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Chimeric antigen receptor (CAR) T-cell therapy has transformed survival outcomes in patients with relapsed and refractory large B-cell lymphoma (LBCL), but it is associated with a variety of side effects. This study examined changes in patient-reported quality of life (QoL) and toxicities, as well as risk factors for worse QoL and toxicities, in the first year after treatment. Patients with LBCL completed questionnaires assessing QoL and toxicity severity before infusion, and 90, 180, and 360 days after infusion. Mixed models were used to examine changes in QoL and toxicities over time, and clinical moderators of change in QoL and toxicities. Patients reported improvements in physical functioning and fatigue in the year after treatment (P values <.01), but there were no changes in pain, anxiety, or depression over time. Patients with active disease at day 90 reported more physical dysfunction at all postinfusion timepoints (Ps ≤ .01) compared to patients who responded to treatment. Similarly, patients with active disease at day 90 reported worsening depression over time, such that at day 360, depressive symptoms were worse for patients with active disease than patients without active disease (P = .02). Patients treated with 4+ lines of prior therapy reported worsening pain and anxiety over time, such that at day 360, both pain and anxiety were significantly worse for patients previously treated with 4 of more lines of therapy than patients treated with fewer lines of therapy (Ps ≤ .01). Regarding toxicities, patients reported decreasing overall toxicity burden up to day 180, with subsequent worsening at day 360 (P = .02). Most patients reported at least one or two grade 2 toxicities at each timepoint. Patients demonstrated unchanging or improved QoL after treatment with CAR T-cell therapy, but active disease and greater prior lines of therapy were associated with worse QoL outcomes over time. Toxicity severity also improved during the first 6 months post-treatment, but worsened thereafter, particularly among patients with active disease after treatment., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the effects of a preoperative, home-based exercise program on fitness and physical function in patients with pancreatic cancer., Background: We previously established a well-tolerated preoperative exercise program after finding a high frequency of sarcopenia and frailty in patients with pancreatic cancer., Methods: In this randomized, controlled trial (NCT03187951), patients with pancreatic cancer were randomized to Arm A: enhanced usual care or Arm B: prescribed aerobic and resistance exercise during neoadjuvant therapy. Patients received nutrition counseling and activity trackers. The primary endpoint was a 6-minute walk distance (6MWD; ≥14 meters improvement was clinically meaningful). Secondary endpoints included additional physical function tests, health-related quality of life, and clinical outcomes., Results: One hundred fifty-one patients were randomized. Objectively measured weekly activity (153.2±135.6 and 159.8±122.8 min in Arm A and B, respectively, P =0.62) and self-reported weekly moderate-to-strenuous physical activity (107.4±160.4 and 129.6±161.6 min in Arm A and Arm B, respectively, P =0.49) were similar, but weekly strength training sessions increased more in Arm B (by 1.8±1.8 vs 0.1±2.4 sessions, P <0.001). 6MWD improved in both Arm A (mean change 18.6±56.8 m, P =0.01) and Arm B (27.3±68.1 m, P =0.002). Quality of life and clinical outcomes did not significantly differ between arms. Pooling patients in both study groups, exercise, and physical activity was favorably associated with physical performance and clinical outcomes., Conclusions: In this randomized trial of prescribed exercise versus enhanced usual care during neoadjuvant therapy for pancreatic cancer, a high volume of physical activity and increased exercise capacity were observed in both arms, highlighting the importance of activity among patients preparing for surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Although CD19-directed chimeric antigen receptor T-cell therapy (CD19.CAR-T) has proven clinical efficacy for multiple refractory B-cell malignancies, over 50% of patients ultimately relapse. Recent evidence has underlined the critical role of the host in determining treatment responses. In this retrospective observational study of 106 patients with relapsed/refractory large B-cell lymphoma receiving standard-of-care CD19.CAR-T, we analyzed the impact of immunometabolic host features and detailed body composition measurements on post-CAR T clinical outcomes. We extracted muscle and adipose tissue distributions from prelymphodepletion CT images and assessed laboratory-based immuno-nutritional scores. Early responders displayed increased total abdominal adipose tissue deposits (TAT: 336 mm3 vs. 266 mm3, P = 0.008) and favorable immuno-nutritional scores compared to nonresponding patients. On univariate Cox regression analysis, visceral fat distribution, sarcopenia, and nutritional indices significantly impacted both progression-free (PFS) and overall survival (OS). Patients with a low skeletal muscle index (SMI; e.g.<34.5), a sarcopenia indicator, exhibited poor clinical outcomes (mOS 3.0 months vs. 17.6 months, log-rank P = 0.0026). Prognostically adverse immuno-nutritional scores were linked to inferior survival [low PNI: HROS, 6.31; 95% confidence interval (CI), 3.35-11.90; P < 0.001]. In a multivariable analysis adjusting for baseline Eastern Cooperative Oncology Group performance status, C-reactive protein, and lactate dehydrogenase, increased TAT was independently associated with improved clinical outcomes (adjusted HROS, 0.27; 95% CI, 0.08-0.90; P = 0.03). We noted particularly favorable treatment outcomes in patients with both increased abdominal fat and muscle mass (TAThigh/SMIhigh: 1-year PFS 50%, 1-year OS 83%). These real-world data provide evidence for a role of body composition and immuno-nutritional status in the context of CD19.CAR-T and suggest that the obesity paradox may extend to modern T cell-based immunotherapies. See related Spotlight by Nawas and Scordo, p. 704., (©2023 The Authors; Published by the American Association for Cancer Research.)

A major gap impeding development of new treatments for cancer-related fatigue is an inadequate understanding of the complex biological, clinical, demographic, and lifestyle mechanisms underlying fatigue. In this paper, we describe a new application of a comprehensive model for cancer-related fatigue: the predisposing, precipitating, and perpetuating (3P) factors model. This model framework outlined herein, which incorporates the emerging field of metabolomics, may help to frame a more in-depth analysis of the etiology of cancer-related fatigue as well as a broader and more personalized set of approaches to the clinical treatment of fatigue in oncology care. Included within this review paper is an in-depth description of the proposed biological mechanisms of cancer-related fatigue, as well as a presentation of the 3P model's application to this phenomenon. We conclude that a clinical focus on organization risk stratification and treatment around the 3P model may be warranted, and future research may benefit from expanding the 3P model to understand fatigue not only in oncology, but also across a variety of chronic conditions.

Spouses offer a primary source of support and may provide critical assistance for behavior change. A diet-exercise intervention previously found efficacious in improving cancer survivors' lifestyle behaviors was adapted to utilize a couples-based approach. The aims were to test the feasibility of this couples-based (CB) intervention and compare its efficacy to the same program delivered to the survivor-only (SO). Twenty-two survivor-spouse couples completed baseline assessments and were randomized to the CB or SO interventions. The study surpassed feasibility benchmarks; 91% of survivors and 86% of spouses completed a 6-month follow-up. Survivors and spouses attended 94% and 91% of sessions, respectively. The SO survivors showed significant improvements on the 30-s chair stand and arm curl tests, weight, and fruit and vegetable (F and V) consumption. The CB survivors showed significant improvements on the 6-min walk and 2-min step tests, body weight, and fat and F and V consumption. Improvement in the 30-s chair stand and arm curl tests was significantly better for SO survivors. The SO spouses showed no significant changes in outcome measures, but the CB spouses showed significant improvements in moderate-to-strenuous physical activity, weight, and fat and F and V consumption. Weight loss was significantly greater in CB spouses compared to SO spouses. Findings demonstrate feasibility, warranting further investigation of CB approaches to promote lifestyle change among cancer survivors and spouses.

Renal medullary carcinoma (RMC) is a lethal malignancy affecting individuals with sickle hemoglobinopathies. Currently, no modifiable risk factors are known. We aimed to determine whether high-intensity exercise is a risk factor for RMC in individuals with sickle cell trait (SCT). We used multiple approaches to triangulate our conclusion. First, a case-control study was conducted at a single tertiary-care facility. Consecutive patients with RMC were compared to matched controls with similarly advanced genitourinary malignancies in a 1:2 ratio and compared on rates of physical activity and anthropometric measures, including skeletal muscle surface area. Next, we compared the rate of military service among our RMC patients to a similarly aged population of black individuals with SCT in the U.S. Further, we used genetically engineered mouse models of SCT to study the impact of exercise on renal medullary hypoxia. Compared with matched controls, patients with RMC reported higher physical activity and had higher skeletal muscle surface area. A higher proportion of patients with RMC reported military service than expected compared to the similarly-aged population of black individuals with SCT. When exposed to high-intensity exercise, mice with SCT demonstrated significantly higher renal medulla hypoxia compared to wild-type controls. These data suggest high-intensity exercise is the first modifiable risk factor for RMC in individuals with SCT.

Background: We previously demonstrated associations between exercise during pancreatic cancer treatment and quality of life and physical fitness prior to pancreatectomy. In this study, we quantified exercise among survivors following pancreatic tumor resection and characterized concordance with established guidelines., Methods: We quantified exercise frequency, duration, and intensity among survivors who underwent pancreatectomy for adenocarcinoma or a neuroendocrine tumor at our center from 2000 to 2017 and compared them with American College of Sports Medicine Guidelines for Cancer Survivors. Additional surveys measured motivation to exercise, barrier self-efficacy, quality of life, and fatigue. Multivariable models were constructed to evaluate associations between clinicodemographic and psychosocial variables and guideline concordance, and between guideline concordance and quality of life and fatigue., Results: Of 504 eligible survivors, 262 (52%) returned surveys. Only 62 participants (24%) reported meeting both aerobic and strengthening guidelines; 103 (39%) reported meeting neither. Adjusted analyses demonstrated that higher autonomous motivation was associated with higher aerobic and strengthening guideline concordance (both p < 0.01). Higher barrier self-efficacy and older age were associated with higher aerobic guideline concordance (p < 0.01). We identified no significant associations between guideline concordance and tumor type, time since surgery, or recent cancer therapy (all p > 0.05). We found favorable associations between aerobic guideline concordance and both quality of life and fatigue (both p < 0.001)., Conclusions: Less than one-quarter of participants exercised sufficiently to meet national exercise guidelines following pancreatectomy. To maximize exercise and related benefits, interventions should help survivors increase intrinsic motivation and overcome barriers to exercise.

Although reliable strategies exist to promote healthy habits that reduce childhood obesity, the sustainability of these strategies remains an ongoing public health challenge. This study aimed to identify factors experienced in a large, multisite project aimed at reducing childhood obesity that might contribute to project sustainability. Hypothesized constructs underpinning sustainability included replicability, continuation of benefits, institutionalization, and community capacity. Key informants (n = 27) completed 60 min, in-depth interviews, which were audio recorded and transcribed. Transcripts were first coded using a combined deductive and inductive approach. Four major themes emerged (with numerous subthemes): developing partnerships, challenges to the sustainability of implemented programming, the importance of intervening in multiple settings, and ongoing implementation and evaluation strategies. Replicability of complex childhood obesity interventions is possible when there are strong partnerships. Benefits can continue to be conferred from programming, particularly when evidence-based strategies are used that employ best practices. Implementation is facilitated by institutionalization and policies that buffer challenges, such as staffing or leadership changes. Community capacity both enhances the sustainability of interventions and develops as a result of strengthening partnerships and policies that support childhood obesity programming., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background . Early childhood is a critical life period for promoting health behaviors, and early child care and education centers (ECECs) are critical settings, as 60% of U.S. children attend ECECs. Yet few programs or curricula that promote physical activity and nutrition in this setting exist. This study explored the acceptability, feasibility, and sustainability of the Sustainability via Active Garden Education (SAGE) program. Method . Preintervention interviews were conducted to inform the design of SAGE and postintervention interviews were conducted to evaluate the implementation of SAGE in the ECEC setting. A constant comparison approach was used to capture emergent themes on acceptability, feasibility, and sustainability from interviews. Participants . ECEC directors ( N = 10, 90% female, 20% Hispanic, 30% African American). Results . Directors expressed that SAGE was acceptable and feasible as it was age-appropriate, engaging, and aligned with existing curricula and accreditation standards. Most directors reported that SAGE improved activity and nutrition related knowledge while building other social and academic skills (e.g., expanding vocabulary) that are critical to this important developmental period. Suggestions for improving the sustainability of the program included stronger parental involvement and opportunities for ECEC staff trainings.

Loss of skeletal muscle and inferior muscle quality are associated with poor prognosis in patients undergoing preoperative treatment for pancreatic cancer, so maintaining skeletal muscle health before surgery may help accelerate patients' functional recovery and improve their quality of life following surgery. While exercise helps maintain or increase skeletal muscle in individuals undergoing cancer treatment, its efficacy during pancreatic cancer treatment is unclear. Accordingly, in this study we compared changes in skeletal muscle quantity (skeletal muscle index [SMI]) and quality (skeletal muscle density [SMD]) during preoperative pancreatic cancer treatment in participants in a home-based exercise program (EP) and a historical cohort of patients who received the usual care (UC) with no formal exercise programming. Recommendations for the EP cohort included both aerobic and resistance exercise. We assessed changes in SMI and SMD using computed tomography scans administered at treatment planning (T0, prior to EP enrollment) and preoperative restaging (T1) for 33 EP and 64 UC patients and compared changes between groups. The UC patients had statistically significant SMI decreases from T0 to T1 (-1.4 ± 3.8 cm 2 /m 2 ; p  = .005), while the EP patients did not (0.2 ± 3.2 cm 2 /m 2 ; p  = .7). The SMI loss was significantly worse for the UC than for the EP patients ( p  = .03). Neither group demonstrated statistically significant changes in SMD from T0 to T1, nor did the groups differ in the amount of change in SMD. An adjusted linear regression model demonstrated that EP participation was significantly associated with better SMI maintenance ( p  = .02). These results suggest that participation in a home-based EP during preoperative treatment may help improve skeletal muscle health and clinical and quality of life outcomes for pancreatic cancer survivors.

Purpose: Sarcopenia and suboptimal performance status are associated with postoperative complications and morbidity in cancer patients. Prehabilitation has emerged as an approach to improve fitness and muscle strength in patients preoperatively. We sought to describe the frequency of sarcopenia and sarcopenic obesity (SO) in a cohort of cancer patients referred for prehabilitation and the association between body composition and physical function., Methods: In this retrospective review of 99 consecutive cancer patients referred for prehabilitation prior to intended oncologic surgery, prehabilitation included physical medicine and rehabilitation (PM&R) physician evaluation of function and physical therapy for individualized home-based exercise. Sarcopenic A was defined using sex-adjusted norms of skeletal muscle (SKM), measured using the sliceOmatic software (TomoVision, 2012) on computed tomography images at baseline. Sarcopenic B was defined by abnormal SKM and physical function. SO was defined as sarcopenia with BMI ≥ 25. Six-minute walk test (6MWT), 5 times sit-to-stand (5×STS), and grip strength were obtained at consultation (baseline) and at preoperative follow-up (if available)., Results: Forty-nine patients (49%) were Sarcopenic A, 28 (28%) SO, and 38 (38%) Sarcopenic B. Age was negatively correlated with SKM ( P  = .0436). There were no significant associations between Sarcopenic A/B or SO with baseline or changes in physical function. Assessed by sex, Sarcopenic A females had low 5×STS ( P  = .04) and Sarcopenic B females had low GS ( P  = .037). Sarcopenic B males had low preoperative GS ( P  = .026). 6MWT and grip strength at baseline were lower than age- and sex-related norms (both P  < .001). Preoperatively, 6MWT distance and 5×STS time improved (both P  < .001). Functional improvement in the sarcopenic and nonsarcopenic patients did not differ according to sex., Conclusions: In this cohort of prehabilitation surgical oncology patients, frequencies of sarcopenia and SO were high, and baseline physical function was abnormal but improved significantly regardless of body composition. These findings suggest that patients have considerable prehabilitation needs and are capable of improving with comprehensive care.

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A ( H3F3A ) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Purpose: We investigated the value of transcriptome sequencing (RNAseq) in ascertaining the consequence of DNA variants on RNA transcripts to improve the diagnostic rate from exome or genome sequencing for undiagnosed Mendelian diseases spanning a wide spectrum of clinical indications., Methods: From 234 subjects referred to the Undiagnosed Diseases Network, University of California-Los Angeles clinical site between July 2014 and August 2018, 113 were enrolled for high likelihood of having rare undiagnosed, suspected genetic conditions despite thorough prior clinical evaluation. Exome or genome sequencing and RNAseq were performed, and RNAseq data was integrated with genome sequencing data for DNA variant interpretation genome-wide., Results: The molecular diagnostic rate by exome or genome sequencing was 31%. Integration of RNAseq with genome sequencing resulted in an additional seven cases with clear diagnosis of a known genetic disease. Thus, the overall molecular diagnostic rate was 38%, and 18% of all genetic diagnoses returned required RNAseq to determine variant causality., Conclusion: In this rare disease cohort with a wide spectrum of undiagnosed, suspected genetic conditions, RNAseq analysis increased the molecular diagnostic rate above that possible with genome sequencing analysis alone even without availability of the most appropriate tissue type to assess.

Background: In the context of health-related interventions, sustainability is the capacity to maintain the changes resulting from the intervention. These can be improved policies, practices or trends intended to improve population health. The Childhood Obesity Research Demonstration (CORD) project was a multi-site, multi-intervention collaboration testing the Obesity Chronic Care Model with interventions for childhood obesity prevention and management. We present the model, definitions and methodology used for the cross-site sustainability evaluation of CORD., Methods: We applied the Ecologic Model of Obesity to childhood obesity interventions to operationalize four sustainability constructs: replicability, continuation of benefits, institutionalization, and community capacity. We used a triangulation approach and employed mixed methods to assess sustainability constructs at each level of the Ecologic Model of Obesity: Micro, Meso, Exo and Macro. We constructed checklists to count and code intervention activities, use of evidence-based practices among providers, and environmental factors and policies hypothesized to influence intervention sustainability. We developed in-depth interviews for principal investigators and project leads. We applied the Wilder Collaboration Factors Inventory with key stakeholders., Results: Lessons learned suggested that sustainability constructs should be clearly identified and operationalized a priori. Constructs must be flexible to account for differences between intervention plans and implementation to obtain robust and informative data., Conclusion: Strong links are needed among researchers, program implementers and communities to accomplish consistent, robust and valuable data collection efforts to assure sustainable and healthy communities., Competing Interests: Competing interestsThe authors declare they have no competing interests., (© The Author(s). 2020.)

Background: Physical activity and exercise appear to benefit patients receiving preoperative treatment for cancer. Supports and barriers must be considered to increase compliance with home-based exercise prescriptions in this setting. Such influences have not been previously examined., Methods: The authors used quantitative and qualitative methods to examine potential physical activity influences among patients who were prescribed home-based aerobic and strengthening exercises concurrent with preoperative chemotherapy or chemoradiation for pancreatic cancer. Physical activity was measured using exercise logs and accelerometers. Social support for exercise and perceived neighborhood walkability were measured using validated surveys. Relationships between influences and physical activity were evaluated using linear regression analyses and qualitative interviews., Results: Fifty patients received treatment for a mean of 16 (9) weeks prior to planned surgical resection. Social support from friends and neighborhood esthetics were positively associated with physical activity (P < .05). In interviews, patients confirmed the importance of these influences and cited encouragement from health care providers and desire to complete and recover from treatment as additional motivators., Conclusions: Interpersonal and environmental motivators of exercise and physical activity must be considered in the design of future home-based exercise interventions designed for patients receiving preoperative therapy for cancer.

Background: Frailty is a syndrome characterized by weakness, slow gait, weight loss, exhaustion, and low activity. We sought to determine whether frailty was associated with age or stage in newly diagnosed patients with pancreatic ductal adenocarcinoma (PDAC), and determine its association with survival., Methods: Consecutive patients with newly diagnosed PDAC of all stages underwent baseline assessment. Frailty (per Fried criteria) was defined as having three or more abnormalities in: grip strength, gait speed, weight loss, self-reported exhaustion, or self-reported physical activity. Baseline clinicodemographic characteristics, anatomic stage, performance status, and laboratory markers of prognosis were included. The association between baseline characteristics, frailty, and survival was determined. The associations of individual frailty measures with age, stage, comorbidities, and performance status were examined. Body composition was measured from computed tomographic images using SliceOMatic software., Results: Of 150 patients enrolled, 8 were excluded because they did not have PDAC on final diagnosis. The median age was 65 years (range, 32-89). Seventy-nine patients (55.6%) were sarcopenic, and 36 (25.4%) were frail. Frailty was associated with increasing comorbidities (P = 0.03) and worse performance status (P < 0.01). During follow-up, 79 patients (56%) died. Frailty was significantly associated with death during the follow-up period (P < 0.001) for the entire cohort, including patients with curative (P = 0.038) and palliative (P = 0.003) treatment plans., Conclusions: Frailty was seen frequently in patients with newly diagnosed PDAC and was not associated with increasing age or more advanced stage. Frailty was a predictor of survival, including patients treated with curative intent., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Guidelines recommend exercise to cancer survivors, but limited data exists regarding exercise among patients undergoing preoperative cancer treatment. We examined differences in weekly self-reported exercise and accelerometer-measured physical activity among participants in a home-based exercise program administered during preoperative treatment for pancreatic cancer., Methods: Participants were encouraged to perform at least 60 min/week of moderate-intensity aerobic exercise and at least 60 min/week of full-body strengthening exercises concurrent with chemotherapy, chemoradiation therapy or both sequentially and received resistance equipment, program instruction, and biweekly follow-up calls to encourage adherence. Self-reported aerobic and strengthening exercise minutes were measured using daily logs, and physical activity was measured objectively using accelerometers., Results: Fifty participants (48% female, mean age 66 ± 8 years) participated for an average of 16 ± 9 preoperative weeks. Participants reported overall means of 126 ± 83 weekly minutes of aerobic exercise and 39 ± 33 weekly minutes of strengthening exercise in daily logs. Participants performed 158.7 ± 146.7 weekly minutes of accelerometer-measured moderate-to-vigorous physical activity. There were no significant differences in exercise or physical activity between treatment phases., Conclusions: These findings suggest that it is feasible to target the entire preoperative course for exercise prescription. Although participants exceeded aerobic exercise recommendations on average, we observed low strengthening exercise adherence and wide variability in self-reported exercise and accelerometer physical activity variables. These findings suggest that additional support, including program adaptations, may be necessary to overcome barriers to exercise or improve motivation when prescribing exercise in this clinical scenario.

Purpose: To investigate relationships among physical activity, changes in physical function, and health-related quality of life (HRQOL) among patients with pancreatic adenocarcinoma enrolled in a home-based exercise prehabilitation program. Methods: Patients with resectable pancreatic adenocarcinoma receiving preoperative chemotherapy and/or chemoradiation were enrolled on this prospective, single-arm trial and were advised to perform ≥60 minutes each of moderate-intensity aerobic exercise and strengthening exercise weekly. Activity was measured via self-report and accelerometers, including moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), and sedentary activity (SA). Physical function measures at baseline and restaging follow-up included 6-minute walk test (6MWT), 5 times sit-to-stand (5×STS), handgrip strength (HGS), 3-m walk for gait speed (GS), and the PROMIS Physical Function Short Form. HRQOL was measured via the FACT-Hep questionnaire. Results: Fifty participants with mean age 66 years (standard deviation = 8 years) were enrolled. The 6MWT, 5×STS, and GS significantly improved from baseline to restaging follow-up (P=.001, P=.049, and P=.009, respectively). Increases in self-reported aerobic exercise, weekly MVPA, and LPA were associated with improvement in 6MWT (β=.19, P=.048; β=.18, P=.03; and β=.08, P=.03, respectively) and self-reported physical functioning (β=.02, P=.03; β=.03, P=.005; and β=.01, P=.02, respectively). Increased weekly LPA was associated with increased HRQOL (β=.03, P=.02). Increased SA was associated with decreased HRQOL (β=-.02,P=.01). Conclusions: Patients with potentially resectable pancreatic cancer exhibit meaningful improvement in physical function with prehabilitation; physical activity was associated with improved physical function and HRQOL. These data highlight the importance of physical activity during treatment for pancreatic cancer.

Background: The changes in body composition that occur in response to therapy for localized pancreatic ductal adenocarcinoma (PDAC) and during the early survivorship period, as well as their clinical significance, are poorly understood., Methods: One hundred twenty-seven consecutive patients with PDAC who received preoperative therapy followed by pancreatoduodenectomy (PD) at a single institution between 2009 and 2012 were longitudinally evaluated. Changes in skeletal muscle (SKM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured on serial computed tomography images obtained upon presentation, prior to pancreatectomy, and approximately 3 and 12 months after surgery., Results: Prior to therapy, patients' mean baseline BMI was 26.5 ± 4.7 kg/m 2 and 63.0% met radiographic criteria for sarcopenia. During a mean 5.4 ± 2.3 months of preoperative therapy, minimal changes in SKM (- 0.5 ± 7.8%, p > 0.05), VAT (- 1.8 ± 62.6%, p < 0.001), and SAT (- 4.8 ± 27.7%, p < 0.001) were observed. In contrast, clinically significant changes were observed on postoperative CT compared to baseline anthropometry: SKM - 4.1 ± 10.7%, VAT - 38.7 ± 30.2%, and SAT - 24.1 ± 22.6% (all p < 0.001) and these changes persisted at one year following PD. While anthropometric changes during preoperative therapy were not independently associated with survival, SKM gain between the postoperative period and one-year follow-up was associated with improved overall survival (OR 0.50, 95% CI 0.29-0.87)., Conclusions: In contrast to the minor changes that occur during preoperative therapy for PDAC, significant losses in key anthropometric parameters tend to occur over the first year following PD. Ongoing SKM loss in the postoperative period may represent an early marker for worse outcomes.

Physical activity is an important target for improving health and well-being among cancer survivors. Cancer clinicians are uniquely positioned to promote physical activity among survivors through follow-up visits for treatment planning and surveillance. Providers should prioritize assessment of guideline-concordant physical activity and facilitate achievement of physical activity guidelines through exercise prescription, goal setting, addressing barriers, and capitalizing on support systems., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Exercise concurrent with neoadjuvant chemotherapy and/or chemoradiation for pancreatic adenocarcinoma (PDAC) may mitigate the decline in function that may occur as a result of the disease or its treatment in the preoperative period. The primary objective of this single-arm prospective trial was to determine adherence to a home-based exercise program administered during preoperative therapy., Methods: Twenty patients from a quaternary cancer center with potentially resectable PDAC were enrolled. Patients were prescribed a minimum of 120 min of moderate-intensity exercise weekly: at least 60 min of aerobic exercise and 60 min of resistance exercise. Self-reported exercise was recorded in daily logs. Functional and survey measures were collected upon enrollment, following preoperative therapy, and 1 month after surgery., Results: Fifteen out of 20 patients participated in the program. They reported a mean (standard deviation (SD)) of 98.6 (69.8) min of aerobic exercise weekly and 57.4 (36.0) min of strengthening exercise weekly over a median of 17 weeks (range, 5-35 weeks) of preoperative therapy, for a mean (SD) of 156.0 (64.5) min of total exercise weekly. Eighty percent reported a mean of least 120 min of total exercise weekly during preoperative therapy. Patients with low baseline physical activity based on the International Physical Activity Questionnaire significantly increased their preoperative physical activity (p = .01). There were no adverse events associated with the exercise program., Conclusions: Patients with PDAC will participate in a home-based exercise program of aerobic and strengthening exercise and will increase physical activity, concurrent with preoperative chemotherapy and/or chemoradiation.

Background: Low physical activity (PA) and fruit and vegetable (F&V) consumption in early childhood are continued public health challenges. This manuscript describes outcomes from two pilot studies for Sustainability via Active Garden Education (SAGE), a program designed to increase PA and F&V consumption among 3 to 5 year old children., Methods: SAGE was developed using community-based participatory research (CBPR) and delivered to children (N = 89) in early care and education centers (ECEC, N = 6) in two US cities. Children participated in 12 one-hour sessions that included songs, games, and interactive learning activities involving garden maintenance and taste tests. We evaluated reach, efficacy, adoption, implementation, and potential for maintenance of SAGE following the RE-AIM framework. Reach was evaluated by comparing demographic characteristics among SAGE participants and residents of target geographic areas. Efficacy was evaluated with accelerometer-measured PA, F&V consumption, and eating in the absence of hunger among children, parenting practices regarding PA, and home availability of F&V. Adoption was evaluated by the number of ECEC that participated relative to the number of ECEC that were recruited. Implementation was evaluated by completion rates of planned SAGE lessons and activities, and potential for maintenance was evaluated with a parent satisfaction survey., Results: SAGE reached ECEC in neighborhoods representing a wide range of socioeconomic status, with participants' sociodemographic characteristics representing those of the intervention areas. Children significantly increased PA during SAGE lessons compared to usual lessons, but they also consumed more calories in the absence of hunger in post- vs. pre-intervention tests (both p < .05). Parent reports did not suggest changes in F&V consumption, parenting PA practices, or home F&V availability, possibly due to low parent engagement. ECEC had moderate-to-high implementation of SAGE lessons and curriculum. Potential for maintenance was strong, with parents rating SAGE favorably and reporting increases in knowledge about PA and nutrition guidelines for young children., Conclusions: SAGE successfully translated national PA guidelines to practice for young children but was less successful with nutrition guidelines. High adoption and implementation and favorable parent reports suggest high potential for program sustainability. Further work to engage parents and families of young children in ECEC-based PA and nutrition programming is needed.

Background: Long term patient-reported symptoms and quality of life (QOL) are important outcome metrics following cancer operations, but have been poorly described in patients who have previously undergone pancreatectomy., Methods: We conducted a cross-sectional survey of recurrence-free survivors of pancreatic ductal adenocarcinoma, periampullary carcinomas, and pancreatic neuroendocrine tumors who had undergone prior pancreatectomy. QOL and symptom burden were measured using the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire, and psychosocial distress was measured using the Hospital Anxiety and Depression Scale., Results: Of 331 eligible patients surveyed, 217 (66%) participated at a median of 53.3 (range, 7.6-214.8) months following pancreatoduodenectomy (PD, n = 165) or distal pancreatectomy (DP, n = 52). Among all patients, overall QOL scores were favorable and influenced by race, histology, and type of surgery. The most common significant symptoms reported were fatigue (82%), back pain (32%), and difficulty with digestion (31%). In general, PD survivors reported better QOL, lower levels of anxiety/depression, greater levels of diarrhea, and improved appetite, constipation, fatigue, anxiety, and depression (P < 0.05) than DP survivors. On both univariate and multivariate regression analysis, DP was negatively associated with QOL., Conclusions: Most disease-free survivors of pancreatic neoplasms report favorable QOL, but gastrointestinal and psychosocial symptoms may exist long after pancreatectomy. J. Surg. Oncol. 2017;115:144-150. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Previous studies by different authors have reported their readmission rates after pancreatectomy as either “30 days from discharge” or “90 days from surgery.” The objective of this study was to determine which of these definitions captures the most surgery-related complications., Methods: A prospectively maintained database at a high volume center was queried to identify all individuals who underwent pancreatectomy between 2000 and 2012 for any diagnosis. The data was analyzed at 30 days after discharge and 90 days after operation. The optimal timing for complication reporting was defined as the time point that maximized the capture of surgery-related readmissions and direct major surgical complications while minimizing the capture of disease (cancer)-related readmissions., Results: There were 1123 patients included during the study time period. The median age was 63 years old, and 55.6% were male. Operations included 833 (74.2%) pancreaticoduodenectomies, 257 (22.9%) distal pancreatectomies, 18 (1.6%) total pancreatectomies, and 15 (1.3%) central pancreatectomies. Surgery-related readmissions occurred in 248 (22%) individuals, while readmission related to malignant disease progression occurred in 25 (2%) individuals. The 30 days from discharge definition captured 184 surgery-related readmissions and 1 disease-related readmission (sensitivity 0.74, specificity 0.96). The 90 days from surgery definition captured 215 surgery-related readmissions and 1 disease-related readmission (sensitivity 0.87, specificity 0.96). Major surgical complication was the only independent factor associated with readmission not captured by the 30 days from discharge definition (p = 0.002, HR 3.94, 95% CI 1.44–12.22)., Conclusion: The 90 days from surgery definition was superior to the 30 days from discharge definition, especially with regards to readmission related to major surgical complications.

Few studies have examined neighborhood influences on physical activity (PA) among low-income African Americans living in public housing. This study measured the associations of PA resources and land use with PA among 216 African Americans living in 12 low-income housing developments in Houston, Texas. Neighborhood measures included both detailed information from in-person audits and geographic information systems (GIS) data. Hierarchical linear regression models tested the associations of neighborhood PA resource availability and quality and land use density and diversity with individual-level, self-reported PA. Land use diversity was positively associated with walking among men after controlling for other neighborhood characteristics. Policies that promote land use diversity or improve the pedestrian environment in areas with diverse destinations may encourage PA among public housing residents.

Objective: To investigate the legitimacy of 90-day mortality as a measure of hepatopancreatobiliary quality., Background: The 90-day mortality rate has been increasingly but not universally reported after hepatopancreatobiliary surgery. The legitimacy of this definition as a measure of surgical quality has not been evaluated., Methods: We retrospectively reviewed the causes of all deaths that occurred within 365 postoperative days in patients undergoing hepatectomy (n = 2811) and/or pancreatectomy (n = 1092) from January 1997 to December 2012. The rates of surgery-related, disease-related, and overall mortality within 30 days, within 30 days or during the index hospitalization, within 90 days, and within 180 days after surgery were calculated., Results: Seventy-nine (3%) surgery-related deaths and 92 (3%) disease-related deaths occurred within 365 days after hepatectomy. Twenty (2%) surgery-related deaths and 112 (10%) disease-related deaths occurred within 365 days after pancreatectomy. The overall mortality rates at 99 and 118 days optimally reflected surgery-related mortality after hepatobiliary and pancreatic operations, respectively. The 90-day overall mortality rate was a less sensitive but equivalently specific measure of surgery-related death., Conclusions and Relevance: The 99- and 118-day definitions of postoperative mortality optimally reflected surgery-related mortality after hepatobiliary and pancreatic operations, respectively. However, among commonly reported metrics, the 90-day overall mortality rate represents a legitimate measure of surgical quality.

Background: The rate of adverse events after pancreatectomy is widely reported as a measure of surgical quality. However, morbidity data are routinely acquired retrospectively and often are reported at 30 days. The authors hypothesized that morbidity after pancreatectomy is therefore underreported. They sought to compare rates of adverse events calculated at multiple time points after pancreatectomy., Methods: The authors instituted an active surveillance system to detect, categorize, and grade the severity of all adverse events after pancreatectomy, using the modified Accordion system and International Study Group of Pancreatic Surgery definitions. All patients and clinical events were monitored directly for at least 90 days after surgery., Results: Of 315 consecutively monitored patients, 239 (76 %) experienced 500 unique adverse events. The absolute number of unique adverse events increased by 32 % between index discharge and 90 days and by 10 % between 30 and 90 days. The number of severe adverse events increased by 96 % between discharge and 90 days and by 29 % between 30 and 90 days. In this study, 16 % of the patients experienced at least one severe adverse event within the index hospitalization, 24 % within 30 postoperative days, and 29 % within 90 days. Among the 80 readmissions that occurred within 90 days, 28 (35 %) occurred later than 30 days after pancreatectomy., Conclusions: Approximately one-third of severe adverse events and readmissions are reported more than 30 days after surgery. All adverse events that occur within 90 days of surgery must be identified and reported for accurate characterization of the morbidity associated with pancreatectomy.

Background: Continuous monitoring technologies such as accelerometers and pedometers are the gold standard for physical activity (PA) measurement. However, inconsistencies in use, analysis, and reporting limit the understanding of dose-response relationships involving PA and the ability to make comparisons across studies and population subgroups. These issues are particularly detrimental to the study of PA across different ethnicities with different PA habits. This systematic review examined the inclusion of published guidelines involving data collection, processing, and reporting among articles using accelerometers or pedometers in Hispanic or Latino populations., Methods: English (PubMed; EbscoHost) and Spanish (SCIELO; Biblioteca Virtual en Salud) articles published between 2000 and 2013 using accelerometers or pedometers to measure PA among Hispanics or Latinos were identified through systematic literature searches. Of the 253 abstracts which were initially reviewed, 57 met eligibility criteria (44 accelerometer, 13 pedometer). Articles were coded and reviewed to evaluate compliance with recommended guidelines (N = 20), and the percentage of accelerometer and pedometer articles following each guideline were computed and reported., Results: On average, 57.1 % of accelerometer and 62.2 % of pedometer articles reported each recommended guideline for data collection. Device manufacturer and model were reported most frequently, and provision of instructions for device wear in Spanish was reported least frequently. On average, 29.6 % of accelerometer articles reported each guideline for data processing. Definitions of an acceptable day for inclusion in analyses were reported most frequently, and definitions of an acceptable hour for inclusion in analyses were reported least frequently. On average, 18.8 % of accelerometer and 85.7 % of pedometer articles included each guideline for data reporting. Accelerometer articles most frequently included average number of valid days and least frequently included percentage of wear time., Discussion: Inclusion of standard collection and reporting procedures in studies using continuous monitoring devices in Hispanic or Latino population is generally low., Conclusions: Lack of reporting consistency in continuous monitoring studies limits researchers' ability to compare studies or draw meaningful conclusions concerning amounts, quality, and benefits of PA among Hispanic or Latino populations. Reporting data collection, computation, and decision-making standards should be required. Improved interpretability would allow practitioners and researchers to apply scientific findings to promote PA.

Background: A well-defined treatment strategy for elderly patients with resectable pancreatic cancer is lacking. Multiple reports have described highly selected older cancer patients who have successfully undergone pancreatectomy. However, multimodality therapy is essential for long-term survival, and elderly patients are at high risk for not receiving adjuvant therapy postoperatively. We sought to describe the treatment patterns and outcomes of a series of elderly patients with pancreatic cancer who were treated with a multimodality strategy that liberally used neoadjuvant therapy., Study Design: We retrospectively reviewed treatment plans, short-term outcomes, and overall survival of all patients 70 years old and older, presenting to our institution over a 9-year period, who were treated for potentially resectable or borderline resectable pancreatic cancer., Results: There were 179 (76%) of 236 patients treated with curative intent. Of these patients, 153 (85%) initiated neoadjuvant therapy: 74 (48%) subsequently underwent pancreatectomy and 79 did not due to disease progression (n = 46), insufficient performance status (n = 23), or other reasons (n = 10). Eleven (42%) of 26 patients who underwent surgery first received postoperative therapy. Among patients treated with curative intent, the median overall survival of all patients initiating neoadjuvant therapy (16.6 months [range 2.1 to 142.7 months]) was similar to that of patients undergoing resection primarily (15.1 months [range 5.4 to 100.8 months]), p = 0.53. After pancreatectomy, patients had a 2% in-hospital mortality rate and 91% were discharged home., Conclusions: Eighty-five percent of all patients 70 years old and older, who underwent pancreatectomy for potentially resectable or borderline resectable pancreatic cancer, received multimodality therapy. More than 90% were discharged home. These data demonstrate a potential role for neoadjuvant therapy in selecting elderly patients for surgery, and support further studies to refine individualized treatment protocols for this high-risk population., (Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Fear of disease recurrence is well documented among cancer survivors, but its significance among patients treated for solid pancreatic and periampullary neoplasms is unknown despite the known risk of recurrence associated with these tumors. We hypothesized that fear of cancer recurrence (FCR) represents a common source of psychosocial distress in this population and sought to characterize subgroups for whom FCR might represent a target for intervention to improve quality of life., Methods: We conducted a cross-sectional study of FCR in patients who were disease-free after potentially curative pancreatectomy for ductal or periampullary adenocarcinoma or pancreatic neuroendocrine tumor. We assessed seven discrete dimensions of FCR using the Fear of Recurrence Inventory and evaluated quality of life and psychosocial distress using the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire and the Hospital Anxiety and Depression Scale., Results: Of 354 eligible patients, 240 (68 %) participated in the study a median of 48 months after potentially curative pancreatectomy. An FCR severity score indicative of frequent fearful thoughts, emotional disturbance and functional impairment was identified in 37, 28, and 35 % of patients with pancreatic adenocarcinoma, nonpancreatic periampullary adenocarcinoma, and pancreatic neuroendocrine tumor, respectively. Anxiety (P < 0.001) and low quality of life (P = 0.028) were independently associated with a clinically significant level of FCR, but histopathologic diagnosis and clinicopathologic markers of prognosis were not., Conclusions: FCR represents a significant concern for one-third of patients after curative surgery for a pancreatic or periampullary tumor, regardless of their actual likelihood of recurrence or disease-related death.

Purpose: Since 1995, the David Geffen School of Medicine at UCLA (DGSOM) has created policies to prevent medical student mistreatment, instituted safe mechanisms for reporting mistreatment, provided resources for discussion and resolution, and educated faculty and residents. In this study, the authors examined the incidence, severity, and sources of perceived mistreatment over the 13-year period during which these measures were implemented., Method: From 1996 to 2008, medical students at DGSOM completed an anonymous survey after their third-year clerkships and reported how often they experienced physical, verbal, sexual harassment, ethnic, and power mistreatment, and who committed it. The authors analyzed these data using descriptive statistics and the students' descriptions of these incidents qualitatively, categorizing them as "mild," "moderate," or "severe." They compared the data across four periods, delineated by milestone institutional measures to eradicate mistreatment., Results: Of 2,151 eligible students, 1,946 (90%) completed the survey. More than half (1,166/1,946) experienced some form of mistreatment. Verbal and power mistreatment were most common, but 5% of students (104/1,930) reported physical mistreatment. The pattern of incidents categorized as "mild," "moderate," or "severe" remained across the four study periods. Students most frequently identified residents and clinical faculty as the sources of mistreatment., Conclusions: Despite a multipronged approach at DGSOM across a 13-year period to eradicate medical student mistreatment, it persists. Aspects of the hidden curriculum may be undermining these efforts. Thus, eliminating mistreatment requires an aggressive approach both locally at the institution level and nationally across institutions.

Background: Although the primary purpose of the US Medical Licensing Examination (USMLE) is assessment for licensure, USMLE scores often are used for other purposes, more prominently resident selection. The Committee to Evaluate the USMLE Program currently is considering a number of substantial changes, including conversion to pass/fail scoring., Methods: A survey was administered to third-year (MS3) and fourth-year (MS4) medical students and residents at a single institution to evaluate opinions regarding pass/fail scoring on the USMLE., Results: Response rate was 59% (n  =  732 of 1249). Reported score distribution for Step 1 was 30% for <220, 38% for 220-240, and 32% for >240, with no difference between MS3s, MS4s, and residents (P  =  .89). Score distribution for Step 2 Clinical Knowledge (CK) was similar. Only 26% of respondents agreed that Step 1 should be pass/fail; 38% agreed with pass/fail scoring for Step 2 CK. Numerical scoring on Step 1 was preferred by respondents who: (1) agreed that the examination gave an accurate estimate of knowledge (odds ratio [OR], 4.23; confidence interval [CI], 2.41-7.43; P < .001); (2) scored >240 (OR, 4.0; CI, 1.92-8.33; P < .001); and (3) felt that acquisition of knowledge might decrease if the examination were pass/fail (OR, 10.15; CI, 3.32-31.02; P < .001). For Step 2 CK, numerical scoring was preferred by respondents who: (1) believed they gained a large amount of knowledge preparing for the examination (OR, 2.63; CI, 1.52-4.76; P < .001); (2) scored >240 (OR, 4.76; CI, 2.86-8.33; P < .001); (3) felt that the amount of knowledge acquired might decrease if it were pass/fail (OR, 28.16; CI, 7.31-108.43; P < .001); and (4) believed their Step 2 CK score was important when applying for residency (OR, 2.37; CI, 1.47-3.84; P < .001)., Conclusions: Students and residents prefer the ongoing use of numerical scoring because they believe that scores are important in residency selection, that residency applicants are advantaged by examination scores, and that scores provide an important impetus to review and solidify medical knowledge.

The authors evaluated semi-quantitatively the influence of the personal interview on the ranking of internal medicine residency applicants by teaching staff interviewers. Pre- and post-interview rankings of 236 student applicants were compared. Approximately a third of the applicants were ranked more favourably, a third less, and a third remained unchanged following the interview. The magnitude and implications of the post-interview changes in rankings are discussed. Although the interview is a controversial component of the residency selection process, the present study indicates that the interview experience can have a major influence on the interviewer of an applicant and the interviewer's ranking of an applicant in a training programme's match list.

Patients with advanced head and neck cancer have significant reduction in their circulating lymphocyte mass which is reflected in decreased numbers of T cells, Fc receptor cells, and in derangements of T lymphocyte functions, i.e., decreased responsiveness to several dilutions of phytohemagglutinin and lack of development of delayed hypersensitivity to 2,4-dinitrochlorobenzene (70% of patients were DNCB (-)). A population of phagocytic cells capable of decreasing lymphocyte responsiveness to mitogens were demonstrated. Removal of these cells resulted in an increment in lymphocyte responsiveness. Immunological impairment seemed to correlate with patients' ability to become sensitized to DNCB. Those patients who were DNCB (+) had less derangement in their immunological parameters. Weekly administration of Corynebacterium parvum in conjunction with chemotherapy did not have a discernible effect on patient's immune reactivity.