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The Taiwanese government launched a universal pay-for-performance (P4P) program in 2006 to promote multidisciplinary care for patients with stage 3b-5 chronic kidney disease (CKD). This study aimed to understand the enrollments, care processes, and outcomes of the P4P program between 2010 and 2018.We conducted a population-based study using the Taiwan National Health Insurance Research Data. We divided the incident dialysis population into joining and not joining P4P groups based on whether patients had joined the pre-ESRD program before dialysis or not. Trends in the medications prescribed, anemia correction, vascular access preparation before dialysis initiation, and cumulative survival rate were compared.The program included more than 100,000 patients with late-stage CKD. Enrollment increased by almost 100% from 2010 to 2018, with increases seen in those over 75 years old (127.5%), male (96.7%), and earlier CKD stages (≥35% stage 3b in 2018). Females were more likely to stay being enrolled. The joining P4P group was prescribed more appropriate medications, such as erythropoietin-stimulating agents and statins. However, a high number of patients were still prescribed metformin (≥40%) and non-steroidal anti-inflammatory drugs (≥20%). Compared to the not joining P4P group, the patients in the P4P group had better anemia management, dialysis preparation, and post-dialysis survival.The patients in the joining P4P program group were delivered more appropriate CKD care and were associated with better survival outcomes. Polices and action plans are needed to extend the coverage of and enrollment in the P4P program.

Human induced pluripotent stem cells (iPSCs), since their discovery in 2007, open a broad array of opportunities for research and potential therapeutic uses. The substantial progress in iPSC reprogramming, maintenance, differentiation, and characterization technologies since then has supported their applications from disease modeling and preclinical experimental platforms to the initiation of cell therapies. In this review, we started with a background introduction about stem cells and the discovery of iPSCs, examined the developing technologies in reprogramming and characterization, and provided the updated list of stem cell biobanks. We highlighted several important iPSC-based research including that on autosomal dominant kidney disease and SARS-CoV-2 kidney involvement and discussed challenges and future perspectives.

Uric acid (UA) is elevated in metabolic syndrome (MS) and diabetes (DM). UA is associated with central obesity and blood glucose and is proposed as a criterion of MS. Previous reports showed that UA could predict renal outcome in CKD. However, recent clinical trials did not demonstrate the benefits of urate-lowering agents (ULA) for renal outcome. Whether the prognostic value of UA for renal outcome is independent of MS or secondary to MS in CKD patients is unknown. Our study included 2500 CKD stage 1–4 Asian patients divided by UA tertiles and MS/DM. In linear regression, UA was associated with obesity, C-reactive protein, and renal function. In Cox regression, high UA was associated with worse renal outcome in non-MS/DM, but not in MS/DM: hazard ratio (95% confidence interval) of UA tertile 3 was 3.86 (1.87–7.97) in non-MS/DM and 1.00 (0.77–1.30) in MS/DM (p for interaction < 0.05). MS was associated with worse renal outcome, but redefined MS (including hyperuricemia as the 6th criteria) was not. In conclusion, hyperuricemia is associated with worse renal outcome in non-MS/DM and is not an independent component of MS in CKD stage 1–4 patients. Hyperuricemia secondary to MS could not predict renal outcome.

RIVER restoration is a popular technique to rehabilitate degraded river habitat. Given the nature of these types of engineering projects, using ecological indicators to monitor the restoration effectiveness has been a traditional approach. However, as this approach emphasizes the post-project performance, environmental impact attributed to a project’s construction phase has received little attention directly or indirectly. This study quantified the carbon footprint of ecological river restoration, using a project in California as a case study. A topographic diversity index (TDI) was developed as a functional unit of the river restoration project, indicating how a restoration project can increase the variation of habitat topography. The results show that river restoration can lead to greenhouse gas emissions ranging from 288 to 336 kg CO2 equivalent (kg CO2e) for every 1% of TDI improvement, or 9–14 kg CO2e per meter stream restored. This study identified that improving raw material acquisition plans and heavy-duty equipment rental decision can be feasible strategies leading to the reduction of carbon footprint.

Iron deficiency is prevalent in women and patients with chronic kidney disease (CKD). Iron deficiency is not only related to anemia but contributes to adverse consequences for the kidney as well. Whether iron status is associated with renal outcomes after considering sex and anemia in patients with CKD stage 1–4 is unclear. Thus, we investigated the association of iron or iron saturation with renal outcomes in a CKD cohort. During a follow-up of 8.2 years, 781 (31.2%) patients met the composite renal outcome of renal replacement therapy and a 50% decline in renal function. In linear regression, iron was associated with sex, hemoglobin (Hb), and nutritional markers. In a fully adjusted Cox regression model, the male patients with normal iron had a significantly decreased risk of renal outcomes (hazard ratio (HR) 0.718; 95% confidence interval (CI) 0.579 to 0.889), but the female patients did not exhibit this association. The non-anemic patients (Hb ≥ 11 g/dL) had a decreased risk of renal outcomes (HR 0.715; 95% CI 0.568 to 0.898), but the anemic patients did not. In the sensitivity analysis, transferrin saturation (TSAT) showed similar results. When comparing iron and TSAT, both indicators showed similar prognostic values. In conclusion, iron deficiency, indicated by either iron or iron saturation, was associated with poor renal outcomes in the male or non-anemic patients with CKD stage 1–4.

Background Despite widespread use, there is no trial evidence to inform β-blocker’s (BB) relative safety and efficacy among patients undergoing hemodialysis (HD). We herein compare health outcomes associated with carvedilol or bisoprolol use, the most commonly prescribed BBs in these patients. Methods We created a cohort study of 9305 HD patients who initiated bisoprolol and 11 171 HD patients who initiated carvedilol treatment between 2004 and 2011. We compared the risk of all-cause mortality and major adverse cardiovascular events (MACEs) between carvedilol and bisoprolol users during a 2-year follow-up. Results Bisoprolol initiators were younger, had shorter dialysis vintage, were women, had common comorbidities of hypertension and hyperlipidemia and were receiving statins and antiplatelets, but they had less heart failure and digoxin prescriptions than carvedilol initiators. During our observations, 1555 deaths and 5167 MACEs were recorded. In the multivariable-adjusted Cox model, bisoprolol initiation was associated with a lower all-cause mortality {hazard ratio [HR] 0.66 [95% confidence interval (CI) 0.60–0.73]} compared with carvedilol initiation. After accounting for the competing risk of death, bisoprolol use (versus carvedilol) was associated with a lower risk of MACEs [HR 0.85 (95% CI 0.80–0.91)] and attributed to a lower risk of heart failure [HR 0.83 (95% CI 0.77–0.91)] and ischemic stroke [HR 0.84 (95% CI 0.72–0.97)], but not to differences in the risk of acute myocardial infarction [HR 1.03 (95% CI 0.93–1.15)]. Results were confirmed in propensity score matching analyses, stratified analyses and analyses that considered prescribed dosages or censored patients discontinuing or switching BBs. Conclusions Relative to carvedilol, bisoprolol initiation by HD patients was associated with a lower 2-year risk of death and MACEs, mainly attributed to lower heart failure and ischemic stroke risk.

The association between body composition and gut microbiota in type 2 diabetes mellitus (DM) remains unknown. To elucidate the correlation of body composition and gut microbiota, we conducted a clinical study to enroll 179 patients with type 2 DM. Body composition of lean tissue index (LTI) and fat tissue index was measured by Body Composition Monitor. Eight pairs of 16S rRNA gene primers specific to Firmicutes, Bacteroidetes, the Clostridium leptum group, Bacteroides, Bifidobacterium, Akkermansia muciniphila, Escherichia coli, and Faecalibacterium prausnitzii were used to measure their abundance by quantitative polymerase chain reaction. The results showed that type 2 DM with higher abundance of phylum Firmicutes and a higher ratio of phyla Firmicutes to Bacteroidetes (phyla F/B ratio) had higher LTI. This significant correlation between phyla F/B ratio and LTI was especially evident in type 2 DM with high body mass index, and independent of glycemic control or dipeptidyl peptidase-4 inhibitor usage. In conclusion, our study demonstrated the positive association of LTI with the abundance of phylum Firmicutes and the phyla F/B ratio in type 2 DM.

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population.Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan.Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10).Conclusions: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

Hypertension is a major risk factor for stroke, atherosclerosis, and other cardiovascular diseases, and obesity is a major risk factor for hypertension. The aim of this longitudinal study was to investigate sex differences in the correlations among obesity-related indices and incident hypertension in a large Taiwanese cohort. We included 21,466 enrollees in the Taiwan Biobank and followed them for 4 years. Of the 21,466 patients enrolled in this study, 6899 (mean age, 49.6 ± 10.9 years) were male and 14,567 (mean age, 49.7 ± 10.0 years) were female. Data on visceral adiposity index (VAI), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), lipid accumulation product (LAP), conicity index (CI), body roundness index (BRI), body mass index (BMI), body adiposity index (BAI), and abdominal volume index (AVI) were collected and analyzed. The results showed that all of the studied obesity-related indices were significantly associated with incident hypertension. Among them, WHtR was the strongest predictor of hypertension in both sexes. In addition, interactions between VAI, LAP, CI, BMI, and AVI with sex on incident hypertension were also statistically significant. CI and AVI were more strongly associated with hypertension in the men than in the women, while VAI, LAP, and BMI were more strongly associated with hypertension in the women. In conclusion, the studied obesity-related indices were found to be predictors of incident hypertension, and there were differences in the associations between the male and female participants. Our findings may imply that reducing body weight may be associated with a lower risk of developing hypertension.

BackgroundFracture Risk Assessment Tool (FRAX) and bone turnover markers (BTMs) predict fractures in the general population. However, the role of FRAX and BTMs in predicting mortality remains uncertain in hemodialysis (HD) patients.MethodsOne hundred and sixty-four HD patients stratified by low or high risk of 10-year fracture probability using FRAX. High risk of fracture was defined as 10-year probability of hip fracture ≥3% or major osteoporotic fracture ≥20%. The association of high risk of fracture and BTMs with all-cause mortality and cardiovascular (CV) mortality were evaluated using multivariate-adjusted Cox regression analysis.ResultsEighty-five (51.8%) patients were classified as high risk of fracture based on FRAX among 164 HD patients. During a mean follow-up period of 3.5 ± 1.0 years, there were 39 all-cause deaths and 23 CV deaths. In multivariate-adjusted Cox regression, high risk of fracture based on FRAX was independently associated with all-cause mortality [hazard ratio (HR): 2.493, 95% confidence interval (CI): 1.026–6.056, p = 0.044) but not with CV mortality (HR: 2.129, 95% CI: 0.677–6.700, p = 0.196). There were no associations between BTMs and mortality risk. Furthermore, lower geriatric nutritional risk index (GNRI) was significantly associated with increased CV mortality (HR: 0.888, 95% CI: 0.802–0.983, p = 0.022) after adjusting by confounding variables.ConclusionHigh risk of fracture using FRAX was an independent predictor of all-cause mortality in patients undergoing HD. FRAX, rather than BTMs, has an important role of prognostic significance in HD patients.

There seems to be a scarcity in literature investigating day-to-day warm-up (WU) variations. We investigated day-to-day variation of psychophysiological responses during Fédération Internationale de Football Association (FIFA) 11+ and dynamic warm-up (DWU) exercises. Twenty-one male collegiate soccer players were randomly assigned to the FIFA 11+ (n = 10) or DWU group (n = 11). Each group performed the assigned WU protocol on three different occasions with a 48-h interval in between. The inter-day variation of the heart rate (HR), time distribution of HR zones, heart rate variability (HRV), estimated energy expenditure (EE), blood lactate (BL) concentration, and the Borg rating of perceived exertion (RPE) were recorded. A two-way repeated measures of analysis of variance was used to compare the differences in chosen variables [group (2) × day (3)]. The coefficient of variation was used to determine the dispersion of the variables over the sessions. The interclass correlation coefficient (ICC) with a two-way random model and a single measure (ICC2,1) was used to determine inter-day reliability. There were no significant differences in time spent at particular HR zones and EE in both groups. The FIFA 11+ exercises showed high reliability of exercise duration, average HR (HRaverage), minimal HR (HRmin), peak HR (HRpeak), and post-exercise RPE. In the DWU group, high reliability was found only in HRaverage, HRpeak, and post-exercise RPE. The FIFA 11+ exercises showed similar EE, exercise HR patterns, BL, and RPE compared to the DWU. The FIFA 11+ program is an intense WU protocol with a characteristically low variation of day-to-day exercise HR and RPE responses.

The incidence of hepatic steatosis is increasing globally, and it is important to identify those at risk to prevent comorbidities. Complete blood count is a simple, convenient, and inexpensive laboratory examination which can be used to obtain white blood cell (WBC) and platelet counts. The aims of this study were to investigate the relationships between WBC and platelet counts with hepatic steatosis, and whether WBC and platelet counts were associated with the severity of hepatic steatosis. We enrolled 1969 participants residing in southern Taiwan who took part in a health survey from June 2016 to September 2018 in this cross-sectional study. None of the participants were heavy alcohol users or had a history of hepatitis B or C. We collected laboratory data, and the severity of hepatic steatosis was determined by abdominal ultrasound. The overall prevalence rate of hepatic steatosis was 42.0%. There were significant trends of stepwise increases in WBC count (p < 0.001) corresponding to the severity of hepatic steatosis. After multivariable linear regression analysis, hepatic steatosis was significantly associated with high WBC count (coefficient β, 0.209; 95% confidence interval (CI), 0.055 to 0.364; p = 0.008) and high platelet count (coefficient β, 12.213; 95% CI, 6.092 to 18.334; p < 0.001); also, higher WBC counts corresponded with the severity of hepatic steatosis.

Short-chain fatty acids (SCFAs) are small molecules ubiquitous in nature. In mammalian guts, SCFAs are mostly produced by anaerobic intestinal microbiota through the fermentation of dietary fiber. Levels of microbe-derived SCFAs are closely relevant to human health status and indicative to gut microbiota dysbiosis. However, the quantification of SCFA using conventional chromatographic approaches is often time consuming, thus limiting high-throughput screening tests. Herein, we established a novel method to quantify SCFAs by coupling amidation derivatization of SCFAs with paper-loaded direct analysis in real time mass spectrometry (pDART-MS). Remarkably, SCFAs of a biological sample were quantitatively determined within a minute using the pDART-MS platform, which showed a limit of detection at the μM level. This platform was applied to quantify SCFAs in various biological samples, including feces from stressed rats, sera of patients with kidney disease, and fermentation products of metabolically engineered cyanobacteria. Significant differences in SCFA levels between different groups of biological practices were promptly revealed and evaluated. As there is a burgeoning demand for the analysis of SCFAs due to an increasing academic interest of gut microbiota and its metabolism, this newly developed platform will be of great potential in biological and clinical sciences as well as in industrial quality control.

Background. Peripheral neuropathy is a common neurological complication in uremic patients, and quantitative sensory testing (QST) is effective for diagnosis of small fiber neuropathy. Malnutrition and arterial stiffness are prevalent in patients undergoing hemodialysis (HD). The associations of small fiber neuropathy with nutritional status and arterial stiffness remain uncertain in maintenance HD patients. Methods. A total of 152 HD patients were included. Geriatric nutritional risk index (GNRI), an indicator of nutritional status, was calculated by serum albumin and actual and ideal body weight. Arterial stiffness was defined as brachial-ankle pulse wave velocity baPWV>1400 cm/s. Small fiber neuropathy was assessed by an abnormal QST threshold of cold and warm sensation in patients’ hands or feet. Multivariate forward logistic regression analysis was performed to examine the associations among abnormal QST threshold, GNRI, and arterial stiffness. Results. baPWV and prevalence of abnormal QST threshold were significantly higher in diabetic patients. Multivariate logistic analyses revealed that older age (OR, 1.081; 95% CI, 1.026–1.139, p=0.003) and male gender (OR, 4.450; 95% CI, 1.250–15.836, p=0.021) were associated with abnormal warm threshold of hands. Furthermore, diabetes (OR, 3.966; 95% CI, 1.351–11.819, p=0.012) and lower GNRI (per 1 unit increase, OR, 0.935, 95% CI, 0.887–0.985, p=0.012) were associated with abnormal cold threshold of feet. Arterial stiffness (OR, 5.479, 95% CI, 1.132–22.870, p=0.020) and higher calcium-phosphorus product (OR, 1.071, 95% CI, 1.013–1.132, p=0.015) were associated with abnormal warm threshold of feet. Conclusions. Lower GNRI and arterial stiffness were significantly associated with small fiber neuropathy in patients undergoing HD. Malnutrition risk and vascular factors might play important roles in small fiber neuropathy among patients undergoing HD.

Background: Many elderly people in Taiwan move to institutional care due to disability or insufficient family resources. This study aimed to understand the place identity and life adaptation of institutional residents and their influencing factors, and to explore the correlation between these two. Methods: This study adopted a cross-sectional survey method. A total of 120 cases were collected with structured questionnaires, and SPSS 22.0 software package was used for statistical analysis. Results: The place identity was the highest in the sense of belonging, while the sense of participation was the worst; adaptation to life was the best in terms of care management, and the worst in terms of adaptation to life and assistive devices. The length of stay in the institution, daily activities, and the number of chronic diseases were significantly different from place identity, and the number of chronic diseases was significantly different from life adaptation. Conclusions: The results of this study can be used as a reference for institutions to improve the quality of care. It is suggested that institutions can organize more activities to promote interaction and participation among residents, to strengthen their local identity and life adaptation.

Denosumab is approved for osteoporosis treatment in subjects with and without chronic kidney disease (CKD). Confirmation is required for its safety, treatment adherence, renal function effect, and mortality in patients with CKD. A retrospective cohort study was conducted to compare new users of denosumab in terms of their two-year drug adherence in all participants (overall cohort) and CKD participants (CKD subcohort), which was defined as baseline estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated using the 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. We defined high adherence (HA) users as receiving three or four doses and low adherence (LA) users as receiving one or two doses. All-cause mortality was analyzed using Kaplan–Meier curves and Cox regression models. In total, there were 1142 subjects in the overall cohort and 500 subjects in the CKD subcohort. HA users had better renal function status at baseline than LD users in the overall cohort. A decline in renal function was only observed among LD users in the overall cohort. In the CKD subcohort, no baseline renal function difference or renal function decline was demonstrated. The all-cause mortality rate of HA users was lower than LA users in both the overall cohort and CKD. A randomized control trial is warranted to target this unique population to confirm our observations.

Exercise and sport practitioners frequently utilize rating of perceived exertion (RPE) to evaluate the players’ psychophysiological strains during training sessions. The subjective rating of physical exertion level during sports training has been shown to have a reciprocal relationship with wellness status during periodic training or competitive seasons. However, the relationship between subjective physical exertions and wellness status during short-term overseas training camps (OTCs) has not been extensively investigated. This study aimed to examine the perceived responses of physical exertions [session-RPE (sRPE), training monotony, and training strain] and wellness status (fatigue, sleep, delayed onset muscle soreness, stress, and mood) measures in elite young adult futsal players from four separate OTCs with different training tasks. Twenty-seven U-20 male national team futsal players voluntarily participated in this study. The players recruited for OTCs were based on their performance during domestic training camps and the tactical demand of the team. The task of each OTCs was defined as: 1) 1st OTC = game-based camp (n = 14); 2) 2nd and 3rd OTC = training-based camp (n = 20 and n = 17, respectively); and 3) 4th OTC = pre-tournament camp (n = 14). The OTCs consisted of 11 training sessions (18.9 hours) and 16 friendly matches (23.8 hours). During daily training sessions and friendly matches, sRPE was used to quantify training load (TL). Additionally, a five-elements general wellness questionnaire was used to evaluate daily wellness status in the morning. The results demonstrated that the mean and sum sRPE in the game-based OTCs were significantly lower compared to the mean sRPE [p < 0.01, effect size (ES) = -4.8; p < 0.01, ES = -2.9] and sum sRPE in the training-based OTCs (p < 0.01, ES = -3.6; p < 0.01, ES = -3.1). The mean (p = 0.01; ES = -2.0) and sum sRPE (p < 0.01; ES = -3.4) in the game-based OTC were also lower than that in the pre-tournament OTC. Conversely, the wellness scores in the game-based OTC were higher compared to the training-based (p = 0.01; ES = 1.8) and the pre-tournament OTCs (p < 0.01; ES = 1.6). There was a negative relationship between mean and sum sRPE and all wellness scores (mean sRPE = r = -0.441 ~ -0.575, p < 0.001; sum sRPE = r = -0.41 ~ -0.559, p < 0.001). Our findings suggested that responses to training sessions, derived from mean and sum sRPE and wellness scores, are dependent upon the task-specific nature of OTCs among elite futsal players. Utilization of mean and sum sRPE and wellness measures to monitor the psychophysiological health during short-term OTCs is recommended.

A high ultrafiltration rate (UFR) is associated with increased mortality in hemodialysis patients. However, whether a high UFR itself or heart failure with fluid overload followed by a high UFR causes mortality remains unknown. In this study, 2615 incident hemodialysis patients were categorized according to their initial cardiothoracic ratios (CTRs) to assess whether UFR was associated with mortality in patients with high or low CTRs. In total, 1317 patients (50.4%) were women and 1261 (48.2%) were diabetic. During 2246 (1087–3596) days of follow-up, 1247 (47.7%) cases of all-cause mortality were noted. UFR quintiles 4 and 5 were associated with higher risks of all-cause mortality than UFR quintile 2 in fully adjusted Cox regression analysis. As the UFR increased by 1 mL/kg/h, the risk of all-cause mortality increased 1.6%. Subgroup analysis revealed that in UFR quintile 5, hazard ratios (HRs) for all-cause mortality were 1.91, 1.48, 1.22, and 1.10 for CTRs of >55%, 50–55%, 45–50%, and

Autosomal Dominant polycystic kidney disease (ADPKD) is the most common inherited adult kidney disease. Although ADPKD is primarily caused by PKD1 and PKD2, the identification of several novel causative genes in recent years has revealed more complex genetic heterogeneity than previously thought. To study the disease-causing mutations of ADPKD, a total of 920 families were collected and their diagnoses were established via clinical and image studies by Taiwan PKD Consortium investigators. Amplicon-based library preparation with next-generation sequencing, variant calling, and bioinformatic analysis was used to identify disease-causing mutations in the cohort. Microsatellite analysis along with genotyping and haplotype analysis was performed in the PKD2 p.Arg803* family members. The age of mutation was calculated to estimate the time at which the mutation occurred or the founder arrived in Taiwan. Disease-causing mutations were identified in 634 families (68.9%) by detection of 364 PKD1, 239 PKD2, 18 PKHD1, 7 GANAB, and 6 ALG8 pathogenic variants. 162 families (17.6%) had likely causative but non-diagnostic variants of unknown significance (VUS). A single PKD2 p.Arg803* mutation was found in 17.8% (164/920) of the cohort in Taiwan. Microsatellite and array analysis showed that 80% of the PKD2 p.Arg803* families shared the same haplotype in a 250 kb region, indicating those families may originate from a common ancestor 300 years ago. Our findings provide a mutation landscape as well as evidence that a founder effect exists and has contributed to a major percentage of the ADPKD population in Taiwan.

Previous studies have reported inconsistent results regarding the associations between metabolic syndrome (MetS) and obesity-related indices and bone mineral density (BMD). However, no previous studies have reported these associations among hemodialysis (HD) patients. The aims of this study were to investigate associations between MetS and its components and BMD T-score in HD patients and also between obesity-related indices and BMD T-score in HD patients with and without MetS. MetS was defined according to the Adult Treatment Panel III for Asians, and BMD T-score was calculated using dual-energy X-ray absorptiometry. Eight obesity-related indices were evaluated, including lipid accumulation product (LAP), visceral adiposity index (VAI), body adiposity index, conicity index (CI), body roundness index (BRI), abdominal volume index (AVI), waist-to-height ratio (WHtR), waist–hip ratio, and body mass index (BMI). One hundred and sixty-four patients undergoing HD were enrolled, and the prevalence of MetS was 61.6%. MetS was significantly associated with high lumbar spine and total hip T-scores. Regarding the MetS components, abdominal obesity and low HDL-C were significantly associated with high lumbar spine, femoral neck, and total hip T-scores, hypertriglyceridemia was significantly associated with high lumbar spine and total hip T-scores, hyperglycemia was significantly associated with a high lumbar spine T-score, whereas high blood pressure was not associated with T-score at any site. In the patients with MetS, BMI, WHtR, AVI, and BRI were significantly associated with T-score at all sites, and high CI, VAI, and LAP were also related to a high lumbar T-score. However, these indices were not associated with T-score at any site in patients without MetS. This study demonstrated positive associations between MetS and its five components and BMD T-score among HD patients. MetS, abdominal obesity, hypertriglyceridemia, and low HDL-cholesterol were associated with low risk of osteoporosis among the HD patients. Furthermore, we found that some obesity-related indices were associated with BMD T-score among HD patients with MetS but not in those without MetS. Our study highlights the importance of BMI, WHtR, AVI, and BRI in predicting the risk of osteoporosis among HD patients with MetS. In clinical practice, they can be easily calculated through simple anthropometric measurements and routine laboratory examinations and be used to quickly and conveniently assess the risk of osteoporosis among HD patients.

The factors associated with the timely creation of distal vascular access for hemodialysis initiation are unclear. We aimed to explore the association between the slope of estimated glomerular filtration rate (eGFR) and the successful usage of vascular access upon hemodialysis initiation. This single center retrospective cohort study enrolled chronic kidney disease patients who undertook a multidisciplinary care program from 2003 to 2016. Using eGFR slope as predictor, we evaluated the vascular access created timely upon hemodialysis initiation. Among the 987 patients, vascular access was created at a median eGFR of 5.8 min/ml/1.73 m2, with a median duration of 3.1 months before hemodialysis. The proportions of vascular access created timely, created not timely (vascular access immature), and not created were 68.5%, 8.8%, and 22.7%, respectively. There was a significant negative association of eGFR upon vascular access creation with eGFR slope (r = − 0.182, P 2/year) had the lowest percentage of vascular access created timely. In the multivariable logistic regression analysis, only higher eGFR upon vascular access creation (P = 0.001) and eGFR slope (P = 0.009) were significantly associated with vascular access created timely. The adjusted odds ratios of each quartile of eGFR slopes for vascular access created timely were 0.46 (95% confidence interval 0.27–0.86), 1.30 (0.62, 2.72), 1.00 (reference), and 0.95 (0.48–1.87), respectively. eGFR slope is associated with the timely creation of vascular access for the initiation of hemodialysis in a reverse-J-shaped pattern and may help determine the time of vascular access creation.

INTRODUCTION: Serum creatinine is crucial in glomerular filtration rate (GFR) estimation. Various methods of measuring GFR have been developed, which vary in their ability to estimate the prevalence of chronic kidney disease (CKD) and predict consequences associated with CKD. The use of different laboratory devices also results in uncertainty in estimated GFR (eGFR). The purpose of our study was to discuss the effect of differences in laboratory devices on eGFR when performing serum creatinine measurements. METHODS: 163 participants aged 51.22 ± 18.66 years were enrolled during a community health screening programme conducted on 18 June 2011. Samples were sent to four different hospitals using four different devices to check serum creatinine by the Jaffe and enzymatic creatinine methods. RESULTS: Using Roche Cobas Integra 400, Beckman LX20, Hitachi 7180 and Toshiba TBA – c8000, the proportion of the population with eGFR < 60 mL/min/1.73 m(2) was 11.04%, 6.75%, 20.25% and 20.86%, respectively. Moreover, 3.68% of the participants had eGFR < 60 mL/min/1.73 m(2) in the laboratory when Roche Cobas Integra 400 was used with the enzymatic creatinine method and compensated Jaffe method. CONCLUSION: Although standardisation of serum creatinine measurement has been achieved by using isotope dilution mass spectrometry, differences in measurement devices still cause substantial bias in the overall results. This affects the application of GFR in the estimation of CKD progression and outcomes associated with CKD.

BACKGROUND AND OBJECTIVES: CKD is a global public health problem. Some cross-sectional studies have associated environmental melamine exposure with kidney diseases, but evidence is limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted this prospective cohort study to enroll patients with eGFR≥30 ml/min per 1.73 m(2) in 2006–2010. Urinary corrected melamine levels (ratio of urinary melamine to urinary creatinine) were measured by liquid chromatography/tandem mass spectrometry at enrollment. Kidney outcomes included doubling of serum creatinine levels, eGFR decline >3 ml/min per 1.73 m(2) per year, and 30% decline in eGFR in the first 2 years. Subjects were followed until targeted kidney outcomes, cancer, death, last contact, or the end of observation in December 2016. RESULTS: In a total of 293 subjects, the median urinary corrected melamine level was 0.97 (interquartile range, 0.43–2.08) μg/mmol. Over a median follow-up period of 7.0 years, serum creatinine levels doubled in 80 subjects (27%). Subjects in the highest tertile of urinary melamine level 12.70 μg/mmol) had a 2.30 (95% confidence interval, 1.25 to 4.23; P3 ml/min per 1.73 m(2) per year and 30% decline in eGFR in the first 2 years. CONCLUSIONS: Urinary melamine level is significantly associated with kidney function deterioration in patients with early-stage CKD.

As an important tool to promote the technical standards for enterprises, a patent alliance can reduce transaction costs and lawsuit disputes as well as accelerate the promotion and application of proprietary technologies. Moreover, it can enlarge the installed base and influence consumers’ expectations by exploiting the network effects of technical standards. As a result, it can be one of the most effective paths to resolve the problem of patent thicket and promote innovation. Based on several theories with respect to the network effects, this study analyzed the connotation and composition of network effects for technical standards and constructed a concept model that can influence innovations using a patent alliance. A questionnaire investigation was conducted, and an analysis was performed using the structural equation to examine the factors affecting the innovation of patent tools as well as their acting paths. The main research conclusions of this study are as follows: (1) patent alliance is a double-edged sword for technical innovation. The factors related to the patent alliance and network effect, such as the installation-foundation effect, consumer expectation, and positive feedback effect, promote innovation. However, the lock-in effect in the network effect hinders the innovation. (2) Identification of intellectual property and partners is the key factor that influences patent alliance innovation. (3) Standardization strategies and the government play the least role among all innovation factors influencing patent alliance.

Patients receiving hemodialysis (HD) have a higher risk of cognitive impairment and dementia than the general population. The accumulation of uremic toxins in the brain causes uremic encephalopathy, however, limited data exists to elucidate the effect of protein-bound uremic toxins on cognitive function. Here we investigate the effect of indole-3 acetic acid (IAA) and hippuric acid (HA), two different protein-bound uremic toxins from amino acid derivatives, on cognitive function by Silico and in a clinical study. Prevalent HD patients were enrolled in two independent hospitals. Serum IAA and HA were measured using mass spectrometry. Cognitive performance was measured using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Cognitive Abilities Screening Instrument (CASI) by trained psychologists. Using silico data to predict the effect of blood-brain barrier penetration was performed. The silico data demonstrated that IAA and HA had positive blood-brain barrier penetration ability. Amongst the 230 HD patients, serum IAA was associated with poor MMSE score (β= -0.90, 95% CI -1.61 to -0.19) and poor CASI score (β= -3.29, 95% CI -5.69 to -0.88) in stepwise multiple linear regression analysis. In logistic regression model, Serum IAA was also associated with cognitive impairment based on MMSE definition (OR, 1.96, 95% CI 1.10, 3.5) and CASI definition (OR, 2.09, 95% CI 1.21, 3.61). There was no correlation between Serum HA levels and cognitive function status. In conclusion, IAA, not HA, was associated with cognitive impairment in HD patients. Further large scale and prospective studies are needed to confirm our findings.

Taiwan implemented national pay-for-performance programs for chronic kidney disease (CKD) care in 2006 and 2011; however, it is unknown whether this affected trends in maintenance dialysis. This study assessed the temporal trends in the incidence, prevalence, and mortality of individuals treated with maintenance dialysis from 2002-2016 in Taiwan.Follow-up study using Taiwan Renal Disease System Databases.Participants who received dialysis for ≥90 days.Age, sex, and calendar year.Incidence, prevalence of maintenance dialysis, or death, ascertained using the National Death Registry database.The estimated annual percentage change was assessed by a generalized linear model, and the association of the programs with changes in the incidence of maintenance dialysis was evaluated using an age-period-cohort model.A total of 144,258 incident cases with a follow-up of 346 million person-years were analyzed during the observed periods. The estimated annual percentage change of the expected crude incidence rate was slightly reduced by 0.41% (95% CI, -1.06 to 0.24) and was more obvious in women and patients aged greater than 70 years; whereas, it was significantly increased in those aged greater than 75 years. After disentangling age and cohort effects, the implementation of the care programs was associated with an overall net drift of -1.09% (95% CI, -1.65 to -0.52) per year and a significant linear reduction in the period rate ratio from 1.06 (95% CI, 1.02-1.09) in the years 2002-2006 to 0.95 (95% CI, 0.92-0.98) in 2012-2016, using years 2007-2011 as reference.The findings of the study may have limited inferences to other countries with different health care systems.The implementation of universal CKD care programs in Taiwan has significantly reduced the long-term trends in the incidence of maintenance dialysis; hence, devoting governmental resources to CKD care and prevention is advocated.

This work presents a novel handheld mastitis detection device for detecting mastitis in dairy cattle, as well as a cattle management information system for managing cattle health information. The management information system comprises of three major subsystems—a mastitis detection device, an information display device, and a cloud database. The mastitis detection device detects and evaluates the degree of mastitis immediately before milking operations are carried out. The information display device shows the health information of the dairy cattle obtained from a cloud database and the database manages the milk production of a dairy farm. The combination of these two devices helps the dairy farmer to verify the mastitis of cattle effectively and find its health information rapidly.

Background and Aims Patients with end-stage kidney disease (ESKD) are characterized by altered gut microbiota, impaired intestinal barrier function, and experienced gut microbiota-derived metabolites related to systemic complications. However, limited studies evaluated the microbial diversity and function in ESKD patients previously. Method Compared to age- and gender-matched subjects without kidney disease, 82 ESKD patients in the discovery cohort and 58 ESKD patients in the validation cohort were investigated for the microbial richness, biodiversity, gut dysbiosis, microbial composition differences, and the functional changes by gut metabolic module analysis. Bacterial derived free form protein-bound uremic toxins were analyzed by mass spectrometry and their association with microbial richness in ESKD patients was determined. Results Compared to controls, an increased α-diversity and distinct β-diversity were found in ESKD (Figure). The increase in α-diversity was correlated with protein-bound uremic toxins, particularly hippuric acid. A higher microbial dysbiosis index (MDI) was found in ESKD patients with the following enriched genera: Facealibacterium, Ruminococcus, Fusobacterium, Dorea, Anaerovorax, Sarcina, Akkermansia, Streptococcus, and Dysgonomonas. MDI at the genus level successfully differentiated between ESKD and controls in the discovery cohort (area under the curve [AUC] of 81.9%) and the validation cohort (AUC of 83.2%). Regarding functional enrichment analysis with gut metabolic modules, ESKD subjects presented with gut microbial function of increased saccharide and amino acid metabolism compared with matched controls. Conclusion An enriched but dysbiotic gut microbiota was presented in ESKD patients, in which the bacteria that were present increase amino acid metabolism linked to the production of protein-bound uremic toxins.

Objective: Harmonizing formulas are associated with beneficial renal outcomes in chronic kidney disease (CKD), but the therapeutic mechanisms are unclear. The study aims to explore the associations of intentions and independent factors with harmonizing formulas prescriptions for patients with CKD.Methods: We conducted a population-based cross-sectional study to explore factors associated with harmonizing formulas prescription. Patients who had been prescribed harmonizing formulas after CKD diagnosis was defined as the using harmonizing formulas group. Disease diagnoses when having harmonizing formula prescriptions and patient characteristics related to these prescriptions were collected.Results: In total, 24,971 patients were enrolled in this analysis, and 5,237 (21%) patients were prescribed harmonizing formulas after CKD diagnosis. The three most frequent systematic diseases and related health problems for which harmonizing formula prescriptions were issued in CKD were symptoms, signs, and ill-defined conditions (24.5%), diseases of the digestive system (20.67%), and diseases of the musculoskeletal system (12.9%). Higher likelihoods of harmonizing formula prescriptions were associated with young age (adjusted odds ratio: 0.98, 95% confidence interval: 0.97–0.98), female sex (1.79, 1.68–1.91), no diabetes (1.20, 1.06–1.36), no hypertension (1.38, 1.27–1.50), no cerebrovascular disease (1.34, 1.14–1.56), less disease severity (0.85, 0.83–0.88), using nonsteroidal anti-inflammatory drugs (NSAIDs) (1.65, 1.54–1.78), and using analgesic drugs other than NSAIDs (1.47, 1.35–1.59).Conclusion: Harmonizing formulas are commonly used for treating symptoms of the digestive and musculoskeletal systems in CKD cases. Further research on harmonizing formula effectiveness with regard to particular characteristics of CKD patients is warranted.

Low transferrin saturation (TSAT), calculated by serum iron divided by total iron-binding capacity (TIBC), indicates iron deficiency. Because malnutrition and inflammation are associated with low TIBC in chronic kidney disease (CKD), TSAT might not reflect iron status or risk for anemia. We examined whether low serum iron was a risk factor for anemia in CKD patients with normal TSAT. Thus we compare the risk for anemia in 2500 CKD stage 1–4 patients divided by TSAT (cutoff: 20%) and serum iron (cutoff: 70 μg/dL in men, 60 μg/dL in women). Our results confirmed low TIBC (

Environmental melamine exposure has been associated with deteriorating kidney function in early-stage chronic kidney disease patients. In this study, a benchmark dose (BMD) approach was used to establish melamine exposure threshold in 293 patients with eGFR ≥ 30 ml/min per 1.73 m2. The patients were enrolled 2006–2010 and followed-up for a median of 7.0 years to monitor kidney outcomes. Average daily intakes (AvDI) of melamine were estimated using one-spot urine samples collected at enrollment. BMDs and corresponding one-sided 95% lower bound (BMDLs) were derived using established dose–response models relating estimated AvDIs and dichotomous kidney outcomes: doubling of serum creatine levels, eGFR decreased > 3 ml/min per 1.73 m2 per year, and >30% decline in eGFR during the first 2 years. In addition, survival time to doubling of serum creatinine and eGFR decline over time were assessed as continuous endpoints. Given a benchmark response of 0.10, BMDLs ranged from 0.74 to 2.03 μ g / k g _ b w / d a y after Bayesian model averaging, a range one to two orders lower than the current WHO recommended tolerable daily intake of 200 μ g / k g _ b w / d a y and the US FDA’s 63 μ g / k g _ b w / d a y . Our results suggest that early-stage CKD patients should strictly refrain from using melamine tableware and related melamine-made products.

Protein-bound uremic toxins (Indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) are both associated with cardiovascular (CV) and all-cause mortality in subjects with chronic kidney disease (CKD). Possible mechanisms have not been elucidated. In hemodialysis patients, we investigated the relationship between the free form of IS and PCS and 181 CV-related proteins. First, IS or PCS concentrations were checked, and high levels were associated with an increased risk of acute coronary syndrome (ACS) in 333 stable HD patients. CV proteins were further quantified by a proximity extension assay. We examined associations between the free form protein-bound uremic toxins and the quantified proteins with correction for multiple testing in the discovery process. In the second step, the independent association was evaluated by multivariable-adjusted models. We rank the CV proteins related to protein-bound uremic toxins by bootstrapped confidence intervals and ascending p-value. Six proteins (signaling lymphocytic activation molecule family member 5, complement component C1q receptor, C–C motif chemokine 15 [CCL15], bleomycin hydrolase, perlecan, and cluster of differentiation 166 antigen) were negatively associated with IS. Fibroblast growth factor 23 [FGF23] was the only CV protein positively associated with IS. Three proteins (complement component C1q receptor, CCL15, and interleukin-1 receptor-like 2) were negatively associated with PCS. Similar findings were obtained after adjusting for classical CV risk factors. However, only higher levels of FGF23 was related to increased risk of ACS. In conclusion, IS and PCS were associated with several CV-related proteins involved in endothelial barrier function, complement system, cell adhesion, phosphate homeostasis, and inflammation. Multiplex proteomics seems to be a promising way to discover novel pathophysiology of the uremic toxin.

BACKGROUND AND AIM Hemodialysis patients are at increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both HBV and HCV infections lead to risks of end-stage liver diseases and extrahepatic manifestations. This study aimed to investigate hepatic and extrahepatic comorbidities in hemodialysis patients with HBV or HCV infections compared with those without viral hepatitis. METHODS A total of 1910 hemodialysis patients, including 159 HCV viremic patients (HCV group), 217 seropositive for HBV surface antigen (HBsAg, HBV group) and 1534 seronegative for both anti-HCV and HBsAg (non-B and non-C [NBNC] group), from 23 hemodialysis centers were enrolled. Comorbidities were classified into 10 categories by the International Classification of Diseases-10th Revision. RESULTS Among the 1910 patients, the mean age was 64.6 years, and 52.7% were male patients. A total of 1834 (96%) patients had at least one comorbidity, and the mean number of comorbidities was 2.9 ± 1.5 per person. The three most common comorbidities were hypertension, diabetes, and ischemic heart diseases. The mean number of comorbidities per person was significantly higher in the HCV group (3.3 ± 1.7) than in the HBV (2.7 ± 1.5, P

Machine Learning (ML) and its applications have been transforming our lives but it is also creating issues related to the development of fair, accountable, transparent, and ethical Artificial Intelligence. As the ML models are not fully comprehensible yet, it is obvious that we still need humans to be part of algorithmic decision-making processes. In this paper, we consider a ML framework that may accelerate model learning and improve its interpretability by incorporating human experts into the model learning loop. We propose a novel human-in-the-loop ML framework aimed at dealing with learning problems that the cost of data annotation is high and the lack of appropriate data to model the association between the target tasks and the input features. With an application to precision dosing, our experimental results show that the approach can learn interpretable rules from data and may potentially lower experts' workload by replacing data annotation with rule representation editing. The approach may also help remove algorithmic bias by introducing experts' feedback into the iterative model learning process.

Uraemic patients undergoing haemodialysis are at high risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We aimed to evaluate the evolutionary seroprevalence of viral hepatitis and the gap in HCV care cascades in this special population by a large-scale surveillance study in Taiwan. Uraemic patients on maintenance haemodialysis from 22 sites (FORMOSA-LIKE group) in 2012 (n = 1,680) and 2019 (n = 2,326) were recruited for this study. The distributions and sequential changes of viral hepatitis markers were analysed. The prevalence of anti-HCV antibody and hepatitis B surface antigen (HBsAg) seropositivity was 13.6% (316/2326) and 11.5% (267/2326), respectively, in 2019 compared with 17.3% (290/1680, P = .002) and 13.6% (229/1680, P = .046), respectively, in 2012. The HCV-viremic rate among anti-HCV-seropositive patients was significantly lower in 2019 than in 2012 (56.3% [178/316] vs. 73.8% [214/290], P

This animal study aimed to elucidate the relationship of low-dose, narrow-band UVB at 308 nm with vitamin D synthesis. C57BL/6 female mice, at 3 weeks-of-age, were randomly divided into the following six groups (n = 6 at each time point of vitamin D measurement), which were: (1) normal diet without UVB irradiation; (2) VDd diet without UVB irradiation; and (3)–(6) VDd diet with 308 nm-UVB irradiation of 12.5, 25, 50, and 100 μω/cm2, respectively. All of the groups needing UVB irradiation received an exposure of 10 min per day, five days per week, and a duration of 3–5 weeks. The mice recovering from severe VDd (plasma total 25-hydroxyvitamin D level increasing from approximately 3 to over 30 ng/mL) only occurred in groups with a UVB irradiation dosage of either 50 or 100 μω/cm2. The optimal, estimated dosage for mice to recover from severe VDd was 355 mJ/cm2 within 3 weeks. Low-dose, narrow-band UVB irradiation at 308 nm is effective in improving VDd in mice. The results obtained, in addition to the especially small side effects of the above UVB irradiation formula, could be further translated to treating VDd-related disorders.

Background We explored the long-term safety and efficacy of ferric citrate in hemodialysis patients in Taiwan, and further evaluated the iron repletion effect and change of iron parameters by different baseline groups. Methods This was a 12-month, Phase IV, multicenter, open-label study. The initial dose of ferric citrate was administered by patients’ clinical condition and further adjusted to maintain serum phosphorus at 3.5–5.5 mg/dL. The primary endpoint was to assess the safety profiles of ferric citrate. The secondary endpoints were to evaluate the efficacy by the time-course changes and the number of subjects who achieved the target range of serum phosphorus. Results A total of 202 patients were enrolled. No apparent or unexpected safety concerns were observed. The most common treatment-emergent adverse events were gastrointestinal-related with discolored feces (41.6%). Serum phosphorus was well controlled, with a mean dose of 3.35±1.49 g/day, ranging from 1.5 to 6.0 g/day. Iron parameters were significantly improved. The change from baseline of ferritin and TSAT were 227.17 ng/mL and 7.53%, respectively (p-trend Conclusions Ferric citrate is an effective phosphate binder with favorable safety profile in ESRD patients. The iron-repletion by ferric citrate is effective, and the increase is limited in patients with a higher baseline. In addition to controlling hyperphosphatemia, ferric citrate also shows additional benefits in the treatment of renal anemia. Clinical trial registration ClinicalTrials.gov ID: NCT03256838; 12/04/2017.

ObjectiveHCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme.DesignThe ERASE-C Campaign is an outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and ‘No-C HD’ (no HCV-viremic subjects at the end of follow-up).ResultsAt the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and ‘No-C HD’ were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively.ConclusionOutreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population.ClinicalTrials.gov identifierNCT03803410 and NCT03891550

Background: Patients with end-stage renal disease (ESRD) have extremely high risks of mortality and morbidity, as well as altered gut microbiota and impaired intestinal barrier function. The translocation of gut-derived molecules in ESRD contributes to systemic complications. In this study, we evaluated the gut microbiome difference in ESRD patients compared to age- and gender-matched subjects without kidney disease in discovery and validation cohorts.Results: Compared to controls with normal renal function, an increased α-diversity and distinct β-diversity were found in ESRD subjects. The increase in α-diversity was correlated with protein-bound uremic toxins, particularly hippuric acid. A higher microbial dysbiosis index (MDI) was found in ESRD patients with the following enriched genera: Facealibacterium, Ruminococcus, Fusobacterium, Dorea, Anaerovorax, Sarcina, Akkemansia, Streptococcus, and Dysgonomonas. MDI at the genus level demonstrated highly differentiated accuracies between ESRD and control subjects in the discovery cohort (area under the curve [AUC] of 81.9%) and between ESRD and control subjects in the validation cohort (AUC of 83.2%). On functional enrichment analysis with gut metabolic modules, ESRD subjects presented with increased saccharide and amino acid metabolism when compared with matched controls.Conclusions: An enriched but dysbiotic gut microbiota was presented in ESRD patients, in which the bacteria that were present increase amino acid metabolism linked to the production of protein-bound uremic toxins.

Background The accurate assessment of liver fibrosis among hemodialysis patients with chronic hepatitis C (CHC) is important for both treatment and for follow up strategies. Applying the non-invasive methods in general population with viral hepatitis have been successful but the applicability of the aminotransferase/platelet ratio index (APRI) or the fibrosis-4 index (FIB-4) in hemodialysis patients need further evaluation. Materials and methods We conducted a prospective, multi-center, uremic cohort to verify the applicability of APRI and FIB-4 in identifying liver fibrosis by reference with the standard transient elastography (TE) measures. Results There were 116 CHC cases with valid TE were enrolled in our analysis. 46 cases (39.6%) were classified as F1, 35 cases (30.2%) as F2, 11 cases (9.5%) as F3, and 24 cases (20.7%) as F4, respectively. The traditional APRI and FIB-4 criteria did not correctly identify liver fibrosis. The optimal cut-off value of APRI was 0.28 and of FIB-4 was 1.91 to best excluding liver cirrhosis with AUC of 76% and 77%, respectively. The subgroup analysis showed that female CHC hemodialysis patients had better diagnostic accuracy with 74.1% by APRI. And CHC hemodialysis patients without hypertension had better diagnostic accuracy with 78.6% by FIB-4. Conclusions This study confirmed the traditional category level of APRI and FIB-4 were unable to identify liver fibrosis of CHC hemodialysis patients. With the adjusted cut-off value, APRI and FIB-4 still showed suboptimal diagnostic accuracy. Our results suggest the necessary of TE measures for liver fibrosis in the CHC uremic population.

BACKGROUND Mobile health (mHealth) management is an emerging strategy of care for patients with chronic diseases. mHealth has developed considerably over recent years, and it has been shown to promote communication between healthcare professionals and patients to improve the early detection of a worsening health status. However, the effect of mHealth management on clinical outcomes of patients with chronic kidney disease (CKD) has not been well-studied. OBJECTIVE The aim of this study was to investigate the additional influence of mHealth on disease knowledge and self-care behavior combined with traditional education compared with only traditional education in patients with CKD. METHODS Kaohsiung Medical University Hospital designed and developed a new healthcare mobile application, called iCKD. The application has several major features, including home-based physiological signal monitoring, disease health education, nutrition analysis, medication reminder, and alarms and a warning system to promote self-care for patients with CKD. Using structured questionnaires of disease knowledge and self-care behavior, trained nurses interviewed patients with CKD who received both mobile and traditional education and those who received only traditional education. After propensity score matching, we analyzed 107 patients who used iCKD and traditional education, and 107 who received traditional education. RESULTS The mean age of all study participants was 63.9±11.5 years, and 59.3 % were male. The patients who used iCKD had higher disease knowledge scores than those who received traditional education (24.6±6.6 v.s. 22.6±5.3, p=0.02). In multivariate analysis, iCKD was significantly and positively associated with disease knowledge scores (β=1.78, p=0.02). Patients with high education level could have greater disease knowledge through using mHealth (β=3.16, p=0.001). However, there was no significant difference in total scores of self-care behavior between the two groups. CONCLUSIONS mHealth can significantly increase disease knowledge in patients with CKD. CLINICALTRIAL

A low-profile RF wire-to-board connector design for 5G mobile communications and WiGig applications is presented in this paper. A new connector structure with a mating height of only 0.7mm to achieve a bandwidth from DC up to 70GHz is proposed. This RF connector design may provide jump wire connections in devices for 5G wireless communications and other millimeter wave systems.

Background and Aims Uremic toxins are crucial non-traditional risk factors for cardiovascular disease in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) were associated with all-cause and cardiovascular mortality in CKD patients, but possible mechanisms have not been fully elucidated. Herein, we explored the association between protein-bound uremic toxins and 181 cardiovascular-specific proteins in patients receiving hemodialysis (HD). Method In the discovery phase, we investigated associations between circulating free form IS and PCS and cardiovascular-specific protein levels quantified by a proximity extension assay of 333 stable HD patients with correction for multiple testing. In the second phase, the independent association was assessed using multivariable-adjusted models. The associations of IS or PCS with cardiovascular-specific proteins levels on a continuous scale were also evaluated. Results Free form IS was negatively associated with six proteins (C-C motif chemokine 15, complement component C1q receptor, perlecan, bleomycin hydrolase, cluster of differentiation 166 antigen, and signaling lymphocytic activation molecule family member 5) and positively associated with one protein (fibroblast growth factor 23). Free form PCS was negatively associated with three proteins (C-C motif chemokine 15, complement component C1q receptor, and interleukin-1 receptor-like 2). Adjusting the multivariable models for classical cardiovascular risk factors at baseline yielded similar results. Conclusion Protein-bound uremic toxins (IS and PCS) were associated with several cardiovascular-specific proteins involved in cell adhesion, endothelial barrier function, inflammation, complement system, and phosphate homeostasis. Multiplex proteomics appears to be a promising way to explore novel aspects of uremic toxin pathophysiology.

Background and Aims Taiwan has a high incidence and prevalence of ESRD (end stage renal disease) in the world and all the medical expenses are covered by national insurance. Therefore, many old ESRD(end stage renal disease) patients received dialysis even had multiple co- morbidity. However, still some old late CKD patients withhold dialysis and chose palliative treatment. This study elucidate the experience of final outcome for those late CKD patients who chose palliative treatment in Taiwan. Method We enrolled 137 CKD stage 5 patients (age: 80.2±8.8 y/o, male/female:85/52) who were interested about palliative treatment since Oct, 2010 till July 2019. We reviewed their co-morbidity to calculate Modified Charlson comorbidity index by medical record and record their laboratory data at enrollment. The differences between two groups were calculated using a Chi-square test for categorical variables and a Mann-Whitney test for continuous variables. All statistical tests were two-tailed and a P value of less than .05 was considered a significant difference. Results After fully discussion, 82(59.9%) patients can accept palliative treatment, 46(33.6%) refuse palliative treatment, 9(6.6%) patients cannot decided palliative treatment or not at first. 79 patient died during study period, median survival time is 163 days. 22 death patients(27.8%) received dialysis before end of life. 10 patients (12.2%) who asked palliative treatment at first and changed their mind to received dialysis. 80% of these patients receive dialysis by double lumen catheter. For those refuse palliative treatment, 43 patient received dialysis and 24(55.8%) patients received dialysis by temporary catheter. These percentage is much higher(55.8%) than other CKD stage 5 patients (26.6%) following at our hospital. Only 13 patient(16.5%) died at home, 24 patients(30.4%) diet at hospice ward and 39(49.4%) patients diet at ordinary ward or intensive care unit. Older age, lower albumin and higher Charlson comorbidity index are found in mortality patients. The median survival time for those patients received dialysis is 467 days. Conclusion After fully explanation, only 59.9% patients can accept withhold dialysis and 12.2% regret later. Those who had interested in palliative treatment had higher percentage to use double lumen catheter for first dialysis. The median survival time for those patients who ever think about withhold dialysis is only 467 days even receiving dialysis. To minimize suffering before end of life and decrease medical expense burden, we still need to do more effort to popularize the concept of withhold dialysis in older and multiple comorbidity patients.

Background and Aims High sensitivity cardiac troponin-T (hs-cTnT) are prognostic markers in patients with stable cardiovascular (CV) disease but limited study investigated the CV outcome association in asymptomatic patients receiving hemodialysis (HD). We evaluated the prognostic value of hs-cTnT in predicting CV events in stable HD patients. Method A total of 341 stable HD patients was included in this prospective cohort study. Baseline hs-cTnT was measured by Roche hs-cTnT assays. Patients were followed up for 3 years or until first CV event, which was defined a composite endpoint of acute coronary syndrome, ischemic stroke, or hospitalization for heart failure. Cox proportional hazards model was used to determine independent predictors of CV events. The importance of hs-cTnT compared to other clinical parameters was evaluated by random forests algorithm in Gini index. Results The HD patients enrolled in this study was 59.2 ± 11.5 87 years old, 53.4% male, 42.5% had diabetes, 76.8% had hypertension, 17.6% had coronary artery disease, and 9.1% had cerebrovascular disease. In multivariate Cox regression analysis, the circulating hs-cTnT levels were independent associated with CV events (HR 2.31; 95% CI 1.21-4.40; p-value=0.011) after adjusting for confounders. Multivariable model showed prognostic significance, with the c-statistics of 0.75. The addition of baseline hs-cTnT to established risk factors improved risk prediction of CV events (c-statistics of 0.76; integrated discrimination improvement = 0.02, P = 0.049). Gini index demonstrated hs-cTnT was more important than other clinical parameters for CV events prediction. Conclusion Circulating hs-cTnT levels independently predicted CV events in chronic HD patients. CV risk in HD patients could be stratified according to hs-cTnT levels. The results suggest the useful property of hs-cTnT as an end-organ damage marker reflecting subclinical cardiac injury.