Faculty Bibliography

BACKGROUND/UNASSIGNED:Increased incidence of cancer has been reported among World Trade Center (WTC)-exposed persons. Aberrant DNA methylation is a hallmark of cancer development. To date, only a few small studies have investigated the relationship between WTC exposure and DNA methylation. The main objective of this study was to assess the DNA methylation profiles of WTC-exposed community members who remained cancer free and those who developed breast cancer. METHODS/UNASSIGNED:WTC-exposed women were selected from the WTC Environmental Health Center clinic, with peripheral blood collected during routine clinical monitoring visits. The reference group was selected from the NYU Women's Health Study, a prospective cohort study with blood samples collected before 9 November 2001. The Infinium MethylationEPIC array was used for global DNA methylation profiling, with adjustments for cell type composition and other confounders. Annotated probes were used for biological pathway and network analysis. RESULTS/UNASSIGNED:, and dysregulation of these genes contributes to cancer immune evasion. CONCLUSION/UNASSIGNED:WTC exposure likely impacts DNA methylation and may predispose exposed individuals toward cancer development, possibly through an immune-mediated mechanism.

Asymptomatic adnexal masses are commonly encountered in daily radiology practice. Although the vast majority of these masses are benign, a small subset have a risk of malignancy, which require gynecologic oncology referral for best treatment outcomes. Ultrasound, using a combination of both transabdominal, transvaginal, and duplex Doppler technique can accurately characterize the majority of these lesions. MRI with and without contrast is a useful complementary modality that can help characterize indeterminate lesions and assess the risk of malignancy is those that are suspicious. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

BACKGROUND:Early-life exposure to phthalates alters behaviors in animals. However, epidemiological evidence on childhood phthalate exposure and attention-deficit/hyperactivity disorder (ADHD) behaviors is limited. METHODS:This study included 243 children from the ReCHARGE (Revisiting Childhood Autism Risks from Genetics and Environment) study, who were previously classified as having autism spectrum disorder (ASD), developmental delay, other early concerns, and typical development in the CHARGE case-control study. Twenty phthalate metabolites were measured in spot urine samples collected from children aged 2-5 years. Parents reported on children's ADHD symptoms at ages 8-18 years using Conners-3 Parent Rating Scale. Covariate-adjusted negative binomial generalized linear models were used to investigate associations between individual phthalate metabolite concentrations and raw scores. Weighted quantile sum (WQS) regression with repeated holdout validation was used to examine mixture effects of phthalate metabolites on behavioral scores. Effect modification by child sex was evaluated. RESULTS:Among 12 phthalate metabolites detected in >75% of the samples, higher mono-2-heptyl phthalate (MHPP) was associated with higher scores on Inattentive (β per doubling = 0.05, 95% confidence interval [CI]: 0.02, 0.08) and Hyperactive/Impulsive scales (β = 0.04, 95% CI: 0.00, 0.07), especially among children with ASD. Higher mono-carboxy isooctyl phthalate (MCiOP) was associated with higher Hyperactivity/Impulsivity scores (β = 0.07, 95% CI: -0.01, 0.15), especially among typically developing children. The associations of the molar sum of high molecular weight (HMW) phthalate metabolites and a phthalate metabolite mixture with Hyperactivity/Impulsivity scores were modified by sex, showing more pronounced adverse associations among females. CONCLUSION/CONCLUSIONS:Exposure to phthalates during early childhood may impact ADHD behaviors in middle childhood and adolescence, particularly among females. Although our findings may not be broadly generalizable due to the diverse diagnostic profiles within our study population, our robust findings on sex-specific associations warrant further investigations.

BACKGROUND:High potency synthetic opioids like fentanyl have continued to replace or contaminate the supply of illicit drugs in North America, with fentanyl test strips (FTSs) often used as a harm reduction tool for overdose prevention. The available evidence to support FTS for harm reduction has yet to be summarized. METHODS:A search of PubMed, Ovid Embase, and Web of Science was conducted in March 2023. A 2-stage review was conducted to screen by title and abstract and then by full text by 2 reviewers. Data were extracted from each study using a standardized template. RESULTS:A total of 91 articles were included, mostly from North America, predominantly reporting on FTS along with other harm reduction tools, and all conducted after 2016. No randomized controlled trials are reported. Robust evidence exists supporting the sensitivity and specificity of FTS, along with their acceptability and feasibility of use for people who use drugs and as a public health intervention. However, limited research is available on the efficacy of FTS as a harm reduction tool for behavior change, engagement in care, or overdose prevention. CONCLUSIONS:Though FTSs are highly sensitive and specific for point of care testing, further research is needed to assess the association of FTS use with overdose prevention. Differences in FTS efficacy likely exist between people who use opioids and nonopioid drugs, with additional investigation strongly needed. As drug testing with point-of-care immunoassays is embraced for nonfentanyl contaminants such as xylazine and benzodiazepines, increased investment in examining overdose prevention is necessary.

This review focuses on the initial imaging in the reproductive age adult population with acute pelvic pain, including patients with positive and negative beta-human chorionic gonadotropin (β-hCG) levels with suspected gynecological and nongynecological etiology. For all patients, a combination of transabdominal and transvaginal pelvic ultrasound with Doppler is usually appropriate as an initial imaging study. If nongynecological etiology in patients with negative β-hCG is suspected, then CT of the abdomen and pelvis with or without contrast is also usually appropriate. In patients with positive β-hCG and suspected nongynecological etiology, CT of the abdomen and pelvis with contrast and MRI of the abdomen and pelvis without contrast may be appropriate. In patients with negative β-hCG and suspected gynecological etiology, CT of the abdomen and pelvis with contrast, MRI of pelvis without contrast, or MRI of pelvis with and without contrast may be appropriate. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

INTRODUCTION/UNASSIGNED:Although prostate magnetic resonance imaging (MRI) is commonly used in the diagnosis, staging and active surveillance of prostate cancer, little is known about patient perspectives on MRI. METHODS/UNASSIGNED:We performed a qualitative study consisting of in-depth, semi-structured interviews of patients with low- and intermediate-risk prostate cancer managed with active surveillance. Interviews focused on experiences with and knowledge of prostate MRI and MRI-ultrasound fusion biopsy during active surveillance. We purposively sampled patients who received prostate MRI as part of their clinical care, conducted interviews until reaching thematic saturation and performed conventional content analysis to analyse data. RESULTS/UNASSIGNED:Twenty patients aged 51-79 years (mean = 68 years) participated in the study. At diagnosis, 17 (85%) had a Gleason grade group 1, and three (15%) had a grade group 2 tumour. Overall, participants viewed prostate MRI as a valuable tool that accurately localizes and monitors prostate cancer over time, and they considered prostate MRI central to active surveillance monitoring. We identified five thematic categories related to MRI use: (1) the experiential aspects of undergoing an MRI scan; (2) the experience of visualizing one's own prostate and prostate cancer; (3) adequacy of provider explanations of MRI results; (4) confidence in prostate MRI in decision-making; and (5) the role of prostate MRI in longitudinal follow-up, including an interest in using MRI to modify the timing of, or replace, prostate biopsy. CONCLUSION/UNASSIGNED:Patients value prostate MRI as a tool that enhances their confidence in the initial diagnosis and monitoring of prostate cancer. This work can inform future studies to optimize patient experience, education and counselling during active surveillance for prostate cancer.

In a workshop sponsored by the U.S. National Heart, Lung, and Blood Institute, experts identified current knowledge gaps and research opportunities in the scientific, conceptual, and ethical understanding of organ donation after the circulatory determination of death and its technologies. To minimize organ injury from warm ischemia and produce better recipient outcomes, innovative techniques to perfuse and oxygenate organs postmortem in situ, such as thoracoabdominal normothermic regional perfusion, are being implemented in several medical centers in the US and elsewhere. These technologies have improved organ outcomes but have raised ethical and legal questions. Re-establishing donor circulation postmortem can be viewed as invalidating the condition of permanent cessation of circulation on which the earlier death determination was made and clamping arch vessels to exclude brain circulation can be viewed as inducing brain death. Alternatively, TA-NRP can be viewed as localized in-situ organ perfusion, not whole-body resuscitation, that does not invalidate death determination. Further scientific, conceptual, and ethical studies, such as those identified in this workshop, can inform and help resolve controversies raised by this practice.