Introduction Anemia is a common complication of chronic kidney disease (CKD) in children; however, the role of inflammation in its pathogenesis remains incompletely understood. Methods To elucidate the role of interleukin (IL)-6 in renal anemia, we induced CKD by adenine diet in juvenile wild-type (WT) and IL-6 deficient ( Il6 KO) mice, and examined serum IL-6 and relevant parameters in children with CKD. Results WT-CKD mice developed anemia despite increases in serum erythropoietin and displayed low serum iron and elevated serum IL-6. IL-6 deficiency resulted in a significant improvement of red blood cell count and hemoglobin in CKD mice. This effect was associated with improvement of hypoferremia by Il6 deletion, likely mediated by hepcidin. However, correction of hypoferremia by oral iron supplementation in WT-CKD mice did not fully replicate the protective effects of Il6 deletion, suggesting an additional iron-independent role for IL-6 in CKD-anemia. Indeed, Il6 deletion mitigated the severity of renal fibrosis and alleviated relative erythropoietin insufficiency in CKD mice. Cytokine profiling in a pediatric CKD cohort demonstrated that of 10 cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, tumor necrosis factor (TNF)-α, and interferon-γ), only IL-6 was significantly (inversely) associated with hemoglobin when adjusted for glomerular filtration rate (GFR). The association between IL-6 and hemoglobin in children with CKD remained significant after adjustment for CKD stage, iron therapy, and hepcidin. Discussion IL-6 contributes to development of anemia in juvenile CKD, through mechanisms that include induction of hypoferremia, aggravation of renal fibrosis, and alteration of the erythropoietin axis. IL-6 appears to be a promising therapeutic target in the management of CKD-anemia.
PURPOSE Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by the human T-cell leukemia virus type 1. Real-world data of ATLL in Latin America are lacking. PATIENTS AND METHODS We analyzed patients with ATLL (acute, lymphomatous, chronic, and smoldering) encountered in 11 Latin American countries between 1995 and 2019. Treatment response was assessed according to the 2009 consensus report. Survival curves were estimated using the Kaplan-Meier method and log-rank test. RESULTS We identified 253 patients; 226 (lymphomatous: n = 122, acute: n = 73, chronic: n = 26, and smoldering: n = 5) had sufficient data for analysis (median age 57 years). Most patients with ATLL were from Peru (63%), Chile (17%), Argentina (8%), and Colombia (7%). Hypercalcemia was positively associated with acute type (57% v lymphomatous 27%, P = .014). The median survival times (months) were 4.3, 7.9, 21.1, and not reached for acute, lymphomatous, chronic, and smoldering forms, with 4-year survival rates of 8%, 22%, 40%, and 80%, respectively. First-line zidovudine (AZT)-interferon alfa (IFN) resulted in an overall response rate of 63% (complete response [CR] 24%) for acute. First-line chemotherapy yielded an overall response rate of 41% (CR 29%) for lymphomatous. CR rate was 42% for etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone versus 12% for cyclophosphamide, vincristine, doxorubicin, and prednisone–like regimen ( P < .001). Progression-free survival at 1 year for acute type patients treated with AZT-IFN was 67%, whereas 2-year progression-free survival in lymphomatous type patients who achieved CR after chemotherapy was 77%. CONCLUSION This study confirms Latin American ATLL presents at a younger age and has a high incidence of lymphomatous type, low incidence of indolent subtypes, and worse survival rates as compared with Japanese patients. In aggressive ATLL, chemotherapy remains the preferred choice for lymphomatous favoring etoposide-based regimen (etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone), whereas AZT-IFN remains a good first-line option for acute subtype.
Background: Coronavirus disease 2019 (COVID-19) has affected millions of people, and several chronic medical conditions appear to increase the risk of severe COVID-19. However, our understanding of COVID-19 outcomes in patients with chronic kidney disease (CKD) remains limited. Methods: This was a retrospective cohort study of patients with and without CKD consecutively admitted with COVID-19 to three affiliated hospitals in New York City. Pre-COVID-19 CKD diagnoses were identified by billing codes and verified by manual chart review. In-hospital mortality was compared between patients with and without underlying CKD. Logistic regression was used to adjust this analysis for confounders and to identify patient characteristics associated with mortality. Results: We identified 280 patients with CKD, and 4098 patients without CKD hospitalized with COVID-19. The median age of CKD group was 75 (65-84) years, and age of non-CKD group 62 (48-75) years. Baseline (pre-COVID-19) serum creatinine in patients with CKD was 1.5 (1.2-2.2) mg/dL. In-hospital mortality was 30% in patients with CKD vs. 19.9% in patients without CKD (p<0.001). The risk of in-hospital death in patients with CKD remained significantly higher after adjustment for comorbidities (hypertension, diabetes mellitus, asthma, and chronic obstructive pulmonary disease), adjusted OR 1.4 [1.1-1.9]. When stratified by age, elderly patients with CKD (above age 70) had higher mortality than their age-matched control patients without CKD. In patients with CKD, factors associated with in-hospital mortality were age (adjusted OR 1.09 [1.06-1.12]), baseline and admission serum phosphorus (adjusted ORs 1.5 [1.03-2.1] and 1.4 [1.1-1.7]), serum creatinine on admission >0.3 mg/dL above the baseline (adjusted OR 2.6 [1.2-5.4]), and diagnosis of acute on chronic kidney injury during hospitalization (adjusted OR 4.6 [2.3-8.9]). Conclusions: CKD is an independent risk factor for COVID-19 associated in-hospital mortality in elderly patients. Acute on chronic kidney injury increases odds of in-hospital mortality in CKD patients hospitalized with COVID-19.
Introduction Studies show a high prevalence of physical inactivity and sedentary behavior among university students. However, the relationship between physical activity and sedentary behavior in medical students is unknown. Objectives To determine the prevalence of physical activity, sedentary behavior, and related factors among medical students at a public university. Methods We conducted an analytical cross-sectional study that included students from the first to the sixth year of medical school. We used the International Physical Activity Questionnaire (IPAQ). We analyzed study variables using Poisson regression, estimating crude and adjusted prevalence ratios. Results The final sample consisted of 513 students, of which 35% of women and 30.1% of all pre-clinical students had a low level of physical activity. Male sex and 20 to 24 age group were associated with a lower prevalence of low level of physical activity. Sedentary behavior was 60.9% among students under 20 years old and 55.5% among pre-clinical students. A lower prevalence of sedentary behavior was found in students over 25 years old, clinical students, and those with high levels of physical activity. Conclusion Most medical students presented a moderate level of physical activity. We found a higher presence of low-level physical activity among females and pre-clinical students. We found that sedentary behavior was higher than reported in similar populations. The relationship between physical activity and lower sedentary behavior was significant only for students with a high-level physical activity.
The Nijmegen Biomedical Study is a population-based cross-sectional study conducted in the eastern part of the Netherlands. As part of the overall study, we provide reference values of estimated glomerular filtration rate (GFR) for this Caucasian population without expressed risk. Age-stratified, randomly selected inhabitants received a postal questionnaire on lifestyle and medical history. In a large subset of the responders, serum creatinine was measured. The GFR was then measured using the abbreviated Modification of Diet in Renal Disease (MDRD) formula. To limit possible bias, serum creatinine was calibrated against measurements performed in the original MDRD laboratory. The study cohort included 2823 male and 3274 female Caucasian persons aged 18-90 years. A reference population of apparently healthy subjects was selected by excluding persons with known hypertension, diabetes, cardiovascular-or renal diseases. This healthy study cohort included 1660 male subjects and 2072 female subjects, of which 869 of both genders were 65 years or older. The median GFR was 85 ml/min/1.73 m 2 in 30-to 34-year-old men and 83 ml/min/1.73 m 2 in similar aged women. In these healthy persons, GFR declined approximately 0.4 ml/min/year. Our study provides age-and gender-specific reference values of GFR in a population of Caucasian persons without identifiable risk.
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