Faculty Bibliography

Improving long-term protective immunity elicited by prime-boost vaccinations requires a deeper understanding of the immunologic outcomes of different vaccine platforms. Given the variety of platforms used to develop vaccines against SARS-CoV-2, we reasoned that SARS-CoV-2 offered an opportunity to compare vaccine platforms in humans. We used flow cytometry and single-cell transcriptomics to explore the B cell response to different homologous and heterologous vaccine regimens. We found that an adenovirus vector prime followed by a messenger RNA (mRNA) vaccine boost showed the greatest short-term B cell expansion and preferentially elicited an activated atypical B cell subset that was associated with antibody binding titers against spike protein. In contrast, an mRNA primary series followed by homologous boost induced a different activated B cell subset with more proliferative potential and high frequencies of a long-lived resting memory subset. Moreover, immunoglobulin A (IgA)-expressing memory B cells had more somatic hypermutations than the predominant IgG-expressing B cell population. This heterogeneity in vaccine-elicited B cell responses underscores the potential of tailoring vaccine regimens that combine different platforms to achieve potent and durable protection against infectious diseases.

PURPOSE/OBJECTIVE:This study aimed to quantitatively assess relative arterial contributions to the quadriceps tendon (QT) using 7-Tesla quantitative magnetic resonance imaging (7T-qMRI), histology and high-resolution computed tomography (micro-CT) in a fresh-frozen human cadaveric model. METHODS:Six human cadaveric knee pairs were obtained (mean age: 43 years; range: 23-61 years). Pre- and post-contrast 7T-qMRI scans were performed to quantify tendonous vascularity. Subsequent algorithm-based quantitative histologic analysis was performed using hematoxylin and eosin staining, with validation by CD31 immunohistochemistry. Qualitative analysis was performed on two additional knee specimens using 98 μm micro-CT imaging. RESULTS:The distal QT demonstrated higher median arterial contributions versus central and proximal regions (distal, 47.4% [interquartile range: 30.8%-64.1%]; central, 28.6% [20.4%-41.5%]; proximal, 11.6% [8.7%-18.4%]), with significantly greater contributions distally versus proximally (Cohen's d = 1.58; p = 0.021). These findings aligned with the sagittal sub-analysis (deep-proximal 17.2 ± 19.3% vs. deep-distal 43.4 ± 20.3%; Cohen's d = 1.32; p = 0.050). Histologic analysis (interobserver-reliability: r = 0.95) corroborated the MRI results (distal QT, 43.5 ± 7.9%; central, 30.7 ± 6.4%; proximal, 25.8 ± 4.1%), with significant differences between distal and both proximal (Cohen's d = 2.81; p < 0.001) and central (Cohen's d = 1.78; p = 0.012) regions. The deep layer was found to have significantly higher arterial contributions (61.6 ± 14.2%) versus the superficial layer (38.4 ± 14.2%) (Cohen's d = 1.64; p = 0.018). The medial and lateral QT demonstrated lower arterial contributions versus middle QT (Cohen's d = 0.96-1.26; p > 0.050). CONCLUSION/CONCLUSIONS:7T-qMRI and algorithm-based histological analysis of arterial QT contributions revealed significantly greater arterial contributions in the distal compared to the proximal as well as in the deep compared to the superficial region. While the central region demonstrated higher arterial contributions than the medial and lateral aspects, these differences were not statistically significant. Given that the majority of injuries affect the distal and central portions of the QT, these findings reinforce the rationale for direct tendon-to-bone repair; however, clinical studies are necessary to confirm these findings. LEVEL OF EVIDENCE/METHODS:Level V, cadaveric study.

BACKGROUND:Sexual health counseling (SHC) is a critical aspect of inflammatory bowel disease (IBD) care. Less is known about sexual health counseling in patients who identify as members of a sexual or gender minority (SGM) group. AIMS/OBJECTIVE:This study aims to characterize patient-reported sexual health counseling in SGM vs. non-SGM patients with IBD. METHODS:We conducted an anonymous, cross-sectional survey of patients over 18 years old with IBD, currently receiving care at a large, tertiary care IBD center. Data collection included demographics, IBD history, and patient recall of SHC. Patients who self-identified as SGM were compared to non-SGM patients, with subgroup analyses by sex assigned at birth. Means were compared using t tests and percentages compared using chi-square analysis. RESULTS:A total of 162 patients (41 SGM and 121 non-SGM) completed the survey. Both groups reported IBD impacted their sexual practices (ranging from 44% non-SGM men to 64% SGM women). SGM patients were more likely to report that their gastroenterologist asked about sexual health compared to non-SGM patients (p < .005). Importantly, 31% of respondents reported seeking SHC from their gastroenterologist (GI), placing GIs among the top sources of information regarding sexual health in this cohort. CONCLUSION/CONCLUSIONS:Most study participants reported that IBD has impacted their sexual practices. SHC rates were low in all study groups despite GI providers being a primary source of information. Clearer recommendations on aspects of SHC could improve quality of care for both SGM and non-SGM patients with IBD.

PURPOSE/OBJECTIVE:We aimed to determine time trends in incidence, treatment and survival of patients with adrenocortical carcinoma in the Netherlands. METHODS:All 685 adult patients with adrenocortical carcinoma diagnosed between 1993 and 2020 in the Netherlands were included, using the nation-wide prospective Netherlands Cancer Registry. RESULTS:The median age-adjusted incidence rate based on the European Standard Population was 1.62 per million person-years [0.83-2.11] and was stable over time. We saw a gradual increase in stage III on diagnosis (13 to 25%) with a stable proportion of stage IV (40%). The five-year survival remained stable over time for stage I-II at 65% and stage III at 35%, while the survival for stage IV increased from 3% in 1993-1996 to 11% in 2017-2020. Since the Dutch Adrenal Network was founded in 2004, more patients were referred to an expert center (p<0.001), which was associated with increased survival (adjusted HR 0.70, 95%CI[0.57-0.85]). Multivariate cox-regression showed increased survival in all stages when treated with adrenalectomy (adjusted HR 0.53, 95%CI[0.43-0.65]) and mitotane therapy (adjusted HR 0.73, 95%CI[0.55-0.98]). In stage IV disease, adrenalectomy, surgical control of disease, chemotherapy and mitotane therapy were associated with increased survival. However, only 58% of mitotane users reached a therapeutic drug level and 59.5% discontinued treatment prematurely. CONCLUSIONS:The incidence of adrenocortical carcinoma is stable over time. The five-year survival for stage I-III remained stable, while the survival for stage IV increased. Factors associated with increased survival are centralization of care, adrenalectomy, surgical control of disease, chemotherapy and mitotane therapy.

PURPOSE/OBJECTIVE:To evaluate the effectiveness and safety of current surgical modalities for nephrolithiasis in ectopic pelvic kidneys, a rare congenital anomaly with limited available evidence. METHODS:A multicenter retrospective study was conducted across 11 high-volume international centers, including 45 patients with congenital pelvic kidneys who underwent flexible ureteroscopy, multimodal-guided percutaneous nephrolithotomy, and laparoscopic pyelolithotomy. Stone-free rate (defined as 0 mm), need for ancillary procedures, and complications (Clavien-Dindo) were assessed. RESULTS:Stones were classified as GUYS II in 51.1% of patients and GUYS III-IV in 48.9%. flexible ureteroscopy was the most common primary treatment (51.1%), followed by multimodal guided - PCNL (33.3%). Multimodal-guided PCNL achieved the highest stone free rate (86.7%) and the lowest requirement for ancillary procedures (OR 9.7; 95% CI 1.8-51 compared with other modalities). The overall final stone free rate for the cohort was 65.9% after a mean of 1.38 procedures per patient. Complications occurred in 13.3% of cases, with only one major event (Clavien-Dindo IVa). CONCLUSIONS:Our findings indicate that multimodal-guided PCNL achieved the highest success rates and required fewer ancillary procedures than other approaches when treating stones in ectopic pelvic kidneys. In contrast, flexible ureterorenoscopy showed lower efficacy and required more ancillary interventions. Complication rates were low and comparable to those observed in anatomically normal kidneys. Although larger cohorts would strengthen these observations, the very low incidence of ectopic pelvic kidneys inherently limits the ability to accumulate large patient numbers.

PURPOSE OF REVIEW/UNASSIGNED:Alzheimer disease (AD) and epilepsy are major causes of neurologic disability and are reciprocally related: epileptiform discharges, subclinical seizures, and epilepsy are more prevalent in patients with AD compared with controls; progressive cognitive impairment commonly afflicts epilepsy patients; and late-onset epilepsy patients have higher rates of new-onset dementia. RECENT FINDINGS/UNASSIGNED:Epidemiologic studies support shared risk factors (e.g., genetic variants, vascular disease, sleep disorders, microbiome) with notable divergences. AD and epilepsy have some overlapping anatomic (e.g., hippocampus, entorhinal, and association cortex), clinical (e.g., memory, attentional, and executive) impairments, and neuropathologic (e.g., amyloid, tau, neurofibrillary tangles) features. Shared clinical and translational challenges include underlying mechanisms (e.g., genetic variants, neuroinflammation, metabolic and mitochondrial dysfunction, excitatory/inhibitory imbalance, microbiome, and sociodemographic factors) and identifying valid and reliable biomarkers (e.g., total tau and phosphorylated tau (p-tau), amyloid deposition, Aβ42/Aβ40 ratio) to assess disease progression, predict outcomes, and assess potentially disease-modifying interventions. SUMMARY/UNASSIGNED:Identifying convergences and divergences between epilepsy and AD may inform our understanding. The clinical, neurophysiologic, neuropathologic, and molecular pathologic changes in AD and epilepsy may reveal pathophysiologic insights and therapeutic opportunities.

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.

This study investigates associations between the strength of local Tobacco Retail Licensing (TRL) laws and adult tobacco use patterns (i.e., cigarette, e-cigarette, and dual use), and differences by sociodemographic characteristics, using California as a case study. We merged data from the American Lung Association's (ALA) State of Tobacco Control Reports and the California Health Interview Survey (CHIS) from 2016 to 2022. We recoded the ALA local policy grades as strongest (highest grade) versus weaker (all other grades). Using quantitative methods, we estimated multilevel multinomial logistic regression models to examine the relationship between the strength of local TRL laws and cigarette and e-cigarette single and dual use among adults aged 25 and older, nesting by city/town. We also examined the potential for effect modification by including interaction terms for race and ethnicity, income, and education in separate models. Our results showed that no associations existed between stronger TRL grades and exclusive cigarette, e-cigarette or dual use in any of the models. Neither were there statistically significant interactions by race and ethnicity, income, or education. These null findings suggest that while TRL laws may potentially be useful to restrict adolescent access, local TRL strength may have few impacts on adult nicotine consumption.

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.