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OBJECTIVE High cervical spinal cord injury (SCI) results in complete loss of upper-limb function, resulting in debilitating tetraplegia and permanent disability. Spontaneous motor recovery occurs to varying degrees in some patients, particularly in the 1st year postinjury. However, the impact of this upper-limb motor recovery on long-term functional outcomes remains unknown. The objective of this study was to characterize the impact of upper-limb motor recovery on the degree of long-term functional outcomes in order to inform priorities for research interventions that restore upper-limb function in patients with high cervical SCI. METHODS A prospective cohort of high cervical SCI (C1–4) patients with American Spinal Injury Association Impairment Scale (AIS) grade A–D injury and enrolled in the Spinal Cord Injury Model Systems Database was included. Baseline neurological examinations and functional independence measures (FIMs) in feeding, bladder management, and transfers (bed/wheelchair/chair) were evaluated. Independence was defined as score ≥ 4 in each of the FIM domains at 1-year follow-up. At 1-year follow-up, functional independence was compared among patients who gained recovery (motor grade ≥ 3) in elbow flexors (C5), wrist extensors (C6), elbow extensors (C7), and finger flexors (C8). Multivariable logistic regression evaluated the impact of motor recovery on functional independence in feeding, bladder management, and transfers. RESULTS Between 1992 and 2016, 405 high cervical SCI patients were included. At baseline, 97% of patients had impaired upper-limb function with total dependence in eating, bladder management, and transfers. At 1 year of follow-up, the largest proportion of patients who gained independence in eating, bladder management, and transfers had recovery in finger flexion (C8) and wrist extension (C6). Elbow flexion (C5) recovery had the lowest translation to functional independence. Patients who achieved elbow extension (C7) were able to transfer independently. On multivariable analysis, patients who gained elbow extension (C7) and finger flexion (C8) were 11 times more likely to gain functional independence (OR 11, 95% CI 2.8–47, p < 0.001) and patients who gained wrist extension (C6) were 7 times more likely to gain functional independence (OR 7.1, 95% CI 1.2–56, p = 0.04). Older age (≥ 60 years) and motor complete SCI (AIS grade A–B) reduced the likelihood of gaining independence. CONCLUSIONS After high cervical SCI, patients who gained elbow extension (C7) and finger flexion (C8) had significantly greater independence in feeding, bladder management, and transfers than those with recovery in elbow flexion (C5) and wrist extension (C6). Recovery of elbow extension (C7) also increased the capability for independent transfers. This information can be used to set patient expectations and prioritize interventions that restore these upper-limb functions in patients with high cervical SCI.

Background: Tumor characteristics such as grade, stage and receptor status are associated with breast cancer (BC) prognosis. Less is known about modifiable factors and BC prognosis. Advanced glycation end-products (AGEs) are reactive metabolites produced as a by-product of sugar metabolism, generated in conditions of increased oxidative stress. AGEs irreversibly accumulate in our tissues over time with pathogenic effects on genetic fidelity, protein function, cell signaling pathways, and chronic inflammatory diseases. The total body AGE pool is composed of endogenous AGEs and exogenous AGEs (consumed mainly through processed foods and those cooked at high temperatures). Serum AGE (sAGE) levels, a reflection of total body AGE, are higher in people with poor diet quality, lower levels of physical activity, and in women with BC compared to healthy controls. AGEs promote growth, migration and invasion in BC cell lines and activate prognostic inflammatory mediators such as interleukin-6 and C-reactive protein. Dietary AGEs have been associated with increased BC risk and increased mortality after BC diagnosis whereas lifestyle interventions can lower dietary and sAGE levels. The impact of sAGE levels, a better estimate of total body AGE than dietary AGE, on BC prognosis has not been previously evaluated. Methods: The Women’s Healthy Eating and Living (WHEL) study randomized 3088 BC patients stage I-III who completed their primary therapy to a high-vegetable, low-fat diet or control and followed for a median of 7.3 years. Main outcomes were invasive BC events (recurrence or new primary N=518), death due to BC (N=262) and deaths from any cause (N=315). sAGE was measured as the AGE metabolite carboxymethyllysine (ug/ml) from WHEL fasting blood specimens at study entry. sAGE was logged and corrected for plate batch effect via linear regression and analyzed in continuous scale and in quintiles. The Kaplan-Meier method and Cox regression model were performed for risk impact of sAGE on overall survival (OS), recurrence free survival (RFS), breast cancer specific survival (BCSS) and distant metastasis free survival (DMFS). We additionally adjusted in Cox models for potential confounding variables (age, race, BMI, smoking, alcohol use, physical activity, tumor characteristics). Results: 2564 participants had sAGE available. After excluding samples for excessive variabilities, 2315 samples were analyzed. Raw corrected sAGE ranged from 0.0-48.15 ug/ml (median 7.39); logged and corrected range -5.04-1.67. sAGE was positively associated with BMI (p Citation Format: Lindsay L. Peterson, Yu Tao, Jingqin Luo, Graham A. Colditz, Yikyung Park, Jennifer A. Ligibel, David Turner. PD12-09 Serum Advanced Glycation End-Products are Associated with Breast Cancer Prognosis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD12-09.

Despite an increased understanding of the impact of socioeconomic status on neurosurgical outcomes, the impact of neighborhood-level social determinants on lumbar spine surgery patient-reported outcomes remains unknown.To evaluate the impact of geographic social deprivation on physical and mental health of lumbar surgery patients.A single-center retrospective cohort study analyzing patients undergoing lumbar surgery for degenerative disease from 2015 to 2018 was performed. Surgeries were categorized as decompression only or decompression with fusion. The area deprivation index was used to define social deprivation. Study outcomes included preoperative and change in Patient-Reported Outcomes Measurement (PROMIS) physical function (PF), pain interference (PI), depression, and anxiety (mean follow-up: 43.3 weeks). Multivariable imputation was performed for missing data. One-way analysis of variance and multivariable linear regression were used to evaluate the association between area deprivation index and PROMIS scores.In our cohort of 2010 patients, those with the greatest social deprivation had significantly worse mean preoperative PROMIS scores compared with the least-deprived cohort (mean difference [95% CI]-PF: -2.5 [-3.7 to -1.4]; PI: 3.0 [2.0-4.1]; depression: 5.5 [3.4-7.5]; anxiety: 6.0 [3.8-8.2], all P.001), without significant differences in change in these domains at latest follow-up (PF: +0.5 [-1.2 to 2.2]; PI: -0.2 [-1.7 to 2.1]; depression: -2 [-4.0 to 0.1]; anxiety: -2.6 [-4.9 to 0.4], all P.05).Lumbar spine surgery patients with greater social deprivation present with worse preoperative physical and mental health but experience comparable benefit from surgery than patients with less deprivation, emphasizing the need to further understand social and health factors that may affect both disease severity and access to care.

Domino liver transplantation (DLT) utilizes a phenotypically normal explant from select recipients as a donor graft in another patient. The procedure is not widely employed and remains restricted to a small number of centers. The purpose of this study was to assess the national profile of DLT in the United States (US) and evaluate current survival outcomes.The United Network for Organ Sharing (UNOS) database was queried for all liver transplants (LT) between 1996 and 2020. Outcomes of interest were long-term graft and patient survival.Of 181,976 LTs performed nationally during the study period, 185 (0.1%) were DLTs. Amyloidosis and maple syrup urine disease (MSUD) accounted for 83% of dominoed allografts. Out of 210 explants with amyloidosis, 103 (49%) were dominoed into secondary recipients. Only 50 (22%) of all MSUD explants (n = 227) were dominoed. Graft survival was 79%, 73% and 53% at 3-, 5- and 10-years, respectively, for DLT recipients. Overall patient survival was 83%, 76% and 57% at 3-, 5- and 10-years.Despite excellent long-term survival outcomes, DLT allografts comprise a very small percentage of the liver donor pool. A large proportion of potential DLTs may be unconscionably excluded despite shortages in deceased donor organs.

With improved survivorship in liver transplantation (LT), there is an emerging focus on functional recovery and health-related quality of life (HRQoL) after surgery. The present study aimed to assess HRQoL after LT using the Patient-Reported Outcomes Measurement Information System (PROMIS).This was a prospective analysis of LT recipients between 2020 and 2021. A total of 238 patients were contacted by phone at 3, 6, and 12 months postoperatively using the PROMIS 29-Profile. Scores were recorded and computed using the HealthMeasures Scoring Service.PROMIS was available for 174 patients at 3 (n = 58), 6 (n = 57), and 12 months (n = 59). Overall, mean PROMIS scores were 47.6 ± 3, 47.6 ± 3, and 47.6 ± 3 at 3, 6, and 12 months, respectively. Most domains improved postoperatively by 12 months except for anxiety and sleep disturbance measures. The lowest domain in the immediate postoperative period was physical functioning, but this had the closest return to normative population values. Pain interference was above the population reference during the initial postoperative period, improving by 12 months where they were below mean population values. Depression and fatigue scores improved by 6 months and appeared to stabilize by 12 months post-LT. Patients demonstrated increased social participation, and scores were remarkably higher than general population means at each timepoint.LT can impact physical, mental, and social health which, in this setting, remains largely unexplored using PROMIS instruments. We report that although overall patient well being can improve, some mental health domains require further consideration during the postoperative period.

Background Traditionally, curative resection was considered the cornerstone of treatment for perihilar cholangiocarcinoma. More recently, liver transplantation (LT) offered an alternative for patients with unresectable disease. The purpose of this study was to assess our experience with perihilar cholangiocarcinoma and LT. Methods A perihilar cholangiocarcinoma protocol was commenced in 2006 whereby diagnosed patients were enrolled onto an institutional registry for LT consideration. Data on patient progression and oncologic outcomes were assessed. Results Fifty-eight patients were initially enrolled onto the protocol and 38 proceeded to LT following neoadjuvant chemoradiation (mean age 55.6 ± 11.4 years). Mean time to LT was 3.7 ± 2 months and, among those transplanted, 14 (37%) had underlying primary sclerosing cholangitis (PSC). Thirteen (34%) patients developed malignant recurrence and there were no differences in disease recurrence between PSC (n = 3) and non-PSC (n = 10) patients (p = 0.32). Overall patient survival was 91%, 58% and 52% at 1-, 3- and 5-years corresponding with 81%, 52% and 46% graft survival, respectively. Conclusion Rigorous patient selection and chemoradiation treatment algorithms can be highly effective in treating perihilar cholangiocarcinoma. For appropriately selected candidates, LT can provide a 52% 5-year survival for patients who would otherwise have no surgical treatment option.

Background: Thyroid cancer incidence has risen dramatically in the United States since the early 1980s. Although the prevalence of obesity has doubled during this time period, the relationship between obesity and thyroid cancer is uncertain.Methods: We examined the association between body mass index (BMI) and thyroid cancer risk in a pooled analysis of five prospective U.S. studies, including 413,979 women and 434,953 men. Proportional hazards models with attained age as the time metric were adjusted for education, race, marital status, smoking, alcohol intake, and (where appropriate) cohort and sex.Results: Over follow-up (mean = 10.3 years), 768 women and 388 men were diagnosed with thyroid cancer. The risk of thyroid cancer was greater with increasing BMI [per 5 kg/m2: HR in women, 1.16 (95% CI, 1.08–1.24); HR in men, 1.21 (95% CI, 0.97–1.49)]. There was no significant heterogeneity between studies (both P > 0.05). For women and men combined, the HRs for overweight (25.0–29.9 kg/m2) and obesity (≥30 kg/m2) compared with normal-weight (18.5–24.9 kg/m2) were 1.20 (95% CI, 1.04–1.38) and 1.53 (95% CI, 1.31–1.79), respectively. We found no significant effect modification by other factors, and the results did not differ significantly by histologic type. A significant positive association for BMI in young adulthood (ages 18–20) with thyroid cancer risk was also observed [per 5-kg/m2 increase: HR, 1.18 (95% CI, 1.03–1.35)].Conclusion: BMI was positively associated with thyroid cancer risk in both men and women.Impact: Our study provides strong evidence that obesity is an independent risk factor for thyroid cancer. Cancer Epidemiol Biomarkers Prev; 20(3); 464–72. ©2011 AACR.

Background: With over 13 million cancer survivors in the United States today, second cancers are of rapidly growing importance. However, data on nontreatment risk factors for second cancers are sparse. We explored the feasibility of pooling data from cohort studies of cancer incidence to investigate second cancer etiology.Methods: We combined data from five prospective studies including more than 800,000 individuals. We compared study designs and populations; evaluated availability of and ability to harmonize risk factor data; compared incidence and survival for common first primary malignancies and incidence of second primary malignancies; and estimated sample size requirements.Results: Overall, 96,513 incident, first primary malignancies were diagnosed during 1985 to 2009. Incidence rates and survival following the first primary varied among the cohorts, but most of the heterogeneity could be explained by characteristics of the study populations (age, sex, smoking, and screening rates). A total of 7,890 second primary cancers (excluding original primary site) were identified, yielding sufficient statistical power (≥80%) for detecting modest associations with risk of all second cancers among survivors of common first primary malignancies (e.g., colorectal cancer); however, there were insufficient events for studying survivors of rarer cancers or identifying risk factors for specific second cancers.Conclusions: Pooling data from cohort studies to investigate nontreatment risk factors for second primary cancers seems feasible but there are important methodologic issues—some of which are barriers to specific research questions—that require special attention.Impact: Increased understanding of nontreatment risk factors for second cancers will provide valuable prevention and surveillance information. Cancer Epidemiol Biomarkers Prev; 23(8); 1598–608. ©2014 AACR.

Supplementary Table 1 from Obesity and Thyroid Cancer Risk among U.S. Men and Women: A Pooled Analysis of Five Prospective Studies

Characteristics of the participating cohorts

Kaplan-Meier survival curves by prediagnostic dietary calcium intakes, stratified by stage, histologic type, and grade

This file contains Supplementary Tables 1-3. Supplementary Table 1 gives the distribution of prostate cancer cases by subtype included in the pooled Analyses of fruit, vegetable, and mature bean consumption and prostate cancer risk. Supplementary Table 2 gives the results of analyses using all main exposures modeled continuously. Supplementary Table 3 provides information on funding information for all cohort studies included in the pooled analysis.

Background: Lung cancer is the leading cause of cancer death. Little is known about whether prediagnostic nutritional factors may affect survival. We examined the associations of prediagnostic calcium intake from foods and/or supplements with lung cancer survival.Methods: The present analysis included 23,882 incident, primary lung cancer patients from 12 prospective cohort studies. Dietary calcium intake was assessed using food-frequency questionnaires at baseline in each cohort and standardized to caloric intake of 2,000 kcal/d for women and 2,500 kcal/d for men. Stratified, multivariable-adjusted Cox regression was applied to compute hazard ratios (HR) and 95% confidence intervals (CI).Results: The 5-year survival rates were 56%, 21%, and 5.7% for localized, regional, and distant stage lung cancer, respectively. Low prediagnostic dietary calcium intake (Conclusions: This large pooled analysis is the first, to our knowledge, to indicate that low prediagnostic dietary calcium intake may be associated with poorer survival among early-stage lung cancer patients.Impact: This multinational prospective study linked low calcium intake to lung cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(7); 1060–70. ©2017 AACR.

PDF file - 217KB, Supplementary Figure 1. Baseline characteristics of participants for each prospective study, by first primary malignancy diagnosis.

PDF file - 23KB, Supplemental Table 1. Characteristics of five prospective epidemiologic cohort studies in this pooled analysis investigating feasibility of studying risk factors for second cancers. Supplemental Table 2. Population-specific standardized incidence ratios^ (SIRs) for first primary malignancies by cohort. Supplemental Table 3. Age-, sex-, and race-standardized incidence rates^ (per 10,000 person-years) for first primary malignancies by cohort.

Background: Relationships between fruit, vegetable, and mature bean consumption and prostate cancer risk are unclear.Methods: We examined associations between fruit and vegetable groups, specific fruits and vegetables, and mature bean consumption and prostate cancer risk overall, by stage and grade, and for prostate cancer mortality in a pooled analysis of 15 prospective cohorts, including 52,680 total cases and 3,205 prostate cancer–related deaths among 842,149 men. Diet was measured by a food frequency questionnaire or similar instrument at baseline. We calculated study-specific relative risks using Cox proportional hazards regression, and then pooled these estimates using a random effects model.Results: We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. In addition, we observed few statistically significant results for other prostate cancer outcomes. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09. There was no evidence of effect modification for any association by age or body mass index.Conclusions: Results from this large, international, pooled analysis do not support a strong role of collective groupings of fruits, vegetables, or mature beans in prostate cancer.Impact: Further investigation of other dietary exposures, especially indicators of bioavailable nutrient intake or specific phytochemicals, should be considered for prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(8); 1276–87. ©2017 AACR.

BackgroundSurvival benefits of self-reported recreational physical activity (PA) during cancer survivorship are well-documented in common cancer types, yet there are limited data on the associations between accelerometer-derived PA of all domains, sedentary behavior, and mortality in large, diverse cohorts of cancer survivors.MethodsParticipants included adults who reported a cancer diagnosis in the National Health and Nutrition Examination Survey and wore an accelerometer for up to 7 days in 2003-2006. Participants were followed for subsequent mortality through 2015. We examined the association of light PA, moderate to vigorous PA, total PA, and sedentary behavior, with all-cause mortality. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographics and health indicators.ResultsA total of 480 participants (mean age of 68.8 years [SD = 12.4] at the time of National Health and Nutrition Examination Survey assessment) reported a history of cancer. A total of 215 deaths occurred over the follow-up period. For every 1-h/d increase in light PA and moderate to vigorous PA (MVPA), cancer survivors had 49% (HR = 0.51, 95% CI = 0.34 to 0.76) and 37% (HR = 0.63 , 95% CI = 0.40 to 0.99) lower hazards of all-cause mortality, respectively. Total PA demonstrated similar associations with statistically significantly lower hazards of death for each additional hour per day (HR = 0.68, 95% CI = 0.54 to 0.85), as did every metabolic equivalents of task-hour per day increase in total PA estimations of energy expenditure (HR = 0.88, 95% CI = 0.82 to 0.95). Conversely, more sedentary time (1 h/d) was not associated with statistically significantly higher hazards (HR = 1.08, 95% CI = 0.94 to 1.23).ConclusionsThese findings reinforce the current recommendations for cancer survivors to be physically active and underscore the continued need for widespread PA promotion for long-term survival in older cancer survivors.

BACKGROUND Although fruit and vegetable intake during adolescence, a potentially sensitive time period for prostate cancer (PCa) development, has been proposed to protect against PCa risk, few studies have investigated the role of adolescent plant product intake in PCa development. METHODS Intake of various vegetables, fruit, and grains by males at ages 12-13 y was examined in relation to later PCa risk and mortality in the NIH-AARP Diet and Health Study. Cox proportional hazards regression was used to calculate HRs and 95% CIs of nonadvanced (n = 14,238) and advanced (n = 2,170) PCa incidence and PCa mortality (n = 760) during 1,729,896 person-years of follow-up. RESULTS None of the plant products examined were associated consistently with all PCa outcomes. However, greater adolescent intakes of tomatoes (P-trend = 0.004) and nonstarch vegetables (P-trend = 0.025) were associated with reduced risk of nonadvanced PCa, and greater intakes of broccoli (P-trend = 0.050) and fruit juice (P-trend = 0.019-0.025) were associated with reduced risk of advanced PCa and/or PCa mortality. Positive trends were also observed for greater intakes of fruit juice (P-trend = 0.002), total fruit (P-trend = 0.014), and dark bread (P-trend = 0.035) with nonadvanced PCa risk and for greater intakes of legumes (P-trend

Background Adolescent intake of animal products has been proposed to contribute to prostate cancer (PCa) development because of its potentially carcinogenic constituents and influence on hormone levels during adolescence. Methods We used data from 159,482 participants in the NIH-AARP Diet and Health Study to investigate associations for recalled adolescent intake of red meat (unprocessed beef and processed red meat), poultry, egg, canned tuna, animal fat and animal protein at ages 12-13 years with subsequent PCa risk and mortality over 14 years of follow-up. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total (n = 17,349), advanced (n = 2,297) and fatal (n = 804) PCa. Results Suggestive inverse trends were observed for adolescent unprocessed beef intake with risks of total, advanced and fatal PCa (multivariable-adjusted P-trends = 0.01, 0.02 and 0.04, respectively). No consistent patterns of association were observed for other animal products by PCa outcome. Conclusion We found evidence to suggest that adolescent unprocessed beef intake, or possibly a correlate of beef intake, such as early-life socioeconomic status, may be associated with reduced risk and mortality from PCa. Additional studies with further early-life exposure information are warranted to better understand this association.

A cluster of factors affects nutritional status among adolescent girls in low- and middle-income countries (LMICs). We investigated the association between school attendance and diet quality among 498 rural adolescent girls (352 attending and 146 not attending school) in Tecpan, Guatemala. In a cross-sectional study, we collected sociodemographic and anthropometric data and characterized the dietary intake using a Food Frequency Questionnaire. We then calculated diet quality using the Healthy Eating Score (HES). Multiple linear regression models were conducted to evaluate the effects of school attendance on diet quality. We found that the overall diet quality among the study participants was poor, according to the HES. However, those who attended school had significantly higher intakes of vitamin A-rich fruits and vegetables (P = 0.04), other fruits (P = 0.01), and milk and milk products (P = 0.004), but a higher intake of fast foods, chips, and saturated fatty acids (P < 0.001). Furthermore, the effects of school attendance on diet quality were significant after adjusting for sociodemographic and lifestyle factors (β coefficient = -1.70, 95% CI: -3.30 to -0.11) but was attenuated when further adjusted for weight status (β coefficient = -1.58, 95% CI: -3.17 to 0.02). Our findings suggest that diet quality among girls in rural Guatemala is poor, particularly among those who do not attend school. To advance our understanding of adolescent diet in LMICs, future studies should include adolescents who are out of school.

PURPOSE: Although a growing body of evidence supports an early-life contribution to prostate cancer (PCa) development, few studies have investigated early-life diet, and only three have examined early-life dairy product intake, a promising candidate risk factor because of its known/suspected influence on insulin-like growth factor levels and height. METHODS: We used recalled dietary data from 162,816 participants in the NIH-AARP Diet and Health Study to investigate associations for milk, cheese, ice cream, total dairy, and calcium intake at ages 12–13 years with incident total (n=17,729), advanced (n=2,348), and fatal PCa (n=827) over 14 years of follow-up. We calculated relative risks (RRs) and 95% confidence intervals (CIs) by Cox proportional hazards regression. RESULTS: We observed suggestive positive trends for milk, dairy, and calcium intake with total and/or advanced PCa (p-trends=0.016–0.148). These trends attenuated after adjustment for additional components of adolescent diet, particularly red meat and vegetables/potatoes. In contrast, suggestive inverse trends were observed for cheese and ice cream intake with total and/or advanced PCa (p-trends=0.043–0.153), and for milk, dairy, and calcium intake with fatal PCa (p-trend=0.045–0.117). CONCLUSION: Although these findings provide some support for a role of adolescent diet in increasing PCa risk, particularly for correlates of milk intake or overall dietary patterns, our protective findings for cheese and ice cream intake with PCa risk and mortality, and for all dairy products with PCa mortality suggest alternative explanations, such as the influence of early-life socioeconomic status, and increased PCa screening, earlier detection, and better PCa care.

Although adolescent diet has been proposed to contribute to prostate cancer (PCa) development, no studies have investigated the relation between adolescent dietary patterns and PCa risk or mortality.Using data from 164,079 men in the NIH-AARP Diet and Health Study, we performed factor analysis to identify dietary patterns at ages 12-13 years and then used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of total (n = 17,861), non-advanced (n = 15,499), advanced (n = 2362), and fatal PCa (n = 832).Although not entirely consistent across analyses, a higher adolescent plant-based pattern (characterised by vegetables, fruits, and dark bread) score was associated with slightly reduced risks of total (fully adjusted HRWe found evidence to support a modest, protective role for a plant-based dietary pattern during adolescence on PCa risk. If confirmed in future studies, our findings may help to inform the development of new, primary prevention strategies for PCa.

Circadian rhythm disruptors (e.g., night-shift work) are risk factors for breast cancer, however studies on their association with prognosis is limited. A small but growing body of research suggests that altered sleep patterns and eating behaviours are potential mechanistic links between circadian rhythm disruptors and breast cancer. We therefore systematically summarised literature examining the influence of circadian rhythm disrupting behaviours on cancer outcomes in women with breast cancer.A systematic search of five databases from inception to January 2021 was conducted. Original research published in English, assessing the relationship between post-diagnosis sleep patters and eating behaviours, and breast cancer outcomes were considered. Risk of bias was assessed using the Newcastle-Ottawa Assessment Scale for Cohort Studies.Eight studies published original evidence addressing sleep duration and/or quality (k = 7) and, eating time and frequency (k = 1). Longer sleep duration (≥ 9 h versus [referent range] 6-8 h) was consistently associated with increased risk of all outcomes of interest (HR range: 1.37-2.33). There was limited evidence to suggest that measures of better sleep quality are associated with lower risk of all-cause mortality (HR range: 0.29-0.97). Shorter nightly fasting duration ( 13 h versus ≥ 13 h) was associated with higher risk of all breast cancer outcomes (HR range: 1.21-1.36).Our review suggests that circadian rhythm disrupting behaviours may influence cancer outcomes in women with breast cancer. While causality remains unclear, to further understand these associations future research directions have been identified. Additional well-designed studies, examining other exposures (e.g., light exposure, temporal eating patterns), biomarkers, and patient-reported outcomes, in diverse populations (e.g., breast cancer subtype-specific, socio-demographic diversity) are warranted.

Few biomarker-based validation studies have examined error in online self-report dietary assessment instruments, and food records (FRs) have been considered less than food frequency questionnaires (FFQs) and 24-hour recalls (24HRs). We investigated measurement error in online and paper-based FFQs, online 24HRs, and paper-based FRs in 3 samples drawn primarily from 3 cohorts, comprising 1,393 women and 1,455 men aged 45–86 years. Data collection occurred from January 2011 to October 2013. Attenuation factors and correlation coefficients between reported and true usual intake for energy, protein, sodium, potassium, and respective densities were estimated using recovery biomarkers. Across studies, average attenuation factors for energy were 0.07, 0.07, and 0.19 for a single FFQ, 24HR, and FR, respectively. Correlation coefficients for energy were 0.24, 0.23, and 0.40, respectively. Excluding energy, the average attenuation factors across nutrients and studies were 0.22 for a single FFQ, 0.22 for a single 24HR, and 0.51 for a single FR. Corresponding correlation coefficients were 0.31, 0.34, and 0.53, respectively. For densities (nutrient expressed relative to energy), the average attenuation factors across studies were 0.37, 0.17, and 0.50, respectively. The findings support prior research suggesting different instruments have unique strengths that should be leveraged in epidemiologic research.

BackgroundLittle is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisure-time physical activity (LTPA) with all-cause and lung cancer–specific mortality among incident lung cancer patients.MethodsUsing self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum recommended range). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) for all-cause and lung cancer–specific mortality after adjustment for major prognostic factors and lifetime smoking history.ResultsOf 20 494 incident lung cancer patients, 16 864 died, including 13 596 deaths from lung cancer (overall 5-year relative survival rate = 20.9%, 95% CI = 20.3% to 21.5%). Compared with inactivity, prediagnosis LTPA of more than 8.3 MET-h per week was associated with a lower hazard of all-cause mortality (multivariable-adjusted HR = 0.93, 95% CI = 0.88 to 0.99), but not with lung cancer–specific mortality (multivariable-adjusted HR = 0.99, 95% CI = 0.95 to 1.04), among the overall population. Additive interaction was found by tumor stage (Pinteraction = .008 for all-cause mortality and .003 for lung cancer–specific mortality). When restricted to localized cancer, prediagnosis LTPA of at least 8.3 MET-h per week linked to 20% lower mortality: multivariable-adjusted HRs were 0.80 (95% CI = 0.67 to 0.97) for all-cause mortality and 0.80 (95% CI = 0.65 to 0.99) for lung cancer–specific mortality.ConclusionsRegular participation in LTPA that met or exceeded the minimum Physical Activity Guidelines was associated with reduced hazards of mortality among lung cancer patients, especially those with early stage cancer.

This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Short Talks from Proffered Abstracts section (PR014) of the Conference Proceedings. Citation Format: Tuo Lan, Mei Wang, AnnaLynn M. Williams, Matthew J. Ehrhardt, Emily R. Finch, Jennifer Q. Lanctot, Shu Jiang, Kevin R. Krull, Gregory T. Armstrong, Melissa M. Hudson, Graham A. Colditz, Leslie Robison, Kirsten K. Ness, Yikyung Park. Sugar Intake and premature aging in adult survivors of childhood cancer in the St. Jude Lifetime (SJLIFE) Cohort [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B004.

Background: Childhood cancer survivors are a growing population at elevated risk for premature aging and age-related chronic health conditions (CHCs) compared to the general population. In the general population, diet affects many hallmarks of aging, including inflammation, metabolic dysfunctions, and molecular and epigenetic changes. We examined associations between dietary patterns and risk of premature aging in adult survivors of childhood cancer. Methods: Adult survivors (18-65 years old, mean [SD] age 31 [8.4] years) of childhood cancer enrolled in SJLIFE between 2007 and 2017 completed a 110-item food frequency questionnaire at enrollment (n=2,904). Sociodemographic, cancer, cancer treatments, and health history were abstracted from medical records; CHCs were clinically validated. Factor analysis was performed to identify dietary patterns specific to the study population. Premature aging was assessed using the Deficit Accumulation Index (DAI) based on 45 age-related CHCs and categorized into low (0.35) aging risk groups. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multinomial logistic regressions adjusting for potential confounders, such as sociodemographics, health behaviors, and cancer treatments. Individuals’ factor scores of each pattern were grouped into quintiles, and a median score of each quintile was entered as a continuous term in regression models. Results: 20% of survivors were at medium- and 8% were at high-risk for premature aging. Survivors at high-risk for premature aging were more likely to be female, smokers, have low socioeconomic status, and have received radiation therapy to head and neck, chest, spine, or abdomen compared to those at low premature aging risk. Three dietary patterns were identified: 1) plant-based, 2) fast-food, and 3) Western contemporary. A plant-based diet was characterized by greater intakes of vegetables, fruits, whole grains, and fish. A higher plant-based diet pattern score was associated with a lower risk of premature aging (OR=0.76, 95% CI: 0.62-0.94 for the high-risk group; OR=0.91, 95% CI: 0.79-1.04 for the medium-risk group). A fast-food diet was characterized by greater intakes of sweets, processed meat, refined grains, potato, high-fat dairy, and soda. A fast-food diet was related to a non-significant increased risk of premature aging (OR=1.20, 95% CI: 0.91-1.57 for the high-risk group; OR=1.18, 95% CI: 0.98-1.43 for the medium-risk group). A Western contemporary diet characterized by greater intakes of meat, pasta/rice, pizza, Mexican food, and fruit juice was associated with an increased risk of premature aging (OR=1.36, 95% CI: 1.05-1.78 for the high-risk group; OR=1.04, 95% CI: 0.87-1.26 for the medium-risk group). Conclusion: Our findings suggest that diet plays a role in aging, and a diet rich in plant-based foods may mitigate the risk of premature aging in childhood cancer survivors. Citation Format: Yikyung Park, Mei Wang, Tuo Lan, AnnaLynn M. Williams, Matthew J. Ehrhardt, Emily R. Finch, Jennifer Q. Lanctot, Shu Jiang, Kevin R. Krull, Gregory T. Armstrong, Melissa M. Hudson, Graham A. Colditz, Leslie Robison, Kirsten K. Ness. Cancer survivor-specific dietary patterns and risk of premature aging in adult survivors of childhood cancer: St. Jude Lifetime (SJLIFE) Cohort [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A019.

Background: In the general population, sugar intake is associated with a wide range of adverse health conditions related to premature aging, including obesity, diabetes, and cardiovascular disease. Childhood cancer survivors are at increased risk of premature aging and mortality compared to their healthy peers and may be especially vulnerable to adverse consequences of excess sugar intake. Objective: To examine the association between sugar and sugar-sweetened beverage intake and premature aging in childhood cancer survivors. Method: A total of 3,322 adult survivors of childhood cancer (age range 18-65 years; mean age: 31 years) in SJLIFE self-reported their typical diet using the 110-item Block Food Frequency Questionnaire. Added sugars included all sugars added to foods during preparation or processing. Total sugar-sweetened beverages are the sum of regular and diet soda and fruit-flavored drinks. Survivors’ sociodemographics, cancer histories, and health conditions were abstracted from medical records. Premature aging was assessed using the Deficit Accumulation Index (DAI) that was a ratio of the number of age-related chronic health conditions each survivor had out of 45 conditions total. The DAI was categorized into low (0.35) aging risk groups. Multinomial logistic regressions (reference: low aging risk group) adjusting for confounders, including sociodemographics, lifestyle factors, cancer treatments, and overall diet quality, were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Survivors’ average total sugar intake was 120 g/day and added sugar intake was 71 g/day. 41% of survivors consumed sugar-sweetened beverages ≥1 time/day, and 26% consumed soda daily; 75% of soda consumed was regular (vs. diet). Survivors with higher consumption of sugar and sugar-sweetened beverages were more likely to be non-Hispanic Black and have lower educational attainment and income. Total sugar intake was associated with a significantly increased risk of premature aging (per 25 g/1,000 kcal increment, OR=1.31 [95% CI: 1.00-1.70] in the medium-risk group; OR=1.52 [95% CI: 1.03-2.25] in the high-risk group). Added sugar intake was associated with a 19% (OR=1.19, 95% CI: 1.07-1.31, per 20 g/1,000 kcal increment) and an 18% (OR=1.18, 95% CI: 1.02-1.37) increased risk of premature aging in the medium- and high-risk group, respectively. Consuming ≥2 servings/day (vs. ≤ 1/week) of total sugar-sweetened beverage was also related to an increased risk of premature aging (OR=1.54 [95% CI: 0.83-2.83] in the medium-risk group; OR=6.71 [95% CI: 2.95-15.2] in the high-risk group). Regular soda, but not diet soda, consumption was associated with premature aging risk. Conclusion: Higher consumption of sugar and sugar-sweetened beverages was associated with an increased risk of premature aging in childhood cancer survivors. Intervention efforts to reduce sugar intake among this vulnerable population are needed. Citation Format: Tuo Lan, Mei Wang, AnnaLynn M. Williams, Matthew J. Ehrhardt, Emily R. Finch, Jennifer Q. Lanctot, Shu Jiang, Kevin R. Krull, Gregory T. Armstrong, Melissa M. Hudson, Graham A. Colditz, Leslie Robison, Kirsten K. Ness, Yikyung Park. Sugar Intake and premature aging in adult survivors of childhood cancer in the St. Jude Lifetime (SJLIFE) Cohort [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr PR014.

BACKGROUND Advanced glycation end products (AGEs) are reactive metabolites produced as a by-product of sugar metabolism and are consumed through the diet in high-fat and highly processed foods. They are associated with chronic inflammatory diseases, and evidence suggests that they play a role in carcinogenesis. The authors evaluated the association of dietary AGE intake and the risk of postmenopausal invasive breast cancer. METHODS This was a prospective cohort study of 183,548 postmenopausal women in the National Institutes of Health-AARP Diet and Health Study. The main outcome was incident invasive breast cancer. AGE intake was estimated from food-frequency questionnaires. Incident breast cancer cases were identified through state cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals for developing breast cancer according to AGE intake quintiles. Multivariable regression models were adjusted for breast cancer risk factors. RESULTS The mean follow-up was 12.8 years, and 9851 breast cancers (1978 advanced stage) were identified. The median AGE daily intake was 5932 kilo units per 100 kilocalories (KU/1000 kcal). Women with higher intake tended to have lower education levels, higher body mass index, less physical activity, were current smokers, and had higher fat and meat intake. The highest quintile of AGE intake (compared with the lowest) was associated with an increased risk of breast cancer (HR, 1.09; 95% CI, 1.02-1.16; P = .03) after adjusting for breast cancer risk factors and particularly was associated with 37% of advanced-stage tumors (HR, 1.37; 95% CI, 1.09-1.74; P

Ovarian cancer is the deadliest gynecologic malignancy, yet the effects on survival of modifiable pre-diagnosis lifestyle factors, such as obesity and physical activity, remain largely unexplored. Our objective was to evaluate the effect of pre-diagnosis BMI and physical activity on ovarian cancer mortality using prospectively collected data.Data on women who developed ovarian cancer after enrollment into the NIH-AARP Diet and Health Study were analyzed. Cancer incidence was ascertained through linkage state cancer registries and consisted of 741 cases of epithelial ovarian cancer.Higher pre-diagnosis BMI was associated with increased overall and ovarian cancer-specific mortality. Comparing women with BMI 25-29.9, 30-34.9 and ≥ 35 to normal weight women, the HRs of overall mortality were 1.18 (95%CI 0.96-1.45), 1.05 (0.82-1.36) and 1.59 (1.14-2.18, p-trend = 0.02). The findings were similar for ovarian cancer-specific mortality comparing women with BMI ≥ 35 to normal weight women (BMI25) with a HR of 1.47 (95%CI 1.03-2.09, p-trend 0.08). Pre-diagnosis physical activity was not associated with mortality, with HRs for overall mortality of 1.06 (95%CI 0.79-1.43), 0.94 (0.72-1.23), 0.98 (0.76-1.25), and 0.98 (0.75-1.28, p-trend = 0.91), comparing women who engaged in vigorous physical activity 1-3 times/month, 1-2 times/week, 3-4 times/week and 5 times/week, respectively, with those who never/rarely engaged in such activity.Women who were obese before developing ovarian cancer had increased mortality than those who were normal weight, but physical activity before diagnosis was not associated with mortality in this study population. These results suggest that maintaining a healthy weight is a powerful preventative tool.

Background Ambient air pollution is a modifiable risk factor for cardiovascular disease, yet uncertainty remains about the size of risks at lower levels of fine particulate matter (PM2.5) exposure which now occur in the USA and elsewhere. Methods We investigated the relationship of ambient PM2.5 exposure with cause-specific cardiovascular disease mortality in 565 477 men and women, aged 50 to 71 years, from the National Institutes of Health-AARP Diet and Health Study. During 7.5 x 106 person-years of follow up, 41 286 cardiovascular disease deaths, including 23 328 ischaemic heart disease (IHD) and 5894 stroke deaths, were ascertained using the National Death Index. PM2.5 was estimated using a hybrid land use regression (LUR) geostatistical model. Multivariate Cox regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CI). Results Each increase of 10 μg/m3 PM2.5 (overall range, 2.9–28.0 μg/m3) was associated, in fully adjusted models, with a 16% increase in mortality from ischaemic heart disease [hazard ratio (HR) 1.16; 95% CI 1.09-1.22] and a 14% increase in mortality from stroke (HR 1.14; CI 1.02-1.27). Compared with PM2.5 exposure Conclusions Long-term exposure to fine particulate air pollution is associated with ischaemic heart disease and stroke mortality, with excess risks occurring in the range of and below the present US long-term standard for ambient exposure to PM2.5 (12 µg/m3), indicating the need for continued improvements in air pollution abatement for CVD prevention.

ImportanceCervical spinal cord injury (SCI) causes devastating loss of upper extremity function and independence. Nerve transfers are a promising approach to reanimate upper limbs; however, there remains a paucity of high-quality evidence supporting a clinical benefit for patients with tetraplegia.ObjectiveTo evaluate the clinical utility of nerve transfers for reanimation of upper limb function in tetraplegia.Design, Setting, and ParticipantsIn this prospective case series, adults with cervical SCI and upper extremity paralysis whose recovery plateaued were enrolled between September 1, 2015, and January 31, 2019. Data analysis was performed from August 2021 to February 2022.InterventionsNerve transfers to reanimate upper extremity motor function with target reinnervation of elbow extension and hand grasp, pinch, and/or release.Main Outcomes and MeasuresThe primary outcome was motor strength measured by Medical Research Council (MRC) grades 0 to 5. Secondary outcomes included Sollerman Hand Function Test (SHFT); Michigan Hand Outcome Questionnaire (MHQ); Disabilities of Arm, Shoulder, and Hand (DASH); and 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS) scores. Outcomes were assessed up to 48 months postoperatively.ResultsTwenty-two patients with tetraplegia (median age, 36 years [range, 18-76 years]; 21 male [95%]) underwent 60 nerve transfers on 35 upper limbs at a median time of 21 months (range, 6-142 months) after SCI. At final follow-up, upper limb motor strength improved significantly: median MRC grades were 3 (IQR, 2.5-4; P = .01) for triceps, with 70% of upper limbs gaining an MRC grade of 3 or higher for elbow extension; 4 (IQR, 2-4; P P Conclusions and RelevanceIn this prospective case series, nerve transfer surgery was associated with improvement of upper limb motor strength and functional independence in patients with tetraplegia. Nerve transfer is a promising intervention feasible in both subacute and chronic SCI.

Nonalcoholic fatty liver disease (NAFLD) is a global public health crisis that affects one quarter of the world population.sup1/supPreventing either cardiometabolic or liver-related complications by achieving weight loss and resolving hepatic steatosis would be the central goal of a NAFLD screening program in the primary care setting. Despite the overwhelming prevalence and the multimodal impact on health posed by NAFLD, specialty society guidelines do not recommend screening for NAFLD in the general population,sup2/suppartly owing to the as-yet unproven cost benefit.

BACKGROUND: Breast cancer survivors are at increased risk for developing second primary cancers compared with the general population. Little is known about whether body mass index (BMI) increases this risk. We examined the association between BMI and second cancers among women with incident invasive breast cancer. METHODS: This retrospective cohort included 6481 patients from Kaiser Permanente Colorado and Washington of whom 822 (12.7%) developed a second cancer (mean follow-up was 88.0 months). BMI at the first cancer was extracted from the medical record. Outcomes included: 1) all second cancers, 2) obesity-related second cancers, 3) any second breast cancer, and 4) estrogen receptor–positive second breast cancers. Multivariable Poisson regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for second cancers associated with BMI adjusted for site, diagnosis year, treatment, demographic, and tumor characteristics. RESULTS: The mean age at initial breast cancer diagnosis was 61.2 (SD = 11.8) years. Most cases were overweight (33.4%) or obese (33.8%) and diagnosed at stage I (62.0%). In multivariable models, for every 5 kg/m(2) increase in BMI, the risk of any second cancer diagnosis increased by 7% (RR = 1.07, 95% CI = 1.01 to 1.14); 13% (RR = 1.13, 95% CI = 1.05 to 1.21) for obesity-related cancers, 11% (RR = 1.11, 95% CI = 1.02 to 1.21) for a second breast cancer, and 15% (RR = 1.15, 95% CI = 1.04 to 1.27) for a second estrogen receptor–positive breast cancer. CONCLUSIONS: We observed a statistically significant increased risk of second cancers associated with increasing BMI. These findings have important public health implications given the prevalence of overweight and obesity in breast cancer survivors and underscore the need for effective prevention strategies.