Search

Yu-Feng Lin,1,2 Tao-Min Huang,2,3 Shuei-Liong Lin,2,4 Vin-Cent Wu,2 Kwan-Dun Wu2 1Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; 2Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 3Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University College of Public Health, Taipei, Taiwan; 4Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan Objective: Prompt assessment of perioperative complications is critical for the comprehensive care of surgical patients. Acute kidney injury requiring dialysis (AKI-D) is associated with high mortality, yet little is known about how long-term outcomes of patients have evolved. The association of AKI-D with postsurgical outcomes has not been well studied.Methods: We investigated patients from the National Health Insurance Research Database and validated by the multicenter Clinical Trial Consortium for Renal Diseases cohort. All patients with AKI-D 18 years or older undergoing four major surgeries (cardiothoracic, esophagus, intestine, and liver) were retrospectively investigated (N=106,573). Patient demographics, surgery type, comorbidities before admission, and postsurgical outcomes, including the in-hospital, 30-day, and long-term mortality together with dialysis dependence were collected.Results: AKI-D is the top risk factor for 30-day and long-term mortality after major surgery. Of 1,664 individuals with AKI-D and 6,656 matched controls, AKI-D during the hospital stay was associated with in-hospital (adjusted hazard ratio [aHR]=3.04, 95% CI 2.79–3.31), 30-day (aHR=3.65, 95% CI 3.37–3.94), and long-term (aHR=3.22, 95% CI 3.01–3.44) mortality. Patients undergoing cardiothoracic surgery (CTS) showed less in-hospital (aHR=0.85, 95% CI 0.75–0.97), 30-day (aHR=0.79, 95% CI 0.70–0.89), and long-term (aHR=0.80, 95% CI 0.72–0.90) mortality compared with non-CTS patients with AKI-D. CTS patients had a high risk of 30-day dialysis dependence (subhazard ratio [sHR]=1.67, 95% CI 1.18–2.38), but the risk of long-term dialysis dependence was similar (sHR=1.38, 95% CI 0.96–2.00) after AKI-D by taking mortality as a competing risk. Non-CTS patients had more comorbidities of sepsis, azotemia, hypoalbuminemia, and metabolic acidosis compared with CTS patients.Conclusion: AKI exhibits paramount effects on postsurgical outcomes that extend well beyond discharge from the hospital. The goal of the perioperative assessment should include the reassurance of enhancing renal function recovery among different surgeries, and optimized follow-up is warranted in attenuating the complications after postsurgical AKI has occurred. Keywords: major surgery, acute kidney injury, postsurgical complication, dialysis dependence, mortality

A high repetition rate, MHz-class, high-brightness electron source is a key element in future high-repetition-rate x-ray free electron laser-based light sources. The VHF-gun, a novel low frequency radio-frequency gun, is the Lawrence Berkeley National Laboratory (LBNL) response to that need. The gun design is based on a normal conducting, single cell cavity resonating at 186 MHz in the VHF band and capable of continuous wave operation while still delivering the high accelerating fields at the cathode required for the high brightness performance. The VHF-gun was fabricated and successfully commissioned in the framework of the Advanced Photo-injector EXperiment, an injector built at LBNL to demonstrate the capability of the gun to deliver the required beam quality. The basis for the selection of the VHF-gun technology, novel design features, and fabrication techniques are described.

Purpose: Voriconazole (VRC) is recommended for the prevention and treatment of invasive fungal infections in children undergoing hematopoietic stem cell transplantation (HSCT). It demonstrates nonlinear pharmacokinetics (PK) and exhibits substantial inter- and intraindividual variability. Phenytoin sodium (PHT) and methylprednisolone (MP) are commonly used in the early stages of HSCT to prevent epilepsy and graft-versus-host disease. Drug-drug interactions between VRC and these medications represent a significant concern in HSCT recipients. This study aims to investigate the effects of coadministration with PHT, MP, and other covariates on VRC metabolism in children with thalassemia (TM) undergoing allogeneic HSCT (Allo-HSCT) using population pharmacokinetics (PPK) and to recommend the optimal dosage regimen for this unique group., Methods: A total of 237 samples from 57 children with TM undergoing Allo-HSCT were collected. Non-linear mixed effects modeling and Monte Carlo simulation (MCS) were applied for PPK analysis and for optimizing VRC dosing, respectively., Results: The VRC data were characterized by a two-compartment model with linear elimination and first-order absorption. All parameters were incorporated in allometric scaling form, with PHT and MP significantly influencing VRC clearance. The MCS revealed a negative correlation between the children's body weight (ranging from 10 to 40 kg) and the required dose. When PHT was co-administered, approximately three times the regular dose of VRC was required. In contrast, when MP was administered together, the dose needed to be increased by 12.5-50%., Conclusion: The proposed regimen improved the probability of target attainment for VRC and may serve as a reference for the individualized administration of VRC in clinical practice., Competing Interests: Declarations. Ethics approval and consent to participate: The Ethics Committee of the First Affiliated Hospital of Guangxi Medical University approved the protocol (NO.2022-KY-031). This study complied with the Declaration of Helsinki and national and institutional standards and informed consent was obtained from legal guardians before participating in the study. Consent for publication: All authors read and approved the final manuscript. All authors agreed to publish this work. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: As an immunosuppressant, mycophenolate mofetil (MMF) is used to prevent graft versus host disease (GVHD) in patients after hematopoietic stem cell transplantation (HCT). This study aimed to establish a population pharmacokinetic model and simulate the dosage protocol in HCT patients with thalassemia (TM) to fill the gap of lacking MMF dosing regimen., Methods: The mycophenolic acid (MPA) plasma concentrations were obtained from HCT patients with TM after using MMF. The population pharmacokinetic (PPK) parameters were obtained by NONMEM (Version VII, Level 2.0; ICON Development Solutions, Ellicott City, MD, USA) program. Monte Carlo simulations were used to determine the optimal dosing., Results: A total of 239 blood samples from 31 pediatric patients were available, the PPK of MPA was described as a two-compartment model. The typical values for MPA clearance (CL), central distribution volume (V 2 ), peripheral distribution volume (V 3 ), intercompartmental clearance (Q), and absorption rate constant (Ka) were 14.9 L/h, 83.5L, 141L, 3.13 L/h, and 1.37/h respectively. The inter-individual variability (IIV) of CL and V 2 were 35% and 41%, respectively. Simulation results suggested that, as the patient's body surface area (BSA) value increased, MMF dosage initiated from 500 mg twice daily was effective., Conclusions: A 'tiered' dosage regimen including patient urea and with doses stratified across BSA quartiles, rather than a 'one dose fits all' regimen, would help individualize MMF therapy in this population., Competing Interests: Declarations. Consent for Publication: All patients in this study have signed informed consent forms and agreed that their data can be published. Author Contributions: Tao-tao Liu designed the research. Lu-lu Niu, Yong-jun Liu, Yun Wu, Tian-min Huang, Ting-qing Wu, Yang Xiao, Xin Chen, Yi-lin Luo, collected and reviewed the data for this study. Lu-lu Niu establishing the PPK model and the simulation of the dosing regimens. Lu-lu Niu wrote the manuscript. All authors contributed to the interpretation of the results, the reviewing of the manuscript, and the decision to submit this manuscript to be published. All authors read and approved the final manuscript. All authors agreed to publish this work Data and Code Availability: The data and code that support the findings of this study are available from the corresponding author upon reasonable request. Ethics Approval and Consent to Participate: The Ethics Committee of the First Affiliated Hospital of Guangxi Medical University approved the protocol (NO.2023-K130-01). This study complied with the Declaration of Helsinki and national and institutional standards. And all recruited patients, and their guardians signed the informed consent form before participating in the study. Consent to Participate: All patients and their guardians had signed informed consent before the study began. Conflict of Interest: The authors declared no conflicts of interest concerning the research, authorship, and publication of this article. Funding: No funding was received for this work., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Dipeptidyl peptidase 4 inhibitors (DPP4is) are considered safe for use in patients with diabetes mellitus and kidney dysfunction. We explored whether usage of DPP4is in patients who recovered from dialysis-requiring acute kidney injury (AKI) could reduce the risk of future cardiac and kidney events., Methods: We used the TriNetX platform to investigate whether the use of DPP4is in diabetes mellitus patients within 90 days of discharge from acute kidney disease could reduce the risk of all-cause mortality, major adverse kidney events (MAKEs), major adverse cardiovascular events (MACEs), and re-dialysis. The patients were followed for 5 years or until the occurrence of significant outcomes, with cohort data collected from 1 January 2016 to 30 September 2022., Results: The cohort utilizing DPP4is comprised 7348 patients with acute kidney disease, while the control group encompassed 229 417 individuals. After applying propensity score matching, 7343 patients (age 66.2 ± 13.4 years; male, 49.9%) who used DPP4is showed a significant reduction in the risk of all-cause mortality [adjusted hazard ratio (aHR) 0.89; E-value 1.50 , MAKEs (aHR 0.86; E-value 1.59), MACEs (aHR 0.91; E-value 1.44), and re-dialysis (aHR 0.73; E-value 2.10) after a median follow-up of 2.4 years., Conclusions: We demonstrated that in diabetes mellitus patients concurrently experiencing acute kidney disease, DPP4i usage could decrease the risk of mortality, MAKEs, MACEs, and re-dialysis. These findings emphasize the pivotal role of tailored treatment strategies involving DPP4i for acute kidney disease patients., Competing Interests: All authors have not conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Certain patient subpopulations requiring dialysis initiation show varied survival rates and chances of ending renal replacement therapy (RRT). Consensus clustering can help identify these subgroups and their dialysis outcomes., Methods: The study included patients who were over 18 years old with urine output above 400 ml per day and an estimated glomerular filtration rate over 15 ml/min/1.73 m 2 . They underwent acute RRT because of systemic demand-capacity imbalance. Using consensus clustering with 33 clinical variables and urea:creatinine ratio (UCR) to the variables to investigate the catabolic demand. Endpoints were all-cause mortality and being dialysis-free at 180-day follow-up after RRT initiation., Results: Of 946 patients (mean 63 ± 17 years and 649 men, 68.6 %) three distinct phenotypes were identified. 509 (53.8%) patients died and 364 (38.5%) patients were weaned off dialysis. Cluster 2 showed better survival (60.23% vs. 53.18% [cluster 1] vs. 45.85% [cluster 3], P < 0.01) and higher possibility to be weaned off RRT (45.24% vs. 38.44% [cluster 1] vs. 31.62% [cluster 3], P < 0.01). High UCR had increased mortality (59.16% vs. 47.75%, P < 0.01) and a lower weaning rates (33.27%; 45.72%, P < .01). UCR with the clustering phenotype improved risk stratification., Conclusions: Among critical patients undergoing RRT due to systemic demand-capacity imbalance, more than half of the patients died. We identified distinct phenotypes in demand-capacity imbalance in a heterogeneous cohort of patients initializing RRT. Additionally, we found that pre-dialysis UCR as a novel predictor for mortality and the likelihood of being dialysis-free., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Computational fluid dynamics (CFD) is an emerging technology applied in the field of cardiovascular medicine, which can obtain hemodynamic data by simulating the blood flow in the patient's heart for cardiac function assessment and disease diagnosis. Left ventricular function plays a key role in the occurrence and development of cardiomyopathies and coronary disease. CFD can reconstruct the left ventricular anatomic structures of patients to clarify pathophysiologic mechanisms and analyze hemodynamic parameters to evaluate left ventricular function, verify surgical efficacy, and guide surgical strategy, which has a positive effect on achieving early diagnosis and reducing mortality from cardiomyopathies and coronary disease. At present, there are still technical limitations in the large-scale clinical application of CFD, and various solutions are being developed and tested, and further improvement and refinement are needed.

Importance: The interplay among baseline kidney function, severity of acute kidney disease (AKD), and post-AKD kidney function has significant associations with patient outcomes. However, a comprehensive understanding of how these factors are collectively associated with mortality, major adverse cardiac events (MACEs), and end-stage kidney disease (ESKD) in patients with dialysis-requiring acute kidney injury (AKI-D) is yet to be fully explored., Objective: To investigate the associations of baseline kidney function, AKD severity, and post-AKD kidney function with mortality, MACEs, and ESKD in patients with AKI-D., Design, Setting, and Participants: This nationwide, population-based cohort study of patients with AKI-D was conducted between January 1, 2015, and December 31, 2018, using data from various health care settings included in the Taiwan nationwide population-based cohort database. Data analysis was conducted from April 28, 2022, to June 30, 2023., Exposure: Exposure to severe AKI and baseline and post-AKD kidney function., Main Outcomes and Measures: The primary outcomes were all-cause mortality and incident MACEs, and secondary outcomes were risks of permanent dialysis and readmission., Results: A total of 6703 of 22 232 patients (mean [SD] age, 68.0 [14.7] years; 3846 [57.4%] male) with AKI-D with post-AKD kidney function follow-up and AKD stage data were enrolled. During a mean (SD) 1.2 (0.9) years of follow-up, the all-cause mortality rate was 28.3% (n = 1899), while the incidence rates of MACEs and ESKD were 11.1% (n = 746) and 16.7% (n = 1119), respectively. After adjusting for known covariates, both post-AKD kidney function and baseline kidney function, but not AKD severity, were independently associated with all-cause mortality, MACEs, ESKD, and readmission. Moreover, worse post-AKD kidney function correlated with progressive and significant increases in the risk of adverse outcomes., Conclusions and Relevance: In this cohort study of patients with AKI-D, more than one-quarter of patients died after 1.2 years of follow-up. Baseline and post-AKD kidney functions serve as important factors associated with the long-term prognosis of patients with AKI-D. Therefore, concerted efforts to understand the transition from post-AKD to chronic kidney disease are crucial.

Background: Postarrest acute kidney injury (AKI) is a major health burden because it is associated with prolonged hospitalization, increased dialysis requirement, high mortality, and unfavorable neurological outcomes. Managing hemodynamic instability during the early postarrest period is critical; however, the role of quantified vasopressor dependence in AKI development in relation to illness severity remains unclear., Methods: A retrospective, observational cohort study that enrolled 411 non-traumatic adult cardiac arrest survivors without pre-arrest end-stage kidney disease between January 2017 and December 2019, grouped according to their baseline kidney function. The criteria for kidney injury were based on the Kidney Disease: Improving Global Outcomes definition and AKI staging system. The degree of vasopressor dependence within the first 24 h following return of spontaneous circulation (ROSC) was presented using the maximum vasoactive-inotropic score ( VIS max )., Results: Of the 411 patients, 181 (44%) had early AKI after ROSC. Patients with AKI showed an increased risk of in-hospital mortality (adjusted OR [aOR] 5.40, 95% CI 3.36-8.69, p < 0.001) and unfavorable neurological outcome (aOR 5.70, 95% CI 3.45-9.43, p < 0.001) compared to patients without AKI. The risk of adverse outcomes increased with illness severity. Patients with vasopressor support had an increased risk of early AKI. A low VIS max was associated with AKI stage 1-2 (aOR 2.51, 95% CI 1.20-5.24), whereas a high VIS max was associated with an increased risk for AKI stage 3 (aOR 2.46, 95% CI 1.28-4.75)., Conclusions: Early AKI is associated with an increased risk of in-hospital mortality and unfavorable neurologic recovery in cardiac arrest survivors. Postarrest VIS max is an independent predictor of the development and severity of AKI following ROSC, regardless of baseline kidney function., Competing Interests: The authors declare no conflict of interest. Chien-Hua Huang is serving as Guest Editor of this journal. We declare that Chien-Hua Huang had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Davide Bolignano., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Background: The optimal strategy of percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) complicated with cardiogenic shock (CS) remains controversial. We aimed to elucidate the renal and cardiovascular impact of culprit-only (C) revascularization versus additional interventions on non-infarct-related arteries., Methods: PubMed, Embase, MEDLINE, and Cochrane Library were searched for relevant literature. A total of 96,812 subjects [C-PCI: 69,986; multi-vessel (MV)-PCI: 26,826] in nine studies (one randomized control trial; eight observational cohort studies) were enrolled., Results: MV-PCI was associated with a higher kidney event rate [relative risk (RR): 1.29, 95% confidence interval (CI): 1.12-1.49; p < 0.001]. However, the all-cause mortality rate was comparable both during admission (RR: 1.07, 95% CI: 0.94-1.22; p = 0.30) and at one year (RR: 0.96, 95% CI: 0.79-1.16; p = 0.65). MV-PCI was associated with a greater risk of stroke (RR: 1.19, 95% CI: 1.08-1.32; p < 0.001) and bleeding events (RR: 1.27, 95% CI: 1.07-1.51; p = 0.006), but reduced risk of recurrent MI (RR: 0.89, 95% CI: 0.82-0.97; p = 0.009) and repeat revascularization (RR: 0.34, 95% CI: 0.16-0.71; p = 0.004). No increased risk of coronary artery bypass grafting was present (RR: 1.09, 95% CI: 0.38-3.17; p = 0.87)., Conclusions: C-PCI was associated with a lower rate of renal dysfunction but not all-cause mortality in patients with CS complicating acute MI., Competing Interests: All the authors declare that they have no conflicts of interest.

Introduction: Sacubitril/valsartan (S/V) reduces all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF), but it may decline their estimated glomerular filtration rates (eGFR). In addition to eGFR, this clinical study aimed to develop a blood urea nitrogen (BUN)-based index to evaluate the status of renal perfusion and then identify predictors of all-cause death or heart transplant in patients with HFrEF receiving S/V., Methods: From the recruited 291 patients with HFrEF who were prescribed S/V from March 2017 to March 2019, we collected demographic, drug history, laboratory, echocardiographic, and clinical data from 1 year before S/V initiation until December 2020. Regression analysis was conducted by fitting Cox's models with time-dependent covariates for the survival time and applying the modern stepwise variable selection procedure. The smoothing spline method was used to detect nonlinearity in effect and yield optimal cut-off values for continuous covariates., Results: In the Cox's model, decreased hemoglobin level, decreased mean left ventricular ejection fraction, declined daily dose of S/V, decreased eGFR within 3 months, and increased BUN levels within 1 month and 9 months over time were significantly associated with an increased risk of all-cause death or heart transplant in patients with HFrEF., Conclusions: Adequate maintenance of renal perfusion is crucial for the continuous use of S/V and to avoid worsening renal function in patients with HFrEF. We defined the maximum increase in BUN levels within a specified period as the Worsening Renal Perfusion Index (WRPSV Index) to capture the prognostic effect of renal hypoperfusion in patients with HFrEF., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI., Methods: In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (&gt; 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence., Results: We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1-25.9), urinary NGAL (DOR 13.8, 95% CI 10.2-18.8), and serum NGAL (DOR 12.6, 95% CI 9.3-17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively., Conclusions: Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients. Trial registration CRD42020207883 , October 06, 2020., (© 2022. The Author(s).)

Aftercare programs' effectiveness for suicide ideators has seldom been reported. This study assessed rates and factors related to the recurrence of suicide-related episodes after the index suicidal ideation episode, index cases, and family members receiving aftercare. This is a secondary data analysis of 1787 suicidal ideation episodes from 1557 individuals reported to the National Suicide Surveillance System in New Taipei City, Taiwan, from January 2012 to June 2013 and followed up until September 2013. Among 1787 index suicidal ideations, 19.1% had recurrences of suicide-related episodes, including suicidal ideation (11.9%), attempt (6.7%), and death (0.5%) within 2 years after index ideation. These recurrences were significantly reduced after the index cases received aftercare twice, three, and four or higher. Family members receiving aftercare twice or more were associated with reduced suicidality in the index cases. Receiving aftercare among index cases was associated with being a woman, suicide due to occupation/finance, and reporting from suicide hotlines. Receiving aftercare among family members was associated with the index cases aged ≤ 19 years old, suicide reasons related to school, occupation/finance, and reporting from schools and hospitals. Aftercare programs for suicide ideators and family members of adolescent suicide ideators (aged ≤ 19 years old) decreased subsequent episodes of suicidal behavior., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The purpose of this study was to establish a new reference chart and growth standards for fetal biometry in Taiwan., Materials and Methods: 2047 singleton pregnancies were enrolled in this study with 15,813 fetal scans between 18 and 40 gestational weeks. A reference chart and normal range for fetal biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) was established by longitudinal quantile regression model. 330 women with comorbidities including gestational hypertension, preeclampsia and gestational diabetes were excluded and 1717 pregnant women were enrolled for the growth standard., Results: The new reference values were significantly larger across all gestational ages compared with the prior National Taiwan University reference chart in 1983. Compared with Intergrowth-21st, the BPD was larger at 18-23 weeks, the AC was larger at 18-24 weeks and the FL was larger at 18-36 weeks whereas they were all smaller at 29-40 weeks for the BPD, at 32-40 weeks for the AC and at 38-40 weeks for the FL. A quantile regression equation of biometry was established. BPD, AC, and FL had weekly growth of 2.5, 9.87 and 2.15 mm. Prepregnancy body weight, height, age, and gestational diabetes increased fetal size. Both gestational and chronic hypertension decreased fetal size., Conclusion: To promote maternal-fetal safety, a new reference chart and growth standard for fetal biometry is necessary to measure fetal growth., Competing Interests: Conflicts of Interest All authors have no conflicts of interest to declare., (Copyright © 2022. Published by Elsevier B.V.)

Background: The role of consolidative chemotherapy (CCT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT) is unclear. We aimed to compare the overall survival (OS) of those treated with vs without CCT via a population based approach., Methods: Eligible LA-ESCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between those with vs without CCT. We also evaluated the OS in supplementary analyses via alternative approaches., Results: Our primary analysis consisted of 368 patients in whom covariates were well balanced after PS weighting. The HR of death when CCT was compared to without was 0.67 (95% confidence interval 0.52-0.86, P = 0.002). The HR of IECM was 0.66 (P = 0.04). The HR of OS remained similarly in favor of CCT in supplementary analyses., Conclusions: We found that CCT was associated with significantly improved OS for LA-ESCC patients treated with dCCRT. Randomized controlled trials were needed to confirm this finding., (© 2022. The Author(s).)

Background: The role of adjuvant concurrent chemoradiotherapy (ACCRT) is unclear for patients with esophageal squamous cell carcinoma (ESCC) who receive esophagectomy with clean margins. We compared the survival of the ACCRT versus observation groups for these patients staged with positron emission tomography (PET) via a population-based approach., Methods: Eligible patients with locally advanced ESCC diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratios (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between the ACCRT and observation groups. We also evaluated overall survival (OS) in subgroups of either with or without lymph node metastases., Results: Our primary analysis consisted of 105 patients in whom the covariates were well balanced after PS weighting. The HR for death when ACCRT was compared with observation was 0.58 (95% confidence interval 0.28-1.21, p = 0.15). The results were also not significantly different for IECM or in the subgroup analyses., Conclusion: We found that for patients with PET-staged ESCC who received esophagectomy with clean margins, the survival was not statistically different between ACCRT and observation. Further studies (randomized or larger sample size) are needed to clarify this issue., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objectives: Blunt chest trauma is often associated with severe pain, reduced lung function and decreased sleep quality. This study aims to investigate the immediate and long-term effect of acupuncture on these factors using a randomized control double-blind design., Methods: A total of 72 patients were randomized into 2 groups: treatment group (press tack acupuncture) and control group (press tack placebo). The face rating scale, numerical rating scale (NRS), portable incentive spirometer and Verran Snyder-Halpern sleep scale were measured at baseline, immediately after the intervention, and at the 4th day, with 2-weeks and 3-months follow-ups., Results: There were no significant changes between the groups at the baseline measurements, with the exception of hypertension comorbidity. Immediately after the intervention and on the 4th day follow-up, the patients in the treatment group showed a significantly lower face rating scale when compared to the control (P < 0.05). There were no significant changes in any of the other measurements between the groups (P > 0.05). Subgroup analysis revealed that the NRS for turn over on the 4th day was reduced significantly in the treatment group of patients without lung contusion (P < 0.05). For patients without pleural drainage, cough NRS in the treatment group was significantly reduced in the 2-week follow-up (P < 0.05)., Conclusions: This study showed that press tack acupuncture effects on pain reduction were inconclusive. However, future studies on the effect of acupuncture on blunt chest trauma patients are needed., Clinical Trial Registration: clinicaltirl.gov: NCT04318496., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Utilizing the optimal mass transportation (OMT) technique to convert an irregular 3D brain image into a cube, a required input format for a U-net algorithm, is a brand new idea for medical imaging research. We develop a cubic volume-measure-preserving OMT (V-OMT) model for the implementation of this conversion. The contrast-enhanced histogram equalization grayscale of fluid-attenuated inversion recovery (FLAIR) in a brain image creates the corresponding density function. We then propose an effective two-phase residual U-net algorithm combined with the V-OMT algorithm for training and validation. First, we use the residual U-net and V-OMT algorithms to precisely predict the whole tumor (WT) region. Second, we expand this predicted WT region with dilation and create a smooth function by convolving the step-like function associated with the WT region in the brain image with a [Formula: see text] blur tensor. Then, a new V-OMT algorithm with mesh refinement is constructed to allow the residual U-net algorithm to effectively train Net1-Net3 models. Finally, we propose ensemble voting postprocessing to validate the final labels of brain images. We randomly chose 1000 and 251 brain samples from the Brain Tumor Segmentation (BraTS) 2021 training dataset, which contains 1251 samples, for training and validation, respectively. The Dice scores of the WT, tumor core (TC) and enhanced tumor (ET) regions for validation computed by Net1-Net3 were 0.93705, 0.90617 and 0.87470, respectively. A significant improvement in brain tumor detection and segmentation with higher accuracy is achieved., (© 2022. The Author(s).)

Objectives: This study aimed to assess the effectiveness of practicing acupressure on the Shenmen and Neiguan acupoints with a view to reduce anxiety and improve the comfort and physical health of patients undergoing thoracoscopic surgery., Methods: A total of 100 hospitalized patients undergoing thoracoscopic surgery were assigned randomly into the experimental ( n = 49) and control groups ( n = 51). Subjects in the experimental group received routine care plus acupressure on the Shenmen and Neiguan acupoints, while those in the control group received regular routine care. The data were collected using demographic information, physical and surgical data, the Visual Analog Scale (VAS)-A, the State-Trait Anxiety Inventory Y Form (STAI-Y1), and Shortened General Comfort Questionnaire scores. The linear mixed model was used to examine the influences of acupressure on VAS-A and STAI-Y1 scores at different time points before and after the surgery to observe group-by-time interactions., Results: The mean age of the subjects was 60.97 years. All subjects had mild-to-moderate anxiety after surgery and showed a statistically significant decline in regression coefficients on the first and second days after the intervention (β = -11.61, p = 0.002; β = -18.71, p < 0.001). Similarly, for STAI-YI scores, the data showed a significant difference in the pre-test and post-test interactions between the two groups (β = 4.72, p = 0.031). Conversely, acupressure did not have a statistically significant difference on comfort (F = 2.953, p = 0.057). Compared with the control subjects, the experimental subjects used less morphine and developed side effects less frequently ( p < 0.01). They were also able to get out of bed after surgery 163.79 min earlier ( p < 0.05)., Conclusions: Acupressure is a simple and easy-to-practice treatment. Acupressure on the Shenmen and Neiguan acupoints reduces anxiety and improves recovery in patients after undergoing thoracoscopic surgery.

There are more single inhaler device triple therapy available for COPD patients now. However, the effect of long-term triple therapy fixed dose combination (FDC) on mortality remains unclear. This study aimed to evaluate the impact of one-year single inhaler device triple therapy, including long-acting β2-agonists (LABAs), long-acting muscarinic receptor antagonists (LAMAs), and inhaled corticosteroids (ICSs), with dual therapies, comprised of either LABA/LAMA or ICS/LABA, on the mortality of patients with COPD. We searched the PubMed, Cochrane library, Web of Science, Embase databases, and clinical trial registry of clinicaltrials.gov and WHO ICTRP. Randomized controlled trials (RCTs) compared single inhaler device triple and dual therapies for 52 weeks were selected for the meta-analysis. The primary endpoint was all-cause mortality. A total of 6 RCTs were selected for the meta-analysis, including 10,274 patients who received single inhaler device triple therapy (ICS/LABA/LAMA FDC) and 12,395 patients who received ICS/LABA or LABA/LAMA dual therapy. Risk of death was significantly lower in the ICS/LABA/LAMA FDC group compared to the LABA/LAMA group (RR = 0.69, 95% CI = 0.53-0.90, p = 0.007). There was no significant difference in mortality between the ICS/LABA/LAMA FDC and ICS/LABA therapy groups (RR = 0.94, 95% CI = 0.72-1.24, p = 0.66). In addition, patients receiving ICS/LABA/LAMA FDC therapy had less moderate or severe exacerbations compared with the dual therapy groups (RR = 0.76, 95% CI = 0.73-0.80, p < 0.001 for LABA/LAMA; RR = 0.84, 95% CI = 0.78-0.90, p < 0.001 for ICS/LABA). By contrast, the risk of pneumonia in the ICS/LABA/LAMA FDC group was higher than in the LABA/LAMA group (RR = 1.43, 95% CI = 1.21-1.68, p < 0.001). In conclusion, ICS/LABA/LAMA FDC therapy could help improve the clinical outcomes of patients with COPD. However, triple therapy could increase the risk of pneumonia in comparison with LABA/LAMA dual therapy.

Background: Critically ill patients with severe acute kidney injury (AKI) requiring kidney replacement therapy (KRT) have a grim prognosis. Recently, multiple studies focused on the impact of KRT initiation time [i.e., accelerated versus watchful waiting KRT initiation (WWS-KRT)] on patient outcomes. We aim to review the results of all related clinical trials., Methods: In this systematic review, we searched all relevant randomized clinical trials from January 2000 to April 2021. We assessed the impacts of accelerated versus WWS-KRT on KRT dependence, KRT-free days, mortality and adverse events, including hypotension, infection, arrhythmia and bleeding. We rated the certainty of evidence according to Cochrane methods and the GRADE approach., Results: A total of 4932 critically ill patients with AKI from 10 randomized clinical trials were included in this analysis. The overall 28-day mortality rate was 38.5%. The 28-day KRT-dependence rate was 13.0%. The overall incident of KRT in the accelerated group was 97.4% and 62.8% in the WWS-KRT group. KRT in the accelerated group started 36.7 h earlier than the WWS-KRT group. The two groups had similar risks of 28-day [pooled log odds ratio (OR) 1.001, P = 0.982] and 90-day (OR 0.999, P = 0.991) mortality rates. The accelerated group had a significantly higher risk of 90-day KRT dependence (OR 1.589, P = 0.007), hypotension (OR 1.687, P < 0.001) and infection (OR 1.38, P = 0.04) compared with the WWS-KRT group., Conclusions: This meta-analysis revealed that accelerated KRT leads to a higher probability of 90-day KRT dependence and dialysis-related complications without any impact on mortality rate when compared with WWS-KRT. Therefore, we suggest the WWS-KRT strategy for critically ill patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Renal replacement therapy (RRT) is an effective rescue therapy for Type 1 cardiorenal syndrome (CRS). Previous studies have demonstrated that type 1 CRS patients with severe renal dysfunction were susceptible to sepsis, and that serum lactate has been correlated with the risk of mortality in patients with sepsis. However, the association between serum lactate level and the prognosis of type 1 CRS patients requiring RRT is unknown., Methods: An inception cohort of 500 type 1 CRS patients who received RRT in a tertiary-care referral hospital in Taiwan from August 2011 to January 2018 were enrolled. The outcomes of interest were dialysis withdrawal and 90-day mortality. The results were further externally validated using sampling data of type 1 CRS patients requiring dialysis from multiple tertiary-care centers., Findings: The 90-day mortality rate was 52.8% and the incidence rate of dialysis withdrawal was 34.8%. Lower pre-dialysis lactate was correlated with a higher rate of dialysis withdrawal and lower rate of mortality. Generalized additive model showed that 4.2 mmol/L was an adequate cut-off value of lactate to predict mortality. Taking mortality as a competing risk, Fine-Gray subdistribution hazard analysis further indicated that a low lactate level (≦ 4.2 mmol/L) was an independent predictor for the possibility of dialysis withdrawal, as also shown in external validation. The interaction of quick Sequential Organ Failure Assessment score and lactate was associated with dialysis dependence in a disease severity-dependent manner. Furthermore, the associations between hyperlactatemia and dialysis dependence were consistent in the patients with and without sepsis., Interpretation: Serum lactate level is accurate and capable of forecasting the prognosis along with qSOFA severity for clinical decision-making for treating type 1 CRS patients. Further studies are needed to validate our results., Funding: This study was supported by grants from Taiwan National Science Council [104-2314-B-002-125-MY3,106-2314-B-002-166-MY3,107-2314-B-002-026-MY3], National Taiwan University Hospital [106-FTN20,106-P02,UN106-014,106-S3582,107-S3809,107-T02,PC1246,VN109-09,109-S4634,UN109-041], Ministry of Science and Technology of the Republic of China [MOST106-2321-B-182-002,106-2314-B-182A-064,MOST107-2321-B-182-004,MOST107-2314-B-182A-138, MOST108-2321-B-182-003,MOST109-2321-B-182-001, MOST108-2314-B-182A-027], Chang Gung Memorial Hospital [CMRPG-2G0361,CMRPG-2H0161,CMRPG-2J0261, CMRPG-2K0091], and Ministry of Health and Welfare of the Republic of China [PMRPG-2L0011]., Competing Interests: HCP, TMH, CYS, NKC, CHT, FYY, TSL, YMC, and VCW reported grants from Taiwan National Science Council, National Health Research Institutes, National Taiwan University Hospital, and Ministry of Science and Technology (MOST) of the Republic of China (Taiwan). No other disclosures were reported., (© 2021 Published by Elsevier Ltd.)

The purpose of this study is to investigate the correlation between glomerular filtration rate (GFR) estimated by different renal function equations and non-vitamin K antagonist oral anticoagulant concentration. Atrial fibrillation patients who aged ≥ 20 years and used dabigatran, rivaroxaban, or apixaban for thromboembolism prevention were enrolled to collect blood samples and measure drug concentrations using ultra-high-performance liquid chromatography with tandem mass spectrometry. The GFR was estimated using the Cockroft-Gault formula (abbreviated as creatinine clearance, CrCL), Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) featuring both creatinine and cystatin C, and the Modification of Diet in Renal Disease Study equation (MDRD). Multivariate regression was used to investigate the associations of different renal function estimates with drug concentrations. A total of 511 participants were enrolled, including 146 dabigatran users, 164 rivaroxaban users and 201 apixaban users. Compared to clinical trials, 35.4% of dabigatran, 4.9% of rivaroxaban, and 5.5% of apixaban concentrations were higher than the expected range (p < 0.001). CKD-EPI and MDRD estimates classified fewer patients as having GFR < 50 mL/min than CrCL in all 3 groups. Both CrCL and CKD-EPI were associated with higher-than-expected ranges of dabigatran or rivaroxaban concentrations. Nevertheless, none of the renal function equations was associated with higher-than-expected apixaban concentrations. For participants aged ≥ 75 years, CKD-EPI may be associated with higher-than-expected trough concentration of dabigatran. In conclusion, CrCL and CKD-EPI both can be used to identify patients with high trough concentrations of dabigatran or rivaroxaban. Among elderly patients who used dabigatran, CKD-EPI may be associated with increased drug concentration., (© 2021. The Author(s).)

It is generally known that a layer of amorphous silicon oxide (SiO 2 ) naturally exists on the surface of silicon, resulting in the growth of gallium oxide (Ga 2 O 3 ) that is no longer affected by substrate crystallinity during sputtering. This work highlights the formation energy between the native amorphous nano-oxide film formed on the Si substrate and monoclinic β-Ga 2 O 3 dominating the preferred orientation prepared for deep ultraviolet photodetectors. The latter were deposited on p-type silicon ( p -Si) with (111) orientation using radio frequency sputtering at 600 °C and post rapid thermal annealing (RTA). The X-ray diffraction (XRD) results indicate both as-deposited and postannealing films with the (400) preferred orientation for a layer thickness of 100 nm. However, slight random orientation with the amorphous structure is mixed in the preferred one for the as-deposited film with a thickness of 200 nm and reduced after being annealed at 800 °C, which is observed by XRD and transmission electron microscopy. Meanwhile, thermal-induced massive twin boundaries (TBs) and stacking faults (SFs) were generated when annealed at 1000 °C, owing to the relaxation of lattice strain by the coherent interface. The interfacial bonding energy per unit area ( E i ) between β-Ga 2 O 3 films with various facets ((001), (010), (100), and (2̅01)) and amorphous SiO 2 was calculated using density functional theory. The E i of β-Ga 2 O 3 (100)/SiO 2 reveals the highest value (0.289 eV/Å 2 ), which is consistent with the (100) preferred orientation of deposited films. The (100) preferred orientation is the driving force for TBs and SFs. The discrimination of responsivities and the photo/dark current contrast ratio ( I ph / I dark ) are inversely proportional to the amorphous structure, grain boundaries, TBs, and SFs. Therefore, optimum metal-semiconductor-metal photodetector performance is achieved for RTA-treated samples at 800 °C with an I ph / I dark of 3.91 × 10 2 and a responsivity of 0.702 A/W (λ peak = 230 nm) at 5 V bias for a 200 nm thin film., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Optimal mass transport (OMT) theory, the goal of which is to move any irregular 3D object (i.e., the brain) without causing significant distortion, is used to preprocess brain tumor datasets for the first time in this paper. The first stage of a two-stage OMT (TSOMT) procedure transforms the brain into a unit solid ball. The second stage transforms the unit ball into a cube, as it is easier to apply a 3D convolutional neural network to rectangular coordinates. Small variations in the local mass-measure stretch ratio among all the brain tumor datasets confirm the robustness of the transform. Additionally, the distortion is kept at a minimum with a reasonable transport cost. The original [Formula: see text] dataset is thus reduced to a cube of [Formula: see text], which is a 76.6% reduction in the total number of voxels, without losing much detail. Three typical U-Nets are trained separately to predict the whole tumor (WT), tumor core (TC), and enhanced tumor (ET) from the cube. An impressive training accuracy of 0.9822 in the WT cube is achieved at 400 epochs. An inverse TSOMT method is applied to the predicted cube to obtain the brain results. The conversion loss from the TSOMT method to the inverse TSOMT method is found to be less than one percent. For training, good Dice scores (0.9781 for the WT, 0.9637 for the TC, and 0.9305 for the ET) can be obtained. Significant improvements in brain tumor detection and the segmentation accuracy are achieved. For testing, postprocessing (rotation) is added to the TSOMT, U-Net prediction, and inverse TSOMT methods for an accuracy improvement of one to two percent. It takes 200 seconds to complete the whole segmentation process on each new brain tumor dataset., (© 2021. The Author(s).)

Hedgehog plays an important role in a wide range of physiological and pathological conditions. Paracrine activation of Hedgehog pathway in stromal cells increases the expression of VEGF, which promotes neovascularization in colorectal cancer and ultimately the growth of colorectal cancer. Berberine (BBR) has anticancer activity. In this study we investigated whether BBR inhibited the growth of colon cancer through suppressing the paracrine sonic hedgehog (SHH) signaling in vitro and in vivo. We showed that BBR (1-10 μM) dose-dependently inhibited the secretion and expression of SHH protein in HT-29 and SW480 cells. BBR did not influence the transcription of SHH, but promoted the degradation of SHH mRNA, thus decreased the SHH mRNA expression in the colorectal cancer cells. In nude mice bearing HT-29 xenograft, oral administration of BBR (100 mg · kg - 1  · d -1 ) or a positive control drug GDC-0449 (100 mg · kg -1  · d -1 ) for 4 weeks markedly suppressed the growth of HT-29 tumor with BBR exhibiting a better antitumor efficacy. The tumor growth inhibition caused by BBR or GDC-0449 was comparable to their respective inhibitory effect on the mouse-specific Gli mRNA expression in the tumor. However, BBR (20 μM) did not affect the expression of human transcription factor Gli1 mRNA in HT-29 and SW480 cells. In conclusion, BBR promotes the degradation of SHH mRNA in colorectal cancer cells, interrupting the paracrine Hedgehog signaling pathway activity thus suppresses the colorectal cancer growth. This study reveals a novel molecular mechanism underlying the anticancer action of BBR.

Background : Hepatocellular carcinoma (HCC) presents a common malignant tumor worldwide. Although kinectin 1 ( KTN1 ) is the most frequently identified antigen in HCC tissues, the detailed roles of KTN1 in HCC remain unknown. This study seeks to clarify the expression status and clinical value of KTN1 in HCC and to explore the complicated biological functions of KTN1 and its underlying mechanisms. Methods : In-house reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of KTN1 in HCC tissues. External gene microarrays and RNA-sequencing datasets were downloaded to confirm the expression patterns of KTN1 . The prognostic ability of KTN1 in HCC was assessed by a Kaplan-Meier curve and a hazard ratio forest plot. The CRISPR/Cas9 gene-editing system was used to knock out KTN1 in Huh7 cells, which was verified by PCR-Sanger sequencing and western blotting. Assays of cell migration, invasion, viability, cell cycle, and apoptosis were conducted to explore the biological functions. RNA sequencing was performed to quantitatively analyze the functional deregulation in KTN1 -knockout cells compared to Huh7-wild-type cells. Upregulated genes that co-expressed with KTN1 were identified from HCC tissues and were functionally annotated. Results : KTN1 expression was increased in HCC tissues (standardized mean difference [SMD] = 0.20 [0.04, 0.37]). High KTN1 expression was significantly correlated with poorer prognosis of HCC patients, and KTN1 may be an independent risk factor for HCC (pooled HRs = 1.31 [1.05, 1.64]). After KTN1 -knockout, the viability, migration, and invasion ability of HCC cells were inhibited. The proportion of HCC cells in the G0-G1 phases increased after KTN1 knockout, which also elevated the apoptosis rates in HCC cells. Several cascades, including innate immune response, chemical carcinogenesis, and positive regulation of transcription by RNA polymerase II, were dramatically changed after KTN1 knockout. KTN1 primarily participated in the cell cycle, DNA replication, and microRNAs in cancer pathways in HCC tissues. Conclusion : Upregulation of KTN1 served as a promising prognosticator in HCC patients. KTN1 promotes the occurrence and deterioration of HCC by mediating cell survival, migration, invasion, cell cycle activation, and apoptotic inhibition. KTN1 may be a therapeutic target in HCC patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aberrantly activated Hedgehog (Hh) pathway is critical for driving the initiation and progression of multiple types of cancers, including medulloblastoma (MB) and basal cellular carcinoma (BCC). The majority of current Hh antagonist function by targeting the transmembrane domain of the oncoprotein Smoothened (Smo), a G-protein-coupled receptor-like receptor of Hh pathway. However, the primary and acquired resistance to current Smo inhibitors raise a critical need to develop next-generation of Smo inhibitors to improve their clinical efficacy. In this study, we identify that FDA approved drug ABT-199 significantly and selectively inhibits the Hh pathway. Mechanistically, ABT-199 acts as a competitive inhibitor of oxysterol by potentially targeting the cysteine rich domain (CRD) of Smo, rather as a BH3 mimetic. ABT-199 obviously inhibits the growth of Hh-driven tumors and possesses capacity of combating the primary and acquired resistance to Smo inhibitors caused by Smo mutations. Our data reposition ABT-199 as a Smo inhibitor for treating Hh-driven tumors, especially for those bearing Smo mutations and resistant to current Smo inhibitors. Meanwhile, our findings strengthen the argument that the CRD of Smo is a promising target for developing novel Smo inhibitors with capacity of combating the resistance to Smo inhibitors.

Introduction: Blunt chest trauma (BCT) accounts for up to 65% of polytrauma patients. In patients with 0 to 2 rib fractures, treatment interventions are typically limited to oral analgesics and breathing exercises. Patients suffering from BCT experience symptoms of severe pain, poor sleep, and inability to perform simple daily life activities for an extended period of time thereafter. In this trial, we aim to investigate the efficacy of acupuncture as a functional and reliable treatment option for blunt chest trauma patients., Methods: The study is designed as a double-blind randomized control trial. We will include 72 patients divided into 2 groups; the acupuncture group (Acu) and placebo group (Con). The acupuncture group will receive true acupuncture using a uniquely designed press tack needle. The control group will receive placebo acupuncture treatment through the use of a similarly designed press tack needle without the needle element. The acupoints selected for both groups are GB 34, GB 36, LI 4, LU 7, ST 36, and TH 5. Both groups will receive 1 treatment only following the initial visit to the medical facility and upon diagnosis of BCT. Patient outcome measurements include: Numerical Rating Scale, Face Rating Scale, respiratory function flowmeter, Verran Snyder-Halpern sleep scale, and the total amount of allopathic medication used. Follow-up time will be scheduled at 4 days, 2 weeks, and lastly 3 months., Expected Outcome: The results of this study can potentially provide a simple and cost-effective analgesic solution to blunt chest trauma patients. This novel study design can serve as supporting evidence for future double-blind studies within the field of acupuncture., Other Information: The study will be conducted in the thoracic surgical department and acupuncture department in China Medical University Hospital, Taichung, Taiwan. The study will be conducted on blunt chest trauma patients and is anticipated to have minimum risk of adverse events. Enrollment of the patients and data collection will start from March 2020. Study completion time is expected in March 2022., Protocol Registration: (CMUH109-REC1-002), (NCT04318496)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We investigated the respective effects of preoperative angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the incidence of postoperative acute kidney injury (AKI) and mortality. Methods: In this nested case-control study, we enrolled 20,276 patients who received major surgery. We collected their baseline demographic data, comorbidities and prescribed medication, the outcomes of postoperative AKI and mortality. AKI was defined by the criteria suggested by KDIGO (Kidney disease: Improving Global Outcome). Logistic regression was used to assess the impact of exposure to ACEIs or ARBs. Results: Compared with patients without ACEI/ARB, patient who received ARBs had a significantly lower risk for postoperative AKI (adjusted odds ratio (OR) 0.82, p = 0.007). However, ACEI users had a higher risk for postoperative AKI than ARB users (OR 1.30, p = 0.027), whereas the risk for postoperative AKI was not significantly different between the ACEI users and patients without ACEI/ARB (OR 1.07, p = 0.49). Compared with patients without ACEI/ARB, both ACEI and ARB users were associated with a reduced risk of long-term all-cause mortality following surgery (OR 0.47, p = 0.002 and 0.60, p < 0.001 in ACEI and ARB users, respectively), without increasing the risk of hyperkalemia during the index hospitalization ( p = 0.20). The risk of long-term all-cause mortality following surgery in ACEIs and ARBs users did not differ significantly (OR 0.74, p = 0.27). Furthermore, the higher the defined daily dose of ARB, the better the protection against AKI provided. Conclusion: Our study revealed that preoperative use of ARBs was associated with reduced postoperative AKI, which is better in high quantity, whereas preoperative use of ACEIs or ARBs were both associated with reduced mortality and did not increase the risk of hyperkalemia., 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 Yang, Huang, Lai, Chou, Tsao, Huang, Lin, Chen, Wu and NSARF study group.)

The levels of fibroblast growth factor 23 (FGF23) rapidly increases after acute kidney injury (AKI). However, the role of FGF23 in AKI is still unclear. Here, we observe that pretreatment with FGF23 protein into ischemia-reperfusion induced AKI mice ameliorates kidney injury by promoting renal tubular regeneration, proliferation, vascular repair, and attenuating tubular damage. In vitro assays demonstrate that SDF-1 induces upregulation of its receptor CXCR4 in endothelial progenitor cells (EPCs) via a non-canonical NF-κB signaling pathway. FGF23 crosstalks with the SDF-1/CXCR4 signaling and abrogates SDF-1-induced EPC senescence and migration, but not angiogenesis, in a Klotho-independent manner. The downregulated pro-angiogenic IL-6, IL-8, and VEGF-A expressions after SDF-1 infusion are rescued after adding FGF23. Diminished therapeutic ability of SDF-1-treated EPCs is counteracted by FGF23 in a SCID mouse in vivo AKI model. Together, these data highlight a revolutionary and important role that FGF23 plays in the nephroprotection of IR-AKI.

Background: Acute kidney injury (AKI) is a common yet possibly fatal complication among critically ill patients in intensive care units (ICU). Although renal replacement therapy (RRT) is an important supportive management for severe AKI patients, the optimal timing of RRT initiation for these patients is still unclear., Methods: In this systematic review, we searched all relevant randomized controlled trials (RCTs) that directly compared accelerated with standard initiation of RRT from PUBMED, MEDLINE, EMBASE, and Cnki.net published prior to July, 20, 2020. We extracted study characteristics and outcomes of being free of dialysis, dialysis dependence and mortality. We rated the certainty of evidence according to Cochrane methods and the GRADE approach., Results: We identified 56 published relevant studies from 1071 screened abstracts. Ten RCTs with 4753 critically ill AKI patients in intensive care unit (ICU) were included in this meta-analysis. In our study, accelerated and standard RRT group were not associated with all-cause mortality (log odds-ratio [OR]: - 0.04, 95% confidence intervals [CI] - 0.16 to 0.07, p = 0.46) and free of dialysis (log OR: - 0.03, 95% CI - 0.14 to 0.09, p = 0.65). In the subgroup analyses, accelerated RRT group was significantly associated with lower risk of all-cause mortality in the surgical ICU and for those who received continuous renal replacement therapy (CRRT). In addition, patients in these two subgroups had higher chances of being eventually dialysis-free. However, accelerated initiation of RRT augmented the risk of dialysis dependence in the subgroups of patients treated with non-CRRT modality and whose Sequential Organ Failure Assessment (SOFA) score were more than 11., Conclusions: In this meta-analysis, critically ill patients with severe AKI would benefit from accelerated RRT initiation regarding all-cause mortality and being eventually free of dialysis only if they were surgical ICU patients or if they underwent CRRT treatment. However, the risk of dialysis dependence was increased in the accelerated RRT group when those patients used non-CRRT modality or had high SOFA scores. All the literatures reviewed in this study were highly heterogeneous and potentially subject to biases. Trial registration CRD42020201466, Sep 07, 2020. https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=201466 .

Background/purpose: Chronic kidney disease (CKD) is a risk factor for contrast associated acute kidney injury (CA-AKI). The risk of renin-angiotensin-aldosterone system inhibitor (RASi) use in patients with CKD before the administration of contrast is not clear., Methods: In this nested case-control study, 8668 patients received contrast computed tomography (CT) from 2013 to 2018 during index administration in a multicenter hospital cohort. The identification of AKI is based on the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria within 48 h after contrast medium used., Results: Finally, 986 patients (age, 63.36 ± 12.22; men, 72.92%) with CKD (estimated glomerular filtration rate (eGFR) = 35.0 ± 19.8 mL/min/1.73 m 2 ) were eligible for analysis. After the index date, RASi users (n = 315) were less likely to develop CA-AKI (13.65% vs 30.4%, p < 0.001), and had a lower hospital mortality (8.25% vs 19.23%, p < 0.001) compared with non-users. The pre-contrast use of RASi decrease the risk of AKI (OR, 0.342, p < 0.001) and hospital mortality (OR, 0.602, p = 0.045). Even a few defined daily doses (DDDs) of RASi treatment, more than 0.02 prior to contrast CT could attenuate CA-AKI. The hospital mortality was higher in RASi non-users if their eGFR value was more than 17.9 mL/min/1.73 m 2 ., Conclusion: RASi use in patients with CKD prior to contrast CT has the potential to mitigate the incidence of AKI and hospital mortality. Even a low dose of RASi will noticeably decrease the risk of AKI and will not increase the risk of hyperkalemia., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020. Published by Elsevier B.V.)

Magnetic attachment system is used to embed in polymethyl methacrylate (PMMA) resin denture base to improve denture stability. However, dislodgement of magnetic attachments from denture base is a major clinical problem. This study is to evaluate the bond strength between PMMA and stainless steel using metal primer and atmospheric pressure plasma jet (APPJ) treatment. Stainless steel discs were treated with Single Bond Universal Adhesive; Palfique Universal Bond; Alloy Primer; heat treatment with Alloy Primer; and 10-s, 20-s, and 30-s APPJ treatment with Alloy Primer. The shear bond strength between PMMA and surface-treated stainless steel was measured using universal testing machine. The effects of N 2 flow rate (60, 50, 40, 30 SLM), thermal cycling, and air quenching on shear bond strength were also investigated. The surface of each disc was examined using X-ray photoelectron spectroscopy and a goniometer. Finally, the temperature of plasma with various N 2 flow rates was measured and the optical emission spectra of the plasma were measured using spectrometer. Alloy Primer produced the highest bond strength. APPJ treatment was effective at enhancing bond strength by cleaning the surface of contaminants. Moreover, APPJ treatment with air quenching increased surface O 2- /OH- and Fe 2 O 3 /FeOOH ratios, reducing the negative influence of thermal cycling on bond strength. Alloy Primer with 20 s of APPJ treatment with a 50-SLM N 2 flow rate and air quenching was the most effective at increasing bond strength., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Acute kidney injury (AKI) is a frequent complication of traumatic injury; however, long-term outcomes such as mortality and end-stage kidney disease (ESKD) have been rarely reported in this important patient population. We compared the long-term outcome of vehicle-traumatic and non-traumatic AKI requiring renal replacement therapy (AKI-RRT). This nationwide cohort study used data from the Taiwan National Health Insurance Research Database. Vehicle-trauma patients who were suffered from vehicle accidents developing AKI-RRT during hospitalization were identified, and matching non-traumatic AKI-RRT patients were identified between 2000 and 2010. The incidences of ESKD, 30-day, and long-term mortality were evaluated, and clinical and demographic associations with these outcomes were identified using Cox proportional hazards regression models. 546 vehicle-traumatic AKI-RRT patients, median age 47.6 years (interquartile range: 29.0-64.3) and 76.4% male, were identified. Compared to non-traumatic AKI-RRT, vehicle-traumatic AKI-RRT patients had longer length of stay in hospital [median (IQR):15 (5-34) days vs. 6 (3-11) days; p < 0.001). After propensity matching with non-traumatic AKI-RRT cases with similar demographic and clinical characteristics. Vehicle-traumatic AKI-RRT patients had lower rates of long-term mortality (adjusted hazard ratio (HR), 0.473; 95% CI, 0.392-0.571; p < 0.001), but similar rates of ESKD (HR, 1.166; 95% CI, 0.829-1.638; p = 0.377) and short-term risk of death (HR, 1.134; 95% CI, 0.894-1.438; p = 0.301) as non-traumatic AKI-RRT patients. In competing risk models that focused on ESKD, vehicle-traumatic AKI-RRT patients were associated with lower ESKD rates (HR, 0.552; 95% CI, 0.325-0.937; p = 0.028) than non-traumatic AKI-RRT patients. Despite severe injuries, vehicle-traumatic AKI-RRT patients had better long-term survival than non-traumatic AKI-RRT patients, but a similar risk of ESKD. Our results provide a better understanding of long-term outcomes after vehicle-traumatic AKI-RRT.

Objectives: To investigate the incidence of active tuberculosis (TB) among COPD patients using fluticasone/salmeterol or budesonide/formoterol, and to identify any differences between these two groups of patients., Methods: The study enrolled COPD patients from Taiwan NHIRD who received treatment with fluticasone/salmeterol or budesonide/formoterol for > 90 days between 2004 and 2011. The incidence of active TB was the primary outcome., Results: Among the intention-to-treat population prior to matching, the incidence rates of active TB were 0.94 and 0.61% in the fluticasone/salmeterol and budesonide/formoterol groups, respectively. After matching, the fluticasone/salmeterol group had significantly higher rates of active TB (adjusted HR, 1.41, 95% CI, 1.17-1.70) compared with the budesonide/formoterol group. The significant difference between these two groups remained after a competing risk analysis (HR, 1.45, 95% CI, 1.21-1.74). Following propensity score matching, the fluticasone/salmeterol group had significantly higher rates of active TB compared with the budesonide/formoterol group (adjusted HR, 1.45, 95% CI, 1.14-1.85). A similar trend was observed after a competing risk analysis (HR, 1.44, 95% CI, 1.19-1.75). A higher risk of active TB was observed in the fluticasone/salmeterol group compared with the budesonide/formoterol group across all subgroups, but some differences did not reach statistical significance., Conclusion: Fluticasone/salmeterol carried a higher risk of active TB compared with budesonide/formoterol among COPD patients.

Objectives: Acute kidney injury (AKI) and acute kidney disease (AKD) are a continuum on a disease spectrum and frequently progress to chronic kidney disease. Benefits of nephrologist subspecialty care during the AKD period after AKI are uncertain., Methods: Patients with AKI requiring dialysis who subsequently became dialysis independent and survived for at least 90 days, defined as the AKD period, were identified from the Taiwanese population's health insurance database. Cox proportional hazard models using death as the competing risk before and after propensity-score matching were applied to evaluate various endpoints., Results: Among a total of 20 260 patients with AKI requiring dialysis who became dialysis independent, only 7550 (37.3%) patients were followed up with by a nephrologist (F/U nephrol group) during the AKD period. During a mean 4.04 ± 3.56 years of follow-up, the patients in the F/U nephrol group were more often administered statin, antihypertensives, angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), diuretics, antiplatelet agents, and antidiabetic agents. The patients in the F/U nephrol group had a lower mortality rate (hazard ratio [HR] = 0.87, P < .001) and were less likely to have major adverse cardiovascular events (MACE) (subdistribution HR [sHR] = 0.85, P < .001), congestive heart failure (CHF) (sHR = 0.81, P < .001), and severe sepsis (sHR = 0.88, P = .008) according to the Cox proportional model after adjusting for mortality as a competing risk. During the AKD period, an increase in the frequency of nephrology visits was associated with improved outcomes., Conclusions: In this population-based cohort, even after weaning off acute dialysis, only a minority of patients visited a nephrologist during the AKD period. We showed that nephrology follow-up is associated with a decrease in MACE, CHF exacerbations, and sepsis, as well as lower mortality; thus it may improve outcomes in patients with AKD., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Proton pump inhibitors (PPIs) have been reported to increase the risk of acute and chronic renal disease. However, the data are unclear in patients with acute kidney injury (AKI) requiring dialysis (AKI-D) who are often candidates for PPIs. To investigate this important issue, we identified 26,052 AKI-D patients from Taiwan's National Health Insurance Research Database weaning from dialysis. During a mean follow-up period of 3.52 years, the PPI users had a higher incidence of end-stage renal disease (ESRD) than the PPI nonusers (P < 0.001). After propensity score matching and treating mortality as a competing risk factor, the PPI users had a higher risk of ESRD (subhazard ratio (sHR) 1.40; 95% confidence interval (CI), 1.31-1.50) and major adverse cardiac events (MACE, sHR 1.53; 95% CI, 1.37-1.71) compared with the PPI nonusers with AKI-D survivors. In conclusion, the use of PPIs was associated with a higher risk of ESRD and MACE, compared with the PPI nonusers in AKI-D patients who weaned from dialysis., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

Objective: This study aimed at investigating the specific roles of laminarin from seaweed ( Laminaria japonica ) in hepatocellular carcinoma (HCC) and its potential mechanisms related to senescence marker protein-30 (SMP-30). Materials and Methods: Human HCC cell lines, including Bel-7404 and HepG2, were incubated with different concentrations of laminarin (0, 5, 15, 25, 35, and 45 mg/mL). The cell viability and apoptosis rates were detected by WST-8 cell proliferation assay and flow cytometry, respectively. Hepa 1-6 tumor-bearing mice were injected with different concentrations of laminarin (400, 800, and 1200 mg/kg·d), and tumor volume and weight were measured. The expression of SMP-30 was detected in laminarin-treated Bel-7404 and HepG2 HCC cells and LO2 normal liver cells by quantitative real-time PCR and Western blotting. Results: The treatment with laminarin (48 h) significantly decreased the viability and increased the apoptosis rates of Bel-7404 and HepG2 cells in a dose-dependent manner. The injection of laminarin also significantly decreased the tumor volumes (beginning on the 10th day) and tumor weights (30 d post-injection) of mice in a dose-dependent manner. In addition, the treatment with laminarin (35 mg/mL for 48 h) significantly upregulated SMP-30 in Bel-7404 and HepG2 cells but not in LO2 cells. Conclusion: Laminarin inhibited the proliferation of Bel-7404 and HepG2 cells and inhibited the growth of tumors in Hepa 1-6 tumor-bearing mice by upregulating SMP-30.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is associated with high risk for complications and mortality. Whether renin-angiotensin system (RAS) inhibitor should be continued or withdrawn in patients with long-term use before cardiac surgery has been lack of consensus., Methods: We performed this prospective observational cohort study and recruited cardiac surgery patients in the surgical intensive care units between 2000 and 2011. These patients were divided into users and non-users of RAS inhibitor. Propensity score matching and multivariable models were performed to investigate the association between renal outcome, mortality, and preoperative use of RAS inhibitor., Results: Preoperative use of RAS inhibitor was identified as the independent protective factor for AKI development (OR 0.41, 95% CI 0.23, 0.63), AKI severity (stage 3 vs. stage 1, OR 0.35, 95% CI 0.18, 0.69), and renal recovery (OR 3.41, 95% CI 1.84, 5.36). Nevertheless, there was no significant protective effect of RAS inhibitor on in-hospital dialysis, in-hospital mortality, and ensuing development of chronic kidney disease (CKD) after AKI. We created a prediction model of CSA-AKI and indicated that preoperative use of RAS inhibitor provided more protective effect in low-risk than high-risk population., Conclusion: Preoperative use of RAS inhibitor was associated with less AKI development and severity, and higher renal recovery. Although more risk reduction of AKI development was shown in low-risk group by our prediction model, continued use of RAS inhibitor before cardiac surgery could provide protective effect in all patients.

Acute kidney injury is a major health care problem. Improving recognition of those at risk and highlighting those who have developed AKI at an earlier stage remains a priority for research and clinical practice. Prediction models to risk-stratify patients and electronic alerts for AKI are two approaches that could address previously highlighted shortcomings in management and facilitate timely intervention. We describe and critique available prediction models and the effects of the use of AKI alerts on patient outcomes are reviewed. Finally, the potential for prediction models to enrich population subsets for other diagnostic approaches and potential research, including biomarkers of AKI, are discussed., (Copyright © 2019. Published by Elsevier Inc.)

Aims: Methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively) in the nostrils of dogs and workers at an animal shelter were cultured. Staphylococcal toxin genes were analysed to identify potential health concerns., Methods and Results: Samples were obtained from 441 dogs and 9 workers. The respective isolation rates of S. aureus and MRSA were 49·0% (216/441) and 1·6% (7/441) for shelter dogs and 44·4% (4/9) and 33·3% (3/9) for workers, respectively. Isolation of S. aureus in summer (61·9%) and in adult dogs (59·2%) were significantly higher than those in winter (35·8%) and in juvenile dogs (33·3%) (P < 0·001), respectively. The predominant enterotoxin genotypes and combination profiles of S. aureus were (sea, seb, seg, sei, sem, sen, seo, seu) and (sea, sea-seb, and seg-sei-sem-sen-seo-seu), respectively, and 20% of isolates carried food poisoning-associated enterotoxins. The se profiles in shelter dogs were different from those in general pet dogs and their owners. MRSA isolates were identified as SCCmec IV and VII, and they shared se combination profiles of (sec-seg-sei-sel-sem-sen-seo-seu) and (seb-sek-seq). MRSA in this shelter had similar microbiological characteristics as those reported in CA-MRSA ST59 in humans., Conclusions: Human health-associated bacteria and food poisoning-related toxin genes were identified. Further evaluations of health concerns in animal shelters are necessary., Significance and Impact of the Study: This is the first study to focus on se prevalence and MRSA characteristics in an animal shelter in Taiwan. The MRSA characteristics determined in this study were similar to those of CA-MRSA strains isolated from communities in the past, indicating potential health risks in cities., (© 2019 The Society for Applied Microbiology.)