A Improving Birth-dose Hepatitis-B Vaccination in a Tertiary Level IV Neonatal Intensive Care Unit.

Background: Perinatal hepatitis B is a global public health concern. To reduce perinatal hepatitis B and its complications, the Hepatitis B vaccine (HBV) is recommended by the New York State Department of Health and Advisory Committee on Immunization Practices within 24 hours of life for infants born with a birth weight ≥2000 g. Infants admitted to the neonatal intensive care unit (NICU) weighing over 2000 g missed their birth dose HBV frequently, which prompted the implementation of a quality improvement initiative to increase birth dose HBV immunization in a level IV NICU in New York. Methods: May 2019 to April 2021 baseline data showed the birth dose HBV rate of infants born ≥2000 g at 24% and 31% within 12 and 24 hours, respectively. The multidisciplinary QI team identified barriers using an Ishikawa cause-and-effect diagram. Our interventions included multidisciplinary collaboration, electronic medical record reminders, education, posters, and improved communication between staff and parents. We aimed to achieve a 25% improvement from the baseline. Results: After 19 months of QI interventions (four Plan-Do-Study-Act cycles), the rate of administering birth dose HBV within 12 hours of life increased from 24% to 56% and within 24 hours from 31% to 64%. Process measure compliance improved, exceeding the 25% target, and showed sustained improvement. Conclusion: This QI initiative improved the rate of eligible infants receiving HBV within the first 24 hours of life in the NICU. This work can serve as a model for other healthcare institutions to improve HBV immunization rates in NICUs.

High terminal creatinine donors should not preclude simultaneous kidney and pancreas transplantation.

BACKGROUND: Simultaneous pancreas and kidney transplantation (SPK) in the setting of end-stage renal disease offers unmatched outcomes in insulin dependent diabetic patients. Donor pool expansion through the transplantation of kidneys with acute kidney injury (AKI) is controversial. METHODS: 59 SPK transplants were classified by presence of donor AKI, defined as donor terminal creatinine ≥ 1.5x the initial creatinine or donor terminal creatinine > 4.0 mg/dL. Endpoints included graft and patient survival, delayed graft function (DGF), serum creatinine, glomerular filtration rate (GFR), Hemoglobin A1c (HbA1c) and acute rejection. RESULTS: The donor AKI group (n = 35) had significantly higher rates of DGF (38 v. 9%, p = 0.01). There was no difference in creatinine or GFR at 1, 3, 6 and 12 months. HbA1c was comparable at 3, 6 and 12 months. There was no significant difference in the percentage of patients that required anti-diabetic agents after transplant (14 v. 4%, p = 0.56). CONCLUSIONS: We observed increased rates of DGF in SPK recipients with donor AKI. However, equivalent outcomes of pancreas and kidney function in both groups were observed.

The Scaffolding Protein IQGAP1 Interacts with NLRC3 and Inhibits Type I IFN Production.

Sensing of cytosolic nucleotides is a critical initial step in the elaboration of type I IFN. One of several upstream receptors, cyclic GMP-AMP synthase, binds to cytosolic DNA and generates dicyclic nucleotides that act as secondary messengers. These secondary messengers bind directly to stimulator of IFN genes (STING). STING recruits TNFR-associated NF-κB kinase-binding kinase 1 which acts as a critical node that allows for efficient activation of IFN regulatory factors to drive the antiviral transcriptome. NLRC3 is a recently characterized nucleotide-binding domain, leucine-rich repeat containing protein (NLR) that negatively regulates the type I IFN pathway by inhibiting subcellular redistribution and effective signaling of STING, thus blunting the transcription of type I IFNs. NLRC3 is predominantly expressed in lymphoid and myeloid cells. IQGAP1 was identified as a putative interacting partner of NLRC3 through yeast two-hybrid screening. In this article, we show that IQGAP1 associates with NLRC3 and can disrupt the NLRC3-STING interaction in the cytosol of human epithelial cells. Furthermore, knockdown of IQGAP1 in THP1 and HeLa cells causes significantly more IFN-ß production in response to cytosolic nucleic acids. This result phenocopies NLRC3-deficient macrophages and fibroblasts and short hairpin RNA knockdown of NLRC3 in THP1 cells. Our findings suggest that IQGAP1 is a novel regulator of type I IFN production, possibly via interacting with NLRC3 in human monocytic and epithelial cells.