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Understanding how sleep affects the glymphatic system and human brain networks is crucial for elucidating the neurophysiological mechanism underpinning aging-related memory declines. We analyzed a multimodal dataset collected through magnetic resonance imaging (MRI) and polysomnographic recording from 72 older adults. A proxy of the glymphatic functioning was obtained from the Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index. Structural and functional brain networks were constructed based on MRI data, and coupling between the two networks (SC-FC coupling) was also calculated. Correlation analyses revealed that DTI-ALPS was negatively correlated with sleep quality measures [e.g., Pittsburgh Sleep Quality Index (PSQI) and apnea-hypopnea index]. Regarding human brain networks, DTI-ALPS was associated with the strength of both functional connectivity (FC) and structural connectivity (SC) involving regions such as the middle temporal gyrus and parahippocampal gyrus, as well as with the SC-FC coupling of rich-club connections. Furthermore, we found that DTI-ALPS positively mediated the association between sleep quality and rich-club SC-FC coupling. The rich-club SC-FC coupling further mediated the association between DTI-ALPS and memory function in good sleepers but not in poor sleepers. The results suggest a disrupted glymphatic-brain relationship in poor sleepers, which underlies memory decline. Our findings add important evidence that sleep quality affects cognitive health through the underlying neural relationships and the interplay between the glymphatic system and multimodal brain networks., (© 2024. The Author(s).)

The Design-Thinking Intergenerational Service-Learning Model (DTISLM), rooted in the biopsychosocial model, aims to empower older adults to improve their chronic-disease management behavior through tailored programs addressing their specific healthcare needs. This study, conducted in Taiwan, used a convenience sampling method ( n = 172) to evaluate the impact of DTISLM on Taiwan's adult day center participants' perception of self-care behaviors, feelings of happiness, depression, and perceived social support using pretest-posttest surveys. The results indicated a significant enhancement in participants' perception of self-care behaviors, reduction in depression score, and improvements in perceived social support following the completion of the program. The findings underscore the efficacy of applying a design-thinking framework in an intergenerational context. Future studies should investigate how the DTISLM can be scaled to various demographics and healthcare settings to enhance its applicability and understand its long-term effects., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study tested how increased modality interactivity (e.g., playing vs. watching a game) can augment empathy and reduce ageism toward older adults among college-aged students. An experiment ( n = 201) examined the effects of playing a video game that featured an older adult protagonist. Relative to those who spectated the game, participants who played the game had increased state empathy on subfactors, including shared affect, empathic motivation, and helping motivation. Moreover, shared affect mediated the link between playing a game featuring an older adult protagonist and ageism. Participants with higher trait empathy showed lower state empathy after playing, whereas participants with lower trait empathy displayed increased post-game state empathy. Overall, the results supported the modality interactivity model suggesting fruitful avenues for future research.

Objectives: Gargling mouthwash is a safe and convenient oral care intervention; it rinses the mouth and increases salivary flow rate. The effectiveness of lemon mouthwash in relieving xerostomia and increasing the salivary flow rate among hemodialysis patients has not been studied. Our study sought to analyze the effectiveness of varying concentrations of lemon in mouthwash solutions on xerostomia and salivary flow rate., Methods: A multi-concentration test was used to assess lemon mouthwash at 20%, 15%, 10%, 5%, and 2.5% concentrations to determine the optimal concentration for relieving dry mouth and increasing salivary flow rate. Generalized estimating equations were used to analyze the differences between various concentrations of lemon mouthwash and baseline values., Results: In total, 44 patients were recruited. The 10% lemon concentration mouthwash was the most effective for increasing salivary flow rate, but the 5% and 2.5% were better accepted by the participants. Our findings can help establish intervention guidelines to relieve xerostomia among hemodialysis patients., Conclusion: Our findings can help establish intervention guidelines to relieve xerostomia among hemodialysis patients., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Backgrounds and Aims : Patients with cirrhosis are susceptible to sepsis and septic shock. Cirrhotic patients also have increased capillary permeability and are prone to developing volume overload. Patients with septic shock may have an enhanced pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), both of which are associated with an unfavorable prognosis. It is plausible that pre-existing hyperpermeability may deteriorate when cirrhotic patients develop septic shock. However, it remains unknown whether PVPI and EVLWI can predict the prognosis of cirrhotic patients with septic shock. Pulse Indicator Continuous Cardiac Output (PiCCO) is an established tool to measure PVPI and EVLWI. Therefore, we conducted this retrospective study to investigate the prognostic significance of PVPI and EVLWI in cirrhotic patients with septic shock using PiCCO monitoring. Methods : We included 83 patients with liver cirrhosis and septic shock. EVLW indexed to actual body weight (aEVLWI), EVLW indexed to predicted body weight (pEVLWI), PVPI, disease severity scores, and other biomarkers were analyzed. We collected the PiCCO data on the first 2 days. Results : The overall 28-day mortality was 43.4%. The values of PVPI, aEVLWI, and pEVLWI on day 2 (PVPID2, aEVLWID2, EVLWID2) were significantly higher in non-survivors. The discriminating power of PVPID2 and EVLWID2 to predict 28-day mortality was tested using the area under a ROC curve. The areas under ROC curves (mean ± SEM) were 0.713 ± 0.061 and 0.650 ± 0.063 for PVPID2 and pEVLWID2. In the multivariate analysis, PVPID2, bilirubin, and lactate were independent factors which predicted 28-day mortality. Conclusions : Higher levels of PVPID2 and pEVLWID2 are associated with higher 28-day mortality rates in cirrhotic patients with septic shock. PVPI and pEVLWI may be useful to guide fluid management in this clinical setting.

Introduction: Disparities in physical fitness between immediately before dialysis (pre-D) and the day following dialysis (non-D) have not been investigated despite potential adverse factors such as fluid status, uremia, and electrolyte levels in the pre-dialysis period. The effect of acute exercise immediately before hemodialysis (HD) on HD-related hypotension remains unclear. We hypothesized that cardiopulmonary performance and muscular strength would be inferior in the immediate pre-D period compared to those non-D., Methods: Twenty patients receiving chronic HD treatments underwent symptom-limited incremental cardiopulmonary exercise testing (CPET) and isokinetic testing both 1-2 h prior to dialysis (pre-D) and non-D. This investigation was a sub-study of a clinical trial assessing the efficacy of a pre-D exercise training program. Blood pressure profiles during HD post-CPET and pre-D exercise training were compared with those during usual HD sessions., Results: No adverse events were observed during the 80 exercise tests. Prior to dialysis, the nadir of the ventilatory equivalent of CO2 was slightly elevated, the resting heart rate was lower, and the peak systolic blood pressure was higher than those non-D. Contrary to our hypothesis, peak INLINEMATH and quadriceps peak torque showed no differences. Blood pressure profiles during HD post-exercise were similar to those during sessions without prior exercise, except for a lower resting systolic blood pressure at the beginning of HD., Conclusion: Cardiopulmonary response and muscular strength in the 1-2 h prior to HD were comparable with those on the day following HD, with only minor clinically insignificant differences. Acute exercise prior to HD did not affect the magnitude of hypotension during HD. This study suggests a potential alternative timing for exercise training or testing in patients undergoing chronic HD., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Immune checkpoint inhibitors (ICIs) have been associated with acute kidney injury (AKI). However, the occurrence rate of ICI-related AKI has not been systematically examined. Additionally, exposure to proton pump inhibitors (PPIs) and non-steroidal anti-inflammatory drugs (NSAIDs) were considered as risk factors for AKI, but with inconclusive results in ICI-related AKI. Our aim was to analyse the occurrence rate of all-cause AKI and ICI-related AKI and the occurrence rates of severe AKI and dialysis-requiring AKI, and to determine whether exposure to PPIs and NSAIDs poses a risk for all-cause and ICI-related AKI., Methods: This study population was adult ICI recipients. A systematic review was conducted by searching MEDLINE, Embase and PubMed through October 2023. We included prospective trials and observational studies that reported any of the following outcomes: the occurrence rate of all-cause or ICI-related AKI, the relationship between PPI or NSAID exposure and AKI development or the mortality rate in the AKI or non-AKI group. Proportional meta-analysis and pairwise meta-analysis were performed. The evidence certainty was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework., Results: A total of 120 studies comprising 46 417 patients were included. The occurrence rates of all-cause AKI were 7.4% (14.6% from retrospective studies and 1.2% from prospective clinical trials). The occurrence rate of ICI-related AKI was 3.2%. The use of PPIs was associated with an odds ratio (OR) of 1.77 [95% confidence interval (CI) 1.43-2.18] for all-cause AKI and an OR of 2.42 (95% CI 1.96-2.97) for ICI-related AKI. The use of NSAIDs was associated with an OR of 1.77 (95% CI 1.10-2.83) for all-cause AKI and an OR of 2.57 (95% CI 1.68-3.93) for ICI-related AKI., Conclusions: Our analysis revealed that approximately 1 in 13 adult ICI recipients may experience all-cause AKI, while 1 in 33 adult ICI recipients may experience ICI-related AKI. Exposure to PPIs and NSAIDs was associated with an increased OR risk for AKI in the current meta-analysis., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Electric cell-substrate impedance sensing (ECIS) is an innovative approach for the label-free and real-time detection of cell morphology, growth, and apoptosis, thereby playing an essential role as both a viable alternative and valuable complement to conventional biochemical/pharmaceutical analysis in the field of diagnostics. Constant improvements are naturally sought to further improve the effective range and reliability of this technology. In this study, we developed poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) conducting polymer (CP)-based bioelectrodes integrated into homemade ECIS cell-culture chamber slides for the simultaneous drug release and real-time biosensing of cancer cell viability under drug treatment. The CP comprised tailored PEDOT:PSS, poly(ethylene oxide) (PEO), and (3-glycidyloxypropyl)trimethoxysilane (GOPS) capable of encapsulating antitumor chemotherapeutic agents such as doxorubicin (DOX), docetaxel (DTX), and a DOX/DTX combination. This device can reliably monitor impedance signal changes correlated with cell viability on chips generated by cell adhesion onto a predetermined CP-based working electrode while simultaneously exhibiting excellent properties for both drug encapsulation and on-demand release from another CP-based counter electrode under electrical stimulation (ES) operation. Cyclic voltammetry curves and surface profile data of different CP-based coatings (without or with drugs) were used to analyze the changes in charge capacity and thickness, respectively, thereby further revealing the correlation between their drug-releasing performance under ES operation (determined using ultraviolet-visible (UV-vis) spectroscopy). Finally, antitumor drug screening tests (DOX, DTX, and DOX/DTX combination) were performed on MCF-7 and HeLa cells using our developed CP-based ECIS chip system to monitor the impedance signal changes and their related cell viability results.

Background: Critically ill patients with acute kidney injury (AKI) have a poor prognosis. Recently, the Acute Disease Quality Initiative (ADQI) proposed to define acute kidney disease (AKD) as acute or subacute damage and/or loss of kidney function post AKI. We aimed to identify the risk factors for the occurrence of AKD and to determine the predictive value of AKD for 180-day mortality in critically ill patients., Methods: We evaluated 11,045 AKI survivors and 5,178 AKD patients without AKI, who were admitted to the intensive care unit between 1 January 2001 and 31 May 2018, from the Chang Gung Research Database in Taiwan. The primary and secondary outcomes were the occurrence of AKD and 180-day mortality., Results: The incidence rate of AKD among AKI patients who did not receive dialysis or died within 90 days was 34.4% (3,797 of 11,045 patients). Multivariable logistic regression analysis indicated that AKI severity, underlying early CKD, chronic liver disease, malignancy, and use of emergency hemodialysis were independent risk factors of AKD, while male gender, higher lactate levels, use of ECMO, and admission to surgical ICU were negatively correlated with AKD. 180-day mortality was highest among AKD patients without AKI during hospitalization (4.4%, 227 of 5,178 patients), followed by AKI with AKD (2.3%, 88 of 3,797 patients) and AKI without AKD (1.6%, 115 of 7,133 patients). AKI with AKD had a borderline significantly increased risk of 180-day mortality (aOR 1.34, 95% CI 1.00-1.78; p  = 0.047), while patients with AKD but no preceding AKI episodes had the highest risk (aOR 2.25, 95% CI 1.71-2.97; p  < 0.001)., Conclusion: The occurrence of AKD adds limited additional prognostic information for risk stratification of survivors among critically ill patients with AKI but could predict prognosis in survivors without prior AKI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pan, Chen, Chen, Huang, Fang and Chen.)

Background: Microlectures comprise short audio or video presentations designed to provide a concise explanation of key concepts or topics., Purpose: The study aimed to develop a microlecture module for a nursing course in medication administration and test whether it could improve learning., Methods: The study had a quasi-experimental design. Four classes of sophomore nursing students were divided into the treatment (n = 109) and control groups (n = 84). Pretests, posttests, integrated examinations, and simulated experiences were employed. Analysis of covariance were used to analyze the students' pretest, posttest, and integrated examination performances., Results: The treatment group performed better than the control group., Conclusions: This study provides nursing educators with a different approach to traditional teaching and sheds light on how to design a microlecture., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Objectives: The objective of this study was to investigate the effect of acupressure on fatigue severity, sleep quality, and psychological status in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) treatment. Design: A single-blinded parallel-group randomized controlled trial. Settings/Location: A medical center in central Java, Indonesia. Subjects: One hundred and six patients who had been receiving HD for at least 3 months were enrolled in this study and randomly assigned to two groups. Interventions: The experimental group received acupressure at K1, ST36, and SP6 acupoints. In contrast, the control group received sham acupressure at 1 cun from these three acupoints. Subjects received acupressure thrice per week for 4 weeks, and pressure on each acupoint was applied for 3 min bilaterally. Outcome measures: The primary outcome was fatigue severity, while sleep quality and psychological status (depression/anxiety) were evaluated as secondary outcomes. Outcomes were assessed using the Brief Fatigue Inventory, Pittsburgh Sleep Quality Index, and Hospital Anxiety and Depression Scale. Results: Acupressure induced a significant medium to large effect on improvement in fatigue ( b  = -1.71, confidence interval [95% CI]: -1.90 to -1.51, ΔR 2  = 0.744), sleep quality ( b  = -5.81, 95% CI: -6.80 to -4.81, ΔR 2  = 0.525), and anxiety ( Estimate  = -3.213, 95% CI: -4.238 to -2.188, pseudo R 2  = 0.292)/depression ( Estimate  = -3.378, 95% CI: -4.432 to -2.325, pseudo R 2  = 0.268) in experimental group patients compared to controls. No adverse events of acupressure were reported during the study process. Conclusions: Acupressure significantly and independently improved fatigue, depression/anxiety, and sleep quality in ESRD patients receiving HD. Clinical Trial Registration: NCT05571007.

Objective: The objective of this study was to determine if hemodialysis patients who have undergone an invasive dental treatment are at risk of developing infective endocarditis., Materials and Methods: This study was a cohort case-control design and used secondary data collected from the National Health Insurance Research Database of Taiwan. The case group and the control group were each comprised of 19,602 hemodialysis patients. The control group was matched for four variables: age, gender, a medical history of diabetes mellitus, and a cerebrovascular event. After matching, the case group and the control group were each comprised of 19,602 hemodialysis patients. Cox regression analysis determined hazard ratios and 95% confidence intervals., Results: Patients were followed up at 1 month and 3 months after receiving invasive dental treatment. The results showed the cohort case-control hazard ratio was 0.88 (95% CI, 0.49, 1.57) 1 month after receiving invasive dental treatment. Three months after receiving IDT, the cohort case-control hazard ratio was 1.04 (95% CI, 0.71, 1.52). Hazard ratios did not differ significantly between groups., Conclusions: Hemodialysis patients who received invasive dental treatment had no greater risk of developing infective endocarditis than matched control patients. The results of this study should alleviate concerns for hemodialysis patients and dentists about invasive dental treatment procedures. We recommend hemodialysis patients undergo invasive dental treatment when needed., Clinical Relevance: The results of this study showed that invasive dental treatment did not increase their risk of developing infective endocarditis. Hemodialysis patients in need of an invasive dental procedure should be encouraged to undergo treatment if the dentist deems it necessary., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: As the aging population is increasing significantly, the communication skills training (CST) on transitional care (TC) is insufficient., Aims: This study aimed to test the effectiveness of an intervention (the online TC CST [OTCCST] and TC) through the perspectives of healthcare providers (HCPs), older patients, and family members., Methods: A total of 38 HCPs caring for older patients were randomized to the experimental (n = 18) or control groups (n = 20), and 84 pairs of patients and family members were enrolled (experimental: n = 42 vs. control: n = 42). The primary outcome was HCP communication confidence; while secondary outcomes included patient quality of life (QoL), activities of daily living (ADL), rehospitalization counts, and family caregiving burden. Data were collected from HCPs using a scale measuring confidence in communicating with patients. Patient outcomes were assessed using the McGill QoL Questionnaire-Revised and Barthel Index. Family members were assessed with the Caregiver Burden Inventory. Rehospitalization counts were tracked for 3 months post-discharge. Data were analyzed using multiple regression analysis., Results: Experimental group HCPs showed a significant improvement in communication confidence over the control group (p = 0.0006). Furthermore, experimental group patients had significantly fewer rehospitalization counts within 3-month post-discharge (p < 0.05). However, no significant group differences were found in patient QoL and ADL nor in family caregiver burden., Conclusion: The OTCCST can effectively improve HCP communication confidence, and the combination of OTCCST and TC can reduce rehospitalization counts for older patients. The OTCCST allows HCPs to learn asynchronously at their convenience, ideal for continuing education, especially during the COVID-19 pandemic., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: In recent years, a national curriculum reform was implemented in undergraduate medical education in Taiwan to reduce clinical rotation training from 3 years to 2 years. The last generation of the old curriculum and the first generation of the new curriculum both graduated in 2019. This study aimed to compare the learning outcomes of the medical students in these two curriculum groups in terms of preparedness for practice during the transition from undergraduate to postgraduate study., Methods: This was a 3-year prospective, longitudinal, comparative cohort study between 2017 and 2020. Medical students from both the 7-year and 6-year curriculum groups received biannual questionnaire surveys starting 18 months before graduation and running until 11 months after graduation. The measurement tools were the Preparedness for Hospital Practice Questionnaire (PHPQ) and Copenhagen Burnout Inventory (CBI). Personal demographic information was also collected. Linear mixed models were used to determine the effect of curriculum change on learners' preparedness and burnout levels., Results: A total of 130 medical students from the two cohorts provided 563 measurements during the study period. Compared to their counterparts following the old curriculum, the participants following the new curriculum showed a lower level of preparedness when first entering clinical rotation (p = 0.027) and just after graduating (p = 0.049), especially in the domains of clinical confidence (p = 0.021) and patient management p = 0.015). The multivariate linear mixed model revealed gradual increases in preparedness and burnout in serial measurements in both curriculum groups. Students following the new curriculum, which involved a shortened clinical rotation, showed a slightly lower overall preparedness (p = 0.035) and the same level of burnout (p = 0.692) after adjustment. The factor of year of change did not show a significant effect on either preparedness (p = 0.258) or burnout (p = 0.457)., Conclusion: Shortened clinical rotation training for medical undergraduates is associated with a decrease in preparedness for practice during the transition from undergraduate to postgraduate study. Clinical confidence and patient management are the main domains affected., (© 2022. The Author(s).)

Background: Folate is a water-soluble vitamin and is essential for maintaining cell functions. Dialysis removes folate, and folate deficiency is reported in patients with end-stage kidney disease (ESKD). However, there is no consensus as to the appropriate dosage of folate supplements and their advantages and disadvantages for patients with ESKD., Methods: This study was based on the electronic medical records of the Chang Gung Research Database (CGRD) of the Chang Gung Medical Foundation. We included patients who were diagnosed with ESKD, initiated hemodialysis, and were given folic acid supplements at any point from 1 January 2001 to 31 December 2019. The patients were divided into weekly and daily folic acid supplementation groups. We reduced the effects of confounding through the inverse probability of treatment weighting based on the propensity score., Results: We identified 2081 and 954 newly diagnosed patients with ESKD, who received daily and weekly folic acid supplements. The mean follow-up time was 5.8 years, and the event rates of arteriovenous access thrombosis were 17.0% and 23.6% in the daily and weekly folic acid supplementation groups (sub-distribution hazard ratio = 0.69, 95% confidence interval = 0.61 to 0.77), respectively. Neither group significantly differed in the occurrence of other clinical events, such as major cardiovascular cardiac events (e.g., myocardial infarction and ischemic stroke), all-cause mortality, cardiovascular death, infection death, malignancy, and adverse effects., Conclusion: a daily 5 mg folic acid supplementation might result in a lower event rate of arteriovenous access thrombosis in patients with ESKD than weekly folic acid supplementation. Further prospective studies are warranted to explore the preventive effect of folate on thrombosis.

Background: Given that the consequences of treatment decisions for end-stage renal disease (ESRD) patients are long-term and significant, good communication skills are indispensable for health care personnel (HCP) working in nephrology. However, HCP have busy schedules that make participation in face-to-face courses difficult. Thus, online curricula are a rising trend in medical education. This study aims to examine the effectiveness of online ESRD communication skills training (CST) concerning the truth-telling confidence and shared decision-making (SDM) ability of HCP., Methods: For this single-center, single-blind study, 91 participants (nephrologists and nephrology nurses) were randomly assigned to two groups, the intervention group (IG) (n = 45) or the control group (CG) (n = 46), with the IG participating in ESRD CST and the CG receiving regular in-service training. Truth-telling confidence and SDM ability were measured before (T0), 2 weeks after (T1), and 4 weeks after (T2) the intervention. Group differences over the study period were analyzed by generalized estimating equations., Results: IG participants exhibited significantly higher truth-telling confidence at T1 than did CG participants (t = 2.833, P = .006, Cohen's d = 0.59), while there were no significant intergroup differences in the confidence levels of participants in the two groups at T0 and T2. Concerning SDM ability, there were no significant intergroup differences at any of the three time points. However, IG participants had high levels of satisfaction (n = 43, 95%) and were willing to recommend ESRD CST to others (n = 41, 91.1%)., Conclusions: ESRD CST enhanced short-term truth-telling confidence, though it is unclear whether this was due to CST content or the online delivery. However, during pandemics, when face-to-face training is unsuitable, online CST is an indispensable tool. Future CST intervention studies should carefully design interactive modules and control for method of instruction., (© 2022. The Author(s).)

Background and Objectives: The glymphatic system, which is robustly enabled during some stages of sleep, is a fluid-transport pathway that clears cerebral waste products. Most contemporary knowledge regarding the glymphatic system is inferred from rodent experiments and human research is limited. Our objective is to explore the associations between human glymphatic function, sleep, neuropsychological performance, and cerebral gray matter volumes., Methods: This cross-sectional study included individuals 60 years or older who had participated in the Integrating Systemic Data of Geriatric Medicine to Explore the Solution for Health Aging study between September 2019 and October 2020. Community-dwelling older adults were enrolled at 2 different sites. Participants with dementia, major depressive disorders, and other major organ system abnormalities were excluded. Sleep profile was accessed using questionnaires and polysomnography. Administered neuropsychological test batteries included Everyday Cognition (ECog) and the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB). Gray matter volumes were estimated based on MRI. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index was used as the MRI marker of glymphatic function., Results: A total of 84 participants (mean [SD] age 73.3 [7.1] years, 47 [56.0%] women) were analyzed. Multivariate linear regression model determined that age (unstandardized β, -0.0025 [SE 0.0001]; p = 0.02), N2 sleep duration (unstandardized β, 0.0002 [SE 0.0001]; p = 0.04), and the apnea-hypopnea index (unstandardized β, -0.0011 [SE 0.0005]; p = 0.03) were independently associated with DTI-ALPS. Higher DTI-ALPS was associated with better ECog language scores (unstandardized β, -0.59 [SE 0.28]; p = 0.04) and better CERAD-NB word list learning delayed recall subtest scores (unstandardized β, 6.17 [SE 2.31]; p = 0.009) after covarying for age and education. Higher DTI-ALPS was also associated with higher gray matter volume (unstandardized β, 107.00 [SE 43.65]; p = 0.02) after controlling for age, sex, and total intracranial volume., Discussion: Significant associations were identified between glymphatic function and sleep, stressing the importance of sleep for brain health. This study also revealed associations between DTI-ALPS, neuropsychological performance, and cerebral gray matter volumes, suggesting the potential of DTI-ALPS as a biomarker for cognitive disorders., (© 2021 American Academy of Neurology.)

Background: Rheumatoid arthritis (RA)-related comorbidities, including cardiovascular disease (CVD), osteoporosis (OP), and interstitial lung disease (ILD), are sub-optimally managed. RA-related comorbidities affect disease control and lead to impairment in quality of life. We aimed to develop consensus recommendations for managing RA-related comorbidities., Methods: The consensus statements were formulated based on emerging evidence during a face-to-face meeting of Taiwan rheumatology experts and modified through three-round Delphi exercises. The quality of evidence and strength of recommendation of each statement were graded after a literature review, followed by voting for agreement. Through a review of English-language literature, we focused on the existing evidence of management of RA-related comorbidities., Results: Based on experts' consensus, eleven recommendations were developed. CVD risk should be assessed in patients at RA diagnosis, once every 5 years, and at changes in DMARDs therapy. Considering the detrimental effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids on CVD risks, we recommend using the lowest possible dose of corticosteroids and prescribing NSAIDs cautiously. The OP/fragility fracture risk assessment includes dual-energy X-ray absorptiometry and fracture risk assessment (FRAX) in RA. The FRAX-based approach with intervention threshold is a useful strategy for managing OP. RA-ILD assessment includes risk factors, pulmonary function tests, HRCT imaging and a multidisciplinary decision approach to determine RA-ILD severity. A treat-to-target strategy would limit RA-related comorbidities., Conclusions: These consensus statements emphasize that adequate control of disease activity and the risk factors are needed for managing RA-related comorbidities, and may provide useful recommendations for rheumatologists on managing RA-related comorbidities., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To analyze changes in saliva flow rate and clinical measures from unstimulated whole saliva (UWS) among patients undergoing hemodialysis for end-stage kidney disease (ESKD)., Background: Chronic hemodialysis causes changes in blood chemistry as well as dry mouth, due to removal of excess fluids. UWS is used to examine saliva flow rate as an indicator of mouth dryness. Whether UWS can be used to measure changes in clinical variables following hemodialysis has not been explored., Design: A cross-sectional quantitative study., Methods: Patients with ESKD were recruited by purposive sampling ( n  = 100) between 1 January and 30 June 2015 from a hospital in northern Taiwan. UWS was collected 1-hour pre-dialysis (T1), mid-dialysis (T2), and 1-hour post-dialysis (T3). Saliva flow rate and clinical variables were analyzed., Results: Saliva flow rate increased significantly from T1 to T3 (Wald χ 2  = 10.40, p  < .01). Changes in saliva from T1 to T3 included decreases in blood urea nitrogen and creatinine (Wald χ 2  = 97.12, p  < .001 and Wald χ 2  = 36.98, p  < .001, respectively). The pH and osmolality also decreased ( p  < .001 and p  < .01, respectively). Changes in electrolytes included decreases in potassium and calcium (Wald χ 2  = 6.71, p  < .05 and Wald χ 2  = 17.64, p  < .01, respectively) and increases in chloride (Wald χ 2  = 17.64, p  < .001)., Conclusion: Our findings demonstrated saliva flow rate and several saliva components were altered during hemodialysis. The total volume of saliva secretion increased following dialysis, which can reduce xerostomia. Therefore, medical personnel could provide interventions of relieving dry mouth symptoms and increasing saliva flow rate before hemodialysis treatment.

Ethnopharmacological Relevance: External-use traditional Chinese medicine (TCM) agents are widely used to relieve the adverse effects of radiation therapy in nasopharyngeal cancer patients., Aim of the Study: Our study aimed to evaluate the influence of external-use TCM agents to relieve radiotherapy-related adverse effects on the efficacy of radiation therapy and the prognosis of nasopharyngeal cancer patients., Materials and Methods: By using the Chang Gung Research Database (CGRD), we analyzed 1823 newly diagnosed nasopharyngeal cancer patients with radiotherapy-related adverse effects between 2001/01 and 2015/12. We used Kaplan-Meier analysis and a Cox regression model to estimate the differences in effects on survival outcomes between two groups, TCM external users and non-TCM external users., Results: We found that TCM external users had significantly better 3-year and 5-year overall survival rates (log-rank test, p = 0.0377 and p = 0.034, respectively) than non-TCM external users. The 3-year and 5-year disease-free survival rates were not statistically significantly different between the groups. We also found a trend of improved 3-year and 5-year overall survival rates in TCM external users with advanced-stage disease, without statistical significance (log-rank test, p = 0.10 and p = 0.089, respectively). The subgroup analysis revealed lower risks of mortality in TCM external users among the nonhypertension, nonhyperlipidemia, nonischemic heart disease, noncirrhosis, and nonchronic kidney disease groups., Conclusions: Our study showed that TCM agents external use could significantly improve 3-year and 5-year overall survival rates in nasopharyngeal cancer patients with radiotherapy-related adverse effects., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Transcript isoforms regulated by alternative splicing can substantially impact carcinogenesis, leading to a need to obtain clues for both gene differential expression and malfunctions of isoform distributions in cancer studies. The Cancer Genome Atlas (TCGA) project was launched in 2008 to collect cancer-related genome mutation raw data from the population. While many repositories tried to add insights into the raw data in TCGA, no existing database provides both comprehensive gene-level and isoform-level cancer stage marker investigation and survival analysis. We constructed Cancer DEIso to facilitate in-depth analyses for both gene-level and isoform-level human cancer studies. Patient RNA-seq data, sample sheets, patient clinical data, and human genome datasets were collected and processed in Cancer DEIso. And four functions to search differentially expressed genes/isoforms between cancer stages were implemented: (i) Search potential gene/isoform markers for a specified cancer type and its two stages; (ii) Search potentially induced cancer types and stages for a gene/isoform; (iii) Expression survival analysis on a given gene/isoform for some cancer; (iv) Gene/isoform stage expression comparison visualization. As an example, we demonstrate that Cancer DEIso can indicate potential colorectal cancer isoform diagnostic markers that are not easily detected when only gene-level expressions are considered. Cancer DEIso is available at http://cosbi4.ee.ncku.edu.tw/DEIso/., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: Medical schools prepare undergraduates for clinical practice. Clinical competencies build up gradually and continuously. Existing literature suggests that new graduates are often unprepared for independent practice. This study aims to validate a Chinese version of a Preparedness for Hospital Practice Questionnaire (PHPQ) in a Taiwanese undergraduate cohort., Methods: The original eight-domain English version PHPQ was translated into Chinese and back-translated for expert panel discussion. The eight domains encompass interpersonal skills, confidence, collaboration, management, science, prevention, holistic care, and self-directed learning. Reliability and validity were checked by Cronbach's alpha and by confirmatory factor analysis (CFA), respectively. Participants were divided into higher and lower preparedness groups according to PHPQ results, and compared by age, sex, professional identity, and perception of educational environment., Results: A total of 129 undergraduate medical students (55% males) participated in the study. The overall Cronbach's alpha was 0.94. Participants were found to be best prepared in the domain of disease prevention (M = 4.37, SD = 0.68) and least prepared in interpersonal skills (M = 2.68, SD = 0.77). A satisfactory goodness of fit data was yield from CFA with a CMIN/DF of 2.02. Higher levels of preparedness are associated with stronger professional identity (p < 0.001) and better perceived learning environment (p < 0.001)., Conclusion: The Chinese version of PHPQ showed good reliability and validity. Preparedness for practice was associated with how learners feel about themselves as doctors and how well they had integrated into medical teamwork., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Risk and prognostic factors for acute kidney injury (AKI) have been published in various studies across various populations. We aimed to explore recent advancements in and provide updated recommendations on AKI risk stratification and information about local AKI risk factors. The Taiwan Acute Kidney Injury Task Force reviewed relevant recently published literature and reached a consensus after group meetings. Systemic review and group discussion were performed. We conducted a meta-analysis according to the PRISMA statement for evaluating the diagnostic performance of the furosemide stress test. Several risk and susceptibility factors were identified through literature review. Contrast-associated AKI prediction models after coronary angiography were one of the most discussed prediction models we found. The basic approach and evaluation of patients with AKI was also discussed. Our meta-analysis found that the furosemide stress test can be used as a prognostic tool for AKI progression and to identify patients with AKI who are at low risk of renal replacement therapy. Factors associated with de novo chronic kidney injury or renal non-recovery after AKI were identified and summarized. Our review provided practical information about early identification of patients at high risk of AKI or disease progression for Taiwan local clinics., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

TAFRO syndrome is an extremely rare form of idiopathic MCD, characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis on bone marrow biopsy, and organomegaly. Like idiopathic MCD, renal involvement is also a common presentation in patients with TAFRO syndrome. Furthermore, membranoproliferative glomerulonephritis (MPGN)-like injury and thrombotic microangiopathy (TMA) are the most reported histopathologic findings of renal biopsy. Several molecular mechanisms have been previously postulated in order to explain the TAFRO syndrome symptoms, including abnormal production of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), etc. The role of these cytokines in renal injury, however, is not well understood. The aim of this review article is to summarize the latest knowledge of molecular mechanisms behind the TAFRO syndrome and their potential role in renal damage.

Background: Translational regulation is one important aspect of gene expression regulation. Dysregulation of translation results in abnormal cell physiology and leads to diseases. Ribosome profiling (RP), also called ribo-seq, is a powerful experimental technique to study translational regulation. It can capture a snapshot of translation by deep sequencing of ribosome-protected mRNA fragments. Many ribosome profiling data processing tools have been developed. However, almost all tools analyze ribosome profiling data at the gene level. Since different isoforms of a gene may produce different proteins with distinct biological functions, it is advantageous to analyze ribosome profiling data at the isoform level. To meet this need, previously we developed a pipeline to analyze 610 public human ribosome profiling data at the isoform level and constructed HRPDviewer database., Results: To allow other researchers to use our pipeline as well, here we implement our pipeline as an easy-to-use software tool called RPiso. Compared to Ribomap (a widely used tool which provides isoform-level ribosome profiling analyses), our RPiso (1) estimates isoform abundance more accurately, (2) supports analyses on more species, and (3) provides a web-based viewer for interactively visualizing ribosome profiling data on the selected mRNA isoforms., Conclusions: In this study, we developed RPiso software tool ( http://cosbi7.ee.ncku.edu.tw/RPiso/ ) to provide isoform-level ribosome profiling analyses. RPiso is very easy to install and execute. RPiso also provides a web-based viewer for interactively visualizing ribosome profiling data on the selected mRNA isoforms. We believe that RPiso is a useful tool for researchers to analyze and visualize their own ribosome profiling data at the isoform level.

Background: Graduating from medical school and beginning independent practice appears to be a major transition for medical students across the world. It is often reported that medical graduates are underprepared for independent practice. Most previous studies on undergraduates' preparedness are cross-sectional. This study aimed to characterize the development and trend of medical students' preparedness and its association with other objective and subjective indicators from the undergraduate to postgraduate periods., Methods: This was a prospective cohort study. The participants were recruited and followed from two years before graduation to the postgraduate period. The preparedness for independent practice, professional identity, and teamwork experience were biannually measured using previously validated questionnaires. The participants' basic demographic information, clinical learning marks from the last two years, and national board exam scores were also collected., Results: A total of 85 participants completed 403 measurements in the 5 sequential surveys. The mean age at recruitment was 23.6, and 58 % of participants were male. The overall total preparedness score gradually increased from 157.3 (SD=21.2) at the first measurement to 175.5 (SD=25.6) at the fifth measurement. The serial individual preparedness scores revealed both temporal differences within the same learner and individual differences across learners. Despite the variations, a clear, steady increase in the overall average score was observed. Participants were least prepared in the domain of patient management at first, but the score increased in the subsequent measurements. The participants with better final preparedness had better professional identity (p<0.01), better teamwork experience (p < 0.01), and higher average clinical rotation marks (p<0.05)., Conclusions: The preparedness for practice of medical students from the undergraduate to postgraduate periods is associated with their professional identity, teamwork experience, and objective clinical rotation endpoint. Although preparedness generally increases over time, educators must understand that there are temporal fluctuations and individual differences in learners' preparedness.

Intratumoral heterogeneity in epidermal growth factor receptor (EGFR)-mutant mutant non-small-cell lung cancer (NSCLC) explains the mixed responses to EGFR-tyrosine kinase inhibitors (TKIs). However, some studies showed tumors with low abundances of EGFR mutation still respond to EGFR-TKI, and the mechanism remained undetermined. Extracellular vesicles (EVs) can transmit antiapoptotic signals between drug-resistant and drug-sensitive cells. Herein, we profiled EVs from EGFR-mutant cells to identify a novel mechanism explaining why heterogenous EGFR-mutant NSCLC patients still respond to EGFR-TKIs. We first demonstrated that the EVs from EGFR-mutant changes the wild-type cells' sensitivity to gefitinib by adding EV directly or coculturing EGFR wild-type (CL1-5) cells and EGFR-mutant (PC9) cells. In animal studies, only the combined treatment of PC9 EV and gefitinib delayed the tumor growth of CL1-5 cells. MicroRNA analysis comparing EV miRNAs from PC9 cells to those from CL1-5 cells showed that mir200 family members are most abundant in PC9 EVs. Furthermore, mir200a and mir200c were found upregulated in plasma EVs from good responders to EGFR-TKIs. Finally, the transfection of CL1-5 cells with miR200c inactivates downstream signaling pathways of EGFR, the EMT pathway, and enhances gefitinib sensitivity. Overall, our results suggest that in heterogeneous EGFR-mutant NSCLC, tumor cells transmit EV miRNAs that may affect sensitivity to EGFR-TKIs and provide potential prognostic biomarkers for EGFR-mutant NSCLC.

Context: The outbreak of coronavirus disease 2019 (CO-VID-19) has rapidly evolved into a global pandemic. Kidney dysfunction is common among patients with COVID-19, and patients who develop acute kidney injury (AKI) have inferior outcomes. There is a growing body of evidence that AKI occurs in a substantial number of patients with COVID-19 and that developing AKI is associated with significantly worse outcomes for COVID-19 patients. The risk for death was amplified when AKI resulted in kidney replacement therapy (KRT). Subject of Review: The Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) conducted a multicenter retrospective observational study enrolling 3,099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) (J Am Soc Nephrol 2021;32:161-176). A total of 637 of 3,099 patients (20.6%) developed AKI treated with KRT (AKI-KRT) within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Predictors of COVID-19 patients' progress to AKI-KRT were higher BMI, higher stages of CKD, lower ratio of the partial pressure of arterial oxygen over the fraction of inspired oxygen (PaO2:FiO2 ratio) on ICU admission, and greater number of vasopressors received on ICU admission. Second Opinion: Recently, some investigations revealed that the independent predictors of COVID-19 with AKI include older age, Black race, diabetes, hypertension, cardiovascular disease, mechanical ventilation, higher interleukin-6 level, and use of vasopressor medications. It seems that the underlying comorbidities with preexisting vascular endothelial damage and/or the more serious critically ill CO-VID-19 patients can contribute to the development of AKI and even AKI-KRT., (© 2021 S. Karger AG, Basel.)

The association between regional economic status and the probability of renal recovery among patients with dialysis-requiring AKI (AKI-D) is unknown. The nationwide prospective multicenter study enrolled critically ill adult patients with AKI-D in four sampled months (October 2014, along with January, April, and July 2015) in Taiwan. The regional economic status was defined by annual disposable income per capita (ADIPC) of the cities the hospitals located. Among the 1,322 enrolled patients (67.1 ± 15.5 years, 36.2% female), 833 patients (63.1%) died, and 306 (23.1%) experienced renal recovery within 90 days following discharge. We categorized all patients into high (n = 992) and low economic status groups (n = 330) by the best cut-point of ADIPC determined by the generalized additive model plot. By using the Fine and Gray competing risk regression model with mortality as a competing risk factor, we found that the independent association between regional economic status and renal recovery persisted from model 1 (no adjustment), model 2 (adjustment to basic variables), to model 3 (adjustment to basic and clinical variables; subdistribution hazard ratio, 1.422; 95% confidence interval, 1.022-1.977; p = 0.037). In conclusion, high regional economic status was an independent factor for renal recovery among critically ill patients with AKI-D.

Deep sequencing of T-cell receptor (TCR) genes is powerful at profiling immune repertoire. To prepare a TCR sequencing library, multiplex polymerase chain reaction (mPCR) is widely applied and is highly efficient. That is, most mPCR products contain the region critical for antigen recognition, which also indicates regular V(D)J recombination. Multiplex PCR, however, may suffer from primer bias. A promising alternative is 5'-RACE, which avoids primer bias by applying only one primer pair. In 5'-RACE data, however, non-regular V(D)J recombination (e.g., TCR sequences without a V gene segment) has been observed and the frequency varies (30-80%) between studies. This suggests that the cause of or how to reduce non-regular TCR sequences is not yet well known by the science community. Although it is possible to speculate the cause by comparing the 5'-RACE protocols, careful experimental confirmation is needed and such a systematic study is still not available. Here, we examined the 5'-RACE protocol of a commercial kit and demonstrated how a modification increased the fraction of regular TCR-β sequences to >85%. We also found a strong linear correlation between the fraction of short DNA fragments and the percentage of non-regular TCR-β sequences, indicating that the presence of short DNA fragments in the library was the main cause of non-regular TCR-β sequences. Therefore, thorough removal of short DNA fragments from a 5'-RACE library is the key to high data efficiency. We highly recommend conducting a fragment length analysis before sequencing, and the fraction of short DNA fragments can be used to estimate the percentage of non-regular TCR sequences. As deep sequencing of TCR genes is still relatively expensive, good quality control should be valuable., Competing Interests: The authors have declared that no competing interests exist.

Background: Food insecurity, limited access to adequate food, in adulthood is associated with poor health outcomes that suggest a pattern of accelerated aging. However, little is known about factors that impact food insecurity in midlife which in turn could help to identify potential pathways of accelerated aging., Methods: Low-income adults (n = 17,866; 2014 National Health Interview Survey), ages 18 to 84, completed a 10-item food security module and answered questions regarding health challenges (chronic conditions and functional limitations) and financial worry. We used multinomial logistic regression for complex samples to assess the association of health challenges and financial worry with food insecurity status and determine whether these associations differed by age group, while adjusting for poverty, sex, race/ethnicity, education, family structure, social security, and food assistance., Results: Food insecurity rates were highest in late- (37.5%) and early- (36.0%) midlife, relative to younger (33.7%) and older (20.2%) age groups and, furthermore, age moderated the relationship between food insecurity and both risk factors (interaction p-values < .05, for both). The effects of poor health were stronger in midlife relative to younger and older ages. Unlike younger and older adults, however, adults in midlife showed high levels of food insecurity regardless of financial worry., Conclusions: Findings suggest that food insecurity in midlife may be more severe than previously thought. Greater efforts are needed to identify those at greatest risk and intervene early to slow premature aging., Competing Interests: The authors have declared that no competing interests exist.

The short isoform of human TIAM2 has been shown to promote proliferation and invasion in various cancer cells. However, the roles of TIAM2S in immune cells in relation to tumor development have not been investigated. To characterize the effects of TIAM2S, we generated TIAM2S-overexpressing mouse lines and found that aged TIAM2S-transgenic (TIAM2S-TG) developed significantly higher occurrence of lymphocytic infiltration and tumorigenesis in various organs, including colon. In addition, TIAM2S-TG is more sensitized to AOM-induced colon tumor development, suggesting a priming effect toward tumorigenesis. In the light of our recent findings that TIAM2S functions as a novel regulator of cellular serotonin level, we found that serotonin, in addition to Cox2, is a unique inflammation marker presented in the colonic lesion sites in the aged TG animals. Furthermore, our results demonstrated that ectopic TIAM2S altered immunity via the expansion of T lymphocytes; this was especially pronounced in CD8 + T cells in combination with CXCL13/BCA-1 pro-inflammatory chemokine in the serum of TIAM2S-TG mice. Consequently, T lymphocytes and B cells were recruited to the lesion sites and stimulated IL-23/IL17A expression to form the tertiary lymphoid organs. Collectively, our research suggests that TIAM2S provokes a pro-inflammatory immune microenvironment permissive to colorectal tumorigenesis through the serotonin-induced immunomodulatory effects.

Purpose: Patients receiving extracorporeal membrane oxygenation (ECMO) commonly develop acute kidney injury (AKI) and frequently require continuous renal replacement therapy (CRRT). The impact of different CRRT modalities on survival in patients receiving ECMO remains unclear., Materials and Methods: Using claims data from Taiwan's National Health Insurance Research Database, a total of 1077 patients who received ECMO and either continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis (CVVHD) for AKI were identified. Inverse probability of treatment weighting was applied using propensity scores to balance the baseline covariates of the two groups. The primary outcome was in-hospital morality., Results: We identified 1077 patients (mean age 57.9; 71.8% men). Postcardiotomy shock (49.2%) was the most frequently reported indication for ECMO. The CVVH group had a lower risk of in-hospital mortality (68.4% vs. 76.9%; odds ratio 0.65; 95% confidence interval [CI] 0.50-0.85) compared with the CVVHD group. The CVVH group also had a shorter mean ICU stay compared with the CVVHD group (mean difference -4.59 days, 95% CI -9.15 to -0.03 days)., Conclusion: Our results suggest that compared with CVVHD, CVVH may be associated with a lower risk of in-hospital mortality in patients with AKI who receive ECMO., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exists., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The mortality rate of patients on extracorporeal membrane oxygenation (ECMO), especially those patients that develop acute kidney injury (AKI) is high. Acute kidney disease (AKD) is a term used to describe the continuum from AKI to chronic kidney disease. However, the role of AKD in predicting the prognosis of patients on ECMO support is unclear., Methods: A total of 168 patients who received ECMO support and survived for more than 7 days at a single hospital from 2003 to 2008 were enrolled for this study and followed up for 10 years or till mortality. Kaplan-Meier analysis and Cox proportional hazards model were used to determine the prognostic factors associated with survival., Results: The median survival times of patients with stage 0, stage 1, stage 2 and stage 3 AKD were ≥ 10 years, 43.9 months, 1 month, and half a month, respectively. There were statistically significant differences in cumulative survival rate between patients with stage 3 AKD and those with stage 0, 1, and 2 AKD (Cox-Mantel log rank test, p<0.001, p<0.001, p = 0.023), and between patients with stage 0 AKD and those with stage 1 and 2 AKD (Cox-Mantel log rank test, p = 0.012, p<0.001). Cox regression analysis revealed that AKD stage (hazard ratio [HR]: 2.576, 95% confidential interval [CI]: 1.268-5.234, p = 0.009 for stage 1; HR: 2.349; 95% CI: 1.101-5.512, p = 0.029 for stage 2; HR: 5.252; 95% CI: 2.715-10.163, p<0.001 for stage 3) was significant independent predictor of survival., Conclusion: AKD stage is an independent predictor of survival in patients on ECMO support., Competing Interests: The authors have declared that no competing interests exist.

Cancer stem cells (CSCs), characterized by self-renewal and unlimited proliferation, lead to therapeutic resistance in lung cancer. In this study, we aimed to investigate the expressions of stem cell-related genes in lung adenocarcinoma (LUAD). The stemness index based on mRNA expression (mRNAsi) was utilized to analyze LUAD cases in the Cancer Genome Atlas (TCGA). First, mRNAsi was analyzed with differential expressions, survival analysis, clinical stages, and gender in LUADs. Then, the weighted gene co-expression network analysis was performed to discover modules of stemness and key genes. The interplay among the key genes was explored at the transcription and protein levels. The enrichment analysis was performed to annotate the function and pathways of the key genes. The expression levels of key genes were validated in a pan-cancer scale. The pathological stage associated gene expression level and survival probability were also validated. The Gene Expression Omnibus (GEO) database was additionally used for validation. The mRNAsi was significantly upregulated in cancer cases. In general, the mRNAsi score increases according to clinical stages and differs in gender significantly. Lower mRNAsi groups had a better overall survival in major LUADs, within five years. The distinguished modules and key genes were selected according to the correlations to the mRNAsi. Thirteen key genes (CCNB1, BUB1, BUB1B, CDC20, PLK1, TTK, CDC45, ESPL1, CCNA2, MCM6, ORC1, MCM2, and CHEK1) were enriched from the cell cycle Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, relating to cell proliferation Gene Ontology (GO) terms, as well. Eight of the thirteen genes have been reported to be associated with the CSC characteristics. However, all of them have been previously ignored in LUADs. Their expression increased according to the pathological stages of LUAD, and these genes were clearly upregulated in pan-cancers. In the GEO database, only the tumor necrosis factor receptor associated factor-interacting protein (TRAIP) from the blue module was matched with the stemness microarray data. These key genes were found to have strong correlations as a whole, and could be used as therapeutic targets in the treatment of LUAD, by inhibiting the stemness features.

Aims and Objectives: To classify hemodialysis patients into subgroups via cluster analysis according to the Somatic Symptoms Disturbance Index, Taiwanese Depression Scale, and Herth Hope Index scores. Patient demands in each cluster were also examined., Background: Overall patient demands among hemodialysis patients have been demonstrated in numerous reports; however, variables among subgroups have not been explored., Methods: Data were analyzed from a cross-sectional survey of 114 hemodialysis patients recruited from dialysis centers in Northern Taiwan. Hope, depression, and symptom disturbance were used as parameters for clustering because they have been shown to be important factors affecting patient demands. A two-step cluster analysis was performed to classify participants into clusters. Patient demands in each cluster were analyzed., Results: Among the 114 participants, there was a negative correlation between hope and depression as well as between hope and symptom disturbance; there was a positive correlation between depression and symptom disturbance. Two clusters were identified: Cluster 1 (n = 49) included patients with moderate levels of hope and symptom disturbance, and high levels of depression; and Cluster 2 (n = 65) included patients with low levels of depression and symptom disturbance and high levels of hope. Demographic profiles differed between the two clusters. Regarding patient demands, medical demand showed the highest average score; whereas, occupational demand exhibited the lowest average score. Psychological and occupational demands differed significantly between the two clusters. The two clusters were defined as subgroups: Cluster 1 was labeled "resting"; Cluster 2 was labeled "active"., Conclusions: Cluster analysis may further classify hemodialysis patients into distinct subgroups base on their specific patient demands. A better understanding of patient demands may help health professionals to provide a holistic individualized treatment to improve patients' outcomes., Competing Interests: The authors have declared that no competing interests exist.

Protein-bound uremic toxins (PBUTs) can cause noxious effects in patients suffering from renal failure as a result of inhibiting the transport of proteins and inducing their structural modification. They are difficult to remove through standard hemodialysis (HD) treatment. Herein, we report an organic bioelectronic HD device system for the effective removal of PBUTs through electrically triggered dissociation of protein-toxin complexes. To prepare this system, we employed electrospinning to fabricate electrically conductive quaternary composite nanofiber mats-comprising multiwalled carbon nanotubes (MWCNTs), poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS), poly(ethylene oxide) (PEO), and (3-glycidyloxypropyl)trimethoxysilane (GOPS)-on conventional polyethersulfone (PES) dialysis membranes. These composite nanofiber platforms exhibited (i) long-term water resistance (due to cross-linking among PSS, PEO, and GOPS), (ii) high adhesion strength on the PES membrane (due to GOPS functioning as an adhesion promoter), (iii) enhanced electrical properties [due to the MWCNTs and PEDOT:PSS promoting effective electrical stimulation (ES) operation in devices containing bioelectronic interfaces (BEI)], and (iv) good anticoagulant ability and negligible hemolysis of red blood cells. We employed this organic BEI electronic system as a novel single-membrane HD device to study the removal efficiency of four kinds of uremic toxins [ p -cresol (PC), indoxyl sulfate, and hippuric acid as PBUTs; creatinine as a non-PBUT] as well as the effects of ES on lowering the protein binding ratio. Our organic BEI devices provided a high rate of removal of PC with low protein loss after 4 h of a simulated dialysis process. It also functioned with low complement activation, low contact activation levels, and lower amounts of platelet adsorption, suggesting great suitability for use in developing next-generation bioelectronic medicines for HD.

Background/purpose: A reliable noninvasive prognostic factor of ANCA-associated vasculitis (AAV) is still lacking, but little research has focused on the value of MPO-ANCA titers in patients with active vasculitis. This study explored the prognostic significance of MPO-ANCA titer in active AAV patients., Methods: Ninety-seven inpatients diagnosed with MPO-ANCA associated vasculitis at Linkou Chang Gung Memorial hospital and Keelung Chang Gung Memorial hospital from January 2005 to December 2016 were enrolled. Serum ANCA titers and basic characteristics of these patients at diagnosis were collected completely Medical records since AAV diagnosis were reviewed to evaluate two years renal and patient outcome., Results: The patients were divided into the two groups according to the median ANCA titers, the more than four times of the normal cut-off value group (high titer group) and the less ANCA titer group (low titer group). The high titer group had significant poor initial renal function (eGFR 16.7 vs 40.7 mL/min/1.73 m 2 , P = 0.006), and significantly lower two-year renal survival (Log rank P < 0.001). Whereas patient survival (Log rank P = 0.894) was not different The Cox regression models revealed that baseline Birmingham Vasculitis Activity Score, eGFR and a 4-fold increase in ANCA titer were associated with the requirement of permanent dialysis. In the subgroup analysis, the ANCA titer was still an important risk factor for renal outcomes (P = 0.036) in patients with better initial renal function (eGFR≧15 mL/min)., Conclusion: This study demonstrated that higher MPO-ANCA titers at diagnosis was associated with poor initial renal function and 2-year renal outcomes., (Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Malnutrition is associated with adverse outcomes in patients with liver cirrhosis. Relevant data about nutrition risk in critically ill cirrhotic patients are lacking. The modified Nutrition Risk in Critically Ill (mNUTRIC) score is a novel nutrition risk assessment tool specific for intensive care unit (ICU) patients. This retrospective study was conducted to evaluate the prevalence and prognostic significance of nutrition risk in cirrhotic patients with acute gastroesophageal variceal bleeding (GEVB) using mNUTRIC scores computed on admission to the intensive care unit. The major outcome was 6-week mortality. One-hundred-and-thirty-one admissions in 120 patients were analyzed. Thirty-eight percent of cirrhotic patients with acute GEVB were categorized as being at high nutrition risk (a mNUTRIC score of ≥5). There was a significantly progressive increase in mortality associated with the mNUTRIC score (χ 2 for trend, p < 0.001). By using the area under a receiver operating characteristic (ROC) curve, the mNUTRIC demonstrated good discriminative power to predict 6-week mortality (AUROC 0.859). In multivariate analysis, the mNUTRIC score was an independent factor associated with 6-week mortality. In conclusion, the mNUTRIC score can serve as a tool to assess nutrition risk in cirrhotic patients with acute GEVB.

Background: Extracorporeal membrane oxygenation (ECMO) is often used in critical patients with severe myocardial failure. However, the mortality rate of patients on ECMO is often high. Recent studies have suggested that endothelial activation with subsequent vascular barrier breakdown is a critical pathogenic mechanism of organ damage and is related to the outcome of critical illness. This study aimed to determine whether endothelial biomarkers can be served as prognostic factors for the outcome of patients on ECMO., Methods: This prospective study enrolled 23 critically ill patients on veno-arterial ECMO in the intensive care units of a tertiary care hospital between March 2014 and February 2015. Serum samples were tested for thrombomodulin, angiopoietin (Ang)-1, Ang-2, and vascular endothelial growth factor (VEGF). Demographic, clinical, and laboratory data were also collected., Results: The overall mortality rate was 56.5%. The combination of Ang-2 at the time of ECMO support (day 0) and VEGF at day 2 had the ability to discriminate mortality (area under receiver operating characteristic curve [AUROC], 0.854; 95% confidence interval: 0.645-0.965)., Conclusions: In this study, we found that the combination of Ang-2 at day 0 and VEGF at day 2 was a modest model for mortality discrimination in this group of patients.

Despite supportive care with renal replacement therapy, acute kidney injury (AKI) remains linked with increased short and long-term mortality, not just because of renal failure but also because of accompanying remote organ dysfunction. Increasing evidence from animal studies suggests that numerous factors contribute both to the development of AKI and the impairment of various vital organs, including pro-inflammatory cytokine expression, leukocyte infiltration, vascular permeability changes, ion channel derangement, oxidative stress, and cell apoptosis. Human studies have reported that AKI with concomitant multi-organ dysfunction is associated with a high death rate. We propose that persistent organ dysfunction after AKI can be considered in relation to three proposed mechanisms (1) classical uremic stress and its associated sequelae (2) systemic inflammation as a consequence of kidney injury (3) treatment-related effects. Using this framework, we discuss the known pathways through which AKI can affect the function of a number of remote organs. We review the short- and long-term clinical impact of AKI on other organ systems and potential mechanisms through which AKI may affect remote organ systems. Further elucidating the effects of AKI on remote organ function may lead to new therapeutic strategies to improve outcomes after AKI., (Copyright © 2018. Published by Elsevier B.V.)

Purpose: The diagnosis of minimal change disease in adults relies mainly on renal biopsy, but this procedure is not without complications. Despite the advancements in technique of percutaneous renal biopsy, biopsy-related complications still occur. Bleeding is one of the major complications, which may lead to hemodynamic instability and, sometimes, even death. Thus, we developed a model to predict MCD for high-risk patients unsuitable for renal biopsy., Methods: We enrolled 142 patients with nephrotic syndrome who received renal biopsy between October 2007 and April 2011 at one tertiary medical center in this study. Demographic, clinical, and prebiopsy laboratory variables were retrospectively recorded and analyzed., Results: The overall prevalence of MCD was 26.8%. Age, hemoglobin levels, 24-hour urine protein, immunoglobulin (Ig) G, and IgE differed significantly between the MCD and non-MCD groups. Logistic regression analysis showed a significant increase in the risk of developing MCD as the number of Ig risk factors, namely, IgG < 450 mg/dl and IgE > 110 mg/dl, increased. Having both risk factors significantly increased the chances of receiving a diagnosis of MCD (by 31.84-fold, P =.007) compared with having neither. Combining the aforementioned clinical model and the 2 Ig risk factors was the best in predicting the diagnosis of MCD, with the area under a receiver-operating characteristic curve of 0.91., Conclusions: Combining clinical model and this 2 Ig risk factors provides physicians simple and valuable clinical markers to diagnose MCD.

(1) Background: Norepinephrine (NE) is the first-line vasoactive agent used in septic shock patients; however, the effect of norepinephrine on dialysis-required septic acute kidney injury (AKI-D) patients is uncertain. (2) Methods: To evaluate the impact of NE on 90-day mortality and renal recovery in septic AKI-D patients, we enrolled patients in intensive care units from 30 hospitals in Taiwan. (3) Results: 372 patients were enrolled and were divided into norepinephrine users and non-users. After adjustment by Inverse probability of treatment weighted (IPTW), there was no significant difference of baseline comorbidities between the two groups. NE users had significantly higher 90-day mortality rate and using NE is a strong predictor of 90-day mortality in the multivariate Cox regression (HR = 1.497, p = 0.027) after adjustment. The generalized additive model disclosed norepinephrine alone exerted a dose⁻dependent effect on 90-day mortality, while other vasoactive agents were not. (4) Conclusion: Using norepinephrine in septic AKI-D patients is associated with higher 90-day mortality and the effect is dose-dependent. Further study to explore the potential mechanism is needed.

Patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) have a high risk of mortality. Few studies have reported prognostic factors for patients receiving plasma exchange (PE) for liver support. We conducted a retrospective analysis using data of 55 patients with severe ACLF (n = 45) and ALF (n = 10) who received standard-volume PE (1-1.5 plasma volume) in the ICU. Hepatitis B virus infection accounts for the majority of ACLF (87%) and ALF (50%) patients. PE significantly improved the levels of total bilirubin, prothrombin time and liver enzymes (P<0.05). Thirteen ACLF patients (29%) and one ALF patient (10%) underwent liver transplantation. Two ALF patients (20%) recovered spontaneously without transplantation. The overall in-hospital survival rates for ACLF and ALF patients were 24% and 30%, and the transplant-free survival rates were 0% and 20%, respectively. For the 14 transplanted patients, the one-year survival rate was 86%. Multivariate analysis showed that pre-PE hemoglobin (P = 0.008), post-PE hemoglobin (P = 0.039), and post-PE CLIF-C ACLF scores (P = 0.061) were independent predictors of survival in ACLF. The post-PE CLIF-C ACLF scores ≥59 were a discriminator predicting the in-hospital mortality (area under the curve = 0.719, P = 0.030). Cumulative survival rates differed significantly between patients with CLIF-C ACLF scores ≤ 58 and those with CLIF-C ACLF scores ≥ 59 after PE (P< 0.05). The findings suggest that PE is mainly a bridge for liver transplantation and spontaneous recovery is exceptional even in patients treated with PE. A higher improvement in the post-PE CLIF-C ACLF score is associated with a superior in-hospital survival rate., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Anemia is a component of the pathological triangle in cardiorenal anemia syndrome and is a risk factor for mortality in acute respiratory distress syndrome. This study assessed the predictive value of anemia for outcomes in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) support. This retrospective study analyzed patients who received ECMO support at the cardiovascular surgery intensive care unit in the study institute between July 2003 and March 2012. Patient data, such as demographic information, etiologies of ECMO implementation, clinical parameters, and in-hospital and 6-month mortality rates, were statistically analyzed. The overall in-hospital mortality rate among the enrolled 295 patients was 55.6%. Multivariate logistical regression analysis indicated that age, albumin levels, sequential organ failure assessment (SOFA) score, and hemoglobin (Hb) level on ECMO day 1 exhibited independent prognostic significance for predicting in-hospital mortality rate. The SOFA score exhibited the highest areas under the receiver operating characteristic curve value (0.812 ± 0.025). The Hb level on ECMO day 1 exhibited satisfactory calibration and discriminatory power. The cumulative 6-month survival rates differed significantly between patients with Hb levels less than and more than 8.85 g/dL (30.6 vs. 54.0%, respectively, P < 0.001). This study indicated that old age, low albumin levels, low Hb levels, and higher SOFA scores on ECMO day 1 increased the risk of mortality. The Hb level is a readily measurable parameter and with good predictive power for critical patients on ECMO., (© 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Purpose: During medical school training, increased stress, depression, and anxiety are common. Certain personality traits, particularly harm avoidance (HA), may increase the risk of psycho-pathological disorders, insomnia, and migraine among medical students. This study evaluated the role HA may play on levels of stress, depression, anxiety, and insomnia among Taiwanese medical students starting their fifth and final year of medical school., Patients and Methods: A series of self-report questionnaires were used to measure the severity of anxiety, depression, and insomnia, as well as somatic symptoms, particularly migraine headache, among 143 Taiwanese fifth-year medical students (94 males and 49 females). Most had normal or mild levels of anxiety, depression, insomnia, and migraine., Results: HA personality trait was significantly associated with depression (all P ≤ 0.001) after adjusting for other factors. HA was not significantly associated with anxiety, insomnia, or migraine headache days., Conclusion: HA personality trait was significantly associated with depression among fifth-year medical students in Taiwan., Competing Interests: Disclosure The authors report no conflicts of interest in this work.