Mortality after Metastatic Breast Cancer: Co-morbidity as a Mediator of Age on Survival, and Delays in Treatment for Breast Cancer Metastasis

Patients with breast cancer metastases have very poor survival. Delays in the initiation of breast cancer treatment may adversely affect survival. Comorbid illness is more common in older women. Comorbid illness may explain effects of age on metastatic breast cancer survival outcomes. Comorbid illness may affect treatment delay.The purpose of the present study was to 1) identify factors related to survival following metastatic breast cancer diagnosis, 2) assess the impact of delay in treatment on survival while controlling for immortal time bias, and 3) evaluate the role of comorbidity as a mediator of survival disparity between younger (≤ 51 years) and older (> 51 years) patients.A total of 557 patients with the initial breast cancer metastasis diagnosis have been followed up between January 1, 1999 and June 30, 2008. Prognostic factors and outcomes of these patients were analyzed using log-rank test and Cox regression model, demonstrating that hypertension, ER/PR, HER2 status, number of metastatic sites, and BMI at metastatic breast cancer diagnosis were the most relevant prognostic factors for survival. Backward stepwise selection of covariates was conducted among 553 patients and showed that treatment delays of > 12 weeks had a marginal impact on poor survival (HR 1.76, 95% CI 0.99-3.13). Moreover, the interval of 12-24 weeks, compared to the interval of 4-12 week was a prognostic factor for survival from first treatment (HR 2.39, 95% CI 1.19-4.77). To assess comorbidity variable as a mediator of age-survival relationship among 553 patients, we applied two approaches: 1) Baron Kenny approach, and 2) alternative assessment to compute the percentage change in the HRs. Hypertension was related to survival (HR 1.45, 95% CI 1.12-1.89) and hypertension augmented Charlson comorbidity score (hCCS) explained survival disparity between young and old patients by 44% compared to 40 % of hypertension and 14% of the Charlson comorbidity score (CCS). Looking for opportunities to improve public health, the present study identifies modifiable factors associated with variable outcomes after diagnosis of metastatic breast cancer

Factors affecting the long-term outcomes of idiopathic membranous nephropathy

Abstract Background We attempted to describe the clinical features and determine the factors associated with renal survival in idiopathic membranous nephropathy (iMN) patients with nephrotic syndrome (NS) and to determine the factors associated with spontaneous complete remission (sCR) and progression to NS in iMN patients with subnephrotic proteinuria. Methods This retrospective study involved 166 iMN patients with NS and 65 patients with subnephrotic proteinuria. The primary end point was a doubling of serum creatinine or initiation of dialysis. In patients with subnephrotic proteinuria, we determined the factors associated with sCR and factors associated with progression to NS. Results Remission of NS was achieved in 125 out of 166 patients (75.3%). Of those who reached remission, 26 patients (20.8%) experienced relapse that was followed by second remission. The relapse or persistence of proteinuria was associated with the primary end points (hazard ratio [HR] = 12.40, P = 0.037, HR = 173, P < 0.001, respectively). In patients with subnephrotic proteinuria, sCR occurred in 35.4% of the patients. The patients with sCR had lower proteinuria and serum creatinine levels and higher serum albumin concentrations at baseline. The serum albumin level at diagnosis was a prognostic factor for progression to NS (Odds ratio [OR] = 0.015, P < 0.001). Conclusions The occurrence of relapse or persistence of proteinuria had negative effects on renal survival in iMN patients with NS, and low serum albumin levels at baseline were associated with non-achievement of sCR and progression to NS

Soluble Epoxide Hydrolase Activity Determines the Severity of Ischemia-Reperfusion Injury in Kidney

Soluble epoxide hydrolase (sEH) in endothelial cells determines the plasma concentrations of epoxyeicosatrienoic acids (EETs), which may act as vasoactive agents to control vascular tone. We hypothesized that the regulation of sEH activity may have a therapeutic value in preventing acute kidney injury by controlling the concentration of EETs. In this study, we therefore induced ischemia-reperfusion injury (IRI) in C57BL/6 mice and controlled sEH activity by intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA). The deterioration of kidney function induced by IRI was partially moderated and prevented by AUDA treatment. In addition, AUDA treatment significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced the down-regulation of sEH, and AUDA administration had no effect on the expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by measuring the substrate epoxyoctadecenoic acid (EpOME) and its metabolite dihydroxyoctadec-12-enoic acid (DHOME). Ischemic injury had no effects on the plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective effect of the sEH inhibitor was achieved by suppression of proinflammatory cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the intrarenal infiltration of inflammatory cells, but promoted endothelial cell migration and neovascularization. The results of this study suggest that treatment with sEH inhibitors can reduce acute kidney injury

Effects of residential greenness on clinical outcomes of patients with chronic kidney disease: a large-scale observation study

Background: As industrialization and urbanization are accelerating, the distribution of green areas is decreasing, particularly in developing countries. Since the 2000s, the effects of surrounding greenness on self-perceived health, including physical and mental health, longevity, and obesity have been reported. However, the effects of surrounding green space on chronic kidney disease are not well understood. Therefore, we investigated the impact of residential greenness on the mortality of chronic kidney disease patients and progression from chronic kidney disease to end-stage renal disease (ESRD). Methods: Using a large-scale observational study, we recruited chronic kidney disease patients (n = 64,565; mean age, 54.0 years; 49.0% of male) who visited three Korean medical centers between January 2001 and December 2016. We investigated the hazard ratios of clinical outcomes per 0.1-point increment of exposure to greenness using various models. Results: During the mean follow-up of 6.8 +/- 4.6 years, 5,512 chronic kidney disease patients developed ESRD (8.5%) and 8,543 died (13.2%). In addition, a 0.1-point increase in greenness reduced all-cause mortality risk in chronic kidney disease and ESRD patients and progression of chronic kidney disease to ESRD in a fully adjusted model. The association between mortality in ESRD patients and the normalized difference vegetation index was negatively correlated in people aged &gt;65 years, who had normal weight, were nonsmokers, and lived in a nonmetropolitan area. Conclusion: Chronic kidney disease patients who live in areas with higher levels of greenness are at reduced risk of all-cause mortality and progression to ESRD.Y

Raw Garlic Consumption and Risk of Liver Cancer: A Population-Based Case-Control Study in Eastern China.

Although the major risk factors for liver cancer have been established, preventive factors for liver cancer have not been fully explored. We evaluated the association between raw garlic consumption and liver cancer in a large population-based case-control study in Eastern China. The study was conducted in Jiangsu, China, from 2003 to 2010. A total of 2011 incident liver cancer cases and 7933 randomly selected population-controls were interviewed. Epidemiological data including raw garlic intake and other exposures were collected, and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were assayed. Overall, eating raw garlic twice or more per week was inversely associated with liver cancer, with an adjusted odds ratio (aOR) of 0.77 (95% confidence interval (CI): 0.62-0.96) compared to those ingesting no raw garlic or less than twice per week. In stratified analyses, high intake of raw garlic was inversely associated with liver cancer among Hepatitis B surface antigen (HBsAg) negative individuals, frequent alcohol drinkers, those having history of eating mold-contaminated food or drinking raw water, and those without family history of liver cancer. Marginal interactions on an additive scale were observed between low raw garlic intake and HBsAg positivity (attributable proportion due to interaction (AP) = 0.31, 95% CI: -0.01-0.62) and heavy alcohol drinking (AP = 0.28, 95% CI: 0.00-0.57). Raw garlic consumption is inversely associated with liver cancer. Such an association shed some light on the potential etiologic role of garlic intake on liver cancer, which in turn might provide a possible dietary intervention to reduce liver cancer in Chinese population

Detection of Hantaan Viral Antigens in Renal Tissues from a Patient with Korean Hemorrhagic Fever in Convalescent Phase

A case of a patient with Korean hemorrhagic fever (KHF) who showed typical clinical manifestations is described for the purpose of reporting the detection of Hantaan viral antigens in renal tissues. The pathophysiologic mechanisms of renal damage are not well known, and several mechanisms including direct renal injury by the virus itself have been proposed to explain the renal lesions and the clinical manifestations. We detected Hantaan viral antigens in renal tissues from a KHF patient in the convalescent phase by the immunohistochemical method using the monoclonal antibodies to Hantaan viral envelope glycoproteins (G1, G2). The immunostainings demonstrated Hantaan viral antigens in the renal tubular epithelial cells, the intraluminal desquamated tubular cells, the infiltrated cells in the interstitium, and the capillary endothelial cells in the interstitium and glomeruli. The presence of viral antigens in renal tissues may support the hypothesis that direct renal injury by the virus is one of the pathophysiologic mechanisms of renal damage in KH

Bioavailable insulin-like growth factor-I as mediator of racial disparity in obesity-relevant breast and colorectal cancer risk among postmenopausal women

Bioavailable insulin-like growth factor (IGF)-I interacts with obesity and exogenous estrogen in a racial disparity in obesity-related cancer risk, yet their interconnected pathways are not fully characterized. We investigated whether circulating bioavailable IGF-I acted as a mediator of the racial disparity in obesity-related cancers such as breast and colorectal (CR) cancers and how obesity and estrogen use regulate this relationship

Dose selection method for pharmacokinetic study in hemodialysis patients using a subpharmacological dose: oseltamivir as a model drug

BACKGROUND: Dose selection is an important step in pharmacokinetic (PK) studies of hemodialysis patients. We propose a simulation-based dose-selection method for PK studies of hemodialysis patients using a subpharmacological dose of oseltamivir as a model drug. METHODS: The concentrations of oseltamivir and its active metabolite, oseltamivir carboxylate (OC), were measured by liquid chromatography-tandem mass spectrometry. To determine a low oseltamivir dose exhibiting PK linearity, a pilot low dose determination investigation (n = 4) was performed using a single administration dose-escalation study. After the dose was determined, a low dose study (n = 10) was performed, and the optimal dose required to reach the hypothetical target OC exposure (area under the concentration-time curve [AUC] of 60,000 ng · hr/mL) was simulated using a nonparametric superposition method. Finally, observed PKs at the optimal dose were compared to the simulated PKs to verify PK predictability. RESULTS: In the pilot low dose determination study, 2.5 mg of oseltamivir was determined to be the low dose. Subsequently, we performed a single-dose PK study with the low oseltamivir dose in an additional group of 10 hemodialysis patients. The predicted AUC(last) of OC following continuous oseltamivir doses was simulated, and 35 mg of oseltamivir corresponded to the hypothetical target AUC(last) of OC. The observed PK profiles of OC at a 35-mg oseltamivir dose and the simulated data based on the low dose study were in close alignment. CONCLUSION: The results indicate that the proposed method provides a rational approach to determine the proper PK dose in hemodialysis patients