differences: the AUC was 58% higher, C max was 29% lower, CL was 42% lower, Vz was 60% larger, and t 1/2 was extended by 10 h compared to healthy controls. Secondary outcomes revealed good tolerability of polymyxin B across all groups, with no serious adverse effects related to renal function. In summary, while kidney function may have a slight impact on the pharmacokinetic of polymyxin B, it does not compromise the drug's therapeutic effectiveness., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Leptospirosis and hantavirus syndrome are two major rodent-borne diseases in Taiwan. Rocahepevirus ratii (RHEV), a virus closely related to hepatitis E virus (HEV, Paslahepevirus balayani ), is emerging and has been reported to cause hepatitis in humans. We employed wastewater-based epidemiology to actively monitor rodent-borne pathogens, and the correlations with human cases were evaluated. Wastewater was collected using grab sampling at 11 sites along a sewer system including influents and effluents at a wastewater treatment plant in Tamsui, New Taipei City, Taiwan, monthly during June 2023 to May 2024. The presence of pathogens was examined by reverse transcription-polymerase chain reaction (RT-PCR). The result showed an overall positivity rate of 38.2% (50/131). Leptospira was detected most often (48/131, 36.6%), and RHEV and hantaviruses were found once each during the study period. Sequencing identified Leptospira interrogans close to isolates from rodents and human cases, while sequences of hantavirus and RHEV were most similar to isolates from rodents. No significant correlation was found with human cases or positive samples for rodent DNA. Here, we present an example of a One Health approach applying wastewater to environmental surveillance for the early detection and prevention of emerging diseases.

Urothelial carcinoma (UC) predominantly arises in the bladder, but upper tract urothelial carcinomas (UTUCs) comprise 5-10% of cases. Patients with end-stage renal disease (ESRD) are at increased risk for UC, and erythropoiesis-stimulating agents (ESAs) are frequently used to manage anemia in ESRD. However, ESA use in cancer patients raises concerns about tumor progression and survival outcomes. This study aimed to assess the impact of ESA use on tumor recurrence, cancer-specific survival (CSS), and overall survival (OS) in patients with ESRD and early-stage UC. We analyzed data from the Chang-Gung Research Database (CGRD) in Taiwan, including 850 patients with ESRD and non-muscle-invasive bladder cancer (NMIBC) and 492 patients with ESRD and localized UTUC. The ESA group was compared to a non-ESA cohort, and inverse probability of treatment weighting (IPTW) was applied to minimize selection bias. Kaplan-Meier curves and log-rank tests were used to evaluate bladder recurrence-free survival, CSS, and OS. In NMIBC patients, ESA use did not significantly affect bladder recurrence-free survival, CSS, or OS. Similarly, ESA use in localized UTUC patients did not increase the risk of bladder recurrence or negatively impact CSS and OS. However, UTUC patients treated with ESA demonstrated a significantly increased risk of contralateral recurrence (P < 0.001). The use of ESA in patients with ESRD and early-stage UC appears safe regarding bladder recurrence, CSS, and OS, but clinicians should remain vigilant for contralateral recurrence in localized UTUC. These findings provide valuable insights into the complex management of anemia in patients with concurrent ESRD and UC, emphasizing the need for tailored clinical monitoring in this high-risk population., Competing Interests: None., (AJCR Copyright © 2024.)

Introduction: Hypoxemia is a common complication of sedation. This meta-analysis aimed to evaluate the efficacy and safety of supraglottic jet oxygenation and ventilation (SJOV) in preventing hypoxemia during sedative procedures., Methods: Randomized controlled trials (RCTs) that compared SJOV with conventional oxygen therapy in sedated patients were searched in five databases (MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure [CNKI], and Google Scholar) from their inception to March 2024. The primary outcome was the proportion of patients who developed hypoxia (SpO 2  < 90%). The secondary outcomes included subclinical respiratory depression (90% ≤ SpO 2  < 95%), severe hypoxemia (SpO 2  < 75%), airway interventions, adverse events, hemodynamics, propofol dosage, and procedure time. The certainty of evidence was determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Results: Twelve trials (n = 3058) were included in the analysis. The evidence suggests that SJOV results in a large reduction in the risk of hypoxemia (risk ratio [RR], 0.26; 95% confidence interval, 0.19-0.36; low certainty) and subclinical respiratory depression (RR, 0.40; low certainty) compared with the control. SJOV likely resulted in a large reduction in the risk of severe hypoxemia (RR, 0.22; moderate certainty). In addition, it may result in a large reduction in the need for jaw lift (RR, 0.22; low certainty) and mask ventilation (RR, 0.13; low certainty). The risk of sore throat probably increases with SJOV (RR, 1.71; moderate certainty), whereas SJOV may result in little to no difference in nasal bleeding (RR, 1.75; low certainty). Evidence is very uncertain regarding the effect of SJOV on hemodynamics (very low certainty) and procedure time (very low certainty). SJOV probably resulted in little to no difference in sedative doses between the groups (moderate certainty)., Conclusion: According to the GRADE approach, SJOV likely results in a large reduction in the risk of severe hypoxemia but probably increases the risk of sore throat. Compared with the control, evidence suggests that SJOV results in a large reduction in the risk of hypoxemia, subclinical respiratory depression, and the need for airway manipulation, with little to no difference in nasal bleeding. The integration of SJOV into clinical practice may help minimize hypoxemic events in at-risk patients., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Overactive bladder (OAB) significantly impairs quality of life in the elderly. Although the intradetrusor injection of botulinum toxin type A (BoNT-A) is a treatment option, its effects on older adults remain uncertain. This study aimed to evaluate the efficacy and safety of BoNT-A intradetrusor injections in elderly OAB patients through a systematic review and meta-analysis. A comprehensive literature search was conducted using the PubMed, Embase, Cochrane Library, Scopus, and CINAHL databases from inception to 30 May 2024. The primary outcomes were improvements in daily urinary incontinence (UI) episodes and patient-reported outcomes, while the secondary outcomes focused on potential adverse events. Four randomized controlled trials with 803 participants were included. BoNT-A injections significantly reduced daily UI episodes at 4-6 weeks (mean difference [MD]: -3.82; 95% confidence interval [CI]: -6.29 to -1.35) and at 12 weeks (MD: -2.17; 95% CI: -3.22 to -1.12). However, BoNT-A was associated with an increased risk of elevated post-void residual (Risk Difference [RD]: 0.154; 95% CI: 0.058 to 0.251) and urinary tract infection (RD: 0.111; 95% CI: 0.005 to 0.217), with no significant difference observed in the initiation of catheterization or hematuria. Trial sequential analysis confirmed a sufficient sample size and statistical power. In conclusion, while BoNT-A effectively manages OAB in the elderly, careful post-injection monitoring is warranted due to its potential risks.

Objectives: Photoangiolytic lasers have yielded significant innovation in laryngeal surgery in the last 25 years. After the discontinuation of the potassium titanyl phosphate (KTP) laser, a novel 445-nm blue laser was developed. The optimal balance between a laser's desired tissue effects and collateral tissue damage is a major determinant of laser selection in microlaryngeal surgery. The shell-less incubation system for the chick chorioallantoic membrane (CAM) simulates the microvasculature of the human vocal fold and is useful for testing effects of laser settings and in simulated surgery. The aim of this study is to compare the tissue effects of the KTP and blue lasers using the shell-less CAM model., Methods: The shell-less incubation system contains: polymethylpentene film (used as a culture vessel), calcium lactate and distilled water supplementations. By using this system, the chick chorioallantoic membrane (CAM) can be fully exposed with a good field for surgery simulation. The effects of the 2 lasers (532 nm KTP and 445 nm blue) were quantified at clinically relevant energy settings and laser distances from target. Measures included imaging real-time vascular reactions in the CAM model, post-procedure histologic analysis of CAM tissue and temperature changes., Results: Vessel coagulation and rupture rates were less common with the blue laser compared with the KTP laser. Histologic analysis demonstrated less tissue disruption with the blue laser. Temperature changes were less with the blue laser., Conclusion: In this CAM model with specific conditions, the blue laser reveals less tissue damage than the KTP laser. Suitable working distance and power setting of the laser are necessary for desired tissue effects. Level of Evidence: Level 3., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Dendritic cell (DC) vaccine is an emerging immunotherapy that could potentially improve glioblastoma survival. The first phase III clinical trial of DC vaccine was recently published. This meta-analysis aims to update and reappraise existing evidence on the efficacy of DC vaccine in patients with glioblastoma., Methods: We searched PubMed, Embase, and Cochrane Library for clinical trials of DC vaccine for glioblastoma. The quality of the studies was assessed using the RoB 2.0 and ROBINS-I tools. The results of overall survival (OS) and progression-free survival (PFS) were pooled using hazard ratios (HRs) with corresponding 95% confidence intervals (CI). Summary effects were evaluated using random effects models. Trial sequential analysis (TSA) was performed., Results: Seven clinical trials involving 3,619 patients were included. DC vaccine plus standard care was associated with significantly improved OS (HR = 0.71; 95% CI, 0.57 - 0.88) and PFS (HR = 0.65; 95% CI, 0.43 - 0.98). In the subgroup of newly diagnosed glioblastoma, DC vaccine was associated with improved PFS (HR = 0.59; 95% CI, 0.39 - 0.90). TSA of OS showed that the cumulative z-score line for the DC vaccine crossed the benefit boundary and reached the required sample size. TSA of PFS and subgroup analysis of newly diagnosed glioblastoma showed that the required sample size was not reached., Conclusions: This updated meta-analysis, which included the first phase III trial of a DC vaccine for glioblastoma, demonstrated that the DC vaccine was associated with improved OS. Moreover, TSA showed that the required sample size was reached, indicating a true-positive result. Future studies are required for patient subgroups with newly diagnosed and recurrent glioblastoma., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Network meta-analysis (NMA) incorporates all available evidence into a general statistical framework for comparing multiple treatments. Standard NMAs make three major assumptions, namely homogeneity, similarity, and consistency, and violating these assumptions threatens an NMA's validity. In this article, we suggest a graphical approach to assessing these assumptions and distinguishing between qualitative and quantitative versions of these assumptions. In our plot, the absolute effect of each treatment arm is plotted against the level of effect modifiers, and the three assumptions of NMA can then be visually evaluated. We use four hypothetical scenarios to show how violating these assumptions can lead to different consequences and difficulties in interpreting an NMA. We present an example of an NMA evaluating steroid use to treat septic shock patients to demonstrate how to use our graphical approach to assess an NMA's assumptions and how this approach can help with interpreting the results. We also show that all three assumptions of NMA can be summarized as an exchangeability assumption. Finally, we discuss how reporting of NMAs can be improved to increase transparency of the analysis and interpretability of the results., (© 2024 The Author(s). Research Synthesis Methods published by John Wiley & Sons Ltd.)

Background: Remimazolam is a novel ultra-short-acting benzodiazepine that has been recently introduced as an alternative to propofol for general anesthesia. While both agents have been compared in terms of safety and efficacy, their relative effects on postoperative quality of recovery (QoR) remain unclear. Therefore, this meta-analysis aimed to compare the effects of remimazolam and propofol on subjective QoR in surgical patients who underwent general anesthesia., Methods: Medline, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched from inception to May 28, 2024 to identify randomized controlled trials comparing remimazolam and propofol in terms of postoperative QoR. The Cochrane risk-of-bias tool (RoB 2) was used to assess study quality. QoR score on postoperative day (POD) 1 (primary outcome), QoR scores on PODs 2-3, QoR dimensions, time to loss of consciousness, other recovery characteristics, and rescue analgesia requirement were evaluated using random-effects meta-analyses., Results: This meta-analysis included 13 studies published between 2022 and 2024 involving 1,418 patients. QoR was evaluated using either the QoR-15 (10 studies) or QoR-40 (3 studies) questionnaire. The pooled results indicated no significant difference in the QoR scores on POD 1 (standardized mean difference: 0.02, 95% confidence interval [CI]: - 0.20, 0.23, P = 0.88, I 2  = 73%) and PODs 2-3 between remimazolam and propofol. Furthermore, no significant differences were observed in QoR dimensions, length of postanesthesia care unit (PACU) stay, and time to extubation as well as in the risks of agitation and postoperative nausea and vomiting. Patients administered remimazolam exhibited slower anesthetic induction (mean difference (MD): 32.27 s) but faster recovery of consciousness (MD: - 1.60 min) than those administered propofol. Moreover, remimazolam was associated with a lower risk of rescue analgesia requirement in the PACU (risk ratio: 0.62, 95% CI: 0.43, 0.89, P = 0.009, I 2  = 0%) but not in the ward., Conclusion: Remimazolam is a potential alternative to propofol for general anesthesia as it offers similar QoR to the latter and has advantages in terms of consciousness recovery and immediate postoperative analgesia requirement., (© 2024. The Author(s).)

As an X-linked inherited lysosomal storage disease that is caused by α-galactosidase A gene variants resulting in progressive accumulation of pathogenic glycosphingolipid (Gb3) accumulation in multiple tissues and organs, Fabry disease (FD) can be classified into classic or late-onset phenotypes. In classic phenotype patients, α-galactosidase A activity is absent or severely reduced, resulting in a more progressive disease course with multi-systemic involvement. Conversely, late-onset phenotype, often with missense variants (e.g., IVS4+919G>A) in Taiwan, may present with a more chronic clinical course with predominant cardiac involvement (cardiac subtype), as they tend to have residual enzyme activity, remaining asymptomatic or clinically silent during childhood and adolescence. In either form, cardiac hypertrophy remains the most common feature of cardiac involvement, potentially leading to myocardial fibrosis, arrhythmias, and heart failure. Diagnosis is established through α-galactosidase enzyme activity assessment or biomarker analyisis (globotriaosylsphingosine, Lyso-Gb3), advanced imaging modalities (echocardiography and cardiac magnetic resonance imaging), and genotyping to differentiate FD from other cardiomyopathy. Successful therapeutic response relies on early recognition and by disease awareness from typical features in classic phenotype and cardiac red flags in cardiac variants for timely therapeutic interventions. Recent advances in pharmacological approach including enzyme replacement therapy (agalsidase alfa or beta), oral chaperone therapy (migalastat), and substrate reduction therapy (venglustat) aim to prevent from irreversible organ damage. Genotype- and gender-based monitoring of treatment effects through biomarker (Lyso-Gb3), renal assessment, and cardiac responses using advanced imaging modalities are key steps to optimizing patient care in FD., Competing Interests: All the authors declare no conflict of interest.

β-Thalassemia is a prevalent type of severe inherited chronic anemia, primarily identified in developing countries. The identification of single nucleotide polymorphisms (SNPs) plays a vital role in the early diagnosis of genetic diseases. Here, we reported the development of an amplification-free fiber optic nanogold-linked sorbent assay method using a fiber optic particle plasmon resonance (FOPPR) biosensor for rapid and ultrasensitive detection of SNPs. Herein, MutS protein was selected as the biorecognition capture probe and immobilized on the sensing region to capture the target mutant DNA, which was hybridized with a single-base mismatched single-stranded DNA labeled by a gold nanoparticle (AuNP). The AuNP acts as a signaling agent to be detected by the FOPPR biosensor when it is bound on the fiber core surface. The method effectively differentiates mismatched double-stranded DNA by MutS protein from perfectly matched/complementary dsDNA. It exhibits an impressively low detection limit for the detection of SNPs at approximately 10 -16 M using low-cost sensor chips and devices. By determination of the ratio of mutant DNA to normal DNA in cell-free genomic DNA from blood samples, this method is promising for diagnosing β-thalassemia in fetuses without invasive testing techniques.

Post-induction hypotension (PIH) is a common and potentially serious complication of general anesthesia. This meta-analysis (Prospero registration number: CRD42024566321) aimed to evaluate the predictive efficacy of the perfusion index (PI) for PIH in patients undergoing general anesthesia. A comprehensive literature search was performed using multiple electronic databases (Google Scholar, EMBASE, Cochrane Library, and MEDLINE). Studies involving adult patients undergoing general anesthesia, with the PI measured before anesthesia induction and reporting PIH incidence, were included. The primary outcome was the diagnostic accuracy of the PI in predicting the probability of PIH. The secondary outcome was the pooled PIH incidence. Eight studies with 678 patients were included. The pooled incidence of PIH was 44.8% (95% confidence interval [CI]: 29.9%-60.8%). The combined sensitivity and specificity of the PI for predicting PIH were 0.84 (95% CI: 0.65-0.94) and 0.82 (95% CI: 0.70-0.90), respectively. The summary receiver operating characteristic (sROC) analysis revealed an area under curve of 0.89 (95% CI: 0.86-0.92). The Deek's funnel plot asymmetry test indicated no significant publication bias. The PI demonstrates high predictive efficacy for PIH in patients undergoing general anesthesia, indicating that it can be a valuable tool for identifying those at risk of PIH.

This study investigated the role of interfacial deformability in bond integrity and strength, particularly in the production of robust joints between harder austenitic stainless steels (SS) during ultrasonic welding. The specimen without the interlayer experienced limited strength enhancement owing to internal cracking from continuous sliding at interfacial temperatures below 0.6 times the melting point (T m ), which is attributed to the limited deformability of the austenitic SS. In contrast, introducing Fe and Ni interlayers between the substrates resulted in a notable increase in the interfacial strength, surpassing 2500 N in the peak load within a reduced welding duration. The correlation between the interfacial strength and the peak temperature suggests that a substantial decrease in hardness below 0.4 T m is sufficient for extensive bond formation. Moreover, dynamic recrystallization (DRX) led to grain refinement in the Fe interlayer owing to shorter weld durations, whereas grain growth was observed in the Ni interlayer due to higher peak temperatures. Both the Fe and Ni interlayers significantly improved the bonding integrity by accommodating plasticity through the above phenomena without severe damage to the substrates, leading to increase of interfacial strength by 24% (2050 N to 2500 N) and reduction of weld duration by 40% (1.5 s in Fe interlayer). In addition, the fracture position after the lap shear test shifted from the edge of the weld area to the SS substrate., (© 2024. The Author(s).)

Objective: This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment., Methods: HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues., Results: ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy., Conclusion: This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions., (© 2024. The Author(s).)

The present systematic review and meta-analysis aimed to compare long-term survival after proximal gastrectomy (PG) and total gastrectomy (TG) for locally advanced proximal gastric cancer (GC). The PubMed, EMBASE and Cochrane CENTRAL databases were searched from their inception to May 2023. Only published two-arm prospective or retrospective studies were included. The selected studies included patients with locally advanced GC who underwent PG or TG and reported quantitative survival outcomes. The primary outcome was overall survival (OS) after gastrectomy. Three studies involving a total of 4,815 patients met the inclusion criteria. The age of the patients ranged from 57.03-64.46 years and 78.80% were male. The estimated 5-year OS probability after TG varied from 30.14 to 72.0%, and from 42.06 to 74.9% after PG. Results of the meta-analyses revealed a significant association between PG and improved OS compared with that of TG, with a pooled hazard ratio of 1.15 (95% CI, 1.05-1.25). No heterogeneity was observed in the included studies (I 2 =0%). Overall, in managing locally advanced GC, PG demonstrated comparable or marginally improved OS compared with TG during postoperative follow-up; however, further meta-analyses are required to provide stronger evidence., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Su et al.)

Purpose: Numerous studies have produced conflicting findings regarding the efficacy of statins in prostate cancer treatment. Our objective was to examine the correlation between statin usage and clinical outcomes in Taiwanese men with de novo metastatic prostate cancer., Materials and Methods: We identified patients diagnosed with de novo metastatic prostate cancer from the Chang Gung Research Database spanning the years 2007 to 2020. To minimize confounding bias, we employed the inverse probability of treatment weighting (IPTW) method. Clinical outcomes were assessed using IPTW-adjusted Kaplan-Meier curves. Multivariate Cox proportional hazard regression analysis was utilized to evaluate the association between mortality and clinical factors., Results: The study cohort comprised 1,716 statin users and 276 non-users. Patients who used statins exhibited a longer median overall survival (85.4 months compared to 58.2 months; p=0.001) and cancer-specific survival (112.6 months compared to 75.7 months; p<0.001) compared to non-users. The median time to the development of castration-resistant status was similar between statin users and non-users (p=0.069). Multivariable Cox proportional hazards regression analysis, after IPTW adjustment, demonstrated that statin use was associated with improved overall survival., Conclusions: Our study indicates that the use of statins following a de novo metastatic prostate cancer diagnosis enhances survival outcomes. However, statins did not appear to delay the onset of castration-resistant status. Further large-scale and long-term studies are warranted to investigate the biological effects of statins in men with prostate cancer., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Objective: This study aimed to assess the impact of preoperative chronic kidney disease (CKD) on the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who underwent standard radical nephroureterectomy (RNU)., Methods: A total of 1172 UTUC patients who received RNU at a single center in Taiwan between February 2005 and August 2019 were included. The patients were categorized into two groups based on their preoperative CKD stage: CKD stage ≤3 (811 patients) and CKD stage >3 (361 patients). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. The study investigated the oncological outcomes, including intravesical recurrence, non-urothelial recurrence, and cancer-specific mortality, stratified by preoperative CKD status., Results: The main findings indicated that UTUC patients with CKD stage >3 in Taiwan exhibited a higher proportion of females (p < 0.001), a greater history of concurrent bladder cancer (p = 0.003), more multifocal tumor behavior (p < 0.001), a higher incidence of carcinoma in situ (p = 0.008), increased rates of intravesical recurrence (p < 0.001), a lower prevalence of smoking history (p = 0.003), lower utilization of adjuvant chemotherapy (p < 0.001), reduced occurrence of non-urothelial recurrence (p < 0.001), and lower cancer-specific mortality (p = 0.006) compared to patients with CKD stage ≤3. Multivariate Cox regression analysis revealed significant differences in intravesical recurrence (p = 0.014) and non-urothelial recurrence (p = 0.006) between the CKD stage >3 and CKD stage ≤3 groups. The study also demonstrated that patients with concurrent bladder cancer and variant histology had higher rates of intravesical recurrence, non-urothelial recurrence, and cancer-specific mortality. The CKD stage >3 group exhibited lower rates of intravesical recurrence (p = 0.0014), higher rates of non-urothelial recurrence (p < 0.0001), and increased cancer-specific mortality (p = 0.0091) compared to the CKD stage ≤3 group in the 5-year free survival analysis., Conclusion: In Taiwan, UTUC patients with CKD stage >3 exhibit distinct characteristics compared to the general population with urothelial carcinoma. They are associated with a non-smoking status, a higher proportion of females, and less aggressive pathological features. Additionally, CKD stage >3 can serve as a clinical indicator for intravesical and non-urothelial recurrence. Further investigation into molecular aspects and treatment modifications for these patients is warranted., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

The chemical screening of an octocoral identifed as Junceella fragilis has led to the isolation of five chlorinated briarane-type diterpenoids, including three known metabolites, gemmacolide X (1), frajunolide I (2), and fragilide F (3), along with two new analogs, 12α-acetoxyfragilide F (4) and 12α-acetoxyjunceellin (5). Single-crystal X-ray diffraction analysis was carried out to determine the absolute configurations of 1 and 2, while the structures of new compounds 4 and 5 were ascertained with 2D NMR experiments. Briaranes 1 and 3-5 were active in enhancing alkaline phosphatase (ALP) activity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: The application of wastewater-based epidemiology to track the outbreak and prevalence of coronavirus disease (COVID-19) in communities has been tested and validated by several researchers across the globe. However, the RNA-based surveillance has its inherent limitations and uncertainties., Objective: This study aims to complement the ongoing wastewater surveillance efforts by analyzing other chemical biomarkers in wastewater to help assess community response (hospitalization and treatment) during the pandemic (2020-2021)., Methods: Wastewater samples (n = 183) were collected from the largest wastewater treatment facility in Suffolk County, NY, USA and analyzed for COVID-19 treatment drugs (remdesivir, chloroquine, and hydroxychloroquine (HCQ)) and their human metabolites. We additionally monitored 26 pharmaceuticals including common over-the-counter (OTC) drugs. Lastly, we developed a Bayesian model that uses viral RNA, COVID-19 treatment drugs, and pharmaceuticals data to predict the confirmed COVID-19 cases within the catchment area., Results: The viral RNA levels in wastewater tracked the actual COVID-19 case numbers well as expected. COVID-19 treatment drugs were detected with varying frequency (9-100%) partly due to their instability in wastewater. We observed a significant correlation (R = 0.30, p < 0.01) between the SARS-CoV-2 genes and desethylhydroxychloroquine (DHCQ, metabolite of HCQ). Remdesivir levels peaked immediately after the Emergency Use Authorization approved by the FDA. Although, 13 out of 26 pharmaceuticals assessed were consistently detected (DF = 100%, n = 111), only acetaminophen was significantly correlated with viral loads, especially when the Omicron variant was dominant. The Bayesian models were capable of reproducing the temporal trend of the confirmed cases., Impact: In this study, for the first time, we measured COVID-19 treatment and pharmaceutical drugs and their metabolites in wastewater to complement ongoing COVID-19 viral RNA surveillance efforts. Our results highlighted that, although the COVID-19 treatment drugs were not very stable in wastewater, their detection matched with usage trends in the community. Acetaminophen, an OTC drug, was significantly correlated with viral loads and confirmed cases, especially when the Omicron variant was dominant. A Bayesian model was developed which could predict COVID-19 cases more accurately when incorporating other drugs data along with viral RNA levels in wastewater., (© 2023. The Author(s).)

Background: The prognostic nutritional index (PNI), integrating nutrition and inflammation markers, has been increasingly recognized as a prognostic predictor in diverse patient cohorts. Recently, its effectiveness as a predictive marker for acute kidney injury (AKI) in various clinical settings has gained attention. This study aims to assess the predictive accuracy of the PNI for AKI in critically ill populations through systematic review and meta-analysis., Methods: A systematic review was conducted using the databases MEDLINE, EMBASE, PubMed, and China National Knowledge Infrastructure up to August 2023. The included trials reported the PNI assessment in adult population with critical illness and its predictive capacity for AKI. Data on study characteristics, subgroup covariates, and diagnostic performance of PNI, including sensitivity, specificity, and event rates, were extracted. A diagnostic test accuracy meta-analysis was performed. Subgroup analyses and meta-regression were utilized to investigate the sources of heterogeneity. The GRADE framework evaluated the confidence in the meta-analysis's evidence., Results: The analysis encompassed 16 studies with 17 separate cohorts, totaling 21,239 patients. The pooled sensitivity and specificity of PNI for AKI prediction were 0.67 (95% CI 0.58-0.74) and 0.74 (95% CI 0.67-0.80), respectively. The pooled positive likelihood ratio was 2.49 (95% CI 1.99-3.11; low certainty), and the negative likelihood ratio was 0.46 (95% CI 0.37-0.56; low certainty). The pooled diagnostic odds ratio was 5.54 (95% CI 3.80-8.07), with an area under curve of summary receiver operating characteristics of 0.76. Subgroup analysis showed that PNI's sensitivity was higher in medical populations than in surgical populations (0.72 vs. 0.55; p < 0.05) and in studies excluding patients with chronic kidney disease (CKD) than in those including them (0.75 vs. 0.56; p < 0.01). Overall, diagnostic performance was superior in the non-chronic kidney disease group., Conclusion: Our study demonstrated that PNI has practical accuracy for predicting the development of AKI in critically ill populations, with superior diagnostic performance observed in medical and non-CKD populations. However, the diagnostic efficacy of the PNI has significant heterogeneity with different cutoff value, indicating the need for further research., (© 2024. The Author(s).)

Objectives: This systematic review and Bayesian network meta-analysis evaluated the efficacy and safety of hydrocortisone combined with fludrocortisone or hydrocortisone alone, compared with placebo in adult patients with septic shock., Data Sources: By extending a prior Cochrane review, databases, including PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov , along with other relevant websites, were searched until August 31, 2023., Study Selection: Randomized controlled trials (RCTs) and observational studies using target trial emulation were included., Data Extraction: The primary outcome was short-term mortality with an emphasis on 28- or 30-day mortality as the main measure and in-hospital or ICU mortality as the nearest surrogate of this measure. Three of the most common adverse events, namely, gastroduodenal bleeding, superinfection, and hyperglycemia, were also considered., Data Synthesis: A total of 19 studies involving 95,841 patients were included. Hydrocortisone plus fludrocortisone showed the lowest short-term mortality versus placebo (odds ratio [OR]: 0.79; 95% credible interval [CrI], 0.64-0.99; number needed to treat [NNT]: 21, range: 12-500; low certainty of evidence) in terms of informative priors. The surface under the cumulative ranking curve values for hydrocortisone plus fludrocortisone, hydrocortisone alone, and placebo were 0.9469, 0.4542, and 0.0989, respectively. Consistent results were observed in RCTs alone and those using a daily 200-mg dose of hydrocortisone. Although gastroduodenal bleeding or superinfection showed no clear increase, hyperglycemia risk increased. The ORs were 0.53 for placebo versus hydrocortisone plus fludrocortisone and 0.64 for placebo versus hydrocortisone alone, with very low certainty of evidence., Conclusions: In adults with septic shock, hydrocortisone plus fludrocortisone improved short-term survival with minimal adverse events compared with hydrocortisone alone or placebo. However, these findings are not definitive due to the limited certainty of evidence and wide NNT range. Additional large-scale, placebo-controlled RCTs are needed to provide conclusive evidence., Competing Interests: Dr. Huang received support for article research from the National Cheng Kung University Hospital, Tainan, Taiwan (NCKUH-11209002). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Purpose: To investigate the prognostic impact of variant histology (VH) on oncological outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) who had undergone radical nephroureterectomy (RNU)., Patients and Methods: A total of 1239 patients with clinically localized UTUC who underwent RNU at a single institution between January 2005 and June 2020 were included. The VH was reviewed by a uro-pathologist at our institution. The Cox regression model was used to perform multivariate analysis, including VH and other established prognostic factors for post-RNU oncological outcomes (intravesical recurrence [IVR], non-urothelial recurrence, and cancer-specific death)., Results: Of the 1239 patients with UTUC, 384 patients (31%) were found to have VH. Advanced tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, open surgery, and renal pelvis had a significantly larger proportion of UTUC with VH compared to pure UTUC (all p < 0.05). VH was an independent prognostic factor associated with less IVR identified by multivariate analysis, more non-urothelial recurrence, and more cancer-specific mortality., Conclusion: Patients with VH account for 31% with UTUC treated with RNU in this cohort. VH was an independent prognostic factor associated with more non-urothelial recurrence and cancer-specific mortality but less IVR., (© 2024 The Japanese Urological Association.)

Introduction: Nerve block success is commonly assessed through a variety of techniques, including testing sensations for temperature over the relevant dermatomes and evaluating pain response (e.g., pin-prick). This meta-analysis aimed to investigate the diagnostic efficacy of Perfusion Index (PI) in identifying failed nerve blocks in patients undergoing upper extremity surgery., Evidence Acquisition: A literature search was conducted using four databases, including Medline (OVID), Google Scholar, EMBASE (OVID), and the Cochrane Database of Systematic Reviews, to identify relevant studies from the inception of the databases until June 2023. The main purpose of this study was to evaluate the diagnostic accuracy of PI values and PI ratios in identifying failed nerve blocks., Evidence Synthesis: Nine studies (published from 2006 to 2022) involving 533 participants (age ranged from 31 to 52 years) were included. The failure rate of nerve blocks ranged from 0% to 18.9%. Pooled results demonstrated promising diagnostic accuracy when using PI values as a predictor of failed nerve block (sensitivity, 77%; specificity, 88.1%; diagnostic odds ratio [DOR], 30.585). Additionally, the analysis of PI ratios as a diagnostic measure showed even higher diagnostic efficacy than using PI values alone, with a sensitivity of 82.9%, specificity of 93.1%, and DOR of 74.543., Conclusions: Our meta-analysis confirmed that the PI values and ratios are promising objective predictors of nerve block failure. The simplicity of these techniques supports their feasibility for routine clinical practice. Further studies focusing on different patient populations, such as pregnant women or the elderly, are needed to validate and expand upon our findings.

In recent years, the automatic machine for microbial identification and antibiotic susceptibility tests has been introduced into the microbiology laboratory of our hospital, but there are still many steps that need manual operation. The purpose of this study was to establish an auto-verification system for bacterial naming to improve the turnaround time (TAT) and reduce the burden on clinical laboratory technologists. After the basic interpretation of the gram staining results of microorganisms, the appearance of strain growth, etc., the 9 rules were formulated by the laboratory technologists specialized in microbiology for auto-verification of bacterial naming. The results showed that among 70,044 reports, the average pass rate of auto-verification was 68.2%, and the reason for the failure of auto-verification was further evaluated. It was found that the main causes reason the inconsistency between identification results and strain appearance rationality, the normal flora in the respiratory tract and urine that was identified, the identification limitation of the mass spectrometer, and so on. The average TAT for the preliminary report of bacterial naming was 35.2 h before, which was reduced to 31.9 h after auto-verification. In summary, after auto-verification, the laboratory could replace nearly 2/3 of manual verification and issuance of reports, reducing the daily workload of medical laboratory technologists by about 2 h. Moreover, the TAT on the preliminary identification report was reduced by 3.3 h on average, which could provide treatment evidence for clinicians in advance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ou, Chang, Chen, Chuang, Tsao, Wu, Kuo, You and Huang.)

Background: Demographics of pulmonary hypertension (PH) has changed a lot over the past forty years. Several recent registries noted an increase in mean age of PH but only a few of them investigated the characteristics of elderly patients. Thus, we aimed to analyze the characteristics of PH in such a population in this study., Methods: This multicenter study enrolled patients diagnosed with PH in group 1, 3, 4, and 5 consecutively from January 1, 2019 to December 31, 2020. A total of 490 patients was included, and patients were divided into three groups by age (≤45 years, 45-65 years, and >65 years)., Results: The mean age of PH patients diagnosed with PH was 55.3 ± 16.3 years of age. There was higher proportion of elderly patients classified as group 3 PH (≤45: 1.3, 45-65: 4.5, >65: 8.1 %; p  = 0.0206) and group 4 PH (≤45: 8.4, 45-65: 14.5, >65: 31.6 %; p  < 0.0001) than young patients. Elderly patients had shorter 6-min walking distance (6 MWD) (≤45 vs. >65, mean difference, 77.8 m [95% confidence interval (CI), 2.1-153.6 m]), lower mean pulmonary arterial pressure (mPAP) (≤45 vs. >65, mean difference, 10.8 mmHg [95% CI, 6.37-15.2 mmHg]), and higher pulmonary arterial wedge pressure (PAWP) (≤45 vs. 45-65, mean difference, -2.1 mmHg [95% CI, -3.9 to -0.3 mmHg]) compared to young patients. Elderly patients had a poorer exercise capacity despite lower mPAP level compared to young population, but they received combination therapy less frequently compared to young patients (triple therapy in group 1 PH, ≤45: 16.7, 45-65: 11.3, >65: 3.8 %; p  = 0.0005). Age older than 65 years was an independent predictor of high mortality for PH patients., Conclusions: Elderly PH patients possess unique hemodynamic profiles and epidemiologic patterns. They had higher PAWP, lower mPAP, and received combination therapy less frequently. Moreover, ageing is a predictor of high mortality for PH patients. Exercise capacity-hemodynamics mismatch and inadequate treatment are noteworthy in the approach of elderly population with PH., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Competing Interests: Declaration of competing interest Ensuring the utmost transparency, the Task Force implements a strict conflict-of-interest review process for clinical practice guidelines development. Prior to and during guideline development, Task Force members were required to disclose any potential conflicts of interest, which the TSA scrutinized to ensure the integrity of the Task Force members. In the development of the guideline, the majority of participants must be individuals without conflicts of interest related to the matter under study.

The prevalence of patients with primary aldosteronism (PA) is about 5%-15% in hypertensive patients, and it is common cause of secondary hypertension in clinical practice. Two major causes of PA are noted, namely bilateral adrenal hyperplasia and aldosterone-producing adenoma, and the general diagnosis is based on three steps: (1) screening, (2) confirmatory testing, and (3) subtype differentiation (Figure 1). The recommendation for screening patients is at an increased risk of PA, here we focus on which patients should be screened for PA, not only according to well-established guidelines but for potential patients with PA. We recommend screening for 1) patients with resistant or persistent hypertension, 2) hypertensive patients with hypokalemia (spontaneous or drug-induced), 3) young hypertensive patients (age <40 years), and 4) all hypertensive patients with a history of PA in first-degree relatives. Moreover, we suggest screening for 1) hypertensive patients themselves or first-degree relatives with early target organ damage, such as stroke and other diseases, 2) all hypertensive patients with a concurrent adrenal incidentaloma, 3) hypertensive patients with obstructive sleep apnea, 4) hypertensive patients with atrial fibrillation unexplained by structural heart defects and/or other conditions resulting in the arrhythmia, 5) hypertensive patients with anxiety and other psychosomatic symptoms, and 6) hypertensive patients without other comorbidities to maintain cost-effectiveness., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Anti-hypertensive medications may affect plasma renin activity and/or plasma aldosterone concentration, misleading the interpretation of the aldosterone-to-renin ratio when screening for primary aldosteronism. The Task Force of Taiwan PA recommends that, when necessary, using α-adrenergic receptor blocking agents, centrally acting α-adrenergic agonists, and/or non-dihydropyridine calcium channel blockers should be considered to control blood pressure before screening for PA. We recommend temporarily holding β-adrenergic receptor blocking agents, mineralocorticoid receptor antagonists, dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and all diuretics before screening for PA. Further large-scale randomized controlled studies are required to confirm the recommendations., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Purpose: There is a growing interest in performing coronary artery and neurovascular interventions via the radial artery; however, few studies have examined the outcomes of transradial carotid stenting. Therefore, our study aimed to compare cerebrovascular outcomes and crossover rates in carotid stenting between transradial and traditional transfemoral approaches., Methods: A systematic review was performed by searching three electronic databases from inception to June 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In addition, random effect meta-analysis was used to pool the odds ratios (ORs) for stroke, transient ischemic attack, major adverse cardiac events, death, major vascular access site complications, and procedure crossover rates between the transradial and transfemoral approaches., Results: A total of 6 studies were included involving a total of n = 567 transradial and n = 6176 transfemoral procedures. The ORs for stroke, transient ischemic attack, and major adverse cardiac events were 1.43 (95% confidence interval, CI 0.72-2.86, I 2  = 0), 0.51 (95% CI 0.17-1.54, I 2  = 0), and 1.08 (95% CI 0.62-1.86, I 2  = 0), respectively. Neither the major vascular access site complication rate (OR 1.11, 95% CI 0.32-3.87, I 2  = 0) nor crossover rate (OR 3.94, 95% CI 0.62-25.11, I 2  = 57%) showed statistically significant differences between the two approaches., Conclusion: The modest quality of the data suggested comparable procedural outcomes between the transradial and transfemoral approaches when performing carotid stenting; however, high level evidence regarding postoperative brain images and risk of stroke in transradial carotid stenting are lacking. Therefore, it is reasonable for interventionists to weigh up the risks of neurological events and potential benefits, including fewer access site complications, before choosing the radial or femoral arteries as access sites. Future large-scale randomized controlled trials are imperative., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: This meta-analysis aimed to evaluate the efficacy and safety of electroacupuncture (EA) in improving postoperative ileus after colorectal surgery., Methods: Electronic databases (e.g. Medline) were screened to identify randomized controlled trials that focused on the association between EA and postoperative ileus. Time to first flatus served as the primary outcome, while the secondary outcomes included time required for the recovery of other gastrointestinal functions (e.g. bowel sound recovery), time to tolerability of liquid/solid food, postoperative pain scores, risk of overall complications, and hospital length of stay., Results: Our meta-analysis focusing on 16 studies with a total of 1562 patients demonstrated positive associations of EA with shorter times to the first flatus [mean difference (MD): -10.1 h, P <0.00001, n =1562], first defecation (MD: -11.77 h, P <0.00001, n =1231), bowel sound recovery (MD: -10.76 h, P <0.00001, n =670), tolerability of liquid (MD: -16.44 h, P =0.0002, n =243), and solid food (MD: -17.21 h, P =0.005, n =582) than those who received standard care. The use of EA was also correlated with a lower risk of overall complications (risk ratio:0.71, P =0.04, n =1011), shorter hospital length of stay (MD: -1.22 days, P =0.0001, n =988), and a lower pain score on postoperative days two (standardized MD: -0.87, P =0.009, n =665) and three (standardized MD: -0.45, P <0.00001, n =795), without a difference in time to first ambulation., Conclusion: Our findings showed an association between EA and enhanced gastrointestinal functional recovery and reduced pain severity following colorectal surgery, highlighting the potential benefits of incorporating EA into perioperative care to enhance recovery outcomes in this setting., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Selective detection of biomarkers at low concentrations in blood is crucial for the clinical diagnosis of many diseases but remains challenging. In this work, we aimed to develop an ultrasensitive immunoassay that can detect biomarkers in serum with an attomolar limit of detection (LOD). We proposed a sandwich-type heterogeneous immunosensor in a 3 × 3 well array format by integrating a resonant waveguide grating (RWG) substrate with upconversion nanoparticles (UCNPs). UCNPs were used to label a target biomarker captured by capture antibody molecules immobilized on the surface of the RWG substrate, and the RWG substrate was used to enhance the upconversion luminescence (UCL) of UCNPs through excitation resonance. The LOD of the immunosensor was greatly reduced due to the increased UCL of UCNPs and the reduction of nonspecific adsorption of detection antibody-conjugated UCNPs on the RWG substrate surface by coating the RWG substrate surface with a carboxymethyl dextran layer. The immunosensor exhibited an extremely low LOD [0.24 fg/mL (9.1 aM)] and wide detection range (1 fg/mL to 100 pg/mL) in the detection of cardiac troponin I (cTnI). The cTnI concentrations in human serum samples collected at different times during cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) chemotherapy in a breast cancer patient were measured by an immunosensor, and the results showed that the CEF chemotherapy did cause cardiotoxicity in the patient. Having a higher number of wells in such an array-based biosensor, the sensor can be developed as a high-throughput diagnostic tool for clinically important biomarkers.

Objectives: This study aimed to conduct a comprehensive and updated systematic review with network meta-analysis (NMA) to assess the outcome benefits of various blood purification modalities for adult patients with severe infection or sepsis., Data Sources: We conducted a search of PubMed, MEDLINE, clinical trial registries, Cochrane Library, and Embase databases with no language restrictions., Study Selection: Only randomized controlled trials (RCTs) were selected., Data Extraction: The primary outcome was overall mortality. The secondary outcomes were the length of mechanical ventilation (MV) days and ICU stay, incidence of acute kidney injury (AKI), and kidney replacement therapy requirement., Data Synthesis: We included a total of 60 RCTs with 4,595 participants, comparing 16 blood purification modalities with 17 interventions. Polymyxin-B hemoperfusion (relative risk [RR]: 0.70; 95% CI, 0.57-0.86) and plasma exchange (RR: 0.61; 95% CI, 0.42-0.91) were associated with low mortality (very low and low certainty of evidence, respectively). Because of the presence of high clinical heterogeneity and intransitivity, the potential benefit of polymyxin-B hemoperfusion remained inconclusive. The analysis of secondary outcomes was limited by the scarcity of available studies. HA330 with high-volume continuous venovenous hemofiltration (CVVH), HA330, and standard-volume CVVH were associated with shorter ICU stay. HA330 with high-volume CVVH, HA330, and standard-volume CVVH were beneficial in reducing MV days. None of the interventions showed a significant reduction in the incidence of AKI or the need for kidney replacement therapy., Conclusions: Our NMA suggests that plasma exchange and polymyxin-B hemoperfusion may provide potential benefits for adult patients with severe infection or sepsis/septic shock when compared with standard care alone, but most comparisons were based on low or very low certainty evidence. The therapeutic effect of polymyxin-B hemoperfusion remains uncertain. Further RCTs are required to identify the specific patient population that may benefit from extracorporeal blood purification., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Introduction: Contrast-induced nephropathy (CIN) is a common complication of percutaneous coronary intervention (PCI). Identifying patients at high CIN risk remains challenging. The triglyceride-glucose (TyG) index may help predict CIN but evidence is limited. We conducted a meta-analysis to evaluate the diagnostic value of TyG index for CIN after PCI., Methods: A systematic literature search was performed in MEDLINE, Cochrane, and EMBASE until August 2023 (PROSPERO registration: CRD42023452257). Observational studies examining TyG index for predicting CIN risk in PCI patients were included. This diagnostic meta-analysis aimed to evaluate the accuracy of the TyG index in predicting the likelihood of CIN. Secondary outcomes aimed to assess the pooled incidence of CIN and the association between an elevated TyG index and the risk of CIN., Results: Five studies (Turkey, n=2; China, n=3) with 3518 patients (age range: 57.6 to 68.22 years) were included. The pooled incidence of CIN was 15.3% [95% confidence interval (CI) 11-20.8%]. A high TyG index associated with increased CIN risk (odds ratio: 2.25, 95% CI 1.82-2.77). Pooled sensitivity and specificity were 0.77 (95% CI 0.59-0.88) and 0.55 (95% CI 0.43-0.68) respectively. Analysis of the summary receiver operating characteristic (sROC) curve revealed an area under the curve of 0.69 (95% CI 0.65-0.73). There was a low risk of publication bias (p = 0.81)., Conclusion: The TyG index displayed a noteworthy correlation with the risk of CIN subsequent to PCI. However, its overall diagnostic accuracy was found to be moderate in nature. While promising, the TyG index should not be used in isolation for CIN screening given the heterogeneity between studies. In addition, the findings cannot be considered conclusive given the scarcity of data. Further large-scale studies are warranted to validate TyG cutoffs and determine how to optimally incorporate it into current risk prediction models., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42023452257, identifier CRD42023452257., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chang, Liu, Huang, Wu, Tsai, Hung, Chen and Feng.)

Background: Intubation is an essential procedure in cardiopulmonary resuscitation (CPR). We conducted a systematic review and meta-analysis of trials and studies comparing the performance of video laryngoscope (VL) and direct laryngoscope (DL) in endotracheal intubation (ETI) during CPR in cardiac arrest (OHCA) patients., Methods: We searched the PUBMED, EMBASE, and Cochrane library databases. We analyzed the first-pass success rate, total intubation time, Cormack-Lehane grade (CL grade), esophageal intubation rate, and dental injury rate among the in-hospital cardiac arrest (IHCA) patients or out-of-hospital cardiac arrest (OHCA) patients. We demonstrated the pooled results of continuous outcomes by mean difference (MD) and dichotomous outcomes by odds ratio (OR), with a 95% confidence interval (CI) using a random-effects model., Results: We obtained six observational studies and one randomized control trial. The pooled results showed a significant increase in first-pass success rate (OR: 1.86, 95% CI: 1.41, 2.47), Cormack-Lehane (CL) grade (OR: 2.01, 95% CI: 1.59,2.53), and a decrease of esophageal intubation rate (OR: 0.25, 95% CI: 0.08, 0.85) in the VL group compared with DL group. Also, a non-significant decrease in dental injury rate [OR: 0.23, 95% CI: 0.05, 1.08) was observed in the VL group compared with the DL group. There was no statistical difference between the VL and DL groups, although the VL group seemed to have a shorter total intubation time (MD: -15.43, 95% CI: -34.67, 3.81). Types of laryngoscopes were not associated with the rate of ROSC [OR 1.01 (0.95,1.07); P = 0.83]. No differences in survival outcomes were observed between the two approaches., Conclusions: Compared to DL, VL was found to be associated with first-pass success and CL grade. We recommend prioritizing VL over DL when performing ETIs for patients with cardiac arrest., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Various approaches have been suggested to identify acute kidney injury (AKI) early and to initiate kidney-protective measures in patients at risk or with AKI. The objective of this study was to evaluate whether care bundles improve kidney outcomes in these patients., Methods: We conducted a systematic review of the literature to evaluate the clinical effectiveness of AKI care bundles with or without urinary biomarkers in the recognition and management of AKI. The main outcomes were major adverse kidney events (MAKEs) consisting of moderate-severe AKI, receipt of renal replacement therapy (RRT), and mortality., Results: Out of 7434 abstracts screened, 946 published studies were identified. Thirteen studies [five randomized controlled trials (RCTs) and eight non-RCTs] including 16,540 patients were eligible for inclusion in the meta-analysis. Meta-analysis showed a lower incidence of MAKE in the AKI care bundle group [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.66-0.81] with differences in all 3 individual outcomes [moderate-severe AKI (OR 0.65, 95% CI 0.51-0.82), RRT (OR 0.63, 95% CI = 0.46-0.88) and mortality]. Subgroup analysis of the RCTs, all adopted biomarker-based approach, decreased the risk of MAKE (OR 0.55, 95% CI 0.41-0.74). Network meta-analysis could reveal that the incorporation of biomarkers in care bundles carried a significantly lower risk of MAKE when compared to care bundles without biomarkers (OR = 0.693, 95% CI = 0.50-0.96), while the usual care subgroup had a significantly higher risk (OR = 1.29, 95% CI = 1.09-1.52)., Conclusion: Our meta-analysis demonstrated that care bundles decreased the risk of MAKE, moderate-severe AKI and need for RRT in AKI patients. Moreover, the inclusion of biomarkers in care bundles had a greater impact than care bundles without biomarkers., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background/purpose: Improved communication can optimize treatment outcomes and patient satisfaction. Findings emphasize the need for tailored communication strategies based on patient characteristics. Implementing communication courses can enhance patient-centered care and reduce conflicts. Therefore, this study examined the feasibility of integrating doctor-patient communication education in Taiwan's dental education system., Materials and Methods: Using interviews and questionnaires, we conducted descriptive statistics and generalized linear mixed-effects model analysis on the importance of doctor-patient communication from the dentist and patient perspectives., Results: More than 600 patient surveys and four interviewed dentists with 20+ years of experience stressed doctor-patient communication in dentistry. Patients' age and income were positively related to the emphasis on physician-patient communication but negatively associated with dental assistants' communication. Dentists valued communication education but differed in its execution and importance., Conclusion: It is recommended to initiate dentist-patient communication education during university studies and continue its practice to adapt to the changing societal dynamics. Individuals with higher socioeconomic status and older age show a greater appreciation for dentist-patient communication, potentially driven by self-promotion, thereby highlighting the diverse nature of doctor-patient relationships. Based on our findings, we suggest to implement the doctor-patient communication courses in Taiwan., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)