Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Identifying and characterizing sources of targeting error in stereotactic procedures is essential to maximizing accuracy, potentially improving surgical outcomes. We aim to describe a generic framework which characterizes sources of stereotactic inaccuracy. METHODS:We assembled a list of stereotactic systems: ROSA, Neuromate, Mazor Renaissance, ExcelsiusGPS, Cirq, STarFix (FHC), Nexframe, ClearPoint, CRW, and Leksell. We searched the literature for qualitative and quantitative work identifying and quantifying potential sources of inaccuracy and describing each system's implementation using Standards for Reporting Qualitative Research guidelines. Our literature search spanned 1969 to 2024, and various studies were included, with formats ranging from phantom studies to systematic reviews. Keyword searches were conducted, and the details about each system were used to create a framework for identifying and describing the unique targeting error profile of each system. RESULTS:We describe and illustrate the details of various sources of stereotactic inaccuracies and generate a framework to unify these sources into a single framework. This framework entails 5 domains: imaging, registration, mechanical accuracy, target planning and adjustment, and trajectory planning and adjustment. This framework was applied to 10 stereotactic systems. CONCLUSION/CONCLUSIONS:This framework provides a rubric to analyze the sources of error for any stereotactic system. Illustrations allow the reader to understand sources of error conceptually so that they may apply them to their practice.

Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655). Neoadjuvant pembrolizumab was associated with suppression of cell cycle/cancer proliferation genes and upregulation of T-cell/interferon-related gene expression. This signature was unique to patients treated with neoadjuvant pembrolizumab and was an independent positive risk factor for survival. Our results demonstrate a clear pharmacodynamic effect of anti-PD1 therapy in glioblastoma and identify pathways that may mediate resistance. However, we did not confirm a survival benefit to neoadjuvant pembrolizumab in recurrent glioblastoma and our secondary endpoint of PFS-6 was 19.5% (95% CI: 9.29-41.2%) for the pooled neoadjuvant cohorts. Our new data suggests some patients may exhibit innate resistance to pre-surgical ICI and require other concomitant therapies to sensitize effectively.

Bartonella quintana infection can lead to bacillary angiomatosis, peliosis hepatis, chronic bacteremia, and culture-negative endocarditis. Transmitted by the human body louse (Pediculus humanus humanus), B. quintana infection has become an emerging disease in recent decades among persons experiencing homelessness. By using retrospective laboratory surveillance, we identified 5 cases of left-sided, culture-negative B. quintana endocarditis among persons in New York, New York, USA, during January 1, 2020-November 23, 2023. Identifications were made by using molecular assays. All patients experienced unsheltered homelessness in the year before hospitalization. Of those patients, 4 experienced heart failure, 3 renal failure, and 2 embolic strokes; 2 died. Aortic valve replacement occurred in 4 cases. A history of possible body louse infestation was found in 4 cases. Clinicians should consider housing status and history of lice exposure in patients with suspected bartonellosis and have a low threshold for diagnostic testing and empiric treatment in patients experiencing homelessness.

INTRODUCTION/UNASSIGNED:In light of the lack of diversity in academic medicine leadership, diversity-related, student-led national medical organizations (NMOs) provide a space for solace and reprieve among common peers while providing an opportunity to develop leadership competencies in a supportive environment. Despite the impact NMOs have had on cultivating generations of leaders in medicine, trainees may not identify opportunities for leadership development that are transferable to future careers in academic medicine. METHODS/UNASSIGNED:We designed and implemented a dynamic 60-minute workshop with an interactive PowerPoint presentation, author-owned video testimonials (from past student leaders of NMOs), two case presentations, and reflection exercises. We assessed learner self-perceived confidence via workshop surveys. The target audience of this module was medical trainees, including medical students, residents, and fellows. RESULTS/UNASSIGNED:Forty-three workshop attendees across three sites submitted partial or complete survey evaluations. Respondents included medical students (77%), with the remainder self-identified as either postbaccalaureate students, residents/fellows, academic faculty, or physicians. A comparison of pre- and postresponses showed a statistically significant increase in confidence in addressing each of the four educational objectives. Participants felt the case presentations offered relevant applicable examples. DISCUSSION/UNASSIGNED:For many trainees, the role that diversity-related NMOs play in developing leadership competencies may be unclear and not articulated in traditional medical curricula. In this module, we provide examples of how NMOs facilitate leadership development and may encourage our diverse trainees to eventually become academic faculty.

INTRODUCTION/BACKGROUND:Current guidelines for treatment for locally advanced pancreatic cancer recommend chemotherapy ± radiation, or radiation alone when multimodal therapy is contraindicated. In a subset of patients, guideline-recommended treatment (GRT) achieves sufficient response to qualify for potentially curative resection. This study evaluated trends in treatment utilization and aimed to identify barriers to GRT. METHODS:Patients with clinical T4M0 disease in the National Cancer Database from 2010 to 2017 were included. Potential predictors were assessed by relative risk regression with Poisson distribution and compared by log-link function. RESULTS:In total, 28 056 patients met the criteria. Among 17 059 (67.67%) patients treated primarily with chemotherapy, 41.19% also had radiation and 8.89% went onto resection. Many received no cancer-directed treatment or failed to receive GRT. Another 710 patients had radiation (±surgery) without chemotherapy despite few contraindications to chemotherapy. Over time, patients were more likely to undergo resection after chemotherapy (aRR = 1.58; p < 0.0001) and less likely to have chemoradiation (aRR = 0.78; p < 0.0001) or go untreated (aRR = 0.90; p < 0.0001). Socioeconomic factors (race, education, income, and insurance status) affected the likelihood of receiving chemotherapy and surgery. Median overall survival (OS) was significantly improved for patients treated with chemotherapy and particularly in those patients who went on to receive RT or undergo surgical resection. OS was also longer for patients treated at high-volume academic centers. Patients insured by Medicaid, Medicare, or those without insurance had worse OS. CONCLUSIONS:Despite improvement over time, many patients go untreated. Clinical factors were influential, but the impact of vulnerable social standing suggests persistent inequity in access to care.

BACKGROUND:Hypertrophic cardiomyopathy is a genetic, life-threatening cardiovascular disease that often goes unidentified in pediatric patients. Patients are often asymptomatic and neither history or physical examination are reliable to detect the disease. The only reliable method to diagnose hypertrophic cardiomyopathy is with echocardiography to look at interventricular septal thickness. Emerging literature has shown that cardiac point-of-care ultrasound (POCUS) performed by pediatric emergency medicine (PEM) physicians is as effective and accurate compared with cardiac echocardiography performed by pediatric cardiologists. OBJECTIVE:The objective of the study was to determine the diagnostic accuracy of POCUS performed by ultrasound-trained PEM physicians in measuring the interventricular septum end diastole (IVSd) thickness in the pediatric emergency department. METHODS:We conducted a prospective, single-center, observational, diagnostic accuracy study to examine the diagnostic accuracy of POCUS in measuring IVSd thickness in pediatric patients who presented to the pediatric emergency department with symptoms that prompted a cardiac POCUS. Cardiac POCUS findings were interpreted by a PEM physician at the bedside and retrospectively by a pediatric cardiologist. Diagnostic concordance of the measurements obtained by the PEM physician and cardiologist was assessed. RESULTS:Forty-eight patients were enrolled. Median patient age was 13.4 years. There was excellent diagnostic agreement on the measurement of the IVSd thickness between PEM physicians and the pediatric cardiologist (81.25% of cases; 39/48). Disagreement was seen in 18.75% of the cases (9/48). The mean error of disagreement was -0.32, with a 95% confidence interval of -0.37 to -0.28. Overall, the mean error of both agreement and disagreement was -0.046, with 95% confidence interval of -0.08 to -0.01 and P value of 0.008. CONCLUSIONS:Point-of-care ultrasound performed by ultrasound-trained PEM physicians to measure pediatric IVSd thickness has a high diagnostic accuracy with excellent agreement with a pediatric cardiologist.

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations^1,2. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants³. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS⁴. Here we assessed the therapeutic potential of RMC-7977 in a comprehensive range of PDAC models. We observed broad and pronounced anti-tumour activity across models following direct RAS inhibition at exposures that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumour versus normal tissues. Treated tumours exhibited waves of apoptosis along with sustained proliferative arrest, whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. In the autochthonous KPC mouse model, RMC-7977 treatment resulted in a profound extension of survival followed by on-treatment relapse. Analysis of relapsed tumours identified Myc copy number gain as a prevalent candidate resistance mechanism, which could be overcome by combinatorial TEAD inhibition in vitro. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS-GTP inhibition in the setting of PDAC and identify a promising candidate combination therapeutic regimen to overcome monotherapy resistance.

INTRODUCTION/UNASSIGNED:This study examined the potential interplay between motor development and intervention in support of action understanding. METHODS/UNASSIGNED:Eighty nine-month-old infants completed a tool-use training session and goal imitation paradigm that assessed action understanding in counterbalanced order. A metric of motor development was obtained using the Early Motor Questionnaire. RESULTS/UNASSIGNED:Results indicated that training improved action understanding, particularly for those infants who started out with lower means-end skills. Results further indicated that infants who did not receive any training experience in the lab beforehand, drew on their existing means-end skills. DISCUSSION/UNASSIGNED:These results emphasize independent contributions of training and motor development on action understanding and shed light on the interaction between training and individual motor readiness in facilitating action understanding in infancy.