Protocol Biopsy After Kidney Transplant: Clinical Application and Efficacy to Detect Allograft Rejection.

Background Kidney transplant rejection is a major cause of graft dysfunction and failure. In recent years, there has been increased interest in renal allograft protocol biopsies to allow earlier detection of acute or chronic graft dysfunction or rejection to improve long-term graft survival and reduce graft failure. This study aimed to determine if renal allograft protocol biopsies performed within the first 12 months after transplantation help detect subclinical graft dysfunction or rejection. Methods We performed a retrospective analysis utilizing SUNY Upstate University Hospital data from January 2016 to March 2022 to assess transplant outcomes and biopsies. The study population was divided into two subgroups: non-protocol biopsies and protocol biopsies within the 12 months post-transplant. Results A total of 332 patients met our inclusion criteria and were included in the study. Patients were divided into two subgroups: 135 patients (40.6%) in the protocol biopsy group and 197 patients (59.4%) with non-protocol indication biopsies during the first year after the transplant. The overall number of rejection episodes reported was eight episodes (4.6%) in the protocol biopsy group and 56 episodes (18.3%) in the non-protocol indication biopsy group, which was significantly higher in the non-protocol biopsy group (P=0.001). Antibody-mediated rejection (ABMR) and T-cell-mediated rejection (TCMR) diagnoses were significantly higher in the non-protocol biopsy group (P=0.03 and P=0.03, respectively). We also mentioned a trend in terms of mixed antibody-mediated rejection and T-cell-mediated rejection diagnosis (P=0.07). One year after the rejection, the mean glomerular filtration rate (GFR) was 56.78 mL/min/1.73m2 in the protocol biopsy group and 49.14 mL/min/1.73m2 in the non-protocol indication biopsy group, and there was no significant difference anymore (P=0.11). The patient survival rate was not significantly higher in the protocol biopsy group compared to the non-protocol indication biopsy group (P=0.42). Conclusion This study suggests that performing protocol biopsies does not significantly benefit rejection rates, graft survival, or renal function within the first 12 months post-transplant. Given these results and the small but non-zero risk of complications associated with protocol biopsies, they should be reserved for those patients at high risk of rejection. It may be more feasible and beneficial to utilize less invasive tests, such as DSA and dd-cfDNA testing, for early diagnosis of a rejection episode.

Reducing Vancomycin Use in a Level IV NICU.

BACKGROUND AND OBJECTIVES: Vancomycin remains one of the most commonly prescribed antibiotics in NICUs despite recommendations to limit its use for known resistant infections. Baseline data revealing substantially higher vancomycin use in our NICU compared to peer institutions informed our quality improvement initiative. Our aim was to reduce the vancomycin prescribing rate in neonates hospitalized in our NICU by 50% within 1 year and sustain for 1 year. METHODS: In the 60-bed level IV NICU of an academic referral center, we used a quality improvement framework to develop key drivers and interventions including (1) physician education with benchmarking antibiotic prescribing rates; (2) pharmacy-initiated 48-hour antibiotic time-outs on rounds; (3) development of clinical pathways to standardize empirical antibiotic choices for early-onset sepsis, late-onset sepsis, and necrotizing enterocolitis; coupled with (4) daily prospective audit with feedback from the antimicrobial stewardship program. RESULTS: We used statistical process u-charts to show vancomycin use declined from 112 to 38 days of therapy per 1000 patient-days. After education, pharmacy-initiated 48-hour time-outs, and development of clinical pathways, vancomycin use declined by 29%, and by an additional 52% after implementation of prospective audit with feedback. Vancomycin-associated acute kidney injury also declined from 1.4 to 0.1 events per 1000 patient-days. CONCLUSIONS: Through a sequential implementation approach of education, standardization of care with clinical pathways, pharmacist-initiated 48-hour time-outs, and prospective audit with feedback, vancomycin days of therapy declined by 66% over a 1-year period and has been sustained for 1 year.

An easily transfectable cell line that produces an infectious reporter virus for routine and robust quantitation of Kaposi's sarcoma-associated herpesvirus reactivation.

Reactivation of Kaposi's sarcoma-associated herpesvirus (KHSV; also known as Human herpesvirus (HHV)-8) from latency is associated with progression to disease. The primary experimental models for studying KSHV reactivation are B lymphocyte cell lines derived from patients with primary effusion lymphoma (PEL). PEL models have remained essential tools for understanding molecular details of latency and reactivation, yet they have shortcomings. In particular, PEL cells are difficult to transfect with plasmid DNA, which limits their routine use in studies that require introduction of exogenous DNA. Moreover, PELs produce poorly infectious virus, which limits functional quantitation of the ultimate step in KSHV reactivation. In this study, we show that a recently published reporter virus system overcomes inherent difficulties of using PELs for studying viral reactivation. Vero rKSHV.294 cells harbor a recombinant reporter KSHV clone and produce infectious virus whose quantitation is strictly dependent on passage to naïve 293 cells. We show that the cells are easily transfectable, and produce significant amount of infectious virus in response to ectopically-expressed lytic switch protein Rta. In thus study, we derive optimal conditions to measure fold reactivation by varying experimental time periods and media volumes in infections and reporter enzyme reactions, and by eliminating background cellular and media activities. By measuring production of infectious virus, we demonstrate that Rta, but not the cellular transactivator Notch Intracellular Domain (NICD)-1, is sufficient to reactivate KSHV from latency. These data confirm previous studies that were limited to measuring viral gene expression in PELs as indicators of reactivation.