1177. Vaccinate Lurie (VaLu) a QI Project to Improve Pediatric Pre-Transplant Immunization Rates

Abstract Background Immunization prior to transplantation is important due to post-transplant immunosuppression. According to a national study, 15% of pediatric solid organ transplant recipients were hospitalized within 5 years post-transplant for a vaccine preventable illness or RSV. At our large academic pediatric hospital approximately 53% of heart and liver transplant recipients in 2016 -2018 were up to date with tetanus and pneumococcal vaccinations. This QI project was designed to improve our pre-transplant vaccination rates to minimize post-transplant infections. Methods An interdisciplinary team was convened including pharmacists, nurses, nurse practitioners, and physicians from cardiology, hepatology, and infectious diseases. After evaluating our current processes and key drivers, we selected interventions to implement via the PDSA model. Our first intervention was to have team members gain access to our statewide vaccine database (ICARE). Our second cycle was to link ICARE to our electronic medical record system (EPIC) for automatic immunization record integration. Process Map Key Driver Diagram Results Our outcome measure was up to date tetanus and pneumococcal vaccines per the CDC recommendations by age at transplant, as documented in the medical record. We saw an improvement in immunization rates to 100% during the third quarter of 2020 with an overall rate of over 80% for late 2019 - mid 2020. With the understanding that our average wait time for a heart and liver transplant was 2.4 and 3.8 months, respectively, the initiation of our QI project and obtaining access to ICARE by our team members was likely related to the improved vaccination rates. Unfortunately, after the team stopped meeting during the pandemic our immunization completion rates have decreased in 2021, despite implementing institutional access to ICARE. Control Chart Conclusion It is possible to obtain optimal immunization rates for pneumococcal and tetanus vaccines in pediatric heart and liver transplant recipients. Our future interventions include improving vaccinations after catch-up recommendations have been made and sustaining our interventions. Additionally, we look to expand our analysis to include outcomes related to vaccine-preventable diseases after transplantation. Disclosures Jacquie Toia, DNP, RN, APN, QarTek (Board Member) Ravi Jhaveri, MD, AstraZeneca (Consultant)Dynavax (Consultant)Elsevier (Other Financial or Material Support, Editorial Stipend as Co-editor in Chief, Clinical Therapeutics)Seqirus (Consultant) </jats:sec

Targeted adenovirus-induced expression of IL-10 decreases thymic apoptosis and improves survival in murine sepsis

Sepsis remains a significant clinical conundrum, and recent clinical trials with anticytokine therapies have produced disappointing results. Animal studies have suggested that increased lymphocyte apoptosis may contribute to sepsis-induced mortality. We report here that inhibition of thymocyte apoptosis by targeted adenovirus-induced thymic expression of human IL-10 reduced blood bacteremia and prevented mortality in sepsis. In contrast, systemic administration of an adenovirus expressing IL-10 was without any protective effect. Improvements in survival were associated with increases in Bcl-2 expression and reductions in caspase-3 activity and thymocyte apoptosis. These studies demonstrate that thymic apoptosis plays a critical role in the pathogenesis of sepsis and identifies a gene therapy approach for its therapeutic intervention

Vitamin A and Vitamin B-12 Concentrations in Relation to Mortality and Morbidity among Children Born to HIV-Infected Women

Vitamin A supplementation starting at 6 months of age is an important child survival intervention; however, not much is known about the association between vitamin A status before 6 months and mortality among children born to HIV-infected women. Plasma concentrations of vitamins A and B-12 were available at 6 weeks of age (n = 576 and 529, respectively) for children born to HIV-infected women and they were followed up for morbidity and survival status until 24 months after birth. Children in the highest quartile of vitamin A had a 49% lower risk of death by 24 months of age compared to the lowest quartile (HR: 0.51, 95% CI: 0.29–0.90; P-value for trend = 0.01). Higher vitamin A levels were protective in the sub-groups of HIV-infected and un-infected children but this was statistically significant only in the HIV-uninfected subgroup. Higher vitamin A concentrations in plasma are protective against mortality in children born to HIV-infected women

Patterns and Predictors of CD4 T-cell Counts Among Children Born to HIV-infected Women in Tanzania

We assessed age-specific CD4 T-cell counts and their determinants among Tanzanian children born to HIV-infected mothers to address a major research gap. A total of 474 HIV-uninfected and 69 HIV-infected children were followed until age of 12 months. Maternal predictors were measured during pregnancy and child predictors at birth and throughout the follow up. Child CD4 T-cell counts were evaluated at the age of 3 months and subsequent 3-month intervals; they decreased linearly among HIV-infected (β = –8 cells per week; 95% CI –12 to –4; P = 0.0003) and increased linearly among HIV-uninfected children (β = 4 cells/week; 95% CI 2–7; P = 0.0008). Decreased child counts were predicted by low child anthropometry, maternal HIV stage ≥2, and maternal mid-upper arm circumference <27 cm among HIV-infected children; and by weight-for-height <–2 z-score, maternal HIV stage ≥2, maternal erythrocyte sedimentation rate <81 mm/h and maternal haemoglobin <8.5 g/dl among HIV-uninfected children. The maternal and child predictors described may serve as intervention targets among HIV-exposed children

Apoptosis is triggered when prosurvival Bcl-2 proteins cannot restrain Bax

A central issue in the control of apoptosis is whether its essential mediators Bax and Bak must be restrained by Bcl-2-like prosurvival relatives to prevent their damaging mitochondria and unleashing apoptosis. The issue is particularly vexed for Bax, which is largely a cytosolic monomer in unstressed cells. To determine whether Bax regulation requires its binding by prosurvival relatives, we replaced a conserved aspartate in its BH3 interaction domain with arginine. Bax D68R functioned and behaved like wild-type Bax in localization and activation but had greatly impaired binding to the prosurvival family members. Nevertheless, Bcl-xL remained able to block apoptosis induced by Bax D68R. Whereas cells with sufficient Bcl-xL tolerated expression of Bax D68R, it provoked apoptosis when Bcl-xL was absent, downregulated, or inactivated. Moreover, Bax D68R rendered membrane bound by a C-terminal anchor mutation overwhelmed endogenous Bcl-xL and killed cells. These unexpected results suggest that engagement of Bax by its prosurvival relatives is a major barrier to its full activation. We propose that the Bcl-2-like proteins must capture the small proportion of Bax molecules with an exposed BH3 domain, probably on the mitochondrial membrane, to prevent Bax-imposed cell death, but that Bcl-xL also controls Bax by other mechanisms

The BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IP3 receptor

Although the presence of a BH4 domain distinguishes the antiapoptotic protein Bcl-2 from its proapoptotic relatives, little is known about its function. BH4 deletion converts Bcl-2 into a proapoptotic protein, whereas a TAT-BH4 fusion peptide inhibits apoptosis and improves survival in models of disease due to accelerated apoptosis. Thus, the BH4 domain has antiapoptotic activity independent of full-length Bcl-2. Here we report that the BH4 domain mediates interaction of Bcl-2 with the inositol 1,4,5-trisphosphate (IP3) receptor, an IP3-gated Ca2+ channel on the endoplasmic reticulum (ER). BH4 peptide binds to the regulatory and coupling domain of the IP3 receptor and inhibits IP3-dependent channel opening, Ca2+ release from the ER, and Ca2+-mediated apoptosis. A peptide inhibitor of Bcl-2-IP3 receptor interaction prevents these BH4-mediated effects. By inhibiting proapoptotic Ca2+ signals at their point of origin, the Bcl-2 BH4 domain has the facility to block diverse pathways through which Ca2+ induces apoptosis.status: publishe