Faculty Bibliography

INTRODUCTION/BACKGROUND:Neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has been linked to dementia risk, but prior studies were limited by small sample sizes. METHODS:We assessed the association between baseline NLR and incident Alzheimer's disease (AD) and Alzeimer's disease and related dementias (AD/ADRD) using electronic health records from New York University (NYU) (n = 284,530) and the Veterans Health Administration [VA] (n = 85,836) Hospitals from 2011 to 2023. AD/ADRD diagnoses were identified via International Classification of Diseases (ICD) codes ≥6 months post-baseline. Cox models and cumulative incidence functions (CIFs) adjusted for demographic and clinical variables, with death as a competing risk. RESULTS:Higher NLR was associated significantly with increased AD/ADRD risk in both cohorts (NYU hazard ratio [HR] = 1.07, 95% confidence interval [CI] 1.02-1.15; VA HR = 1.21, 95% CI 1.10-1.34). Spline analysis further confirmed a continuous dose-response relationship, and subgroup analyses showed higher risk among female and Hispanic patients. DISCUSSION/CONCLUSIONS:Elevated NLR is independently associated with higher AD/ADRD risk across diverse populations, highlighting the role of systemic inflammation and neutrophil-mediated pathways in neurodegeneration.

BACKGROUND:Sugary drink taxes have been implemented in several U.S. jurisdictions, but we know little about the impact of taxes on calories purchased in restaurants. The impact may differ in restaurant (vs. non-restaurant) settings because restaurant consumers may be less likely to travel to other jurisdictions for a single meal, choose no beverage or non-taxed beverages, decrease their beverage size, or order combo meals where the drink is bundled with other items at a single price. METHODS AND FINDINGS/RESULTS:We used six years of transaction-level sales data (2015-2020) from 7,341 Taco Bell restaurant locations to estimate the association of sugary drink policies with beverage calories purchased in the drive-through setting of fast food restaurants over time. Taco Bell restaurants represents a large sample size of data from several U.S. jurisdictions across a long follow-up period, which is unique in the literature. We defined the treatment group as restaurants in five jurisdictions where taxes were ever implemented (Albany, CA; Cook County, IL; Oakland, CA; Philadelphia, PA; Seattle, WA) (n = 60 restaurants). We identified a group of comparison restaurants where taxes were never implemented using synthetic control methods (n = 60 restaurants). We used a difference-in-differences design with calendar month and restaurant fixed effects to compare changes in outcomes between groups between the baseline (3-14 months prior to tax implementation) and 3- to 24-month follow-up periods, overall and by jurisdiction. Our primary outcome measure was beverage calories per transaction, from individually-purchased beverages and combo meals (separately). In the baseline period, average beverage calories per transaction were 51.1 (SD = 8.6) in the tax group and 42.3 (SD = 7.4) in the comparison group; and 119.5 (SD = 15.3) and 115.0 (SD = 23.0) beverage calories per transaction in combo meals. Overall, we observed no association between taxes and changes in beverage calories per transaction between groups during the follow-up period, including from individual beverage items (difference-in-differences = -0.3 (95% CI [-0.8, 1.2]) and combo meals (difference-in-differences = -4.3 (95% CI [-13.5, 5.0]). We observed similar results by location, except in Oakland, CA, where customers purchased 16.8 (95% CI 19.6, 14.1) fewer beverage calories per transaction from combo meals; the association was null after conditioning on the purchase of a beverage (difference-in-differences = -1.01 [-4.93, 2.92)]). The main limitations of our study methodology include the exclusion of beverage calorie data from in-store transactions and that the majority of the restaurants in our sample were located in Cook County. CONCLUSIONS:Though we observed differences in certain jurisdictions, overall our findings suggest that sugary drink taxes may not be effective in reducing beverage calorie consumption in fast food restaurants.

The management of non-obstructive azoospermia (NOA) is challenging. Even the most successful intervention for this condition, microsurgical testicular sperm extraction (microTESE) with IVF-ICSI, is not successful at least 40% of the time. Varicocele is present in 15% of young men, and varicocelectomy improves fertility outcomes in men with palpable varicoceles and abnormal semen analyses. Unfortunately, there are limited investigations into the effect of varicocelectomy in men with NOA. Uncontrolled cohort studies report the return of sperm to the ejaculate after treatment of the varicoceles in men with NOA. That finding should be viewed in the context that sperm are found in the subsequent semen analyses of men with NOA without any intervention. Limited controlled studies do report higher rates of sperm retrieval during microTESE in men with treated varicoceles compared to controls. The histopathology of testis biopsies obtained during varicocelectomy correlates with the return of sperm to the semen and sperm retrieval rates during subsequent microTESE. The evidence supporting varicocele treatment in men with NOA is very limited, and clinicians should make this fact clear when counseling patients with these conditions.

BACKGROUND:Arsenic exposure remains a major global health concern, and early-life exposure has been linked to cancer, cardiovascular disease, and diabetes. Epigenetic biomarkers of aging may capture long-term effects of arsenic, yet whether exposure during sensitive developmental windows leaves detectable epigenetic signatures decades later remains unclear. Socioeconomic status (SES) may modify these relationships, yet its role as a modifier has not been examined. METHODS:We leveraged a natural experiment in northern Chile, where municipal drinking-water arsenic concentrations were extremely high from 1958 to 1972. Decades later, leukocyte DNA methylation was measured among 358 adults (mean age = 65.7 years) using the Illumina EPIC v2 array. Arsenic concentration at birth (0-860 μg/L) was assigned from historical water records. Current exposure was measured in urine (2-646 μg/g creatinine). We evaluated associations of birth and current arsenic exposure with epigenome-wide methylation and epigenetic aging, incorporating multiplicative interaction and stratification by SES. RESULTS:<0.05), especially among lower-SES individuals (PC-PhenoAge: b = 0.16, 95% CI = 0.02, 0.29; DunedinPACE: b = 0.0035, 95% CI = 0.00016, 0.0069). CONCLUSION/CONCLUSIONS:Early-life arsenic exposure was associated with accelerated epigenetic aging in adulthood, whereas current exposure was associated with CpG-specific methylation changes, particularly among socioeconomically disadvantaged individuals.

BACKGROUND:Myocardial infarction with non-obstructive coronary arteries (MINOCA) has several underlying causes, including mimicking conditions in some cases. Imaging is recommended to identify MINOCA etiologies, but it remains unclear which patients are most likely to have abnormal findings. We characterized MINOCA mechanisms, analyzed predictors of imaging abnormalities and explored sex differences. METHODS:We enrolled patients with clinical diagnosis of MI in an international, prospective, diagnostic study at 28 sites in US, Canada and UK. After a women-only phase, we included both sexes. Individuals with ≥50% diameter stenosis or coronary dissection on angiography, or alternate causes for the clinical presentation, were excluded. Participants had multi-vessel coronary optical coherence tomography (OCT) during index coronary angiography and cardiac magnetic resonance imaging (CMR) within one week. Independent core laboratories interpreted imaging, blinded to other results. RESULTS:Among 754 patients enrolled, 389 had MINOCA and 336 with MINOCA underwent OCT (270 women and 66 men); CMR was completed in 284 (85%). An OCT-defined culprit lesion was identified in 45% (116/270 women [43% ] and 35/66 men [53%], p=0.18). CMR demonstrated an ischemic pattern in 114/284 (40%), similar by sex (96/225 women [43%] vs. 18/59 men [31%], p=0.12). A non-ischemic pattern was observed in 23% (23% of women, 25% of men, p=0.78). We identified a cause of the clinical presentation in 79% of patients with both tests completed: 59% had an ischemic cause of MINOCA and 20% had a non-ischemic mimicking condition. OCT alone found a MINOCA etiology in 151/336 (45%) and CMR alone in 180/284 (63%). Predictors of an OCT culprit lesion included age, abnormal angiogram, and number of vessels imaged, but 27% of normal angiograms harbored a culprit lesion. Predictors of abnormal CMR were peak troponin, shorter time to CMR, and non-Asian race, but CMR was abnormal in 40% when troponin was <4-fold above the upper reference limit. CONCLUSIONS:The combination of multi-vessel coronary OCT and CMR in patients with a clinical diagnosis of MINOCA confirmed MI in 59% and identified an alternate cause (MINOCA mimic) in 20%. Clinical factors had limited utility to predict imaging abnormalities. No sex differences in imaging results were detected.

BACKGROUND AND AIM/UNASSIGNED:Extended-release injectable naltrexone (XR-Naltrexone) is an effective treatment for opioid use disorder (OUD); however, initiation can be challenging as it requires an opioid-free period. This exploratory analysis examines patient characteristics associated with successful initiation of XR-Naltrexone in the National Drug Abuse Treatment Clinical Trials Network (CTN-0051) Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment (X:BOT) trial. METHODS/UNASSIGNED:Patient demographics and clinical variables associated with successful XR-Naltrexone initiation were examined among 283 participants with OUD randomized to XR-Naltrexone in the X:BOT trial. Variables included severity of opioid use, characteristics of opioid and other substance use, treatment history, psychiatric history, baseline depression, and pain. Logistic regression models were used to estimate the effect of variables on the odds of induction success. RESULTS/UNASSIGNED:204 (72%) of 283 participants randomized to receive XR-Naltrexone completed successful induction. Housing status and pain were significantly associated with XR-Naltrexone induction status. Reported homelessness was significantly associated with higher odds of successful XR-Naltrexone induction (OR: 2.31; 95% CI: 1.12, 4.76). Individuals that reported moderate or extreme pain on the EuroQoL had half the odds of successful induction compared to those without pain (OR: 0.49; 95% CI: 0.27, 0.89). CONCLUSIONS/UNASSIGNED:Among patients with OUD initiating treatment on inpatient units, homelessness was associated with greater likelihood of successfully initiating XR-Naltrexone, while chronic pain was associated with lower likelihood of XR-Naltrexone initiation. Future research on XR-Naltrexone initiation should consider tailoring treatment based on housing status and other social determinants, and evaluation and management of pain.

INTRODUCTION/BACKGROUND:Safety net hospitals (SNHs), defined as the members of America's essential hospitals, are lifelines for over 28 million uninsured and Medicaid-dependent Americans, yet systemic inequities trap both patients and institutions in a vicious cycle. METHODS:A narrative review was performed to examine the impact of late-stage cancer presentations on patient outcomes and cost implications. RESULTS:Late-stage cancer diagnoses (stages III and IV) are more common at SNHs than other hospitals, likely due to limited access to preventative services. The higher rate of late-stage diagnoses leads to a higher cost of treatment. In fact, patients with stage IV cancer incur 60%-80% higher treatment costs than those with early-stage diagnoses. CONCLUSIONS:SNHs are a vital source of health care for vulnerable populations across the country, with 75% of the SNH patient population being uninsured or underinsured. SNHs more frequently see patients with advanced stage cancers and disproportionately bear the expense of caring for these patients. American College of Surgeons accreditation, which emphasizes screening, quality improvement and strict standards, provides a roadmap to earlier detection and standardized high-quality care. However, only half of SNHs have American College of Surgeons quality accreditations in place, and only 12% of SNHs nationwide have American College of Surgeons cancer-related accreditations in place. Barriers to accreditation include staffing shortages and budget constraints, exacerbated by reductions in disproportionate share hospital funding and anticipated cuts to Medicare and Medicaid funding. Despite these challenges, the long-term benefits of accreditation outweigh the investment. Addressing these barriers is crucial to ensuring that SNHs can provide high-quality care to vulnerable populations.

BACKGROUND:The role of modifiable environmental factors in Alzheimer's disease (AD) risk remains poorly understood. Built environment features such as neighbourhood walkability (NW) may influence long-term cognitive health among women. METHODS:The New York University Women's Health Study recruited 14 273 cognitively healthy women aged 35-65 years between 1985 and 1991, with follow-up for over 30 years. We geocoded residential addresses for each participant to derive a validated four-item baseline NW measure and a two-item average annual NW index over the follow-up period. We conducted a nested case-control study of 1865 AD cases identified via linkage to Medicare claims during follow-up matched to 3730 controls on age, race/ethnicity and Medicare coverage using risk-set sampling. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals for AD in relation to tertiles of NW measures, adjusting for potential confounders. Subgroup analyses examined potential effect modification. RESULTS:Compared with women living in areas with the lowest baseline NW, those in the middle and highest tertiles had lower odds of having a diagnosis of AD during follow-up, with an OR of 0.95 (0.82-1.11) and 0.83 (0.71-0.98), respectively (P-trend = .03). Results were similar when using average annual NW. The association did not differ appreciably by age, smoking status, education or body mass index. CONCLUSIONS:Higher midlife NW was associated with reduced odds of AD later in life. These findings highlight the potential for built environment interventions to promote cognitive health and support healthy ageing in women.