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Background: Recently, there have been conflicting results reporting an increased risk of AR or MR associated with oral fluoroquinolones (FQs).This study investigated whether the use of FQs increases the risk of mitral regurgitation (MR) or aortic regurgitation (AR)., Methods: A retrospective cohort study was conducted by using the Taiwan National Health Insurance research database. A unidirectional case-crossover design without selecting controls from an external population was adopted in this study. A total of 26,650 adult patients with new onset of AR or MR between January 1, 2000, and December 31, 2012, were identified. The risk of outcomes was compared between the hazard period and one of the randomly selected referent periods of the same individuals., Results: Before exclusion of pneumonia diagnosed within 2 months before the index date, patients who took FQs had a significantly greater risk of AR or MR (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.30-1.77), any AR (combined AR and MR) (aOR 1.50, 95% CI 1.10-2.04), and any MR (combined AR and MR) (aOR 1.37, 95% CI 1.16-1.62). After exclusion of pneumonia, FQs exposure remained significantly associated with a greater risk of MR (aOR 1.38, 95% CI 1.17-1.62) and any MR (aOR 1.25, 95% CI 1.05-1.48)., Conclusions: The findings suggested that patients treated with FQs could be warned about the potential risk for MR even after considering the possibility of protopathic bias. Reducing unnecessary FQs prescriptions may be considered to reduce the risk of valvular heart disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The choice of an artificial mitral valve (MV) is a crucial clinical decision that affects the long-term survival and quality of life of patients. However, current guidelines recommend selecting MV based on patient age and life expectancy at the time of mitral valve replacement (MVR), without considering the etiology of MV disease. This study aimed to investigate whether MV disease etiology should be considered when choosing a valve for MVR and to evaluate the impact of MV disease etiology on long-term patient survival., Methods: Using data (2002-2018) from Taiwan's National Health Insurance Research Database, the authors conducted a nationwide retrospective cohort study to compare the biological and mechanical valves in terms of all-cause mortality as the primary outcome. The inverse probability of the treatment weighting method was used to reduce the effects of the confounding factors. The following etiologies were assessed: infective endocarditis, rheumatic heart disease, ischemic mitral regurgitation, and degenerative mitral regurgitation., Results: In patients aged below 70 years, it was observed that mechanical valves demonstrated an association with benefits compared to biological valves in the context of survival. In patients with infective endocarditis aged below 72 years, mechanical valves were associated with survival benefits, but not in those with stroke during hospitalization. These valves were also found to be linked with survival advantages for patients with rheumatic heart disease aged below 60 years and for those with degenerative mitral regurgitation aged below 72 years. However, no age-dependent effects of valve type on all-cause mortality were observed in patients with ischemic mitral regurgitation., Conclusion: The etiology of MV disease appears to be important in the selection of a suitable MV and determination of a cutoff age for mechanical and biological MVR., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), are characterized by uncontrolled inflammatory responses, neutrophil activation and infiltration, damage to the alveolar capillary membrane, and diffuse alveolar injury. Neutrophil extracellular traps (NETs), formed by activated neutrophils, contribute significantly to various inflammatory disorders and can lead to tissue damage and organ dysfunction. Corilagin, a compound found in Phyllanthus urinaria, possesses antioxidative and anti-inflammatory properties. In this study, we investigated the protective effects and underlying mechanisms of corilagin in hydrochloric acid (HCl)/lipopolysaccharide (LPS)-induced lung injury. Mice received intraperitoneal administration of corilagin (2.5, 5, or 10 mg/kg) or an equal volume of saline 30 min after intratracheal HCl/LPS administration. After 20 h, lung tissues were collected for analysis. Corilagin treatment significantly mitigated lung injury, as evidenced by reduced inflammatory cell infiltration, decreased production of proinflammatory cytokines, and alleviated oxidative stress. Furthermore, corilagin treatment suppressed neutrophil elastase expression, reduced NET formation, and inhibited the expression of ERK, p38, AKT, STAT3, and NOX2. Our findings suggest that corilagin inhibits NET formation and protects against HCl/LPS-induced ALI in mice by modulating the STAT3 and NOX2 signaling pathways.

Background: Mitral valve (MV) disease is the most common form of valvular heart disease. Findings that indicate women have a higher risk for unfavorable outcomes than men remain controversial. This study aimed to determine the sex-based differences in epidemiological distributions and outcomes of surgery for MV disease., Methods and results: Overall, 18,572 patients (45.3% women) who underwent MV surgery between 2001 and 2018 were included. Outcomes included in-hospital death and all-cause mortality during follow up. Subgroup analysis was conducted across different etiologies, including infective endocarditis (IE), degenerative, ischemic, and rheumatic mitral pathology. The overall MV repair rate was lower in women than in men (20.5% vs. 30.6%). After matching, 6,362 pairs (woman : man=1 : 1) of patients were analyzed. Women had a slightly higher risk for in-hospital death than men (10.8% vs. 9.8%; odds ratio [OR]: 1.11, 95% confidence interval [CI]: 0.99-1.24; P=0.075). Women tended to have a higher incidence of de novo dialysis (9.8% vs. 8.6%; P=0.022) and longer intensive care unit stay (8 days vs. 7.1 days; P<0.001). Women with IE had poorer in-hospital outcomes than men; however, there were no sex differences in terms of all-cause mortality., Conclusions: Sex-based differences of MV intervention still persist. Although long-term outcomes were comparable between sexes, women, especially those with IE, had worse perioperative outcomes than men.

In 2023, the National Science Foundation (NSF) and the National Institute of Health (NIH) brought together engineers, scientists, and clinicians by sponsoring a conference on computational modelling in neurorehabiilitation. To facilitate multidisciplinary collaborations and improve patient care, in this perspective piece we identify where and how computational modelling can support neurorehabilitation. To address the where, we developed a patient-in-the-loop framework that uses multiple and/or continual measurements to update diagnostic and treatment model parameters, treatment type, and treatment prescription, with the goal of maximizing clinically-relevant functional outcomes. This patient-in-the-loop framework has several key features: (i) it includes diagnostic and treatment models, (ii) it is clinically-grounded with the International Classification of Functioning, Disability and Health (ICF) and patient involvement, (iii) it uses multiple or continual data measurements over time, and (iv) it is applicable to a range of neurological and neurodevelopmental conditions. To address the how, we identify state-of-the-art and highlight promising avenues of future research across the realms of sensorimotor adaptation, neuroplasticity, musculoskeletal, and sensory & pain computational modelling. We also discuss both the importance of and how to perform model validation, as well as challenges to overcome when implementing computational models within a clinical setting. The patient-in-the-loop approach offers a unifying framework to guide multidisciplinary collaboration between computational and clinical stakeholders in the field of neurorehabilitation., (© 2024. The Author(s).)

Recent experimental studies have highlighted the beneficial effects of curcumin on liver injury induced by acetaminophen (APAP). However, the specific molecular mechanisms underlying curcumin's hepatoprotective effects against APAP-induced liver injury remain to be fully elucidated. This study aimed to investigate the therapeutic effect of curcumin on APAP-induced liver injury using a mouse model. In the experiment, mice were subjected to an intraperitoneal hepatotoxic dose of APAP (300 mg/kg) to induce hepatotoxicity. After 30 min of APAP administration, the mice were treated with different concentrations of curcumin (0, 10, 25, or 50 mg/kg). After 16 h, mice with hepatotoxicity showed elevated levels of serum alanine transaminase (ALT), aspartate transaminase (AST), hepatic myeloperoxidase (MPO), TNF-α, and IL-6, and decreased levels of glutathione (GSH). Moreover, there was an increased infiltration of neutrophils and macrophages following intraperitoneal injection of APAP. However, curcumin-treated mice displayed a pronounced reduction in serum ALT, AST, hepatic MPO, TNF-α, and IL-6 levels, coupled with a notable elevation in GSH levels compared to the APAP-treated hepatotoxic mice. Moreover, curcumin treatment led to reduced infiltration of neutrophils and macrophages. Additionally, curcumin inhibited the phosphorylation of ERK and NF-kB proteins while reducing the expression of cyclooxygenase-2 (COX-2). These findings highlight the hepatoprotective potential of curcumin against APAP-induced liver injury through the suppression of the ERK, NF-kB, and COX-2 signaling pathways.

Background: Biologic prostheses are being increasingly used for aortic and mitral valve replacement (AVR and MVR). This study evaluated the long-term durability of bioprosthetic valves in the mitral and aortic positions, as no well-designed population-based studies have addressed this issue before., Methods: Using Taiwan's National Health Insurance Research Database, we compared biologic valve durability in the mitral and aortic positions in patients hospitalized between 2001 and 2017, with reoperation as the primary outcome. Both between-subject and within-subject designs were used, and the propensity score matching cohort (1:1 ratio) was created for the former., Results: We identified a total of 10,308 patients, 5462 of whom received AVR, 3901 received MVR, and 945 received double valve replacement. Both AVR and MVR cohorts had 2259 patients after matching. During a mean follow-up of 4.2 years (range, 1 day to 17.9 years), the reoperation rate in the MVR cohort (3.5%) was higher than that in the AVR cohort (2.6%) (hazard ratio 1.41; 95% CI, 1.01-1.98). A higher risk of all-cause death was observed in the MVR cohort (36.5%) than in the AVR cohort (32.6%) (hazard ratio 1.21; 95% CI, 1.10-1.34). Among patients receiving double valve replacement with the same prosthesis type, valves implanted in the aortic position were considerably less likely to require reimplantation., Conclusions: Bioprosthetic valve placement in the aortic position is associated with superior outcomes in terms of durability, long-term mortality, and perioperative morbidity. Developing novel interventions and enhancing valve durability would expand bioprosthesis use for valve replacement., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The sutureless valve has gained popularity for degenerative aortic valve stenosis but not congenital bicuspid aortic valve (BAV) due to anatomical challenges. We reviewed our modified implant techniques for patients with BAV., Methods: From June 2015 to June 2019, 66 patients with aortic valve stenosis were treated with the Perceval sutureless valve, 20 of whom had BAV. The demographics, type of BAV (the Sievers classification), and associated pathologies, surgical outcomes, and midterm hemodynamics were recorded., Results: The median age was 64 (range: 49-81) years and the Society of Thoracic Surgeons score was 2.186 (range: 0.407-6.384). Annular plication was performed in 9 (75%) of 12 type 0 and 3 (37.5%) of 8 type I, with implanted valve sizes of M, L, and XL in 6, 10, 4 cases, respectively. Three patients, all type 0 in the initial learning periods, required intraoperative redeployment due to malposition of the valve. The final implant was successful in all without conversion to traditional prosthesis. The median extubation time was 4 hours and the durations of intensive care unit and hospital stay were 1 and 6 days. At a median follow-up of 46 (23-72) months, there was one late mortality due to hemorrhagic stroke sequel. The last echo revealed none had more than mild paravalvular leakage and the mean transvalvular pressure gradient remained stable at 9.70 (range: 6.94-15.0) mm Hg., Conclusion: The sutureless valve can achieve satisfactory outcomes in BAV without paravalvular leakage and excellent hemodynamics. It may serve as the benchmark for transcatheter aortic valve implantation in this unique population., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Fluoroquinolone use can be associated with an increased risk of aortic aneurysm (AA) or aortic dissection (AD). The US Food and Drug Administration recently warned against fluoroquinolone use for high-risk patients, such as those with Marfan syndrome. However, the association between fluoroquinolone use and AA/AD risk was unknown in these high-risk patients and therefore it was studied in this work., Methods and results: Data were collected from a national database between 2000 and 2017 for 550 patients with AA/AD and any congenital aortic disease (mean age 41.5 years; 415 with Marfan syndrome). A case cross-over study was conducted to compare the risk of aortic events (AA/AD) associated with fluoroquinolone and amoxicillin use between the hazard period (from -60 days to -1 day) and a randomly selected reference period (-180 to -121 days; -240 to -181 days; and -300 to -241 days). Compared to the reference period without fluoroquinolone use, fluoroquinolone use during the hazard period was not associated with a greater risk of AA/AD (1.09% vs. 1.09%; odds ratio [OR] 1.000; 95% confidence interval [CI] 0.32-3.10), AA (OR 0.67; 95% CI 0.11-3.99), or AD (OR 1.33; 95% CI 0.30-5.96) in patients with congenital aortic disease or Marfan syndrome. This lack of association was maintained in subgroup analysis, including Marfan syndrome or not, age (≤50 vs. >50 years) and sex., Conclusions: Fluoroquinolone use was not associated with an increased risk of AA/AD in patients with congenital aortic disease, including Marfan syndrome. More evidence is required for a fluoroquinolone pharmacovigilance plan in these patients.

Background: The long-term outcomes of surgical ablation for atrial fibrillation (AF) during cardiac surgery remain unclear., Methods: This nationwide population-based retrospective cohort study used data from Taiwan's National Health Insurance Research Database. Overall, 11,459 patients undergoing coronary artery bypass graft, valve, or aortic surgery and diagnosed as having AF between January 1, 2001, and December 31, 2016, were included. To reduce possible selection bias, we created a propensity score-matched cohort and compared outcomes between groups. The outcomes of interest were long-term survival and late ischemic stroke., Results: The surgical ablation group had a significantly lower risk of all-cause mortality (5.74 and 7.69 events per 100 patient-years, respectively; hazard ratio, 0.75; 95% CI, 0.69-0.81) and ischemic stroke after discharge (1.88 and 2.52 events per 100 patient-years, respectively; subdistribution hazard ratio, 0.78; 95% CI, 0.67-0.91). AF ablation performed concomitantly with coronary artery bypass graft surgery, tissue aortic valve replacement, tissue mitral valve replacement, or mitral valve repair led to significantly better long-term survival (P = .0176, P = .0001, P < .0001, P < .0001, respectively). The surgical ablation group also had better long-term survival than the matched general AF population (log-rank test, P < .001)., Conclusions: Concomitant AF ablation during cardiac surgery is safe, does not increase the rate of perioperative complications, and confers the benefit of long-term survival after cardiac surgery in adults. AF ablation also improved cardiac surgery patients' long-term survival compared with the matched general AF population., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Opioids provide good analgesic effect in burn patients during acute phase, but these patients may develop tolerance after prolonged exposure. Alternative analgesic strategies such as peripheral nerve blocks appear to provide adequate pain control while sparing opioid-related side effects. The purpose of this study was to evaluate intravenous patient-controlled analgesia (IV-PCA) and continuous peripheral nerve block (CPNB-PCA) in severe burn patients with relatively young age undergoing repeated debridement and large-area full thickness skin graft (FTSG)., Methods: The records of victims in dust explosion in Taiwan in 2016 from Chang Gung Memorial Hospital Pain Service Database between 2016 June and 2017 December were evaluated. The patients' demographic data including age, gender, weight, burn area, degree of burn, type of PCA regimen (IV-PCA versus CPNB-PCA), size of FTSG, and adverse effects were collected., Results: The total in-hospital morphine consumption was significantly lower in CPNB-PCA than IV-PCA group. A trend of decrease in numerical rating scores (NRS) was observed for both groups and CPNB group had comparable NRS than IV-PCA group at rest. On movement, CPNB grouped had significantly lower NRS than IV-PCA on post-operative day 3., Conclusion: Our study demonstrated that in patients requiring high dosage of opioid, CPNB may be a suitable alternative for pain control.

Preoperative renal dysfunction is associated with mortality in patients with acute type A aortic dissection (ATAAD) repair. However, the long-term outcome of chronic kidney dysfunction (CKD) in ATAAD is unclear. The study aimed to evaluate the long-term outcome of CKD in patients with ATAAD repair. We retrospectively studied patients with ATAAD repair using data from the Taiwan's National Health Insurance Research Database between July 1, 2004, and December 31, 2013. The outcomes of interest included all-cause mortality, readmission due to any cause, redo aortic surgery, major adverse cardiac and cerebrovascular events, and liver and renal outcomes. There were 3328 patients who received ATAAD repair. These patients were divided into CKD and non-CKD groups. In-hospital mortality in the CKD group was significantly higher than that in the non-CKD group (32.5% vs 18.8%, respectively, odds ratio 2.14, 95% confidence interval [CI] 1.37-3.36). During long-term follow-up, patients with CKD had higher risks of all-cause mortality including in-hospital death (52.6% vs 32.5%; hazard ratio 1.83, 95% CI 1.32-2.55), mortality after discharge (29.7% vs 16.8%; hazard ratio 2.09, 95% CI 1.02-4.29), and readmission rates (67.1% vs 51.6%; subdistribution hazard ratio 2.00, 95% CI 1.43-2.79). However, no significant difference was observed between the dialysis and non-dialysis groups. On the basis of our results, patients with CKD carry a poor long-term outcome after ATAAD repair. Cardiac surgeons should be aware of this condition when dealing with ATAAD repair., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Hemodynamic stability is important during neurointerventional procedures. However, ICP or blood pressure may increase due to endotracheal extubation. The aim of this study was to compare the hemodynamic effects of sugammadex and neostigmine with atropine in neurointerventional procedures during emergence from anesthesia., Methods: Patients undergoing neurointerventional procedures were allocated to the sugammadex group (Group S) and the neostigmine group (Group N). Group S was administered IV 2 mg/kg sugammadex when a train-of-four (TOF) count of 2 was present, and Group N was administered neostigmine 50 mcg/kg with atropine 0.2 mg/kg at a TOF count of 2. We recorded heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure (MAP), and peripheral arterial oxygen saturation during administration of the reverse agent and at 2, 5, 10, 15, 30, 120 min, and 24 h thereafter. The primary outcome was blood pressure and heart rate change after the reversal agent was given. The secondary outcomes were systolic blood pressure variability standard deviation (a measure of the amount of variation or dispersion of a set of values), systolic blood pressure variability-successive variation (square root of the average squared difference between successive blood pressure measurements), nicardipine use, time-to-TOF ratio ≥0.9 after the administration of reversal agent, and time from the administration of the reversal agent to tracheal extubation., Results: A total of 31 patients were randomized to sugammadex, and 30 patients were randomized to neostigmine. Except for anesthesia time, there were no significant differences in any of the clinical characteristics between the two groups. The results demonstrated that the increase in MAP from period A to B was significantly greater in Group N than in Group S (regression coefficient = -10, 95% confidence interval = -17.3 to -2.7, P = 0.007). The MAP level was significantly increased from period A to B in the neostigmine group (95.1 vs. 102.4 mm Hg, P = 0.015), but it was not altered in Group S. In contrast, the change in HR from periods A to B was not significantly different between groups., Conclusion: We suggest that sugammadex is a better option than neostigmine in interventional neuroradiological procedures due to the shorter extubation time and more stable hemodynamic change during emergence., 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 Tsai, Chen, Wong and Chou.)

Purpose: This prospective study investigated the preventive effect of transcutaneous electrical nerve stimulation (TENS) for postoperative thirst., Design: This experimental study was conducted with the CONSORT checklist., Methods: A total of 105 surgical patients who received general anesthesia were recruited from a medical center. Each patient was randomly assigned to the experimental group (n = 53; 20 min of TENS) or the control group (n = 52; routine care). In each group, oral moisture wetness was measured at 1 min, 20 min, and 50 min post-surgery. Descriptive and inferential statistics (Chi-square test, t test, one-way ANOVA, and generalized estimating equation (GEE) regression analysis) were performed to assess the proposed relationships., Findings: The two groups showed similar characteristics at baseline. The oral moisture wetness was significantly higher in the experimental group than the control group at each post-surgery assessment time (all P < .001). The GEE results showed that patients in the experimental group reported more oral moisture wetness than patients in the control group., Conclusions: This study demonstrated that TENS can reduce thirst reported by patients after general anesthesia. Thus, this method may have clinical applications for managing postoperative thirst., (Copyright © 2022. Published by Elsevier Inc.)

Background: The impact of sex-related differences in patients receiving extracorporeal membrane oxygenation support (ECMO) support is still inconclusive. This population-based study aimed to investigate sex differences in short- or long-term outcomes in order to improve clinical practice., Methods: Patients who received ECMO between 2001 to 2017 were identified from the Taiwan National Health Insurance Research Database. Propensity score matching with a 1:1 ratio was conducted in female-to-male groups, to reduce confounding of baseline covariates. Outcomes included in-hospital mortality, all-cause mortality, all-cause readmission, and ECMO-related complications. Logistic regression analysis, Cox proportional hazard model, and join point regression were used to compare sex differences in both short- or long-term outcomes., Results: In total, 7,010 matched patients from 11,734 ECMO receivers were included for analysis. The use of ECMO increased dramatically in past years, although the proportion of females was still lower than males. There was a decreasing trend of females undergoing ECMO over time. Female patients have lower risks of in-hospital mortality (64.08% in females vs 66.48% in males; P = 0.0352) and ECMO-related complications compared with males. Furthermore, females also had favorable long-term late outcomes such as all-cause mortality (73.35% in females vs 76.98% in males; P = 0.009) and readmission rate (6.99% in females vs 9.19% in males; P = 0.001)., Conclusions: Female patients had more favorable in-hospital and long-term survival outcomes. Despite improvement in modern ECMO technique and equipment, ECMO remains underutilized in eligible female patients. Thus, females should undergo ECMO treatment if available and indicated., Trial Registration: The institutional review board of Chang Gung Memorial Hospital approved all data usage and the study protocol (registration number: 202100151B0C502; date of registration: 23/08/2021)., (© 2023. The Author(s).)

There is scarce evidence about the surgeon learning curve of acute type A aortic dissection surgery and whether the optimal procedure number exists when training a cardiovascular surgeon. A total of 704 patients with acute type A aortic dissection surgery performed by 17 junior surgeons who can identify their first career surgery from January 1, 2005, to December 31, 2018, are included. The surgeon experience volume is defined as the cumulative number of acute type A aortic dissection surgery of the surgeon since January 1, 2005. The primary outcome was in-hospital mortality. The possibility of non-linearity and cutoffs for surgeon experience volume level was explored using a restricted cubic spline model. The results revealed that more surgeon experience volume is significantly correlated to a lower in-hospital mortality rate (r = - 0.58, P = 0.010). The RCS model shows for an operator who reaches 25 cumulative volumes of acute type A aortic dissection surgery, the average in-hospital mortality rate of the patients can be below 10%. Furthermore, the longer duration from the 1st to 25th operations of the surgeon is significantly correlated to a higher average in-hospital mortality rate of the patients (r = 0.61, p = 0.045). Acute type A aortic dissection surgery has a prominent learning curve in terms of improving clinical outcomes. The findings suggest fostering high-volume surgeons at high-volume hospitals can achieve optimal clinical outcomes., (© 2023. The Author(s).)

Acetaminophen (APAP) overdose causes acute liver injury via oxidative stress, uncontrolled inflammatory response, and subsequent hepatocyte death. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a potent source of cellular reactive oxygen species (ROS) and may contribute to oxidative stress in many inflammatory processes. Corilagin, a component of Phyllanthus urinaria , possesses antioxidant, anti-inflammatory, and hepatoprotective effects. We evaluated the mechanisms underlying the protective effect of corilagin against acetaminophen-induced liver injury. Mice were intraperitoneally administrated 300 mg/kg APAP or equal volume of saline (control), with or without various concentrations of corilagin (0, 1, 5, or 10 mg/kg) administered after 30 min. All animals were sacrificed 16 h after APAP administration, and serum and liver tissue assays including histology, immunohistochemistry, and Western blot assay were performed. Corilagin post-treatment significantly attenuated APAP-induced liver injury ( p < 0.005), inflammatory cell infiltration, hepatic proinflammatory cytokine levels, and hepatic oxidative stress. Furthermore, corilagin attenuated the protein levels of NOX1, NOX2, signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) in APAP-induced liver injury. These results indicated that the antioxidant, anti-inflammatory, and protective effects of corilagin in APAP-induced liver injury might involve the regulation of interleukin (IL)-6/STAT3 and mitogen-activated protein kinase (MAPK)/NF-κB signaling pathways through NOX-derived ROS., Competing Interests: The authors declare no conflict of interest.

Background: Atrial fibrillation is the most common cardiac arrythmia and causes many complications. Sinus rhythm restoration could reduce late mortality of atrial fibrillation patients. The Maze procedure is the gold standard for surgical ablation of atrial fibrillation. Higher surgical volume has been documented with favorable outcomes of various cardiac procedures such as mitral valve surgery and aortic valve replacement. We aimed to determine the volume-outcome relationship (i.e., association between surgical volume and outcomes) for the concomitant Maze procedure during major cardiac surgeries., Methods: This nationwide population-based cohort study retrieved data from the Taiwan National Health Insurance Research Database. Adult patients undergoing concomitant Maze procedures during 2010-2017 were identified; consequently, 2666 patients were classified into four subgroups based on hospital cumulative surgery volumes. In-hospital outcomes and late outcomes during follow-up were analyzed. Logistic regression and Cox proportional hazards model were used to analyze the volume-outcome relationship., Results: Patients undergoing Maze procedures at lower-volume hospitals tended to be frailer and had higher comorbidity scores. Patients in the highest-volume hospitals had a lower risk of in-hospital mortality than those in the lowest-volume hospitals [adjusted odds ratio, 0.30; 95% confidence interval (CI), 0.15-0.61; P < 0.001]. Patients in the highest-volume hospitals had lower rates of late mortality than those in the lowest-volume hospitals, including all-cause mortality [adjusted hazard ratio (aHR) 0.53; 95% CI 0.40-0.68; P < 0.001] and all-cause mortality after discharge (aHR 0.60; 95% CI 0.44-0.80; P < 0.001)., Conclusions: A positive hospital volume-outcome relationship for concomitant Maze procedures was demonstrated for in-hospital and late follow-up mortality. The consequence may be attributed to physician skill/experience, experienced multidisciplinary teams, and comprehensive care processes. We suggest referring patients with frailty or those requiring complicated cardiac surgeries to high-volume hospitals to improve clinical outcomes., Trial Registration: the institutional review board of Chang Gung Memorial Hospital approved all data usage and the study protocol (registration number: 202100151B0C502)., (© 2023. The Author(s).)

Background: To determine the relationship between hospital surgical volume and mortality risk and valve repair rate in infective endocarditis (IE) surgery., Methods: Using the Taiwan National Health Insurance Research Database, 3873 patients were identified who underwent surgery between 2000 and 2013. The cumulative hospital volume of valve surgery for IE was calculated, and patients were divided into 4 subgroups according to the quartile. Outcomes were mortality and valve repair rate and the cut point of referral excellence., Results: The distribution of IE surgery has been shifting to lower-volume hospitals over the years. The global disease severity (Charlson Comorbidity Index score) of patients was greater in the lowest-volume hospital than in the highest-volume hospital (2.4 vs 2.0). The crude in-hospital mortality rate was 15.8% and 9.4% for the lowest- and highest-volume hospitals, respectively, with a significant difference (adjusted odds ratio: 1.86, 95% confidence interval: 1.22-2.85) after adjustment of baseline characteristics including the Charlson Comorbidity Index score. The mitral valve repair rate increased with the increase in cumulative volume. During a mean follow-up period of 4.4 years, 324 (41.9%) and 254 (30.9%) patients died in the lowest- and highest-volume subgroups, respectively, and the difference was significant (adjusted hazard ratio: 1.59, 95% confidence interval: 1.21-2.10)., Conclusions: A higher cumulative volume of IE surgery is associated with a lower risk of mortality and a higher likelihood of successful mitral valve repair. Therefore, interfacility transfer to a high-volume hospital may improve outcomes of IE surgery., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to evaluate the treatment effects after molar distalization using modified C-palatal plates in patients with Class II malocclusion with maxillary sinus pneumatization., Methods: This study consisted of 70 lateral cephalograms derived from cone-beam computerized tomography images of 35 patients with Class II malocclusion (mean age 22.3 ± 7.4 years) who had undergone bilateral total arch distalization of the maxillary dentition using modified C-palatal plates. The samples were divided into 2 groups according to sinus pneumatization; group 1 (n = 40), cephalograms with sinus pneumatization and group 2 (n = 30) cephalograms without sinus pneumatization. Paired t tests and independent-sample t tests were used to compare the changes in each group and between groups., Results: The distal movement of the maxillary first molars was 4.3 mm for group 1 and 3.5 mm for group 2, with the intrusion of 1.4 mm and 2.5 mm, respectively. There was no statistically significant difference between the 2 groups. Group 1 showed 3.5° of distal tipping of the maxillary second molars, which was significantly greater than the 0.2° in group 2 (P <0.05). The total treatment period, including distalization, was 2.2 years for group 1 and 1.9 years for group 2, but the difference was not significant., Conclusions: There was no significant difference in the amount of distal movement and intrusion of the maxillary first molars between groups 1 and 2. Therefore, these results suggest that regardless of sinus pneumatization, molar distalization using temporary skeletal anchorage devices in Class II patients can be performed as a nonextraction treatment., (Copyright © 2022 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Background: Adequate pain control is of crucial importance to patient recovery and satisfaction following abdominal surgeries. The optimal analgesia regimen remains controversial in liver resections. Methods: Three groups of patients undergoing open hepatectomies were retrospectively analyzed, reviewing intravenous patient-controlled analgesia (IV-PCA) versus IV-PCA in addition to bilateral rectus sheath and subcostal transversus abdominis plane nerve blocks (IV-PCA + NBs) versus patient-controlled thoracic epidural analgesia (TEA). Patient-reported pain scores and clinical data were extracted and correlated with the method of analgesia. Outcomes included total morphine consumption and numerical rating scale (NRS) at rest and on movement over the first three postoperative days, time to remove the nasogastric tube and urinary catheter, time to commence on fluid and soft diet, and length of hospital stay. Results: The TEA group required less morphine over the first three postoperative days than IV-PCA and IV-PCA + NBs groups (9.21 ± 4.91 mg, 83.53 ± 49.51 mg, and 64.17 ± 31.96 mg, respectively, p < 0.001). Even though no statistical difference was demonstrated in NRS scores on the first three postoperative days at rest and on movement, the IV-PCA group showed delayed removal of urinary catheter (removal on postoperative day 4.93 ± 5.08, 3.87 ± 1.31, and 3.70 ± 1.30, respectively) and prolonged length of hospital stay (discharged on postoperative day 12.71 ± 7.26, 11.79 ± 5.71, and 10.02 ± 4.52, respectively) as compared to IV-PCA + NBs and TEA groups. Conclusions: For postoperative pain management, it is expected that the TEA group required the least amount of opioid; however, IV-PCA + NBs and TEA demonstrated comparable postoperative outcomes, namely, the time to remove nasogastric tube/urinary catheter, to start the diet, and the length of hospital stay. IV-PCA with NBs could thus be a reliable analgesic modality for patients undergoing open liver resections.

Objectives: The effect of previous coronary stenting on subsequent coronary artery bypass graft is inconclusive., Methods: We used Taiwan's National Health Insurance Database to retrospectively evaluate patients with multivessel coronary artery bypass graft between January 2000 and December 2013. Overall, 32,335 patients who received coronary artery bypass graft were included, of whom 3028 had previous coronary stenting. Propensity-score matching yielded 2977 cases each for evaluation under the previous stenting and no stenting groups. The 30-day mortality and major adverse cardiac events, including all-cause mortality, acute myocardial infarction, and revascularization, were considered primary outcomes., Results: The number of coronary artery bypass grafts decreased per year. However, the percentage of patients who had previous coronary stent implantation before coronary artery bypass graft increased steadily (P for trend <.001), and the average number of stents implanted in a patient also increased per year (P for trend <.001). The previous stent group had a significantly greater 30-day mortality rate than did the no-stent group (7.2% vs 5.0%; odds ratio, 1.47; 95% confidence interval, 1.19-1.82). The previous stent group had a greater rate of revascularization (14.4% and 10.0%; subdistribution hazard ratio, 1.50; 95% confidence interval, 1.30-1.74) in the last follow-up at year 13., Conclusions: Previous coronary stenting before coronary artery bypass graft for multivessel coronary artery disease significantly increased 30-day mortality but did not affect late survival. However, patients who had coronary stenting before coronary artery bypass graft experienced more revascularization events during late follow-up., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Gastrodin is a major active phenolic glycoside extract from Gastrodia elata, an important herb used in traditional medicine. Previous research has reported that gastrodin possesses anti-inflammatory and anti-oxidant properties. Therefore, we aimed to investigate its hepatoprotective effects and mechanisms on acetaminophen (APAP)-induced liver injury in a mouse model. Mice included in this study were intraperitoneally administered with a hepatotoxic APAP dose (300 mg/kg). At 30 min after APAP administration, gastrodin was intraperitoneally injected at concentrations of 0, 15, 30, and 45 mg/kg. Then, all mice were sacrificed at 16 h after APAP injection for further analysis. The results showed that gastrodin treatment ameliorated acute liver injury caused by APAP, as indicated by serum alanine aminotransferase level, hepatic myeloperoxidase activity, and cytokine (TNF-α, IL-1β, and IL-6) production. It also significantly decreased hepatic malondialdehyde activity but increased superoxide dismutase activity. In addition, gastrodin decreased ERK/JNK MAPK expression but promoted Nrf2 expression. These results demonstrated that gastrodin may be a potential therapeutic target for the prevention of APAP-induced hepatotoxicity via amelioration of the inflammatory response and oxidative stress, inhibition of ERK/JNK MAPK signaling pathways, and activation of Nrf2 expression levels., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Acute lung injury (ALI) and acute respiratory distress syndrome are clinically life-threatening diseases. Corilagin, a major polyphenolic compound obtained from the herb Phyllanthus urinaria , has anti-inflammatory and antioxidant properties, and in this study, we sought to evaluate the protective effects and mechanisms of corilagin on lipopolysaccharide (LPS)-induced ALI in mice. ALI was induced in the mice by the intratracheal administration of LPS, and following 30 min of LPS challenge, corilagin (5 and 10 mg/kg body weight) was administered intraperitoneally. At 6 h post-LPS administration, lung tissues were collected for analysis. Corilagin treatment significantly attenuated inflammatory cell infiltration, the production of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, and oxidative stress in lung tissues. In addition, corilagin inhibited the LPS-induced expression of NOX2, ERK, and NF- κ B. Corilagin has anti-oxidative and anti-inflammatory effects, and can effectively reduce ALI via attenuation of the NOX2 and ERK/NF- κ B signaling pathways.

Background: Rheumatic heart disease remains a major cause of cardiovascular death worldwide. Limited real-world nationwide data are available to compare the long-term outcomes between mitral valve repair and replacement in rheumatic heart disease., Methods: We identified adult patients with rheumatic heart disease who underwent mitral valve repair or replacement surgery between 2000 and 2013 from Taiwan's National Health Insurance Research Database. Outcomes of interest included operation-related complications, all-cause mortality, and mitral valve reoperation rate. Propensity score matching at a 1:1 ratio was conducted to mitigate possible confounding factors., Results: A total of 5086 patients with rheumatic heart disease who underwent mitral valve surgery were identified. Of those, 489 (9.6%) and 4597 (90.4%) underwent mitral valve repair and mitral valve replacement, respectively. After propensity score matching was applied, each group had 467 patients. No difference in risk of in-hospital mortality was observed between groups. With a mean follow-up of 6 years, the mitral valve repair group had comparable risks of all-cause mortality with the mitral valve replacement group (33.4% vs 32.5%; hazard ratio, 1.01; 95% confidence interval, 0.81-1.25). However, higher risks of mitral valve reoperation were observed in the mitral valve repair group (subdistribution hazard ratio, 4.32; 95% confidence interval, 2.02-9.23). Previous percutaneous transvenous mitral commissurotomy was identified as a risk factor of mitral valve reoperation in the repair group., Conclusions: Among patients with rheumatic heart disease, mitral valve repair is not associated with superior long-term outcomes. Patients should be carefully selected for mitral valve repair because of its higher reoperation rate, particularly those with previous percutaneous transvenous mitral commissurotomy., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

No study has evaluated the effect of dexmedetomidine in patients who received surgery for type A aortic dissection. This is the first study to evaluate the effect of dexmedetomidine in aortic dissection patients. This study was executed using data from the Chang Gung Research Database in Taiwan. The CGRD contains the multi-institutional standardized electronic medical records from seven Chang Gung Memorial hospitals, the largest medical system in Taiwan. We retrospectively evaluate patients who received surgery for acute type A aortic dissection between January 2014 and December 2018. Overall, 511 patients were included, of whom 104 has received dexmedetomidine infusion in the postoperative period. One-to-two propensity score-matching yielded 86 cases in the dexmedetomidine group and 158 cases in the non-dexmedetomidine group. The in-hospital mortality and composite outcome including all-cause mortality, acute kidney injury, delirium, postoperative atrial fibrillation, and respiratory failure, were considered primary outcomes. The in-hospital mortality and composite outcome were similar between groups. The risk of Acute Kidney Injury Network stage 3 acute kidney injury was significantly lower in the dexmedetomidine group than in the non-dexmedetomidine group (8.1% vs 19.0%; OR, 0.38; 95% CI, 0.17-0.86; p = 0.020. The risk of newly-onset dialysis was also significantly lower in the dexmedetomidine group than in the non-dexmedetomidine group (4.7% vs 13.3%; OR, 0.32; 95% CI, 0.11-0.90; p = 0.031). Post-operative dexmedetomidine infusion significantly reduced the rate of severe acute kidney injury and newly-onset dialysis in patients who received surgery for acute type A aortic dissection., (© 2022. The Author(s).)

Objective: The aim of this study is to evaluate the sex-related differences on the risks of perioperative and late outcomes for adult acute aortic dissection (AAD) patients following surgical management., Methods and Results: By using Taiwan National Health Insurance Research Database, totally 1,410 female and 3,432 male patients were identified to first-ever receive type A AAD open surgery or type B AAD stenting treatment from 2004 to 2013. We assessed the sex-related difference on outcomes, including in-hospital mortality, all-cause mortality, aortic death, redo aortic surgery, ischemic stroke, and depression during the follow-up period. The analysis was done separately for type A and type B surgeries., Results: On average, female patients diagnosed with AAD were older than males. There was no significant sex difference of in-hospital mortality or all-cause mortality for both type A open and type B stent surgeries. The risk of redo aortic surgery was significantly greater in males than females (7.8% vs. 4%; unadjusted subdistribution hazard ratio [SHR] 0.51, 95% CI 0.38-0.69) for type A open surgery, but not for type B stent surgery. Noticeably, the risk of newly-diagnosed depression was significantly greater in females than males (8% vs. 5.1%; unadjusted SHR 1.6, 95% CI 1.24-2.06) for type A open surgery, but not for type B stent surgery., Conclusions: No significant sex-related difference was found for the in-hospital mortality or accumulative all-cause mortality. However, there were more redo aortic surgeries for males and more postoperative depression for females in type A AAD population., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Outcomes of sex differences in major cardiac surgery remain controversial. A comprehensive understanding of sex differences in major adult cardiac surgery could provide better knowledge of risk factors, management strategy and short-term or long-term outcomes. The present study aimed to investigate sex differences in the risks of outcomes of major cardiac surgeries and subgroup analyses of different valve types., Design: Population-based nationwide cohort study., Setting: Data were obtained from National Health Insurance Research Database (NHIRD) in Taiwan., Participants: A total of 66 326 adult patients (age ≥20 years; 30.3% women) who underwent a first major cardiac surgery (isolated coronary artery bypass graft (CABG), isolated valve or concomitant bypass/valve) from 2000 to 2013 were identified via Taiwan NHIRD., Main Outcome Measures: Outcomes of primary interest were in-hospital death and all-cause mortality during follow-up period. Propensity score matching was conducted as a secondary analysis for the sensitivity test., Results: Women who underwent isolated CABG tended to have greater risks of both in-hospital (OR 1.37; 95% CI 1.26 to 1.49) and late outcomes (HR 1.26; 95% CI 1.22 to 1.31). Women after concomitant CABG/valve also had a greater in-hospital (OR 1.19; 95% CI 1.01 to 1.40) and long-term mortality (HR 1.14; 95% CI 1.05 to 1.24). Women after isolated mitral valve repair have a non-favourable outcome of in-hospital mortality (OR 1.70; 95% CI 1.01 to 2.87). Women who did not receive an isolated aortic valve replacement had more favourable all-cause mortality outcome (HR 0.90; 95% CI 0.84 to 0.96). Secondary analysis in the propensity score-matching cohort demonstrated results similar to the primary analysis., Conclusions: Female patients who underwent procedures involving CABG (with or without concurrent valvular intervention) had generally worse outcomes. However, the results of isolated valve surgery were variable on the basis of the type of intervened valve., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Current international normalized ratio (INR) guidelines are based on trials involving European and US populations. To our knowledge, no adequate study involving Asian patients has been conducted to date., Objective: To evaluate the association between INR and anticoagulation-related outcomes in an Asian population after mechanical aortic valve replacement (AVR) or mitral VR (MVR)., Design, Setting, and Participants: This retrospective cohort study was conducted between 2001 and 2018, with follow-up until December 31, 2018, among patients who underwent AVR, MVR, or combined AVR-MVR at 3 medical centers and 4 regional hospitals and contributed electronic medical records to the Chang Gung Research Database. Exclusion criteria were missing demographic characteristics, younger than 20 years, fewer than 2 INR records, and having died during the hospitalization of the index surgery., Main Outcomes and Measures: Bleeding and thromboembolic complications were analyzed. The possibility of nonlinearity and cutoff potential for the INR were explored using a logistic regression model, which considered the INR a restricted cubic spline (RCS) variable., Results: The study population consisted of 900 patients, with 525 (58.3%) men and 375 (41.7%) women and a mean (SD) age of 52.0 (12.5) years. Overall, 474 (52.7%) received AVR alone, 329 (36.6%) received MVR alone, and 97 (10.8%) received combined AVR-MVR. All patients had at least 2 INR examinations after discharge, providing 16 676 INR records for the AVR group and 18 207 for the MVR and combined AVR-MVR groups. In the AVR group, the RCS model showed that higher risks of composite thromboembolic events were associated with an INR of less than 2.0 or greater than 2.6 vs an INR of 2.0, and a higher risk of bleeding events was associated with an INR of less than 1.8 or greater than 2.4 vs an INR of 2.0. When treating the INR as a categorical variable, the risk of composite thromboembolic and composite bleeding events was significantly higher among patients with INRs less than 1.5 (adjusted odds ratio [aOR], 2.55; 95% CI, 1.37-4.73) and with INRs of 3.0 or greater (aOR, 3.48; 95% CI, 1.95-6.23) vs those with INRs between 2.0 and 2.5.In the MVR and combined AVR-MVR groups, higher risks of composite thromboembolic events were associated with an INR of less than 2.1 or greater than 2.7 vs an INR of 2.5, and a higher risk of bleeding events was associated with an INR of less than 2.1 or greater than 2.8 vs an INR of 2.5. When treating the INR as a categorical variable, the risk of a composite bleeding events was significantly higher among patients with INRs of 3.5 or greater (aOR, 2.25; 95% CI, 1.35-3.76) vs those with INRs between 2.5 and 3.0., Conclusions and Relevance: Among Asian patients in this study, the incidence of thromboembolic events in the MVR group with INRs in the range of 2.0 to 2.5 was not significantly higher than that among those with INRs in the range of 2.5 to 3.0; in the AVR group, the incidence for those with INRs in 1.5 to 2.0 range was not significantly higher than for those with INRs in the range of 2.0 to 2.5.

Background: Emergency endotracheal intubations outside the operating room (OR) are associated with high complications. We compare the outcome of emergency endotracheal intubation in the general ward, the intensive care unit (ICU) and the emergency department (ED)., Methods: We retrospectively analyzed adult patients requiring emergency endotracheal intubation that called for anesthesiologists at our tertiary care institution from January 1, 2015 to December 31, 2016. We evaluated the outcomes, including aspiration, hemodynamic collapse, pneumothorax, emergency tracheostomy, and survival to hospital discharge in the general ward, ICU, and ED., Results: There were 416 non-OR emergency endotracheal intubation calls for the anesthesiologist. Among these areas, the ED had the highest proportion of difficult endotracheal (DET) intubation (n = 144 [80.4%]), followed by the general ward (n = 85 [66.4%]), and then the ICU (n = 65 [59.6%]). The incidence of hemodynamic collapse was higher in the general ward (n = 44 [34.4%]) than the ICU (n = 18 [16.5%]) or the ED (n = 16 [9.0%]). We reported the survival rate of the general ward (55.5%), which was lower than the ICU (63.3%) and the ED (80.4%). Among these locations, the ED had the highest rate of neurologically intact (91%) to hospital discharge, compared to the ICU (56.6%) and the general ward (55%). As for the ED, although there was no difference in survival between non-preventive and preventive intubations, preventive intubations was associated with high neurological intact with hospital discharge., Conclusion: Emergency and DET intubation in the general ward and ICU resulted in a higher incidence of hemodynamic collapse and mortality than those performed in the ED. Early calls for the anesthesiologist for DET intubation without medications in the ED resulted in a higher rate of neurologically intact survival to hospital discharge., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2020 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Acetaminophen (APAP) overdose is the major cause of drug-induced liver injury and acute liver failure. Approximately 10% of APAP is metabolized by cytochrome P450 (CYP2E1) into toxic N -acetyl-p-benzoquinone imine (NAPQI). CYP2E1 also contributes to ethanol metabolism, especially during conditions of high blood ethanol concentration. Acute and chronic ethanol consumption appears to have opposite effects on APAP-induced liver injury. We determined the effects of different doses, pre- and post-treatment, and various schedules of ethanol exposure in APAP-induced liver injury. Treatment with ethanol (0.5 g/kg) after 1 h of APAP (300 mg/kg) administration decreased serum ALT levels, histopathological features, and inflammatory cell infiltration. Moreover, ethanol treatment 1 h after APAP treatment reduced APAP-induced liver injury compared with later administration. Interestingly, ethanol pretreatment did not provide any protective effect. Furthermore, ethanol treatment was associated with a significant decrease in ERK and AKT phosphorylation during the acute injury phase. Ethanol exposure also increased CYP2E1 expression and decreased PCNA expression during the liver regeneration phase.

Introduction: The study aimed to reveal how the fraction of inspired oxygen (FIO2) affected the value of mixed venous oxygen saturation (SvO2) and the accuracy of Fick-equation-based cardiac output (Fick-CO)., Methods: Forty two adult patients who underwent elective cardiac surgery were enrolled and randomly divided into 2 groups: FIO2 < 0.7 or >0.85. Under stable general anesthesia, thermodilution-derived cardiac output (TD-CO), SvO2, venous partial pressure of oxygen, hemoglobin, arterial oxygen saturation, arterial partial pressure of oxygen, and blood pH levels were recorded before surgical incision., Results: Significant differences in FIO2 values were observed between the 2 groups (0.56 ± 0.08 in the <70% group and 0.92 ± 0.03 in the >0.85 group; P < .001). The increasing FIO2 values lead to increases in SvO2, venous partial pressure of oxygen, and arterial partial pressure of oxygen, with little effects on cardiac output and hemoglobin levels. When comparing to TD-CO, the calculated Fick-CO in both groups had moderate Pearson correlations and similar linear regression results. Although the FIO2 <0.7 group presented a less mean bias and a smaller limits of agreement, neither group met the percentage error criteria of <30% in Bland-Altman analysis., Conclusion: Increased FIO2 may influence the interpretation of SvO2 and the exacerbation of Fick-CO estimation, which could affect clinical management., Trial Registration: ClinicalTrials.gov ID number: NCT04265924, retrospectively registered (Date of registration: February 9, 2020)., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Aortic dissection (AD) is a life-threatening emergency, and lumican (LUM) is a potential Biomarker for AD diagnosis. We investigated LUM expression patterns in patients with AD and explored the molecular functions of Lum in AD mice model., Methods: LUM expression patterns were analyzed using aortic tissues of AD patients, and serum soluble LUM (s-LUM) levels were compared between patients with acute AD (AAD) and chronic AD (CAD). Lum-knockout (Lum-/-) mice were challenged with β-aminopropionitrile (BAPN) and angiotensin II (Ang II) to induce AD. The survival rate, AD incidence, and aortic aneurysm (AA) in these mice were compared with those in BAPN-Ang II-challenged wildtype (WT) mice. Tgf-β/Smad2, Mmps, Lum, and Nox expression patterns were examined., Results: LUM expression was detected in the intima and media of the ascending aorta in patients with AAD. Serum s-LUM levels were significantly higher in patients with AAD than CAD. Furthermore, AD-associated mortality and thoracic aortic rupture incidence were significantly higher in the Lum-/- AD mice than in the WT AD mice. However, no significant pathologic changes in AA were observed in the Lum-/- AD mice compared with the WT AD mice. The BAPN-Ang II-challenged WT and Lum-/- AD mice had higher Tgf-β, p-Smad2, Mmp2, Mmp9, and Nox4 levels than those of non-AD mice. We also found that Lum expression was significantly higher in the BAPN-Ang II-challenged WT in comparison to the unchallenged WT mice., Conclusion: LUM expression was altered in patients with AD display increased s-LUM in blood, and Lum-/- mice exhibited augmented AD pathogenesis. These findings support the notion that LUM is a biomarker signifying the pathogenesis of injured aorta seen in AAD. The presence of LUM is essential for maintenance of connective tissue integrity. Future studies should elucidate the mechanisms underlying LUM association in aortic changes., Competing Interests: The authors have declared that no competing interests exist.

Background: Patients are prone to permanent pacemaker implantation (PPM) after valve surgery, yet current data on the effects of postoperative PPM are scarce and large-scale studies are lacking. The aim of this study was to determine rates and long-term outcomes of PPM after cardiac valve surgery., Methods and results: A total of 24,014 patients who received valve surgery from 2000 to 2013 were identified from the Taiwan National Health Insurance Research Database. The number of valve surgeries and the proportion of PPM implantations after valve surgery increased (P<0.001). After 1 : 5 propensity score matching, 602 and 3,010 patients were categorized to the PPM and non-PPM groups, respectively. Late outcomes included all-cause mortality, cardiovascular death, sepsis, and readmission due to any cause. The mean follow up was 4.3 years. PPM was associated with a higher all-cause mortality rate (33.6% vs. 29.8%; hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.98-1.32), though not significant at the threshold of P<0.05. PPM was also associated with higher all-cause mortality rates in subgroups that received mitral valve (MV) replacement surgery, combined aortic valve replacement (AVR) with MV surgeries, and combined AVR with tricuspid valve surgeries., Conclusions: The PPM rate after valve surgery is increasing, and is associated with short-term adverse effects. Patients with PPM may have a higher long-term mortality rate.

The Perceval sutureless valve has gained in popularity for treating degenerative aortic valve stenosis but not for congenital type 0 bicuspid aortic valve owing to anatomic challenges. We modified implant techniques following the four principles of ECHO-an acronym for elasticity, circularity, height, and orientation-to prevent paravalvular leakage and malposition., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to compare the outcomes of tricuspid valve (TV) repair versus replacement for patients with infective endocarditis (IE)., Methods: In this nationwide population-based cohort study, we identified 704 patients from Taiwan National Health Insurance Research Database who underwent TV surgery due to IE between 2000 and 2013. Of them, 412 (58.5%) underwent TV repair and 292 (41.5%) underwent TV replacement, and their perioperative and late outcomes were analysed. Confounding was reduced using the inverse probability of treatment weighting on propensity score., Results: After inverse probability of treatment weighting, the in-hospital mortality rate between the 2 groups was not significantly different. However, patients who received TV repair had lower rates of perioperative complications, including massive blood transfusion, de novo dialysis and deep wound infection; longer ICU and hospital stays; and higher hospital cost. Regarding late outcomes, TV repair was associated with lower risks of all-cause readmission [subdistribution hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.60-0.78; P < 0.001], readmission for adverse liver outcomes (subdistribution HR 0.75, 95% CI 0.58-0.97; P = 0.025), new permanent pacemaker implantation (subdistribution HR 0.27, 95% CI 0.15-0.48; P < 0.001) and all-cause mortality (HR 0.60, 95% CI 0.51-0.71; P < 0.001) than TV replacement., Conclusions: For IE, TV repair is associated with better early and late outcomes than TV replacement. A repair-first strategy is recommended for patients with IE for whom TV surgery is indicated., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Recent population-based studies have revealed that the use of fluoroquinolones (FQs) is associated with an increased risk of aortic dissection (AD) and aneurysm (AA). However, no evidence is available on whether FQs increase adverse events in patients who had been diagnosed with AD or AA., Objectives: This study investigated whether the use of FQs increases the risk of aortic-related adverse events and death in this high-risk population., Methods: A retrospective cohort study was conducted by using the Taiwan National Health Insurance Research Database. A total of 31,570 adult patients who survived after admission for AD or AA between 2001 and 2013 were identified. We divided each calendar year into 6 data units (2 months) for each patient and each year during follow-up. Covariates and exposure of interest (FQs) were reassessed every 2 months. We used another common antibiotic, amoxicillin, as a negative control exposure., Results: Exposure to FQs was associated with a higher risk of all-cause death (adjusted hazard ratio: 1.61; 95% confidence interval: 1.50 to 1.73), aortic death (adjusted hazard ratio: 1.80; 95% confidence interval: 1.50 to 2.15), and later aortic surgery. However, amoxicillin exposure was not significantly associated with risk of any of the outcomes. A subgroup analysis revealed that the effect of FQs was not significantly different between the AD and AA groups., Conclusions: Relative to amoxicillin use, FQ exposure in patients with AD or AA was associated with a higher risk of adverse outcomes. FQs should not be used by high-risk patients unless no other treatment options are available., Competing Interests: Funding Support and Author Disclosures This work was supported by a grant from Chang Gung Memorial Hospital, Taiwan: CMRPG3K1951, CMRPG3J0661, CMRPG3L0101 and BMRPD95 (to Dr. Chen). This work was also supported by the Ministry of Science and Technology grant MOST-108-2314-B-182A-141 (to Dr. Chen). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: The associations between long-term treatment of aortic dissection with various medications and late patient outcomes are poorly understood., Objective: To compare late outcomes after long-term use of β-blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or other antihypertensive medications (controls) among patients treated for aortic dissection., Design, Setting, and Participants: This population-based retrospective cohort study using the National Health Insurance Research Database in Taiwan included 6978 adult patients with a first-ever aortic dissection who survived to hospital discharge during the period between January 1, 2001, and December 31, 2013, and who received during the first 90 days after discharge a prescription for an ACEI, ARB, β-blocker, or at least 1 other antihypertensive medication. Data analysis was conducted from July 2019 to June 2020., Exposure: Long-term use of β-blockers, ACEIs, or ARBs, with use of other antihypertensive medications as a control., Main Outcomes and Measures: The primary outcomes of interest were all-cause mortality, death due to aortic aneurism or dissection, later aortic operation, major adverse cardiac and cerebrovascular events, hospital readmission, and new-onset dialysis., Results: Of 6978 total participants, 3492 received a β-blocker, 1729 received an ACEI or ARB, and 1757 received another antihypertension drug. Compared with patients in the other 2 groups, those in the β-blocker group were younger (mean [SD] age, 62.1 [13.9] years vs 68.7 [13.5] years for ACEIs or ARBs and 69.9 [13.8] years for controls) and comprised more male patients (2520 [72.2%] vs 1161 [67.1%] for ACEIs or ARBs and 1224 [69.7%] for controls). The prevalence of medicated hypertension was highest in the ACEI or ARB group (1039 patients [60.1%]), followed by the control group (896 patients [51.0%]), and was lowest in the β-blocker group (1577 patients [45.2%]). Patients who underwent surgery for type A aortic dissection were more likely to be prescribed β-blockers (1134 patients [32.5%]) than an ACEI or ARB (309 patients [17.9%]) or another antihypertension medication (376 patients [21.4%]). After adjusting for multiple propensity scores, there were no significant differences in any of the clinical characteristics among the 3 groups. No differences in the risks for all outcomes were observed between the ACEI or ARB and β-blocker groups. The risk of all-cause hospital readmission was significantly lower in the ACEI or ARB group (subdistribution hazard ratio [HR], 0.92; 95% CI, 0.84-0.997) and β-blocker group (subdistribution HR, 0.87; 95% CI, 0.81-0.94) than in the control group. Moreover, the risk of all-cause mortality was lower in the ACEI or ARB group (HR, 0.79; 95% CI, 0.71-0.89) and the β-blocker group (HR, 0.82; 95% CI, 0.73-0.91) than in the control group. In addition, the risk of all-cause mortality was lower in the ARB group than in the ACEI group (HR, 0.85; 95% CI, 0.76-0.95)., Conclusions and Relevance: The use of β-blockers, ACEIs, or ARBs was associated with benefits in the long-term treatment of aortic dissection.

Abstract: The aim of this study was to evaluate the effect of beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) after cardiac surgery in the liver cirrhosis (LC) patients. We conducted a population-based cohort study using data from the Taiwanese National Health Insurance Research Database (NHIRD) from 2001 to 2013. The outcomes of interest included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE) and liver and renal outcomes. Among 1470 LC patients, 35.6% (n = 524) received beta-blockers and 33.4% (n = 491) were prescribed ACEIs and/or ARBs after cardiac surgery. The risk of negative liver outcomes was significantly lower in the ARB group compared with the ACEI group (9.6% vs 22.7%, hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.31-0.83). Furthermore, the risk of MACCE (44.2% vs 54.7%, HR 0.79, 95% CI 0.65-0.96), all-cause mortality (35.3% vs 46.4%, HR 0.74, 95% CI 0.60-0.92), composite liver outcomes (9.6% vs 16.5%, HR 0.56, 95% CI 0.38-0.85) and hepatic encephalopathy (2.7% vs 5.7%, HR 0.45, 95% CI 0.21-0.94) were lower in the ARB group than the control group. Our study demonstrated that ARBs provide a greater protective effect than ACEIs in regard to long-term outcomes following cardiac surgery in patients with LC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Negative experiences in dental clinics can induce anxiety in patients, and the effects are particularly pronounced in children. When behavior guidance methods (eg, direct observation, tell-show-do, and ask-tell-ask) fail, general anesthesia is an important alternative; however, the procedure of anesthesia can also induce fear and anxiety. This study assessed the effectiveness of guided imagery in relieving the anxiety associated with dental surgery in children and caregivers., Design: A prospective randomized trial with two groups., Methods: The guided imagery in this study was meant to establish a rapport between the medical team and the patient, by encouraging the child to imagine having an adventure while riding in a spacecraft. Anxiety levels and behavior were measured using five well-established scales: the modified Yale Preoperative Scale-Short Form, the State-Trait Anxiety Inventory-6 items, the Watcha score, the Pediatric Anesthesia Emergent Delirium scale, and the Posthospitalization Behavioral Questionnaire-Ambulatory Surgery., Findings: The results indicate that the guided imagery had no significant effects on anxiety levels., Conclusions: Guided imagery is a low-cost, easy-to-implement, interesting exercise capable of enhancing interactions between nursing staff and children. It may also help to condition children to the environment and thereby assist them in overcoming their fears., (Copyright © 2020 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Corilagin is a major active polyphenolic tannins extracted from Phyllanthus urinaria , an important herb used in traditional medicine. Previous reports demonstrated that corilagin possesses antioxidant and anti-inflammatory properties. Therefore, this study aimed to evaluate its hepatoprotective effects and mechanisms on acetaminophen (APAP)-induced liver injury in mice. Mice included in this study were intraperitoneally injected with a hepatotoxic APAP dose (300 mg/kg). After a 30 min of APAP administration, corilagin was injected intraperitoneally at concentrations of 0, 1, 5, 10, and 20 mg/kg. Then, after 16 h of corilagin treatment, mice were sacrificed for further analysis. APAP overdose significantly elevated the serum ALT level, hepatic myeloperoxidase (MPO) activity, cytokines (TNF-α, IL-1β, and IL-6) production, malondialdehyde (MDA) activity, and ERK/JNK MAPK and NF-κB protein expressions. Corilagin treatment significantly decreased these parameters in a dose-dependent manner (1-20 mg/kg). This study demonstrated that corilagin may be a potential therapeutic target for the prevention of APAP-induced hepatotoxicity by down-regulating the inflammatory response and by inhibiting ERK/JNK MAPK and NF-κB signaling pathways., Competing Interests: None., (AJTR Copyright © 2020.)

Background Octogenarians (≥80 years old) are high-risk patients for acute aortic dissection (AAD) surgery. However, no population-based study has investigated the late outcomes of AAD surgery in octogenarians. This study aimed to investigate the late outcomes of AAD surgery in octogenarians. Methods and Results A total of 3998 patients who received AAD surgery from 2005 to 2013 were identified from the Taiwan National Health Insurance Research Database. In-hospital complications and late outcomes including all-cause mortality, major adverse cardiac and cerebrovascular event, respiratory failure, and redo aortic surgery were evaluated. The risks of late outcomes between octogenarians and nonoctogenarians were compared using the multivariable Cox proportional hazard model or Fine and Gray competing model. The numbers of the octogenarians who underwent type A and B AAD surgeries were 206 (6%; 206/3423) and 79 (13.7%; 79/575), respectively. Compared with the nonoctogenarians, the type A octogenarians had higher risks of in-hospital mortality and several in-hospital complications, whereas the type B octogenarians did not. Furthermore, compared with the nonoctogenarians, the type A octogenarians had a higher risk of all-cause mortality (61.7% vs 32.5%; hazard ratio [HR], 2.35; 95% CI, 1.95-2.84) and a higher cumulative incidence of major adverse cardiac and cerebrovascular event and respiratory failure, and the type B octogenarians demonstrated a higher risk of all-cause mortality (44.3% vs 30.4%; HR, 1.74; 95% CI, 1.18-2.55). The octogenarians receiving AAD surgeries had higher mortality rates than the normal octogenarian population. Conclusions Octogenarians receiving AAD surgeries exhibit worse late outcomes than nonoctogenarian counterparts.

Endovascular aneurysm repair (EVAR) and thoracic endovascular aortic repair (TEVAR) are effective and minimally invasive treatment options for high-risk surgical candidates. Nevertheless, knowledge about the management of aortic stent graft therapy in chronic kidney disease (CKD) is scarce. This study aimed to examine outcomes after EVAR and TEVAR in patients with CKD.Utilizing data from the Taiwan National Health Insurance Research Database, we retrospectively assessed patients who underwent EVAR and TEVAR therapy between January 1, 2006, and December 31, 2013. Patients were divided into CKD and non-CKD groups. Outcomes were in-hospital mortality, all-cause mortality, readmission, heart failure, and major adverse cardiac and cerebrovascular events.There were 1019 patients in either group after matching. The CKD group had a higher in-hospital mortality rate than the non-CKD group (15.2% vs 8.3%, respectively; odds ratio, 1.92; 95% confidence interval [CI], 1.46-2.54). Patients with CKD had higher risks of all-cause mortality including in-hospital death (46.1% vs 33.1%; hazard ratio [HR], 1.61; 95% CI, 1.35-1.92), readmission rate (62.6% vs 55.0%; subdistribution HR [SHR], 1.61; 95% CI, 1.32-1.69), redo stent (7.8% vs 6.2%; SHR, 1.50; 95% CI, 1.09-2.07), and major adverse cardiac and cerebrovascular events (13.3% vs 8.8%; SHR, 1.50; 95% CI, 1.15-1.95). The subgroup analysis did not demonstrate a variation in mortality between the TEVAR and EVAR cohorts (P for interaction = .725). The dialysis group had higher risks of all-cause mortality and readmission than the CKD without dialysis and non-CKD groups.Among EVAR/TEVAR recipients, CKD was independently associated with higher in-hospital mortality, postoperative complication, and all-cause mortality rates. Patients with end-stage renal disease on dialysis had worse outcomes than those in the CKD non-dialysis and non-CKD groups.

Background: Aortic dissection (AD) is a life-threatening emergency. However, the heritability and association of family history with late outcomes are unclear., Objectives: The purpose of this study was to evaluate the effect of family history of AD on the incidence and prognosis of AD and estimate the heritability and environmental contribution in AD in Taiwan., Methods: Both cross-sectional and cohort studies were conducted using Taiwan National Health Insurance database. A registry parent-offspring relationship algorithm was used to reconstruct the genealogy of this population for heritability estimation. The cross-sectional study included 23,868 patients with a diagnosis of AD in 2015. The prevalence and adjusted relative risks (RRs) were evaluated, and the liability threshold model was used to examine the effects of heritability and environmental factors. Furthermore, a 1:10 propensity score-matched cohort comprising AD patients with or without a family history of AD was included to compare late outcomes in the cohort study., Results: A family history of AD in first-degree relatives was associated with an RR of 6.82 (95% confidence interval [CI]: 5.12 to 9.07). The heritability of AD was estimated to be 57.0% for genetic factors, and 3.1% and 40.0% for shared and nonshared environmental factors, respectively. After excluding individuals with Marfan syndrome or bicuspid aortic valve, a family history of AD was associated with an RR of 6.56 (95% CI: 4.92 to 8.77) for AD. Furthermore, patients with AD and a family history of AD had a higher risk of later aortic surgery than those with AD without a family history (subdistribution hazard ratio: 1.40; 95% CI: 1.12 to 1.76)., Conclusions: A family history of AD was a strong risk factor for AD. Furthermore, patients with AD with a family history of AD had a higher risk of later aortic surgery than those with no family history of AD., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Extracorporeal membrane oxygenation (ECMO) is used for life support in patients with liver cirrhosis (LC). However, there have been no studies evaluating the outcome of ECMO support in patients with LC., Methods: Using Taiwan's National Health Insurance (NHI) database, we retrospectively evaluated patients with LC who received veno-venous or veno-arterial ECMO between 1 January 2000 and 31 December 2013. The outcomes included ECMO-related complications, in-hospital mortality, all-cause mortality and long-term outcomes in patients with and without LC., Results: A total of 7003 patients who received ECMO, of whom 233 (3.3%) had LC, were eligible for analysis. The LC patients who received ECMO support had a significantly higher risk of in-hospital mortality than the non-LC group (76.4% vs 60.7%; odds ratio 1.97; 95% confidence interval 1.44-2.70). The LC group also had a higher risk of complications, including de novo dialysis and massive blood transfusion with >10 units of red blood cells. Patients ≥65 years of age, patients with respiratory disease, patients with hypoalbuminaemia and liver transplant patients had higher in-hospital and 1-year mortality. The mortality rates for patients with 2 or more risk factors were 90.3% and 95.8%, respectively. LC was associated with a higher incidence of all-cause mortality and liver-related outcomes during follow-up., Conclusions: Our findings raise questions regarding the utility of ECMO for LC patients, especially when >2 risk factors have been identified. ECMO support for LC patients should be used with caution and with careful patient selection., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)