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Background and Purpose: We aimed to investigate the prognostic value of peritumoral and intratumoral computed tomography (CT)-based radiomics during the course of radiotherapy (RT) in patients with laryngeal and hypopharyngeal cancer (LHC)., Materials and Methods: A total of 92 eligible patients were 1:1 randomly assigned into training and validation cohorts. Pre-RT and mid-RT radiomic features were extracted from pre-treatment and interim CT. LASSO-Cox regression was used for feature selection and model construction. Time-dependent area under the receiver operating curve (AUC) analysis was applied to evaluate the models' prognostic performances. Risk stratification ability on overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox regression. The associations between radiomics and clinical parameters as well as circulating lymphocyte counts were also evaluated., Results: The mid-RT peritumoral (AUC: 0.77) and intratumoral (AUC: 0.79) radiomic models yielded better performance for predicting OS than the pre-RT intratumoral model (AUC: 0.62) in validation cohort. This was confirmed by Kaplan-Meier analysis, in which risk stratification depended on the mid-RT peritumoral (p = 0.009) and intratumoral (p = 0.003) radiomics could be improved for OS, in comparison to the pre-RT intratumoral radiomics (p = 0.199). Multivariate analysis identified mid-RT peritumoral and intratumoral radiomic models as independent prognostic factors for both OS and PFS. Mid-RT peritumoral and intratumoral radiomics were correlated with treatment-related lymphopenia., Conclusion: Mid-RT peritumoral and intratumoral radiomic models are promising image biomarkers that could have clinical utility for predicting OS and PFS in patients with LHC treated with RT., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chien-Yu Lin reports that this study was supported by grants from Chang Gung Memorial Hospital, Taiwan [grant numbers CIRPG3I0011-3, CMRPG3M0681-2, CORPG3N0081]., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to interrogate if the use of postoperative chemoradiotherapy (POCRT) correlated with superior oncological outcomes for certain subgroups of patients with high-risk salivary gland carcinoma (SGC), compared with postoperative radiotherapy (PORT) alone., Methods: This multicenter retrospective study included 411 patients with surgically resected SGC who underwent PORT (n = 263) or POCRT (n = 148) between 2000 and 2015. Possible correlations of clinical parameters with outcomes were examined using the Kaplan-Meier analysis and Cox proportional-hazards regression model., Results: The median follow-up of survivors is 10.9 years. For the entire cohort, adding concurrent chemotherapy to PORT was not associated with OS, PFS, or LRC improvement. However, patients with nodal metastasis who underwent POCRT had significantly higher 10-year OS (46.2% vs. 18.2%, P = 0.009) and PFS (38.7% vs. 10.0%, P = 0.009) rates than those treated with PORT alone. The presence of postoperative macroscopic residual tumor (R2 resection) was identified as an independent prognosticator for inferior OS (P = 0.032), PFS (P = 0.001), and LRC (P = 0.007). Importantly, POCRT significantly correlated with higher 10-year LRC rates in patients with R2 resection (74.2% vs. 40.7%, P = 0.034) or adenoid cystic carcinoma (AdCC, 97.6% vs. 83.6%, P = 0.039). On multivariate analyses, the use of POCRT significantly predicted superior OS (P = 0.037) and PFS (P = 0.013) for node-positive patients and LRC for patients with R2 resection (P = 0.041) or AdCC (P = 0.005)., Conclusions: For surgically resected SGC, POCRT was associated with improved long-term OS and PFS for patients with nodal metastasis and superior LRC for patients with R2 resection or AdCC., 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 © 2023 Elsevier B.V. All rights reserved.)

The world healthcare system is actively seeking possible solutions for the rapid growth of kidney disease threats. The Taiwan Renal Data System (TWRDS) was central in assisting kidney health and care policymaking to reduce end-stage kidney disease incidence and mortality. This article summarizes the TWRDS framework, recent applications, and developments to provide new insights for some international researchers to promote planetary kidney health. The TWRDS originated in 1987 for the accreditation and quality monitoring of dialysis units and was connected with enriched health claim databases after the implementation of universal national health insurance in Taiwan in 1995. As a healthcare information centre, TWRDS has published annual reports forming indispensable instructions for renal care improvement since 2014. The TWRDS possesses three main functions: (1) kidney disease surveillance; (2) offering rich materials for research purposes; (3) achieving precision prevention and care through complex algorithms. In the new era, TWRDS can help build a more resilient society against communicable disease threats by integrating remote sensor techniques for developing future remote healthcare structures, as well as identifying kidney health inequity populations and promoting healthcare resources distributed equity. The global healthcare system is facing escalating burdens of non-communicable disease care due to the rapidly growing elderly population. Therefore, a considerable-scale data system is an essential decision-supportive tool in promoting an evidence-based, resilient, sustainable, equity care environment. Undoubtedly, TWRDS experience is a practical example of leveraging healthcare providers' decisions, care outcomes, and renovation., (© 2023 The Authors. Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Background: Low ocular perfusion pressure (OPP), which depends on the mean arterial pressure (MAP) and intraocular pressure (IOP), is associated with glaucoma. We studied 24-h MAP dysregulations and OPP in relation to the progression of glaucoma damage., Methods: We retrospectively analyzed 155 normal-tension glaucoma (NTG) and 110 primary open-angle glaucoma (POAG) patients aged 18 years old followed at the University Hospital Leuven with repeated visual field tests ( n  = 7000 measures, including both eyes) who underwent 24-h ambulatory blood pressure monitoring. Twenty-four-hour MAP dysregulations were variability independent of the mean (VIM), and the five lowest dips in MAP readings over 24 h. OPP was the difference between 2/3 of the MAP and IOP. Glaucoma progression was the deterioration of the visual field, expressed as decibel (dB) changes in mean deviation analyzed by applying multivariable linear mixed regression models., Results: The mean age was 68 years (53% were women). High 24-h VIMmap was associated with glaucoma progression in POAG ( P  < 0.001) independently of the 24-h MAP level. The estimated changes in mean deviation in relation to dip MAP measures ranged from -2.84 dB [95% confidence interval (CI) -4.12 to -1.57] to -2.16 dB (95% CI -3.46 to -0.85) in POAG. Reduced OPP along with high variability and dips in MAP resulted in worse mean deviation deterioration., Conclusion: The progression of glaucoma damage associates with repetitive and extreme dips in MAP caused by high variability in MAP throughout 24 h. This progression exacerbates if 24-h MAP dysregulations occur along with reduced OPP., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Cardiac rehabilitation is a comprehensive intervention recommended in international and Taiwanese guidelines for patients with acute myocardial infarction. Evidence supports that cardiac rehabilitation improves the health-related quality of life, enhances exercise capacity, reduces readmission rates, and promotes survival in patients with cardiovascular disease. The cardiac rehabilitation team is comprehensive and multidisciplinary. The inpatient, outpatient, and maintenance phases are included in cardiac rehabilitation. All patients admitted with acute myocardial infarction should be referred to the rehabilitation department as soon as clinically feasible. Pre-exercise evaluation, including exercise testing, helps physicians identify the risks of cardiac rehabilitation and organize appropriate exercise prescriptions. Therefore, the Taiwan Myocardial Infarction Society (TAMIS), Taiwan Society of Cardiology (TSOC), and Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation (TACVPR) address this consensus statement to assist healthcare practitioners in performing cardiac rehabilitation in patients with acute myocardial infarction., Competing Interests: All the authors declare no conflict of interest.

Introduction: In the era of precision preventive medicine, susceptible genetic markers for oro-/hypopharyngeal squamous cell carcinoma (OPSCC) have been investigated for genome-wide associations., Materials and Methods: A case-control study including 659 male head and neck squamous cell carcinoma (HNSCC) patients, including 331 oropharyngeal cancer, treated between March 1996 and December 2016 and 2400 normal controls was performed. A single-nucleotide polymorphism (SNP) array was used to determine genetic loci that increase susceptibility to OPSCC., Results: We analyzed the allele frequencies of 664,994 autosomal SNPs in 659 HNSCC cases; 7 SNPs scattered in loci of chromosomes 5, 7, 9, 11, and 19 were significant in genome-wide association analysis (Pc < 1.0669 × 10 -7 ). In OPSCCs (n = 331), two clustered regions in chromosomes 4 and 6 were significantly different from the controls. We successfully identified a missense alteration of the SNP region in alcohol dehydrogenase 1B (ADH1B) (https://genome.ucsc.edu; hg38); the top correlated locus was rs1229984 (p = 1 × 10 -11 ). Adjusted for environmental exposure, including smoking, alcohol, and areca quid, a region in chromosome 12, related to alcohol metabolism, was found to independently increase the susceptibility to OPSCC. The ADH1B rs1229984 AA genotype had better overall survival compared to the AG and GG genotypes (p = 0.042) in OPSCC. The GG genotype in rs1229984 was significantly associated with a younger age of onset than other genotypes (p = 0.001 and <0.001, respectively) in OPSCC patients who consumed alcohol., Conclusion: ADH1B was an important genetic locus that significantly correlated with the development of OPSCCs and patient survival., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. Here, we aimed to elucidate the transitions of dialysis status in the unplanned first dialysis patients and determine factors associated with their outcomes. A total of 50,315 unplanned first dialysis patients aged more than 18 years were identified from the National Health Insurance Dataset in Taiwan between 2001 and 2012. All patients were followed for 5 years for the transitions in dialysis status, including robust (dialysis-free), sporadic dialysis, continued dialysis, and death. Furthermore, factors associated with the development of continued dialysis and death were examined by the Cox proportional hazard models. After 5 years after the first dialysis occurrence, there were 5.39% with robust status, 1.67% with sporadic dialysis, 8.45% with continued dialysis, and 84.48% with death. Notably, we have identified common risk factors for developing maintenance dialysis and deaths, including male gender, older age, diabetes, coronary heart disease, stroke, heart failure, sepsis, and surgery. There was an extremely high mortality rate among the first unplanned dialysis patients in Taiwan. Less than 10% of these patients underwent continued dialysis during the 5-year follow-up period. This study highlighted the urgent need for interventions to improve patient outcomes., (© 2023. Springer Nature Limited.)

Background: Iron deficiency (ID) is a common comorbidity among patients with heart failure and reduced ejection fraction (HFrEF), and is associated with poorer outcomes independent of anemia. This study aimed to evaluate the prevalence and prognostic significance of ID in Taiwanese patients with HFrEF., Methods: We included HFrEF patients from two multicenter cohorts at different periods. The multivariate Cox regression analysis was applied to assess the risk of outcomes associated with ID, accounting for the varying risk of death., Results: Of the 3612 patients with HFrEF registered from 2013 to 2018, 665 patients (18.4%) had available baseline iron profile measurements. Of these, 290 patients (43.6%) were iron deficient; 20.2% had ID+/anemia+, 23.4% ID+/anemia-, 21.5% ID-/anemia+, and 34.9% ID-/anemia-. Regardless of anemia status, patients with coexisting ID had a higher risk than those without ID (all-cause mortality: 14.3 vs 9.5 per 100 patient-years, adjusted hazard ratio [HR] 1.33; 95% confidence interval [CI], 0.96-1.85; p = 0.091; cardiovascular mortality: 10.5 per 100 patient-years vs 6.1, adjusted HR 1.54 [95% CI, 1.03-2.30; p = 0.037]; cardiovascular mortality or first unplanned hospitalization for HF: 36.7 vs 19.7 per 100 patient-years, adjusted HR 1.57 [95% CI, 1.22-2.01; p < 0.001]). Among patients eligible for treatment in the IRONMAN trial design (43.9%), parenteral iron therapy was estimated to reduce heart failure hospitalizations and cardiovascular deaths by 13.7 per 100 patient-years., Conclusion: Iron profiles were tested in less than one-fifth of the Taiwanese HFrEF cohort. ID was present in 43.6% of tested patients and was independently associated with poor prognosis in these patients., 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.)

Hybrid breeding employs heterosis, which could potentially improve the yield and quality of a crop. Genomic selection (GS) is a promising approach for the selection of quantitative traits in plant breeding. The main objectives of this study are to (i) propose a GS-based approach to identify potential parental lines and superior hybrid combinations from a breeding population, which is composed of hybrids produced by a half diallel mating design; (ii) develop a software package for users to carry out the proposed approach. An R package, designated EHPGS, was generated to facilitate the employment of the genomic best linear unbiased model considering additive plus dominance marker effects for the hybrid performance evaluation. The R package contains a Bayesian statistical algorithm for calculating genomic estimated breeding value (GEBVs), GEBV-based specific combining ability, general combining ability, mid-parent heterosis, and better-parent heterosis. Three datasets that have been published in literature, including pumpkin (Cucurbita maxima), maize (Zea mays), and wheat (Triticum aestivum L.), were reanalyzed to illustrate the use of EHPGS., (© 2023. The Author(s).)

We investigated the prognostic utility of preoperative neck lymph node-to-primary tumor maximum standardized uptake value ratios (NTRs) in oral cavity squamous cell carcinoma (OSCC). We retrospectively reviewed the medical records of 141 consecutive patients who were diagnosed as having OSCC and had received fluorodeoxyglucose-positron emission tomography within 2 weeks prior to radical surgery between 2009 and 2018. To determine the optimal NTR cutoff, receiver operating characteristic analysis for overall survival (OS) was executed. The NTR's prognostic value for disease-free survival (DFS) and OS were determined through Cox proportional hazards analysis and the Kaplan-Meier method. We determined the median (range) follow-up duration to be 35.2 (2.1-122.4) months. The optimal NTR cutoff was 0.273, and patients with a higher NTR (≥0.273) exhibited significantly worse DFS and OS ( p = 0.010 and 0.003, respectively). A higher NTR (≥0.273) predicted poorer DFS (hazard ratio: 2.696, p = 0.008) and OS (hazard ratio: 4.865, p = 0.003) in multivariable analysis. We created a nomogram on the basis of the NTR, and it could accurately predict OS (concordance index: 0.774). Preoperative NTRs may be a useful prognostic biomarker for DFS and OS in patients with OSCC who have undergone surgery. NTR-based nomograms may also be helpful prognostic tools in clinical trials.

Whether the modified Glasgow prognostic score (mGPS) is useful for patients with head and neck squamous cell carcinoma (HNSCC) remains controversial. An electronic database search on EMBASE, PubMed, and the Cochrane Library from inception to 30 June 2022 was performed for study selection and data extraction. The associations between the mGPS and survival outcomes were evaluated using a random-effects meta-analysis and expressed as pooled hazard ratios (HRs) and 95% CIs. We included 11 studies involving a total of 2017 patients with HNSCC. A higher mGPS was associated with poorer progression-free survival (HR = 2.39, 95% CI 1.69-3.38), overall survival (HR = 2.40, 95% CI 1.94-2.98), disease-specific survival (HR = 2.57, 95% CI 1.71-3.88), and disease-free survival (HR = 2.67, 95% CI 1.51-4.73, all p ≤ 0.001) in HNSCC. The mGPS can function as a valid prognostic biomarker for patients diagnosed as having HNSCC., (© 2023 Wiley Periodicals LLC.)

High blood pressure (BP) and type-2 diabetes (T2DM) are forerunners of chronic kidney disease and left ventricular dysfunction. Home BP telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling risk stratification and personalized prevention. UPRIGHT-HTM (NCT04299529) is an investigator-initiated, multicenter, open-label, randomized trial with blinded endpoint evaluation designed to assess the efficacy of HTM plus UPP (experimental group) over HTM alone (control group) in guiding treatment in asymptomatic patients, aged 55-75 years, with ≥5 cardiovascular risk factors. From screening onwards, HTM data can be freely accessed by all patients and their caregivers; UPP results are communicated early during follow-up to patients and caregivers in the intervention group, but at trial closure in the control group. From May 2021 until January 2023, 235 patients were screened, of whom 53 were still progressing through the run-in period and 144 were randomized. Both groups had similar characteristics, including average age (62.0 years) and the proportions of African Blacks (81.9%), White Europeans (16.7%), women 56.2%, home (31.2%), and office (50.0%) hypertension, T2DM (36.4%), micro-albuminuria (29.4%), and ECG (9.7%) and echocardiographic (11.5%) left ventricular hypertrophy. Home and office BP were 128.8/79.2 mm Hg and 137.1/82.7 mm Hg, respectively, resulting in a prevalence of white-coat, masked and sustained hypertension of 40.3%, 11.1%, and 25.7%. HTM persisted after randomization (48 681 readings up to 15 January 2023). In conclusion, results predominantly from low-resource sub-Saharan centers proved the feasibility of this multi-ethnic trial. The COVID-19 pandemic caused delays and differential recruitment rates across centers., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: We aimed to probe the hemoglobin-albumin-lymphocyte-platelet (HALP) score's prognostic value in oral cavity squamous cell carcinoma (OSCC)., Methods: Medical data of 350 patients with primary operated OSCC were retrospectively reviewed. We derived the optimal HALP cutoff by executing receiver operating characteristic curve analysis, and patients were then grouped based on this cutoff value. Cox proportional hazards model were used to discover survival outcome-associated factors., Results: We derived the optimal HALP cutoff as 35.4. A low HALP score (<35.4) predicted poorer overall and disease-free survival (hazard ratio: 2.29 and 1.92, respectively; both p < 0.001) and was significantly associated with OSCC aggressiveness. We established a HALP-based nomogram that accurately predicted overall survival (concordance index: 0.784)., Conclusion: The HALP score may be a useful prognostic biomarker in patients with OSCC undergoing surgery, and the HALP-based nomogram can be a promising prognostic tool in clinical setting., (© 2023 Wiley Periodicals LLC.)

Background: People living with HIV (PLWH) have an increased risk of developing cardiovascular diseases (CVD). As speckle-tracking echocardiography (STE) has been used to detect subclinical myocardial abnormalities, this study aims to detect early cardiac impairment among Asian PLWH using STE and to investigate the associated risk factors., Methods: We consecutively recruited asymptomatic PLWH without previous CVD from a medical center of Taiwan, and their cardiac function was evaluated by conventional echocardiogram and STE. Enrolled PLWH were classified as antiretroviral therapy (ART)-experienced and ART-naive, and multivariable regressions were used to assess the association between myocardial strain and risk factors including traditional CVD and HIV-associated factors., Results: A total of 181 PLWH (mean age: 36.4 ± 11.4 years, 173 males) were recruited and conventional echocardiogram parameters were within normal ranges. Decreased myocardial strain across the myocardium was found, with a mean left ventricular (LV) global longitudinal strain of -18.7 ± 2.9%. The LV strain in the ART-experienced group (-19.0 ± 2.9%) was significantly better than the ART-naive group (-17.9 ± 2.8%), despite a younger age and lesser CVD risk factors in the ART-naive group. Hypertension [B = 1.92, 95% confidence interval (95% CI) 0.19-3.62, p  = 0.029] and ART-naive with both low and high viral loads (VL) (B = 1.09, 95% CI 0.03-2.16, p  = 0.047; and B = 2.00, 95% CI, 0.22-3.79, p  = 0.029) were significantly associated with reduced myocardial strain., Conclusion: This is the first and largest cohort using STE to investigate myocardial strain in Asian PLWH. Our results suggest that hypertension and detectable VL are associated with impaired myocardial strain. Thus, timely ART administration with VL suppression and hypertension control are crucial in preventing CVD when making the management parallel with the improved life expectancy of PLWH on ART., 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., (© 2023 Liao, Toh, Chang, Yang, Chen, Tang and Strong.)

Calorie restriction (CR) and fasting affect lifespan, disease susceptibility and response to acute injury across multiple animal models, including ischaemic injuries such as myocardial infarction or kidney hypoxia. The cargo and function of circulating extracellular vesicles (EV) respond to changes in host physiology, including exercise, injury, and other interventions. Thus, we hypothesised that EVs induced following CR may reflect some of the beneficial properties of CR itself. In a pilot study, EVs were isolated from mice following 21 days of 30 % CR, and from eight human donors after 72 h water-only fasting. EV size, concentration and morphology were profiled by NTA, western blot and cryoEM, and their function was assessed using multiple assays related to ischaemic diseases. We found that EVs from post-fasting samples better protected cardiac cells from hypoxia/reperfusion (H/R) injury compared to pre-fasting EVs. However, there was no difference when used to treat H/R-injured kidney epithelial cells. Post-fasting derived EVs slowed the rate of fibroblast migration and slightly reduced macrophage inflammatory gene expression compared to pre-fasting derived EVs. Lastly, we compared miRNA cargos of pre- and post-fasting human serum EVs and found significant changes in a small number of miRNAs. We conclude that fasting appears to influence EV cargo and function, with varied effects worthy of further exploration., Competing Interests: There are no conflicts of interest to declare., (© 2023 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Objectives: According to the NCCN guidelines, there is weak evidence to support the use of elective neck dissection (END) in early-stage oral cavity squamous cell carcinoma (OCSCC). We sought to examine the indications for END in patients with cT1N0M0 OCSCC defined according to the AJCC Staging Manual, Eight Edition., Methods: Of the 3886 patients diagnosed with cT1N0M0 included in the study, 2065 underwent END and 1821 neck observation., Results: The 5-year outcomes for patients who received END versus neck observation before and after propensity score matching (n = 1406 each) were as follows: neck control, 96 %/90 % (before matching), p < 0.0001; 96 %/90 % (after matching), p < 0.0001; disease-specific survival (DSS), 93 %/92 % (before matching), p = 0.0227; 93 %/92 % (after matching), p = 0.1436. Multivariable analyses revealed that neck observation, depth of invasion (DOI) > 2.5 mm, and poor differentiation were independent risk factors for 5-year outcomes. Upon the application of a scoring system ranging from 0 (no risk factor) to 3 (presence of the three risk factors), the following 5-year rates were observed: neck control, 98 %/95 %/84 %/85 %; DSS, 96 %/93 %/88 %/85 %; and overall survival, 90 %/86 %/79 %/59 %, respectively (all p < 0.0001). The survival outcomes of patients with scores of 0 and 1 were similar. The occult metastasis rates in the entire study cohort, DOI > 2.5 mm, and poor differentiation were 6.8 %/9.2 %/17.1 %, respectively., Conclusion: Because all patients who received neck observation had a score of 1 or higher, END should be performed when a DOI > 2.5 mm or poorly differentiated tumors are present. Under these circumstances, 48.6 % (1888/3886) of cT1N0M0 patients may avoid END without compromising oncological outcomes., 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 © 2023. Published by Elsevier Ltd.)

Background: Angiotensin receptor neprilysin inhibitor (ARNI) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) are emerging medical treatments for decompensated heart failure (HF) with reduced ejection fraction. In clinical practice, the combination of ARNI and SGLT2i cannot be administered owing to the poor hemodynamic status in patients with HF with reduced ejection fraction (HFrEF). This study aimed to compare different strategies of HF management for ARNI first or SGLT2i first in such a population., Methods: From January 2016 to December 2021, 165 patients were diagnosed with HFrEF and New York Heart Association functional class ≥II and already received optimal medical treatment. Ninety-five patients received the ARNI-first strategy, and 70 patients received the SGLT2i-first strategy according to the physician's choice. Age, sex, hemodynamic condition, etiologies of HF, comorbidities, serum creatinine, N-terminal pro-B-type natriuretic peptide (NT-ProBNP), echocardiographic parameters, and clinical outcomes were compared between the ARNI and SGLT2i-first strategy groups., Results: In the SGLT2i-first group, the median interval between the addition of the second medication was longer (ARNI-first vs. SGLT2i-first; 74 [49-100] days vs. 112 [86-138] days; p = 0.044). Improvement in left ventricular ejection fraction (LVEF), change in left atrial dimension, and change in left ventricular end-diastolic and end-systolic volume (LVESV) did not differ between the two groups. The incidence of HF hospitalization, cardiovascular mortality, and all-cause mortality did not differ between the two groups. A non-significant trend of lower NT-proBNP levels (ARNI-first vs. SGLT2i-first; 1383 [319-2507] pg/mL vs. 570 [206-1314] pg/mL; p = 0.055) and significantly higher discontinuation rate of diuretic agents (ARNI-first vs. SGLT2i- first; 6.8% vs. 17.5%; p = 0.039) were noted in the SGLT2i-first group. When early combination (≤14D) compared to late combination (>14D), better positive remodeling of LVESV presented significantly in early combination subgroups., Conclusions: In patients with symptomatic HFrEF, SGLT2i-first strategy may provide a higher possibility of discontinuing diuretic agents than the ARNI-first strategy. Changes in LV performance, progression of renal function, and clinical outcomes did not differ between the two groups. Early combination (≤14D) provided better LV remodeling., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

We introduced a novel squamous cell carcinoma inflammatory index (SCI) and explored its prognostic utility for individuals with operable oral cavity squamous cell carcinomas (OSCCs). We retrospectively analyzed data from 288 patients who were given a diagnosis of primary OSCC from January 2008 to December 2017. The SCI value was derived by multiplying the serum squamous cell carcinoma antigen and neutrophil-to-lymphocyte ratio values. We appraised the associations of the SCI with survival outcomes by performing Cox proportional hazards and Kaplan-Meier analyses. We constructed a nomogram for survival predictions by incorporating independent prognostic factors in a multivariable analysis. By executing a receiver operating characteristic curve analysis, we identified the SCI cutoff to be 3.45, and 188 and 100 patients had SCI values of <3.45 and ≥3.45, respectively. The patients with a high SCI (≥3.45) were associated with worse disease-free survival and overall survival than those with a low SCI (<3.45). An elevated preoperative SCI (≥3.45) predicted adverse overall survival (hazard ratio [HR] = 2.378; p < 0.002) and disease-free survival (HR = 2.219; p < 0.001). The SCI-based nomogram accurately predicted overall survival (concordance index: 0.779). Our findings indicate that SCI is a valuable biomarker that is highly associated with patient survival outcomes in OSCC.

Background: A new definition of metabolically healthy obesity (MHO) has recently been proposed to stratify the heterogeneous mortality risk of obesity. Metabolomic profiling provides clues to metabolic alterations beyond clinical definition. We aimed to evaluate the association between MHO and cardiovascular events and assess its metabolomic pattern., Methods: This prospective study included Europeans from two population-based studies, the FLEMENGHO and the Hortega study. A total of 2339 participants with follow-up were analyzed, including 2218 with metabolomic profiling. Metabolic health was developed from the third National Health and Nutrition Examination Survey and the UK biobank cohorts and defined as systolic blood pressure < 130 mmHg, no antihypertensive drugs, waist-to-hip ratio < 0.95 for women or 1.03 for men, and the absence of diabetes. BMI categories included normal weight, overweight, and obesity (BMI < 25, 25-30, ≥ 30 kg/m 2 ). Participants were classified into six subgroups according to BMI category and metabolic healthy status. Outcomes were fatal and nonfatal composited cardiovascular events., Results: Of 2339 participants, the mean age was 51 years, 1161 (49.6%) were women, 434 (18.6%) had obesity, 117 (5.0%) were classified as MHO, and both cohorts had similar characteristics. Over a median of 9.2-year (3.7-13.0) follow-up, 245 cardiovascular events occurred. Compared to those with metabolically healthy normal weight, individuals with metabolic unhealthy status had a higher risk of cardiovascular events, regardless of BMI category (adjusted HR: 3.30 [95% CI: 1.73-6.28] for normal weight, 2.50 [95% CI: 1.34-4.66] for overweight, and 3.42 [95% CI: 1.81-6.44] for obesity), whereas those with MHO were not at increased risk of cardiovascular events (HR: 1.11 [95% CI: 0.36-3.45]). Factor analysis identified a metabolomic factor mainly associated with glucose regulation, which was associated with cardiovascular events (HR: 1.22 [95% CI: 1.10-1.36]). Individuals with MHO tended to present a higher metabolomic factor score than those with metabolically healthy normal weight (0.175 vs. -0.057, P = 0.019), and the score was comparable to metabolically unhealthy obesity (0.175 vs. -0.080, P = 0.91)., Conclusions: Individuals with MHO may not present higher short-term cardiovascular risk but tend to have a metabolomic pattern associated with higher cardiovascular risk, emphasizing a need for early intervention., (© 2023. The Author(s).)

Background: Osteoradionecrosis (ORN) of the jaw requires a differential diagnosis to exclude cancer recurrence. Here, we sought to develop a scoring system comprising 18 F-FDG PET/CT parameters for distinguishing between the two conditions in patients with oral squamous cell carcinoma (OSCC)., Methods: The study consisted of 103 OSCC patients with suspected ORN of the jaw. All participants underwent 18 F-FDG PET/CT imaging within 6 months of diagnostic histopathology. Following extraction of PET parameters, we identified clinical and imaging predictors of mandibular recurrence-free survival (MRFS) using receiver operating characteristic curve analysis and multivariate Cox regression models., Results: The results of histopathology revealed mandibular cancer recurrence in 24 patients (23.3%). Multivariate Cox regression analyses identified an age at diagnosis ≤ 52 years (P = 0.013), a location of the SUVmax voxel with soft tissue predominance (P = 0.019), and mandibular total lesion glycolysis (TLG) > 62.68 g (P < 0.001) as independent risk factors for MRFS. A scoring system was devised with scores from 0 (no risk factor) to 3 (presence of all three risk factors). High-risk patients with a score of 2-3 compared with score of 0-1 had a significantly higher likelihood of mandibular cancer recurrence (hazard ratio: 32.50, 95% confidence interval: 8.51-124.18, P < 0.001). The scoring system had a sensitivity of 87.50%, a specificity of 82.28%, and an accuracy of 83.50% for identifying mandibular cancer recurrence., Conclusions: The scoring system of our study is clinically useful for identifying mandibular cancer recurrence in patients with suspected ORN of the jaw., (© 2023. The Author(s).)

Background: Marginal mandibulectomy with or without additional mandibulotomy could represent the alternatives to avoid segmental mandibulectomy in carefully selected tongue cancers., Aim and Objectives: This study investigated a subgroup of tongue cancers with suspected involvement to the alveolar bone because of the shallow and deformed mouth floor. We aimed to compare the functional outcomes, postoperative complications, and disease control efficacy between the 2 different marginal mandibulectomy approaches, with or without additional mandibulotomy., Materials and Methods: A retrospective study of 29 marginal mandibulectomies and 26 combined mandibulotomies for tongue cancer wide excisions and flap reconstruction at Chang Gung Memorial Hospital Linkou Branch during 2014 to 2019 was performed., Results: The combined mandibulotomy group had more advanced T-status ( P < 0.001) and greater tumor diameters ( P < 0.001) but not increased preexisting trismus, bone invasions, or positive margins. The additional mandibulotomy increased flap necrosis ( P = 0.044), late infections ( P = 0.004), and tongue movement limitations ( P = 0.044) but not osteoradionecrosis. Osteoradionecrosis was unrelated to the resected mandibular length or the mandibulotomy sites. Feeding tube dependence was greater in the combined group at discharge ( P = 0.014), but no long-term differences were noted. Kaplan-Meier overall survival ( P = 0.052) and disease-free survival ( P = 0.670) were both comparable between the 2 groups., Conclusions: The combined procedure of mandibulotomy and marginal mandibulectomy in large tongue cancers without bone invasions is associated with increased soft tissue-related complications but not bone-related complications. However, comparable disease control, survival, and long-term tube feeding outcomes were noted., Competing Interests: Conflicts of interest: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Key Message: A practical approach is developed to determine a cost-effective optimal training set for selective phenotyping in a genomic prediction study. An R function is provided to facilitate the application of the approach. Genomic prediction (GP) is a statistical method used to select quantitative traits in animal or plant breeding. For this purpose, a statistical prediction model is first built that uses phenotypic and genotypic data in a training set. The trained model is then used to predict genomic estimated breeding values (GEBVs) for individuals within a breeding population. Setting the sample size of the training set usually takes into account time and space constraints that are inevitable in an agricultural experiment. However, the determination of the sample size remains an unresolved issue for a GP study. By applying the logistic growth curve to identify prediction accuracy for the GEBVs and the training set size, a practical approach was developed to determine a cost-effective optimal training set for a given genome dataset with known genotypic data. Three real genome datasets were used to illustrate the proposed approach. An R function is provided to facilitate widespread application of this approach to sample size determination, which can help breeders to identify a set of genotypes with an economical sample size for selective phenotyping., (© 2023. The Author(s).)

Topological magnetic monopoles (TMMs), also known as hedgehogs or Bloch points, are three-dimensional (3D) non-local spin textures that are robust to thermal and quantum fluctuations due to the topology protection 1-4 . Although TMMs have been observed in skyrmion lattices 1,5 , spinor Bose-Einstein condensates 6,7 , chiral magnets 8 , vortex rings 2,9 and vortex cores 10 , it has been difficult to directly measure the 3D magnetization vector field of TMMs and probe their interactions at the nanoscale. Here we report the creation of 138 stable TMMs at the specific sites of a ferromagnetic meta-lattice at room temperature. We further develop soft X-ray vector ptycho-tomography to determine the magnetization vector and emergent magnetic field of the TMMs with a 3D spatial resolution of 10 nm. This spatial resolution is comparable to the magnetic exchange length of transition metals 11 , enabling us to probe monopole-monopole interactions. We find that the TMM and anti-TMM pairs are separated by 18.3 ± 1.6 nm, while the TMM and TMM, and anti-TMM and anti-TMM pairs are stabilized at comparatively longer distances of 36.1 ± 2.4 nm and 43.1 ± 2.0 nm, respectively. We also observe virtual TMMs created by magnetic voids in the meta-lattice. This work demonstrates that ferromagnetic meta-lattices could be used as a platform to create and investigate the interactions and dynamics of TMMs. Furthermore, we expect that soft X-ray vector ptycho-tomography can be broadly applied to quantitatively image 3D vector fields in magnetic and anisotropic materials at the nanoscale., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC., Methods: Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse., Results: The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p < 0.0001 (AHR: 3.10 [2.69 - 3.57]) and OS: 49% versus 22%, p < 0.0001 (AHR: 3.32 [2.89 - 3.81])., Conclusion: After adjustment for potential confounders and PS matching, early relapse was an adverse prognostic factor for survival outcomes in patients with OCSCC. Our findings may have significant implications for risk stratification., (© 2023. The Author(s).)

Importance: Older patients with hypertension receiving intensive systolic blood pressure control (110-130 mm Hg) have lower incidences of cardiovascular events than those receiving standard control (130-150 mm Hg). Nevertheless, the mortality reduction is insignificant, and intensive blood pressure management results in more medical costs from treatments and subsequent adverse events., Objective: To examine the incremental lifetime outcomes, costs, and cost-effectiveness of intensive vs standard blood pressure control in older patients with hypertension from the health care payer's perspective., Design, Setting, and Participants: This economic analysis was conducted with a Markov model to examine the cost-effectiveness of intensive blood pressure management among patients aged 60 to 80 years with hypertension. Treatment outcome data from the Trial of Intensive Blood-Pressure Control in Older Patients With Hypertension (STEP trial) and different cardiovascular risk assessment models for a hypothetical cohort of STEP-eligible patients were used. Costs and utilities were obtained from published sources. The incremental cost-effectiveness ratio (ICER) against the willingness-to-pay threshold was used to evaluate whether the management was cost-effective. Extensive sensitivity, subgroup, and scenario analyses were performed to address uncertainty. The US and UK population using race-specific cardiovascular risk models were conducted in the generalizability analysis. Data for the STEP trial were collected from February 10 to March 10, 2022, and were analyzed for the present study from March 10 to May 15, 2022., Interventions: Hypertension treatments with a systolic blood pressure target of 110 to 130 mm Hg or 130 to 150 mm Hg., Main Outcomes and Measures: Incremental lifetime quality-adjusted life-years (QALYs), costs, and ICER are discounted at the given rates annually., Results: After simulating 10 000 STEP-eligible patients assumed to be 66 years of age (4650 men [46.5%] and 5350 women [53.5%]) in the model, the ICER values were ¥51 675 ($12 362) per QALY gained in China, $25 417 per QALY gained in the US, and £4679 ($7004) per QALY gained in the UK. Simulations projected that the intensive management in China being cost-effective were 94.3% and 100% below the willingness-to-pay thresholds of 1 time (¥89 300 [$21 364]/QALY) and 3 times (¥267 900 [$64 090]/QALY) the gross domestic product per capita, respectively. The US had 86.9% and 95.6% probabilities of cost-effectiveness at $50 000/QALY and $100 000/QALY, respectively, and the UK had 99.1% and 100% of probabilities of cost-effectiveness at £20 000 ($29 940)/QALY and £30 000 ($44 910)/QALY, respectively., Conclusions and Relevance: In this economic evaluation, the intensive systolic blood pressure control in older patients produced fewer cardiovascular events and had acceptable costs per QALY gained, well below the typical willingness-to-pay thresholds. The cost-effective advantages of intensive blood pressure management in older patients were consistent over various clinical scenarios across different countries.

SsrA and SmpB are known to play important roles in translational quality control and are essential for virulence in many human and animal pathogenic bacteria. The physiological roles and contribution of SsrA and SmpB to plant pathogen are unclear. Here, we present evidence to show that ssrA and smpB are involved in pathogenesis of Xanthomonas campestris pathovar campestris, the cause of black rot diseases in crucifers. The ssrA and smpB mutants exhibited defects in bacterial attachment, cell motility, and extracellular enzyme activity. The mutation of ssrA and smpB also resulted in a reduction in temperature tolerance. These altered phenotypes of the ssrA and smpB mutants could be complemented to wild-type levels by the intact ssrA and smpB genes. This is the first demonstration of the roles of SsrA and SmpB in phytopathogen., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but are accompanied by dose-limiting cardiotoxicity. We elucidate the progression and severity of cardiac function over time, in the absence of cardioprotection, which less is known about., Methods: This PRISMA-guideline-adherent review was registered on PROSPERO (CRD42022373496)., Results: 26 studies met the eligibility criteria including a total of 910 patients. The overall reduction in post-anthracycline pooled mean left ventricular ejection fraction (LVEF) in placebo arms of the included randomised-controlled trials was 4.5% (95% CI, 2.6 to 6.4). The trend in LVEF showed a progressive decline until approximately 180 days, after which there was no significant change. Those receiving a cumulative anthracycline dose of 300 mg/m2 experienced a more profound reduction. The overall pooled risk of a 10% absolute decline in LVEF from baseline, or a decline to an LVEF below 50%, was 17% (95% CI: 11 to 24; I2 = 71%). Sensitivity analyses of baseline LVEF and trastuzumab treatment status did not yield significant differences., Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines is required.

Background: Studies have indicated that a low albumin-to-globulin ratio (AGR) before treatment is linked to poor prognosis of many cancers, but the prognostic impact of AGR remains controversial in head and neck cancer (HNC). This meta-analysis examined the prognostic value of AGR in HNC. Methods: We systematically searched the Embase, PubMed, and Cochrane library for relevant articles from inception to July 22, 2022. Studies conducted from 2000 to 2022 exploring the prognostic value of AGR in HNC were retrieved. We employed a random-effects model and calculated pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) to examine the associations of AGR with survival outcome. Results: Our analysis included nine studies involving 3211 patients with HNC. The pooled results revealed significant associations between low pretreatment AGRs and poor disease-free survival (HR = 1.97, 95% CI 1.58-2.45, p < 0.001), distant metastasis-free survival (HR = 1.64, 95% CI 1.25-2.16, p < 0.001), overall survival (HR = 2.18, 95% CI 1.65-2.88, p < 0.001), T3-T4 status (OR = 2.22, 95% CI 1.43-3.44, p < 0.001), stage III-IV disease (OR = 2.62, 95% CI 1.62-4.23, p < 0.001), and lymph node metastasis (OR = 1.95, 95% CI 1.29-2.82, p = 0.001) in patients with HNC. Conclusion: AGR can serve as a prognostic biomarker in managing HNC, and a low pretreatment AGR is strongly associated with adverse survival outcomes and advanced cancer status. Additional large-scale prospective trials must be conducted to assess the validity of our findings., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To investigate the effectiveness and safety of angiotensin receptor-neprilysin inhibitors (ARNIs) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min per 1.73 m 2 ), which have been excluded from the landmark trials., Patients and Methods: This study examined 3281 patients pooled from two multicenter HFrEF cohorts, and 661 patients with baseline eGFR less than 30 mL/min per 1.73 m 2 were further analyzed (the Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry: May 1, 2013 to October 31, 2014, and the Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study: March 1, 2017, to December 31, 2018). Propensity score matching was performed to adjust for confounders. At 1-year follow-up, all-cause mortality, total heart failure hospitalizations, renal function, and left ventricular ejection fraction (LVEF) were used as the endpoints., Results: After propensity score matching, 510 patients (age, 69.8±13.9 years; male, 61.0%; mean LVEF, 29.8±7.3%; mean eGFR, 19.8±9.0 mL/min per 1.73 m 2 ) were included in the final analysis, including 278 patients receiving ARNI treatment (ARNI group) and 232 patients not on ARNI treatment (non-ARNI group). Baseline characteristics were comparable between the two groups. At 1 year, eGFR and LVEF measurements were significantly higher in the ARNI group than in the non-ARNI group (25.0±17.1 mL/min per 1.73 m 2 vs 21.4±17.5 mL/min per 1.73 m 2 ; P=.04; and 40.1±12.9% vs. 33.1±10.8%, P<.001, respectively). The ARNI group had significantly lower risks of 1-year all-cause mortality (19.4 vs 30.9 per 100-person year; P=.02), and total HF rehospitalizations (70.0 vs 110.4 per 100-person year; P=.01) than non-ARNI users., Conclusion: Our results show the effectiveness of ARNIs in HFrEF patients with advanced chronic kidney disease in a real-world setting., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

With the promising cardiovascular benefits in the STEP and SPRINT trials, the 2022 Taiwan's hypertension guidelines redefined the hypertension threshold as 130/80 mmHg and a universal blood-pressure target of <130/80 mmHg. This study's objective was to examine the cost-effectiveness of the intensive blood-pressure target for hypertensive patients using estimated lifetime medical costs and quality-adjusted life years (QALY) from the Taiwan national payer's perspective. We developed a lifetime Markov model comparing the intensive and conservative blood-pressure targets. Incremental cost-effectiveness ratio (ICER) against the willing-to-pay thresholds at the one-time [US$34,000(NT$1,020,000)] and three-time [US$100,000(NT$3,000,000)] gross domestic product per capita were defined as very cost-effect and only cost-effective. The cost-effectiveness in different age stratifications and cardiovascular risks treated with a more intensive target (120 mmHg) were examined in the subgroup analyses. The new blood-pressure treatment target produced more lifetime medical costs [US$31,589(NT$947,670) versus US$26,788(NT$803,640)] and QALYs (12.54 versus 12.25), and the ICER was US$16,589(NT$497,670), which was 99.1% and 100% probability of a very cost-effective and cost-effective strategy. The ICERs in all age stratifications had more than a 90% probability of being very cost-effective, and ICERs decreased with age. More intensive control in patients with high cardiovascular risks produced a lower ICER [US$14,547(NT$436,410)]. In conclusion, Taiwan's new blood-pressure treatment target can prevent more cardiovascular events with acceptable costs per QALY below the willing-to-pay thresholds. The cost-effectiveness of intensive control is consistent across different ages and more pronounced with the increase in age and cardiovascular risk., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Objectives: Perineural invasion (PNI) was quantitatively analyzed in oral squamous cell carcinoma (OSCC) specimens obtained by radical surgery to correlate with survival outcomes. Methods: This is a retrospective study that reviewed the Cancer registry data between 2009 and 2015. Inclusion criteria were oral cavity cancer, treatment by radical surgery, presence of PNI, and available pathologic samples for S100 staining. Patients with M1 disease and those with synchronous or metachronous cancer during staging work-up were excluded. All pathologic samples were reviewed to confirm PNI status and processed by immunohistochemical staining for S100 to quantify PNI. Pathologic information and staging results were also reviewed, and clinical outcomes were analyzed. Results: The retrospective study included 92 patients; 63 had intratumoral PNI (IPNI) and 29 had extratumoral PNI (EPNI). The average number of PNI foci (APNI) was higher in the EPNI group than in the IPNI group (6.7 vs 3.8, t -test 2-tail significance  =  0.021). The 3-year overall survival (OS) and time-to-recurrence (TTR) rates of all patients were 82.5% and 81.2%, respectively. Univariate analysis showed that pathological T4 or N2-3 stage correlated with poor OS, whereas APNI ≥4 correlated with poor TTR. In multivariate analysis, only the pathological N2-3 stage was significantly correlated with poor OS, whereas only APNI ≥ 4 was an independent factor of poor TTR. The 3-year TTR rates were 92.4% and 65.6% for diseases with APNI < 4 and ≥ 4, respectively ( P   =  .008). Conclusions: In patients with OSCC with PNI, a greater amount of PNI identified by S100 staining indicated a poorer TTR regardless of stage and other prognostic factors. Quantification of PNI by S100 immunohistochemistry is a potential method for prognosis prediction.

Background: Some sodium-glucose co-transporter-2 (SGLT2) inhibitors showed benefits on heart failure (HF), but different SGLT2/SGLT1 selectivity might influence the treatment effect. This study aimed to meta-analyze the treatment effects of SGLT2 inhibitors and the diversity of receptor selectivity for patients with and without HF., Methods: Randomized controlled trials were searched in PubMed, Embase, Cochrane databases and ClinicalTrials.gov registry from inception to October 2020. The interest outcomes were analyzed with random-effects models and presented with a risk ratio (RR) and 95% confidence interval (CI). Subgroup analyses examined the treatment effects among SGLT2 inhibitors with different SGLT2/SGLT1 selectivity., Results: The final analyses included 10 trials and 52,607 patients. The RR of total cardiovascular (CV) death or hospitalization for HF (HHF) between SGLT2 inhibitors and placebo was 0.79 (95% CI 0.74-0.84, I2 = 31%). With SGLT2 inhibitors, HF patients had reduced mortality risks (RR 0.89, 95% CI 0.80-0.99, I2 = 0), and non-HF patients had lower risks of major adverse CV events (RR 0.92, 95% CI 0.85-0.99, I2 = 0). The risk reduction of HHF was consistent in groups of HF (RR 0.72, 95% CI 0.64-0.80, I2 = 8%) and non-HF (RR 0.74, 95% CI 0.61-0.89, I2 = 0), but the effect of the low SGLT2/SGLT1 selectivity inhibitor was insignificant in non-HF patients., Conclusion: The efficacy of SGLT2 inhibitors on risk reduction of total CV death or HHF is consistent with the previous studies. The regimen is beneficial for reducing mortality in patients with HF and major adverse CV events in those without HF. Different SGLT2/SGLT1 selectivity may differ in the treatment effects in patients with and without HF., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The implication of sepsis-induced cardiomyopathy (SIC) to prognosis is controversial, and its association with mortality at different stages remains unclear. We conducted a systematic review and meta-analysis to understand the association between SIC and mortality in septic patients., Methods: We searched and appraised observational studies regarding the mortality related to SIC among septic patients in PubMed and Embase from inception until 8 July 2021. Outcomes comprised in-hospital and 1-month mortality. We adopted the random-effects model to examine the mortality risk ratio in patients with and without SIC. Meta-regression, subgroup, and sensitivity analyses were applied to examine the outcome's heterogeneity., Results: Our results, including 20 studies and 4,410 septic patients, demonstrated that SIC was non-statistically associated with increased in-hospital mortality, compared to non-SIC (RR 1.28, [0.96-1.71]; p = 0.09), but the association was statistically significant in patients with the hospital stay lengths longer than 10 days (RR 1.40, [1.02-1.93]; p = 0.04). Besides, SIC was significantly associated with a higher risk of 1-month mortality (RR 1.47, [1.17-1.86]; p < 0.01). Among SIC patients, right ventricular dysfunction was significantly associated with increased 1-month mortality (RR 1.72, [1.27-2.34]; p < 0.01), while left ventricular dysfunction was not (RR 1.33, [0.87-2.02]; p = 0.18)., Conclusions: With higher in-hospital mortality in those hospitalized longer than 10 days and 1-month mortality, our findings imply that SIC might continue influencing the host's system even after recovery from cardiomyopathy. Besides, right ventricular dysfunction might play a crucial role in SIC-related mortality, and timely biventricular assessment is vital in managing septic patients., (© 2022. The Author(s).)

A reliable prognostic stratification of patients with locally advanced hypopharyngeal cancer who had been treated with concurrent chemoradiotherapy (CCRT) is crucial for informing tailored management strategies. The purpose of this retrospective study was to develop robust and objective magnetic resonance imaging (MRI) radiomics-based models for predicting overall survival (OS) and progression-free survival (PFS) in this patient population. The study participants included 198 patients (median age: 52.25 years (interquartile range = 46.88-59.53 years); 95.96% men) who were randomly divided into a training cohort ( n = 132) and a testing cohort ( n = 66). Radiomic parameters were extracted from post-contrast T1-weighted MR images. Radiomic features for model construction were selected from the training cohort using least absolute shrinkage and selection operator-Cox regression models. Prognostic performances were assessed by calculating the integrated area under the receiver operating characteristic curve (iAUC). The ability of radiomic models to predict OS (iAUC = 0.580, 95% confidence interval (CI): 0.558-0.591) and PFS (iAUC = 0.625, 95% CI = 0.600-0.633) was validated in the testing cohort. The combination of radiomic signatures with traditional clinical parameters outperformed clinical variables alone in the prediction of survival outcomes (observed iAUC increments = 0.279 [95% CI = 0.225-0.334] and 0.293 [95% CI = 0.232-0.351] for OS and PFS, respectively). In summary, MRI radiomics has value for predicting survival outcomes in patients with hypopharyngeal cancer treated with CCRT, especially when combined with clinical prognostic variables.

Ultraviolet C (UVC) radiation has been considered a possible option to alleviate the seriousness of black spots on bananas during preservation which help increase economic efficiency. In this study, using 275 nm UVC light-emitting diodes (LEDs), a preliminary cavity with dimensions of 30 × 30 × 30 cm was designed and fabricated to aid in reducing black spots on bananas with the aim of application in the factory conveyor belts. The UVC irradiance distribution was thoroughly monitored for many sections at different box heights in both simulation and measurement, with a dominant range of 6-9 W/m 2 in the middle. Afterward, trials were conducted in vitro and in vivo at different selected UVC doses. The results in vitro revealed that a dose of over 0.36 kJ/m 2 has an excellent effect on inhibiting the colonial germination of fungal Colletotrichum musae, a common species of fungi causing black spot disease on bananas. In vivo conditions, with a short exposure time of around 5 s, the black spots on UVC-irradiated banana peel significantly reduced with minimal sensory damage compared to a control banana via observation after seven days from treatment. Finally, the optimal UVC dose is proposed from 0.030 to 0.045 kJ/m 2 for the one-time treatment when considering the upper surface of the banana. With flexibility advantage and short exposure time, the fabricated cavity (box) promises to bring a lot of application potential to aid banana preservation in factories and households., (© 2022. The Author(s).)

Aims: Sacubitril/valsartan (SAC/VAL) has been used in patients with heart failure and reduced ejection fraction (HFrEF), and cardiac resynchronization therapy (CRT) could benefit the HFrEF patients with wide QRS durations. This study aimed to evaluate the clinical impacts of SAC/VAL on reverse cardiac remodelling in CRT-eligible and CRT-ineligible HFrEF patients with different QRS durations., Methods and Results: The TAROT-HF study was a multicentre, observational study enrolling patients who initiated SAC/VAL from 10 hospitals since 2017. Patients with baseline left ventricular ejection fraction (LVEF) ≤ 35% were classified into two groups: (i) Group 1: CRT-eligible group, patients with left bundle branch block (LBBB) morphology plus QRS duration ≥130 ms or non-LBBB morphology plus QRS duration ≥150 ms; and (ii) Group 2: CRT-ineligible group. Propensity score matching was performed to adjust for confounders, and 1168 patients were analysed. Baseline characteristics were comparable between the two groups. The improvements in LVEF and left ventricular end-systolic volume index (LVESVi) were more significant in Group 2 than in Group 1 after 1 year SAC/VAL treatment (LVEF: 8.4% ± 11.3% vs. 4.5% ± 8.1%, P < 0.001; change percentages in LVESVi: -14.4% ± 25.9% vs. -9.6% ± 23.1%, P = 0.004). LVEF improving to ≥50% in Groups 1 and 2 constituted 5.2% and 20.2% after 1 year SAC/VAL treatment (P < 0.001). Multivariate analyses showed that wide QRS durations were negatively associated with the reverse cardiac remodelling in these HFrEF patients with SAC/VAL treatment., Conclusion: Despite SAC/VAL treatment, wide QRS durations are associated with lower degrees of left ventricular improvement than narrow ones in the HFrEF patients. Optimal intervention timing for the CRT-eligible patients requires further investigation., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Rice blast caused by Magnaporthe oryzae is a dangerous threat to rice production and food security worldwide. Breeding and proper deployment of resistant varieties are effective and environmentally friendly strategies to manage this notorious disease. However, a highly dynamic and quickly evolved rice blast pathogen population in the field has made disease control with resistance germplasms more challenging. Therefore, continued monitoring of pathogen dynamics and application of effective resistance varieties are critical tasks to prolong or sustain field resistance. Here, we report a team project that involved evaluation of rice blast resistance genes and surveillance of M. oryzae field populations in Taiwan. A set of International Rice Research Institute-bred blast-resistant lines (IRBLs) carrying single blast resistance genes was utilized to monitor the field effectiveness of rice blast resistance. Resistance genes such as Ptr (formerly Pita2 ) and Pi9 exhibited the best and most durable resistance against the rice blast fungus population in Taiwan. Interestingly, line IRBLb-B harboring the Pib gene with good field protection has recently shown susceptible lesions in some locations. To dissect the genotypic features of virulent isolates against the Pib resistance gene, M. oryzae isolates were collected and analyzed. Screening of the AvrPib locus revealed that the majority of field isolates still maintained the wild-type AvrPib status but eight virulent genotypes were found. Pot3 insertion appeared to be a major way to disrupt the AvrPib avirulence function. Interestingly, a novel AvrPib double-allele genotype among virulent isolates was first identified. Pot2 repetitive element-based polymerase chain reaction (rep-PCR) fingerprinting analysis indicated that mutation events may occur independently among different lineages in different geographic locations of Taiwan. This study provides our surveillance experience of rice blast disease and serves as the foundation to sustain rice production.

We investigate flow-induced structural organization in a dilute suspension of tumbling red blood cells (RBCs) under confined shear flow. For small Reynolds ( Re = 0.1) and capillary numbers ( Ca ), with fully coupled hydrodynamic interaction (HI) and without interparticle adhesion, we find that HI between the biconcave discoid particles prompts the formation of layered RBC chains and synchronized rotating RBC pairs, referred here as "waltzing doublets." As the volume fraction ϕ increases, more waltzing doublets appear in RBC files. Stronger shear stress disrupts structural arrangements at higher Ca . We find that the flow-induced organization of waltzing doublets changes how the suspension viscosity varies with ϕ qualitatively. The intrinsic viscosity is particularly sensitive to microstructural rearrangement, increasing (decreasing) with ϕ at low (high) Ca that correlates with the change in the fraction of doublets. We verified flow-induced collective motion with comparison to two-cell simulations in which the cell volume fraction is controlled by varying the domain volume.

Methods to probe and understand the dynamic response of materials following impulsive excitation are important for many fields, from materials and energy sciences to chemical and neuroscience. To design more efficient nano, energy, and quantum devices, new methods are needed to uncover the dominant excitations and reaction pathways. In this work, we implement a newly-developed superlet transform-a super-resolution time-frequency analytical method-to analyze and extract phonon dynamics in a laser-excited two-dimensional (2D) quantum material. This quasi-2D system, 1T-TaSe 2 , supports both equilibrium and metastable light-induced charge density wave (CDW) phases mediated by strongly coupled phonons. We compare the effectiveness of the superlet transform to standard time-frequency techniques. We find that the superlet transform is superior in both time and frequency resolution, and use it to observe and validate novel physics. In particular, we show fluence-dependent changes in the coupled dynamics of three phonon modes that are similar in frequency, including the CDW amplitude mode, that clearly demonstrate a change in the dominant charge-phonon couplings. More interestingly, the frequencies of the three phonon modes, including the strongly-coupled CDW amplitude mode, remain time- and fluence-independent, which is unusual compared to previously investigated materials. Our study opens a new avenue for capturing the coherent evolution and couplings of strongly-coupled materials and quantum systems., (© 2022. The Author(s).)

Background: Systemic hypoperfusion plays a pivotal role in the pathogenesis of primary open-angle glaucoma (POAG). Extreme dips in mean arterial pressure (MAP) due to high 24-h variability are associated with POAG, however, whether this is driven by diurnal or nocturnal dips remains undocumented. We aimed this study to investigate the association of POAG damage with variability and dips in the diurnal and nocturnal MAP., Methods: We conducted a retrospective longitudinal study that included 110 POAG patients who underwent 24-h ambulatory blood pressure monitoring. Our outcomes included (i) functional [visual field defects expressed as mean deviation (MD)] and (ii) structural (optic disc cupping obtained from cup-to-disc ratio) glaucoma damage. MAP variability independent of the mean (VIMmap) was computed for diurnal and nocturnal MAP. Dips were the five diurnal and three nocturnal lowest drops in MAP. We also calculated the night-to-day ratio. We applied mixed models to evaluate the progression of visual field defects and optic disc cupping in relation to diurnal and nocturnal MAP measures., Results: The mean age was 64.0 y (53% women). The median follow-up was 9 years. In adjusted mixed models, functional progression of glaucoma damage was associated with VIMmap (-2.57 dB change in MD per every 3 mmHg increase in VIMmap; P < 0.001) and diurnal MAP dips (changes in the MD ranged from -2.56 to -3.19 dB; P < 0.001). Every 5 mmHg decrease in the nocturnal MAP level was associated with -1.14 dB changes in MD [95% confidence interval (CI), -1.90 to -0.40] and 0.01 larger optic disc cupping (95% CI, 0.01-0.02). Lower night-to-day ratio was also related to both outcomes ( P ≤ 0.012). Functional glaucoma damage worsened if nocturnal hypotension was combined with high variability or extreme dips in the diurnal MAP ( P ≤ 0.022)., Conclusion: Progression of glaucoma damage in POAG associates with high variability and extreme dips in the diurnal MAP. Structural glaucoma damage seems more vulnerable to nocturnal hypotension. Ambulatory blood pressure monitoring allows the assessment of sporadic diurnal and persistent nocturnal hypotension episodes. These phenotypes might offer an opportunity to improve the risk-stratification of open-angle glaucoma (OAG)., 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 Melgarejo, Eijgen, Wei, Maestre, Al-Aswad, Liao, Mena, Vanassche, Janssens, Verhamme, Keer, Stalmans and Zhang.)

Background: In the treatment of oral cavity squamous cell carcinoma (OCSCC), surgical quality measures which are expected to affect outcomes, including the achievement of a clear margin, are surgeon-dependent but might not be invariably associated with hospital volume. Our objective was to explore surgical margin variations and survival differences of OCSCC between two highest-volume hospitals in Taiwan., Materials and Methods: A total of 2009 and 1019 patients with OCSCC who were treated at the two highest-volume Taiwanese hospitals (termed Hospital 1 and Hospital 2, respectively) were included. We examined how a pathological margin <5 mm impacted patient outcomes before and after propensity score (PS) matching., Results: The prevalence of margins <5 mm was markedly lower in Hospital 1 than in Hospital 2 (34.5%/65.2%, p <0.0001). Compared with Hospital 2, tumor severity was higher in Hospital 1. On univariable analysis, being treated in Hospital 2 (versus Hospital 1; hazard ratio [HR] for 5-year disease-specific survival [DSS] = 1.34, p =0.0002; HR for 5-year overall survival [OS] = 1.17, p =0.0271) and margins <5 mm (versus ≥5 mm; HR for 5-year DSS = 1.63, p <0.0001; HR for 5-year OS = 1.48, p <0.0001) were identified as adverse factors. The associations of treatment in Hospital 2 and margins <5 mm with less favorable outcomes remained significant after adjustment for potential confounders in multivariable analyses, as well as in the PS-matched cohort. The 5-year survival differences between patients operated in Hospital 1 and Hospital 2 were even more pronounced in the PS-matched cohort (before PS matching: DSS, 79%/74%, p =0.0002; OS, 71%/68%, p =0.0269; after PS matching: DSS, 84%/72%, p <0.0001; OS, 75%/66%, p <0.0001). In the entire cohort, the rate of adjuvant therapy was found to be lower in patients with margins ≥5 mm than in those with margins <5 mm (42.7% / 57.0%, p <0.0001)., Conclusions: Within the two highest-volume hospitals in Taiwan, patients with OCSCC with a clear margin status (≥5 mm) achieved more favorable outcomes. These results have clinical implications and show how initiatives aimed at improving the margin quality can translate in better outcomes. A clear margin status can reduce the need for adjuvant therapy, ultimately improving quality of life., 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 Liao, Lee, Lee, Ng, Liu, Chien, Lin, Wang, Terng, Hua, Chen, Chen, Tsai, Kang, Tsai, Chu, Lin, Fan, Wang, Hsieh, Yeh, Lin, Tsao, Yen, Cheng, Fang, Huang, Lee, Fang, Wang, Lin, Hsin and Wen.)

Laryngeal preserving concurrent chemoradiation has been advocated for hypopharyngeal cancers. The use of radiotherapy (RT) in the larynx could lead to increased rates of radionecrosis. In this study, we investigated a rare but disastrous complication, carotid blow-out syndrome (CBS), related with the persistent radionecrosis. Retrospective cohort study. This retrospective study enrolled hypopharyngeal cancer patients with biopsy-proven pharyngeal and laryngeal chondronecrosis (PLCRN), which was rated by the Chandler Grading System. From 2002 to 2018, a total of 346 hypopharygeal cancer patients received upfront radiation therapy, 13 PLCRN patients were identified in a rate of 3.8%. All PLRN patients received RT with a mean radiation dose of 70.81 ± 0.85 Gy. All patients had Chandler Grade IV at the time of presentation, which was a mean of 15.08 months (range: 5-109 months) from the time of cancer diagnosis to PLCRN diagnosis. In 5 of the 13 PLCRN patients developed CBS. Three of the CBS originated from superior thyroid artery, one from lingual artery and one from the carotid artery. Three (60%) of the 5 CBS patients expired due to loss of airway and hemodynamic instability. Two (40%) were rescued by emergent airway secure and emergent angiographic embolization. Persistent PLCRN could lead to disastrous vascular complications. CBSs were demonstrated to be more frequently originated from the branches of carotid artery rather than carotid artery per se. Clinical alert with early airway protection could strive for time to do interventions and prevent mortalities., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To investigate the factors affecting hemodialysis patients' self-management ability at a dialysis center in Taiwan., Background: Taiwan has the highest incidence and prevalence of end-stage kidney disease (ESKD) in the world. Over 90% of patients with ESKD receiving hemodialysis (HD) and self-management behaviors are critical among these patients. Failure to adhere to self-managed care increases the cost of medical care and the risk of morbidity and mortality., Methods: In this cross-sectional study, a total of 150 HD patients were observed for their self-management behaviors and the factors influencing these behaviors including education level, comorbid conditions, biochemical analysis, depression, and social support, etc., were analyzed., Results: Self-management behaviors in HD patients were significantly impaired in the presence of diabetes mellitus, hypertension, anemia, hypoalbuminemia, and depression. The major predictor of patients' self-management was depression, explaining 14.8% of the total variance. Further addition of social support, hypertension, and diabetes mellitus into the regression model increased the total explained variance to 28.6%. Of the various domains of self-management, the partnership domain received the highest score, whereas emotional processing received the lowest score., Conclusions: This study found the important factors influencing self-management behaviors; through this acknowledgement and early correction of these factors, we hope to improve HD patients' individual life quality and further decrease their morbidity and mortality.

Epidemiological evidence has suggested that modifiable lifestyle factors play a significant role in the risk of head and neck cancer (HNC). However, few studies have established risk prediction models of HNC based on sex and tumor subsites. Therefore, we predicted HNC risk by creating a risk prediction model based on sex- and tumor subsites for the general Taiwanese population. This study adopted a case-control study design, including 2961 patients with HNC and 11,462 healthy controls. Multivariate logistic regression and nomograms were used to establish HNC risk prediction models, which were internally validated using bootstrap sampling. The multivariate logistic regression model indicated that age, education level, alcohol consumption, cigarette smoking, passive smoking, coffee consumption, and body mass index are common HNC predictors in both sexes, while the father's ethnicity, betel-nut-chewing habits, and tea consumption were male-specific HNC predictors. The risk factors of the prediction model for the HNC tumor subsite among men were the same as those for all patients with HNC. Additionally, the risks of alcohol consumption, cigarette smoking, and betel nut chewing varied, based on the tumor subsite. A c-index ranging from 0.93 to 0.98 indicated that all prediction models had excellent predictive ability. We developed several HNC risk prediction models that may be useful in health promotion programs.

Background: Fat deposition is associated with adverse outcomes. Waist-to-hip (WHR) ratio is a simple feasible index to assess fat distribution. Lipoprotein particle composition in relation to WHR and to what extent their association is mediated by insulin sensitivity are less investigated., Methods: In 504 randomly recruited Flemish (mean age: 48.9 years; women: 51.6%), we analyzed the lipoprotein particle constitutions using nuclear magnetic resonance spectroscopy. WHR obesity described a WHR of ≥ 0.85 for women or 0.9 for men. Insulin sensitivity was evaluated by the homeostasis model assessment-estimated insulin resistance (HOMA-IR). SCORE-2 risk algorithm was applied to estimate 10-year cardiovascular risk. Statistical methods included multivariable-adjusted linear regression analysis, logistic regression analysis, and mediation analysis., Results: The prevalence of WHR obesity was 54.6%, approximately 3 times of BMI-determined obesity (19.1%). Individuals with WHR obesity had significantly higher metabolic complications, such as hypertension (57.1%), dyslipidemia (61.8%), and insulin resistance (14.2%). WHR and WHR obesity were positively associated with total very-low-density lipoprotein (VLDL) particle concentration, remnant cholesterol, and triglycerides, but were negatively associated with VLDL particle size (P ≤ 0.027), independent of body mass index and other covariates. WHR was inversely associated with total high-density lipoprotein (HDL) particle concentration, whereas WHR obesity was inversely associated with HDL cholesterol (P ≤ 0.039). Neither WHR nor WHR obesity was associated with the concentration of total low-density lipoprotein (LDL) particles, LDL particle size, and LDL cholesterol (P ≥ 0.089). In the mediation analysis, insulin sensitivity significantly mediated the effect of WHR on total VLDL particle concentration (mediation percentage: 37.0%), remnant cholesterol (47.7%), and HDL cholesterol (41.1%). Individuals with WHR obesity were at increased cardiovascular risk, regardless of LDL cholesterol (P ≤0.028). In WHR obesity, higher total VLDL particle concent36ration and remnant cholesterol, and lower HDL cholesterol were associated with an increased cardiovascular risk (P≤ 0.002)., Conclusions: Upper-body fat deposition was independently associated with an unfavorable lipoprotein profile, and insulin sensitivity significantly mediated this association. LDL cholesterol might underestimate lipid abnormality for people with upper-body obesity and lowering VLDL particles and remnant cholesterol might potentially reduce the residual cardiovascular risk., 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 Wei, Marrachelli, Melgarejo, Liao, Janssens, Verhamme, Vanassche, Van Aelst, Monleon, Redón and Zhang.)

Background: Perineural invasion (PNI), a form of local invasion defined as the ability of cancer cells to invade in, around, and through nerves, has a negative prognostic impact in oral cavity squamous cell carcinoma (OCSCC). Unfortunately, the diagnosis of PNI suffers from a significant degree of intra- and interobserver variability. The aim of this pilot study was to develop a deep learning-based human-enhanced tool, termed domain knowledge enhanced yield (Domain-KEY) algorithm, for identifying PNI in digital slides., Methods: Hematoxylin and eosin (H&E)-stained whole-slide images (WSIs, n = 85) were obtained from 80 patients with OCSCC. The model structure consisted of two parts to simulate human decision-making skills in diagnostic pathology. To this aim, two semantic segmentation models were constructed (i.e., identification of nerve fibers followed by the diagnosis of PNI). The inferred results were subsequently subjected to post-processing of generated decision rules for diagnostic labeling. Ten H&E-stained WSIs not previously used in the study were read and labeled by the Domain-KEY algorithm. Thereafter, labeling correctness was visually inspected by two independent pathologists., Results: The Domain-KEY algorithm was found to outperform the ResnetV2&#95;50 classifier for the detection of PNI (diagnostic accuracy: 89.01% and 61.94%, respectively). On analyzing WSIs, the algorithm achieved a mean diagnostic accuracy as high as 97.50% versus traditional pathology. The observed accuracy in a validation dataset of 25 WSIs obtained from seven patients with oropharyngeal (cancer of the tongue base, n = 1; tonsil cancer, n = 1; soft palate cancer, n = 1) and hypopharyngeal (cancer of posterior wall, n = 2; pyriform sinus cancer, n = 2) malignancies was 96%. Notably, the algorithm was successfully applied in the analysis of WSIs to shorten the time required to reach a diagnosis. The addition of the hybrid intelligence model decreased the mean time required to reach a diagnosis by 15.0% and 23.7% for the first and second pathologists, respectively. On analyzing digital slides, the tool was effective in supporting human diagnostic thinking., Conclusions: The Domain-KEY algorithm successfully mimicked human decision-making skills and supported expert pathologists in the routine diagnosis of PNI., Competing Interests: Y-HH, Y-AC, Y-CL, MD-TC and Y-YL are employees of JelloX Biotech Inc. The remaining 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. This study received funding from JelloX Biotech Inc. (grant number 2020-00-346B). The funder was involved in the deep learning process and analysis., (Copyright © 2022 Lee, Yang, Lin, Hsieh, Chen, Chang, Lin and Liao.)

The outcome of acute kidney injury (AKI) as a result of aminoglycosides (AGs) use remains uncertain in patients without prior chronic kidney disease (CKD). Therefore, we explored the outcomes of AGs use on AKI episodes associated with renal recovery and progress in patients without prior CKD in Taiwan. This was a retrospective cohort study by using the Taipei Medical University Research Database from January 2008 to December 2019. 43,259 individuals without CKD who had received parenteral AGs were enrolled. The exposed and unexposed groups underwent propensity score matching for age, gender, patients in intensive care unit/emergency admission, and covariates, except serum hemoglobin and albumin levels. We identified an exposed group of 40,547 patients who used AGs (median age, 54.4 years; 44.3% male) and an unexposed group of 40,547 patients without AG use (median age, 55.7 years; 45.5% male). There was the risk for AKI stage 1 (adjusted hazard ratio [HR] 1.34; 95% confidence interval [CI] 1.00-1.79; p = 0.05) in patients that used AGs in comparison with the control subjects. Moreover, patients using AGs were significantly associated neither with the progression to acute kidney disease (AKD) stages nor with the progression to end-stage renal disease (ESRD) on dialysis. Further analyzed, there was an increased risk of AKI episodes for serum albumin levels less than 3.0 g/dL and hemoglobin levels less than 11.6 g/dL. Among patients without prior CKD, AGs-used individuals were associated with AKI risks, especially those at relatively low albumin (< 3.0 g/dL) or low hemoglobin (< 11.6 g/dL). That could raise awareness of AGs prescription in those patients in clinical practice., (© 2022. The Author(s).)

Introduction: End-stage kidney disease (ESKD) patients who need renal replacement therapy need to face a dialysis modality decision: the choice between hemodialysis (HD) and peritoneal dialysis (PD). Although the global differences in HD/PD penetration are affected by health-care policies, these two modalities may exert different effects on survival in patients with ESKD. Although Taiwan did not implicate PD as first policy, we still need to compare patients’ outcomes using two modalities in a nation-wise database to determine future patients’ care and health policies. Methods: We used the nationwide Taiwan Renal Registry Data System (TWRDS) database from 2005 to 2012 and included 52,900 patients (48,371 on HD and 4529 on PD) to determine all-cause and cardiovascular mortality among ESKD patients. Results: Age-matched survival probability from all-cause mortality was significantly lower in patients on PD than in those on HD (p < 0.05). The adjusted hazard ratios of 3-year and 5-year all-cause and cardiovascular mortality were significantly higher in PD compared with HD. The presence of comorbid conditions including myocardial infarction, coronary artery disease (CAD), diabetes mellitus (DM), hypoalbuminemia, hyperferritinemia and hypophosphatemia was related with significantly higher all-cause and CV mortality in PD patients. No significant difference was noted among younger patients <45 years of age regardless of DM and/or comorbid conditions. Conclusion: Although PD did not have the survival advantage compared to HD in all dialysis populations, PD was related with superior survival in younger non-DM patients, regardless of the presence of comorbidities. Similarly, for younger ESKD patients without the risk of CV disease, both PD and HD would be suitable dialysis modalities.