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Abstract Background Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS). Methods FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied. Results There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (−7.6 points, P = 0.02) and mobility (−4.2, P = 0.02), the number of reported symptoms was associated with worse depression (−2.7 per symptom, P = 0.009) and anxiety (−2.3, P = 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (−2.8 per visit, P < 0.001) and fatigue (−2.4, P = 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (+9.3, P = 0.03). Conclusions PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes.

Objective The aim of this study was to determine if computed tomography (CT) angiography using an individualized transition delay (CTA-ID) would facilitate reductions in injection rate and iodine dose. Methods The CTA-ID was performed in 20 patients with routine injection rate and iodine dose; 20 patients with injection rate lowered by 1 mL/s; and 40 patients with injection rate lowered by 1 mL/s with 29% less iodine. Routine CTAs in the same or size-matched patients served as controls. Diagnostic image quality and intra-arterial CT numbers were assessed. Results The median transition delay between aortic threshold and CTA-ID image acquisition was significantly longer than with conventional bolus tracking (mean increase, 13.3 seconds; P < 0.0001), with image quality being the same or better. Intra-arterial CT numbers were 200 Hounsfield units or greater for 80 of 80 CTA-ID, but not for 6 of 49 (12%) internal control or for 11 of 80 (14%) size-matched control patients. Conclusion The CTA-ID bolus-tracking software alters transition delays to permit diagnostic CTA examinations despite slower injection rate and less iodine.

Loss of muscle mass and function, or sarcopenia, is a common feature of cirrhosis and contributes significantly to morbidity and mortality in this population. Sarcopenia is a main indicator of adverse outcomes in this population, including poor quality of life, hepatic decompensation, mortality in patients with cirrhosis evaluated for liver transplantation (LT), longer hospital and intensive care unit stay, higher incidence of infection following LT, and higher overall health care cost. Although it is clear that muscle mass is an important predictor of LT outcomes, many questions remain, including the best modality for assessing muscle mass, the optimal cut‐off values for sarcopenia, the ideal timing and frequency of muscle mass assessment, and how to best incorporate the concept of sarcopenia into clinical decision making. For these reasons, we assembled a group of experts to form the North American Working Group on Sarcopenia in Liver Transplantation to use evidence from the medical literature to address these outstanding questions regarding sarcopenia in LT. We believe sarcopenia assessment should be considered in all patients with cirrhosis evaluated for liver transplantation. Skeletal muscle index (SMI) assessed by computed tomography constitutes the best‐studied technique for assessing sarcopenia in patients with cirrhosis. Cut‐off values for sarcopenia, defined as SMI < 50 cm 2 /m 2 in male and < 39 cm 2 /m 2 in female patients, constitute the validated definition for sarcopenia in patients with cirrhosis. Conclusion: The management of sarcopenia requires a multipronged approach including nutrition, exercise, and additional pharmacological therapy as deemed necessary. Future studies should evaluate whether recovery of sarcopenia with nutritional management in combination with an exercise program is sustainable as well as how improvement in muscle mass might be associated with improvement in clinical outcomes.

PurposePhoton‐counting‐detector‐computed tomography (PCD‐CT) allows separation of multiple, simultaneously imaged contrast agents, such as iodine (I), gadolinium (Gd), and bismuth (Bi). However, PCDs suffer from several technical limitations such as charge sharing, K‐edge escape, and pulse pile‐up, which compromise spectral separation of multi‐energy data and degrade multi‐contrast imaging performance. The purpose of this work was to determine the performance of a dual‐source (DS) PCD‐CT relative to a single‐source (SS) PCD‐CT for the separation of simultaneously imaged I, Gd, and Bi contrast agents.MethodsPhantom experiments were performed using a research whole‐body PCD‐CT and head/abdomen‐sized phantoms containing vials of different I, Gd, Bi concentrations. To emulate a DS‐PCD‐CT, the phantoms were scanned twice on the SS‐PCD‐CT using different tube potentials for each scan. A tube potential of 80 kV (energy thresholds = 25/50 keV) was used for low‐energy tube, while the high‐energy tube used Sn140 kV (Sn indicates tin filter) and thresholds of 25/90 keV. The same phantoms were scanned also on the SS‐PCD‐CT using the chess acquisition mode. In chess mode, the 4 × 4 subpixels within a macro detector pixel are split into two sets based on a chess‐board pattern. With each subpixel set having two energy thresholds, chess mode allows four energy‐bin data sets, which permits simultaneous multi‐contrast imaging. Because of this design, only 50% area of each detector pixel is configured to receive photons of a pre‐defined threshold, leading to 50% dose utilization efficiency. To compensate for this dose inefficiency, the radiation dose for this scan was doubled compared to DS‐PCD‐CT. A 140 kV tube potential and thresholds = 25/50/75/90 keV were used. These settings were determined based on the K‐edges of Gd, and Bi, and were found to yield good differentiation of I/Gd/Bi based on phantom experiments and other literature. The energy‐bin images obtained from each scan (scan pair) were used to generate I‐, Gd‐, Bi‐specific image via material decomposition. Root‐mean‐square‐error (RMSE) between the known and measured concentrations was calculated for each scenario. A 20‐cm water cylinder phantom was scanned on both systems, which was used for evaluating the magnitude of noise, and noise power spectra (NPS) of I/Gd/Bi‐specific images.ResultsPhantom results showed that DS‐PCD‐CT reduced noise in material‐specific images for both head and body phantoms compared to SS‐PCD‐CT. The noise level of SS‐PCD was reduced from 2.55 to 0.90 mg/mL (I), 1.97 to 0.78 mg/mL (Gd), and 0.85 to 0.74 mg/mL (Bi) using DS‐PCD. NPS analysis showed that the noise texture of images acquired on both systems is similar. For the body phantom, the RMSE for SS‐PCD‐CT was reduced relative to DS‐PCD‐CT from 10.52 to 2.76 mg/mL (I), 7.90 to 2.01 mg/mL (Gd), and 1.91 to 1.16 mg/mL (Bi). A similar trend was observed for the head phantom: RMSE reduced from 2.59 (SS‐PCD) to 0.72 (DS‐PCD) mg/mL (I), 2.02 to 0.58 mg/mL (Gd), and 0.85 to 0.57 mg/mL (Bi).ConclusionWe demonstrate the feasibility of performing simultaneous imaging of I, Gd, and Bi materials on DS‐PCD‐CT. Under the condition without cross scattering, DS‐PCD reduced the RMSE for quantification of material concentration in relative to a SS‐PCD‐CT system using chess mode.

Objectives: Intensive interdisciplinary treatment is emerging as an effective treatment of chronic pain in youth. These programs often include a parental component with the belief that targeting parental distress and responses to a child’s pain will improve outcomes. However, few studies have evaluated the impact of a parental intervention in the interdisciplinary treatment of pediatric chronic pain. The present study consists of a nonrandomized pre-post design to evaluate change in psychological and behavioral functioning of parents who participated in intensive parent programming that utilized cognitive-behavioral therapy and acceptance and commitment therapy, delivered within the context of an interdisciplinary intensive 3-week pain treatment program for youth with chronic pain. Materials and Methods: Two hundred twelve parents and their children participated in the study, with 116 participants completing 3-month follow-up measures. Parents completed measures of depressive symptoms, pain catastrophizing, protective responses, and psychological flexibility at admission, discharge, and 3 months after the program. Child functional disability was assessed at the same time points. We examined change in parent factors over time, while controlling for change in child distress. Results: Parents reported significant improvements in all areas of functioning from admission to discharge and improvements were maintained at 3-month follow-up. Discussion: This study provides evidence suggesting parent interventions can be effective in reducing parent distress and behaviors known to be associated with child outcomes.

Significance Statement Kidney stone recurrence can manifest with symptoms from stone passage or with asymptomatic changes in kidney stone burden revealed by radiography. In a multicenter, prospective cohort study, the authors demonstrate that substantially more asymptomatic and self-managed symptomatic kidney stone recurrence occur in stone formers than has been appreciated, as many studies consider only symptomatic recurrence that results in clinical care. Among first-time symptomatic stone formers, 54% had an asymptomatic kidney stone; half of those with such a stone passed it within 5 years (but only half who did so experienced symptoms). The findings also show that when a more comprehensive definition of recurrence that includes all symptomatic and radiological manifestations is used, risk factors better predict kidney stone recurrence, thus supporting a comprehensive assessment of recurrence in clinical trials. Background Meaningful interpretation of changes in radiographic kidney stone burden requires understanding how radiographic recurrence relates to symptomatic recurrence and how established risk factors predict these different manifestations of recurrence. Methods We recruited first-time symptomatic stone formers from the general community in Minnesota and Florida. Baseline and 5-year follow-up study visits included computed tomography scans, surveys, and medical record review. We noted symptomatic recurrence detected by clinical care (through chart review) or self-report, and radiographic recurrence of any new stone, stone growth, or stone passage (comparing baseline and follow-up scans). To assess the prediction of different manifestations of recurrence, we used the Recurrence of Kidney Stone (ROKS) score, which sums multiple baseline risk factors. Results Among 175 stone formers, 19% had symptomatic recurrence detected by clinical care and 25% detected by self-report; radiographic recurrence manifested as a new stone in 35%, stone growth in 24%, and stone passage in 27%. Among those with a baseline asymptomatic stone (54%), at 5 years, 51% had radiographic evidence of stone passage (accompanied by symptoms in only 52%). Imaging evidence of a new stone or stone passage more strongly associated with symptomatic recurrence detected by clinical care than by self-report. The ROKS score weakly predicted one manifestation—symptomatic recurrence resulting in clinical care ( c -statistic, 0.63; 95% confidence interval, 0.52 to 0.73)—but strongly predicted any manifestation of symptomatic or radiographic recurrence (5-year rate, 67%; c -statistic, 0.79; 95% confidence interval, 0.72 to 0.86). Conclusions Recurrence after the first stone episode is both more common and more predictable when all manifestations of recurrence (symptomatic and radiographic) are considered.

e21004 Background: Pembrolizumab (PEMBRO) and combination ipilimumab + nivolumab (IPI+NIVO) are FDA-approved immunotherapies for advanced melanoma (AM). HRQoL was better maintained with PEMBRO vs IPI in KEYNOTE-006. CheckMate-067 reported no clinically meaningful HRQoL differences with IPI+NIVO vs IPI. As randomized trial data are lacking, we compared HRQoL outcomes in AM between PEMBRO and IPI+NIVO in real-world clinical settings. Methods: A prospective, observational study was conducted with sponsor blinded to sites, and sites blinded to sponsor; nine oncologists from 9 US academic centers and affiliated satellite clinics enrolled AM patients (pts) age ≥18 years initiating first-line PEMBRO or IPI+NIVO between June 2017 – March 2018. The European Organization for the Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ C30) and EQ-5D-5L were administered at baseline and weeks 6, 12, 18, and 24 following therapy. Least squared (LS) mean changes in HRQoL scores from baseline were compared using mixed-effects models for repeated measures, adjusting for baseline covariates. Results: A total of 225 PEMBRO and 187 IPI+NIVO pts were enrolled, with > 95% questionnaire completion rates through week 24. At baseline, PEMBRO pts were more likely > age 65 (49% vs 37%, p = .011), stage IV disease (92% vs 85%; p = .002), and higher comorbidity index (1.0 vs 0.6; p < .001) compared with IPI+NIVO pts. Adjusted EORTC global health status/quality of life (GHS) LS mean changes from baseline showed greater improvement with PEMBRO vs. IPI+NIVO at 12, 18 and 24 weeks. At week 24, PEMBRO pts achieved a 3.3-point improvement (95% CI = 0.8, 5.7) and IPI+NIVO pts had no significant change (1.0, 95% CI = -1.6, 3.5), with a LS mean difference of 2.3 points (p = .037; 95% CI = 0.14, 4.51). At week 24, the EQ-5D visual analogue scale increased 1.0 (95% CI, -1.2, 3.2) for PEMBRO vs IPI+NIVO which decreased 0.9 (95% CI = -3.2, 1.3), with a statistically significant LS mean difference of 2.0 (95% CI = 0.4, 3.9; p = .045). Conclusions: Results from 2 measures suggest HRQoL was maintained vs. baseline in both PEMBRO and IPI+NIVO pts, with a significant between-group difference favoring PEMBRO in GHS over 24 weeks.