Faculty Bibliography

BACKGROUND:Patients with prostate cancer suffer significant sexual dysfunction after treatment which negatively affects them and their partners psychologically, and strain their relationships. AIM/OBJECTIVE:We convened an international panel with the aim of developing guidelines that will inform clinicians, patients and partners about the impact of prostate cancer therapies (PCT) on patients' and partners' sexual health, their relationships, and about biopsychosocial rehabilitation in prostate cancer (PC) survivorship. METHODS:The guidelines panel included international expert researchers and clinicians, and a guideline methodologist. A systematic review of the literature, using the Ovid MEDLINE, Scopus, CINAHL, PsychINFO, LGBT Life, and Embase databases was conducted (1995-2022) according to the Cochrane Handbook for Systematic Reviews of Interventions. Study selection was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Each statement was assigned an evidence strength (A-C) and a recommendation level (strong, moderate, conditional) based on benefit/risk assessment. Data synthesis included meta-analyses of studies deemed of sufficient quality (3), using A Measurement Tool to Assess Systematic Reviews (AMSTAR). OUTCOMES/RESULTS:Guidelines for sexual health care for patients with prostate cancer were developed, based on available evidence and the expertise of the international panel. RESULTS:The guidelines account for patients' cultural, ethnic, and racial diversity. They attend to the unique needs of individuals with diverse sexual orientations and gender identities. The guidelines are based on literature review, a theoretical model of sexual recovery after PCT, and 6 principles that promote clinician-initiated discussion of realistic expectations of sexual outcomes and mitigation of sexual side-effects through biopsychosocial rehabilitation. Forty-seven statements address the psychosexual, relationship, and functional domains in addition to statements on lifestyle modification, assessment, provider education, and systemic challenges to providing sexual health care in PC survivorship. CLINICAL IMPLICATIONS/CONCLUSIONS:The guidelines provide clinicians with a comprehensive approach to sexual health care for patients with prostate cancer. STRENGTHS & LIMITATIONS/UNASSIGNED:The strength of the study is the comprehensive evaluation of existing evidence on sexual dysfunction and rehabilitation in prostate cancer that can, along with available expert knowledge, best undergird clinical practice. Limitation is the variation in the evidence supporting interventions and the lack of research on issues facing patients with prostate cancer in low and middle-income countries. CONCLUSION/CONCLUSIONS:The guidelines document the distressing sexual sequelae of PCT, provide evidence-based recommendations for sexual rehabilitation and outline areas for future research. Wittmann D, Mehta A, McCaughan E, et al. Guidelines for Sexual Health Care for Prostate Cancer Patients: Recommendations of an International Panel. J Sex Med 2022;19:1655-1669.

Chronic kidney disease (CKD) is defined by a low glomerular filtration rate or high albuminuria, and affects 15-20% of adults globally. CKD increases the risk of various adverse outcomes, but cardiovascular disease (CVD) is of particular relevance because it is the leading cause of death in this clinical population. CKD is associated with several CVD outcomes, including coronary heart disease, stroke, peripheral artery disease, arrhythmias, heart failure and venous thrombosis. Notably, CKD is particularly strongly associated with severe CVD outcomes such as CVD mortality, heart failure and lower extremity amputations. This broad impact of CKD on the cardiovascular system probably reflects the involvement of several pathophysiological mechanisms that link CKD to CVD development - shared risk factors (for example, diabetes and hypertension), changes in bone mineral metabolism, anaemia, volume overload, inflammation and the presence of uraemic toxins. Understanding the status of CKD is crucial for appropriate CVD risk prediction in CKD populations. However, major clinical guidelines are not consistent in their incorporation of CKD measures for CVD risk prediction. Mitigating CVD risk in patients with CKD effectively requires multidisciplinary care that involves nephrologists, cardiologists and other health professionals, as well as further work to address current research and implementation gaps.

Human papillomavirus (HPV) is currently linked to almost 35,000 new cases of cancer in women and men each year in the United States. Gardasil-9 (Merck & Company), the only HPV vaccine now available in the United States, is nearly 100% effective at preventing precancers caused by oncogenic HPV types. In the United States, however, only about one half of adolescents are up to date with HPV vaccination. It is well known that health care clinicians' recommendations play a significant role in parents' decisions regarding HPV vaccination. A growing body of literature examines specific communication strategies for promoting uptake of the HPV vaccine. A comprehensive review of the evidence for each of these strategies is needed. The authors searched the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, and Web of Science Complete databases for original articles with a defined clinician communication strategy and an outcome of HPV vaccine uptake or intention to vaccinate (PROSPERO registry no. CRD42020107602). In total, 46 studies were included. The authors identified two main strategies with strong evidence supporting their positive impact on vaccine uptake: strong recommendation and presumptive recommendation. Determinations about a causal relationship were limited by the small numbers of randomized controlled trials. There is also opportunity for more research to determine the effects of motivational interviewing and cancer-prevention messaging.

BACKGROUND:Gender diversity in young adolescents is understudied outside of referral clinics. We investigated gender diversity in an urban, ethnically diverse sample of adolescents from the general population and examined predictors and associated mental health outcomes. METHODS:The study was embedded in Generation R, a population-based cohort of children born between 2002 and 2006 in Rotterdam, the Netherlands (n = 5727). At ages 9-11 and 13-15 years, adolescents and/or their parents responded to two questions addressing children's contentedness with their assigned gender, whether they (a) 'wished to be the opposite sex' and (b) 'would rather be treated as someone from the opposite sex'. We defined 'gender-variant experience' when either the parent or child responded with 'somewhat or sometimes true' or 'very or often true'. Mental health was assessed at 13-15 years, using the Achenbach System of Empirically Based Assessment. RESULTS:Less than 1% of the parents reported that their child had gender-variant experience, with poor stability between 9-11 and 13-15 years. In contrast, 4% of children reported gender-variant experience at 13-15 years. Adolescents who were assigned female at birth reported more gender-variant experience than those assigned male. Parents with low/medium educational levels reported more gender-variant experience in their children than those with higher education. There were positive associations between gender-variant experience and symptoms of anxiety, depression, somatic complaints, rule-breaking, and aggressive behavior as well as attention, social, and thought problems. Similar associations were observed for autistic traits, independent of other mental difficulties. These associations did not differ by assigned sex at birth. CONCLUSIONS:Within this population-based study, adolescents assigned females were more likely to have gender-variant experience than males. Our data suggest that parents may not be aware of gender diversity feelings in their adolescents. Associations between gender diversity and mental health symptoms were present in adolescents.

OBJECTIVES/OBJECTIVE:To examine racial and ethnic differences in maternal social support in infancy and the relationship between social support and mother-infant health behaviors. METHODS:Secondary analysis of baseline data from a multisite obesity prevention trial that enrolled mothers and their two-month-old infants. Behavioral and social support data were collected via questionnaire. We used modified Poisson regression to determine association between health behaviors and financial and emotional social support, adjusted for sociodemographic characteristics. RESULTS:826 mother-infant dyads (27.3% Non-Hispanic Black, 18.0% Non-Hispanic White, 50.1% Hispanic and 4.6% Non-Hispanic Other). Half of mothers were born in the U.S.; 87% were Medicaid-insured. There were no racial/ethnic differences in social support controlling for maternal nativity. U.S.-born mothers were more likely to have emotional and financial support (rate ratio [RR] 1.14 95% confidence interval [CI]: 1.07, 1.21 and RR 1.23 95% CI: 1.11, 1.37, respectively) versus mothers born outside the U.S. Mothers with financial support were less likely to exclusively feed with breast milk (RR 0.62; 95% CI: 0.45, 0.87) yet more likely to have tummy time ≥12min (RR 1.28; 95% CI: 1.02, 1.59) versus mothers without financial support. Mothers with emotional support were less likely to report feeding with breast milk (RR 0.82; 95% CI: 0.69, 0.97) versus mothers without emotional support. CONCLUSIONS:Nativity, not race or ethnicity, is a significant determinant of maternal social support. Greater social support was not universally associated with healthy behaviors. Interventions may wish to consider the complex nature of social support and population-specific social support needs.

RATIONALE & OBJECTIVE/UNASSIGNED:The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on hospitalizations in general and on dialysis patients in particular. This study modeled the impact of COVID-19 on hospitalizations of dialysis patients in 2020. STUDY DESIGN/UNASSIGNED:Retrospective cohort study. SETTING & PARTICIPANTS/UNASSIGNED:Medicare patients on dialysis in calendar year 2020. PREDICTORS/UNASSIGNED:COVID-19 status was divided into 4 stages: COVID1 (first 10 days after initial diagnosis), COVID2 (extends until the Post-COVID stage), Post-COVID (after 21 days with no COVID-19 diagnosis), and Late-COVID (begins after a hospitalization with a COVID-19 diagnosis); demographic and clinical characteristics; and dialysis facilities. OUTCOME/UNASSIGNED:The sequence of hospitalization events. ANALYTICAL APPROACH/UNASSIGNED:A proportional rate model with a nonparametric baseline rate function of calendar time on the study population. RESULTS/UNASSIGNED:A total of 509,609 patients were included in the study, 63,521 were observed to have a SARS-CoV-2 infection, 34,375 became Post-COVID, and 1,900 became Late-COVID. Compared with No-COVID, all 4 stages had significantly greater adjusted risks of hospitalizations with relative rates of 18.50 (95% CI, 18.19-18.81) for COVID1, 2.03 (95% CI, 1.99-2.08) for COVID2, 1.37 (95% CI, 1.35-1.40) for Post-COVID, and 2.00 (95% CI, 1.89-2.11) for Late-COVID. LIMITATIONS/UNASSIGNED:For Medicare Advantage patients, we only had inpatient claim information. The analysis was based on data from the year 2020, and the effects may have changed due to vaccinations, new treatments, and new variants. The COVID-19 effects may be somewhat overestimated due to missing information on patients with few or no symptoms and possible delay in COVID-19 diagnosis. CONCLUSIONS/UNASSIGNED:We discovered a marked time dependence in the effect of COVID-19 on hospitalization of dialysis patients, beginning with an extremely high risk for a relatively short period, with more moderate but continuing elevated risks later, and never returning to the No-COVID level.

Background Chimeric antigen receptor (CAR) T-cell therapy has shown clinical efficacy in hematologic cancers, but success is limited in solid tumors due to a lack of tumor-specific targets that distinguish cancer from normal cells and an immunosuppressive tumor microenvironment.1 Integrating synthetic biology and comprehensive molecular profiling of tumors may provide active and tolerable approaches to CAR T-cell therapy in patients with solid tumors. Human leukocyte antigen (HLA) loss of heterozygosity (LOH) in tumors offers a definitive tumor vs normal discriminator target for CAR T-cell therapy.2 The Tmod platform3,4 is a modular logic-gated CAR T system comprising different versions including a carcinoembryonic antigen (CEA)- or mesothelin (MSLN)-targeting CAR activator and a separate blocker receptor targeting HLA-A*02 or other HLA alleles to protect normal cells. Compared with existing immunohistochemistry (IHC) tests, Tempus xT-Onco is a standard-of-care next-generation sequencing (NGS) assay5 that detects somatic alterations including HLA LOH and generates whole transcriptome RNA data (eg, CEA or MSLN expression) and a tumor immune infiltration profile, which can effectively identify patients appropriate for Tmod CAR T-cell therapy. Methods HLA LOH in solid tumors was assessed with paired germline and somatic DNA sequencing. Common driver mutations, microsatellite instability status, and tumor mutational burden were examined in HLA-A LOH or HLA-A intact cohorts. Tumor expression of CEA and MSLN was evaluated via RNA sequencing and compared with immunohistochemistry (IHC) results. Results A total of 21,053 tumor samples in the Tempus database were compared with their matched-normal samples. HLA-A LOH was detected in 16% of 10,867 advanced solid tumors (table 1) and similar LOH frequencies were observed among common HLA-A alleles. Clinical factors and molecular biomarkers were similar between HLA-A LOH and HLA-A intact cohorts. High CEA expression was seen in IHC-positive patients. Conclusions The frequency of HLA-A LOH in solid tumors in the Tempus database is similar to that reported in the Cancer Genome Atlas.6 Tempus xT-Onco reliably detects HLA LOH and quantifies CEA and MSLN expression. Based on these data, patients with solid tumors are now being prospectively screened for HLA LOH using xT-Onco in an ongoing tissue banking study (BASECAMP-1, NCT04981119), preparing for future interventional protocols

BACKGROUND:The first 1000 days of a child's life are increasingly recognized as a critical window for establishing a healthy growth trajectory to prevent childhood obesity and its associated long-term comorbidities. The purpose of this manuscript is to detail the methods for a multi-site, comparative effectiveness trial designed to prevent childhood overweight and obesity from birth to age 2 years. METHODS:This study is a multi-site, individually randomized trial testing the comparative effectiveness of two active intervention arms: 1) the Greenlight intervention; and 2) the Greenlight Plus intervention. The Greenlight intervention is administered by trained pediatric healthcare providers at each well-child visit from 0 to 18 months and consists of a low health literacy toolkit used during clinic visits to promote shared goal setting. Families randomized to Greenlight Plus receive the Greenlight intervention plus a health information technology intervention, which includes: 1) personalized, automated text-messages that facilitate caregiver self-monitoring of tailored and age-appropriate child heath behavior goals; and 2) a web-based, personalized dashboard that tracks child weight status, progress on goals, and electronic Greenlight content access. We randomized 900 parent-infant dyads, recruited from primary care clinics across six academic medical centers. The study's primary outcome is weight for length trajectory from birth through 24 months. CONCLUSIONS:By delivering a personalized and tailored health information technology intervention that is asynchronous to pediatric primary care visits, we aim to achieve improvements in child growth trajectory through two years of age among a sample of geographically, socioeconomically, racially, and ethnically diverse parent-child dyads.

The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize low-dose CT (LDCT) lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1161 proteins in a nested-case control study within 2 prospective cohorts (n = 252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n = 479 cases and 479 controls). Eligible participants had a current or former history of smoking and cases were diagnosed up to 3 years following blood draw. The Nodule Malignancy project measured 1078 proteins among participants with a heavy smoking history within four LDCT screening studies (n = 425 cases diagnosed up to 5 years following blood draw, 430 benign-nodule controls, and 398 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n = 1696 cases and 2926 subcohort representatives), and in the Nodule Malignancy project within five LDCT screening studies (n = 675 cases, 680 benign-nodule controls, and 648 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.

Understanding of human brain development has advanced rapidly as the field of developmental cognitive neuroscience (DCN) has matured into an established scientific discipline. Despite substantial progress, DCN lags behind other related disciplines in terms of diverse representation, standardized reporting requirements for socio-demographic characteristics of participants in pediatric neuroimaging studies, and use of intentional sampling strategies to more accurately represent the socio-demographic, ethnic, and racial composition of the populations from which participants are sampled. Additional efforts are needed to shift DCN towards a more inclusive field that facilitates the study of individual differences across a variety of cultural and contextual experiences. In this commentary, we outline and discuss barriers within our current scientific practice (e.g., research methods) and beliefs (i.e., what constitutes good science, good scientists, and good research questions) that contribute to under-representation and limited diversity within pediatric neuroimaging studies and propose strategies to overcome those barriers. We discuss strategies to address barriers at intrapersonal, interpersonal, community, systemic, and structural levels. Highlighting strength-based models of inclusion and recognition of the value of diversity in DCN research, along with acknowledgement of the support needed to diversify the field is critical for advancing understanding of neurodevelopment and reducing health inequities.