Urinary Tract Infection 1 Year After Kidney Transplant: Effect on Kidney Transplant Outcomes.

OBJECTIVES: Transplant is the gold standard treatment for end-stage renal disease, and yet infectious complications frequently arise in kidney recipients in the context of immunosuppression therapy, with urinary tract infection being the most common. We aimed to assess the prevalence of posttransplant urinary tract infections in kidney transplant recipients and assess the effects on kidney allograft and overall patient outcomes. MATERIAL AND METHODS: We performed a retrospective analysis of data from State University of New York Upstate University Hospital from January 2016 to November 2022 to assess transplant outcomes in patients who underwent a kidney transplant at our center and met the inclusion criteria. RESULTS: There were 507 renal allograft recipients who met our inclusion criteria and were assessed for the incidence of urinary tract infection within the first year after transplant. Urinary tract infection was recurrent in 113 transplant recipients (55.6%) within the first year, and 118 (58.1%) were on prophylactic antibiotics at urinary tract infection diagnosis. We observed no relation between recurrence of urinary tract infection and use of prophylactic antibiotics (P = .21). Overall allograft survival rate was 92.1% in the urinary tract infection group and 96.7% in the group without urinary tract infection, which was significantly different (P = .02). Urinary tract infection significantly affected allograft survival (hazard ratio, 3.51; 95% CI, 1.49-8.23; P = .004). Overall patient survival rates were 86.7% and 91.4% in the groups with and without urinary tract infection, respectively (P = .08). CONCLUSIONS: We determined that allograft survival was significantly greater in the group without urinary tract infection versus the urinary tract infection group. We found no relation between urinary tract infection recurrence and prophylactic antibiotics. We also found that overall patient survival was not significantly different in the group with urinary tract infection versus the group without urinary tract infection.

Effects of a 12-week, seated, virtual, home-based tele-exercise programme compared with a prerecorded video-based exercise programme in people with chronic neurological impairments: protocol for a randomised controlled trial.

INTRODUCTION: Exercise is vital to staying well and preventing secondary complications in people with chronic neurological impairments (CNI). Appropriate exercise is often inaccessible to this population. The purpose of the study is to investigate the effects of a seated, virtual exercise programme on heart rate, recovery, fatigue, pain, motivation, enjoyment and quality of life in people with CNI. METHODS AND ANALYSIS: Individuals with CNI will be screened for eligibility, and 60 participants will be randomised 1:1 into either a live or prerecorded group. There is no geographical limitation to where participants reside, since participation is virtual. The study will be coordinated by one site in White Plains, New York, USA. The live group will exercise with an instructor via Zoom while the prerecorded group will exercise at their chosen time using prerecorded videos, 3×/week for 12 weeks. PRIMARY OUTCOME MEASURES: change in heart rate during exercise/recovery. SECONDARY OUTCOME MEASURES: fatigue, motivation, level of pain and exertion, physical well-being, enjoyment of physical activity, motivation and quality of life. Outcomes will be assessed at baseline, midpoint, end of study and 1-month poststudy. Adverse events, medication changes and physical activity will be tracked throughout. Within-group and between-group comparisons will be performed by using analysis of covariance and regression. ETHICS AND DISSEMINATION: BRANY IRB approval: 22 September 2020, protocol #20-08-388-512. All participants will provide written informed consent. Results will be disseminated through presentations, publications and ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04564495.

Conjugation Dependent Interaction of Folic Acid with Folate Binding Protein.

Serum proteins play a critical role in the transport, uptake, and efficacy of targeted drug therapies, and here we investigate the interactions between folic acid-polymer conjugates and serum folate binding protein (FBP), the soluble form of the cellular membrane-bound folate receptor. We demonstrate that both choice of polymer and method of ligand conjugation affect the interactions between folic acid-polymer conjugates and serum FBP, resulting in changes in the folic acid-induced protein aggregation process. We have previously demonstrated that individual FBP molecules self-aggregate into nanoparticles at physiological concentrations. When poly(amidoamine) dendrimer-folic acid conjugates bound to FBP, the distribution of nanoparticles was preserved. However, the dendritic conjugates produced larger nanoparticles than those formed in the presence of physiologically normal human levels of folic acid, and the conjugation method affected particle size distribution. In contrast, poly(ethylene glycol)-folic acid conjugates demonstrated substantially reduced binding to FBP, did not cause folic acid-induced aggregation, and fully disrupted FBP self-aggregation. On the basis of these results, we discuss the potential implications for biodistribution, trafficking, and therapeutic efficacy of targeted nanoscale therapeutics, especially considering the widespread clinical use of poly(ethylene glycol) conjugates. We highlight the importance of considering specific serum protein interactions in the rational design of similar nanocarrier systems. Our results suggest that prebinding therapeutic nanocarriers to serum FBP may allow folate-specific metabolic pathways to be exploited for delivery while also affording benefits of utilizing an endogenous protein as a vector.