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Chuen-Chau Chang,1– 3,&ast; Chun-Chieh Yeh,4,5 Cheng Tiong,6,7 Mao-Feng Sun,8 Jaung-Geng Lin,8 Yih-Giun Cherng,3,9 Ta-Liang Chen,2,3,10,&ast; Chien-Chang Liao1– 3,8,11 1Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan; 2Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 3Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 5Department of Surgery, University of Illinois, Chicago, IL, USA; 6Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 7Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 9Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; 10Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 11Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chien-Chang Liao, Department of Anesthesiology, Taipei Medical University Hospital, 252 Wuxing St, Taipei, 110, Taiwan, Email ccliao@tmu.edu.tw; jacky48863027@yahoo.com.twObjective: Sustained hyperlipidemia contributes to fatty liver and liver cirrhosis. Red yeast rice (RYR) effectively improved the lipid profile; however, the effects of RYR on the risk of incident liver cirrhosis remain to be elucidated. We aimed to evaluate the beneficial effects of RYR use on the risk and outcome of liver cirrhosis.Patients and methods: We identified 156,587 adults who had newly diagnosed hyperlipidemia in 2010– 2016 from health insurance data in this retrospective cohort study. Using propensity score matching, we selected 34,367 patients who used RYR and 34,367 patients who used lovastatin. Events of incident liver cirrhosis that occurred in the two cohorts during the follow-up period of 2010– 2019 were identified. We calculated adjusted hazard ratios (HRs) and 95% confidence intervals (Cis) for liver cirrhosis risk associated with RYR use in the multiple Cox proportional hazard model.Results: Compared with patients who used lovastatin, patients who used RYR had a decreased risk of liver cirrhosis (HR 0.60, 95% CI 0.57– 0.63), and this association was significant in various subgroups. A biological gradient relationship between the frequency of RYR use and decreased liver cirrhosis was observed (p for trend < 0.0001). Reduced postcirrhosis jaundice (HR 0.56, 95% CI 0.43– 0.72), ascites (HR 0.37, 95% CI 0.28– 0.50), hepatic coma (HR 0.36, 95% CI 0.26– 0.50), and mortality (HR 0.48, 95% CI 0.38– 0.61) were also associated with RYR use.Conclusion: We demonstrated the beneficial effects of RYR use on the risk and outcome of liver cirrhosis; however, the lack of compliance data should be considered. However, our study did not infer causality or claim the superiority of RYR over lovastatin.Keywords: hyperlipidemia, liver cirrhosis, lovastatin, outcome, red yeast rice, risk

Li-Chin Sung,1– 4 Chuen-Chau Chang,5– 7 Chun-Chieh Yeh,8,9 Yih-Giun Cherng,5,10 Ta-Liang Chen,5,7,11 Chien-Chang Liao5– 7,12,13 1Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 2Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 3Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan; 4Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan; 7Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 8Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 9Department of Surgery, University of Illinois, Chicago, IL, USA; 10Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; 11Department of Anesthesiology, Wang Fang Hospital, Taipei Medical University, Taipei, Taiwan; 12Research Center of Big Data and Meta‑Analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 13School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, TaiwanCorrespondence: Chien-Chang Liao, Department of Anesthesiology, Taipei Medical University Hospital, 252 Wuxing Street, Taipei, 11031, Taiwan, Tel +886-2-2737-2181, ext. 8310, Fax +886-2-2736-7344, Email ccliao@tmu.edu.tw; jacky48863027@yahoo.com.twObjective: To evaluate the complications and mortality after noncardiac surgeries in patients who underwent previous coronary artery bypass grafting (CABG).Methods: We used insurance data and identified patients aged ≥ 20 years undergoing noncardiac surgeries between 2010 and 2017 in Taiwan. Based on propensity-score matching, we selected an adequate number of patients with a previous history of CABG (within preoperative 24 months) and those who did not have a CABG history, and both groups had balanced baseline characteristics. The association of CABG with the risk of postoperative complications and mortality was estimated (odds ratio [OR] and 95% confidence interval [CI]) using multiple logistic regression analysis.Results: The matching procedure generated 2327 matched pairs for analyses. CABG significantly increased the risks of 30-day in-hospital mortality (OR 2.28, 95% CI 1.36– 3.84), postoperative pneumonia (OR 1.49, 95% CI 1.12– 1.98), sepsis (OR 1.49, 95% CI 1.17– 1.89), stroke (OR 1.53, 95% CI 1.17– 1.99) and admission to the intensive care unit (OR, 1.75, 95% CI 1.50– 2.05). The findings were generally consistent across most of the evaluated subgroups. A noncardiac surgery performed within 1 month after CABG was associated with the highest risk for adverse events, which declined over time.Conclusion: Prior history of CABG was associated with postoperative pneumonia, sepsis, stroke, and mortality in patients undergoing noncardiac surgeries. Although we raised the possibility regarding deferral of non-critical elective noncardiac surgeries among patients had recent CABG when considering the risks, critical or emergency surgeries were not in the consideration of delay surgery, especially cancer surgery.Keywords: adverse events, coronary artery bypass surgery, noncardiac surgeries, postoperative complications, postoperative mortality

Ying-Hsuan Tai,1,2,* Chuen-Chau Chang,2– 4 Chun-Chieh Yeh,5,6 Li-Chin Sung,7 Chaur-Jong Hu,8 Yih-Giun Cherng,1,2 Ta-Liang Chen,2,4,9,* Chien-Chang Liao2– 4,10,11 1Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 2Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan; 4Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 5Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 6Department of Surgery, University of Illinois, Chicago, IL, USA; 7Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 8Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 9Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 10Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 11School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Chien-Chang LiaoDepartment of Anesthesiology, Taipei Medical University Hospital, 252 Wuxing Street, Taipei 110, TaiwanEmail jacky48863027@yahoo.com.twYih-Giun CherngDepartment of Anesthesiology, Shuang Ho Hospital, New Taipei City, TaiwanEmail stainless@s.tmu.edu.twObjective: To evaluate the long-term risk of stroke and poststroke adverse outcomes in patients with heart failure (HF).Methods: We used research data from Taiwan’s National Health Insurance Program from 2000 to 2005 and identified 20,072 adults aged ≥ 30 years who were newly diagnosed with HF. Frequency matching based on age and sex was used to select a comparison cohort consisting of 80,288 adults without HF. Events of incident stroke were identified from medical claims during the 2000– 2013 follow-up period. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the association of stroke with HF were calculated with a multiple Cox proportional hazard model. Another nested stroke cohort study of 480,604 hospitalized stroke patients determined the adjusted odds ratios (ORs) and 95% CIs for adverse events after stroke in patients with and without HF between 2000 and 2009.Results: Compared with the non-HF cohort, HF patients had an increased risk of stroke (HR 2.32, 95% CI 2.21– 2.43), including ischemic stroke and hemorrhagic stroke. The association between HF and stroke was significant in both sexes and in patients in all age groups and with various medical conditions. Previous HF was associated with poststroke mortality (OR 1.40, 95% CI 1.31– 1.50), pneumonia (OR 1.33, 95% CI 1.28– 1.38), and septicemia (OR 1.30, 95% CI 1.23– 1.37).Conclusion: HF was associated with a higher risk of stroke, and patients with HF had more complications and greater mortality after stroke.Keywords: heart failure, adverse outcome, risk, stroke

Yih-Giun Cherng,1,2 Chuen-Chau Chang,2–4 Chun-Chieh Yeh,5,6 Yung-Ho Hsu,7 Ta-Liang Chen,2,8,* Chien-Chang Liao2–4,9,10*1Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 2Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan; 4Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 5Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 6Department of Surgery, University of Illinois, Chicago, USA; 7Department of Nephrology, Shuan Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 8Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 9School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 10Research Center of Big Data and Meta-analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan*These authors contributed equally to this workObjective: To evaluate the complications, mortality, and medical expenditures after nonurological surgical procedures in patients with chronic kidney disease (CKD).Methods: Using claims data of Taiwan’s National Health Insurance, we conducted a matched cohort study of 35,643 patients with CKD who underwent nonurological surgeries in 2008–2013. By using a propensity-score matching procedure, 35,643 non-CKD patients were selected for comparison. Logistic regression was used to calculate the odds ratios (ORs) and the 95% confidence intervals (CIs) of postoperative complications and in-hospital mortality associated with CKD.Results: The results showed that patients with CKD had higher risks of postoperative septicemia (OR: 1.78, 95% CI: 1.68–1.89), pneumonia (OR: 1.60, 95% CI: 1.48–1.73), stroke (OR: 1.34, 95% CI: 1.24–1.44), and in-hospital mortality (OR: 2.17, 95% CI: 1.90–2.47) compared with non-CKD patients. Longer hospital stays and higher medical expenditures after nonurological surgical procedures were noted in CKD patients. The association between CKD and postoperative adverse events was significant in both sexes, all of the age groups, and the other subgroups. Histories of myocardial infarction, epilepsy, and ages greater than 70 years were factors that were significantly associated with postoperative adverse events.Conclusion: Compared with non-CKD patients, surgical patients with CKD exhibited more adverse events, with risks of in-hospital mortality that were approximately 2-fold higher after nonurinary surgery. These findings suggest an urgent need to revise the protocols for postoperative care in this population.Keywords: chronic kidney disease, surgery, outcome

Objectives: To compare the success and complication rates of radial artery catheterization using ultrasound guidance versus the conventional palpation technique in obese patients by anesthesia residents with similar levels of experience in both methods, and to measure the skin-to-artery distance of radial, brachial, and dorsalis pedis arteries using ultrasound with standardized anatomic landmarks., Design: Prospective, randomized controlled trial SETTING: Single tertiary center PARTICIPANTS: Eighty adults with a body mass index (BMI) ≥30 kg/m 2 INTERVENTIONS: Ultrasound guidance or conventional palpation method MEASUREMENTS AND MAIN RESULTS: The primary outcome was the first-attempt success rate of arterial catheterization. The skin-to-artery distance of the radial artery was significantly greater in the BMI groups of 40 to 49 kg/m 2 and ≥50 kg/m 2 compared to the BMI group of 30 to 39 kg/m 2 (mean difference, 1.0 mm; 95% confidence interval [CI], 0.4-1.7; p = 0.0029) for BMI 40-49 kg/m 2 vs 30-39 kg/m 2 and 1.5 mm (95% CI, 0.6-2.4 mm; p = 0.0015) for ≥50 kg/m 2 vs 30-39 kg/m 2 . Similar findings were observed for the brachial artery. BMI was inversely associated with first-attempt success rates (p = 0.0145) and positively with time to successful catheterization (p = 0.0271). The first-attempt success and vascular complication rates of catheterization did not differ significantly between the ultrasound guidance group (65.0% and 52.5%, respectively) and the conventional palpation group (70.0% [p = 0.6331] and 57.5% [p = 0.6531], respectively)., Conclusion: The results of this study do not support the routine use of ultrasonography during radial arterial catheterizations for obese adults when junior practitioners perform the procedure., 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 © 2024 Elsevier Inc. All rights reserved.)

Peritoneal dialysis (PD) is a widely used sustainable kidney replacement therapy. Prolonged use of PD fluids is associated with mesothelial-mesenchymal transition, peritoneal fibrosis, and eventual ultrafiltration (UF) failure. However, the impact of pressure on the peritoneum remains unclear. In the present study, we hypothesized increased pressure is a potential contributing factor to peritoneal fibrosis and investigated the possible mechanisms. In vitro experiments found that pressurization led to a mesenchymal phenotype, the expression of fibrotic markers and inflammatory factors in human mesothelial MeT-5A cells. Pressure also increased cell proliferation and augmented cell migration potential in MeT-5A cells. The mouse PD model and human peritoneum equilibrium test (PET) data both showed a positive association between higher pressure and increased small solute transport, along with decreased net UF. Mechanistically, we found that significant upregulation of CD44 in mesothelial cells upon pressurization. Notably, the treatment of CD44 neutralizing antibodies prevented pressure-induced phenotypic changes in mesothelial cells, while a CD44 inhibitor oligo-fucoidan ameliorated pressure-induced peritoneal thickening, fibrosis, and inflammation in PD mice. To conclude, intraperitoneal pressure results in peritoneal fibrosis in PD via CD44-mediated mesothelial changes and inflammation. CD44 blockage can be utilized as a novel preventive approach for PD-related peritoneal fibrosis and UF failure.

Background: Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults are often masked by physical health conditions. In younger adults, depression is associated with deficits in pupil light reflex and eye blink rate, suggesting the potential use of these responses as biomarkers for LLD., Methods: We conducted a study using video-based eye-tracking to investigate pupil and blink responses in LLD patients (n = 25), older (OLD) healthy controls (n = 29), and younger (YOUNG) healthy controls (n = 25). The aim was to determine whether there were alterations in pupil and blink responses in LLD compared to both OLD and YOUNG groups., Results: LLD patients displayed significantly higher blink rates and dampened pupil constriction responses compared to OLD and YOUNG controls. While tonic pupil size in YOUNG differed from that of OLD, LLD patients did not exhibit a significant difference compared to OLD and YOUNG controls. GDS-15 scores in older adults correlated with light and darkness reflex response variability and blink rates. PHQ-15 scores showed a correlation with blink rates, while MoCA scores correlated with tonic pupil sizes., Conclusions: The findings demonstrate that LLD patients display altered pupil and blink behavior compared to OLD and YOUNG controls. These altered responses correlated differently with the severity of depressive, somatic, and cognitive symptoms, indicating their potential as objective biomarkers for LLD., (© 2024. The Author(s).)

Background: There are limited real-world data regarding the use of droperidol for antiemetic prophylaxis in intravenous patient-controlled analgesia (IV-PCA). This study aimed to evaluate the antiemetic benefits and sedation effects of droperidol in morphine-based IV-PCA., Methods: Patients who underwent major surgery and used morphine-based IV-PCA at a medical center from January 2020 to November 2022 were retrospectively analyzed. The primary outcome was the rate of any postoperative nausea and/or vomiting (PONV) within 72 h after surgery. Propensity score matching was used to match patients with and without the addition of droperidol to IV-PCA infusate in a 1:1 ratio. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs)., Results: After matching, 1,104 subjects were included for analysis. The addition of droperidol to IV-PCA reduced the risk of PONV (aOR: 0.49, 95% CI: 0.35-0.67, p < 0.0001). The antiemetic effect of droperidol was significant within 36 h after surgery and attenuated thereafter. Droperidol was significantly associated with a lower risk of antiemetic uses (aOR: 0.58, 95% CI: 0.41-0.80, p = 0.0011). The rate of unintentional sedation was comparable between the patients with (9.1%) and without (7.8%; p = 0.4481) the addition of droperidol. Postoperative opioid consumption and numeric rating scale acute pain scores were similar between groups., Conclusions: The addition of droperidol to IV-PCA reduced the risk of PONV without increasing opiate consumption or influencing the level of sedation. However, additional prophylactic therapies are needed to prevent late-onset PONV., (© 2023. The Author(s).)

Background: Inflammatory bowel disease (IBD) is associated with lacrimal gland dysfunction and ocular inflammation. The objective of this research was to elucidate the temporal relationships between IBD, dry eye disease (DED), and corneal surface damage., Methods: In a matched nationwide cohort study, we evaluated the risk of DED and corneal surface damage associated with IBD. Multivariable Cox proportional hazards regression analyses were implemented to estimate the risk of ocular complications., Results: A total of 54,293 matched pairs were included for analyses. The median follow-up time was 8.3 years (interquartile range: 5.5 - 10.5). The period incidence of DED was 8.18 and 5.42 per 1000 person-years in the IBD and non-IBD groups, respectively. After adjusting for confounders, statistically significant associations were found between IBD and DED [adjusted hazard ratio (aHR): 1.43, 95% confidence interval (CI): 1.35 - 1.51, p < 0.0001], Sjögren's syndrome-related (aHR: 1.67, 95% CI:1.46 - 1.90, p < 0.0001) and non-Sjögren's syndrome-related subtypes (aHR: 1.38, 95% CI: 1.30 - 1.46, p < 0.0001). Furthermore, increased risks of corneal surface damage (aHR: 1.13, 95% CI: 1.03 - 1.24, p = 0.0094) among the patients with IBD were observed when compared with the controls. Other independent factors associated with corneal surface damage were age (aHR: 1.003), sex (male vs. female, aHR: 0.85), and monthly insurance premium (501-800 vs. 0-500 U.S. dollars, aHR: 1.45; ≥ 801 vs. 0-500 U.S. dollars, aHR: 1.32)., Conclusions: Our results suggested that IBD was an independent risk factor for DED and ocular surface damage. Clinical strategies are needed to prevent visual impairment or losses in these susceptible patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Study Objective: The prevention of perioperative hypothermia after anesthesia induction is a critical concern in patients undergoing abdominal surgery. The effectiveness of various warming systems for preventing hypothermia and shivering when applied to specific areas of the body remains undetermined., Design: Systematic review and network meta-analysis., Setting: Operating room., Intervention: Five electronic databases were searched, including only randomized control trials (RCTs) reporting the effects of warming systems applied to specific body sites on the intraoperative core temperature and postoperative risk of shivering in adults undergoing abdominal surgery. A multivariate random-effects network meta-analysis with a frequentist framework was implemented for data analysis., Measurements: The primary outcome was the core body temperature 60 and 120 min after anesthesia induction for abdominal surgery. The secondary outcome was the incidence of postoperative shivering., Results: This review comprised a total of 24 RCTs including 1119 patients. At 60 and 120 min after anesthesia induction, a forced-air warming system applied to the upper body (0.3 °C and 95% confidence intervals = [0.3 to 0.4], 1.0 °C [0.7 to 1.3]), lower body (0.4 °C [0.3 to 0.5], 0.9 °C [0.5 to 1.2]), and underbody (0.5 °C [0.5 to 0.6], 1.2 °C [0.9 to 1.6]) was superior to passive insulation in terms of core body temperature regulation. Compared with passive insulation, the forced-air warming system applied to the lower body (odds ratio = 0.06) or underbody (0.44) and the electric heating blanket to the lower body (0.02) or the whole body (0.07) significantly reduced the risk of shivering., Conclusions: The results of this NMA revealed that forced-air warming with an underbody blanket effectively elevates core body temperatures in 60 and 120 min after induction of anesthesia and prevents shivering in patients recovering from abdominal surgery., Competing Interests: Declaration of Competing interest The authors declare no potential conflicts of interest regarding the authorship and publication of this article., (Copyright © 2023. Published by Elsevier Inc.)

Background: Shared decision making using patient decision aids (PtDAs) was established over a decade ago, but few studies have evaluated its efficacy in Asian countries. We therefore evaluated the application of PtDAs in a decision conflict between two muscle relaxant reversal agents, neostigmine and sugammadex, and sequentially analyzed the regional differences and operating room turnover rates., Methods: This multicenter, outcome-assessor-blind, randomized controlled trial included 3,132 surgical patients from two medical centers admitted between March 2020 and August 2020. The patients were randomly divided into the classical and PtDA groups for pre-anesthesia consultations. Their clinicodemographic characteristics were analyzed to identify variables influencing the choice of reversal agent. On the day of the pre-anesthesia consultation, the patients completed the four SURE scale (sure of myself, understand information, risk-benefit ratio, encouragement) screening items. The operating turnover rates were also evaluated using anesthesia records., Results: Compared with the classical group, the PtDA group felt more confident about receiving sufficient medical information (P < 0.001), felt better informed about the advantages and disadvantages of the medications (P < 0.001), exhibited a superior understanding of the benefits and risks of their options (P < 0.001), and felt surer about their choice (P < 0.001). Moreover, the PtDA group had a significantly greater tendency to choose sugammadex over neostigmine (P < 0.001)., Conclusions: PtDA interventions in pre-anesthesia consultations provided surgical patients with clear knowledge and better support. PtDAs should be made available in other medical fields to enhance shared clinical decision-making.

Background: Previous observational studies have shown that people with dental scaling (DS) had decreased risk of stroke. However, limited information is available on the association between DS and poststroke outcomes. The present study aimed to evaluate the effects of regular DS on the complications and mortality after stroke., Methods: We conducted a retrospective cohort study of 49,547 hospitalized stroke patients who received regular DS using 2010-2017 claims data of Taiwan's National Health Insurance. Using a propensity-score matching procedure, we selected 49,547 women without DS for comparison. Multiple logistic regressions were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of poststroke complications and in-hospital mortality associated with regular DS., Results: Stroke patients with regular DS had significantly lower risks of poststroke pneumonia (OR 0.58, 95% CI 0.54-0.63), septicemia (OR 0.58, 95% CI 0.54-0.63), urinary tract infection (OR 0.68, 95% CI 0.66-0.71), intensive care (OR 0.81, 95% CI 0.78-0.84), and in-hospital mortality (OR 0.66, 95% CI 0.62-0.71) compared with non-DS stroke patients. Stroke patients with regular DS also had shorter hospital stays (p < 0.0001) and less medical expenditures (p < 0.0001) during stroke admission than the control group. Lower rates of poststroke adverse events in patients with regular DS were noted in both sexes, all age groups, and people with various types of stroke., Conclusion: Stroke patients with regular DS showed fewer complications and lower mortality compared with patients had no DS. These findings suggest the urgent need to promote regular DS for this susceptible population of stroke patients., (© 2023. The Author(s).)

Background: Hepatocellular carcinoma (HCC) remains an aggressive malignancy with a poor prognosis and a leading cause of cancer-related mortality globally. Cumulative evidence suggests critical roles for endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in chronic liver diseases. However, the role of ER stress in HCC pathogenesis, aggressiveness and therapy response remains unclear and understudied., Objectives: Against this background, the present study evaluated the therapeutic efficacy and feasibility of notopterol (NOT), a furanocoumarin and principal component of Notopterygium incisum , in the modulation of ER stress and cancer stemness, and the subsequent effect on liver oncogenicity., Methods: An array of biomolecular methods including Western blot, drug cytotoxicity, cell motility, immunofluorescence, colony and tumorsphere formation, flow-cytometric mitochondrial function, GSH/GSSG ratio, and tumor xenograft ex vivo assays were used in the study., Results: Herein, we demonstrated that NOT significantly suppresses the viability, migration, and invasion capacity of the human HCC HepJ5 and Mahlavu cell lines by disrupting ATF4 expression, inhibiting JAK2 activation, and downregulating the GPX1 and SOD1 expression in vitro. NOT also markedly suppressed the expression of vimentin (VIM), snail, b-catenin, and N -cadherin in the HCC cells, dose-dependently. Treatment with NOT significantly attenuated cancer stem cells (CSCs)-like phenotypes, namely colony and tumorsphere formation, with the concomitant downregulation of stemness markers OCT4, SOX2, CD133, and upregulated PARP-1 cleavage, dose-dependently. We also demonstrated that NOT anticancer activity was strongly associated with increased cellular reactive oxidative stress (ROS) but, conversely, reduced mitochondrial membrane potential and function in the HepJ5 and Mahlavu cells in vitro. Our tumor xenograft studies showed that compared with sorafenib, NOT elicited greater tumor growth suppression without adverse changes in mice body weights. Compared with the untreated control and sorafenib-treated mice, NOT-treated mice exhibited markedly greater apoptosis ex vivo, and this was associated with the co-suppression of stemness and drug-resistance markers OCT4, SOX2, ALDH1, and the upregulation of endoplasmic reticulum stress and oxidative stress factors PERK and CHOP., Conclusions: In summary, we demonstrated for the first time that NOT exhibits strong anticancer activity via the suppression of cancer stemness, enhanced endoplasmic reticulum stress and increased oxidative stress thus projecting NOT as a potentially effective therapeutic agent against HCC.

Autoimmune thyroid diseases (ATDs) are potentially connected to lacrimal gland dysfunction and ocular surface disruption. This study aimed to evaluate the relationships between ATD, dry eye disease (DED), and corneal surface damage. In a matched nationwide cohort study, we used Taiwan's National Health Insurance research database to compare the incidences of DED and corneal surface damage between subjects with and without ATD. Multivariable Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the ophthalmological outcomes. A total of 50,251 matched pairs with 748,961 person-years of follow-up were included for analysis. The incidence of DED was 16.37 and 8.36 per 1000 person-years in the ATD and non-ATD groups, respectively. ATDs were significantly associated with increased DED (aHR: 1.81, 95% CI: 1.73-1.89, p < 0.0001). This association was generally consistent across the subgroups of age, sex, different comorbidity levels, and use of systemic corticosteroids or not. Furthermore, patients with ATD had a higher risk of corneal surface damage compared with non-ATD subjects (aHR: 1.31, 95% CI: 1.19-1.44, p < 0.0001), including recurrent corneal erosions (aHR: 2.00, 95% CI: 1.66-2.41, p < 0.0001) and corneal scars (aHR: 1.26, 95% CI: 1.01-1.59, p = 0.0432). Other independent factors for corneal surface damage were age, sex, diabetes mellitus, Charlson Comorbidity Index scores, and use of systemic corticosteroids. Our results suggested that ATDs were associated with higher risks of DED and corneal surface damage. Considering the high prevalence of ATD, prophylactic and therapeutic strategies should be further developed to prevent irreversible vision loss in this susceptible population.

Background: Chronic exposure to nicotine may change pain perception and promote opioid intake. This study aimed to evaluate the putative effect of cigarette smoking on opioid requirements and pain intensity after surgery., Methods: Patients who underwent major surgery and received intravenous patient-controlled analgesia (IV-PCA) at a medical center between January 2020 and March 2022 were enrolled. Patients' preoperative smoking status was assessed using a questionnaire by certified nurse anesthetists. The primary outcome was postoperative opioid consumption within 3 days after surgery. The secondary outcome was the mean daily maximum pain score, assessed using a self-report 11-point numeric rating scale, and the number of IV-PCA infusion requests within three postoperative days. Multivariable linear regression models were used to calculate the regression coefficient (beta) and 95% confidence interval (CI) for the association between smoking status and outcomes of interest., Results: A total of 1162 consecutive patients were categorized into never smokers (n = 968), former smokers (n = 45), and current smokers (n = 149). Current smoking was significantly associated with greater postoperative opioid consumption (beta: 0.296; 95% CI, 0.068-0.523), higher pain scores (beta: 0.087; 95% CI, 0.009-0.166), and more infusion requests (beta: 0.391; 95% CI, 0.073-0.710) compared with never smokers. In a dose-dependent manner, smoking quantity (cigarette per day) was positively correlated with both intraoperative (Spearman's rho: 0.2207, p = 0.007) and postoperative opioid consumption (Spearman's rho: 0.1745, p = 0.033) among current smokers., Conclusion: Current cigarette smokers experienced higher acute pain, had more IV-PCA infusion requests, and consumed more opioids after surgery. Multimodal analgesia with nonopioid analgesics and opioid-sparing techniques, along with smoking cessation should be considered for this population., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Systemic lupus erythematosus (SLE) potentially involves multiple parts of the ocular system, including the lacrimal glands and the cornea. The present study sought to assess the risk of aqueous-deficient dry eye disease (DED) and corneal surface damage in patients with SLE. We conducted a population-based cohort study using Taiwan's National Health Insurance research database to compare the risks of DED and corneal surface damage between subjects with and without SLE. Proportional hazard regression analyses were used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the study outcomes. The propensity score matching procedure generated 5083 matched pairs with 78,817 person-years of follow-up for analyses. The incidence of DED was 31.90 and 7.66 per 1000 person-years in patients with and without SLE, respectively. After adjusting for covariates, SLE was significantly associated with DED (aHR: 3.30, 95% CI: 2.88-3.78, p < 0.0001) and secondary Sjögren's syndrome (aHR: 9.03, 95% CI: 6.86-11.88, p < 0.0001). Subgroup analyses demonstrated that the increased risk of DED was augmented among patients with age < 65 years and female sex. In addition, patients with SLE had a higher risk of corneal surface damage (aHR: 1.81, 95% CI: 1.35-2.41, p < 0.0001) compared to control subjects, including recurrent corneal erosion (aHR: 2.98, 95% CI: 1.63-5.46, p = 0.0004) and corneal scar (aHR: 2.23, 95% CI: 1.08-4.61, p = 0.0302). In this 12-year nationwide cohort study, we found that SLE was associated with increased risks of DED and corneal surface damage. Regular ophthalmology surveillance should be considered to prevent sight-threatening sequelae among patients with SLE.

Rheumatoid arthritis is potentially connected to ocular disorders, such as corneal inflammation and lacrimal gland destruction. This study aimed to evaluate the risk of dry eye disease (DED) and corneal surface damage among patients with rheumatoid arthritis. In a nationwide cohort study, we utilized Taiwan’s National Health Insurance research database and conducted propensity score matching to compare the risks of DED and corneal surface damage between patients with and without rheumatoid arthritis. Proportional hazards regression analyses were used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the outcomes of interest. The matching procedure generated 33,398 matched pairs with 501,377 person-years of follow-up for analyses. The incidence of DED was 23.14 and 10.25 per 1000 person-years in patients with and without rheumatoid arthritis, respectively. After adjusting for covariates, rheumatoid arthritis was significantly associated with DED (aHR: 2.03, 95% CI: 1.93−2.13, p < 0.0001). The association was generally consistent across the subgroups of age, sex, use of systemic corticosteroids, and different comorbidity levels. In addition, patients with rheumatoid arthritis had a higher risk of corneal surface damage (aHR: 1.36, 95% CI: 1.21−1.51, p < 0.0001) compared to control subjects. Other independent factors for corneal surface damage were age and sleeping disorders. Rheumatoid arthritis was associated with an increased risk of DED and corneal surface damage. Ophthalmological surveillance is required to prevent vision-threatening complications in this susceptible population.

Sugammadex has several pharmacological advantages over neostigmine, including faster reversal of neuromuscular blockade and fewer adverse effects. However, the economic impact of sugammadex remains controversial due to the considerable heterogeneity of study designs and clinical settings in previous studies. In a post-hoc analysis of a randomized controlled trial, we evaluated patients who underwent elective surgeries and general anesthesia with endotracheal intubation in a medical center in Taiwan between March 2020 and August 2020. Patients were divided into either the sugammadex or neostigmine group based on the neuromuscular blocking drug used. Propensity score matching was used to balance the baseline patient characteristics between the two groups. The patient’s recovery from anesthesia and the putative cost-effectiveness of sugammadex versus neostigmine was assessed. Derived cost-effectiveness using personnel costs in the operating room and the post-anesthesia care unit was estimated using multiple linear regression models. A total of 2587 and 1784 patients were included before and after matching, respectively. Time to endotracheal extubation was significantly shorter in the sugammadex group (mean 6.0 ± standard deviation 5.3 min) compared with the neostigmine group (6.6 ± 6.3 min; p = 0.0032). In addition, the incidence of bradycardia was significantly lower in the sugammadex group (10.2%) compared with the neostigmine group (16.9%; p < 0.001). However, the total costs were significantly lower in the neostigmine group (50.6 ± 21.4 United States dollars) compared with the sugammadex group (212.0 ± 49.5 United States dollars). Despite improving postoperative recovery, the benefits of sugammadex did not outweigh its higher costs compared with neostigmine, possibly due to the low costs of labor in Taiwan’s healthcare system.

Background: The influence of alcoholic liver disease (ALD) on the postoperative outcomes is not completely understood. Our purpose is to evaluate the complications and mortality after nonhepatic surgeries in patients with ALD., Methods: We conducted a retrospective cohort study included adults aged 20 years and older who underwent nonhepatic elective surgeries using data of Taiwan's National Health Insurance, 2008-2013. Using a propensity-score matching procedure, we selected surgical patients with ALD (n = 26,802); or surgical patients without ALD (n = 26,802) for comparison. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of postoperative complications and in-hospital mortality associated with ALD., Results: Patients with ALD had higher risks of acute renal failure (OR 2.74, 95% CI 2.28-3.28), postoperative bleeding (OR 1.64, 95% CI 1.34-2.01), stroke (OR 1.51, 95% CI 1.34-1.70) septicemia (OR 1.47, 95% CI 1.36-1.58), pneumonia (OR 1.43, 95% CI 1.29-1.58), and in-hospital mortality (OR 2.64, 95% CI 2.24-3.11) than non-ALD patients. Patients with ALD also had longer hospital stays and higher medical expenditures after nonhepatic surgical procedures than the non-ALD patients. Compared with patients without ALD, patients with ALD who had jaundice (OR 4.82, 95% CI 3.68-6.32), ascites (OR 4.57, 95% CI 3.64-5.74), hepatic coma (OR 4.41, 95% CI 3.44-5.67), gastrointestinal hemorrhage (OR 3.84, 95% CI 3.09-4.79), and alcohol dependence syndrome (OR 3.07, 95% CI 2.39-3.94) were more likely to have increased postoperative mortality., Conclusion: Surgical patients with ALD had more adverse events and a risk of in-hospital mortality after nonhepatic surgeries that was approximately 2.6-fold higher than that for non-ALD patients. These findings suggest the urgent need to revise the protocols for peri-operative care for this population., (© 2022. The Author(s).)

Sedative−hypnotic misuse is associated with psychiatric diseases and overdose deaths. It remains uncertain whether types of anesthesia affect the occurrence of new postoperative uses of sedative−hypnotics (NPUSH). We used reimbursement claims data of Taiwan’s National Health Insurance and conducted propensity score matching to compare the risk of NPUSH between general and neuraxial anesthesia among surgical patients who had no prescription of oral sedative−hypnotics or diagnosis of sleep disorders within the 12 months before surgery. The primary outcome was NPUSH within 180 days after surgery. Multivariable logistic regression models were used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 92,222 patients were evaluated after matching. Among them, 15,016 (16.3%) had NPUSH, and 2183 (4.7%) were made a concomitant diagnosis of sleep disorders. General anesthesia was significantly associated both with NPUSH (aOR: 1.17, 95% CI: 1.13−1.22, p < 0.0001) and NPUSH with sleep disorders (aOR: 1.11, 95% CI: 1.02−1.21, p = 0.0212) compared with neuraxial anesthesia. General anesthesia was also linked to NPUSH that occurred 90−180 days after surgery (aOR: 1.12, 95% CI: 1.06−1.19, p = 0.0002). Other risk factors for NPUSH were older age, female, lower insurance premium, orthopedic surgery, specific coexisting diseases (e.g., anxiety disorder), concurrent medications (e.g., systemic steroids), postoperative complications, perioperative blood transfusions, and admission to an intensive care unit. Patients undergoing general anesthesia had an increased risk of NPUSH compared with neuraxial anesthesia. This finding may provide an implication in risk stratification and prevention for sedative−hypnotic dependence after surgery.

Background: Obese people have a higher risk of difficult laryngoscopy due to their thick neck, large tongue, and redundant pharyngeal soft tissue. However, there is still no established predictive factor for difficult laryngoscopy in obese population., Methods: We conducted a prospective assessor-blind observational study to enroll adult patients with a body mass index of 30 kg·m-2 or higher undergoing laparoscopic sleeve gastrectomy at a medical center between May 2020 and August 2021. Conventional morphometric characteristics along with ultrasonographic airway parameters were evaluated before surgery. The primary outcome was difficult laryngoscopy, defined as a Cormack and Lehane's grade III or IV during direct laryngoscopy. Logistic regression analyses were performed to evaluate the association between included factors and difficult laryngoscopy. Discrimination performance of predictive factors was assessed using area under the receiver operating characteristic curve (AUC)., Results: A total of 80 patients were evaluated, and 17 (21.3%) developed an event of difficult laryngoscopy. Univariate analyses identified five factors associated with difficult laryngoscopy, including age, sex, hypertension, neck circumference, and cross-sectional area of tongue base. After adjusting for these variables, neck circumference was the only independent influential factor, adjusted odds ratio: 1.227 (95% confidence interval, 1.009-1.491). Based on Youden's index, the optimal cutoff of neck circumference was 49.1 cm with AUC: 0.739 (sensitivity: 0.588, specificity: 0.889; absolute risk difference: 0.477, and number needed to treat: 3)., Conclusion: Greater neck circumference was an independent risk factor for difficult laryngoscopy in obese patients. This finding provides a way of reducing unanticipated difficult airway in this high-risk population., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

The purpose of this phase I clinical trial is to assess the safety and tolerability of allogeneic adipose tissue-derived stem cells (ADSCs) among chronic kidney disease (CKD) patients. 12 eligible CKD patients with an estimated glomerular filtration rate (eGFR) of 15-44 ml/min/1.73 m 2 received one dose of intravenous allogeneic ADSCs (ELIXCYTE ® ), as 3 groups: 3 low dose (6.4 × 10 7 cells in total of 8 ml), 3 middle dose (19.2 × 10 7 cells in total of 24 ml) and 6 high dose (32.0 × 10 7 cells in total of 40 ml) of ELIXCYTE ® and evaluated after 48 weeks. Primary endpoint was the safety profiles in terms of incidence of adverse events (AEs) and serious adverse event (SAE). Two subjects in high dose group experienced a total of 2 treatment-related AEs which are Grade 1 slow speech and Grade 1 bradyphrenia after the infusion. One subject in middle dose group experienced an SAE unlikely related to treatment, grade 2 proteinuria. No fatal AE was reported in this study. An increase in eGFR was observed in 7 out of 12 subjects (58%) at Week 24 and in 6 of 12 subjects (50%) by Week 48. By Week 24, an increase in eGFR by more than 20% among all CKD patients with baseline eGFR ≧ 30 ml/min/1.73 m 2 as compared to only 2 subjects in baseline eGFR < 30 ml/min/1.73 m 2  group. No significant reduction in proteinuria was noted among all subjects. This phase I trial demonstrated single-dose intravenous ELIXCYTE was well tolerated in moderate-to-severe CKD patients and its preliminary efficacy warrants future studies., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The influence of red yeast rice (RYR) on the risk of incident stroke remains underexplored. We aimed to compare the risk of stroke between people with and without use of RYR prescriptions. We used research data from the National Health Insurance Program in Taiwan and identified 34,723 adults (aged ≥20 years) who first received the RYR prescription from 2010 to 2014. To select the appropriate control group, we used frequency matching by age and sex (case-control ratio = 1 : 1) and identified a non-RYR cohort that included 34,723 adults who first received lovastatin. Events of an incident stroke that occurred during the follow-up period of 2010-2017 were identified from medical claims. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of stroke risk associated with RYR prescription were calculated in the multiple Cox proportional hazard model. Compared with the non-RYR cohort, patients who received RYR prescriptions had a decreased risk of stroke (HR 0.65, 95% CI 0.59-0.71), including hemorrhagic stroke (HR 0.60, 95% CI 0.44-0.83), ischemic stroke (HR 0.49, 95% CI 0.43-0.57), and other types of strokes (HR 0.53, 95% CI 0.42-0.67). The association between RYR prescription and stroke risk was significant in both sexes and in people aged more than 40 years, as well as in those individuals with various medical conditions. The frequency of RYR prescription (HR 0.57, 95% CI 0.50-0.64) was associated with a decreased risk of stroke with a dose-response relationship ( p for trend<0.0001). This study showed a potentially positive effect of RYR on the risk of stroke. However, compliance with medication use should be cautioned. The findings of this study require future studies to validate the beneficial effects of RYR prescription on stroke risk., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Chuen-Chau Chang et al.)

Acute kidney disease (AKD) comprises acute kidney injury (AKI). However, whether the AKD staging system has prognostic values among AKI patients with different baseline estimated glomerular filtration (eGFR) remains a controversial issue. Algorithm-based approach was applied to identify AKI occurrence and to define different AKD stages. Risk ratio for major adverse kidney events (MAKE), including (1) eGFR decline > 35% from baseline, (2) initiation of dialysis, (3) in-hospital mortality of different AKD subgroups were identified by multivariable logistic regression. Among the 4741 AKI patients identified from January 2015 to December 2018, AKD stages 1-3 after AKI was common (53% in the lower baseline eGFR group and 51% in the higher baseline eGFR group). In the logistic regression model adjusted for demographics and comorbidities at 1-year follow-up, AKD stages 1/2/3 (AKD stage 0 as reference group) were associated with higher risks of MAKE (AKD stage: odds ratio, 95% confidence interval [95% CI], AKD 1: 1.85, 1.56-2.19; AKD 2: 3.43, 2.85-4.12; AKD 3: 10.41, 8.68-12.49). Regardless of baseline eGFR, staging criteria for AKD identified AKI patients who were at higher risk of kidney function decline, dialysis and mortality. Post-AKI AKD patients with severer stage need intensified care and timely intervention., (© 2022. The Author(s).)

Background and Objectives : Although complications after liver resection for hepatic cancer are common, the long-term impact of these complications on oncological outcomes remains unclear. This study aimed to investigate the potential effect of high-grade postoperative complications on long-term mortality and cancer recurrence after surgical resection of hepatocellular carcinoma. Materials and Methods : In a retrospective cohort study, patients undergoing curative liver resection for primary hepatocellular carcinoma between 2005 and 2016 were evaluated. The Clavien-Dindo (CD) grading system was used to classify patients into two groups of either high-grade complications (grade III or IV) or none or low-grade complications (grade 0 to II) within 30 days after surgery. The primary endpoint was all-cause mortality. Secondary endpoints were cancer-specific mortality and cancer recurrence. Weighted Cox proportional hazards regression models were used to calculate the adjusted hazard ratio (aHR) with a 95% confidence interval (CI) for the outcomes of interest. Results : A total of 1419 patients with a median follow-up time of 46.6 months were analysed. Among them, 93 (6.6%) developed high-grade complications after surgery. The most common complications were bile leakage ( n = 30) in CD grade III and respiratory failure ( n = 13) in CD grade IV. High-grade complications were significantly associated with all-cause mortality (aHR: 1.78, 95% CI: 1.55-2.06) and cancer-specific mortality (aHR: 1.34, 95% CI: 1.13-1.60), but not cancer recurrence (aHR: 0.92, 95% CI: 0.84-1.02). Independent influential factors for complications were sex, diabetes mellitus, clinically significant portal hypertension, oesophageal varices, multifocal cancer, intraoperative blood loss, and anaesthesia duration. Conclusions : Patients who had high-grade postoperative complications had a greater risk of long-term mortality after liver resection for hepatocellular carcinoma. Prevention of postoperative complications may serve as an effective strategy for improving long-term survival.

Background: Despite the continual improvements in dialysis treatments, mortality in end-stage kidney disease (ESKD) remains high. Many mortality prediction models are available, but most of them are not precise enough to be used in the clinical practice. We aimed to develop and validate two prediction models for 3-month and 1-year patient mortality after dialysis initiation in our population., Methods: Using population-based data of insurance claims in Taiwan, we included more than 210,000 patients who initiated dialysis between January 1, 2006, and June 30, 2015. We developed two prognostic models, which included 9 and 11 variables, respectively (including age, sex, myocardial infarction, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, peptic ulcer disease, malignancy, moderate to severe liver disease, and first dialysis in intensive care unit)., Results: The models showed adequate discrimination (C-statistics were 0.80 and 0.82 for 3-month and 1-year mortality, respectively) and good calibration. In both our models, the first dialysis in the intensive care unit and moderate-to-severe liver disease were the strongest risk factors for mortality., Conclusion: The prediction models developed in our population had good predictive ability for short-term mortality in patients initiating dialysis in Taiwan and could help in decision-making regarding dialysis initiation, at least in our setting, supporting a patient-centered approach to care., (© 2021. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Obese patients are predisposed to rapid oxygen desaturation during tracheal intubation. We aimed to compare the risk of desaturation between high-flow nasal oxygenation (HFNO) and classical facemask oxygenation (FMO) during rapid sequence intubation for elective surgery in obese patients. Adults with a body mass index ≥30 kg·m−2 undergoing laparoscopic sleeve gastrectomy at a medical center were randomized into the HFNO group (n = 40) and FMO group (n = 40). In the HFNO group, patients used a high-flow nasal cannula to receive 30 to 50 L·min−1 flow of heated and humidified 100% oxygen. In the FMO group, patients received a fitting facemask with 15 L·min−1 flow of 100% oxygen. After 5-min preoxygenation, rapid sequence intubation was performed. The primary outcome was arterial desaturation during intubation, defined as a peripheral capillary oxygen saturation (SpO2) <92%. The risk of peri-intubation desaturation was significantly lower in the HFNO group compared to the FMO group; absolute risk reduction: 0.20 (95% confidence interval: 0.05−0.35, p = 0.0122); number needed to treat: 5. The lowest SpO2 during intubation was significantly increased by HFNO (median 99%, interquartile range: 97−100) compared to FMO (96, 92−100, p = 0.0150). HFNO achieved a higher partial pressure of arterial oxygen (PaO2) compared to FMO, with medians of 476 mmHg (interquartile range: 390−541) and 397 (351−456, p = 0.0010), respectively. There was no difference in patients’ comfort level between groups. Compared with standard FMO, HFNO with apneic oxygenation reduced arterial desaturation during tracheal intubation and enhanced PaO2 among patients with obesity.

The clinical efficacy of spectral entropy monitoring in improving postoperative recovery remains unclear. This trial aimed to investigate the impact of M-Entropy (GE Healthcare, Helsinki, Finland) guidance on emergence from anesthesia and postoperative delirium in thoracic surgery. Adult patients undergoing video-assisted thoracoscopic surgery for lung resection at a medical center were randomly allocated into the M-Entropy guidance group (n = 39) and the control group (n = 37). In the M-Entropy guidance group, sevoflurane anesthesia was titrated to maintain response and state entropy values between 40 and 60 intraoperatively. In the control group, the dosing of sevoflurane was adjusted based on clinical judgment and vital signs. The primary outcome was time to spontaneous eye opening. M-Entropy guidance significantly reduced the time proportion of deep anesthesia (entropy value <40) during surgery, mean difference: −21.5% (95% confidence interval (CI): −32.7 to −10.3) for response entropy and −24.2% (−36.3 to −12.2) for state entropy. M-Entropy guidance significantly shortened time to spontaneous eye opening compared to clinical signs, mean difference: −154 s (95% CI: −259 to −49). In addition, patients of the M-Entropy group had a lower rate of emergence agitation (absolute risk reduction: 0.166, 95% CI: 0.005−0.328) and delirium (0.245, 0.093−0.396) at the postanesthesia care unit. M-Entropy-guided anesthesia hastened awakening and potentially prevented emergence agitation and delirium after thoracic surgery. These results may provide an implication for facilitating postoperative recovery and reducing the complications associated with delayed emergence and delirium.

Background: Current practice guidelines recommend the use of nasal cannula as an alternative pre-oxygenation method for tracheal intubation. However, the efficacy of high-flow nasal oxygenation versus standard facemask oxygenation has not been fully evaluated., Methods: We searched PubMed, Cochrane Library, and ClinicalTrials.gov for English-language studies published from January 1, 2000 to November 30, 2021. We included randomized controlled trials which compared high-flow nasal oxygenation and facemask oxygenation as the pre-oxygenation maneuver. Primary outcome was arterial partial pressure of oxygen (PaO2) after pre-oxygenation. Secondary outcomes were safe apnea time, arterial desaturation during intubation, lowest peripheral capillary oxygen saturation during intubation, and patient comfort score. Random-effects models and Mantel-Haenszel method were used for data synthesis., Results: A total of 16 randomized controlled trials and 1148 patients were included. High-flow nasal oxygenation achieved a higher PaO2 compared with facemask, mean difference: 64.86 mm Hg (95% confidence interval [CI]: 32.33-97.40, P < .0001). Safe apnea time was longer in high-flow nasal oxygenation, mean difference: 131.03 seconds (95% CI: 59.39-202.66, P < .0001). There was no difference in the risk of peri-intubation desaturation or lowest peripheral capillary oxygen saturation between groups. Patient comfort score was higher in high-flow nasal oxygenation, mean difference: 1.00 (95% CI: 0.46-1.54, P = .0003)., Conclusion: High-flow nasal oxygenation better enhanced PaO2 and extended safe apnea time and is not inferior to facemask oxygenation in preventing desaturation during tracheal intubation. High-flow nasal oxygenation may be considered as an alternative method, especially for patients with a potential difficult airway., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Patients who previously suffered a stroke have increased risks of mortality and complications after surgeries, but the optimal anesthesia method is not fully understood. We aimed to compare the outcomes after surgeries for stroke patients who received general anesthesia (GA) and neuraxial anesthesia (NA). Using health insurance research data, we identified 36,149 stroke patients who underwent surgeries from 1 January 2008 to 31 December 2013. For balancing baseline covariates, the propensity-score-matching procedure was used to select adequate surgical patients who received GA and NA at a case-control ratio of 1:1. Multiple logistic regressions were applied to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for postoperative mortality and complications between surgical patients with prior stroke who received GA and NA. Among the 4903 matched pairs with prior stroke, patients with GA had higher risks of pneumonia (OR 2.00, 95% CI 1.62-2.46), pulmonary embolism (OR 3.30, 95% CI 1.07-10.2), acute renal failure (OR 3.51, 95% CI 1.13-2.10), intensive care unit stay (OR 3.74, 95% CI 3.17-4.41), and in-hospital mortality (OR 2.02, 95% CI 1.16-3.51) than those who received NA. Postoperative adverse events were associated with GA in patients aged more than 60 years and those who received digestive surgery (OR 3.11, 95% CI 2.08-4.66). We found that stroke patients undergoing GA had increased postoperative complications and mortality after surgery compared with those who received NA. However, these findings need more validation and evaluation by clinical trials.

Gastroenteritis promotes the development of systemic inflammation and a hypercoagulable state. There are limited data regarding the association between gastroenteritis and acute myocardial infarction (AMI). We aimed to evaluate the risk of AMI after an episode of gastroenteritis. In this nested case-control study, we selected patients who were hospitalized for AMI ( N = 103,584) as a case group during 2010-2017 and performed propensity score matching (case-control ratio 1:1) to select eligible controls from insurance research data in Taiwan. We applied multivariable logistic regressions to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of AMI associated with recent gastroenteritis within 14 days before AMI. We also compared the outcomes after AMI in patients with or without gastroenteritis. A total of 1381 patients (1.3%) with AMI had a prior episode of gastroenteritis compared to 829 (0.8%) among the controls. Gastroenteritis was significantly associated with a subsequent risk of AMI (adjusted OR: 1.68, 95% CI: 1.54-1.83), which was augmented in hospitalizations for gastroenteritis (adjusted OR: 2.50, 95% CI: 1.20-5.21). The outcomes after AMI were worse in patients with gastroenteritis than in those without gastroenteritis, including increased 30-day in-hospital mortality (adjusted OR: 1.28, 95% CI: 1.08-1.52), medical expenditure, and length of hospital stay. Gastroenteritis may act as a trigger for AMI and correlates with worse post-AMI outcomes. Strategies of aggressive hydration and/or increased antithrombotic therapies for this susceptible population should be further developed.

This retrospective study aimed to investigate the effect of diabetes mellitus (DM) on the risks of end-stage kidney disease (ESKD) and post-liver transplantation (post-LT) mortality. Using data from the National Health Insurance Research Database, Taiwan, 3,489 patients who received a LT between 1 January 2005, and 31 December 2015, were enrolled in this study and divided into the pre-existing DM, post-LT DM (PLTDM), and without DM groups. All subjects were followed up from 1 year after LT to the index date for ESKD, and the occurrence of death, or until 31 December 2016. Of the 3,489 patients with LT, 1,016 had pre-existing DM, 215 had PLTDM, and 2,258 had no DM pre- or post-LT. The adjusted HRs of ESKD were 1.77 (95% Confidence Interval [CI], .78-3.99) and 2.61 (95% CI, 1.63-4.18) for PLTDM group and pre-existing DM group compared to without DM group, respectively. For the risk of death, the adjusted HRs were 1.05 (95% CI, .72-1.55) and 1.28 (95% CI, 1.04-1.59) for PLTDM group and pre-existing DM group compared to those without DM group, respectively. The sensitivity analysis for the risk of ESKD and death also revealed the consistent result. Pre-existing DM has significant increase the risk of post-LT ESKD and mortality. The role of PLTDM should be explored to explain postoperative morbidity and mortality., 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 © 2022 Lee, Wu, Chan, Chen, Hsu, Wu and Cherng.)

Background and Aims: The effects of influenza vaccination (IV) on the outcomes of patients with kidney disease (KD) are not completely understood. We aimed to evaluate and compare the outcomes during admission of KD between elderly patients who did or did not receive an IV within the previous 12 months., Methods: We used health insurance research data in Taiwan and conducted a population-based cohort study that included 22,590 older people aged ≥ 65 years who were hospitalized for KD in 2008-2013. We performed propensity score matching (case-control ratio 1:1) to select 4386 eligible IV recipients and 4386 nonrecipient controls for comparison. The adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of IV associated with complications and mortality during KD admission were calculated using multivariable logistic regression analyses., Results: During hospitalization for KD, IV was significantly associated with lower risks of 30-day in-hospital mortality (OR 0.56, 95% CI 0.39-0.82), septicemia (OR 0.77, 95% CI 0.68-0.87), and intensive care (OR 0.85, 95% CI 0.75-0.96). Additionally, IV recipients had a shorter length of hospital stay and lower medical expenditure than nonrecipients. Subgroup analyses further showed that the association of IV with reduced adverse events was confined to patients aged ≥ 75 years., Conclusions: Previous IV was associated with reduced risks of complications and mortality and in elderly patients hospitalized for KD. We raised the possibility and suggested the need to promote IV for this susceptible population of patients with KD., Competing Interests: The authors have declared that no competing interests exist.

Migraine headaches can be provoked by surgical stress and vasoactive effects of anesthetics of general anesthesia in the perioperative period. However, it is unclear whether general anesthesia increases the migraine risk after major surgery. Incidence and risk factors of postoperative migraine are also largely unknown. We utilized reimbursement claims data of Taiwan's National Health Insurance and performed propensity score matching analyses to compare the risk of postoperative migraine in patients without migraine initially who underwent general or neuraxial anesthesia. Multivariable logistic regressions were applied to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for migraine risk. A total of 68,131 matched pairs were analyzed. The overall incidence of migraine was 9.82 per 1000 person-years. General anesthesia was not associated with a greater risk of migraine compared with neuraxial anesthesia (aORs: 0.93, 95% CI: 0.80-1.09). This finding was consistent across subgroups of different migraine subtypes, uses of migraine medications, and varying postoperative periods. Influential factors for postoperative migraine were age (aOR: 0.99), sex (male vs. female, aOR: 0.50), pre-existing anxiety disorder (aOR: 2.43) or depressive disorder (aOR: 2.29), concurrent uses of systemic corticosteroids (aOR: 1.45), ephedrine (aOR: 1.45), and theophylline (aOR: 1.40), and number of emergency room visits before surgery. There was no difference in the risk of postoperative migraine between surgical patients undergoing general and neuraxial anesthesia. This study identified the risk factors for postoperative migraine headaches, which may provide an implication in facilitating early diagnoses and treatment.

Obesity increases the risk of prolonged emergence from general anesthesia due to the delayed release of anesthetic agents from body fat. This trial aimed to evaluate the effects of sevoflurane and desflurane along with anesthetic depth monitoring on emergence time from anesthesia in obese patients. Adults with a body mass index ≥ 30 kg·m -2 undergoing laparoscopic sleeve gastrectomy at a medical center were randomized into four groups: sevoflurane or desflurane anesthesia with or without M-Entropy guidance on anesthetic depth in a ratio of 1:1:1:1. In the M-Entropy guidance groups, the dosage of sevoflurane and desflurane was adjusted to achieve response and state entropy values between 40 and 60 during surgery. In the non-M-Entropy guidance groups, the dosage of anesthetics was titrated according to clinical signs. Primary outcome was time to spontaneous eye opening. A total of 80 participants were randomized. Compared to sevoflurane, desflurane anesthesia significantly reduced the time to spontaneous eye opening [mean difference (MD): -129 s; 95% confidence interval (CI): -211, -46], obeying commands (-160; -243, -77), tracheal extubation (-172; -266, -78), and leaving operating room (-148; -243, -54). M-Entropy guidance further reduced time to eye opening (MD: -142 s; 99.2% CI: -276, -8), tracheal extubation (-199; -379, -19), and leaving operating room (-190; -358, -23) in the desflurane but not the sevoflurane group. M-Entropy guidance significantly reduced the risk of agitation during emergence, i.e., risk difference: -0.275 (95% CI: -0.464, -0.086); and number needed to treat: 4. Compared to sevoflurane, using desflurane to maintain general anesthesia accelerated the return of consciousness in obese patients. M-Entropy guidance further hastened awakening in patients using desflurane and prevented emergence agitation.

Background: Procedural sedation reduces patients' discomfort and anxiety, facilitating performance of the examination and intervention. However, it may also cause adverse events, including airway obstruction and hypoxia. We conducted this systematic review and meta-analysis to evaluate the efficacy of high-flow nasal oxygenation (HFNO) compared with that of standard oxygen therapy in adult patients undergoing procedural sedation., Methods: We identified randomized controlled trials published before November 2020 based on PubMed, Embase, and Cochrane Library databases and ClinicalTrials.gov registry. Intraprocedural desaturation [peripheral oxygen saturation (SpO 2 ) < 90%] was evaluated as the primary outcome. The secondary outcomes were the lowest SpO 2 , need for airway intervention, oxygen therapy-related complications, and patient, operator, and anesthetist's satisfaction., Results: Six trials with a total of 2633 patients were reviewed. Patients using HFNO compared with standard oxygen therapy had a significantly lower risk of intraprocedural desaturation [risk ratio 0.18, 95% confidence interval (CI) 0.04-0.87]. The lowest intraprocedural SpO 2 in HFNO group was significantly higher than that in standard oxygen therapy group (mean difference 4.19%, 95% CI 1.74-6.65)., Conclusions: Compared with standard oxygen therapy, HFNO may reduce the risk of desaturation and increase the lowest SpO 2 in adult patients undergoing sedation for medical procedures., (© 2021. The Author(s).)

The influence of physician specialty on the outcomes of kidney diseases (KDs) remains underexplored. We aimed to compare the complications and mortality of patients with admissions for KD who received care by nephrologists and non-nephrologist (NN) physicians. We used health insurance research data in Taiwan to conduct a propensity-score matched study that included 17,055 patients with admissions for KD who received care by nephrologists and 17,055 patients with admissions for KD who received care by NN physicians. Multivariable logistic regressions were conducted to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for 30-day mortality and major complications associated with physician specialty. Compared with NN physicians, care by nephrologists was associated with a reduced risk of 30-day mortality (OR 0.29, 95% CI 0.25-0.35), pneumonia (OR 0.82, 95% CI 0.76-0.89), acute myocardial infarction (OR 0.68, 95% CI 0.54-0.87), and intensive care unit stay (OR 0.78, 95% CI 0.73-0.84). The association between nephrologist care and reduced admission adverse events was significant in every age category, for both sexes and various subgroups. Patients with admissions for KD who received care by nephrologists had fewer adverse events than those who received care by NN physicians. We suggest that regular nephrologist consultations or referrals may improve medical care and clinical outcomes in this vulnerable population.

Objectives: Periodontal disease is prevalent in patients with chronic kidney disease (CKD) and potentially associated with kidney function decline. However, it is uncertain whether periodontal disease affects the risk of mortality and morbidity in patients with advanced CKD., Materials and Methods: Taiwan's National Health Insurance Research Database was used to conduct a nationwide population-based cohort study. Propensity score matching procedures were performed to select people with stage 5 CKD and to compare the long-term risk of mortality, end-stage renal disease, and major adverse cardiovascular events (MACE) between people with and without periodontal disease. Multivariable Cox regression analyses were conducted to calculate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the outcome of interest., Results: A total of 8119 subjects with stage 5 CKD were initially included. After matching to demographic and clinical covariates, 1254 subjects with 7099 person-years of follow-up were selected for analyses. Periodontal disease was not associated with long-term risks of all-cause mortality (aHR: 0.77, 95% CI: 0.49-1.22), progression to end-stage renal disease (aHR: 0.91, 95% CI: 0.75-1.10), or MACE (aHR: 1.18, 95% CI: 0.91-1.53). These findings were generally consistent across subgroups of age, sex, comorbid diabetes, uses of systemic antibiotic, and different dental procedures., Conclusions: Periodontal disease is not a predictor for long-term mortality or morbidity in patients with advanced CKD., Clinical Relevance: These results provide important evidence to elucidate the relationship between periodontitis and critical clinical outcomes of advanced CKD., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The association between pancreatitis and acute myocardial infarction or stroke remains incompletely understood. This study aimed to evaluate the long-term risk of acute atherosclerotic cardiovascular disease (ASCVD) in people with acute and chronic pancreatitis. Using research database of Taiwan's National Health Insurance, we identified 2678 patients aged ≥ 20 years with newly diagnosed pancreatitis in 2000-2008. A cohort of 10,825 adults without pancreatitis was selected for comparison, with matching by age and sex. Both cohorts were followed from 2000 to the end of 2013, and incident acute ASCVD was identified during the follow-up period. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of acute ASCVD associated with pancreatitis were calculated. Compared with the comparison cohort, the adjusted HR of acute ASCVD were 1.76 (95% CI 1.47-2.12) and 3.42 (95% CI 1.69-6.94) for people with acute pancreatitis and chronic pancreatitis, respectively. A history of alcohol-related illness (HR 9.49, 95% CI 3.78-23.8), liver cirrhosis (HR 7.31, 95% CI 1.81-29.5), and diabetes (HR 6.89, 95% CI 2.18-21.8) may worsen the risk of acute ASCVD in patients with chronic pancreatitis. Compared with people had no pancreatitis, patients with acute pancreatitis who had alcohol-related illness (HR 4.66, 95% CI 3.24-6.70), liver cirrhosis (HR 4.44, 95% CI 3.05-6.47), and diabetes (HR 2.61, 95% CI 2.03-3.36) were at increased risk of acute ASCVD. However, the cumulative use of metformin was associated with a reduced risk of acute ASCVD in the acute pancreatitis cohort (HR 0.30, 95% CI 0.17-0.50). Compared with the control group, patients with acute or chronic pancreatitis were more likely to have an increased risk of acute ASCVD, while the use of metformin reduced the risk of acute ASCVD. Our findings warrant a survey and education on acute ASCVD for patients with acute and chronic pancreatitis., (© 2021. The Author(s).)

Whether aortic stenosis (AS) increases perioperative risk in noncardiac surgery remains controversial. Limited information is available regarding adequate anesthetic techniques for patients with AS. Using the reimbursement claims data of Taiwan's National Health Insurance, we performed propensity score matching analyses to evaluate the risk of adverse outcomes in patients with or without AS undergoing noncardiac surgery between 2008 and 2013. We also compared the perioperative risk of AS patients undergoing general anesthesia or neuraxial anesthesia. Multivariable logistic regressions were applied to calculate the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for postoperative mortality and major complications. The matching procedure generated 9741 matched pairs for analyses. AS was significantly associated with 30-day in-hospital mortality (aOR 1.31, 95% CI 1.03-1.67), acute renal failure (aOR 1.42, 95% CI 1.12-1.79), pneumonia (aOR 1.16, 95% CI 1.02-1.33), stroke (aOR 1.14, 95% CI 1.01-1.29), and intensive care unit stay (aOR 1.38, 95% CI 1.27-1.49). Compared with neuraxial anesthesia, general anesthesia was associated with increased risks of acute myocardial infarction (aOR 3.06, 95% CI 1.22-7.67), pneumonia (aOR 1.80, 95% CI 1.32-2.46), acute renal failure (aOR 1.82, 95% CI 1.11-2.98), and intensive care (aOR 4.05, 95% CI 3.23-5.09). The findings were generally consistent across subgroups. AS was an independent risk factor for adverse events after noncardiac surgery. In addition, general anesthesia was associated with greater postoperative complications in AS patients compared to neuraxial anesthesia. This real-world evidence suggests that neuraxial anesthesia should not be contraindicated in patients with AS., (© 2021. The Author(s).)

The risk and outcomes of diabetes in patients with epilepsy remains unclear. We evaluated these risks using an epilepsy cohort analysis and a diabetes admission analysis. In the epilepsy cohort analysis, we identified 2854 patients with newly diagnosed epilepsy in 2000-2008 from the research data of National Health Insurance in Taiwan. Using Propensity-score matching by sociodemographic factors and medical conditions, we selected 22,832 people without epilepsy as a non-exposed cohort for comparison. Follow-up events of diabetes from January 1, 2000 until December 31, 2013 were ascertained from medical claims. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of diabetes associated with epilepsy were calculated using multiple Cox proportional hazard models. In the diabetes admission analysis, we identified 92,438 hospitalized diabetes patients, 930 of whom had a history of epilepsy. Adjusted odds ratios (ORs) and 95% CIs of adverse events after diabetes associated with previous epilepsy were calculated using multiple logistic regressions. The adjusted HR of diabetes in the cohort with epilepsy was 1.31 (95% CI 1.14-1.50) compared to the non-epilepsy cohort. Previous epilepsy was associated with post-diabetes adverse events, such as pneumonia (OR 1.68, 95% CI 1.37-2.07), urinary tract infection (OR 1.83, 95% CI 1.55-2.16), and septicemia (OR 1.34, 95% CI 1.09-1.65). In conclusion, epilepsy was associated with higher risk of diabetes and adverse post-diabetes outcomes. Diabetes prevention and attention to post-diabetes adverse events are needed for this susceptible population., (© 2021. The Author(s).)

Periodontitis is prevalent in patients with chronic kidney disease (CKD) and is also associated with kidney function decline. It is unclear whether dental scaling treatment prevents the progression of CKD. In a nationwide cohort study, Taiwan's National Health Insurance Research Database was used to select people with CKD. Propensity score-matching procedures were performed to compare the long-term risk of end-stage renal disease (ESRD) between CKD patients with and without the receipt of dental scaling. A total of 33,637 matched pairs with CKD were included, with 503,373 person-years of follow-up for analyses. Dental scaling was significantly associated with a lower risk of ESRD (adjusted hazard ratio (aHR): 0.83, 95% confidence interval (CI): 0.77-0.90). In addition, there was a dose-dependent relationship between the frequency of dental scaling and a reduced risk of ESRD. Dental scaling was also linked to reduced risks of major adverse cardiovascular events (aHR: 0.91, 95% CI: 0.87-0.95), sepsis (aHR: 0.81, 95% CI: 0.77-0.85), and all-cause mortality (aHR: 0.81, 95% CI: 0.76-0.87). Dental scaling was significantly associated with lower risks of progression to ESRD in patients with CKD. Regular dental scaling may serve as a prophylactic measure for kidney function decline.

Background: Treating advanced colon cancer remains challenging in clinical settings because of the development of drug resistance and distant metastasis. Mechanisms underlying the metastasis of colon cancer are complex and unclear., Methods: Computational analysis was performed to determine genes associated with the exosomal long noncoding (lncRNA) plasmacytoma variant translocation 1 (PVT1)/vascular endothelial growth factor A (VEGFA) axis in patients with colon cancer. The biological importance of the exosomal lncRNA PVT1/VEGFA axis was examined in vitro by using HCT116 and LoVo cell lines and in vivo by using a patient-derived xenograft (PDX) mouse model through knockdown (by silencing of PVT1) and overexpression (by adding serum exosomes isolated from patients with distant metastasis (M-exo))., Results: The in silico analysis demonstrated that PVT1 overexpression was associated with poor prognosis and increased expression of metastatic markers such as VEGFA and epidermal growth factor receptor (EGFR). This finding was further validated in a small cohort of patients with colon cancer in whom increased PVT1 expression was correlated with colon cancer incidence, disease recurrence, and distant metastasis. M-exo were enriched with PVT1 and VEGFA, and both migratory and invasive abilities of colon cancer cell lines increased when they were cocultured with M-exo. The metastasis-promoting effect was accompanied by increased expression of Twist1, vimentin, and MMP2. M-exo promoted metastasis in PDX mice. In vitro silencing of PVT1 reduced colon tumorigenic properties including migratory, invasive, colony forming, and tumorsphere generation abilities. Further analysis revealed that PVT1, VEGFA, and EGFR interact with and are regulated by miR-152-3p. Increased miR-152-3p expression reduced tumorigenesis, where increased tumorigenesis was observed when miR-152-3p expression was downregulated., Conclusion: Exosomal PVT1 promotes colon cancer metastasis through its association with EGFR and VEGFA expression. miR-152-3p targets both PVT1 and VEGFA, and this regulatory pathway can be explored for drug development and as a prognostic biomarker., Competing Interests: The authors declare that they have no potential financial competing interests whereby they may in any way gain or lose financially from the publication of this manuscript at present or in the future. Additionally, no nonfinancial competing interests are involved in the manuscript., (Copyright © 2021 Shiue-Wei Lai et al.)

Background: Hepatitis virus is a major risk factor for liver cancer. The mitochondrial dysfunction IFN gamma-related pathways are activated after virus infection. Jak family-related protein is involved in the downstream of IFN gamma-related pathways. However, the effect of the IFNGR-JAK-STAT pathway acting as functional regulators of their related protein expression on virus infection and hepatocellular carcinoma (HCC) remains unclear. Interestingly, the role of the DNA repair gene (PARP1) in therapy resistant cancers also has not been studied and explored well. In this study, we hypothesized that momelotinib could suppress the progression of HCC by targeting Jak family related and PARP1 DNA repair protein. Based on this observation, we link the relevant targets of the JAK family and the potential applications of targeted therapy inhibitors., Methods: We analyzed possible synergism between momelotinib and sorafenib in hepatitis virus-associated liver cancer. Immunostaining, colony formation assay, cell invasion, migration, and tumorsphere-formation assay were used for drug cytotoxicity, cell viability, and possible molecular mechanism., Result: We first demonstrated that the expression of Jak1 and 2 is significantly upregulated in vHCC than in nvHCC/normal liver tissues. In addition, the gene expression of IFN gamma-related pathways is activated after virus infection. Additionally, we found that momelotinib significantly inhibited the growth of HCC cells and reduces the expression of Jak2, which showed the importance of momelotinib in targeting Jak2 and reducing tumorigenesis in HCC. Meanwhile, momelotinib effectively inhibited the IFNGR-JAK-STAT pathway and reduced the migratory/invasive ability of vHCC cells through down-regulating EMT biomarkers (E-cadherin and vimentin), transcription factor (Slug), and significantly inhibits the DNA damage repair enzyme PARP1. It also induced cell apoptosis of vHCC cells. Furthermore, the combined effect of momelotinib and sorafenib both at in vitro and in vivo synergistically suppresses the proliferation of vHCC cells and effectively reduces the tumor burden., Conclusions: Our results showed that momelotinib effectively suppressed the expression of the IFNGR-JAK-STAT-PARP1 pathway, which results in the downregulation of cancer stem cell genes and enhances the antitumor efficacy of sorafenib by initiating the expression of apoptosis-related genes and inhibiting the DNA repair gene in vHCC cells, thus maximizing its therapeutic potential for patients with HCC.

Background: Systemic inflammation correlates closely with tumor invasion and may predict survival in cancer patients. We aimed to compare the prognostic value of various inflammation-based markers in patients with hepatocellular carcinoma., Methods: We consecutively enrolled 1450 patients with primary hepatocellular carcinoma undergoing surgical resection at the medical center between 2005 and 2016 and assessed them through September 2018. Prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio along with their perioperative dynamic changes were analyzed regarding their predictive ability of postoperative disease-free survival and overall survival. We calculated the adjusted hazard ratio (HR) and 95% CI of the association between inflammation-based markers and survival using multiple Cox proportional hazards models. Youden's index of receiver operating characteristics curves was used to determine optimal cut-off points., Results: Prognostic nutritional index was an independent predictor for both disease-free survival (<50.87 vs ≥50.87, HR: 1.274, 95% CI, 1.071-1.517, p = 0.007) and overall survival (<46.65 vs ≥46.65, HR: 1.420, 95% CI, 1.096-1.842, p = 0.008). Besides, the relative change of neutrophil-to-lymphocyte ratio predicted overall survival (<277% vs ≥277%, HR: 1.634, 95% CI, 1.266-2.110, p < 0.001). Combination of both markers offered better prognostic performance for overall survival than either alone. Body mass index, liver cirrhosis, chronic kidney disease, and tumor diameter were significantly associated with both markers., Conclusion: Prognostic nutritional index and perioperative relative change of neutrophil-to-lymphocyte ratio independently predict postoperative survival in patients undergoing surgical resection of hepatocellular carcinoma. These results provided important evidence for risk stratification and individualized anti-cancer therapy., Competing Interests: Conflicts of interest: Dr Ming-Chih Hou and Dr Mei-Yung Tsou, editorial board members at Journal of the Chinese Medical Association, have no roles in the peer review process of or decision to publish this article. The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Drug resistance mainly drives GBM patients to poor prognoses because drug-resistant glioblastoma cells highly defend against apoptotic insults. This study was designed to evaluate the effects of cobalt chloride (CoCl 2 ) on hypoxic stress, autophagy, and resulting apoptosis of human and mouse drug-resistant glioblastoma cells. Treatment of drug-resistant glioblastoma cells with CoCl 2 increased levels of hypoxia-inducible factor- (HIF-) 1 α and triggered hypoxic stress. In parallel, the CoCl 2 -induced hypoxia decreased mitochondrial ATP synthesis, cell proliferation, and survival in chemoresistant glioblastoma cells. Interestingly, CoCl 2 elevated the ratio of light chain (LC)3-II over LC3-I in TMZ-resistant glioblastoma cells and subsequently induced cell autophagy. Analyses by loss- and gain-of-function strategies further confirmed the effects of the CoCl 2 -induced hypoxia on autophagy of drug-resistant glioblastoma cells. Furthermore, knocking down HIF-1 α concurrently lessened CoCl 2 -induced cell autophagy. As to the mechanisms, the CoCl 2 -induced hypoxia decreased levels of phosphoinositide 3-kinase (PI3K) and successive phosphorylations of AKT and mammalian target of rapamycin (mTOR) in TMZ-resistant glioblastoma cells. Interestingly, long-term exposure of human chemoresistant glioblastoma cells to CoCl 2 sequentially triggered activation of caspases-3 and -6, DNA fragmentation, and cell apoptosis. However, pretreatment with 3-methyladenine, an inhibitor of autophagy, significantly attenuated the CoCl 2 -induced autophagy and subsequent apoptotic insults. Taken together, this study showed that long-term treatment with CoCl 2 can induce hypoxia and subsequent autophagic apoptosis of drug-resistant glioblastoma cells via targeting the PI3K-AKT-mTOR pathway. Thus, combined with traditional prescriptions, CoCl 2 -induced autophagic apoptosis can be clinically applied as a de novo strategy for therapy of drug-resistant GBM patients., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2021 Yuan-Wen Lee et al.)

Background: Little was know about the association between the CHA2DS2-VASc score and postoperative outcomes. Our purpose is to evaluate the effects of CHA2DS2-VASc score on the perioperative outcomes in patients with atrial fibrillation (AF)., Methods: We identified 47,402 patients with AF over the age of 20 years who underwent noncardiac surgeries between 2008 and 2013 from claims data of the National Health Insurance in Taiwan. The CHA2DS2-VASc score was used to evaluate postoperative complications, mortality and the consumption of medical resources by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Compared with patients with a CHA2DS2-VASc score of 0, patients with scores ≥ 5 had an increased risk of postoperative septicemia (OR 2.76, 95% CI 2.00-3.80), intensive care (OR 2.55, 95% CI 2.12-3.06), and mortality (OR 2.04, 95% CI 1.14-3.64). There was a significant positive correlation between risk of postoperative complication and the CHA2DS2-VASc score (P < 0.0001)., Conclusion: The CHA2DS2-VASc score was highly associated with postoperative septicemia, intensive care, and 30-day mortality among AF patients. Cardiologists and surgical care teams may consider using the CHA2DS2-VASc score to evaluate perioperative outcome risks in patients with AF.

The impact of heart failure (HF) on postoperative outcomes is not completely understood. Our purpose is to investigate complications and mortality after noncardiac surgeries in people who had HF. In the analyses of research data of health insurance in, we identified 32,808 surgical patients with preoperative HF and 32,808 patients without HF undergoing noncardiac surgeries. We used a matching procedure with propensity score and considered basic characteristics, coexisting diseases, and information of index surgery between patients with and without HF. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for complications and mortality after noncardiac surgeries in patients with HF were analyzed in multivariate logistic regressions. HF increased the risks of postoperative acute myocardial infarction (OR 2.51, 95% CI 1.99-3.18), pulmonary embolism (OR 2.46, 95% CI 1.73-3.50), acute renal failure (OR 1.97, 95% CI 1.76-2.21), intensive care (OR 1.93, 95% CI 1.85-2.01), and 30-day in-hospital mortality (OR 1.80, 95% CI 1.59-2.04). Preoperative emergency care, inpatient care, and injections of diuretics and cardiac stimulants due to heart failure were also associated with mortality after surgery. Patients with HF had increased complications and mortality after noncardiac surgeries compared with those without HF. The surgical care team may consider revising the protocols for perioperative care in patients with HF.

Microsaccades, small saccadic eye movements occurring during fixation, have been suggested to be modulated by various sensory, cognitive, and affective processes relating to arousal. Although the modulation of fatigue-related arousal on microsaccade behavior has previously been characterized, the influence of other aspects of arousal, such as emotional arousal, is less understood. Moreover, microsaccades are modulated by cognitive processes (e.g., voluntary saccade preparation) that could also be linked to arousal. To investigate the influence of emotional arousal, saccade preparation, and global luminance levels on microsaccade behavior, emotional auditory stimuli were presented prior to the onset of a fixation cue whose color indicated to look either at the peripheral stimulus (pro-saccade) or in the opposite direction of the stimulus (anti-saccade). Microsaccade behavior was found to be significantly modulated by saccade preparation and global luminance level, but not emotional arousal. In the pro- and anti-saccade task, microsaccade rate was lower during anti-saccade preparation as compared to pro-saccade preparation, though microsaccade dynamics were comparable during both trial types. Our results reveal a differential role of arousal linked to emotion, fatigue, saccade preparation, and global luminance level on microsaccade behavior., 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 © 2021 Chen, Yep, Hsu, Cherng and Wang.)

Saccades are often directed toward a stimulus that provides useful information for observers to navigate the visual world. The quality of visual signals of a stimulus is influenced by global luminance, and the pupil constricts or dilates after a luminance increase or decrease, respectively, to optimize visual signals for further information processing. Although luminance level changes regularly in the real environment, saccades are mostly studied in the luminance-unchanged setup. Whether pupillary responses triggered by global luminance changes modulate saccadic behavior are yet to be explored. Through varying background luminance level in an interleaved pro- and anti-saccade paradigm, we investigated the modulation of pupillary luminance responses on the generation of reflexive and voluntary saccades. Subjects were instructed to either automatically look at the peripheral stimulus (pro-saccade) or to suppress the automatic response and voluntarily look in the opposite direction from the stimulus (anti-saccade). Level of background luminance was increased (light), decreased (dark), or unchanged (control) during the instructed fixation period. Saccade reaction time distributions of correct pro- and anti-saccades in the light and dark conditions were differed significantly from those in the control condition. Moreover, the luminance condition modulated saccade kinematics, showing reduced performances in the light condition than in the control condition, particularly in pro-saccades. Modeling results further suggested that both pupil diameter and pupil size derivative significantly modulated saccade behavior, though effect sizes were small and mainly mediated by intersubject differences. Together, our results demonstrated the influence of pupillary luminance responses on the generation of pro- and anti-saccades., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)