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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.

Influenza vaccine effectively reduced risks for in-hospital death or hospitalization, regardless of statin use., Debates on whether statin use reduces the effectiveness of influenza vaccines against critical illness and death among persons >65 years of age continue. We conducted a study of 9,427,392 persons >65 years of age who did and did not receive influenza vaccinations during 12 consecutive influenza seasons, 2000–01 through 2011–12. Using data from Taiwan’s National Health Insurance Research Database, we performed propensity score-matching to compare vaccinated persons with unvaccinated controls. After propensity score-matching, the vaccinated group had lower risks for in-hospital death from influenza and pneumonia and for hospitalization for pneumonia and influenza, circulatory conditions, and critical illnesses compared with the unvaccinated group. We stratified the 2 groups by statin use and analyzed data by interaction analysis and saw no statistically significant difference. We found that influenza vaccine effectively reduced risks for hospitalization and death in persons >65 years of age, regardless of statin use.

Vascular diseases are commonly observed in patients with autosomal dominant polycystic kidney disease (ADPKD). We aim to investigate the differences in the risk for arteriovenous fistula or graft (AVF/AVG) dysfunction in haemodialysis (HD) patients with and without ADPKD. 557 ADPKD and 1671 non-ADPKD patients were enrolled in the study after propensity score matching. The primary outcome measure is the incidence rate of AVF/AVG dysfunction. The incidence rates and risks of AVF/AVG dysfunction (per 100 person-years) for ADPKD and non-ADPKD patients were (1) 38.83 and 48.99 [SHR = 0.79, P = 0.137], respectively, for within 90 days, (2) 45.85 and 51.31 [SHR = 0.90, P = 0.300], respectively, for within 180 days, (3) 44.42 and 41.40 [SHR = 1.08, P = 0.361], respectively, for within the first year, (4) 27.38 and 24.69 [SHR = 1.09, P = 0.168], respectively, for within 5 years, (5) 17.35 and 13.80 [SHR = 1.19, P = 0.045], respectively, for between the 1st and 10th year, and (6) 25.40 and 21.22 [SHR = 1.14, P = 0.031], respectively, for all periods. ADPKD patients had lower incidence rates of AVF/AVG dysfunction within the first 180 days than non-ADPKD patients, but presented a higher incidence rate after 1 year of AVF/AVG creation and onwards.

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

PurposeThis study aimed to compare the oncological outcomes and surgical complications of patients with upper tract urothelial carcinoma (UTUC) treated with different minimally invasive techniques for nephroureterectomy.MethodsFrom the updated data of the Taiwan UTUC Collaboration Group, a total of 3,333 UTUC patients were identified. After excluding ineligible cases, we retrospectively included 1,340 patients from 15 institutions who received hand-assisted laparoscopic nephroureterectomy (HALNU), laparoscopic nephroureterectomy (LNU) or robotic nephroureterectomy (RNU) between 2001 and 2021. Kaplan-Meier estimator and Cox proportional hazards model were used to analyze the survival outcomes, and binary logistic regression model was selected to compare the risks of postoperative complications of different surgical approaches.ResultsAmong the enrolled patients, 741, 458 and 141 patients received HALNU, LNU and RNU, respectively. Compared with RNU (41.1%) and LNU (32.5%), the rate of lymph node dissection in HALNU was the lowest (17.4%). In both Kaplan-Meier and univariate analysis, the type of surgery was significantly associated with overall and cancer-specific survival. The statistical significance of surgical methods on survival outcomes remained in multivariate analysis, where patients undergoing HALNU appeared to have the worst overall (p = 0.007) and cancer-specific (p = 0.047) survival rates among the three groups. In all analyses, the surgical approach was not related to bladder recurrence. In addition, HALNU was significantly associated with longer hospital stay (p = 0.002), and had the highest risk of major Clavien-Dindo complications (p = 0.011), paralytic ileus (p = 0.012), and postoperative end-stage renal disease (p ConclusionsMinimally invasive surgery can be safe and feasible. We proved that compared with the HALNU group, the LNU and RNU groups have better survival rates and fewer surgical complications. It is crucial to uphold strict oncological principles with sophisticated technique to improve outcomes. Further 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.

Peritoneal dialysis (PD) is a treatment modality for end-stage renal disease (ESRD) patients. Dextrose is a common osmotic agent used in PD solutions and its absorption may exacerbate diabetes mellitus, a common complication of ESRD. PD solutions also contain glucose degradation products (GDPs) that may lead to encapsulating peritoneal sclerosis (EPS), a severe complication of PD. A previous study showed that far-infrared (FIR) therapy improved a patient’s gastrointestinal symptoms due to EPS. Due to limited literature on the matter, this study aims to investigate dialysate GDPs and peritoneal function in diabetic patients on PD. Thirty-one PD patients were enrolled and underwent 40 min of FIR therapy twice daily for six months. We demonstrated the effect of FIR therapy on the following: (1) decrease of methylglyoxal (p = 0.02), furfural (p = 0.005), and 5-hydroxymethylfurfural (p = 0.03), (2) increase of D/D0 glucose ratio (p = 0.03), and (3) decrease of potassium levels (p = 0.008) in both DM and non-DM patients, as well as (4) maintenance and increase of peritoneal Kt/V in DM and non-DM patients, respectively (p = 0.03). FIR therapy is a non-invasive intervention that can decrease dialysate GDPs in PD patients by improving peritoneal transport rate and solute removal clearance, while also maintaining dialysis adequacy.

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.

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded, the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage (p &lt, 0.001) and the presence of lymphovascular invasion (p = 0.002), whereas patients with UT often had synchronous bladder tumor (p &lt, 0.001), and were more likely to bear multiple lesions (p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121&ndash, 1.767, p = 0.003, cancer-specific survival: HR 1.562, 95% CI 1.169&ndash, 2.085, p = 0.003, disease-free survival: HR 1.363, 95% CI 1.095&ndash, 1.697, p = 0.006, bladder-recurrence-free survival: HR 1.411, 95% CI 1.141&ndash, 1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT.

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.

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 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.

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.

High serum lipid levels are independent predictors of mortality risk in the general population. Recent data suggest that this may not apply in the older populations, and even acts in the opposite direction. In consideration of the frail state, minimum amount of physical activity (60–100 minutes each week) may be more suitable for older individuals but its role in lipid profiles has never been explored. Between 2006 and 2010, we conducted a cohort study of 83,820 participants aged ≥65 years using the Taipei City Elderly Health Examination Database. Participants were classified as inactive, low or high in their level of physical activity. Older individuals with lowest quintile of total cholesterol, non-HDL and HDL were associated with increased risk of all-cause mortality compared to those with other quintile of these lipid profiles. Compared to inactive older individuals, both low (adjusted hazard ratios [aHR] 0.75, 95% confidence interval [CI] 0.70–0.81) and high active older individuals (aHR 0.55, 95% CI 0.51–0.59) were associated with lower risks of mortality. Physical activity, even minimum volume of exercise, in older people has to be encouraged to reduce the increased risk of mortality from low serum lipid levels.

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.

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

Whether elevated serum uric acid levels (SUA) predict renal dysfunction remains controversial in the elderly. Therefore, we investigated the association between SUA and early renal function decline defined as an estimated glomerular filtration rate (eGFR) reduction ≥30% over 2 years. From 2001 to 2010, we conducted a longitudinal cohort study comprising 44,078 participants aged ≥65 years in the Taipei City Elderly Health Examination Database. Participants were classified by 1-mg/dL increment of SUA. We used multivariable logistic and Cox regression analyses to compare the risk of early renal function decline in different SUA groups. Compared to the reference SUA group of 5.0–5.9 mg/dL, hyperuricemic participants had increased risks of eGFR decline, starting at SUA ≥6.0 mg/dL (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] = 1.00–1.45). The risk progressively elevated as SUA increased, with the highest in the SUA ≥10.0 mg/dL group (aOR = 3.20, CI = 2.39–4.28). Multivariable Cox regression further confirmed that hyperuricemia was 1.12-fold (CI = 1.03–1.22, SUA ≥6.0 mg/dL) to 1.6-fold (CI = 1.37–1.86, SUA ≥10.0 mg/dL) more likely to develop early eGFR decline. Hyperuricemia-associated increased risks for early eGFR decline were consistent across subgroup and sensitivity analyses. Collectively, SUA ≥6.0 mg/dL independently predicted early renal dysfunction with eGFR decline ≥30% over 2 years in older people.

ObjectivesAnimal and ex vitro studies suggested lipid-lowering agents (LLAs) may be used as an adjunct to standard anti- tuberculosis (TB) treatment. No human study has been conducted to date. Using the Taiwan National Health Insurance Research Database (NHIRD), the current population-based cohort study sought to examine the association between use of LLAs and outcomes of patients with pulmonary TB receiving anti-TB treatment.MethodsUsing a NHIRD from 2003 to 2010, this population-based cohort study retrospectively examined the association between LLAs (statins or fibrates) and the outcomes of patients with pulmonary TB receiving anti-TB treatment.ResultsA total of 1452 adult patients newly diagnosed with pulmonary TB during the study period were identified and compared with 5808 matched patients. In the LAA cohort, 1258 received statin, and 295 received fibrate. Compared with patients who did not take LLA, patients who took oral LLAs had similar incidence of treatment completion at 9, 12, and 24 months.ConclusionsNeither statins nor fibrates provide clinical benefit superior to that achieved with standard anti-tuberculosis treatment. Future clinical trials should investigate the effects of statins and fibrates on short-course standard anti-TB therapy.

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