Proteins Secreted by Lung Cancer Cells Induce the Onset of Proteinuria via Focal Adhesion Kinase Signaling in Mice.

Paraneoplastic nephrotic syndrome (PNS) is a complication seen in cancer patients. Ultrastructural examination shows the accumulation of proteins and the presence of foot process (FP) effacement in the glomeruli of PNS patients. Previously, we reported that orthotopic xenografts of Lewis lung carcinoma 1 in C57BL/6 mice caused them to develop lung cancer with albuminuria. This implies that these mice can be used as a model of human disease and suggests that Lewis lung carcinoma 1 cell-secreted proteins (LCSePs) contain nephrotoxic molecules and cause inflammation in renal cells. As podocyte effacement was present in glomeruli in this model, such podocyte injury may be attributable to either soluble LCSeP or LCSeP deposits triggering pathological progression. LCSePs in conditioned media was concentrated for nephrotoxicity testing. Integrin-focal adhesion kinase (FAK) signaling and inflammatory responses were evaluated in podocytes either exposed to soluble LCSePs or seeded onto substrates with immobilized LCSePs. FAK phosphorylation and interleukin-6 expression were higher in podocytes attached to LCSePs substrates than in those exposed to soluble LCSePs. Notably, LCSeP-based haptotaxis gave rise to altered signaling in podocytes. When podocytes were stimulated by immobilized LCSePs, FAK accumulated at focal adhesions, synaptopodin dissociated from F-actin, and disrupting the interactions between synaptopodin and α-actinin was observed. When FAK was inhibited by PF-573228 in immobilized LCSePs, the association between synaptopodin and α-actinin was observed in the podocytes. The association of synaptopodin and α-actinin with F-actin allowed FP stretching, establishing a functional glomerular filtration barrier. Therefore, in this mouse model of lung cancer, FAK signaling prompts podocyte FP effacement and proteinuria, indicative of PNS.

Shared decision-making for renal replacement treatment and illness perception in patients with advanced chronic kidney disease.

BACKGROUND: Current healthcare trends emphasize the use of shared decision-making (SDM) for renal replacement treatment (RRT) in patients with chronic kidney disease (CKD). This is crucial to understand the relationship between SDM and illness perception of CKD patients. Few studies have focused on SDM and illness perception status of CKD patients and the impact of illness perception on RRT after SDM. METHODS: In this cross-sectional study, we used a questionnaire with purposive sampling from March 2019 to February 2020 at the nephrology outpatient department of a medical center in southern Taiwan. The nephrology medical team in this study used the SHARE five-step model of SDM to communicate with the patients about RRT and Brief Illness Perception Questionnaire (BIPQ) was applied to evaluate illness perception of these patients at the beginning of SDM. According to the SDM decision time, the study participants were classified general and delayed SDM groups. The distribution between SDM groups was estimated using independent two sample t-test, chi-squared test or Fisher's exact test. The correlation between illness perception and SDM decision time were illustrated and evaluated using Spearman's correlation test. A p-value less than 0.05 is statistically significant. RESULTS: A total of 75 patients were enrolled in this study. The average time to make a dialysis decision after initiating SDM was 166.2 ± 178.1 days. 51 patients were classified as general group, and 24 patients were classified as delayed group. The median SDM decision time of delayed group were significantly longer than general group (56 vs. 361 days, P < 0.001). Our findings revealed that delayed group was significantly characterized with not created early surgical assess (delayed vs. general: 66.7% vs. 27.5%, p = 0.001) compared to general group. The average BIPQ score was 54.0 ± 8.1 in our study. We classified the patients into high and low illness perception group according to the median score of BIPQ. The total score of BIPQ in overall participants might increase by the SDM decision time (rho = 0.83, p = 0.830) and the linear regression line also showed consistent trends between BIPQ and SDM decision time in correspond cohorts. However, no statistically significant findings were found. CONCLUSIONS: The patients with advanced chronic kidney disease took an average of five and a half months to make a RRT decision after undergoing SDM. Although there is no statistical significance, the trend of illness perception seems correlated with decision-making time. The stronger the illness perception, the longer the decision-making time. Furthermore, shorter decision times may be associated with earlier establishment of surgical access. We need more research exploring the relationship between illness perception and SDM for RRT in CKD patients.

Comparison of effectiveness and safety between ticagrelor and clopidogrel in patients with acute coronary syndrome and on dialysis in Taiwan.

AIMS: This study aimed to evaluate and compare the effectiveness and safety between clopidogrel and ticagrelor in acute coronary syndrome (ACS) with renal dysfunction. METHODS: We conducted a retrospective cohort study on patients on chronic dialysis and whose admission diagnosis between 1 July 2013 and 31 December 2016 included ACS. The primary effectiveness endpoint was a major adverse cardiovascular event (MACE), and the primary safety endpoint was a major bleeding event. The application of propensity scores through the inverse probability of treatment weighting (IPTW) was applied to the study groups. Cox regression was used to estimate hazard ratios (aHRs) of study endpoints. In addition, the competing risk was adjusted using the Fine and Gray competing risk model. RESULTS: There were 1915 patients in the clopidogrel group and 270 patients in the ticagrelor group. At 12 months, the ticagrelor group had higher risks for MACE (aHR with IPTW: 1.29; 95% CI 1.16-1.44); death (aHR with IPTW: 1.65; 95% CI 1.47-1.86) and cardiac death (subdistribution HR [SHR] with IPTW: 1.64; 95% CI 1.41-1.91), compared with those in the clopidogrel group. For major bleeding event, the risk was significantly higher with ticagrelor than with clopidogrel (SHR with IPTW: 1.49; 95% CI 1.34-1.65). In terms of the risk for any bleeding event, there was no significant difference between the two groups (SHR with IPTW: 1.05; 95% CI 0.95-1.17). CONCLUSIONS: Compared with clopidogrel, ticagrelor was associated with higher MACE, death, cardiac death and major bleeding risk within 12 months in patients with ACS and on dialysis.

Incidence and survival variations of upper tract urothelial cancer in Taiwan (2001-2010).

OBJECTIVES: To assess temporal patterns and regional differences in the incidence rate, and factors associated with survival of urinary tract urothelial carcinoma. METHODS: The medical records of 8830 patients with new diagnoses of urinary tract urothelial carcinoma in the years 2001-2010 were retrieved from Taiwan National databases. Temporal trends, regional disparity and related survival factors were evaluated using the Cochran-Armitage trend test, local Moran's I statistic and log-rank test, respectively. RESULTS: The annual urinary tract urothelial carcinoma incidence rates (standardized by age) were steady at approximately 3.14-3.41 per 100 000 person-years. Notably, women had a significantly higher annual urinary tract urothelial carcinoma incidence than men in most of the years studied (range of female-to-male annual standardized rate ratio: 2.08-3.25), and diabetes prevalence in urinary tract urothelial carcinoma increased significantly from 12.3% to 23.4% per year over the 10 years. High urinary tract urothelial carcinoma incidence cluster areas other than the latest endemic area of "blackfoot disease" were newly identified by local Moran's I statistic (P < 0.05). Furthermore, older age, male sex, end-stage kidney disease and more advanced tumor grade were associated with lower 5-year overall survival probabilities in the 2001-2015 cohort. CONCLUSIONS: The incidence and survival of urinary tract urothelial carcinoma over the decade 2001-2010 were different according to population and regional features. Various urinary tract urothelial carcinoma screening, prevention, treatment and care plans should be developed depending on age, sex, comorbidity and area of residence.

Multidisciplinary care program in pre-end-stage kidney disease from 2010 to 2018 in Taiwan.

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

Nomenclature and diagnostic criteria for acute kidney injury - 2020 consensus of the Taiwan AKI-task force.

Acute kidney injury (AKI) is a common syndrome that has a significant impact on prognosis in various clinical settings. To evaluate whether new evidence supports changing the current definition/classification/staging systems for AKI suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline, the Taiwan AKI-TASK Force, composed of 64 experts in various disciplines, systematically reviewed the literature and proposed recommendations about the current nomenclature and diagnostic criteria for AKI. The Taiwan Acute Kidney Injury (TW-AKI) Consensus 2020 was established following the principles of evidence-based medicine to investigate topics covered in AKI guidelines. The Taiwan AKI-TASK Force determined that patients with AKI have a higher risk of developing chronic kidney disease, end-stage renal disease, and death. After a comprehensive review, the TASK Force recommended using novel biomarkers, imaging examinations, renal biopsy, and body fluid assessment in the diagnosis of AKI. Clinical issues with regards to the definitions of baseline serum creatinine (sCr) level and renal recovery, as well as the use of biomarkers to predict renal recovery are also discussed in this consensus. Although the present classification systems using sCr and urine output for the diagnosis of AKI are not perfect, there is not enough evidence to change the current criteria in clinical practice. Future research should investigate and clarify the roles of the aforementioned tools in clinical practice for AKI.

Establishment of an outreach, grouping healthcare system to achieve microelimination of HCV for uremic patients in haemodialysis centres (ERASE-C).

OBJECTIVE: HCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme. DESIGN: The ERASE-C Campaign is an outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and 'No-C HD' (no HCV-viremic subjects at the end of follow-up). RESULTS: At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and 'No-C HD' were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively. CONCLUSION: Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population. CLINICALTRIALSGOV IDENTIFIER: NCT03803410 and NCT03891550.

Evolutionary seroepidemiology of viral hepatitis and the gap in hepatitis C care cascades among uraemic patients receiving haemodialysis in Taiwan-the Formosa-Like Group.

Uraemic patients undergoing haemodialysis are at high risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We aimed to evaluate the evolutionary seroprevalence of viral hepatitis and the gap in HCV care cascades in this special population by a large-scale surveillance study in Taiwan. Uraemic patients on maintenance haemodialysis from 22 sites (FORMOSA-LIKE group) in 2012 (n = 1,680) and 2019 (n = 2,326) were recruited for this study. The distributions and sequential changes of viral hepatitis markers were analysed. The prevalence of anti-HCV antibody and hepatitis B surface antigen (HBsAg) seropositivity was 13.6% (316/2326) and 11.5% (267/2326), respectively, in 2019 compared with 17.3% (290/1680, P = .002) and 13.6% (229/1680, P = .046), respectively, in 2012. The HCV-viremic rate among anti-HCV-seropositive patients was significantly lower in 2019 than in 2012 (56.3% [178/316] vs. 73.8% [214/290], P < .001). The HCV treatment rate increased from 2.3% (5/217) in 2012 to 21.7% (49/226) in 2019 (P < .001). In the sequential analysis of the 490 patients who participated in both screens, 17 of the 55 HCV-viremic patients became HCV RNA seronegative, including 13 by antivirals and four spontaneously. By contrast, one anti-HCV-seropositive but nonviremic patient became viremic, and six anti-HCV-seronegative patients became anti-HCV-seropositive in 2019. The annual incidence of new HCV was 0.2%/year. Seven HBsAg-seropositive patients experienced HBsAg loss (1.25%/year). Two patients had new anti-HBc seropositivity (new HBV exposure: 0.57%/year). The seroprevalence of viral hepatitis decreased in an 8-year follow-up but remained prevalent, and the treatment of HCV infection was underutilized in uraemic patients. Additional efforts are needed to enhance the HCV treatment uptake of uraemic patients. Clinical Trial IDs: NCT03803410, NCT01766895.

Comorbidities in patients with chronic hepatitis C and hepatitis B on hemodialysis.

BACKGROUND AND AIM: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both HBV and HCV infections lead to risks of end-stage liver diseases and extrahepatic manifestations. This study aimed to investigate hepatic and extrahepatic comorbidities in hemodialysis patients with HBV or HCV infections compared with those without viral hepatitis. METHODS: A total of 1910 hemodialysis patients, including 159 HCV viremic patients (HCV group), 217 seropositive for HBV surface antigen (HBsAg, HBV group) and 1534 seronegative for both anti-HCV and HBsAg (non-B and non-C [NBNC] group), from 23 hemodialysis centers were enrolled. Comorbidities were classified into 10 categories by the International Classification of Diseases-10th Revision. RESULTS: Among the 1910 patients, the mean age was 64.6 years, and 52.7% were male patients. A total of 1834 (96%) patients had at least one comorbidity, and the mean number of comorbidities was 2.9 ± 1.5 per person. The three most common comorbidities were hypertension, diabetes, and ischemic heart diseases. The mean number of comorbidities per person was significantly higher in the HCV group (3.3 ± 1.7) than in the HBV (2.7 ± 1.5, P < 0.001) and NBNC groups (2.9 ± 1.5, P = 0.004), mainly due to the higher prevalence of ischemic heart disease, respiratory disorders, and mental/behavioral disorders. The HBV and NBNC groups exhibited comparable burdens of comorbidities. CONCLUSIONS: Hemodialysis patients had a high prevalence of multiple comorbidities. Hemodialysis patients with HCV exhibited a higher burden of comorbidities, especially ischemic heart diseases, respiratory disorders, and mental/behavioral disorders, than HBV and NBNC patients did.

The Association of Targeted Gut Microbiota with Body Composition in Type 2 Diabetes Mellitus.

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

Risk factors and prognosis assessment for acute kidney injury: The 2020 consensus of the Taiwan AKI Task Force.

Risk and prognostic factors for acute kidney injury (AKI) have been published in various studies across various populations. We aimed to explore recent advancements in and provide updated recommendations on AKI risk stratification and information about local AKI risk factors. The Taiwan Acute Kidney Injury Task Force reviewed relevant recently published literature and reached a consensus after group meetings. Systemic review and group discussion were performed. We conducted a meta-analysis according to the PRISMA statement for evaluating the diagnostic performance of the furosemide stress test. Several risk and susceptibility factors were identified through literature review. Contrast-associated AKI prediction models after coronary angiography were one of the most discussed prediction models we found. The basic approach and evaluation of patients with AKI was also discussed. Our meta-analysis found that the furosemide stress test can be used as a prognostic tool for AKI progression and to identify patients with AKI who are at low risk of renal replacement therapy. Factors associated with de novo chronic kidney injury or renal non-recovery after AKI were identified and summarized. Our review provided practical information about early identification of patients at high risk of AKI or disease progression for Taiwan local clinics.

Blood pressure modifies outcomes in patients with stage 3 to 5 chronic kidney disease.

Observational studies have demonstrated that low blood pressure is related to poor clinical outcomes in patients with chronic kidney disease (CKD). Subgroup analyses from the SPRINT trial showed that targeting systolic blood pressure under 120 mmHg is less beneficial for patients with CKD. Although malnutrition and inflammation are common in patients with advanced CKD, such patients are usually excluded from clinical trials. Therefore, we hypothesized that malnutrition-inflammation-cachexia syndrome could explain this J-shaped relationship. To test this, we studied 2441 patients with CKD stages 3-5 who received anti-hypertensive treatment for at least one year. Averaged blood pressures of the first year were used in the analyses. Fine-Gray competing risks regression showed a J-shaped relationship between continuous systolic blood pressure and end-stage kidney disease (ESKD) with a nadir risk at a systolic blood pressure of 120 mmHg. Adjusted sub-distribution hazard ratios of categorical systolic blood pressure 100-109 and 110-119 mmHg were 2.17 (95% confidence interval: 1.21-3.89) and 1.37 (0.94-1.99) for ESKD, respectively, compared with systolic blood pressures of 120-129 mmHg. Cox regression also showed J-shaped relationships between continuous systolic or diastolic blood pressures, and the composite outcomes of cardiovascular events and all-cause mortality. Logistic regression demonstrated the odds ratios of blood pressure components for Malnutrition-Inflammation Scores over 4 were J-shaped. Sub-distribution hazard ratios of systolic blood pressure 100-119 mmHg for ESKD was higher in those with a Malnutrition-Inflammation Score over 4, compared to 0.93 (0.53-1.63) in those with a score of 4 or under with significant interaction. Thus, malnutrition-inflammation-cachexia syndrome is associated with low blood pressure and modifies the J-shaped relationship in patients with advanced CKD.

Predominant global glomerulosclerosis in patients of upper urinary tract urothelial carcinoma with pre-existing renal function impairment is a predictor of poor renal outcomes.

BACKGROUND: Incidence of renal dysfunction and risks of progression to end-stage renal disease (ESRD) were reported higher in upper urinary tract urothelial carcinoma (UTUC) than in renal cell carcinoma (RCC) patients after unilateral nephrectomy. METHODS: Totally 193 renal cancer patients, including 132 UTUC and 61 RCC, were studied to clarify whether the pathological changes of the kidney remnant removed from nephrectomy and the clinical factors might predict the risk of ESRD. Renal tubulointerstitial (TI) score and global glomerulosclerosis (GGS) rate were examined by one pathologist and two nephrologists independently under same histopathological criteria. RESULTS: The glomerular filtration rates at the time of surgery were lower in UTUC than RCC groups (p < 0.001). Average GGS score and average TI rate were higher in UTUC than in RCC groups (p < 0.001; p < 0.001). Competitive risk factor analysis revealed that abnormal GGS rate not related to age, predominant in UTUC with pre-existing renal function impairment, was a histopathological predictor of poor renal outcomes (creatinine doubling or ESRD) within 5 years in UTUC patients. CONCLUSION: Pre-existing renal function and pathological change of kidney remnant in both UTUC and RCC have the value for prediction of renal outcomes.

Association of brain white matter lesions and atrophy with cognitive function in chronic kidney disease.

OBJECTIVES: Cognitive impairment is common in patients with chronic kidney disease (CKD), possibly leading to poor outcomes. However, the correlation between brain structural abnormalities and cognitive impairment remains unclear. The aim of this study was to investigate the impairment of specific cognitive domains and their association with brain structural abnormalities. METHODS: Patients with CKD of at least stage 3 who were not on hemodialysis were enrolled. All participants underwent comprehensive neuropsychological testing in five cognitive domains. Ventricular atrophy, sulcal atrophy, medial temporal atrophy, and white matter changes were assessed using brain magnetic resonance imaging according to standard protocols. RESULTS: Eighty-seven patients and 50 controls were enrolled. Patients with CKD exhibited decreased cognitive function relative to controls. Compared with patients with stage 3 CKD, those with advanced stage (stages 4 or 5) had poorer cognitive performance, more pronounced white matter hyperintensity (WMH) and more severe ventricular atrophy. Among CKD patients, executive function (ß = -.23, P = .043) and attention (ß = -.29, P = .004) were associated with WMH in controlled analyses. However, no cognitive impairment was associated with ventricular atrophy. CONCLUSION: Patients with CKD exhibited cognitive impairment and brain structural abnormalities including WMH and general brain atrophy. Impairment of attention and executive dysfunction were associated with WMH.

Patient assessment of chronic kidney disease self-care using the chronic kidney disease self-care scale in Taiwan.

AIM: Self-care represents the 'action' element of self-management. This study aimed to use the chronic kidney disease self-care (CKDSC) scale to examine factors associated with self-care and aspects of self-care deficits among CKD patients in Taiwan. METHODS: A cross-sectional investigation was conducted using the CKDSC scale with 449 CKD patients in Taiwan. The CKDSC is a 16-item questionnaire with five subscales, including medication adherence, diet control, exercise, smoking behaviours and blood pressure monitoring. Patient demographic and clinical factors taht may affect CKD self-care were analyzed in the multivariable regression models. RESULTS: Overall CKDSC scores were significantly higher for women (P = 0.020), older patients (P < 0.001), higher education (P = 0.033), BMI <24 kg/m2 (P = 0.005), later CKD stage or participants in the CKD care programme. Early-stage CKD patients had significantly lower for medication adherence, diet control, and blood pressure monitoring. Patients who participated in the CKD care programme had higher for medication adherence, diet control and regular exercise habits. CONCLUSION: The CKDSC scale is a tool to assess patient self-care. However, given the CKDSC tool is in Chinese, future studies should validate it in CKD patients in other languages or countries before it can be considered for general use.

Successful management of type IV hypersensitivity reactions to human insulin analogue with injecting mixtures of biphasic insulin aspart and dexamethasone.

Although hypersensitivity reaction to insulin was supposed to be less-frequent with current insulin analogue, case reports with different types of allergic reactions to insulin analogue were still reported. The most common form is type I hypersensitivity reaction with IgE-mediated. Besides, type III (IgG and IgM-mediated) and type IV (T-cell mediated delayed reaction) hypersensitivity reactions were also reported. Here we presented a long-standing type 2 diabetes with insulin requirements with hypersensitivity reactions to insulin actrapid, insulin aspart, insulin glargine, insulin detemir, and biphasic insulin aspart 30. Insulin desensitization was performed as initial management but failed as skin biopsy with immunohistochemical staining proved type IV hypersensitivity reaction. We continued with the next treatment approach using subcutaneous injection with the mixture of biphasic insulin aspart 30 and dexamethasone to alleviate allergy, and the result was successful with steroid-free biphasic insulin aspart 30 injection eight months later. Besides, the treatment effect had lasted after ten years even with switched type of insulin analogue from biphasic insulin aspart 30 to insulin glargine and insulin aspart. The case report demonstrated a good example of how clinicians deal with the rare but important questions of hypersensitivity reactions to insulin analogue.

Decreased incidence of gout in diabetic patients using pioglitazone.

Objective: The incidence and prevalence of gout are increasing, but the management is poor. Considering the increased prevalence of gout in the diabetic population, this study evaluated the effects of pioglitazone, an insulin resistance inhibitor, on the incidence of gout in the diabetic population. Methods: We used data from the National Health Insurance program in Taiwan. The pioglitazone cohort contained 30 100 patients and each patient was age and sex matched with three non-pioglitazone users who were randomly selected from the diabetic population. Cox proportional hazards regression analysis was conducted to estimate the effects of pioglitazone on the incidence of gout in the diabetic population. Results: The incidence of gout was significantly lower in pioglitazone users than in non-pioglitazone users [adjusted hazard ratio (aHR) 0.81 (95% CI 0.78, 0.85)]. The HR for the incidence of gout was lower in both male [aHR 0.80 (95% CI 0.75, 0.85)] and female [aHR 0.83 (95% CI 0.78, 0.88)] pioglitazone users than in non-pioglitazone users. An analysis of three age groups (<40, 40-59 and ⩾60 years) revealed that the HRs of both the 40-59 years [aHR 0.78 (95% CI 0.73, 0.83)] and the ⩾60 years [aHR 0.85 (95% CI 0.80, 0.91)] age groups were significantly lower among pioglitazone users than non-pioglitazone users. Conclusion: Compared with the non-pioglitazone users, the incidence of gout in the diabetic population using pioglitazone was less.

Decreased incidence of diabetes in patients with gout using benzbromarone.

Objective: Insulin resistance is inversely correlated with the clearance rate of uric acid, which may indicate that improvement in the clearance rate of uric acid could reduce insulin resistance. Considering the increased prevalence of diabetes mellitus (DM) in the gout population, this study evaluated the effects of benzbromarone, a uricosuric agent, on the incidence of DM in the gout population. Methods: We used data from the Taiwan National Health Insurance program. The benzbromarone user cohort included 8678 patients; each patient was age- and sex-matched with one benzbromarone non-user who was randomly selected from the gout population. The Cox proportional hazard regression analysis was conducted to estimate the effects of benzbromarone on the incidence of DM in the gout population. Results: The incidence of DM was significantly lower in benzbromarone users than in benzbromarone non-users [adjusted hazard ratio (HR) = 0.86; 95% CI: 0.79, 0.94]. The HR for the incidence of DM was lower in male benzbromarone users (adjusted HR = 0.77; 95% CI: 0.69, 0.86) than in benzbromarone non-users. An analysis of three age groups (<40, 40-59 and ⩾60 years) indicated that the HRs of the age groups of 40-59 years (adjusted HR = 0.86; 95% CI: 0.76, 0.98) and ⩾60 years (adjusted HR = 0.82; 95% CI: 0.71, 0.94) were significantly lower among benzbromarone users than among benzbromarone non-users. Conclusion: In the gout population, the incidence of DM was lower in benzbromarone users than in benzbromarone non-users.

Dialysis Increases the Risk of Bladder Recurrence in Patients with Upper Tract Urothelial Cancer: A Population-Based Study.

BACKGROUND: The relation of dialysis to tumor recurrence in patients with upper tract urothelial cancer (UTUC) is unknown; however, a limited number of small-scale studies suggest that patients with renal diseases prior to UTUC are more likely to exhibit bladder recurrence. We performed a population-based analysis to determine the effect of dialysis on bladder recurrence for patients with UTUC. METHODS: This retrospective cohort study included patients diagnosed with UTUC (2002-2007) from the Taiwan National Cancer Registry and divided them into two groups-dialysis and non-dialysis groups. These patients were followed up until bladder recurrence, death, or the end of 2010. Competing risk analyses adjusting covariates and death were applied to determine the relation of dialysis and bladder recurrence. RESULTS: Of the 5141 eligible patients, 548 (10.7%) were undergoing dialysis. The cumulative bladder recurrence was significantly higher in the dialysis group than in the non-dialysis group (29% vs. 21%, modified log-rank p < 0.001). In the multivariable analysis, the dialysis group exhibited a 64% increased bladder recurrence risk (cause-specific hazard ratio 1.64, 95% confidence interval 1.34-2.01, p < 0.001), which was confirmed using stratification and propensity score weighting methods. The other prognostic factors for bladder recurrence were sex, diabetes, cardiac disorder, Charlson Comorbidity Index, and tumor grade. CONCLUSIONS: Despite unknown reasons, approximately one-tenth of patients with UTUC have experienced dialysis treatment. Patients undergoing dialysis have a higher risk of bladder recurrence. Various treatment and screening strategies should be developed for dialysis and non-dialysis patients.

Factors associated with type 2 diabetes in patients with vascular dementia: a population-based cross-sectional study.

BACKGROUND: Incidence of dementia is growing rapidly and affects many people worldwide. Type 2 diabetes mellitus (DM) might link cognitive decline and dementia, but the reasons for this association remain unclear. Our study explored the factors associated with type 2 DM in patients with dementia. METHODS: Patients (n = 40,404) with vascular dementia were identified in Taiwan's 1997 to 2008 National Health Insurance Research Database and divided into a DM group and non-DM group. Eleven comorbidities were identified and categorized into four groups: cardiovascular and cerebrovascular diseases, digestive system diseases, renal and metabolic system diseases, and cancer. The associations of these factors with type 2 DM were explored through multivaraible logistic regression. RESULTS: Of the patients with dementia, 22.5% had DM. Associated with a higher likelihood of DM in this population were female sex (adjusted odds ratio [OR]: 1.44, 95% confidence interval [CI]: 1.36-1.52), young age (range of adjusted OR: 0.55-1.13), low income (range of adjusted OR: 1.09-1.18), and renal and metabolic system diseases (OR: 2.81, 95% CI: 2.64-2.98). CONCLUSIONS: The findings of this study suggest that clinicians should encourage patients with dementia to receive regular glucose impairment screening if they are female, have low socioeconomic status, or have renal or metabolic diseases.