Faculty Bibliography

IMPORTANCE/UNASSIGNED:Increasing numbers of children are conceived using infertility treatment; concerns remain about potential effects on child neurodevelopment. OBJECTIVE/UNASSIGNED:To evaluate whether infertility treatment is associated with child neurodevelopment and whether such an association may be attributable to underlying subfecundity. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study was conducted among mother-child dyads in the National Institutes of Health Environmental Influences on Child Health Outcomes Cohort, with infants conceived between 1998 and 2022. Associations of subfecundity and infertility treatment with neurodevelopmental outcomes were assessed among children ages 2 to 10 years. Data were analyzed from May 14, 2025, to March 31, 2026. EXPOSURE/UNASSIGNED:Subfecundity was defined as prior consultation for, treatment of, or diagnosis of infertility for either partner; at least 2 prior miscarriages; or ever having had unprotected heterosexual intercourse for 12 months without conceiving. Infertility treatment was categorized as in vitro fertilization (IVF) or non-IVF treatment. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Harmonized caregiver responses to the Strengths and Difficulties Questionnaire and the Child Behavior Checklist yielded continuous raw scores for externalizing and internalizing problems. The total raw Social Responsiveness Scale (SRS) score quantified autism-like symptoms. Caregivers reported physician diagnosis of autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). RESULTS/UNASSIGNED:Among 15 382 mother-infant dyads, there were 14 191 unique maternal participants (mean [SD] age at delivery, 30.9 [5.33] years; 8780 parous participants [57.1%]). ASD and ADHD were diagnosed in 876 offspring (7.6%) and 819 offspring (7.1%), respectively. In generalized linear models, subfecundity was associated with higher externalizing problem and SRS scores among all pregnancies (externalizing problems: b = 0.47 [95% CI, 0.14-0.81]; SRS score: b = 1.08 [95% CI, 0.01-2.14]) and when restricted to natural conceptions (externalizing problems: b = 0.45 [95% CI, 0.07-0.83]; SRS score: b = 1.12 [95% CI, -0.09 to 2.34]). Offspring of parents with subfecundity had higher odds of ASD (overall: odds ratio [OR], 1.27 [95% CI, 1.03-1.57]; natural conceptions: OR, 1.31 [95% CI, 1.04-1.64]). Children conceived via non-IVF treatment had higher odds of ADHD compared with those conceived via natural conception with subfecundity (OR, 1.77 [95% CI, 1.16-2.68]) or without subfecundity (OR, 1.54 [95% CI, 1.05-2.25]). There were no significant associations for IVF treatment. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this large US cohort study, subfecundity was associated with elevated scores for caregiver-reported symptoms of behavioral problems and higher odds of ASD diagnosis, independent of infertility treatment. Non-IVF treatment was associated with ADHD, warranting further research into specific indications for treatment that may increase risk of offspring neurodevelopmental problems.

Localized treatment of oligometastatic liver disease can improve both local control and survival. The liver is a frequent site of metastases from colorectal, breast, and lung cancers, but most patients are not eligible for surgical resection due to lesion number, location, or comorbidities. For these patients, non-surgical ablative methods such as radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) and increasingly microwave ablation (MWA) are used. RFA was used as the primary comparator in this review because it represents the most historically established and widely reported ablative modality in the comparative radiotherapy literature. While RFA has been the traditional approach, SBRT is emerging as a promising alternative, offering precise, non-invasive treatment. SBRT may be especially useful for larger lesions or tumors in locations where RFA is difficult to perform. However, high-quality evidence and large-scale trials are still needed to confirm its efficacy and define its role. This review compares the strengths and limitations of both methods and provides practical guidance for clinical decision-making in the treatment of patients with inoperable liver metastases.

BACKGROUND: ("Dutch") transgenic mice develop aging-related learning deficits and accumulate endogenously generated non-fibrillar aggregates (NFAs) of amyloid beta (Aβ) and amyloid precursor protein α-carboxy terminal fragments. NFA-Aβ correlates with synaptic loss and memory deficits more closely than does fibrillar Aβ. METHODS: mice. RESULTS: mice developed physiological abnormalities in post-tetanic potentiation, synaptic fatigue, synaptic vesicle replenishment, and an aging-related reduction in mitochondrial complex I activity. Single-cell RNA sequencing showed that excitatory neurons exhibited an altered transcriptomic profile involving "protein translation" and "oxidative phosphorylation." DISCUSSION/CONCLUSIONS:Accumulation of NFA-Aβ alters neuronal metabolism but does not activate inflammation. Depletion of all forms of Aβ may be required to eliminate Aβ toxicity with anti-amyloid antibodies.

INTRODUCTION/UNASSIGNED:To ensure Alzheimer's disease-modifying treatments can be initiated in diverse populations, efficient pathways to obtain timely diagnoses are required. METHODS/UNASSIGNED:This interim sub-analysis of a multicenter US study included cross-sectional surveys and interviews with neurologists at 12 diverse sites to assess real-world lecanemab use. RESULTS/UNASSIGNED:testing to inform risk/benefit decisions. Infusions usually started within 6 months of diagnosis. Delayed/incomplete referrals were identified as the most significant barrier in the current patient pathway. DISCUSSION/UNASSIGNED:These findings demonstrate the feasibility of lecanemab integration in diverse clinical settings and highlight the importance of primary care physician engagement, optimization of referral pathways, and expanding BBM use in improving timely diagnosis, equitable access, and early treatment initiation.

Lead exposure remains a significant public health problem, and even within current standards, most individuals have limited means to avoid it. Regulating or removing toxic exposures remains a priority, but complementary nearer-term protections are needed. We previously observed that health insurance coverage attenuated associations of blood lead levels with two DNA methylation-based biomarkers of morbidity and mortality: GrimAge2 and DunedinPoAm. In this study, we evaluated whether healthcare access could account for or modify these relationships. We conducted a cross-sectional analysis of 2,312 adults aged 50-84 years from the 1999-2002 National Health and Nutrition Examination Survey (NHANES). Survey-weighted generalized linear models were used to test effect modification of the lead-epigenetic aging relationship by health insurance and by healthcare access, defined as having a routine place of healthcare. In models adjusted for demographic, socioeconomic, lifestyle, and health factors, insurance significantly modified associations of lead with epigenetic age. Although model estimates remained comparable, interactions were no longer statistically significant after healthcare access was added as a covariate for GrimAge2 (β_insured = 0.08, 95%CI_insured: -0.08, 0.23, β_uninsured = 0.60, 95%CI_uninsured: -0.10, 1.28, P_interaction = 0.09) and DunedinPoAm (β_insured = 0.001, 95%CI_insured: -0.002, 0.003, β_uninsured = 0.01, 95%CI_uninsured: -0.003, 0.02, P_interaction = 0.09). Healthcare access alone did not significantly modify the associations of lead with either biomarker in models with or without insurance as a covariate. These findings suggest that healthcare access may partially contribute to the attenuation of lead-related epigenetic aging observed among insured adults and a need for further research to better understand these complex relationships.

Although mandibular implant-supported overdentures demonstrate high survival rates, uncertainty remains regarding their long-term biologic stability and maintenance burden, particularly across different attachment systems. Sixty edentulous patients were fitted with two-implant mandibular overdentures either by locator-type or ball retainers and followed up to a 5 years. At last follow-up, the survival rate of implants was 98.3% and 93.3% in terms of prostheses success; mean change of marginal bone was low. Maintenance requirements were frequent and mostly minor including insert/ matrix replacement and relines. Hence, long-term success is to be measured not just by survival.

BACKGROUND:"Business, like life, is all about how you make people feel. It's that simple and it's that hard" says Danny Meyer, the restauranteur and CEO of the Union Square Hospitality Group in New York. Similarly, Maya Angelou famously said that people will never forget how you made them feel, though they may forget what you said or did. In neurosurgery, we are doing two things at once: something very technical and something very human. The core thesis of this hospitality philosophy is that whereas the technical aspect of our job is critically important, it represents 49% of our success. The human aspect of our work represents 51%, ever so slightly more important. SUMMARY/CONCLUSIONS:We will explore how hospitality has impacted the practice of and a career in neurosurgery over a 35-year period, based on the principles outlined by Danny Meyer in his 2006 book Setting the Table. We will define the difference between service, the technical delivery of a product (e.g., a surgical procedure), and hospitality, how the delivery of that service makes someone feel; if someone feels you are on their side, hospitality is present. We will also define the 51% rule for hiring: one is invited onto our team based 49% on technical skill and 51% on these hospitality-related human qualities (optimistic warmth, intelligence, work ethic, empathy, self-awareness, and integrity). KEY MESSAGES/CONCLUSIONS:Hospitality has played a transformative role in a neurosurgery career: in developing a destination academic practice, managing complications, overcoming challenges, and in building an outstanding team. In our opinion, hospitality plays a significant role in pediatric neurosurgery, driving growth in activity and excellence. As Danny says "it takes both great service and great hospitality to rise to the top."

PURPOSE/OBJECTIVE:Central nervous system (CNS) involvement in multidrug-resistant tuberculosis (MDR-TB) is associated with high morbidity, and evidence guiding the use of standardized all-oral regimens in intracranial disease is limited. We describe radiographic evolution of a presumed cerebellar tuberculoma during BPaLM-based therapy for MDR-TB. METHODS:We report the clinical course, microbiologic data, treatment regimen, and serial neuroimaging of a man in his 30s with pulmonary MDR-TB, pleural involvement, and a small peripherally enhancing cerebellar lesion compatible with a tuberculoma. RESULTS:The patient presented with respiratory symptoms and mild headache, and was diagnosed with cavitary pulmonary tuberculosis, pleural involvement, and a small left cerebellar lesion. Further evaluation showed no ataxia, dizziness, or focal neurologic deficits. Sputum acid-fast culture was positive for Mycobacterium tuberculosis, and rapid molecular testing demonstrated rifampin resistance. Whole-genome sequencing confirmed resistance to rifampin, isoniazid, and ethambutol, and did not identify mutations associated with resistance to pyrazinamide, fluoroquinolones, linezolid, clofazimine, or bedaquiline. Treatment was transitioned to BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin) with adjunctive corticosteroids early in the course. Sputum cultures converted to negative approximately 6 weeks after treatment initiation. Serial brain MRI demonstrated progressive reduction in lesion size at 9 weeks, residual punctate enhancement at 21 weeks, near-complete resolution by 44 weeks, and complete radiographic resolution on subsequent imaging. The patient completed 52 weeks of therapy and remained clinically stable, without neurologic deficits or relapse more than 2 years after treatment completion. CONCLUSION/CONCLUSIONS:This case describes radiographic resolution of a small presumed cerebellar tuberculoma during extended BPaLM/BPaL-based therapy for disseminated MDR-TB, highlighting the evidence gap for standardized all-oral regimens in CNS drug-resistant tuberculosis.

Many individuals hospitalized due to severe viral infections develop mental and physical sequelae, which could potentially be prevented by targeted interventions for those at risk. Our goal was to develop and externally validate an algorithm for predicting mental and physical symptoms after SARS-CoV-2 hospitalization utilizing routinely collected clinical data. Participants were included from two independent samples of the German National Pandemic Cohort Network (NAPKON): a model development sample (SUEP; N = 451; mean age: 55.6 ± 15.3; 36.2% female) and an external validation sample (HAP: N = 158; mean age: 55.1 ± 12.1; 39.9% female). Machine learning models leveraging demographic, clinical and biological variables collected at the time of admission were employed to predict Patient-Reported Outcomes Measurement Information System scores (PROMIS) across 7 domains (physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain) three months after SARS-CoV-2 hospitalization. Shapley Additive exPlanation values were used to provide interpretable information about key predictive factors. Approximately 15-20% of participants reported moderate to severe impairment in at least one PROMIS domain three months after hospitalization. For the mental health composite score, the best-performing model achieved RMSE = 1.833 ± 0.341 and R² = 0.927 ± 0.031 in SUEP and RMSE = 3.131 and R² = 0.893 in HAP. For the physical health composite, the best-performing model achieved RMSE = 2.908 ± 0.703 and R² = 0.824 ± 0.052 in SUEP and RMSE = 3.019 and R² = 0.850 in HAP. Furthermore, the models achieved high predictive performance across all individual PROMIS domain scores in both samples. We provide an externally validated methodology for accurately predicting mental and physical symptomatology following hospitalization due to a severe viral infection. This approach may facilitate the development of a brief risk stratification tool at the point of hospitalization, enabling early identification of at-risk patients, improving the prediction accuracy of subsequent psychological and physical sequelae, and supporting timely preventive interventions.