Estimated glomerular filtration rate slopes on tenofovir alafenamide.

OBJECTIVES: The aim of the study was to analyse and compare estimated glomerular filtration rate (eGFR) slopes during exposure to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in individuals who initiated TAF, regardless of prior regimen, before October 2016. METHODS: An observational cohort study was conducted at 11 clinics in the UK and Ireland. Mixed effects models with random intercept and time terms fitted were used to generate and compare eGFR slopes while participants were exposed to TDF and TAF, with adjustment for age, eGFR at TDF/TAF initiation, gender, ethnicity, and time-updated CD4 cell count and HIV RNA measurements. RESULTS: Data were available for 357 subjects (median age 50 years; 80% male; 82% white/other ethnicity; 51% men who have sex with men; median nadir CD4 count 216 cells/µL). The median duration of exposure to TAF was 2.0 (interquartile range 1.6, 2.3) years. At TAF initiation, the median CD4 count was 557 cells/µL, the median eGFR was 80 mL/min/1.73 m2, and 86% had suppressed HIV infection. The mean adjusted eGFR slope during TDF and TAF exposure was -2.08 [95% confidence interval (CI) -2.24, -1.92] and 1.18 (95% CI 0.20, 1.52) mL/min/1.73 m2/year, respectively (P < 0.001). Individuals who experienced rapid eGFR decline (> 3 or 5 mL/min/1.73 m2/year) while receiving TDF experienced significant eGFR recovery while on TAF (P < 0.001). CONCLUSIONS: Significant improvement in eGFR slope was observed in patients who switched from TDF- to TAF-containing antiretroviral regimens. These data provide further support for the renal safety of TAF, and for switching those who experience progressive worsening of renal function from TDF to TAF.

Pattern of failure in anaplastic glioma patients with an IDH1/2 mutation.

PURPOSE: The current study aimed to assess patterns of failure (PoF) in anaplastic glioma (AG) patients managed with intensity-modulated radiation therapy (IMRT) and their relationship to molecular subtype. METHODS: The outcomes of AG patients managed between 2008 and 2014 and entered into a prospective database were assessed, including PoF. AG was initially defined using the WHO 2007 classification, but for analysis, patients were subsequently recategorised based on WHO 2016 as anaplastic oligodendroglioma (AOD), astrocytoma isocitrate dehydrogenase (IDH) mutant (AAmut) or astrocytoma IDH wildtype (AAwt). Management involved IMRT and temozolomide (TMZ), including from 2011 patients with an IDH mutation (IDHmut) planned with 18F-fluoroethyltyrosine (FET) and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET). PoF was local, marginal or distant in relation to the IMRT volume. Relapse-free survival (RFS) was calculated from the start of IMRT. RESULTS: A total of 156 patients were assessed, with median follow-up of 5.1 years. Of these patients, 75% were IDHmut, 44% were managed at first or later relapse and 73% received TMZ. Relapse occurred in 68 patients, with 6­year RFS of 75.0, 48.8 and 2.5% for AOD, AAmut and AAwt, respectively (p < 0.001). There was a component of local relapse in 63%, of marginal relapse in 19% and of distant relapse in 37% of relapses. Isolated local, marginal and distant relapse was evident in 51, 9 and 22%, respectively. A distant relapse pattern was more frequent in IDHmut compared to IDHwt patients (26% vs. 45%, p = 0.005), especially within the first 2 years post-IMRT. In multivariate analysis, distant relapse remained associated with AAmut (p < 0.002) and delayed IMRT until the second relapse (p < 0.001). CONCLUSION: Although patients with IDH-mutated AG have improved outcomes, there was a higher proportion of distant relapses occurring during the 2 years after IMRT.

Diagnosis of upper limb lymphedema: development of an evidence-based approach.

BACKGROUND: The diagnosis of secondary upper limb lymphedema (LE) is complicated by the lack of an agreed-upon measurement tool and diagnostic threshold. The aim of this study was to determine which of the many commonly used and normatively determined clinical diagnostic thresholds has the best diagnostic accuracy of secondary upper limb LE, when compared to diagnosis by an appropriate reference standard, lymphoscintigraphy. MATERIAL AND METHODS: The arms of women treated for breast cancer with and without a previous diagnosis of LE, as well as healthy controls, were assessed using lymphoscintigraphy, bioimpedance spectroscopy (BIS) and perometry. Dermal backflow score determined from lymphoscintigraphy imaging assessment (reference standard) was compared with diagnosis by both commonly used and normatively determined diagnostic thresholds for volume and circumference measurements as well as BIS. RESULTS: For those with established dermal backflow, all commonly used and normatively determined diagnostic thresholds accurately identified presence of LE compared with lymphoscintigraphy diagnosis. In participants with mild to moderate changes in dermal backflow, only a normatively determined diagnostic threshold, set at two standard deviations above the norm, for arm circumference and full arm BIS were found to have both high sensitivity (81% and 76%, respectively) and specificity (96% and 93%, respectively). For this group, strong, and clinically useful, positive (23 and 10, respectively) and negative likelihood (0.2 and 0.3) ratios were found for both the circumference and bioimpedance diagnostic thresholds. CONCLUSION: For the first time, evidence-based clinical diagnostic thresholds have been established for secondary LE. With mild LE, normatively determined circumference and BIS thresholds are superior to the commonly used thresholds.