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To identify whether urolithiasis with or without hydronephrosis has an impact on acute kidney injury (AKI) in patients with urinary tract infection (UTI). This study aimed to identify whether urolithiasis with or without hydronephrosis has an impact on AKI in patients with UTI. This retrospective study enrolled hospitalized UTI patients who underwent imaging in an acute care setting from January 2006 to April 2019. Of the 1113 participants enrolled, 191 (17.2%) had urolithiasis and 76 (6.8%) had ureteral stone complicated with hydronephrosis. Multivariate logistic regression analysis showed that in UTI patients with urolithiasis, the presence of ureteral stone with concomitant hydronephrosis was an independent risk factor for AKI (odds ratio [OR] 2.299, 95% confidence interval [CI] 1.112–4.755, P = 0.025). In addition, urolithiasis was associated with an increased risk for AKI (OR 2.451, 95% CI 1.369–4.389, P = 0.003) in UTI patients without hydronephrosis. The presence of ureteral stone with hydronephrosis increases the risk for AKI of UTI patients with urolithiasis, and urolithiasis remains a risk factor of AKI in UTI patients without hydronephrosis.

Hyperuricemia has been associated with chronic kidney disease (CKD) progression. The antihyperuricemic febuxostat's potential renoprotective effect has been demonstrated in stage 1–3 CKD. Large‐scale studies comparing the renoprotective potential of febuxostat and allopurinol in advanced CKD are lacking. We exclusively selected 6,057 eligible patients with predialysis stage 5 CKD prescribed either febuxostat or allopurinol using the National Health Insurance Research Database in Taiwan during 2012–2015. There were 69.57% of allopurinol users and 42.01% febuxostat users who required long‐term dialysis (P

Erythropoietic medications such as including erythropoietin (EPO) are known to be neuroprotective and to correlate with improved cognitive functions. However, it is not known whether supplementation with EPO reduces the risk of dementia in end-stage renal disease (ESRD) patients receiving hemodialysis (HD). Here, we determined whether EPO levels correlate with the incidence of different dementia subtypes, including Alzheimer's disease (AD), vascular dementia (VaD), and unspecified dementia (UnD), and whether such associations vary with annual cumulatively defined daily doses (DDDs) of EPO for ESRD patients receiving HD. This retrospective study included data from 43,906 adult ESRD patients who received HD between 1999 and 2010. Using hazard ratios and Cox regression models, we found that patients receiving EPO had a 39% lower risk of general dementia than those in the non-EPO group. Similarly, the risks of VaD and UnD was lower for patients in the EPO cohort. The risk of dementia was further reduced in HD patients treated with EPO in combination with iron. Our results suggest that the use of EPO medications in HD patients is associated with a reduced risk of VaD and UnD, but not AD, regardless of whether EPO is used alone or in combination with iron.

Background Targeting higher hemoglobin levels with erythropoietin to treat anemia in patients with chronic kidney disease is associated with increased cardiovascular risk, including that of stroke. The risks of the subtypes of stroke, ischemic, hemorrhagic, and unspecified, following the administration of erythropoietin in patients with end‐stage renal disease receiving hemodialysis remain unclear. Methods and results Overall, 12 948 adult patients with end‐stage renal disease treated during 1999 to 2010 who had undergone hemodialysis were included. The study end points were the incidences of stroke and its subtypes. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) of stroke and its subtypes in erythropoietin recipients compared with nonrecipients. Patients in the erythropoietin cohort did not have an increased risk of stroke compared with those in the nonerythropoietin cohort (adjusted HR, 1.03; 95% CI, 0.92–1.15). Compared with patients in the nonerythropoietin cohort, the risks of ischemic, hemorrhagic, or unspecified stroke were not higher in patients in the erythropoietin cohort (adjusted HRs, 1.08 [95% CI, 0.93–1.26], 0.96 [95% CI, 0.78–1.18], and 1.03 [95% CI, 0.80–1.32], respectively). Increased risks of stroke and its subtypes were not observed with even large annual defined daily doses of erythropoietin (>201). Conclusions Erythropoietin in patients receiving hemodialysis is not associated with increased risk of stroke or any of its subtypes.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for the fourth leading cause of all cancer deaths. Scientific evidence has found that plant extracts seem to be a reliable choice due to their multitarget effects against HCC. Juniperus communis has been used for centuries in traditional medicine and its anticancer properties have been reported. As a result, the purpose of the study was to investigate the anticancer effect and mechanism of J. communis extract (JCo extract) on HCC in vitro and in vivo. In the present study, we found that JCo extract inhibited the growth of human HCC cells by inducing cell cycle arrest at the G0/G1 phase, extensive apoptosis and suppressing metastatic protein expressions in HCC cells. Moreover, the combinational treatment of JCo and VP-16 was found to enhance the anticancer effect, revealing that JCo extract might have the potential to be utilized as an adjuvant to promote HCC treatment. Furthermore, in vivo study, JCo extract significantly suppressed HCC tumor growth and extended the lifespan with no or low systemic and pathological toxicity. JCo extract significantly up-regulated the expression of pro-apoptotic proteins and tumor suppressor p53, suppressed VEGF/VEGFR autocrine signaling, down-regulated cell cycle regulatory proteins and MMP2/MMP9 proteins. Overall, our results provide a basis for exploiting JCo extract as a potential anticancer agent against HCC.

Cedrus atlantica is widely used in herbal medicine. However, the anti-cancer activity of C. atlantica extract (CAt extract) has not been clarified in hepatocellular carcinoma. In the study, we elucidated the anti-hepatoma capacity of CAt extract on HCC in vitro and in vivo. To explore the anti-hepatoma mechanisms of the CAt extract in vitro, HCC and normal cells were treated with the CAt extract, which showed marked inhibitory effects on HCC cells in a dose-dependent manner; in contrast, the CAt extract treatment was less cytotoxic to normal cells. In addition, our results indicate that the CAt extract induced apoptosis via caspase-dependent and independent apoptosis pathways. Furthermore, the CAt extract inhibited HCC tumor cell growth by restraining cell cycle progression, and it reduced the signaling of the AKT, ERK1/2, and p38 pathways. In the xenograft model, the CAt extract suppressed HCC tumor cell growth and prolonged lifespan by inhibiting PCNA protein expression, repressing part of the VEGF-induced autocrine pathway, and triggering strong expression of cleaved caspase-3, which contributed to cell apoptosis. Moreover, the CAt extract did not induce any obvious changes in pathological morphology or body weight, suggesting it had no toxicity. CAt extract exerted anti-tumor effects on HCC in vitro and in vivo. Thus, CAt extract could be used as a potential anti-cancer therapeutic agent against HCC.

Breast cancer is the second most common malignancy in women. Current clinical therapy for breast cancer has many disadvantages, including metastasis, recurrence, and poor quality of life. Furthermore, it is necessary to find a new therapeutic drug for breast cancer patients to meet clinical demand. n-Butylidenephthalide (BP) is a natural and hydrophobic compound that can inhibit several tumors. However, BP is unstable in aqueous or protein-rich environments, which reduces the activity of BP. Therefore, we used an LPPC (Lipo-PEG-PEI complex) that can encapsulate both hydrophobic and hydrophilic compounds to improve the limitation of BP. The purpose of this study is to investigate the anti-tumor mechanisms of BP and BP/LPPC and further test the efficacy of BP encapsulated by LPPC on SK-BR-3 cells. BP inhibited breast cancer cell growth, and LPPC encapsulation (BP/LPPC complex) enhanced the cytotoxicity on breast cancer by stabilizing the BP activity and offering endocytic pathways. Additionally, BP and LPPC-encapsulated BP induced cell cycle arrest at the G0/G1 phase and might trigger both extrinsic as well as intrinsic cell apoptosis pathway, resulting in cell death. Moreover, the BP/LPPC complex had a synergistic effect with doxorubicin of enhancing the inhibitory effect on breast cancer cells. Consequently, LPPC-encapsulated BP could improve the anti-cancer effects on breast cancer in vitro. In conclusion, BP exhibited an anti-cancer effect on breast cancer cells, and LPPC encapsulation efficiently improved the cytotoxicity of BP via an acceleration of entrapment efficiency to induce cell cycle block and apoptosis. Furthermore, BP/LPPC exhibited a synergistic effect in combination with doxorubicin.

Background. An increased incidence of end-stage renal disease (ESRD) in stroke patients has not been confirmed. The aim of this population-based study was to examine the risk of ESRD in stroke patients in Taiwan. Methods. We conducted a nationwide cohort study of 442 355 patients newly diagnosed with stroke, but without prior history of ESRD. Data were collected from Taiwan’s National Health Insurance claims data during 2000–2008. Incidence and standardized incidence ratio (SIR) of ESRD were calculated using the general population of Taiwan as the reference. Results. Among all stroke patients, 7813 (1.77%) developed ESRD with a mean follow-up of 4.11 years. The SIR for ESRD was 2.78 [95% confidence interval (CI): 2.72–2.84] among stroke patients of all ages and was 22.73 (95% CI: 20.39–25.20) for patients aged 25–44 years. Male patients with stroke had a higher risk of ESRD (SIR: 2.94, 95% CI: 2.85–3.03) among stroke patients of all ages, and it was 23.41 (95% CI: 20.46– 26.36) for male patients aged 25–44 years. Conclusions. Increased risk of ESRD in stroke patients is confirmed in Taiwan, and male patients between ages 25 and 44 years were at higher risk of ESRD compared with their counterparts in the general population. The clinical implication of our results is to closely monitor renal function in stroke patients, particularly those of younger age.

Chronic kidney disease (CKD) has become a burden of health care globally. However, data on epidemiology, clinical features, and outcomes of urinary tract infection (UTI) in this population are scarce. This study aims to retrospectively review such data. Materials and methods: A retrospective cohort study was conducted from 1 January 2005 to 31 December 2011 in patients with CKD requiring hospitalization. Patients who had upper and lower UTIs were compared for demography and clinical data. Logistic regression was used to assess which variables were associated with upper UTI. Results: A total of 276 bacteriuria patients were admitted to our ward with upper and lower UTIs. The average ages of the upper and lower UTI patients were 59.21 ± 16.54 and 71.18 ± 14.77 years, respectively. The results of logistic regression analysis showed that age (OR 0.946, P < 0.001), female sex (OR 4.695, P < 0.001), and renal stones (OR 8.232, P < 0.001) were independently associated with upper UTI. Conclusion: This study shows that patients with CKD and UTIs were elderly, and that females were prone to have more bacteriuria and upper UTIs than males. In addition, patients who had renal stones were more prone to have upper UTI than other bacteriuria patients. Aggressive treatment of renal stones should be considered in these patients.

Introduction. Severe sepsis and septic shock are associated with substantial mortality. However, few studies have assessed the risk of septic shock among patients who suffered from urinary tract infection (UTI).Materials and Methods. This retrospective study recruited UTI cases from an acute care hospital between January 2006 and October 2012 with prospective data collection.Results. Of the 710 participants admitted for UTI, 80 patients (11.3%) had septic shock. The rate of bacteremia is 27.9%; acute kidney injury is 12.7%, and the mortality rate is 0.28%. Multivariable logistic regression analyses indicated that coronary artery disease (CAD) (OR: 2.521, 95% CI: 1.129–5.628,P=0.024), congestive heart failure (CHF) (OR: 4.638, 95% CI: 1.908–11.273,P=0.001), and acute kidney injury (AKI) (OR: 2.992, 95% CI: 1.610–5.561,P=0.001) were independently associated with septic shock in patients admitted with UTI. In addition, congestive heart failure (female, OR: 4.076, 95% CI: 1.355–12.262,P=0.012; male, OR: 5.676, 95% CI: 1.103–29.220,P=0.038, resp.) and AKI (female, OR: 2.995, 95% CI: 1.355–6.621,P=0.007; male, OR: 3.359, 95% CI: 1.158–9.747,P=0.026, resp.) were significantly associated with risk of septic shock in both gender groups.Conclusion. This study showed that patients with a medical history of CAD or CHF have a higher risk of shock when admitted for UTI treatment. AKI, a complication of UTI, was also associated with septic shock. Therefore, prompt and aggressive management is recommended for those with higher risks to prevent subsequent treatment failure in UTI patients.

Objective The purpose of this study is to compare the characteristics of those ertapenem-treated adult patients with and without development of seizures, and identify the associated factors for the development of seizures. Methods This retrospective study was conducted at Chia-Yi Christian Hospital from January 2012 to December 2014. Patients developing seizures during their ertapenem treatment course were identified as case patients. Those without seizures who had received ertapenem for at least five days were considered as the pool of control patients. For each case patient, four matched patients from the control pool were randomly selected as the final control group, based on age, gender, and the date of ertapenem prescription. Results A total of 1706 ertapenem-treated patients were identified, 33 (1.9%) individuals developed seizures with the enrollment of 132 matched control patients. Among these 33 patients, the average age was 79.3 ± 7.5 years, and 20 (60.6%) were male. The mean Charlson co-morbidity score was 4.5 ± 2.4, and the first episode of seizure happened 3.3 ± 2.6 days after receiving ertapenem. In multivariate logistic regression analysis, the independent predictors associated with the development of ertapenem-associated seizures were old stroke (OR, 14.36; 95% CI, 4.38–47.02; p < 0.0001), undergoing brain images within one year prior to the admission (OR, 5.73; 95% CI, 1.78–18.43; p = 0.0034), low hemoglobin level (OR, 3.88; 95% CI, 1.28–12.75; p = 0.0165) and low platelet count (OR, 4,94; 95% CI, 1.56–15.68; p = 0.0067) at presentations, and protective factors against the development of seizures were heart failure (OR, 0.04; 95% CI, 0.00–0.63; p = 0.0222), concomitant use of steroids (OR, 0.19; 95% CI, 0.05–0.77; p = 0.0201), or antiplatelet agents (OR, 0.12; 95% CI, 0.02–0.63, p = 0.0123) with ertapenem. Conclusions The development of ertapenem-associated seizures may occur more frequently and much earlier due to its widespread use in treating drug-resistant pathogens, especially when these pathogens emerged worldwide.Our study would help physician to estimate the risk of developing seizure among patients receiving ertapenem.

The goal of this study was to compare the clinical and pathological features of urothelial carcinoma (UC) identified in patients with end-stage renal disease (ESRD) and advanced-stage chronic kidney disease (CKD). The predictive value of CKD on patient mortality in these UC patients was also analyzed.From January 1997 to December 2008, 141 patients with pathologically proven UC with stage 4/5 CKD (predialysis) and patients with ESRD receiving long-term dialysis were identified under an institutional review board approval protocol. The medical records and survival outcome of these patients were reviewed.A total of 141 UC patients with renal diseases (n = 97, 68.8%, of stage 4/5 CKD; n = 44, 31.2%, at dialysis) were enrolled. Patients with stage 4/5 CKD were significantly older, male gender, less anemic and more likely to have higher prevalence of diabetes mellitus (P0.05). We noticed a more significant increase in the frequency of high-stage UC (24.7% and 6.8%) and a larger tumor size (50.5% and 27.3%) in patients with stage 4/5 CKD, compared with patients with ESRD (P0.05). Old age at the time of dialysis initiation in patients with ESRD [hazard ratio (HR) = 1.121, P = 0.039], male gender (HR = 6.822, P = 0.016) and high-stage tumors (HR = 5.012, P = 0.008) in patients with stage 4/5 CKD were independent predictors of mortality from UC.Patients with stage 4/5 CKD had more aggressive histological UC patterns than did patients with ESRD.

Only few studies have reported that betel nut (BN) chewing is independently associated with chronic kidney disease (CKD); however, the sample size was relatively small. This study was to explore further the association between BN chewing and CKD using a larger case series.We retrospectively reviewed the records of a health check-up program from 2003 to 2009. Laboratory tests, medical history and status of cigarette smoking, alcohol drinking and BN chewing were compared between CKD and non-CKD groups. We checked interaction effects between BN chewing and all other covariates, and conducted multivariate logistic regression analysis to explore the risk of CKD with BN chewing.A total of 27 482 participants (15 491 females and 11 991 males, mean age 58.02 ± 11.85 years) were included in the study, of whom 4519 (16.4%) had CKD and 1608 (5.9%) chewed BN. CKD prevalence in the chewers was higher than in the non-chewers in all age groups per decade. BN chewing was significantly associated with CKD in overall subjects (odds ratio (OR) = 1.23, P = 0.027) and also in the male (OR = 1.23, P = 0.035), non-drinking (OR = 1.62, P = 0.000), non-diabetic (OR = 1.27, P = 0.021), and non-proteinuric groups (OR = 1.30, P = 0.013). This relationship was insignificant in female, drinking, diabetic and proteinuric groups.The association between BN chewing and CKD seemed conditional on demographics, health behaviours, and underlying co-morbidities. This association should be interpreted cautiously.

Taiwan is a highly endemic area for urothelial carcinoma (UC) and chronic kidney disease (CKD). We evaluate the gender effect on the relationship between renal outcome and clinical characteristics of CKD patients with UC.The clinical and pathologic records of 404 patients were retrospectively analyzed. We calculated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) equation, and staged CKD status according to K/DOQI guideline.The female group had a significantly higher proportion (67.6% vs 29.0%, P 0.001) of upper urinary tract urothelial carcinoma (UUT-UC). Pathologically, the frequency of high T stage UC (32.4% and 19.1%; P = 0.003), high-grade UC (89.4% and 75.6%; P = 0.001), and larger UC (51.4% and 37.8%; P = 0.009) in the female patients were significantly higher, when compared with the male group. Male gender, diabetes, anemia, poor preoperative renal function, UUT-UC, and low-grade tumor were independent risk factors of poor renal outcome by multivariate analysis in these UC patients. Diabetes was a risk factor of poor renal outcome in male UUT-UC patients, but not in the female patients (P = 0.009).Female gender had a more aggressive histological urothelial carcinoma pattern than male patients did, but paradoxically had a more favorable renal outcome.

Acute kidney injury (AKI) is associated with high morbidity and mortality. Urinary tract infection (UTI) may be associated with sepsis or septic shock, and cause sudden deterioration of renal function. This study investigated the clinical characteristics and change of renal function to identify the risk factors for development of AKI in UTI patients. This retrospective study was conducted in a tertiary referral center. From January 2006 to January 2013, a total of 790 UTI patients necessitating hospital admission were included for final analysis. Their demographic and clinical characteristics and comorbidities were collected and compared. Multivariate logistic regression analysis was performed to evaluate the risk factors for AKI in UTI patients. There were 97 (12.3%) patients developing AKI during hospitalization. Multivariate logistic regression analysis showed that patients with older age (OR 1.02, 95% CI 1.00-1.04, P = 0.04), diabetes mellitus (DM) (OR 2.23, 95% CI 1.35-3.68, P = 0002), upper UTI (OR 2.63, 95% CI 1.53-4.56, P = 0001), afebrile during hospitalization (OR 1.71, 95% CI 1.04-2.83, P = 0036) and lower baseline eGFR [baseline eGFR 45-59 mL/min/1.73 m2 (OR 2.12, 95% CI 1.12-4.04, P = 0.022), baseline eGFR 30-44 mL/min/1.73 m2 (OR 4.44, 95% CI 2.30-8.60 P < 0.001) baseline eGFR < 30 mL/min/1.73 m2 (OR 4.72, 95% CI 2.13-10.45, P