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Background and objectives BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. Design, setting, participants, & measurements Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. Results At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively ( P =0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P= 0.47) and 6 months (82.1% versus 90.5%; P =0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. Conclusions A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression.

APOL1 gene variants are associated with end-stage renal disease in African Americans. Here we investigate the impact of recipient APOL1 (apolipoprotein L-1) gene distributions on kidney allograft outcomes. We conducted a retrospective analysis of 119 African American kidney transplant recipients, and found that 58 (48.7%) carried two APOL1 kidney disease risk variants. Contrary to the association seen in native kidney disease, there is no difference in allograft survival at 5 years post-transplant for recipients with high-risk APOL1 genotypes. Thus, we were able to conclude that APOL1 genotypes do not increase risk of allograft loss after kidney transplantations, and carrying 2 APOL1 risk alleles should not be an impediment to transplantation.

Background and objectives: Nearly 30% of renal transplant recipients develops BK viremia, a prerequisite for BK nephropathy. Case reports have evaluated treatment options for BK virus, but no controlled studies have assessed prophylactic therapies. Fluoroquinolone antibiotics were studied for prevention of BK viremia after renal transplantation. Design, setting, participants, & measurements: This retrospective analysis evaluated adult renal transplant recipients with at least one BK viral load (blood) between 90 and 400 days after transplantation. Six to 12 months of co-trimoxazole was used for Pneumocystis prophylaxis. In sulfa-allergic/-intolerant patients, 6 to 12 months of atovaquone with 1 month of a fluoroquinolone was used. Fluoroquinolones can inhibit BK DNA topoisomerase. The two groups studied were those that received 30 days of levofloxacin or ciprofloxacin after transplantation and those that did not. The primary endpoint was BK viremia rates at 1 year. Of note, of the 160 patients not receiving fluoroquinolone prophylaxis, 40 received a fluoroquinolone for treatment of a bacterial infection within 3 months after transplantation. Subgroup analysis evaluating these 40 patients against the 120 who had no exposure to fluoroquinolones was completed. Results: A 1-month fluoroquinolone course after transplantation was associated with significantly lower rates of BK viremia at 1 year compared with those with no fluoroquinolone. In the subgroup analysis, exposure to fluoroquinolone for treatment of bacterial infections within 3 months after transplantation was associated with significantly lower 1-year rates of BK viremia. Conclusions: This analysis demonstrates that fluoroquinolones are effective at preventing BK viremia after renal transplantation.

The current case study involves a 14-year-old adolescent male with a history of epilepsy who displayed psychogenic pseudoseizures and non-compliance in response to being at school or having to complete chores or homework. The aims of the treatment intervention were to decrease the target behaviours and increase alternative desirable behaviours using the principles of behaviour modification and cognitive strategies for stress and anxiety management. It was expected that providing no reinforcement for the target behaviours would result in a decrease in their frequency, duration and intensity. In addition, it was predicted that contingent positive reinforcement of alternative desirable behaviours would increase their occurrence in place of the undesirable target behaviours. It was also expected that the use of cognitive and behavioural anxiety management strategies would decrease the levels of subjective stress reported. The results of the intervention supported these hypotheses. Pseudoseizure behaviour was reduced significantly in the early stages of intervention and maintained across the remainder of the treatment program, except for a reoccurrence in response to treatment termination. Noncompliant behaviour was also reduced significantly across the intervention. The results of this case study support existing research on the use of cognitive behaviour therapy in the treatment of psychogenic pseudoseizures in children and adolescents.

Summary Background and objectives Acute rejection remains a problem in renal transplantation. This study sought to determine the utility of a noninvasive cytokine assay in screening of acute rejection. Design, setting, participants, & measurements In this observational cross-sectional study, 64 patients from two centers were recruited upon admission for allograft biopsy to investigate acute graft dysfunction. Blood was collected before biopsy and assayed for a panel of 21 cytokines secreted by PBMCs. Patients were classified as acute rejectors or nonrejectors according to a classification rule derived from an initial set of 32 patients (training cohort) and subsequently validated in the remaining patients (validation cohort). Results Although six cytokines (IL-1β, IL-6, TNF-α, IL-4, GM-CSF, and monocyte chemoattractant protein-1) distinguished acute rejectors in the training cohort, logistic regression modeling identified a single cytokine, IL-6, as the best predictor. In the validation cohort, IL-6 was consistently the most accurate cytokine (area under the receiver-operating characteristic curve, 0.85; P =0.006), whereas the application of a prespecified cutoff level, as determined from the training cohort, resulted in a sensitivity and specificity of 92% and 63%, respectively. Secondary analyses revealed a strong association between IL-6 levels and acute rejection after multivariate adjustment for clinical characteristics ( P Conclusions In this pilot study, the measurement of a single cytokine can exclude acute rejection with a sensitivity of 92% in renal transplant recipients presenting with acute graft dysfunction. Prospective studies are needed to determine the utility of this simple assay, particularly for low-risk or remote patients.

Background. Although there is ample evidence about the role of adaptive immunity in the development of chroni allograft dysfunction, little is known about the contribution of innate immunity to this process. Herein, we studied th relationship between inflammation, chronic biopsy scores, and anti-human leukocyte antigen (HLA) circulating a] loantibodies in a cohort of 57 patients recruited at our center. Methods. Available biopsies (n=27) were graded for chronic lesion scores according to Banff criteria. The production on cytokines by peripheral blood mononuclear cells after 48 hr of culture under resting conditions was quantified by Lumineux Tumor necrosis factor (TNF)-α secretion assay and depletion studies were used to identify the source of these cytokines. Results. There was a high correlation between the levels of interleukin (IL)-1β, IL-6, and TNF-α (r>0.8, P

Objectives: Patient preference studies are increasingly used to inform decision-making during the medical product lifecycle but are rarely used to inform early stages of drug development. The primary aim of this study is to quantify treatment preferences of patients with neuromuscular disorders, which represent serious and debilitating conditions with limited or no treatment options available. Methods: This quantitative patient preferences study was designed as an online survey, with a cross-over design. This study will target two different diseases from the neuromuscular disorders disease group, myotonic dystrophy type 1 (DM1) and mitochondrial myopathies (MM). Despite having different physio-pathological pathways both DM1 and MM manifest in a clinically similar manner and may benefit from similar treatment options. The sample will be stratified into three subgroups: two patient groups differentiated by age of symptom onset and one caregivers group. Each subgroup will be randomly assigned to complete two of three different preference elicitation methods at two different time points: Q-methodology survey, discrete choice experiment, and best-worst scaling type 2, allowing cross-comparisons of the results across each study time within participants and within elicitation methods. Additional variables such as sociodemographic, clinical and health literacy will be collected to enable analysis of potential heterogeneity. Ethics and Dissemination: This study protocol has undergone ethical review and approval by the Newcastle University R&D Ethics Committee (Ref: 15169/2018). All participants will be invited to give electronic informed consent to take part in the study prior accessing the online survey. All electronic data will be anonymised prior analysis. This study is part of the Patient Preferences in Benefit-Risk Assessments during the Drug Life Cycle (IMI-PREFER) project, a public-private collaborative research project aiming to develop expert and evidence-based recommendations on how and when patient preferences can be assessed and used to inform medical product decision making.