When Dialysis "Becomes Life": Pediatric Caregivers' Lived Experiences Obtained From Patient-Reported Outcomes Measures.

Introduction: Qualitative research reveals significant caregiver impact resulting from managing children requiring chronic dialysis but offers few quantitative measures of their lived experiences. Materials and Methods: This cross-sectional study included 25 caregivers of children on chronic peritoneal dialysis (PD) and hemodialysis (HD) enrolled from 2018 to 2019 at a large pediatric dialysis program in the U.S.Patient Reported Outcomes Measures Information System (PROMIS) measures and free text commentary were collected and analyzed to evaluate the self-reported impact and wellbeing of these caregivers. Results: Among all dialysis modalities, caregivers' positive affect (43.4 ± 10) and general life satisfaction (45.1 ± 11.5) were significantly lower than the general adult population. Compared with HD caregivers, PD caregivers demonstrated significantly more fatigue and sleep disturbance and less positive affect and life satisfaction. Amongst HD caregivers, sleep disturbance, positive affect, and meaning/purpose differed significantly from the general population. Analyses of text commentary revealed that caregivers also expressed the feelings of loss, importance of knowing the impact of dialysis prior to initiation, need for a support group, and value of home nursing. Conclusions: Caregivers of children on chronic dialysis had significantly poorer self-rated health and wellbeing compared with the general adult population. This may be due in part to their feelings of social isolation. Our findings highlight opportunities to improve caregivers' lived experiences.

Promoting safe sexual practices and sexual health maintenance in pediatric and young adult solid organ transplant recipients.

The majority of Americans make their sexual debut during their adolescent years. Preventing pregnancy and STI during this period is vital to ensuring health and safety. As survival has improved after pediatric SOT, chronically immunosuppressed adolescents seek guidance in their medical home on matters of sexual health. Transplant practitioners often do not feel equipped to fully address these needs. This review serves as an introductory sexual preventive care resource for adolescent and young adult (AYA) SOT recipients. First, we review data on safety, efficacy, and use of contraceptive options currently available for transplant recipients with child-bearing potential. Then, we suggest a personalized sexual health discussion focusing on the diagnosis and prevention of STIs in adolescent and young adult transplant recipients. Finally, we present recommendations for STI screening of asymptomatic patients, use of index of suspicion and diagnostic testing in symptomatic patients, and opportunities to optimize STI prevention strategies. Data compiled from studies of adult SOT recipients, general population studies, and published guidelines are often extrapolated for use, as limited data exist in AYA SOT recipients. This informational dearth underscores the need for future research to better characterize the unique needs of AYA SOT recipients.

Use of public health service increased risk kidneys in pediatric renal transplant recipients.

With the opioid epidemic and expansion of "IR" classification, 25% of deceased donors are categorized PHS-IR. Studies have assessed utilization of PHS-IR organs among adults, but little is known about pediatric recipients. This retrospective cohort study from 2004-2016 (IR period) aimed to: (a) assess IR kidney utilization patterns between adults and children; (b) identify recipient factors associated with transplant from IR donors among pediatric kidney recipients; and (c) determine geography's role in IR kidney utilization for children. The proportion of pediatric recipients receiving IR kidneys was significantly lower than adults (P < 0.001), even when stratified by donor mechanism of death (non-overdose/overdose) and era. In mixed effects models accounting for clustering within centers and regions, older recipient age, later era (post-PHS-IR expansion), and blood type were associated with significantly higher odds of receiving an IR kidney (17 years era 5: OR 5.16 [CI 2.05-13.1] P < 0.001; 18-21 years era 5: OR 2.72 [CI 1.05-7.06] P = 0.04; blood type O: OR 1.32 [CI 1.06-1.64] P = 0.013). The median odds ratio for center within region was 1.77 indicating that when comparing two patients in a region, the odds of receiving an IR kidney were 77% higher for a patient from a center with higher likelihood of receiving an IR kidney. Utilization of PHS-IR kidneys is significantly lower among pediatric recipients versus adult counterparts. More work is needed to understand the reasons for these differences in children in order to continue their access to this life-prolonging therapy.

Thymic stromal lymphopoietin blocks early stages of breast carcinogenesis.

Advances in the field of cancer immunology, including studies on tumor-infiltrating CD8+ cytotoxic T lymphocytes (CTLs), have led to new immunotherapeutics with proven efficacy against late-stage cancers. However, the antitumor potential of the immune system in targeting early-stage cancers remains uncertain. Here, we demonstrated that both genetic and chemical induction of thymic stromal lymphopoietin (TSLP) at a distant site leads to robust antitumor immunity against spontaneous breast carcinogenesis in mice. Breast tumors exposed to high circulating levels of TSLP were arrested at an early adenoma-like stage and were prevented from advancing to late carcinoma and metastasis. Additionally, CD4+ Th2 cells mediated the antitumor effects of TSLP, challenging the notion that Th2 cells only promote cancer. We also discovered that TSLP is expressed by the breast tumor cells themselves and acts to block breast cancer promotion. Moreover, TSLP-induced immunity also blocked early stages of pancreatic cancer development. Together, our findings demonstrate that TSLP potently induces immunity directed against early stages of breast cancer development without causing inflammation in the normal breast tissue. Moreover, our results highlight a previously unappreciated function of the immune system in controlling the early development of cancer and establish a fundamental role for TSLP and Th2 cells in tumor immunity against early-stage cancers.

Blood pressure variability in children with primary vs secondary hypertension.

Increased blood pressure variability (BPV) is correlated with adverse cardiovascular (CV) events in adults. However, there has been limited research on its effect in the pediatric population. Additionally, BPV differences between primary and secondary hypertension (HTN) are not known. Children with primary and secondary HTN underwent 24-hour ambulatory blood pressure monitoring and echocardiography studies. BPV measures of standard deviation (SD), average real variability (ARV), and range were calculated for the 24-hour, daytime, and nighttime periods. Seventy-four patients (median age, 13.5 years; 74% boys) were examined, 40 of whom had primary HTN. Body mass index z score and age were independent predictors of systolic ARV (R(2) =0.14) and SD (R(2) =0.39). There were no statistically significant differences in overall or wake period BPV measures between secondary or primary HTN groups, but sleep period diastolic SD was significantly greater in the secondary HTN group (9.26±3.8 vs 7.1±2.8, P=.039). On multiple regression analysis, secondary HTN was associated with increased sleep period diastolic SD (P=.025). No metrics of BPV in the overall, wake, and sleep periods were found to be significantly associated with left ventricular hypertrophy (LVH). The results of this study do not show a strong relationship between overall or wake BPV with primary vs secondary HTN, but the association of secondary HTN with sleep period diastolic BPV deserves further exploration. Contrary to expectation, the findings of this study failed to indicate a relationship between BPV and LVH for all patients as well for primary hypertensive and secondary hypertensive patients.

Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects.

OBJECTIVE: Experimental studies suggest that adipose inflammation is etiologically linked to obesity-induced systemic disease. Our goal was to characterize the state of inflammation in human fat in relation to vascular function and metabolic parameters in obese individuals. METHODS AND RESULTS: We collected subcutaneous abdominal fat in 77 obese subjects (BMI >or=30 kg/m(2)) and quantified adipose macrophage population using targeted immunohistochemistry. Brachial artery vasodilator function was examined using high-resolution vascular ultrasound. In 50 subjects, an inflamed adipose phenotype characterized by tissue macrophage accumulation in crown-like structures was associated with systemic hyperinsulinemia and insulin resistance (HOMA-IR 5.5+/-4.5 versus 2.6+/-1.9, P=0.002) and impaired endothelium-dependent flow-mediated vasodilation (8.5+/-4.4% versus 10.8+/-3.8%, P<0.05), as compared to subjects with quiescent noninflamed adipose architecture (n=27). Macrophage retention in fat was linked to upregulated tissue CD68 and tumor necrosis factor (TNF)-alpha mRNA expression in addition to increased plasma hs-CRP. CONCLUSIONS: In a cohort of obese subjects, we demonstrate that proinflammatory changes in adipose tissue are associated with systemic arterial dysfunction and insulin resistance. These findings suggest that adipose inflammation may be linked to vascular injury and increased cardiovascular risk in obese subjects.

Spatial and temporal influences on bacterial profiling of forensic soil samples.

Bacterial content may be helpful in differentiating forensic soil samples; however, the effectiveness of bacterial profiling depends on several factors, including uniqueness among different habitat types, the level of heterogeneity within a habitat, and changes in bacterial communities over time. To examine these, soils from five diverse habitats were tested over a 1 year period using terminal restriction fragment length polymorphism (TRFLP) analysis. Soil samples were collected at central locations monthly, and 10 feet in cardinal directions quarterly. Similarity indices were found to be least related among habitats, while the greatest bacterial similarities existed among collection locations within a habitat. Temporally, however, bacterial content varied considerably, and there was substantial overlap in similarity indices among habitats during different parts of the year. Taken together, the results indicate that while bacterial DNA profiling may be useful for forensic soil analysis, certain variables, particularly time, must be considered.

Endothelial dysfunction in obesity: etiological role in atherosclerosis.

PURPOSE OF REVIEW: To review studies of vascular endothelial dysfunction in obesity, discuss potential mechanisms of disease, and address the therapeutic effects of weight loss interventions on arterial health. RECENT FINDINGS: Endothelial dysfunction represents the earliest abnormality in the development of vascular disease, and is pathophysiologically linked to subsequent atherosclerosis progression and cardiovascular disease events. Obesity is closely associated with a number of established cardiovascular risk factors, including diabetes mellitus, insulin resistance, dyslipidemia, and hypertension that are cumulatively damaging to the endothelium. In addition, there is now a growing recognition of non-traditional risk factors as potential modulators of the endothelial phenotype in obesity, including fat tissue production of proatherogenic adipokines, oxidative stress, and chronic inflammation. Clinical studies have demonstrated that even modest weight loss reverses endothelial dysfunction, and the restoration of arterial homeostasis could potentially reduce cardiovascular risk. SUMMARY: Obesity is associated with altered arterial homeostasis and endothelial dysfunction. Mechanisms of disease are related to a complex interplay of metabolic and inflammatory factors that coordinately improve along with arterial function in response to weight loss interventions.

HIV transmission risk practices in rural persons living with HIV disease.

BACKGROUND: Little is known about continued high-risk sexual behavior of persons living with HIV disease in rural areas of the United States. However, as HIV seroprevalence rates increase in rural communities, there is an urgent need to develop interventions to assist HIV-infected rural individuals who have difficulty refraining from high-risk sex. GOAL: To characterize patterns of continued high-risk sex among 216 men and women living with HIV disease in rural areas of 12 states. STUDY DESIGN: Cross-sectional, self-administered survey. RESULTS: Thirty-two percent of men and 38% of women reported that all of their sex partners in the previous 3 months were HIV-seronegative. Among the 33% of men who engaged in anal sex, 59% never or rarely used condoms. Of the 55% of women who engaged in vaginal sex in the previous 3 months, 31% never used condoms. CONCLUSION: Culturally contextualized interventions are needed to initiate and facilitate the risk-reduction efforts of HIV-infected rural persons.