Faculty Bibliography

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.

Treatment with the hypomethylating agent 5-azacytidine (AZA) increases survival in high-risk (HR) myelodysplastic syndrome (MDS) patients, but predicting patient response and overall survival remains challenging. To address these issues, we analyzed mutational and transcriptional profiles in CD34+ hematopoietic stem/progenitor cells (HSPCs) before and following AZA therapy in MDS patients. AZA treatment led to a greater reduction in the mutational burden in both blast and hematological responders than non-responders. Blast and hematological responders showed transcriptional evidence of pre-treatment enrichment for pathways such as oxidative phosphorylation, MYC targets, and mTORC1 signaling. While blast non-response was associated with TNFa signaling and leukemia stem cell signature, hematological non-response was associated with cell-cycle related pathways. AZA induced similar transcriptional responses in MDS patients regardless of response type. Comparison of blast responders and non-responders to normal controls, allowed us to generate a transcriptional classifier that could predict AZA response and survival. This classifier outperformed a previously developed gene signature in a second MDS patient cohort, but signatures of hematological responses were unable to predict survival. Overall, these studies characterize the molecular consequences of AZA treatment in MDS HSPCs and identify a potential tool for predicting AZA therapy responses and overall survival prior to initiation of therapy.

This article traces the evolution of the Big Events framework since it began as an attempt to understand why sociopolitical transitions in the Former Soviet Union, South Africa, and Indonesia were followed by HIV outbreaks. Big Events frameworks have evolved over time, but all versions try to concretize how macrosocial changes lead to social, personal and environmental changes that shape risk environments and drug use or other behavioral patterns in ways that may lead to epidemics. Important stages in the evolution of the Big Events framework included understanding that the sequelae of Big Events were contingent rather than deterministic, and the development of new survey measures to understand pathways through which Big Events affect social and epidemiologic outcomes. On a broader level, the Big Events framework is a useful crystallization and application of more abstract sociological, social epidemiologic and Marxist frameworks about upstream/downstream relationships and how major social changes are related to epidemics. As such, they raise issues of how to conduct research on dialectical interaction processes. On another level, this article traces the Big Events "style of thought" as Mannheim (Mannheim, 1971) termed it, within the historical context of changes in public health and social science theory, particularly during and after the 1960s.

OBJECTIVE:The objective of this study is to estimate health-related quality of life (HRQoL) by continuous BMI by age, sex, and demographic group in the United States. METHODS:We estimated HRQoL (overall and by domain) by continuous BMI using SF-6D (Short-Form Six-Dimension) data from 182,778 respondents ages 18 years and older from the repeated cross-sectional Medical Expenditure Panel Survey (MEPS) 2008 to 2016. We adjusted for BMI self-report bias and for potential confounding between BMI and HRQoL. RESULTS:(95% CI: 26.45-26.55) for male individuals. By BMI category, excess weight contributed to HRQoL loss of 0.0349 for obesity overall, rising to 0.0724 for class III obesity. By domain, pain was the largest cause of HRQoL loss for obesity (26%), followed by role limitations (22%). CONCLUSIONS:HRQoL is lower for people with excess body weight across a broad range of ages and BMI levels, especially at high levels of BMI, with pain being the largest driver of HRQoL loss. These findings highlight the importance of promoting a healthy weight for the entire population while also targeting efforts to prevent extreme weight gain over the life course.

This study aimed to evaluate the dose-dependent brain temperature effects of transcranial photobiomodulation (t-PBM). Thirty adult subjects with major depressive disorder were randomized to three t-PBM sessions with different doses (low: 50 mW/cm², medium: 300 mW/cm², high: 850 mW/cm²) and a sham treatment. The low and medium doses were administered in continuous wave mode, while the high dose was administered in pulsed wave mode. A 3T MRI scanner was used to perform proton magnetic resonance spectroscopy (¹H-MRS). A voxel with a volume of 30 × 30 × 15 mm³ was placed on the left prefrontal region. Brain temperature (°C) was derived by analyzing ¹H-MRS spectrum chemical shift differences between the water (~ 4.7 ppm) and N-acetyl aspartate (NAA) (~ 2.01 ppm) peaks. After quality control of the data, the following group numbers were available for both pre- and post-temperature estimations: sham (n = 10), low (n = 11), medium (n = 10), and high (n = 8). We did not detect significant temperature differences for any t-PBM-active or sham groups post-irradiation (p-value range = 0.105 and 0.781). We also tested for potential differences in the pre-post variability of brain temperature in each group. As for t-PBM active groups, the lowest fluctuation (variance) was observed for the medium dose (σ² = 0.29), followed by the low dose (σ² = 0.47), and the highest fluctuation was for the high dose (σ² = 0.67). t-PBM sham condition showed the overall lowest fluctuation (σ² = 0.11). Our ¹H-MRS thermometry results showed no significant brain temperature elevations during t-PBM administration.

OBJECTIVES/OBJECTIVE:This study investigates the prevalence of the use of reusable menstrual materials in LMICs, examines differences in prevalence between countries and areas, and identifies individual and country-level factors associated with their use. METHODS:Data from Multiple Indicator Cluster surveys conducted between 2017 and 2020 in LMICs were used. Prevalence estimates and 95% CIs were calculated for overall, rural, and urban areas. Multivariable logistic regression was used to identify individual and country-level factors associated with the use of reusable menstrual materials. RESULTS:The study included 42 surveys from LMICs, with 1653850 weighted women and girls aged 15-49 years. The overall prevalence of the use of reusable menstrual materials was 12.1% (95% CI 12.1-12.2), with significant variation between and within countries, ranging from 0.5% (0.3-0.8) in Serbia to 97.2% (96.5-97.9) in Sao Tome and Principe. The prevalence was higher in rural areas (23.9% [23.8-24.0]) than in urban areas (6.2% [6.2-6.2]), with significant differences between most countries. Use of reusable menstrual materials was associated with lower education levels, being married, low economic status, living in Asia and Africa, living in countries with lower GDP, living in rural areas, and limited availability of private places to wash menstrual materials. The prevalence of the use of reusable menstrual materials had an inverse linear relationship with the country's GDP. CONCLUSIONS:The study found that the use of reusable menstrual materials is more prevalent among women and girls in rural areas, those with lower education levels, lower economic status, and those living in countries with lower GDP. Given these disparities, policies and initiatives targeted at improving menstrual health in LMICs should focus on socioeconomically disadvantaged groups to ensure they have access to safe and appropriate menstrual materials.

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?

BACKGROUND:rVSVΔG-ZEBOV-GP is the first approved vaccine with clinical efficacy against Ebola virus disease. Although a seroprotective threshold has not been defined for those at occupational risk of exposure, the current vaccine strategy is to attain a sustained high level of antibody titres. The aim of this trial was to explore the effects of delayed boosting upon both the height and duration of antibody titres following primary immunisation. METHODS:plaque-forming unit per mL of VSVΔG-ZEBOV-GP. 18 months later, individuals who consented and were still eligible were randomly assigned 1:1 to receive either a homologous booster dose or no booster. Study visits for safety and serial blood collections for antibody titres were done on enrolled participants at months 0, 1, 3, 6, 12, 18, 19, 24, 30, and 36. Through July, 2021, a web-based application was used for randomisation, including assignments with schedules for each of the five sites using mixed permuted blocks. The trial was not masked to participants or site staff. The primary endpoint was a comparison of geometric mean titres (GMTs) of anti-Ebola virus glycoprotein IgG antibody at month 36 (ie, 18 months after randomisation) for all randomly assigned participants who completed the 36 months of follow-up (primary analysis cohort). Investigators were aware of antibody titres from baseline (enrolment) through month 18 but were masked to summary data by randomisation group after month 18. This study is registered with ClinicalTrials.gov (NCT02788227). FINDINGS/RESULTS:Of the 248 participants who enrolled and received their primary immunisation, 114 proceeded to the randomisation step at month 18. The two randomisation groups were balanced: 57 participants (24 [42%] of whom were female; median age was 42 years [IQR 35-50]) were randomly assigned to the booster group and 57 (24 [42%] of whom were female; median age was 42 years [IQR 36-51]) to the no-booster group. Of those randomly assigned, 92 participants (45 in the booster group and 47 in the no-booster group) completed 36 months of follow-up. At 18 months after primary immunisation, GMTs in the no-booster group increased from a baseline of 10 ELISA units (EU)/mL (95% CI 7-14) to 1451 EU/mL (1118-1882); GMTs in the booster group increased from 9 EU/mL (6-16) to 1769 EU/mL (1348-2321). At month 19, GMTs were 31 408 EU/mL (23 181-42 554) for the booster group and 1406 EU/mL (1078-1833) for the no-booster group; at month 36, GMTs were 10 146 EU/mL (7960-12 933) for the booster group and 1240 EU/mL (984-1563) for the no-booster group. Accordingly, the geometric mean ratio (GMR) of antibody titres had increased almost 21-fold more in the booster versus no-booster group at 1 month after booster administration (GMR 20·6; 95% CI 18·2-23·0; p<0·0001) and was still over 7-fold higher at month 36 (GMR 7·8; 95% CI 5·5-10·2; p<0·0001). Consistent with previous reports of this vaccine's side-effects, transient mono-articular or oligo-articular arthritis was diagnosed in 18 (9%) of 207 primary vaccination recipients; after randomisation, arthritis was diagnosed in one (2%) of 57 participants in the no-booster group. No new cases of arthritis developed after booster administration. Four serious adverse events occurred following randomisation: one (epistaxis) in the booster group and three (gastrointestinal haemorrhage, prostate cancer, and tachyarrhythmia) in the no-booster group. None of the serious adverse events was judged attributable to the booster vaccination assignment. INTERPRETATION/CONCLUSIONS:In addition to no new safety concerns and in marked contrast to earlier trials evaluating short-term boosting, delaying a rVSVΔG-ZEBOV-GP booster until month 18 resulted in an increase in GMT that remained several-fold above the no-booster group GMT for at least 18 months. These findings could have implications for defining the optimal timing of booster doses as pre-exposure prophylaxis in populations at ongoing risk for Ebola virus exposure. FUNDING/BACKGROUND:The Division of Intramural Research and the Division of Clinical Research of the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health, Canadian Immunization Research Network through the Public Health Agency of Canada, Canadian Institutes of Health Research, and the US Defense Threat Reduction Agency.

The astrocyte, a major glial cell type in the central nervous system (CNS), is widely regarded as a functionally diverse mediator of homeostasis. During development and throughout adulthood, astrocytes have essential roles, such as providing neuron metabolic support, modulating synaptic function, and maintaining the blood-brain barrier (BBB). Recent evidence continues to underscore their functional heterogeneity and importance for CNS maintenance, as well as how these cells ensure optimal CNS and immune responses to disease, acute trauma, and infection. Advances in our understanding of neuroimmune interactions complement our knowledge of astrocyte functional heterogeneity, where astrocytes are now regarded as key effectors and propagators of immune signaling. This shift in perspective highlights the role of astrocytes not merely as support cells, but as active participants in CNS immune responses.

INTRODUCTION/BACKGROUND:Autonomy during residency is crucial to the training and development of competent surgeons. An essential component of this process is the 'teaching assistant (TA)' case, an indispensable opportunity for residents to gain confidence and hone intraoperative skills. However, high-quality data on the volume and diversity of cases that graduates perform are scarce. METHODS:A retrospective analysis was performed from publicly collected data of operative case logs from general surgery residents graduating from ACGME-accredited programs from 2006 to 2023. Data on the median overall number of surgeon chief and TA cases were retrieved. Collected data were organized based on sub-specialties. The Mann-Kendall trend test was used to investigate trends in TA cases and surgeon chief operative volume. RESULTS:Between 2007 and 2023, the surgeon chief cases gradually increased from 229 to 274 (19.6 ​% increase; τ ​= ​0.610, p ​= ​0.001). There was a concurrent 72.7 ​% increase in TA cases from a median of 22-38 (τ ​= ​0.574, p ​= ​0.001). Surgeon chief (283 per resident) and TA cases (43 per resident) peaked in 2018-2019 and 2016-2017. The uptrend in TA cases was associated with the significant increase in colorectal (τ ​= ​0.559, p ​= ​0.001), general surgery-other (τ ​= ​0.404, p ​= ​0.018), and hepatopancreaticobiliary (HPB) (τ ​= ​0.596, p ​= ​0.001) subspecialties. Trauma and vascular surgery did not change significantly. With respect to total chief cases, general surgery-other (τ ​= ​0.956, p=<0.001), HPB (τ ​= ​0.713, p=<0.001) and colorectal (τ ​= ​0.522, p ​= ​0.004) volume increased. There was no significant change in trauma and foregut volume, while the volume of endocrine (τ ​= ​-0.485, p ​= ​0.006) and vascular surgery (τ ​= ​0.603, p ​= ​0.001) dropped significantly. The procedural category with the highest chief and TA volume was 'colorectal tract - large intestine.' Most procedural categories (53.49 ​%) retained a median of 0 teaching cases. No chief cases were logged for the specialties generally not considered part of general surgery (genitourinary, nervous system, orthopedics, and gynecology), although a median of 1 surgeon chief genitourinary case was recorded from 2018 to 2023. CONCLUSIONS:Over the past seventeen years, there has been a gradual uptrend in the number of surgeon chief and TA cases. While this is a positive indicator of improved autonomy, further research must focus on strategies to improve resident autonomy to train well-rounded surgeons safely.