Prehabilitation in our most frail surgical patients: are wearable fitness devices the next frontier?
CURRENT OPINION IN ORGAN TRANSPLANTATION
2016; 21 (2): 188-193
Serum elevation of B lymphocyte stimulator does not increase regulatory B cells in glioblastoma patients undergoing immunotherapy
CANCER IMMUNOLOGY IMMUNOTHERAPY
2016; 65 (2): 205-211
Frailty is the concept of accumulating physiologic declines that make people less able to deal with stressors, including surgery. Prehabilitation is intervention to enhance functional capacity before surgery. Frailty and prehabilitation among transplant populations and the role of wearable fitness tracking devices (WFTs) in delivering fitness-based interventions will be discussed.Frailty is associated with increased complications, longer length of hospital stay and increased mortality after surgery. Frail kidney transplant patients have increased delayed graft function, mortality and early hospital readmission. Frail lung or liver transplant patients are more likely to delist or die on the waitlist. Prehabilitation can mitigate frailty and has resulted in decreased length of hospital stay and fewer postsurgical complications among a variety of surgical populations. Increasingly, WFTs are used to monitor patient activity and improve patient health. Interventions using WFTs have resulted in improved activity, weight loss and blood pressure.Frailty is a measurable parameter that identifies patients at risk for worse health outcomes and can be mitigated through intervention. Prehabilitation to reduce frailty has been shown to improve postsurgical outcomes in a variety of populations. WFTs are being integrated in healthcare delivery for monitoring and changing health behavior with promising results.
View details for DOI 10.1097/MOT.0000000000000295
View details for Web of Science ID 000371883900018
View details for PubMedID 26859220
A Systematic Review of Race and Ethnicity in Hepatitis C Clinical Trial Enrollment.
Journal of the National Medical Association
2016; 108 (1): 24-29
Regulatory B cells that secrete IL-10 (IL-10(+) Bregs) represent a suppressive subset of the B cell compartment with prominent anti-inflammatory capacity, capable of suppressing cellular and humoral responses to cancer and vaccines. B lymphocyte stimulator (BLyS) is a key regulatory molecule in IL-10(+) Breg biology with tightly controlled serum levels. However, BLyS levels can be drastically altered upon chemotherapeutic intervention. We have previously shown that serum BLyS levels are elevated, and directly associated, with increased antigen-specific antibody titers in patients with glioblastoma (GBM) undergoing lymphodepletive temozolomide chemotherapy and vaccination. In this study, we examined corresponding IL-10(+) Breg responses within this patient population and demonstrate that the IL-10(+) Breg compartment remains constant before and after administration of the vaccine, despite elevated BLyS levels in circulation. IL-10(+) Breg frequencies were not associated with serum BLyS levels, and ex vivo stimulation with a physiologically relevant concentration of BLyS did not increase IL-10(+) Breg frequency. However, BLyS stimulation did increase the frequency of the overall B cell compartment and promoted B cell proliferation upon B cell receptor engagement. Therefore, using BLyS as an adjuvant with therapeutic peptide vaccination could promote humoral immunity with no increase in immunosuppressive IL-10(+) Bregs. These results have implications for modulating humoral responses in human peptide vaccine trials in patients with GBM.
View details for DOI 10.1007/s00262-015-1784-3
View details for Web of Science ID 000368719200008
View details for PubMedID 26759007
Testosterone Levels Influence Mouse Fetal Leydig Cell Progenitors Through Notch Signaling
BIOLOGY OF REPRODUCTION
2013; 88 (4)
The African American/Black population in the United States (US) is disproportionately affected by hepatitis C virus (HCV) and has lower response rates to current treatments. This analysis evaluates the participation of African American/Blacks in North American and European HCV clinical trials. The data source for this analysis was the PubMed database. Randomized controlled clinical trials (RCT) on HCV treatment with interferon 2a or 2b between January 2000 and December 2011 were reviewed. Inclusion criteria included English language and participants 18 years or older with chronic HCV. Exclusion criteria included non-randomized trials, case reports, cohort studies, ethnic specific studies, or studies not using interferon-alfa or PEG-interferon. Of the 588 trials identified, 314 (53.4%) fit inclusion criteria. The main outcome was the rate of African American/ Black participation in North American HCV clinical trials. A meta-analysis comparing the expected and observed rates was performed. Of the RCT's that met search criteria, 123 (39.2%) reported race. Clinical trials in North America were more likely to report racial data than European trials. Racial reporting increased over time. There was a statistically significant difference among the expected and observed participation of African Americans in HCV clinical trials in North America based on the prevalence of this disease within the population. The burden of HCV among African Americans in North America is not reflected in those clinical trials designed to treat HCV. Research on minority participation in clinical trials and how to increase minority participation in clinical trials is needed.
View details for DOI 10.1016/j.jnma.2015.12.004
View details for PubMedID 26928485
Leydig cells are the steroidogenic lineage of the mammalian testis that produces testosterone, a key hormone required throughout male fetal and adult life for virilization and spermatogenesis. Both fetal and adult Leydig cells arise from a progenitor population in the testis interstitium but are thought to be lineage-independent of one another. Genetic evidence indicates that Notch signaling is required during fetal life to maintain a balance between differentiated Leydig cells and their progenitors, but the elusive progenitor cell type and ligands involved have not been identified. In this study, we show that the Notch pathway signals through the ligand JAG1 in perivascular interstitial cells during fetal life. In the early postnatal testis, we show that circulating levels of testosterone directly affect Notch signaling, implicating a feedback role for systemic circulating factors in the regulation of progenitor cells. Between Postnatal Days 3 and 21, as fetal Leydig cells disappear from the testis and are replaced by adult Leydig cells, the perivascular population of interstitial cells active for Notch signaling declines, consistent with distinct regulation of adult Leydig progenitors.
View details for DOI 10.1095/biolreprod.112.106138
View details for Web of Science ID 000317471700014
View details for PubMedID 23467742