A Comparative Study of AI-Based Automated and Manual Postprocessing of Head and Neck CT Angiography: An Independent External Validation with Multi-Vendor and Multi-Center Data.

PURPOSE: To externally validate the performance of automated postprocessing (AP) on head and neck CT Angiography (CTA) and compare it with manual postprocessing (MP). METHODS: This retrospective study included head and neck CTA-exams of patients from three tertiary hospitals acquired on CT scanners from five manufacturers. AP was performed by CerebralDoc. The image quality was assessed using Likert scales, and the qualitative and quantitative diagnostic performance of arterial stenosis and aneurysm, postprocessing time, and scanning radiation dose were also evaluated. RESULTS: A total of 250 patients were included. Among these, 55 patients exhibited significant stenosis (≥ 50%), and 33 patients had aneurysms, diagnosed using original CTA datasets and corresponding multiplanar reconstructions as the reference. While the scores of the V4 segment and the edge of the M1 segment on volume rendering (VR), as well as the C4 segment on maximum intensity projection (MIP), were significantly lower with AP compared to MP across vendors (all P < 0.05), most scores in AP demonstrated image quality that was either superior to or comparable with that of MP. Furthermore, the diagnostic performance of AP was either superior to or comparable with that of MP. Moreover, AP also exhibited advantages in terms of postprocessing time and radiation dose when compared to MP (P < 0.001). CONCLUSION: The AP of CerebralDoc presents clear advantages over MP and holds significant clinical value. However, further optimization is required in the image quality of the V4 and M1 segments on VR as well as the C4 segment on MIP.

Therapy as prevention toward HCV elimination in maintenance hemodialysis: a multi-center, prospective cohort study.

Background: The World Health Organization has established interim guidance for hepatitis C virus (HCV) elimination. We aimed to prove the concept of "treatment as prevention" by conducting a prospective HCV elimination program for hemodialysis (HD) patients. Methods: A universal HCV screen was launched in 22 HD centers in 2019. HCV-viremic patients were linked to care with direct-acting antivirals (DAAs). The second screen was performed in 2021 to evaluate the effect of link-to-care in lowering the prevalence of HCV viremia and the incidence of HCV new/re-infections. Results: Of 2336 patients enrolled in the first screening in 2019, 320 (13.7%) were seropositive for anti-HCV and 181 (7.7%) were HCV-viremic. Of 152 patients successfully linked to treat with DAA, 140 (92.1%) patients achieved a sustained virological response. Of them, 1733 patients participated in the second surveillance. Five anti-HCV-negative patients experienced anti-HCV seroconversion. Of 119 DAA-cured patients and 102 spontaneous HCV clearance patients, none had HCV reinfection. The annual incidence of HCV new infection was 0.1%. Sixty-one of the 620 (9.8%) newly enrolled patients were anti-HCV-seropositive in the second survey. The overall HCV-viremic rate decreased from 7.7% in 2019 to 0.6% (15/2353) in 2021. At the institutional level, 45.5% (10/22) eradicated HCV and 82% (18/22) of HD units had no HCV new infections or reinfections. Conclusions: The link-to-care project proved the concept of "treatment as prevention" by which HCV microelimination helps to prevent reinfection and new infections in the HD population.Trial registration: ClinicalTrials.gov identifier: NCT03803410 and NCT03891550.

Performance of deep learning-based autodetection of arterial stenosis on head and neck CT angiography: an independent external validation study.

PURPOSE: To externally validate the performance of automated stenosis detection on head and neck CT angiography (CTA) and investigate the impact factors using an independent bi-center dataset with digital subtraction angiography (DSA) as the ground truth. MATERIAL AND METHODS: Patients who underwent head and neck CTA and DSA between January 2019 and December 2021 were retrospectively included. The degree of stenosis was automatically evaluated using CerebralDoc based on CTA. The performance of CerebralDoc across levels (per-patient, per-region, per-vessel, and per-segment) and thresholds (≥ 50%, ≥ 70%, and = 100%) was evaluated. Logistic regression was performed to identify independent factors associated with false negative results. RESULTS: 296 patients were analyzed. Specificity across levels and thresholds was high, exceeding 92%. The area under the curve ranged from poor (0.615, 95% CI: 0.544, 0.686; at the region-based analysis for stenosis ≥ 70%) to excellent (0.945, 95% CI: 0.905, 0.985; at the patient-based analysis for stenosis ≥ 50%). Sensitivity ranged from 0.714 (95% CI: 0.675, 0.750) at the segment-based analysis for stenosis ≥ 70% to 0.895 (95% CI: 0.849, 0.919) at the patient-based analysis for stenosis ≥ 50%. The multiple logistic regression analysis revealed that false negative results were primarily more likely to specific stenosis locations (particularly the M2 segment and skull base segment of the internal carotid artery) and occlusion. CONCLUSIONS: CerebralDoc has the potential to automated stenosis detection on head and neck CTA, but further efforts are needed to optimize its performance.

The prognostic value of URR equals that of Kt/V for all-cause mortality in Taiwan after 10-year follow-up.

Kt/V and URR (urea reduction ratio) measurements represent dialysis adequacy. Single-pool Kt/V is theoretically a superior method and is recommended by the Kidney Disease Outcomes Quality Initiative guidelines. However, the prognostic value of URR compared with Kt/V for all-cause mortality is unknown. The effect modifiers and cut-off values of the two parameters have not been compared. We investigated 2615 incident hemodialysis patients with URR of 72% and Kt/V (Daugirdas) of 1.6. The average patient age was 59 years, 50.7% were female, and 1113 (40.2%) died within 10 years. URR and Kt/V were both positively associated with nutrition factors and female sex and negatively associated with body weight and heart failure. In Cox regression mod-els for all-cause mortality, the hazard ratios (HRs) of high URR groups (65-70%, 70-75%, and > 75%) and the URR < 65% group were 0.748 (0.623-0.898), 0.693 (0.578-0.829), and 0.640 (0.519-0.788), respectively. The HRs of high Kt/V groups (Kt/V 1.2-1.4, 1.4-1.7, and > 1.7) and the Kt/V < 1.2 group were 0.711 (0.580-0.873), 0.656 (0.540-0.799), and 0.623 (0.498-0.779), respec-tively. In subgroup analysis, Kt/V was not associated with all-cause mortality in women. The prognostic value of URR for all-cause mortality is as great as that of Kt/V. URR > 70% and Kt/V > 1.4 were associated with a higher survival rate. Kt/V may have weaker prognostic value for women.

Non-insulin-based insulin resistance indices for predicting all-cause mortality and renal outcomes in patients with stage 1-4 chronic kidney disease: another paradox.

Non-insulin-based insulin resistance (IR) indices serve as the indicators of metabolic syndrome (MetS) but have limited value for predicting clinical outcomes. Whether the obesity paradox affects the predictive value of these indicators in patients with chronic kidney disease (CKD) remains unknown. We investigated whether MetS and non-insulin-based IR indices can predict all-cause mortality and renal outcomes in a prospective observational study with stage 1-4 CKD Asians (N = 2,457). These IR indices were associated with MetS. A Cox regression model including body mass index (BMI) revealed an association between MetS and renal outcomes. Among the IR indices, only high triglyceride-glucose (TyG) index was associated with adverse renal outcomes: the hazard ratio of Q4 quartile of the TyG index was 1.38 (1.12-1.70). All-cause mortality was marginally associated with MetS but not high IR indices. Low TyG and TyG-BMI indices as well as low BMI and triglyceride were paradoxically associated with increased risks of clinical outcomes. The triglyceride-to-high-density lipoprotein cholesterol ratio and metabolic score for IR indices were not associated with clinical outcomes. In conclusion, MetS and TyG index predict renal outcome and obesity paradox affects the prediction of IR indices in patients with stage 1-4 CKD.

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.

The Association between Iron Deficiency and Renal Outcomes Is Modified by Sex and Anemia in Patients with Chronic Kidney Disease Stage 1-4.

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

High risk of renal outcome of metabolic syndrome independent of diabetes in patients with CKD stage 1-4: The ICKD database.

AIMS: To investigate whether metabolic syndrome (MetS) could predict renal outcome in patients with established chronic kidney disease (CKD). MATERIALS AND METHODS: We enroled 2500 patients with CKD stage 1-4 from the Integrated CKD care programme, Kaohsiung for delaying Dialysis (ICKD) prospective observational study. 66.9% and 49.2% patients had MetS and diabetes (DM), respectively. We accessed three clinical outcomes, including all-cause mortality, RRT, and 50% decline in estimated glomerular filtration rate events. RESULTS: The MetS score was positively associated with proteinuria, inflammation, and nutrition markers. In fully adjusted Cox regression, the hazard ratio (HR) (95% confidence interval) of MetS for composite renal outcome (renal replacement therapy, and 50% decline of renal function) in the DM and non-DM subgroups was 1.56 (1.15-2.12) and 1.31 (1.02-1.70), respectively, while that for all-cause mortality was 1.00 (0.71-1.40) and 1.27 (0.92-1.74). Blood pressure is the most important component of MetS for renal outcomes. In the 2 by 2 matrix, compared with the non-DM/non-MetS group, the DM/MetS group (HR: 1.62 (1.31-2.02)) and the non-DM/MetS group (HR: 1.33 (1.05-1.69)) had higher risks for composite renal outcome, whereas the DM/MetS group had higher risk for all-cause mortality (HR: 1.43 (1.09-1.88)). CONCLUSIONS: MetS could predict renal outcome in patients with CKD stage 1-4 independent of DM.

White Spot Syndrome Virus (WSSV) Inhibits Hippo Signaling and Activates Yki To Promote Its Infection in Penaeus vannamei.

White spot syndrome virus (WSSV) is a serious threat to shrimp aquaculture, especially Pacific white shrimp, Penaeus vannamei, the most farmed shrimp in the world. Activation of the Hippo-Yki signaling pathway, characterized by the intracellular Hippo-Wts kinase cascade reactions and the phosphorylation and cytoplasmic retention of Yki, is widely involved in various life activities. The current work established the fundamental structure and signal transduction profile of the Hippo-Yki pathway in P. vannamei and further investigated its role in viral infection. We demonstrated that WSSV promoted the dephosphorylation and nuclear translocation of Yki, suggesting that Hippo signaling is impaired and Yki is activated after WSSV infection in shrimp. In vivo, Yki gene silencing suppressed WSSV infection, while Hippo and Wts silencing promoted it, indicating a positive role of Hippo signaling in antiviral response. Further analyses showed that Yki suppressed Dorsal pathway activation and inhibited hemocyte apoptosis in WSSV-infected shrimp, while Hippo and Wts showed opposite effects, which contributed to the role of Hippo signaling in WSSV infection. Therefore, the current study suggests that WSSV annexes Yki to favor its infection in shrimp by inhibiting Hippo signaling. IMPORTANCE White spot syndrome virus (WSSV) is one of the most harmful viral pathogens to shrimp. The pathological mechanism of WSSV infection remains unclear to date. The Hippo-Yki signaling pathway is important for various biological processes and is extensively involved in mammalian immunity, but little is known about its role in infectious diseases in invertebrates. Based on revealing the fundamental structure of the shrimp Hippo pathway, this study investigated its implication in the pathogenesis of WSSV disease. We demonstrated that WSSV enhanced Yki activation by inhibiting Hippo signaling in shrimp. The activated Yki promoted WSSV infection by inhibiting hemocyte apoptosis and suppressing the activation of Dorsal, an NF-κB family member in shrimp that is critical for regulating antiviral response. Therefore, this study suggests that WSSV can hijack the Hippo-Yki signaling pathway to favor its infection in shrimp.

A novel chitinase Chi6 with immunosuppressive activity promotes white spot syndrome virus (WSSV) infection in Penaeus vannamei.

Chitinases, a group of glycosylase hydrolases that can hydrolyze chitin, are involved in immune regulation in animals. White spot syndrome virus (WSSV) causes huge losses to crustacean aquaculture every year. We identified a novel chitinase Chi6 from Pacific white shrimp Penaeus vannamei, which contains a catalytic domain but no chitin-binding domain. The Chi6 expression was regulated by multiple immune signaling pathways and increased after immune stimulations. Silencing of Chi6 by RNAi in vivo did not affect Vibrio parahaemolyticus infection, but significantly increased the survival rate of WSSV-infected shrimp. The expression of multiple WSSV immediate early and structural genes was also decreased upon Chi6 silencing. The recombinant Chi6 protein showed no effect on bacterial growth but could attenuate shrimp hemocyte phagocytosis. The mRNA levels of several key elements and downstream genes of the MAPK and Dorsal pathways in Chi6-silenced shrimp were significantly up-regulated, suggesting an inhibitory effect of Chi6 on humoral immune response. Moreover, Chi6 enhanced the regulatory effect of Dorsal on the expression of WSSV ie1 gene. Therefore, Chi6 promotes WSSV infection through immunosuppression and regulation of WSSV gene expression. Targeting Chi6 could be a potential strategy for controlling WSSV disease in shrimp farming.

High Ultrafiltration Rate Is Associated with Increased All-Cause Mortality in Incident Hemodialysis Patients with a High Cardiothoracic Ratio.

A high ultrafiltration rate (UFR) is associated with increased mortality in hemodialysis patients. However, whether a high UFR itself or heart failure with fluid overload followed by a high UFR causes mortality remains unknown. In this study, 2615 incident hemodialysis patients were categorized according to their initial cardiothoracic ratios (CTRs) to assess whether UFR was associated with mortality in patients with high or low CTRs. In total, 1317 patients (50.4%) were women and 1261 (48.2%) were diabetic. During 2246 (1087−3596) days of follow-up, 1247 (47.7%) cases of all-cause mortality were noted. UFR quintiles 4 and 5 were associated with higher risks of all-cause mortality than UFR quintile 2 in fully adjusted Cox regression analysis. As the UFR increased by 1 mL/kg/h, the risk of all-cause mortality increased 1.6%. Subgroup analysis revealed that in UFR quintile 5, hazard ratios (HRs) for all-cause mortality were 1.91, 1.48, 1.22, and 1.10 for CTRs of >55%, 50−55%, 45−50%, and <45%, respectively. HRs for all-cause mortality were higher in women and patients with high body weight. Thus, high UFRs may be associated with increased all-cause mortality in incident hemodialysis patients with a high CTR, but not in those with a low CTR.

The Hippo-Yki Signaling Pathway Positively Regulates Immune Response against Vibrio Infection in Shrimp.

In the Hippo pathway, activation of Hippo and Warts (Wts) kinases results in the phosphorylation of Yorkie (Yki), to prevent its nuclear translocation. Shrimp aquaculture is threatened by Vibrio genus bacteria. In this study, we examine the role of the Hippo pathway in immune defense against Vibrio parahaemolyticus in Pacific white shrimp Penaeus vannamei. We show that V. parahaemolyticus infection promotes the expression of Yki and facilitates the dephosphorylation and nuclear translocation of Yki, indicating the inhibition of Hippo signaling upon bacterial infection. There is a complex regulatory relationship between the Hippo pathway components Hippo, Wts, and Yki and the immune-related transcription factors Dorsal, Relish, and STAT. Silencing of Hippo and Wts weakened hemocyte phagocytosis, while the silencing of Yki enhanced it, suggesting a positive regulation of shrimp cellular immunity by Hippo signaling activation. In vivo silencing of Hippo and Wts decreased the survival rates of V. parahaemolyticus-infected shrimp and elevated the bacterial content in tissues, while the silencing of Yki showed the opposite results. This suggests that the activation of Hippo signaling and the inhibition of Yki enhance antibacterial immunity in shrimp.

Normal weight and waist obesity indicated by increased total body fat associated with all-cause mortality in stage 3-5 chronic kidney disease.

Patients with chronic kidney disease (CKD) demonstrate a survival benefit with a high body mass index (BMI); this is the obesity paradox. Central obesity has a higher prognostic value than BMI, even in those with normal weight. Whether total body fat percentage (TBF%) provides more information than BMI and waist circumference (WC) remains unknown. We included 3,262 Asian patients with stage 3-5 CKD and divided these patients by TBF% and waist-to-height ratio (WHtR) quartiles (Q1-Q4). TBF% was associated with BMI, WC, nutritional markers, and C-reactive protein. In all patients, BMI but not TBF% or WHtR demonstrated a survival paradox. In patients with BMI <25 kg/m2, but not in those with BMI ≥ 25 kg/m2, TBF% Q4 and WHtR Q4 were associated with all-cause mortality, with hazard ratios [HRs; 95% confidence intervals (CIs)] of 2.35 (1.31-4.22) and 1.38 (1.06-1.80), respectively. The HRs of TBF% Q4 for all-cause mortality were 2.90 (1.50-5.58) in patients with a normal WC and 3.81 (1.93-7.50) in patients with normal weight and normal WC (All P for interaction < 0.05). In conclusion, TBF% can predict all-cause mortality in patients with advanced CKD and a normal weight, normal WC, or both.

Predictive Value of HbA1c and Metabolic Syndrome for Renal Outcome in Non-Diabetic CKD Stage 1-4 Patients.

Glycated hemoglobin (HbA1c) levels are commonly used to indicate long-term glycemic control. An HbA1c level of 6.5−5.7% is defined as pre-diabetes and is proposed as a criterion for diagnosing metabolic syndrome (MetS). However, HbA1c levels can be affected by chronic kidney disease (CKD). Whether HbA1c is associated with clinical outcomes in nondiabetic CKD patients with or without MetS is still unknown. This study included 1270 nondiabetic CKD stage 1−4 Asian patients, divided by HbA1c and MetS. Through linear regression, HbA1c was positively associated with age, waist circumference, hemoglobin levels, and C-reactive protein and was negatively associated with malnutrition−inflammation. HbA1c levels were 5.5% (0.6%) and 5.7% (0.6%) in non-MetS and MetS, respectively (p < 0.001). In Cox regression, higher-level HbA1c was associated with worse composite renal outcome in MetS patients, but with better renal outcome in non-MetS patients: Hazard ratio (HR) (95% confidence interval [CI]) of HbA1c ≥5.7%, compared with HbA1c <5%, was 2.00 (1.06−3.78) in MetS and 0.25 (0.14−0.45) in non-MetS. An association between HbA1c and all-cause mortality was not found. In conclusion, higher HbA1c levels are associated with worse renal outcomes in nondiabetic CKD stage 1−4 patients modified by the presence of MetS.

Hyperuricemia, a Non-Independent Component of Metabolic Syndrome, Only Predicts Renal Outcome in Chronic Kidney Disease Patients without Metabolic Syndrome or Diabetes.

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

A kelch motif-containing protein KLHDC2 regulates immune responses against Vibrio parahaemolyticus and white spot syndrome virus in Penaeus vannamei.

The kelch motif-containing proteins are widely present in organisms and known to be involved in various biological processes, but their roles in immunity remain unclear. In this study, a kelch motif-containing protein KLHDC2 was identified from Pacific white shrimp Penaeus vannamei and its immune function was investigated. The klhdc2 gene was widely expressed in shrimp tissues and its protein product was mainly present in the nucleus. Expression of klhdc2 was regulated by shrimp NF-κB family members Dorsal and Relish, and changed after immune stimulation. KLHDC2 could enhance the immune defense against Vibrio parahaemolyticus in shrimp but inhibit that against white spot syndrome virus (WSSV). Further analyses showed that KLHDC2 did not affect the phagocytosis of hemocytes but regulated the expression of a series of immune effector genes. KLHDC2 has a complex regulatory relationship with Dorsal and Relish, which may partly contribute to its positive role in antibacterial response by regulating humoral immunity. Moreover, the regulatory effect of KLHDC2 on WSSV ie1 gene contributed to its negative effect on antiviral response. Therefore, the current study enrichs the knowledge on the Kelch family and helps to learn more about the regulatory mechanism of shrimp immunity.

Association between Body Mass Index and Renal Outcomes Modified by Chronic Kidney Disease and Anemia: The Obesity Paradox for Renal Outcomes.

Obesity-related nephropathy is associated with renal function progression. However, some studies have associated a high body mass index (BMI) with improved renal outcomes­this is referred to as the obesity paradox for renal outcomes, especially in relation to advanced chronic kidney disease (CKD). Central obesity can explain the obesity paradox in all-cause mortality. However, whether obesity or central obesity is associated with renal outcomes (renal replacement therapy or a 50% decline in the estimated glomerular filtration rate) in patients with advanced CKD remains unclear. Our study included 3605 Asian patients with CKD stages 1−5 divided into six groups according to their BMI (between 15 and 35 kg/m2). Through linear regression, BMI was positively associated with hemoglobin and albumin at CKD stages 4 and 5. In the competing risk Cox regression model, a high BMI (27.5−35 kg/m2) was associated with renal outcomes at CKD stages 1−3, but not stages 4 and 5. A high BMI was associated with renal outcomes in patients with hemoglobin ≥11 g/dL, but not <11 g/dL. A high waist-to-hip ratio was not associated with renal outcomes. We conclude that the CKD stage and anemia may explain the obesity paradox in renal outcomes in patients with CKD.

Reduced Incidence of Stroke in Patients with Gout Using Benzbromarone.

Gout is strongly associated with the incidence of atherosclerotic events, including stroke and myocardial infarction. Considering the increased prevalence of stroke in the population with gout, the aim of this study was to evaluate the effects of benzbromarone, a uricosuric agent, on the incidence of stroke in the population with gout. We used data from the Taiwanese National Health Insurance Registration Database (NHIRD). The benzbromarone user cohort included 15,143 patients; each patient was age- and sex-matched with one non-user randomly selected from the population with gout. Cox proportional hazard regression analysis was conducted to estimate the effects of benzbromarone on the incidence of stroke in the population with gout. The incidence of stroke was significantly lower in benzbromarone users than in benzbromarone non-users. The HR for the incidence of stroke was lower in male benzbromarone users than in non-users. An analysis of three age groups (<40, 40-59, and ≥60 years) indicated that the HRs in those aged 40-59 years and ≥60 years were significantly lower among benzbromarone users than non-users. In the population with gout, the incidence of stroke was lower in benzbromarone users than in benzbromarone non-users.

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.

Association between the risk of heart failure hospitalization and end-stage renal disease with digoxin usage in patients with cardiorenal syndrome: A population-based study.

Background: The management of the coexistence of heart disease and kidney disease is increasingly challenging for clinicians. Chronic kidney disease (CKD) is not only a prevalent comorbidity of patients with heart failure but has also been identified as a noteworthy risk factor for all-cause mortality and poor clinical outcomes. Digoxin is one of the commonest treatments for heart disease. There are few trials investigating the role of digoxin in patients with cardiorenal syndrome (CRS). This study aims to examine the association between digoxin usage and clinical outcomes in patients with CRS in a nationwide cohort. Method: We conducted a population-based study that included 705 digoxin users with CRS; each patient was age, sex, comorbidities, and medications matched with three non-users who were randomly selected from the CRS population. Cox proportional hazards regression analysis was conducted to estimate the effects of digoxin on the incidence of all-cause mortality, congestive heart failure (CHF) hospitalization, coronary artery disease (CAD) hospitalization, and end-stage renal disease (ESRD). Results: The all-cause mortality rate was significantly higher in digoxin users than in non-users (adjusted hazard ratio [aHR] = 1.26; 95% confidence interval [CI] = 1.09-1.46, p = 0.002). In a subgroup analysis, there was significantly high mortality in the 0.26-0.75 defined daily dose (DDD) subgroup of digoxin users (aHR = 1.49; 95% CI = 1.23-1.82, p<0.001). Thus, the p for trend was 0.013. With digoxin prescription, the CHF hospitalization was significantly higher [subdistribution HR (sHR) = 1.17; 95% CI = 1.05-1.30, p = 0.004], especially in the >0.75 DDD subgroup (sHR = 1.19; 95% CI = 1.01-1.41, p = 0.046; p for trend = 0.006). The digoxin usage lowered the coronary artery disease (CAD) hospitalization in the > 0.75 DDD subgroup (sHR = 0.79; 95% CI = 0.63-0.99, p = 0.048). In renal function progression, more patients with CRS entered ESRD with digoxin usage (sHR = 1.34; 95% CI = 1.16-1.54, p<0.001). There was a significantly greater incidence of ESRD in the < 0.26 DDD and 0.26-0.75 DDD subgroups of digoxin users (sHR = 1.32; 95% CI = 1.06-1.66, p = 0.015; sHR = 1.44; 95% CI = 1.18-1.75; p for trend<0.001). Conclusion: Digoxin should be prescribed with caution to patients with CRS.