Citations

AbstractIntroductionLittle is known about effects of physical activity (PA) in genetically driven early‐onset autosomal dominant Alzheimer's disease (AD).MethodsA total of 372 individuals participating at the Dominantly Inherited Alzheimer Network study were examined to evaluate the cross‐sectional relationship of PA with cognitive performance, functional status, cognitive decline, and AD biomarkers in cerebrospinal fluid. Mutation carriers were categorized as high or low exercisers according to WHO recommendations.ResultsMutation carriers with high PA showed significantly better cognitive and functional performance and significantly less AD‐like pathology in cerebrospinal fluid than individuals with low PA. Mutation carriers with high PA scored 3.4 points better on Mini Mental State Examination at expected symptom onset and fulfilled the diagnosis of very mild dementia 15.1 years later compared with low exercisers.DiscussionThese results support a beneficial effect of PA on cognition and AD pathology even in individuals with genetically driven autosomal dominant AD.

This commentary is on the case series by Sa et al. on pages 490–496 of this issue.

Background Computed tomography (CT) of the paranasal sinuses is the diagnostic reference standard for chronic rhinosinusitis and related inflammatory sinus pathology. Nasal nitric oxide (nNO) levels have been investigated as a diagnostic tool in sinus disease because it decreases with sinus obstruction. Objective The primary aim of the study was to determine the correlation of passive (baseline) and dynamic (humming) nNO to CT findings of sinus inflammation and to sinonasal symptoms measured by the modified Sinonasal Outcome Test (26 items) (SNOT-26). Methods From June 2015 through January 2016, subjects had baseline and humming nNO levels measured with a chemiluminescence NO analyzer, and each subject underwent CT imaging and completed the SNOT-26 survey. CT images were scored using the Lund–Mackay (LM) system (LM scores >3 indicated sinus inflammation). Correlation was measured by linear and ordinal regression analysis that compared SNOT-26 scores, LM scores, and nNO measurements. Results Fourteen subjects were recruited. LM scores had a positive pairwise correlation with total SNOT-26 scores ( R 2 = .1457; correlation = .3817) and nasal-specific SNOT-26 scores ( R 2 = .4036; correlation = .6353). Baseline nasal nNO scores had a negative pairwise correlation with LM scores ( R 2 = .1580; correlation = −.3582), total SNOT-26 scores ( R 2 = .1515; correlation = −.3893), and nasal-specific SNOT-26 scores ( R 2 = .0805; correlation = −.4343). Although baseline nNO levels correlated with LM and SNOT-26 scores, humming nNO levels did not show a similar correlation. Conclusion Baseline passive nNO may be a useful and inexpensive point-of-care screening test for sinonasal opacification.

Abstract Jagim, AR, Camic, CL, Askow, A, Luedke, J, Erickson, J, Kerksick, CM, Jones, MT, and Oliver, JM. Sex differences in resting metabolic rate among athletes. J Strength Cond Res 33(11): 3008–3014, 2019—The purpose of this study was to compare differences in resting metabolic rate (RMR) between sexes in Division III National Collegiate Athletic Association (NCAA) collegiate athletes and to identify predictors of RMR. Sixty-eight male (M) (age: 20.1 ± 1.5 years; height: 181.8 ± 5.9 cm; body mass (BM): 93.7 ± 16.3 kg; and body fat%: 16.3 ± 8.6%) and 48 female (F) athletes (age: 19.4 ± 1.3 years; height: 166.5 ± 6.0 cm; BM: 63.4 ± 12.7 kg; and body fat%: 21.5 ± 6.3%) participated in a single day of testing, which included determination of RMR using indirect calorimetry and air displacement plethysmography to measure fat mass and fat-free mass (FFM). An independent-samples t -test was used to compare differences in body composition and RMR between sexes, and regression analysis was used to identify predictors of RMR. Men had a significantly higher absolute RMR (M: 2,481 ± 209 vs. F: 1,553 ± 193 kcals·d −1 ; p < 0.001), but when adjusted for BM (M: 25.6 ± 8.3 vs. F: 25.9 ± 2.5 kcals·kg −1 BM per day; p = 0.82) and FFM (M: 31.1 ± 10.6 vs. F: 33.6 ± 3.8 kcals·kg −1 FFM per day; p = 0.12), these differences became nonsignificant. Regression analysis indicated that BM in both men (β = 0.73) and women (β = 0.88) was the strongest predictor of RMR. The results of the current study indicate minimal differences in RMR between sexes among athletic populations when adjusted for BM and FFM. In the current group of athletes, BM seems to account for the largest variability in RMR.

TPS7573 Background: The PD-1/PD-L1 pathway is an important immune checkpoint used by tumor cells and may provide an effective target for enhancing anticancer immune response. In DLBCL, high PD-L1 expression has been identified as a negative prognostic factor for overall survival. Durvalumab (MEDI4736) is a high-affinity human IgG1 monoclonal Ab that selectively blocks PD-L1 binding to PD-1 and CD80, and preliminary preclinical and clinical activity support the study of durvalumab in high-risk DLBCL subtypes. The primary study objective is to explore the clinical activity of durvalumab with R-CHOP in non-activated B-cell–like (non-ABC) and durvalumab with lenalidomide + R-CHOP (R2-CHOP) in ABC previously untreated DLBCL; secondary objectives are to evaluate safety and identify biomarkers predictive of clinical response. Methods: This is a phase II, two-arm, open-label, global, multicenter study of durvalumab combinations in patients with previously untreated, high-risk DLBCL (MEDI4736-DLBCL-001; EUDRA CT 2015-005173-20; NCT03003520). High risk was defined as Ann Arbor stage III/IV or II with bulky disease (≥7.0 cm), along with intermediate-high/high IPI ≥3 or NCCN-IPI ≥4; patients must also have CD20+ DLBCL, ECOG PS 0-2, and no prior antilymphoma therapy. All patients receive durvalumab + R-CHOP21 in induction cycle 1 simultaneous to cell-of-origin (COO) analysis by gene expression profiling with NanoString technology. Beginning with cycle 2, Arm A (non-ABC) receives durvalumab 1125 mg IV on day 1 with 6 or 8 cycles of R-CHOP21; Arm B (ABC) receives the same durvalumab + R-CHOP21 doses with oral lenalidomide 15 mg/day on days 1-14. Both arms receive durvalumab consolidation 1500 mg IV on day 1 q28d for ≤12 months from induction cycle 1, day 1. The primary endpoint is 2-y progression-free survival (PFS); secondary endpoints include clinical response to treatment in biomarker-defined subpopulations (tumor and peripheral blood) and safety as assessed per NCI CTCAE v4.03 criteria. Exploratory endpoints include PFS at 12 mo, complete response, and PK/PD. Recruitment is ongoing, with a target enrollment of 120 patients. Clinical trial information: NCT03003520.

7056 Background: No therapies are approved for MDS after HMA failure. 04-24 was a single-arm study to evaluate best BMBL response as a potential surrogate for OS in higher-risk (HR) MDS pts who progressed on or after an HMA. Rigo is a Ras-mimetic that inhibits the RAS-RAF-MEK pathway, which is frequently activated in HR MDS (Athuluri-Divakar Cell 2016; Gil-Bazo Cancer Biol Ther 2016). Methods: Eligible MDS pts had 5-30% BMBL confirmed within 6 wks pre-study and progression per International Working Group (IWG) 2006 criteria on or after HMAs within 2 yrs. Rigo 1800 mg/24 hrs was continuously infused over 72 hrs q 2 wks × 8 cycles, then q 4 wks until progression or unacceptable toxicity. Primary endpoint was relationship of best BMBL IWG response to OS by Kaplan Meier method. Results: 64 pts were treated (median 5 cycles, range 1-32+), with 61% male, median age 73 (range 47-87), median prior HMA duration 10.8 mos (range 1.2-70.2). Revised International Prognostic Scoring System scores were low 2%, intermediate 11%, high 27%, very high 53%, and unknown 8%. ≥Grade 3 adverse events in ≥10% of pts were anemia 19%, thrombocytopenia 19%, and febrile neutropenia 16%. At the analysis time 40 pts (63%) had died. Best BMBL IWG response was marrow complete response (mCR) 14 pts (22%), stable disease (SD) 30 (47%), progressive disease (PD) 15 (23%), and failure (early death/withdrawal) 5 (8%); 2 mCR pts had transplant. Median OS was 7.0 mos (95% confidence interval 4.8-10.8). Landmark median OS (from day of best BMBL response) was mCR not reached; SD 6.3 mos; PD 3.3 mos. Median OS of mCR+SD was 8.5 mos, with log-rank p = 0.011 (mCR+SD OS to PD OS). Conclusions: BMBL response is a predictor of survival for MDS pts receiving Rigo after HMA failure, confirming findings in earlier Phase 1/2 studies (Silverman ASCO 2015 Abstr 7017). Based on earlier results identifying an MDS subset benefitting from Rigo (Garcia-Manero Lancet Oncol 2016; ASCO 2016 Abstr 165681), a randomized Phase 3 trial of Rigo vs physician’s choice (INSPIRE) is ongoing to determine if Rigo improves survival after HMA failure within 9 cycles. Clinical trial information: NCTO 1928537.