Faculty Bibliography

In 2022, 1 in 8 people in the world were living with obesity, and lifestyle interventions that include diet, exercise, and behavioral modification have been the foundation for management of obesity. Recently, pharmacologic therapies have been developed for management of obesity, the newest of these being glucagon-like peptide 1 receptor agonists. With the development of new pharmacologic options, the American Gastroenterological Association developed a guideline in 2022 to provide evidence-based recommendations for the pharmacologic management of obesity in adults and recommended, for adults with obesity or overweight with weight-related complications who have had an inadequate response to lifestyle interventions, adding pharmacologic agents to lifestyle interventions over continuing lifestyle interventions alone. In this article, 2 experts review the available evidence to answer the following questions: How effective are lifestyle interventions for the treatment of obesity? How effective are pharmacologic interventions for the treatment of obesity? Given these options, how do you engage in a shared decision-making discussion to develop a mutually agreed-on treatment plan?

OBJECTIVE:Vocal tremor (VT) poses treatment challenges due to uncertain pathophysiology. VT is typically classified into two phenotypes: isolated vocal tremor (iVT) and essential tremor-related voice tremor (ETvt). The impact of phenotypes on upper aerodigestive tract physiology during swallowing remains unclear. Qualitative and quantitative measures were employed to characterize tremor phenotypes and investigate the effects on swallowing physiology. METHODS:Eleven ETvt participants (1 Male, 10 Female; x̄ age = 74) and 8 iVT participants (1 Male, 7 Female; x̄ age = 71) swallowed 20 mL boluses in cued and uncued conditions under standardized fluoroscopic visualization. Sustained/a/productions were captured to assess the rate and extent of fundamental frequency (F0) modulation. Penetration and Aspiration Scale (PAS) scores were obtained and swallowing biomechanics were captured using Swallowtail™ software. Participants also completed the Swallowing Quality of Life (SWAL-QOL) questionnaire. RESULTS:Hypopharyngeal transit was faster in both VT phenotypes compared with Swallowtail™ normative reference data. Total pharyngeal transit times, however, were only faster in patients with iVT, relative to reference data. No significant differences were observed on the SWAL-QOL or PAS between tremor phenotypes. SWAL-QOL scores revealed that these patients rarely reported dysphagia symptoms. CONCLUSIONS:Subtle differences in swallowing patterns were observed across VT phenotypes, possibly related to adaptive mechanisms resulting in quicker pharyngeal bolus transit. Most patients did not report swallowing issues or dysphagia symptoms. This study is foundational for larger studies on this challenging population. LEVEL OF EVIDENCE/METHODS:4 Laryngoscope, 134:4599-4603, 2024.

DHPS deficiency syndrome is an ultra-rare neurodevelopmental disorder (NDD) which results from biallelic mutations in the gene encoding the enzyme deoxyhypusine synthase (DHPS). DHPS is essential to synthesize hypusine, a rare amino acid formed by post-translational modification of a conserved lysine in eukaryotic initiation factor 5 A (eIF5A). DHPS deficiency syndrome causes epilepsy, cognitive and motor impairments, and mild facial dysmorphology. In mice, a brain-specific genetic deletion of Dhps at birth impairs eIF5A^HYP-dependent mRNA translation. This alters expression of proteins required for neuronal development and function, and phenotypically models features of human DHPS deficiency. We studied the role of DHPS in early brain development using a zebrafish loss-of-function model generated by knockdown of dhps expression with an antisense morpholino oligomer (MO) targeting the exon 2/intron 2 (E2I2) splice site of the dhps pre-mRNA. dhps knockdown embryos exhibited dose-dependent developmental delay and dysmorphology, including microcephaly, axis truncation, and body curvature. In dhps knockdown larvae, electrophysiological analysis showed increased epileptiform activity, and confocal microscopy analysis revealed reduced arborisation of GABAergic neurons. Our findings confirm that hypusination of eIF5A by DHPS is needed for early brain development, and zebrafish with an antisense knockdown of dhps model features of DHPS deficiency syndrome.

OBJECTIVE:To examine associations between cognitive stimulation in the home at 6 months and maternal feeding styles at 24 months, direct intervention effects of Smart Beginnings (SB) on feeding styles, and potential indirect effects of SB on feeding styles via earlier intervention effects on cognitive stimulation. STUDY DESIGN/METHODS:Single-blind, two-site randomized clinical trial (RCT) of the SB intervention. SB integrates PlayReadVIP, a universal, pediatric primary care-based program, and Family Check-Up (FCU), a targeted secondary home-based parenting intervention. Mother-infant dyads (N=327) were randomized at birth to standard pediatric care or the SB intervention. Linear regression analyses determined associations between cognitive stimulation at 6 months and maternal feeding styles at 24 months, a secondary data analysis. Direct intervention impacts on feeding styles, a secondary RCT outcome, were also assessed and mediation analyses explored intervention effects on feeding styles via earlier intervention impacts on cognitive stimulation. RESULTS:Cognitive stimulation was significantly associated with higher responsive and lower indulgent feeding styles. SB mothers were less likely to exhibit pressuring styles compared with controls (Effect Size [ES]=-0.12, p=0.02). Although no direct intervention effects were found on responsive or indulgent feeding styles, indirect effects of SB were evident on these feeding styles through intervention-induced increases in cognitive stimulation in the SB group. CONCLUSION/CONCLUSIONS:This study found positive linkages between cognitive stimulation in the home and later feeding styles. Additionally, the SB intervention was associated with less pressured feeding and indirect pathways mediated by intervention effects on cognitive stimulation. Implications for early childhood parenting interventions are discussed.

Across species, navigation is crucial for finding both resources and shelter. In vertebrates, the hippocampus supports memory-guided goal-directed navigation, whereas in arthropods the central complex supports similar functions. A growing literature is revealing similarities and differences in the organization and function of these brain regions. We review current knowledge about how each structure supports goal-directed navigation by building internal representations of the position or orientation of an animal in space, and of the location or direction of potential goals. We describe input pathways to each structure - medial and lateral entorhinal cortex in vertebrates, and columnar and tangential neurons in insects - that primarily encode spatial and non-spatial information, respectively. Finally, we highlight similarities and differences in spatial encoding across clades and suggest experimental approaches to compare coding principles and behavioral capabilities across species. Such a comparative approach can provide new insights into the neural basis of spatial navigation and neural computation.

Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and increased access to neuroimaging. While most exhibit nonmalignant behavior, a subset of meningiomas are biologically aggressive and are associated with treatment resistance, resulting in significant neurologic morbidity and even mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system (CNS) tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official World Health Organization (cIMPACT-NOW) working group. Additionally, clinical equipoise still remains on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas including field-leading experts, have prepared this comprehensive consensus narrative review directed toward clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality-of-life studies, and management strategies for unique meningioma patient populations. In each section, we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.

Conscientious objection is a legally protected right of medical professionals to recuse themselves from patient care activities that conflict with their personal values. Anesthesiology is different from most specialties with respect to conscientious objection in that the focus is to facilitate safe, efficient, and successful performance of procedures by others, rather than to perform the treatment in question. This could give rise to a unique, somewhat indirect ethical tension between the application of conscientious objection and potential infringement upon patient autonomy and well-being. While some situations have clear grounds and precedent for conscientious objection (e.g., abortion, or futile procedures), newer procedures, such as gender-affirming surgery and xenotransplantation, may trigger conscientious objection for complex reasons. This review discusses ethical, legal, and practical aspects of conscientious objection; challenges to anesthesia groups, departments, and healthcare organizations when conscientious objection is invoked by anesthesiologists; and strategies to help mitigate the ethical dilemmas.

During infectious disease epidemics, accurate diagnostic testing is key to rapidly identify and treat cases, and mitigate transmission. When a novel pathogen is involved, building testing capacity and scaling testing services at the local level can present major challenges to healthcare systems, public health agencies, and laboratories. This mixed methods study examined lessons learned from the scale-up of SARS-CoV-2 testing services in New York City (NYC), as a core part of NYC's Test & Trace program. Using quantitative and geospatial analyses, the authors assessed program success at maximizing reach, equity, and timeliness of SARS-CoV-2 diagnostic testing services across NYC neighborhoods. Qualitative analysis of key informant interviews elucidated key decisions, facilitators, and barriers involved in the scale-up of SARS-CoV-2 testing services. A major early facilitator was the ability to establish working relationships with private sector vendors and contractors to rapidly procure and manufacture necessary supplies locally. NYC residents were, on average, less than 25 min away from free SARS-CoV-2 diagnostic testing services by public transport, and services were successfully directed to most neighborhoods with the highest transmission rates, with only one notable exception. A key feature was to direct mobile testing vans and rapid antigen testing services to areas based on real-time neighborhood transmission data. Municipal leaders should prioritize fortifying supply chains, establish cross-sectoral partnerships to support and extend testing services, plan for continuous testing and validation of assays, ensure open communication feedback loops with CBO partners, and maintain infrastructure to support mobile services during infectious disease emergencies.

BACKGROUND AND AIMS/OBJECTIVE:Patients with intermediate-risk pulmonary embolism (PE) commonly present with a significantly reduced cardiac index (CI). However, the identification of this more severe profile requires invasive hemodynamic monitoring. Whether inferior vena cava (IVC) contrast reflux, as a marker of worse right ventricular function, can predict invasive hemodynamics has not been explored. METHODS:This was a single-center retrospective study over a 3-year period of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization. CT pulmonary angiograms were reviewed, and contrast reflux was graded as no/minimal reflux (limited to the IVC) or substantial (opacification including hepatic veins) based on an established scale. RESULTS:were 62.6 %, 93.1 %, 94.6 %, and 56.2 %, respectively. These findings remained significant in a multivariable model and were similar when isolating for intermediate-risk patients (n = 72, 85 %). CONCLUSIONS:The degree of contrast reflux is highly specific for a reduced cardiac index in PE even when isolating for intermediate-risk patients. Real-time prediction of a hemodynamic profile may have added value in the risk-stratification of PE.