Background: We assessed whether immunohistologic markers for glomerular or tubulointerstitial injury might provide better correlations with ongoing renal function and disease activity as compared with the WHO classification or the NIH activity and chronicity indices in lupus nephritis. Methods: Thirty-three patients with clinically defined systemic lupus underwent renal biopsy over a 1-year period at Hospital Loayza in Lima, Peru. Biopsy specimens were evaluated for macrophages, proliferating cells, α-actin expression, and type IV collagen deposition in both glomeruli and the tubulointerstitium and the results compared with the current WHO and NIH classifications in relation to the clinical presentation. Results: Patients with WHO class IV lupus nephritis were more likely to have lower serum complements, greater proteinuria and hematuria, and worse renal function. An elevated NIH activity index correlated with microhematuria, proteinuria, and impaired renal function, whereas an elevated chronicity index correlated with renal function, hypertension, and microhematuria, but not with proteinuria. The presence of glomerular macrophages correlated with both glomerular α-actin expression and type IV collagen deposition, but did not correlate with renal function or proteinuria. In contrast, interstitial macrophages correlated not only with interstitial collagen deposition and myofibroblast accumulation, but also correlated with both renal function and the presence of nephrotic syndrome. Conclusions: Both the WHO classification and the NIH activity/chronicity indices correlate with clinical manifestations of lupus nephritis. While glomerular macrophage accumulation correlates with mesangial cell activation (α-actin expression) and collagen deposition, and interstitial macrophage accumulation correlates with interstitial fibroblast activation and collagen deposition, only interstitial macrophages correlate with renal function. Of particular interest will be future studies to determine whether these markers correlate with the prognosis.
Sepsis is a severe dysregulated immune response to infection. Sepsis deaths represent 9% of cancer deaths in the U.S. Evidence of the effect of specific cancer sites on sepsis mortality risk remains limited, and no research has evaluated the effect of cancer treatment on the risk of sepsis death. We examined whether cancer sites and treatments differentially affect the risk of sepsis death compared to other-cause mortality, among the 94,784 Hawaii participants in the Multiethnic Cohort, including 29,255 cancer cases, using competing risk Cox proportional hazards regression. Cancer diagnosis at any site was associated with similar increases in sepsis and non-sepsis mortality risk (HR: 3.39 and 3.51, resp.). Colorectal cancer differentially affected the risk of sepsis and non-sepsis mortality with a 40% higher effect on the risk of sepsis death compared with non-sepsis mortality (RRR: 1.40; 95% CI: 1.14–1.72). Lung cancer was associated with a significantly lower increase in sepsis compared to non-sepsis mortality (HR: 1.22 and 3.0, resp.; RRR: 0.39). Radiation therapy had no effect on sepsis mortality but was associated with higher risk of non-sepsis mortality (HR: 0.90 and 1.16, resp.; RRR: 0.76), whereas chemotherapy was associated with higher risk of both sepsis and non-sepsis mortality (HR: 1.31 and 1.21, resp.). We conclude that the risk of sepsis-related mortality is differentially affected by cancer sites and treatments. These associations were consistent across sexes and ethnic groups.
e12500 Background: Evidence has linked weight gain and obesity to increased breast cancer risk, poorer outcomes, decreased survivorship, and increased risk of recurrence. Adjuvant therapies can increase weight gain, making tailored exercise interventions beneficial in maintaining a healthy weight. In this study, body composition changes were examined after a 12-week exercise program in a cohort of breast cancer survivors. Methods: The Breast Cancer Exercise Rehabilitation Research Study recruited breast cancer survivors to undergo a 12-week exercise program (NCT04013568) and examine body composition changes. Measurements taken included anthropometry (waist circumference, waist-to-hip ratio, BMI), DXA body composition measurements (fat mass-visceral and subcutaneous, trunk to limb, muscle mass-appendicular, and whole body), and BIA (Bio-electrical Impedance Analysis-muscle, fat, and water). 34 participants completed the exercise program and baseline and post-12-week measurements were obtained. Descriptive statistics and a paired t-test analysis was done to analyze changes in body composition using SAS onDemand. A correlation analysis between measurements simple to do in clinic and DXA measurements were run to determine proxy use for DXA. Results: After a 12-week exercise program, reductions in body fat via DXA scan, BIA, and InBody (whole body fat, whole body fat %, trunk fat, leg fat, body fat %, hip width at maximum girth, body fat mass, and percent body fat) were observed. Additionally, increases in lean mass (Appendicular Lean Mass (ALM)/height2, Appendicular Lean/height2, ALM index, and lean body mass), whole body mass measured by DXA, basal metabolic rate, water retention (extracellular water and total body water), and skeletal muscle mass were observed. Correlation analysis revealed BMI can be used as a surrogate measure for whole body mass measured by DXA (r=0.91, p<0.001) and can be utilized to measure change over time. Skinfold sum showed moderate correlation for measuring subcutaneous fat mass by DXA (r=0.45, p=0.0096). Conclusions: In our population of breast cancer survivors, a 12-week exercise program did show various changes in body composition according to InBody, DXA, and BIA measurements. DXA and InBody measurements were feasible, making it readily available for patients. Additionally, simple measures such as BMI and skinfold sum showed moderate to strong correlation with DXA measurements, validating use of these measurements in routine practice. Clinical trial information: NCT04013568. [Table: see text]
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