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Background The benefit of adjuvant chemotherapy was investigated for patients with T3 upper urinary tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy. Methods This is a multicenter retrospective observational study of 482 patients with pathological T3 N0 and Nx UTUC who underwent radical nephroureterectomy with and without adjuvant chemotherapy. The median overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) of patients who received adjuvant chemotherapy were analyzed to determine predictors of patient prognosis. Results Of the 482 patients, 140 (29.0%) received adjuvant chemotherapy. Adjuvant chemotherapy showed a benefit only for the median DFS rate (58% vs 49%; p = 0.04). Multivariate analyses revealed that adjuvant chemotherapy improved median DFS (HR 0.537; CI 0.35–0.83; p = 0.005). Surgical margin also significantly influenced median OS (HR 4.038; p

Purpose Laparoscopic radical nephroureterectomy (LNU) has gradually become the new standard treatment for localized upper tract urothelial cancer (UTUC). With more blunt dissection and tactile sensation, hand-assisted LNU might shorten the operative time compared with the pure laparoscopic approach. However, whether the use of the hand-assisted or the pure laparoscopic approach has an effect on oncological outcomes remains unclear. Methods We retrospectively identified 629 patients with non-metastatic UTUC who underwent hand-assisted (n = 515) or pure LNU (n = 114) at 9 hospitals in Taiwan between 2004 and 2019. Overall survival, cancer-specific survival, recurrence-free survival, and bladder recurrence-free survival were compared between these two groups using inverse-probability of treatment weighting (IPTW) derived from the propensity scores for baseline covariate adjustment. Results The median follow-up period was 32.9 and 28.7 months in the hand-assisted and the pure groups, respectively. IPTW-adjusted Cox proportional hazards models showed that the laparoscopic approach (pure vs. hand-assisted) was not significantly associated with all-cause mortality (HR 0.79, 95% CI 0.49-1.24, p = 0.304), cancer-specific mortality (HR 0.88, 95% CI 0.51-1.51, p = 0.634), or extra-vesical recurrence (HR 0.65, 95% CI 0.41-1.04, p = 0.071). However, the pure laparoscopic approach was significantly associated with lower intra-vescial recurrence (HR 0.64, 95% CI 0.43-0.96, p = 0.029) for patients who underwent LNU. Kaplan-Meier curves also revealed that the pure laparoscopic approach was associated with better bladder recurrence-free survival compared with the hand-assisted laparoscopic approach in both the original cohort and the IPTW-adjusted cohort (log-rank p = 0.042 and 0.027, respectively). Conclusions The performance of hand-assisted or pure LNU does not significantly affect the all-cause mortality, cancer-specific mortality, or extra-vesical recurrence for patients with non-metastatic UTUC. However, the hand-assisted laparoscopic approach could increase the risk of intra-vesical recurrence for patients who undergo LNU.

PurposeThis study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU).MethodsIn this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late (>90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan–Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression.ResultsOf the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166−3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137−3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival.ConclusionsFor patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival.

Erythropoiesis-stimulating agents (ESA) are used to treat anemia in hemodialysis (HD) patients. We investigated the role of inflammation and accumulation of environmental toxins (perfluorinated chemicals (PFCs), such as perfluorooctanoic acid and perfluorooctane sulfonate) in the erythropoietic response of HD patients who receive a fixed monthly continuous erythropoietin receptor activator (CERA) dosage. Forty-five patients underwent three successive phases of ESA treatment for two months each (phase one: 100 µg CERA once monthly; phase two: 50 µg CERA twice monthly; phase three: 100 µg CERA once monthly). Patient data were collected to determine the association of various factors with erythropoietic response (change in hematocrit). Liquid chromatography-tandem mass spectrometry was used to analyze perfluorinated chemicals. Twenty-eight patients exhibited a poor erythropoietic response that was significantly associated with: age > 80 years, initial hematocrit > 36%, glucose > 200 mg/dL, alanine aminotransferase > 21 U/L, c-reactive protein > 1 mg/dL, interleukin−6 > 10 ng/mL, lactate dehydrogenase ≤ 190 U/L, and chloride ≤ 93 mEq/L. There was also a borderline significant association between inflammation and PFCs, although PFCs failed to show any impact on ESA response. Age, glucose, chloride, liver function, and inflammation may be associated with cost-effective fixed CERA dosage administered at an increased frequency.

The peritoneal equilibration test (PET) is a semi-quantitative measurement that characterizes the rate of transfer of solutes and the water transfer rate across the peritoneum in patients treated with peritoneal dialysis (PD). The results of the PET are used to maximize daily peritoneal ultrafiltration and solute clearances. Previous studies have shown that high transport status is associated with ultrafiltration failure, malnutrition, and reduced survival; however, the way in which peritoneum transport characteristics affect peritonitis risk is unknown. In the current cohort study, we recruited 898 incident-PD patients and used intention-to-treat analysis to test if baseline PET affected the subsequent 3-year peritonitis rate. Among all recruited PD patients, 308 (34.2%) developed peritonitis within three years. Multivariate Cox regression analysis showed that the high-transport group has the greatest peritonitis risk (HR 1.98, 95% CI: 1.08–3.62) even after an adjustment for demographics, comorbid diseases, and biochemical measurements. We concluded that a baseline high peritoneal membrane transport rate is an independent risk factor for peritonitis in incident PD patients.

PurposeWe aimed to evaluate the impact of preoperative local symptoms on prognosis after radical nephroureterectomy in patients with upper tract urothelial carcinoma (UTUC).MethodsThis retrospective study consisted of 2,662 UTUC patients treated at 15 institutions in Taiwan from 1988 to 2019. Clinicopathological data were retrospectively collected for analysis by the Taiwan UTUC Collaboration Group. The Kaplan-Meier method was used to calculate overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS). The prognostic value of preoperative local symptoms in OS, CSS, DFS, and BRFS was investigated using Cox proportional hazards models.ResultsThe median follow-up was 36.6 months. Among 2,662 patients, 2,130 (80.0%) presented with hematuria and 398 (15.0%) had symptomatic hydronephrosis at diagnosis. Hematuria was associated with less symptomatic hydronephrosis (p <0.001), more dialysis status (p = 0.027), renal pelvic tumors (p <0.001), and early pathological tumor stage (p = 0.001). Symptomatic hydronephrosis was associated with female patients (p <0.001), less dialysis status (p = 0.001), less bladder cancer history (p <0.001), ureteral tumors (p <0.001), open surgery (p = 0.006), advanced pathological tumor stage (p <0.001), and postoperative chemotherapy (p = 0.029). Kaplan-Meier analysis showed that patients with hematuria or without symptomatic hydronephrosis had significantly higher rates of OS, CSS, and DFS (all p <0.001). Multivariate analysis confirmed that presence of hematuria was independently associated with better OS (HR 0.789, 95% CI 0.661–0.942) and CSS (HR 0.772, 95% CI 0.607–0.980), while symptomatic hydronephrosis was a significant prognostic factor for poorer OS (HR 1.387, 95% CI 1.142–1.683), CSS (HR 1.587, 95% CI 1.229–2.050), and DFS (HR 1.378, 95% CI 1.122–1.693).ConclusionsPreoperative local symptoms were significantly associated with oncological outcomes, whereas symptomatic hydronephrosis and hematuria had opposite prognostic effects. Preoperative symptoms may provide additional information on risk stratification and perioperative treatment selection for patients with UTUC.

Convalescence after hernia repair is one of the main focuses for hernia surgeons. We analyzed our prospectively collected data to identify possible predictive factors for post-operative acute and chronic pain. We prospectively collected the demographic data and peri-operative findings. Post-operative acute pain was evaluated with Visual Analog Pain Scale. The chronic pain (pain persists for > 6 months since operation) was also recorded. From June 2008 to August 2018, there were 807 patients with 1029 sites of inguinal hernia enrolled in our analysis. Pain before operation was associated with the severity of acute pain on OP (operation) day, POD 1 (post-operative day 1), and POD 7 (post-operative day 7). Younger patients had significantly higher post-operative acute pain on OP day, POD 1, and POD 7. The staple mesh fixation method resulted in a higher pain score at OP day and POD 1. The predictive factors for chronic pain were sex (female), young age (

Objectives: The aim of this study was to determine the long-term incidence of cryptococcosis in kidney transplant recipients (KTRs) and to analyze its risk factors. Methods: This retrospective population-based cohort study analyzed data obtained from Taiwan’s National Health Insurance Research Database for KTRs during 2000–2012 and matched cohorts. Both populations were followed until death, development of cryptococcosis, or December 2013. Results: A total of 4,933 KTRs and 49,930 matched patients were included. The cryptococcosis incidence rates for the KTR cohort and matched cohort were 10.59 and 0.4 per 10,000 person-years, respectively. The hazard ratio for cryptococcosis among KTRs was 26.65 (p

BackgroundThe advantage of adjuvant chemotherapy for upper urinary tract urothelial cancer (UTUC) has been reported, whereas its impact on upper tract cancer with variant histology remains unclear. We aimed to answer the abovementioned question with our real-world data.Design, Setting, and ParticipantsPatients who underwent radical nephroureterectomy (RNU) and were confirmed to have variant UTUC were retrospectively evaluated for eligibility of analysis. In the Taiwan UTUC Collaboration database, we identified 245 patients with variant UTUC among 3,109 patients with UTUC who underwent RNU after excluding patients with missing clinicopathological information.InterventionThose patients with variant UTUC were grouped based on their history of receiving adjuvant chemotherapy or not.Outcome Measurements and Statistical AnalysisPropensity score matching was used to reduce the treatment assignment bias. Multivariable Cox regression model was used for the analysis of overall, cancer-specific, and disease-free survival.Results and LimitationsFor the patients with variant UTUC who underwent adjuvant chemotherapy compared with those without chemotherapy, survival benefit was identified in overall survival in univariate analysis (hazard ratio (HR), 0.527; 95% confidence interval (CI), 0.285–0.973; p = 0.041). In addition, in multivariate analysis, patients with adjuvant chemotherapy demonstrated significant survival benefits in cancer-specific survival (OS; HR, 0.454; CI, 0.208–0.988; p = 0.047), and disease-free survival (DFS; HR, 0.324; 95% CI, 0.155–0.677; (p = 0.003). The main limitations of the current study were its retrospective design and limited case number.ConclusionsAdjuvant chemotherapy following RNU significantly improved cancer-related survivals in patients with UTUC with variant histology.

The clinical efficacy of adjuvant chemotherapy in upper tract urothelial carcinoma (UTUC) is unclear. We aimed to assess the therapeutic outcomes of adjuvant chemotherapy in patients with advanced UTUC (pT3-T4) after radical nephroureterectomy (RNU). We retrospectively reviewed the data of 2108 patients from the Taiwan UTUC Collaboration Group between 1988 and 2018. Comprehensive clinical features, pathological characteristics, and survival outcomes were recorded. Univariate and multivariate Cox proportional hazards models were used to evaluate overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Of the 533 patients with advanced UTUC included, 161 (30.2%) received adjuvant chemotherapy. In the multivariate analysis, adjuvant chemotherapy was significantly associated with a reduced risk of overall death (hazard ratio (HR), 0.599; 95% confidence interval (CI), 0.419–0.857; p = 0.005), cancer-specific mortality (HR, 0.598; 95% CI, 0.391–0.914; p = 0.018), and cancer recurrence (HR, 0.456; 95% CI, 0.310–0.673; p < 0.001). The Kaplan–Meier survival analysis revealed that patients receiving adjuvant chemotherapy had significantly better five-year OS (64% vs. 50%, p = 0.002), CSS (70% vs. 62%, p = 0.043), and DFS (60% vs. 48%, p = 0.002) rates compared to those who did not receive adjuvant chemotherapy. In conclusion, adjuvant chemotherapy after RNU had significant therapeutic benefits on OS, CSS, and DFS in advanced UTUC.

PurposeThis study aimed to compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) without clinical lymph node metastasis (cN0) undergoing lymph node dissection (LND) during radical nephroureterectomy (NU).MethodsFrom the updated data of the Taiwan UTUC Collaboration Group, a total of 2726 UTUC patients were identified. We only include patients with ≥ pT2 stage and enrolled 658 patients. The Kaplan–Meier estimator and Cox proportional hazards model were used to analyze overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) in LND (+) and LND (−) groups.ResultsA total of 658 patients were included and 463 patients without receiving LND and 195 patients receiving LND. From both univariate and multivariate survival analysis, there are no significant difference between LND (+) and LND (-) group in survival rate. In LND (+) group, 18.5% patients have pathological LN metastasis. After analyzing pN+ subgroup, it revealed worse CSS (p = 0.010) and DFS (p < 0.001) compared with pN0 patients.ConclusionsWe found no significant survival benefit related to LND in cN0 stage, ≥ pT2 stage UTUC, irrespective of the number of LNs removed, although pN+ affected cancer prognosis. However, from the result of pN (+) subgroup of LND (+) cohort analysis, it may be reasonable to not perform LND in patients with cT2N0 stage due to low positive predictive value of pN (+). In addition, performing LND may be considered for ureter cancer, which tends to cause lymphatic and hematogenous tumor spreading. Further large prospective studies are needed to validate our findings.

Tumor multifocality and location are prognostic factors for upper tract urothelial carcinoma (UTUC). However, confounding effects can appear when these two factors are analyzed together. Therefore, we aimed to investigate the impact of tumor distribution on the outcomes of multifocal UTUC after radical nephroureterectomy. From the 2780 UTUC patients in the Taiwan UTUC Collaboration Group, 685 UTUC cases with multifocal tumors (defined as more than one tumor lesion in unilateral upper urinary tract) were retrospectively included and divided into three groups: multiple renal pelvic tumors, multiple ureteral tumors, and synchronous renal pelvic and ureteral tumors included 164, 152, and 369 patients, respectively. We found the prevalence of carcinoma in situ was the highest in the synchronous group. In multivariate survival analyses, tumor distribution showed no difference in cancer-specific and disease-free survival, but there was a significant difference in bladder recurrence-free survival. The synchronous group had the highest bladder recurrence rate. In summary, tumor distribution did not influence the cancer-specific outcomes of multifocal UTUC, but synchronous lesions led to a higher rate of bladder recurrence than multiple renal pelvic tumors. We believe that the distribution of tumors reflects the degree of malignant involvement within the urinary tract, but has little significance for survival or disease progression.

Long-term peritoneal dialysis (PD) can lead to detrimental changes in peritoneal membrane function, which may be related to the accumulation of glucose degradation products. A previous study demonstrated that 6 months of far-infrared (FIR) therapy may decrease glucose degradation products in PD dialysate. Due to limited literature on this matter, this study aims to investigate the effect of FIR therapy on the peritoneal membrane transport characteristics of PD patients. Patients were grouped according to baseline peritoneal transport status: lower transporters (low and low-average) and higher transporters (high-average and high). Both groups underwent 40 min of FIR therapy twice daily for 1 year. In lower transporters, FIR therapy increased weekly dialysate creatinine clearance (6.91 L/wk/1.73 m2, p = 0.04) and D/P creatinine (0.05, p = 0.01). In higher transporters, FIR therapy decreased D/P creatinine (−0.05, p = 0.01) and increased D/D0 glucose (0.05, p = 0.006). Fifty percent of high transporter patients shifted to high-average status after FIR therapy. FIR therapy may decrease D/P creatinine for patients in the higher transporter group and cause high transporters to shift to high-average status, which suggests the potential of FIR therapy in improving peritoneal membrane function in PD patients.

Sodium glucose cotransporter-2 inhibitors (SGLT2i), a novel antidiabetic drug blocks the reabsorption of glucose in proximal tubules of kidney, are demonstrated to have cardiovascular and renal benefits for people with diabetes. The benefits are associated with the significant increase of intrarenal angiotensin-converting enzyme II (ACE2) expression and blood volume contraction. However, the increased ACE2 may be detrimental to patients infected with the coronavirus infection 2019 (COVID-19), which is found to invade cells via the entry receptor of ACE2. Besides, an SGLT2i-induced natriuretic effect may also increase the risk of acute kidney injury and affect the hemodynamic stability during systemic infection disease. In this article, we explain the mechanisms why the use of SGLT2i in people with diabetes may lead to worse outcomes and suggest clinician to judiciously use it during COVID-19 pandemic.

Background A high incidence of upper urinary tract urothelial carcinoma has been reported in the southwestern area of Taiwan, where arsenic water contamination was considered the main cause. However, there is no definite proof to show a correlation between arsenic water contamination and upper urinary tract urothelial carcinoma. To investigate the clinical and epidemiological features of patients with upper urinary tract urothelial carcinoma between arsenic water endemic and non-endemic areas, we analyzed patients in terms of characteristics, stratified overall survival, disease-free survival, and cancer-specific survival. Methods The records of a total of 1194 patients diagnosed with upper urinary tract urothelial carcinoma were retrospectively reviewed. Clinical data and current medical status were collected from the medical records. Statistical analyses were performed to determine the clinical variables and stratified survival curves between endemic and non-endemic groups. Results Female predominance was revealed in both endemic and non-endemic groups (male:female ratio = 1:1.2–1.4). No statistical differences were found in histological types, staging, and tumor size between the two groups. Nonetheless, patients with characteristics of aging and having end-stage renal disease were outnumbered in the non-endemic group, while a higher prevalence of previous bladder tumors and more ureteral tumors were found in the endemic group. Adjusted stratified cumulative survival curves suggested a poorer prognosis in endemic patients, especially in disease-free survival of early stage disease. Conclusions A higher mortality rate with more previous bladder cancer history and ureteral tumors was seen in patients with upper urinary tract urothelial carcinoma residing in the arsenic water contamination area. This may be attributed to the long-term carcinogenic effect of arsenic underground water.

Patients with systemic lupus erythematosus (SLE) have a higher risk of vascular complications. This retrospective cohort study aimed to analyze the differences in the risk of arteriovenous fistula or graft (AVF/AVG) dysfunction in hemodialysis patients with and without SLE from Taiwan’s National Health Insurance Database over a 10-year period. AVF/AVG dysfunction is defined as the occurrence of the first episode of intervention after vascular access creation. A total of 1366 HD patients with SLE had higher incidence rates of AVF/AVG dysfunction than 4098 non-SLE HD patients in the following 4 periods: (1) after 1 year (incidence rates = 15.21% and 13.01%, respectively; subdistribution hazard ratio (SHR) = 1.16; P = 0.007), (2) 1st-to-10th-year period (15.36% and 13.25%; SHR = 1.16; P = 0.007), (3) 5th-to-10th-year period (11.91% and 8.1%; SHR = 1.42; P = 0.003), and (4) overall period (23.53% and 21.66%; SHR = 1.09; P = 0.027). In conclusion, there were significantly higher incidence rates of AVF/AVG dysfunction in SLE patients during the long-term follow-up period. Vascular access function should be monitored regularly by clinical examinations, especially after 1 year and during 5 to 10 years, to improve AVF/AVG patency and dialysis adequacy in SLE patients undergoing maintenance hemodialysis.

Laparoscopic radical nephroureterectomy (LNU) has gradually become the new standard treatment for localized upper tract urothelial cancer (UTUC). With more blunt dissection and tactile sensation, hand-assisted LNU might shorten the operative time compared with the pure laparoscopic approach. However, whether the use of the hand-assisted or the pure laparoscopic approach has an effect on oncological outcomes remains unclear.We retrospectively identified 629 patients with non-metastatic UTUC who underwent hand-assisted (n = 515) or pure LNU (n = 114) at 9 hospitals in Taiwan between 2004 and 2019. Overall survival, cancer-specific survival, recurrence-free survival, and bladder recurrence-free survival were compared between these two groups using inverse-probability of treatment weighting (IPTW) derived from the propensity scores for baseline covariate adjustment.The median follow-up period was 32.9 and 28.7 months in the hand-assisted and the pure groups, respectively. IPTW-adjusted Cox proportional hazards models showed that the laparoscopic approach (pure vs. hand-assisted) was not significantly associated with all-cause mortality (HR 0.79, 95% CI 0.49-1.24, p = 0.304), cancer-specific mortality (HR 0.88, 95% CI 0.51-1.51, p = 0.634), or extra-vesical recurrence (HR 0.65, 95% CI 0.41-1.04, p = 0.071). However, the pure laparoscopic approach was significantly associated with lower intra-vescial recurrence (HR 0.64, 95% CI 0.43-0.96, p = 0.029) for patients who underwent LNU. Kaplan-Meier curves also revealed that the pure laparoscopic approach was associated with better bladder recurrence-free survival compared with the hand-assisted laparoscopic approach in both the original cohort and the IPTW-adjusted cohort (log-rank p = 0.042 and 0.027, respectively).The performance of hand-assisted or pure LNU does not significantly affect the all-cause mortality, cancer-specific mortality, or extra-vesical recurrence for patients with non-metastatic UTUC. However, the hand-assisted laparoscopic approach could increase the risk of intra-vesical recurrence for patients who undergo LNU.

Background The clinical effect of atrial fibrillation (AF)-related ischemic cardiovascular events in patients undergoing peritoneal dialysis (PD) remains uncertain. This study aimed to investigate the risk of ischemic events in patients undergoing PD with new-onset AF compared with that in patients without AF and ascertain the association between the CHA2DS2-VASc score and risk of ischemic stroke. Methods This nationwide, population-based cohort study used data from Taiwan's National Health Insurance Research Database from 1998 to 2011 for patients receiving PD with or without new-onset AF. The clinical endpoints included ischemic stroke, all-cause death, and in-hospital cardiovascular death. Results Patients undergoing PD with new-onset AF (N = 505) had significantly higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.98; 95% CI, 1.40-2.80), all-cause death (aHR, 1.61; 95% CI, 1.40-1.85), and in-hospital cardiovascular death (aHR, 1.82; 95% CI, 1.50.2.21) compared with those in patients undergoing PD without AF. After considering in-hospital death as a competing risk, AF remained associated with an increased risk of ischemic stroke (hazard ratio [HR], 1.67; 95% CI, 1.17-2.37). The CHA2DS2-VASc score was associated with the risk of ischemic stroke (HR, 1.28; 95% CI, 1.12-1.46). Conclusion The risks of ischemic stroke, all-cause death, and in-hospital cardiovascular death were significantly higher in patients undergoing PD with AF than those in patients without AF. The CHA2DS2-VASc score remained associated with the risk of ischemic stroke in patients undergoing PD with AF.

Objective High incidence of upper urinary tract urothelial carcinoma has been reported in South- Western area of Taiwan, where arsenic water contamination was considered to be the main cause. However, there is no definite proof to show the correlation between the arsenic water contamination and upper urinary tract urothelial carcinoma. To investigate the clinical and epidemiological features of the patients with upper urinary tract urothelial carcinoma between arsenic water endemic and non-endemic areas, we analyzed patients in terms of characteristics, stratified overall survival, disease-free survival and cancer-specific survival Method The records of a total 1194 patients diagnosed with upper urinary tract urothelial carcinoma were retrospectively reviewed. Clinical data and current medical status were collected from medical records. Statistical analyses were performed to determine the clinical variables and stratified survival curves between endemic and non-endemic groups. Results Female predominance was revealed in both endemic and non-endemic groups (Male:Female=1:1.2- 1.4). No statistical differences were found in histological types, staging and tumor size among two groups. Nonetheless, patients with characteristics of aging and having end stage renal disease outnumbered in non-endemic group while higher prevalence of previous bladder tumor and more ureteral tumor were found in endemic group. Adjusted stratified cumulative survival curves suggested poorer prognosis fashion in endemic patients, especially in disease free survival of early stage disease. Conclusions Higher mortality rate with more previous bladder cancer history and ureteral tumor were seen in patients with upper urinary tract urothelial carcinoma residing in arsenic water contamination area. This may attribute to the long-term carcinogenesis effect of arsenic underground water.

Additional file 1: Supplementary Table. The ICD diagnosis codes of indications for pregabalin

Objective The objective of this study is to determine whether vaccination against influenza is associated with a reduced risk of acute kidney injury (AKI) in a nationwide cohort of adults aged ≥65 years. Methods We investigated a total of 13,270 patients aged ≥65 years who were hospitalized for AKI between 2000 and 2013 from Taiwan's National Health Insurance Research Database. Each AKI case was matched with one control subject according to duration of follow-up, age, sex, monthly income, urbanization level, and baseline comorbidities. Odds ratios (ORs) for AKI associated with exposure to the influenza vaccine in the previous year were calculated in a nested case-control analysis. Results Influenza vaccination in the previous year was associated with a lower risk of AKI (adjusted OR 0.67, 95% confidence interval [CI] 0.63–0.72). Compared with a reference group of unvaccinated individuals with no influenza infection, vaccination with no influenza infection was associated with a lower risk of AKI (adjusted OR 0.68, 95% CI 0.64–0.73). Lack of vaccination and presence of influenza infection was associated with a higher risk of AKI (adjusted OR 1.78, 95% CI 1.57–2.01), whereas the risk of AKI was insignificant in vaccinated patients who developed influenza (adjusted OR 1.01, 95% CI 0.69–1.18). Conclusions The risk of AKI was 37% lower among older people who received vaccination against influenza in a real-world setting. Further work is required to clarify causality.

Background: To estimate the clinical and economic impact of intensive care unit-acquired bloodstream infections in Taiwan. Methods: The first episodes of intensive care unit-acquired bloodstream infections in patients ≥ 20 years of age in the Taiwanese population were identified in the National Health Insurance Research Database and in the Taiwan Nosocomial Infections Surveillance (2007-2015) dataset. Propensity score-matching (1:2) of demographic data, comorbidities, and disease severity was performed to select a comparison cohort from a pool of intensive care unit patients without intensive care unit-acquired infections from the same datasets. Results: After matching, the in-hospital mortality of 14,369 patients with intensive care unit-acquired bloodstream infections was 44.38%, compared to 33.50% for 28,738 intensive care unit patients without bloodstream infections. The 14-day mortality rate was also higher in the bloodstream infections cohort (4,367, 30.39% vs. 6,860 deaths, 23.87%, respectively; p < 0.001). Furthermore, the patients with intensive care unit-acquired bloodstream infections had a prolonged length of hospitalization after their index date (18 [IQR 7–39] vs. 10 days [IQR 4–21], respectively; p < 0.001) and a higher healthcare cost (16,086 [IQR 9,706–26,131] vs. 10,731 US dollars [IQR 6,375–16,910], respectively; p < 0.001). The excessive hospital stay and healthcare cost per case were 12.77 days and 7,646 US dollars, respectively. Similar results were observed in subgroup analyses of various World Health Organization’s priority pathogens and Candida spp. Conclusions: Intensive care unit-acquired bloodstream infections in critically ill patients were associated with increased mortality, longer hospital stays, and higher healthcare costs.

This study was conducted to determine the protective effect of influenza vaccine against primary major adverse cardiovascular events (MACEs) in elderly patients, especially those with influenza-like illness (ILI).This retrospective, population-based case-control study of an elderly population (age≥65 years) was conducted using Taiwan's National Health Insurance Research Database (2000-2013). One control was selected for each MACE case (n=80,363 each), matched according to age, year of study entry, and predisposing factors for MACEs. ILI and MACEs (myocardial infarction [MI] and ischemic stroke) were defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Odds ratios (ORs) were calculated for the association between MACEs and vaccination.Influenza vaccination received in the previous year was associated with reduced risks of primary MACEs overall (adjusted OR [aOR] 0.80, 95% CI 0.78-0.82, P.001), MI (aOR 0.80, 95% CI 0.76-0.84, P.001), and ischemic stroke (aOR 0.80, 95% CI 0.77-0.82, P.001). ILI diagnosed in the previous year was associated with increased risks of MACEs (aOR 1.24, 95% CI 1.18-1.29, P.001), MI (aOR 1.46, 95% CI 1.34-1.59, P.001), and ischemic stroke (aOR 1.16, 95% CI 1.10-1.22, P.001). Vaccination attenuated the heightened risks associated with ILI (MACEs: aOR 0.99, 95% CI 0.92-1.07, P=.834; MI: aOR 1.05, 95% CI 0.92-1.21, P=.440; ischemic stroke: aOR 0.96, 95% CI 0.89-1.05, P=.398).Results of this study suggest that influenza vaccination is associated with reduced primary MACE risks in the elderly population, including those with ILI.

An increased risk of adverse cardiovascular events was reported for concomitant use of proton-pump inhibitors (PPIs) in patients taking antiplatelet agents. The present study aimed at determining whether PPI use alone could be associated with first-time ischemic stroke.This was a retrospective nationwide study using database from Taiwan National Health Insurance and involved subjects aged ≥20 years. In propensity score-matched analysis, patients with current PPI use were compared with propensity score-matched PPI non-use controls at a 1:1 ratio. Patients with prior stroke or hospitalization before the index date were excluded. The primary outcome measure was hospitalization with a primary diagnosis of ischemic stroke during 120-day follow-up. A parallel analysis adopting a nested case-control design was carried out. Patients hospitalized for a first-time ischemic stroke were identified and were compared with matched controls using conditional logistic regression analyses focusing on PPI use before the index date.The propensity score-matched analysis included 198,148 PPI treatment courses and control periods without PPI use. PPI use was associated with a higher risk of hospitalization due to ischemic stroke with a hazard ratio of 1.36 (95% confidence interval (CI) 1.14-1.620, P=0.001). Based on subgroup analysis, patients aged60 years were more susceptible (P=0.043 for interaction), whereas gender, history myocardial infarction, diabetes mellitus, hypertension, use of antiplatelet agents of non-steroidal anti-inflammatory drugs, or type of PPIs had no effect on the risk. In the nested case-control analysis, 15,378 patients hospitalized owing to ischemic stroke were identified and were compared with 15,378 matched controls. An association between PPI use and increased cerebrovascular risks was identified, and the adjusted odds ratios for PPI use were 1.77 (95% CI 1.45-2.18, P0.001) within 30 days, 1.65 (95% CI 1.31-2.08, P0.001) between 31 and 90 days, and 1.28 (95% CI 1.03-1.59, P=0.025) between 91 and 180 days before the onset of first-time ischemic stroke.PPI use is associated with an increased risk of first-time ischemic stroke in the general population, and the risk is independent of antiplatelet agents. However, caution should be exercised when considering its clinical relevance as the magnitude of association was modest and a cause-and-effect relationship remained to be established.

Context Although there is evidence to support the beneficial effects of statins on major cardiovascular events, few studies address the protective effect of statins on limb outcome. Objective To investigate whether the use of statin is associated with a risk reduction in lower-extremity amputation in type 2 diabetes mellitus (DM) patients with peripheral arterial disease (PAD). Design Observational cohort study. Setting A nationwide DM database in Taiwan from 2000 to 2011. Patients A total of 69,332 patients aged ≥20 years with DM and PAD were identified. Intervention Patients were divided into three groups: 11,409 patients were statin users, 4430 patients used nonstatin lipid-lowering agents, and 53,493 patients were nonusers. Main outcome measures The primary outcome was lower-extremity amputation. Secondary outcomes were in-hospital cardiovascular death and all-cause mortality. Results Compared with nonusers, statin users were associated with lower risks of lower-extremity amputation [adjusted hazard ration (aHR), 0.75; 95% confidence interval (CI), 0.62 to 0.90], in-hospital cardiovascular death (aHR, 0.78; 95% CI, 0.69 to 0.87), and all-cause mortality (aHR, 0.73; 95% CI, 0.69 to 0.77). In the propensity score matching analysis, the effect of statin on the risk of lower-extremity amputation was consistent. Only statin users were associated with the risk reduction of lower-extremities amputation (HR, 0.77; 95% CI, 0.61 to 0.97) and cardiovascular death (HR, 0.78; 95% CI, 0.68 to 0.89) when taking competing risk of death into consideration. Conclusions Compared with statin nonusers who were never treated with lipid-lowering drugs, this study found that statin users had a lower risk of lower-extremity amputation and cardiovascular death in patients with DM and PAD.

Background Although theophylline has been shown to have anti-inflammatory effects, the therapeutic use of theophylline before sepsis is unknown. The aim of our study was to determine the effect of theophylline on COPD patients presenting with sepsis. Methods This nationwide, population-based, propensity score-matched analysis used data from the linked administrative databases of Taiwan's National Health Insurance program. Patients with COPD who were hospitalized for sepsis between 2000 and 2011 were divided into theophylline users and non-users. The primary outcome was 30-day mortality. The secondary outcome was in-hospital death, intensive care unit admission, and need for mechanical ventilation. Cox proportional hazard model and conditional logistic regression were used to calculate the risk between groups. Results A propensity score-matched cohort of 51,801 theophylline users and 51,801 non-users was included. Compared with non-users, the 30-day (HR 0.931, 95% CI 0.910–0.953), 180-day (HR 0.930, 95% CI 0.914–0.946), 365-day (HR 0.944, 95% CI 0.929–0.960) and overall mortality (HR 0.965, 95% CI 0.952–0.979) were all significantly lower in theophylline users. Additionally, the theophylline users also had lower risk of in-hospital death (OR 0.895, 95% CI 0.873–0.918) and need for mechanical ventilation (OR 0.972, 95% CI 0.949–0.997). Conclusions Theophylline use is associated with a lower risk of sepsis-related mortality in COPD patients. Pre-hospital theophylline use may be protective to COPD patients with sepsis.

Objective: The mechanism of the beneficial effect of calcium-channel blockers (CCBs), especially verapamil, on the development of type 2 diabetes mellitus (T2DM) has been described. This study compared the incidence of T2DM in adults prescribed oral verapamil and propensity score–matched adults prescribed other oral CCBs. Methods: This retrospective population-based cohort study used Taiwan’s National Health Insurance Research Database from 2000 to 2011. T2DM was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Results: During follow-up periods of 41,958 and 42,118 person-years, 269 of 4930 patients in the verapamil cohort and 340 of 4930 patients in the matched cohort, respectively, developed T2DM. The incidence rates were 6.41 and 8.07 per 1000 population per year among verapamil and other CCB users, respectively. The adjusted hazard ratio (HR) for T2DM associated with use of verapamil (vs. other CCBs) was 0.80 [95% confidence interval (CI), 0.68 to 0.94; P = 0.006]. After exclusion of patients followed for Conclusions: In patients with no known history of diabetes mellitus, oral verapamil use was associated with a decreased incidence of T2DM compared with other CCBs.

Convalescence after hernia repair is one of the main focuses for hernia surgeons. We analyzed our prospectively collected data to identify possible predictive factors for post-operative acute and chronic pain.We prospectively collected the demographic data and peri-operative findings. Post-operative acute pain was evaluated with Visual Analog Pain Scale. The chronic pain (pain persists for 6 months since operation) was also recorded.From June 2008 to August 2018, there were 807 patients with 1029 sites of inguinal hernia enrolled in our analysis. Pain before operation was associated with the severity of acute pain on OP (operation) day, POD 1 (post-operative day 1), and POD 7 (post-operative day 7). Younger patients had significantly higher post-operative acute pain on OP day, POD 1, and POD 7. The staple mesh fixation method resulted in a higher pain score at OP day and POD 1. The predictive factors for chronic pain were sex (female), young age ( 65 years), having no past history of hypertension, pain before operation, and mesh material.A younger age and inguinal pain before operation were the main predictive factors for higher post-operative pain. Younger patients, females, having inguinal pain before surgery, and using heavy weight mesh have a higher risk of chronic pain.

BACKGROUND Since the introduction of robot-assisted laparoscopic surgery, a variety of conventional laparoscopic procedures have been explored via this approach. In the robotic era, most of the reported robot-assisted laparoscopic hernia repairs were performed with the trans-abdominal pre-peritoneal approach. According to the evidence extrapolated from laparoscopic ventral hernia repair, simultaneous fascial defect closure and mesh repair can significantly decrease the risk of seroma formation and recurrence over those without fascial closure. Therefore, we describe our novel technique of robot-assisted total extra-peritoneal (TEP) repair with primary fascial closure and pre-peritoneal mesh and its preliminary clinical outcomes. METHODS We retrospectively reviewed our prospectively collected hernia database from October 2017 to July 2019, which included 26 consecutive patients with primary or recurrent groin hernias. Patients' baseline characteristics and perioperative outcomes were compared and analyzed. Perioperative factors included operative time, visual analog scale (VAS) score (0-100), hospital stay, perioperative complications, time to return to normal activity, and the modified Medical Outcome Study (MOS; item 3-12/36 items) score. RESULTS All procedures were completed successfully without conversion to open or conventional laparoscopic surgery. The patients' age ranged from 28 to 74 years (median 57.5). The mean operative time was 115 minutes (range 95-172 min). There were no major procedure-related complications. Only four cases experienced asymptomatic seromas, which were detected by ultrasonography; and all resolved spontaneously within 6 weeks after the operation. The VAS and modified MOSs revealed quick recovery after robot-assisted endoscopic TEP repair. CONCLUSIONS Robot-assisted endoscopic TEP repair combined with primary fascial closure and pre-peritoneal mesh is a safe and feasible technique for groin hernia repair.

Glue mesh fixation is thought to cause less pain compared to tack mesh fixation during laparoscopic total extraperitoneal inguinal hernia repair (TEP). However, the clinical benefits of glue mesh fixation are still controversial. This study aimed to evaluate the acute pain, chronic pain, and recurrence rate between these two fixation methods. After reviewing all patients in our prospective hernia repair database from February 2008 to December 2017, we identified 583 patients who underwent TEP with tack mesh fixation and 70 patients with glue fixation by a single surgeon. Acute post-operative pain and activity level were evaluated using a Visual Analog Score (VAS) and the modified Medical Outcome Study (MOS) score. The primary endpoint was chronic pain 6 months after TEP. The secondary endpoints were acute pain, activity level, complications, and recurrence. After adjustment for potential confounding factors, the glue mesh fixation had significant lower VAS at 2 h post operation during rest and coughing and on the first day after surgery during coughing (p = 0.005, p

ObjectivesTo estimate the clinical and economic impact of intensive care unit-acquired bloodstream infections in Taiwan.DesignRetrospective cohort study.SettingNationwide Taiwanese population in the National Health Insurance Research Database and the Taiwan Nosocomial Infections Surveillance (2007–2015) dataset.ParticipantsThe first episodes of intensive care unit-acquired bloodstream infections in patients ≥20 years of age in the datasets. Propensity score-matching (1:2) of demographic data, comorbidities and disease severity was performed to select a comparison cohort from a pool of intensive care unit patients without intensive care unit-acquired infections from the same datasets.Primary and secondary outcome measuresThe mortality rate, length of hospitalisation and healthcare cost.ResultsAfter matching, the in-hospital mortality of 14 234 patients with intensive care unit-acquired bloodstream infections was 44.23%, compared with 33.48% for 28 468 intensive care unit patients without infections. The 14-day mortality rate was also higher in the bloodstream infections cohort (4323, 30.37% vs 6766 deaths, 23.77%, respectively; pCandida spp.ConclusionsIntensive care unit-acquired bloodstream infections in critically ill patients were associated with increased mortality, longer hospital stays and higher healthcare costs.

Background Although recent clinical trials raised concerns about the risk for heart failure (HF) in dipeptidyl peptidase-4 (DPP-4) inhibitor use, data on the cardiovascular risks in the patients with pre-existing HF are still lacking. Methods We used Taiwan9s National Health Insurance Research Database to identify 196 986 patients diagnosed with type 2 diabetes mellitus (T2DM) who had previous history of HF between 2009 and 2013. This population included 30 204 DPP-4 inhibitor users and 166 782 propensity score-matched DPP-4 inhibitor non-users. The outcomes of interest were all-cause mortality, combination of myocardial infarction (MI) and ischaemic stroke, and hospitalisation for HF. Results The incidence in DPP-4 users compared with non-users was 67.02 vs 102.85 per 1000 person-years for all-cause mortality, 37.89 vs 47.54 per 1000 person-years for the combination of MI and ischaemic stroke, 12.70 vs 16.18 per 1000 person-years for MI and 26.37 vs 32.46 per 1000 person-years for ischaemic stroke. The risk of all-cause mortality was lower in DPP-4 inhibitor users (HR 0.67, 95% CI 0.64 to 0.70), combination of MI and stroke (HR 0.81, 95% CI 0.76 to 0.87), MI (HR 0.80, 95% CI 0.71 to 0.89) and ischaemic stroke (HR 0.83, 95% CI 0.76 to 0.89) than in non-users. Notably, the risk of hospitalisation for HF did not differ significantly between groups. The results were similar after accounting for death as a competing risk. Conclusions In this nationwide T2DM cohort, the risks of mortality and the combination of MI and ischaemic stroke were lower for patients receiving DPP-4 inhibitors than for those who did not receive such treatment. DPP-4 inhibitor use was not associated with a higher risk of hospitalisation for HF even in patients with pre-existing HF.

Rationale: Patients with sepsis who survive to hospital discharge may present with ongoing high morbidity and mortality. However, little is known about the risk of long-term, all-cause mortality and cardiovascular outcomes after sepsis.Objectives: Our study aimed to investigate the long-term clinical outcomes in sepsis survivors.Methods: In this nationwide population-based study, data from patients with sepsis were retrieved from Taiwan’s National Health Insurance Research Database between 2000 and 2002. Each sepsis survivor was 1:1 propensity-matched to control subjects from two different control populations: subjects who were in the general population and subjects who were hospitalized for a nonsepsis diagnosis. The primary outcomes were all-cause mortality, major adverse cardiovascular events, myocardial infarction, heart failure, stroke, and sudden cardiac death or ventricular arrhythmia.Measurements and Main Results: Compared with matched population control subjects, sepsis survivors had higher risks...

Objective To examine the risk of acute kidney injury (AKI) in a nationwide cohort of patients with type 2 diabetes initiating dipeptidyl peptidase-4 (DPP-4) inhibitors. Patients and Methods This nested case-control study of a cohort of adult DPP-4 inhibitor users with type 2 diabetes who were hospitalized for AKI between January 1, 2010, and December 31, 2013, was conducted using Taiwan's National Health Insurance Research Database. Each AKI case was matched with one control subject according to duration of follow-up, age, sex, urbanization level, monthly income, comorbidity severity, and well-known predisposing factors for AKI. Odds ratios (ORs) for AKI were calculated according to current, recent, or past use of DPP-4 inhibitors. Results A total of 6752 cases with AKI and 6752 matched controls were analyzed. The exposure prevalence of DPP-4 inhibitor use in the previous year was higher among patients with AKI (adjusted OR, 1.20; 95% CI, 1.05-1.36; P =.006). In a stratified analysis, the association was significant for current DPP-4 inhibitor use (adjusted OR, 1.26; 95% CI, 1.08-1.48; P =.004), but not for recent or past use. Conclusion In this large contemporary cohort, DPP-4 inhibitor users had an increased risk of AKI development compared with nonusers. Further research is warranted to investigate the mechanism underlying this association.

The 2014 Eighth Joint National Committee guidelines for hypertension management emphasize the upper limit of blood pressure (BP) as the target for treatment in the elderly population. Given the uncertainty regarding optimal BP range, we aimed to investigate the association between observed BP and subsequent mortality in older people.We extracted data from 128,765 participants ≥65 years of age who underwent annual health examinations in a retrospective, observational community-based study from 2001 to 2010. Seated BP was measured using an oscillometric device. The outcomes were all-cause and cardiovascular mortality.As compared to participants with systolic BP at 130 to 139 mm Hg, the risk of all-cause mortality was significantly higher among those with110 (adjusted hazard ratios [aHRs], 1.12; 95% confidence interval [CI], 1.05-1.20), 140 to 149 (aHR, 1.08; 95% CI, 1.03-1.14), 150 to 159 (aHR, 1.07; 95% CI, 1.01-1.17), 160 to 169 (aHR, 1.11; 95% CI, 1.04-1.19), and ≥170 mm Hg (aHR, 1.25; 95% CI, 1.17-1.33), whereas the differences were not significant for those with 110 to119 (aHR, 1.06; 95% CI, 1.00-1.12) and 120 to 129 mm Hg (aHR, 1.03; 95% CI, 0.97-1.08). Similarly, diastolic BP at 40 to 79 mm Hg was associated with the lowest risk of all-cause mortality. The J-shaped curve relationship between BP and cardiovascular mortality was also observed.Observed systolic and diastolic BP other than 110 to 139 and 40 to 79 mm Hg, respectively, were associated with a worse outcome. Our large cohort study supports the J-shaped mortality with observed BP in older people.

To evaluate the long-term survival rate of critically ill sepsis survivors following cardiopulmonary resuscitation on a national scale.Retrospective and observational cohort study.Data were extracted from Taiwan's National Health Insurance Research Database.A total of 272,897 ICU patients with sepsis were identified during 2000-2010. Patients who survived to hospital discharge were enrolled. Post-discharge survival outcomes of ICU sepsis survivors who received cardiopulmonary resuscitation were compared with those of patients who did not experience cardiopulmonary arrest using propensity score matching with a 1:1 ratio.None.Only 7% (n = 3,207) of sepsis patients who received cardiopulmonary resuscitation survived to discharge. The overall 1-, 2-, and 5-year postdischarge survival rates following cardiopulmonary resuscitation were 28%, 23%, and 14%, respectively. Compared with sepsis survivors without cardiopulmonary arrest, sepsis survivors who received cardiopulmonary resuscitation had a greater risk of all-cause mortality after discharge (hazard ratio, 1.38; 95% CI, 1.34-1.46). This difference in mortality risk diminished after 2 years (hazard ratio, 1.11; 95% CI, 0.96-1.28). Multivariable analysis showed that independent risk factors for long-term mortality following cardiopulmonary resuscitation were male sex, older age, receipt of care in a nonmedical center, higher Charlson Comorbidity Index score, chronic kidney disease, cancer, respiratory infection, vasoactive agent use, and receipt of renal replacement therapy during ICU stay.The long-term outcome was worse in ICU survivors of sepsis who received in-hospital cardiopulmonary resuscitation than in those who did not, but this increased risk of mortality diminished at 2 years after discharge.

Renin-angiotensin-aldosterone system blockers are the preferred antihypertensive medications in patients with diabetes and prior stroke. This study aimed to compare the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in terms of major adverse cardiac events (MACEs) in patients with diabetes who survived ischemic stroke.We conducted an observational, nationwide, propensity score-matched cohort study using Taiwan's National Health Insurance Research Database. Patients aged at least 20 years with type 2 diabetes who initiated ACEI (n = 15,959) or ARB (n = 23,929) use within 90 days after discharge for first ischemic stroke between January 2000 and December 2011 were allocated to ACEI and ARB groups, respectively. The primary outcomes were MACEs (myocardial infarction, ischemic stroke, and cardiovascular mortality). The secondary outcomes were hospitalization for acute kidney injury and hyperkalemia. Intention-to-treat and as-treated models were used.Intention-to-treat analysis showed no significant difference between the ACEI and ARB groups in the outcomes of MACEs [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.95-1.04], including ischemic stroke (HR, 1.01; 95% CI, 0.97-1.06), myocardial infarction (HR, 1.06; 95% CI, 0.95-1.18), and cardiovascular mortality (HR, 0.98; 95% CI, 0.91-1.06). As-treated analysis produced similar results. Additionally, the groups showed no difference in the risk of hospitalization for acute kidney injury or hyperkalemia.Our study supports the hypothesis that the risks of MACEs and two additional secondary outcomes in patients with diabetes who survived ischemic stroke did not differ according to ACEI versus ARB use.

Background and objective Recent observational studies have shown that sleep apnoea (SA) is associated with increased risk of incident CKD. However, the contribution of SA relative to common traditional CKD risk factors remains unknown. The aims of this study were to investigate the long-term risk of incident CKD events following SA diagnosis and compare the relative contributions of SA, diabetes and hypertension. Methods Data were retrieved from Taiwan's National Health Insurance Research Database during the period between 2000 and 2010 for this retrospective cohort study. The cohorts are composed of patients (age ≥ 20 years) newly diagnosed with SA and matched subjects without SA. The two cohorts were followed until the occurrence of CKD, death or the end of 2010. Results The sample is composed of 43 434 individuals (8687 patients with SA and 34 747 matched non-SA subjects). A total of 157 new CKD events in patients with SA and 298 events in the matched non-SA cohort were recorded during a mean follow-up period of 3.9 years (incidence rates, 4.5 and 2.2/per 1000 person-years). The risk of CKD development was greater among patients with SA than in the matched non-SA cohort (adjusted hazard ratio (aHR) 1.58, 95% confidence interval ( CI): 1.29–1.94). The contribution of SA to the CKD hazard was similar to that of hypertension (aHR 1.17, 95% CI: 0.68–2.01, P = 0.56), whereas that of diabetes remained significantly higher (aHR 2.17, 95% CI: 1.21–3.90, P = 0.01). Conclusion SA was associated with an increase in the risk of CKD incidence similar to that of hypertension. See Editorial, page 578

Background— Whether oral anticoagulant use should be considered in patients undergoing hemodialysis with atrial fibrillation (AF) remains controversial because of the uncertainty regarding risk-benefit assessments. The purpose of this study was to investigate the risk of ischemic stroke in patients undergoing hemodialysis with new-onset AF, in comparison with those without arrhythmia. Methods and Results— This nationwide, population-based, propensity score–matched cohort study used data from Taiwan’s National Health Insurance Research Database during 1998 to 2011 for patients on hemodialysis with new-onset nonvalvular AF and matched subjects without arrhythmia. The clinical end points were ischemic stroke (fatal or nonfatal), all-cause death, and other serious adverse cardiovascular events. In comparison with the matched cohort, patients with AF (n=6772) had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.13–1.43), all-cause death (aHR, 1.59; 95% CI, 1.52–1.67), in-hospital cardiovascular death (aHR, 1.83; 95% CI, 1.71–1.94), myocardial infarction (aHR, 1.33; 95% CI, 1.17–1.51), and hospitalization for heart failure (aHR, 1.90; 95% CI, 1.76–2.05). After considering in-hospital death as a competing risk, AF significantly increased the risk of heart failure (HR, 1.56; 95% CI, 1.45–1.68), but not those of ischemic stroke and myocardial infarction. Additionally, the predictive value of the CHA 2 DS 2 –VASc score for ischemic stroke was diminished in the competing-risk model. Conclusions— The risk of stroke was only modestly higher in patients undergoing hemodialysis with new-onset AF than in those without AF, and it became insignificant when accounting for the competing risk of in-hospital death.

Background Previous studies have demonstrated that high estimated glomerular filtration rate (eGFR) is paradoxically associated with an increased risk of mortality, and the association becomes more predominant in older people. However, the role of malnutrition–inflammation–cachexia syndrome (MICS) in the association between eGFR and mortality has never been explored. Methods We conducted a community-based cohort study using data from the Taipei City Elderly Health Examination Database, collected during the period 2001–10. All participants aged ≥65 years were included and stratified by the absence or presence of MICS, which is defined as the presence of at least one of the following markers: body mass index

Purpose To determine whether migraine is associated with an increased risk of developing ocular motor cranial nerve palsies (OMCNP). Design Nationwide retrospective cohort study. Participants Medical records of patients with migraine who were entered in the National Health Insurance Research Database (NHIRD) between 2005 and 2009 were retrieved from the NHIRD in Taiwan. Two cohorts were selected: patients with migraine (n = 138 907) and propensity score–matched controls (n = 138 907). Main Outcome Measures Cohorts were followed until the end of 2010, death, or occurrence of cranial nerve (CN)3, CN4, or CN6 palsies. A Cox proportional hazards regression model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs), which were used to compare to the risk of developing CN3, CN4, and CN6 palsy between cohorts. Results After a mean follow-up period of 3.1 years (range, 1–6 years), the migraine cohort exhibited a greater risk of developing subsequent CN3, CN4, and CN6 palsies compared with the control cohort (HR, 2.67, P P P Conclusions Migraine is an unrecognized risk factor for OMCNP development in adults. Further studies are needed to validate our findings and to delineate the exact pathophysiologic mechanisms linking migraine and OMCNP.

Background and Purpose: The aim of this nationwide cohort study was to evaluate whether the occurrence of isolated 3rd, 4th or 6th cranial nerve (CN) palsies is associated with a higher risk of ischemic stroke. Methods: This study utilized data from Taiwan Longitudinal Health Insurance Database during 1995-2012. Subjects aged 20 years or older who had isolated CN 3/4/6 palsies diagnosed by a neurologist or ophthalmologist between January 2000 and December 2011 were included. A set of propensity score matched, randomly sampled patients who had never been diagnosed with CN 3/4/6 palsies were extracted to constitute the control group (cases and controls = 1:4). All subjects were followed until death, loss due to follow-up or completion of the study. Cox proportional hazard regression model stratified by matched pairs was used to estimate the hazards ratio (HR) of ischemic stroke. Results: A total of 657 patients with isolated CN 3/4/6 palsies (61.1% male, mean age 54.8 years) were identified. Compared with control group, the patients with isolated CN 3/4/6 palsies exhibited an increased risk of ischemic stroke (CN3: adjusted HR 3.69 (95% CI 2.20-6.19); CN4: 2.71 (95% CI 1.11-6.64); CN6: 2.15 (95% CI 1.31-3.52)). The association between CN 3/4/6 palsies and ischemic stroke was detected in both separate subgroup and sensitivity analyses. Conclusions: The patients with CN 3/4/6 palsies exhibited an increased risk of developing ischemic stroke. Therefore, isolated ocular motor nerves palsies appear to represent an unrecognized risk factor for ischemic stroke, and these require further confirmation and exploration.

Background The comorbidity profile, especially cancer risk, of narcoleptic patients has seldom been explored. We used a nationwide database to evaluate the risk of cancer among adult narcoleptic patients. Methods We conducted the cohort study using National Health Insurance Research Database from 2000 to 2009. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort with that of the general population. Results 2833 narcoleptic patients were identified after excluding patients with antecedent malignancy and age younger than 18 years old. The study cohort was observed for 15,913 person-years during a 10-year period. The median follow-up interval was 5.6 ± 3.0 years. Seventy-four cancers occurred in during the follow-up. The risk of all cancers was found significantly increased in adult narcoleptic patients (SIR 1.32; 95% CI, 1.04–1.66, p = 0.0248). Regarding sex, the overall cancer risk was increased in female patients (SIR 1.52; 95% CI, 1.05–2.13, p = 0.026). Furthermore, females were found to have more head and neck cancers (SIR 6.17; 95% CI, 1.66-15.80, p = 0.009) and gastric cancers (SIR 4.87; 95% CI, 1.31–12.48, p = 0.02). For males, the incidence of overall and specific cancer types was not significantly increased. Conclusions Adult narcoleptic patients had a higher risk for cancer. Further research is warranted to elucidate the mechanism underlying its association.

In a large observational database study of add-on treatments to metformin, the addition of dipeptidyl peptidase-4 (DPP-4) inhibitors was associated with a lower risk for all-cause mortality, stroke...

To compare the renal outcomes in patients of unilateral renal cell carcinoma (RCC) with upper tract urothelial carcinoma (UTUC) following surgical resection of the tumor-bearing kidney, and to investigate the potential predictors in renal function decline.In this retrospective cohort study, 319 RCC patients undergoing radical nephrectomy (RN) and 297 UTUC patients undergoing radical nephroureterectomy were recruited from a tertiary medical center between 2001 and 2010. Demographic data, co-morbidity, smoking habit, baseline estimated glomerular filtration rate (eGFR) calculated by chronic kidney disease-epidemiology equation, as well as tumor staging of RCC and UTUC, were recorded. The primary endpoint was serum creatinine doubling and/or end-stage renal disease (ESRD) necessitating long-term dialysis. Cox proportional hazard model and Fine and Gray's competing risk regression accounting for death were used to model renal outcome.UTUC patients had a higher incidence rate of renal function deterioration than RCC patients did (15.01 vs. 2.68 per 100 person-years, p0.001). In Cox proportional hazard model and Fine and Gray's competing risk regression, UTUC was significantly associated with increased risk of creatinine doubling and/or ESRD necessitating dialysis (hazard ratio, 3.13; 95% confidence interval, 2.01-4.87) as compared to RCC following unilateral RN. Nevertheless, our study is observational in nature and cannot prove causality.UTUC per se is strongly associated with kidney disease progression as compared to RCC following unilateral nephrectomy. Further studies are needed to elucidate this association.

Objective Gastro-esophageal reflux disease (GERD) is a highly prevalent disorder; however, important questions remain regarding the link between GERD and extra-esophageal cancers. This nationwide cohort study investigated the risk of developing head and neck cancers (HNCs) among patients with GERD. Methods Newly diagnosed GERD patients aged ≥20 years without antecedent cancer were included. Case data were obtained from the National Health Insurance Research Database covering period from 1998 to 2010. We compared the standardized incidence ratios (SIRs) of cancer among GERD patients with those of the general population. Results A total of 98 cancers were identified among the 39,845 GERD patients in the study, representing 128,361 person-years. The SIR for all cases of cancer was 1.59 (95% CI 1.29–1.93). GERD patients exhibited significantly higher SIRs for oropharyngeal (SIR 3.58, 95% CI 1.85–6.25) and hypopharyngeal (SIR 3.96, 95% CI 2.35–6.26) cancers. Male patients had a significantly higher risk of HNCs (SIR 1.70, 95% CI 1.36–2.10), particularly oropharyngeal (SIR 4.01, 95% CI 2.00–7.17) and hypopharyngeal (SIR 3.91, 95% CI 2.28–6.26) cancers. Following adjustment for age and co-morbidities, the hazard ratio was 9.06 (95% CI 4.70–17.44) for males compared to females. Conclusion There may be a potential association between GERD and risk of HNCs, which however merits further studies to confirm the causal relationship. Our observations indicate a need for careful extra-esophageal examination of patients with acid reflux. Our findings also underline the importance of raising awareness among clinicians regarding the possibility of concurrent HNCs in GERD patients with refractory laryngo-pharyngeal symptoms.

Background The link between elevated serum uric acid ( SUA ) levels and cardiovascular disease ( CVD )–related mortality in the elderly population remains inconclusive. Nutritional status influences both SUA and CVD outcomes. Therefore, we investigated whether SUA ‐predicted mortality and the effect‐modifying roles of malnourishment in older people. Methods and Results A longitudinal Taiwanese cohort including 127 771 adults 65 years and older participating in the Taipei City Elderly Health Examination Program from 2001 to 2010 were stratified by 1‐mg/dL increment of SUA . Low SUA (2 . Study outcomes were all‐cause and CVD ‐related mortality. Cox models were used to estimate hazard ratios ( HRs ) of mortality, after adjusting for 20 demographic and comorbid covariates. Over a median follow‐up of 5.8 years, there were 16 439 all‐cause and 3877 CVD ‐related deaths. Compared with the reference SUA strata of 4 to SUA HR , 1.16; 95% confidence interval, 1.07–1.25) and ≥8 mg/dL ( HR , 1.13; confidence interval, 1.06–1.21), with progressively elevated risks at both extremes. Similarly, increasingly higher CVD ‐related mortality was found at the SUA level HR , 1.19; confidence interval, 1.00–1.40) and ≥7 mg/dL ( HR , 1.17; confidence interval, 1.04–1.32). Remarkably, among the low SUA (CVD ‐related mortality. This modifying effect of malnourishment remained consistent across subgroups. Conclusions SUA ≥8 or CVD ‐related mortality in the elderly, particularly in those with malnourishment.