Zaslow, Shari J.

Abstract Background Cardiac implantable electronic device infection (CIEDI) is a serious complication, occurring in approximately 1% of implantations. In addition to antimicrobial therapy, complete device extraction is considered essential for definitive cure. However, this may not always be feasible due to a variety of factors. In select cases, long-term chronic antibiotic suppression (CAS) has been used, yet clinical characteristics and outcomes of patients who received CAS have scarcely been reported. Methods A descriptive study analyzing all adult (age > 18) patients with definite CIEDI who received CAS between 2016 and 2023 across the Mayo Clinic Enterprise (Arizona, Florida, Minnesota, and Upper Midwest) was conducted. Patients with either ventricular assist devices or fungal infection were excluded. Results A total of 321 patients were diagnosed with definite CIEDI during the study period. A total of 37 (8.7%) patients received CAS due to device retention. The median age was 77.5 [IQR 70.5, 87.5] with 32.4% female. Permanent pacemakers were involved in most (64.9%) infections. Approximately one-third (32.4%) of patients had a prosthetic valve. The median time from initial device implantation to CIEDI was 10.6 years [IQR 4.8, 18.1]. CIED-related infective endocarditis was present in 70.3% of cases and 67.6% had lead involvement. The most commonly isolated organisms were Staphylococcus aureus (29.7%), coagulase-negative staphylococci (27%), Enterococcus faecalis (13.5%) and Streptococci (13.5%). Other pathogens or culture-negative cases comprised 16.3%. The primary reason for device retention and CAS was poor surgical candidacy. Doxycycline was the most commonly used agent for CAS, accounting for 37.8% of cases. The average length of suppression was 469.0 days [IQR158.0, 1264.0]. The rate of relapse was 8.1% with all occurring within 90 days of diagnosis. One year mortality was 27.0%. Conclusion CAS may be a feasible option for patients with device retention, although a small proportion experience CIEDI relapse. Unexpectedly, the pathogen distribution among CAS recipients differed from that seen in a general CIED infection population, highlighting selection bias and the distinct clinical characteristics of patients managed with CAS. Disclosures Larry M. Baddour, MD, UpToDate, Inc.: Royalty payments (authorship duties).

Key Points Serum glycerol-3-phosphate (G3P) levels were significantly associated with higher fibroblast growth factor 23 levels in ESKD. Pathway and mediation analyses identified the pentose phosphate pathway as the top mediator of the relationship between serum G3P and fibroblast growth factor 23. The role of G3P in ESKD provides new insights into potential therapeutic targets for CKD-mineral and bone disorder. Background Fibroblast growth factor 23 (FGF23) is a key regulator of mineral metabolism that is independently associated with mortality in patients with ESKD. Glycerol-3-phosphate (G3P), a byproduct of glycolysis that can be derived from injured kidneys, stimulates FGF23 production. We aimed to determine if serum G3P is associated with FGF23 levels in patients with ESKD and identify potential molecular pathways that mediate their relationship. Methods We conducted a cross-sectional study of 99 nondiabetic patients with ESKD on hemodialysis. We used linear regression to examine the association between G3P terciles and log-transformed C-terminal FGF23 levels, adjusting for demographics, coronary artery disease, serum calcium, phosphorus, and parathyroid hormone. Mann–Whitney U tests compared 247 serum metabolite levels between the first and third FGF23 terciles; significant metabolites ( P < 0.01) were selected for pathway enrichment analyses. Top pathway scores were used in mediation analyses. Results The median age of participants was 54 years (interquartile range [IQR], 44–63), 38% were women, 71% self-identified as Black, and 27% had coronary artery disease. The median FGF23 level was 777 (interquartile range, 222–1310) RU/ml. In adjusted analyses, compared with participants with the lowest G3P tercile, those with the highest G3P tercile had a 95% higher FGF23 level (95% Confidence Interval, 6% to 260%; P = 0.04). Of the 27 metabolites significantly associated with FGF23 levels, pathway enrichment analysis identified the pentose phosphate pathway as the top hit (impact score=0.33, false discovery rate-adjusted P value = 0.01). The pentose phosphate pathway mediated the relationship between G3P and FGF23, resulting in a 62% change in the β coefficient. Conclusions In nondiabetic patients with ESKD on hemodialysis, serum G3P positively correlated with serum C-terminal FGF23, and this relationship was mediated by the pentose phosphate pathway. Exploring the pentose phosphate pathway could yield critical mechanistic insights into the regulation of FGF23, enhancing our understanding of its broader biologic functions.