Faculty Bibliography

INTRODUCTION/BACKGROUND:Though brain fog is common in Long-coronavirus disease 2019 (Long-COVID), the incidence of mild cognitive impairment (MCI) is unknown. METHODS:In an observational cohort study, recovered COVID-positive, Long-COVID, and COVID-negative subjects underwent blinded evaluation using National Alzheimer's Coordinating Center (NACC) and National Institute on Aging (NIA) -Alzheimer's Association diagnostic criteria for dementia and MCI. The cumulative incidence of MCI was calculated for each group, and the hazard of MCI was compared between groups. RESULTS:Among 260 subjects, the cumulative incidence of MCI over 4.4 years was higher with Long-COVID (27%) versus recovered-COVID (5%) or COVID-negative status (1%). There was a higher hazard of MCI for patients with Long-COVID compared to those without (hazard ratio [HR] 3.93, 95% confidence interval [CI] 1.86-8.31, p < 0.001), and specifically for the Alzheimer's disease (AD) -related MCI subtype (HR 3.20, 95% confidence interval [CI] 1.14-9.00, p = 0.027). DISCUSSION/CONCLUSIONS:The cumulative incidence and adjusted hazard of MCI (and specifically AD-related MCI) at 4.4 years was significantly higher among Long-COVID patients compared to recovered-COVID and COVID-negative controls.

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) characterized by progressive bone marrow fibrosis and extramedullary hematopoiesis. Patients with MF are at increased risk of heart failure (HF) and pulmonary hypertension (PH), which are associated with morbidity and mortality. Ruxolitinib is used in MF to palliate symptom. Whether treatment with ruxolitinib impacts risk of HF hospitalization or new PH in MF is unknown. This was a retrospective cohort of MF patients without prior HF. Outcomes were HF hospitalization or new PH and all-cause death. A total of 144 patients were included, 46 (31.9%) were on ruxolitinib, 40.3% were female and 78.5% were White race. Ruxolitinib treatment was associated with lower risk of HF hospitalization or new PH (adjusted subhazard ratio 0.27, 95% CI 0.10-0.73) but not all-cause death (adjusted HR 0.85, 95% CI 0.42-1.72). Prospective, randomized studies are needed to confirm the impact of ruxolitinib on cardiovascular outcomes among patients with MF.

BACKGROUND:Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. METHODS:Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. FINDINGS/RESULTS:In 2023, there were an estimated 2·30 million (95% uncertainty interval [UI] 2·01 to 2·61) breast cancer incident cases, 764 000 deaths (672 000 to 854 000), and 24·1 million (21·3 to 27·5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44·2 per 100 000 person-years [31·2 to 58·4]), the age-standardised mortality rate (ASMR) was the highest (24·1 per 100 000 [16·8 to 31·9]). The highest ASIR was in the high-income group (75·7 per 100 000 [67·1 to 84·0]), and the lowest ASMR was in the upper-middle-income group (11·2 per 100 000 [10·2 to 12·3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147·2% (38·1 to 271·7), compared with a 1·2% (-11·5 to 17·2) change in the high-income group. The ASMR decreased in the high-income group, changing by -29·9% (-33·6 to -25·9), but increased by 99·3% (12·5 to 202·9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28·3% (16·6 to 38·9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3·56 million (2·29 to 4·83), with 1·37 million (0·841 to 2·02) deaths. INTERPRETATION/CONCLUSIONS:The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2·5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. FUNDING/BACKGROUND:Gates Foundation, St Jude Children's Research Hospital.

The convergence of artificial intelligence (AI) and neuroscience represents one of medicine's most profound intellectual partnerships. Neuronal architecture has inspired computational methods, while computational models, evolving from theoretical constructs to transformative clinical tools, are reshaping neurological practice. As AI systems attempt to augment diagnostic accuracy, treatment planning, and patient care, neurologists must develop fluency in these technologies to harness their potential while navigating their limitations and dangers. AI-related publications have exponentially increased in recent years, yet many neurologists lack the foundational computer science background needed to critically evaluate and most safely and effectively implement these tools in clinical practice. This article serves to outline the historical foundations linking neuroscience to computing, examine core concepts of the past and current AI landscape in neurology, and describe methodologies that aim to revolutionize neurological care.

BACKGROUND::Cardiometabolic risk factors contribute to cognitive decline and cerebrovascular pathology and are more prevalent among non-Hispanic Black (NHB) adults than non-Hispanic White (NHW) adults, with the greatest burden observed in males. METHODS::We analyzed 974 male participants (581 non-Hispanic White [NHW], 393 NHB) from the Healthy Aging Brain Study – Health Disparities baseline visit. Multivariable linear regression models were used to examine associations between cardiometabolic risk factors, including hypertension, diabetes, dyslipidemia, obesity, and tobacco dependence, and outcomes of cognitive domain performance (memory, executive function, processing speed, and language) and white matter hyperintensity burden, adjusting for age, education, apolipoprotein ε4 status, and race. Population intervention models (PIM), a counterfactual regression-based approach, were applied to estimate projected changes in cognition and WMH burden under hypothetical scenarios in which individual cardiometabolic risk factors were absent, with analyses stratified by racial ethnicity and mutually adjusted for the other cardiometabolic risks. RESULTS::Diabetes was associated with lower memory (β = −0.14, 95% CI: −0.27 to −0.01) and language (β = −0.15, 95% CI: −0.29 to −0.02). Tobacco dependence was linked to poorer performance across all domains (β range = −0.20 to −0.29). Hypertension was associated with greater WMH volume (β = 0.61, 95% CI: 0.09 to 1.12). PIM analyses projected memory gains from eliminating diabetes of 0.027 (95% CI: 0.002–0.052) in NHW and 0.039 (95% CI: 0.004–0.075) in NHB males, and gains from eliminating tobacco dependence of 0.015 (95% CI: 0.004–0.027) and 0.056 (95% CI: 0.017–0.098), respectively. Removing hypertension was projected to reduce WMH by −0.394 (95% CI: −0.769 to −0.014) in NHW and −0.481 (95% CI: −0.940 to −0.018) in NHB participants.

BACKGROUND AND AIMS/OBJECTIVE:Nitazenes are a novel subclass of synthetic opioids that have been increasingly implicated in the United States (US) overdose crisis. Despite their growing presence in the illicit drug supply, national trends have not been systematically evaluated. This study aimed to describe temporal and geographic patterns in nitazene detections and assess substances co-involved in nitazene-positive biospecimens. DESIGN/METHODS:Cross-sectional study using forensic data from two national sources: the US Drug Enforcement Administration's National Forensic Laboratory Information System (NFLIS) and the Center for Forensic Science Research & Education's (CFSRE) NPS Discovery Program. SETTING AND CASES/METHODS:Nitazene detections in all 50 US states and the District of Columbia between 2019 and 2024. MEASUREMENTS/METHODS:We quantified annual nitazene detections overall and by individual nitazene analog, US Census region and state. Temporal trends were modeled using piecewise linear regression with a Poisson distribution and log link, nationally and by region. NPS Discovery data were used to characterize substances co-involved with nitazene-positive biospecimens. FINDINGS/RESULTS:Between 2019 and 2024, 7117 nitazene analog reports were submitted to NFLIS, increasing from 43 in 2019 to 1905 in 2024. Counts rose sharply from 2019 to 2021 [count ratio = 7.32; 95% confidence interval (CI) = 2.22-24.20] but did not increase statistically significantly from 2021 to 2024 (count ratio = 1.08; 95% CI = 1.00-1.17). Early detections were predominated by isotonitazene (97.7% of NFLIS nitazene reports in 2019) but later shifted toward metonitazene and protonitazene (29.5% and 30.1%, respectively, in 2024). NPS Discovery identified 361 nitazene-positive biospecimens, increasing from 11 in 2019 to 113 in 2024, with counts increasing by approximately 45% per year (count ratio = 1.45; 95% CI = 1.23-1.71). Nearly all nitazene-positive biospecimens (98.3%) had at least one co-detected substance, most commonly fentanyl (54.6%). CONCLUSIONS:Nitazene detections increased sharply across the United States between 2019 and 2024, with shifting patterns in the prevalence of individual nitazenes and extensive polysubstance involvement. These findings highlight the need to strengthen drug testing capacity, expand epidemiological surveillance and implement targeted public health interventions to mitigate harms associated with this emerging class of synthetic opioids.

INTRODUCTION/BACKGROUND:Postoperative urinary retention (POUR) is a common complication following inguinal hernia repair (IHR), and it can be influenced by the type of neuromuscular blockade reversal medication used, especially acetylcholinesterase inhibitors. Among the available options for neuromuscular blockade reversal, Sugammadex has gained significant popularity due to its effectiveness, speed, and safety profile. Additionally, some studies suggest that it prevents POUR compared to acetylcholinesterase inhibitors. We aimed to perform a systematic review and meta-analysis to assess the POUR rates with the use of Sugammadex after IHR. METHODS:PubMed, EMBASE, Cochrane, LILACS, and Web of Science databases were systematically searched without date or language restrictions from inception to October 2024. The databases were searched for studies comparing Sugammadex with other medications for neuromuscular blockade reversal after IHR. The primary outcome was POUR. RESULTS:< .001), with a relative risk reduction of 89%. CONCLUSION/CONCLUSIONS:Sugammadex is associated with a significantly lower risk of POUR following IHR when compared to other medications for neuromuscular blockade reversal following IHR. Despite its higher cost and decreased availability in some centers, the use of Sugammadex should be strongly considered as the preferred option to prevent POUR and minimize the need for hospital readmissions.

AIM/UNASSIGNED:Inadequate adherence to colorectal cancer screening reduces individual and population level health benefits. Blood-based tests offer a new modality that may help patients overcome barriers, but there are concerns about the impact of patients switching from existing guideline-recommended screening modalities. This study estimates the population health outcomes and cost-effectiveness of offering blood-based testing using a validated individual-level simulation model based on patient preference evidence from randomized controlled trials. MATERIALS AND METHODS/UNASSIGNED:In this study, a validated discrete-event simulation model was used to evaluate the performance of different combinations of colorectal cancer screening strategy preferences per 10,000 screened individuals beginning at age 45. Preferences for screening options were informed by randomized controlled trials of patients with and without the option of blood-based testing. Adherence to initial patient preferences over a simulated lifetime was modeled as: (1) assumed 100% adherence and (2) longitudinal using a calibrated model. Simulated outcomes included clinical outcomes and cost-effectiveness from a healthcare sector perspective. A strategy was deemed cost-effective at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year gained. RESULTS/UNASSIGNED:The introduction of blood-based testing to an unscreened population with evidence from randomized controlled trials is projected to increase colorectal cancer deaths averted by 35% to 116% and from 68% to 247% relative to no screening, for stated preference and revealed preference scenarios, respectively. These outcomes are cost-effective, with incremental cost-effectiveness ratios ranging from $63,994 to $85,497 and from $30,464 to $54,764 across stated preference and revealed preference scenarios, respectively. LIMITATIONS/UNASSIGNED:Given limited data, natural history and real-world longitudinal adherence to screening are based on evidence-informed assumptions. CONCLUSIONS/UNASSIGNED:Using a simulation model to extrapolate data from two recent trials, we demonstrate that the introduction of blood-based tests has the potential to lead to cost-effective increases in the number of CRC deaths averted among the unscreened population.