Academic productivity and career trajectory of international medical graduates in US neurosurgery residency programs.

OBJECTIVE: The objective of this study was to review and compare the research experiences and career outcomes of international medical graduates (IMGs) with those of US medical graduates (USMGs). METHODS: Neurosurgery graduates from 2018 to 2020 were evaluated on the basis of medical school, degree, residency program, publications before and during residency, postresidency fellowships, and career progression. Publications were further categorized by author order and type (laboratory, comprehensive clinical, or short communication). RESULTS: Of 550 neurosurgery graduates, 39 (7%) were IMGs, with the largest percentages from India (8/39, 21%) and in a residency position in Pennsylvania (5/39, 13%). Prior to residency, IMGs had a higher median number of all publications (4 vs 1, p < 0.001), first-author articles (2 vs 0, p < 0.001), comprehensive clinical articles (1 vs 0, p = 0.002), and short communication articles (1 vs 0, p < 0.001) than USMGs. Similarly, the median number of papers published by IMGs during residency was also higher compared with that of USMGs for all publications (20 vs 9, p = 0.004), laboratory articles (1 vs 0, p < 0.001), and short communication articles (4 vs 3, p = 0.04). The percentage of early academic appointments was higher for IMGs (25/39, 64%) than for USMGs (232/511, 45%) (p = 0.03). No significant difference was observed between the percentages of postresidency clinical fellowships completed by IMGs (28/39, 72%) and USMGs (302/511, 59%) (p = 0.15). No statistical significance was found between the ranking of neurosurgery residency programs attended by IMGs and USMGs (p = 0.65). CONCLUSIONS: The results indicate that IMGs often exhibit higher academic productivity than USMGs. Although there was no discernible difference in residency program rankings or postresidency fellowships completed, early academic appointments were more prevalent among IMGs.

Gesture encoding in human left precentral gyrus neuronal ensembles.

Understanding the cortical activity patterns driving dexterous upper limb motion has the potential to benefit a broad clinical population living with limited mobility through the development of novel brain-computer interface (BCI) technology. The present study examines the activity of ensembles of motor cortical neurons recorded using microelectrode arrays in the dominant hemisphere of two BrainGate clinical trial participants with cervical spinal cord injury as they attempted to perform a set of 48 different hand gestures. Although each participant displayed a unique organization of their respective neural latent spaces, it was possible to achieve classification accuracies of ~70% for all 48 gestures (and ~90% for sets of 10). Our results show that single unit ensemble activity recorded in a single hemisphere of human precentral gyrus has the potential to generate a wide range of gesture-related signals across both hands, providing an intuitive and diverse set of potential command signals for intracortical BCI use.

Differences in Protein Capture by SP3 and SP4 Demonstrate Mechanistic Insights of Proteomics Cleanup Techniques.

The goal of proteomics experiments is to identify proteins to observe changes in cellular processes and diseases. One challenge in proteomics is the removal of contaminants following protein extraction, which can limit protein identifications. Single-pot, solid-phase-enhanced sample preparation (SP3) is a cleanup technique in which proteins are captured on carboxylate-modified particles through a proposed hydrophilic-interaction-liquid-chromatography (HILIC)-like mechanism. Recent results have suggested that proteins are captured in SP3 due to a protein-aggregation mechanism. Solvent precipitation, single-pot, solid-phase-enhanced sample preparation (SP4) is a newer cleanup technique that employs protein aggregation to capture proteins without modified particles. We hypothesize that differences in capture mechanisms of SP3 and SP4 affect which proteins are identified by each cleanup technique. Herein, we assess the proteins identified and enriched using SP3 versus SP4 for MCF7 subcellular fractions and correlate protein capture in each method to protein hydrophobicity. Our results indicate that SP3 captures more hydrophilic proteins through a combination of HILIC-like and protein-aggregation mechanisms, while SP4 captures more hydrophobic proteins through a protein-aggregation mechanism. Ultimately, we demonstrate that protein-capture mechanisms are distinct, and the selection of a cleanup technique that yields high proteome coverage is dependent on protein-sample hydrophobicity. Data has been deposited into MassIVE (MSV000094130) and ProteomeXchange (PXD049965).

Outpatient Patient Controlled Analgesia (PCA) for the Palliative Care Patient.

This study explores the under-researched domain of patient-controlled analgesia (PCA) for cancer pain management in adult outpatients, focusing on the transition from patient-controlled analgesia pumps (PCA pump) to oral medications. While existing literature primarily addresses the use of PCA in inpatient settings, this descriptive study investigates the initiation of outpatient PCA in palliative care patients. The retrospective chart review includes data from all admissions between July 1, 2014, and December 31, 2020. Among the 49 identified patients, 41 were admitted for cancer-related pain, with an indication for PCA such as insufficient pain relief, highly fluctuating pain, or inadequate response to other routes. Of these patients, 13 were successfully transitioned from outpatient PCA to oral opioids. The study underscores the effective use of PCA as a transitional tool following a pain crisis that necessitates inpatient admission. Future research avenues could explore healthcare utilization, length of stay, and required outpatient resources, such as home visits or telehealth, for optimal PCA use in outpatient settings.

Phototaxis is a satiety-dependent behavioral sequence in Hydra vulgaris.

Understanding how internal states like satiety are connected to animal behavior is a fundamental question in neuroscience. Hydra vulgaris, a freshwater cnidarian with only twelve neuronal cell types, serves as a tractable model system for studying state-dependent behaviors. We find that starved Hydra consistently move towards light, while fed Hydra do not. By modeling this behavior as a set of three sequences of head orientation, jump distance, and jump rate, we demonstrate that the satiety state only affects the rate of the animal jumping to a new position, while the orientation and jump distance are unaffected. These findings yield insights into how internal states in a simple organism, Hydra, affect specific elements of a behavior, and offer general principles for studying the relationship between state-dependent behaviors and their underlying molecular mechanisms.

Phosphodiesterase-5 inhibition collaborates with vaccine-based immunotherapy to reprogram myeloid cells in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is highly lethal and resistant to immunotherapy. Although immune recognition can be enhanced with immunomodulatory agents including checkpoint inhibitors and vaccines, few patients experience clinical efficacy because the tumor immune microenvironment (TiME) is dominated by immunosuppressive myeloid cells that impose T cell inhibition. Inhibition of phosphodiesterase-5 (PDE5) was reported to downregulate metabolic regulators arginase and iNOS in immunosuppressive myeloid cells and enhance immunity against immune-sensitive tumors including head and neck cancers. We show for the first time that combining a PDE5 inhibitor, tadalafil, with a mesothelin-specific vaccine, anti-PD1, and anti-CTLA4 yields antitumor efficacy even against immune-resistant PDAC. To determine immunologic advantages conferred by tadalafil, we profiled the TiME using mass cytometry and single-cell RNA analysis with Domino to infer intercellular signaling. Our analyses demonstrated that tadalafil reprograms myeloid cells to be less immunosuppressive. Moreover, tadalafil synergized with the vaccine, enhancing T cell activation including mesothelin-specific T cells. Tadalafil treatment was also associated with myeloid-T cell signaling axes important for antitumor responses (e.g., Cxcr3, Il12). Our study shows that PDE5 inhibition combined with vaccine-based immunotherapy promotes pro-inflammatory states of myeloid cells, activation of T cells, and enhanced myeloid-T cell crosstalk to yield antitumor efficacy against immune-resistant PDAC.

State-Level Household Energy Insecurity and Diabetes Prevalence Among US Adults, 2020.

The objective of this study was to examine the state-level association between household energy insecurity and diabetes prevalence in 2020. We obtained 1) state-level data on household energy characteristics from the 2020 Residential Energy Consumption Survey and 2) diagnosed diabetes prevalence from the US Diabetes Surveillance System. We found states with a higher percentage of household energy insecurity had greater diabetes prevalence compared with states with lower percentages of energy insecurity. Interventions related to energy assistance may help reduce household energy insecurity, mitigate the risk of diabetes-related complications, and alleviate some of the burden of diabetes management during extreme temperatures.

Mathematical modeling of meningioma volume change after radiation treatment.

OBJECTIVE: Meningiomas are the most common primary central nervous tumor and are often treated with radiation therapy. This study examines the long-term volumetric changes of intracranial meningiomas in response to radiation therapy. The objective is to analyze and model the volumetric changes following treatment. METHODS: Data from a retrospective single-institution database (2005-2015) were used, with inclusion criteria being patients with a diagnosis of meningiomas, along with additional inclusion criteria consisting of treatment with radiation, having at least three magnetic resonance imaging (MRI) scans with one or more before and after radiation treatment, and the patients following up for at least eighteen months. Exclusion criteria consisted of patients less than 18 years old, patients receiving surgery and/or adjuvant chemotherapy following radiation, and patients without any available details regarding radiation treatment parameters. Tumor volumes were measured via T1-weighted post-contrast MRI and calculated using the ABC/2 ellipsoidal approximation, a method allowing for the measurement of non-linear growth volume reduction. RESULTS: Of 48 meningioma patients considered, 10 % experienced post-radiation growth, while 75 % witnessed a ≥50 % decrease in volume over a follow-up period of 0.3-14.9 years. Median decay rate was 0.81, and within 1.17 years, 90 % achieved the predicted volume reduction. Predicted vs. actual volumes showed a mean difference of 0.009 ± 0.347 cc. Initial tumor volumes strongly correlated (Pearson's R=0.98, R-squared=0.96) with final asymptotic volumes, which had a median of 1.50 cc, with interquartile range (IQR) = [0.39, 3.67]. CONCLUSION: 90 % of patients achieved tumor-volume reduction at 1.17 years post-treatment, reaching a non-zero asymptote strongly correlated with initial tumor volume, and 75 % experienced at least a 50 % volume decrease. Individual volume changes for responsive meningiomas can be modeled and predicted using exponential decay curves.

Diagnostic Performance of Renal Contrast Excretion on Early Phase CT Myelography in Spontaneous Intracranial Hypotension.

BACKGROUND AND PURPOSE: Early opacification of the renal collecting system during CT myelography (CTM) performed for the evaluation of Spontaneous Intracranial Hypotension (SIH) has been demonstrated in prior studies. However, these investigations often included CTMs scanned >30 minutes after intrathecal contrast injection, a longer delay than the myelographic techniques used in current practice. The purpose of this study was to determine whether renal contrast excretion (RCE) measured during this earlier time period (≤30 minutes) can discriminate patients with SIH from patients without SIH. MATERIALS AND METHODS: Single-center, retrospective cohort of consecutive patients presenting for evaluation of possible SIH between July 2021-May 2022. RCE was measured in both renal hila using standardized (5-15mm3) ROIs. ROC curves were constructed comparing RCE between patients with SIH to patients without SIH in the overall cohort, and within the subgroup of patients with negative myelograms. RESULTS: The study cohort included 190 subjects. Both unadjusted and adjusted models demonstrated a statistically significant increase in renal contrast density among patients with SIH compared to those without SIH (p-values ≤ 0.001). The ROC curve showed moderate discrimination between these groups (AUC 0.76). However, using clinically meaningful test criteria of sensitivity >90% or specificity >90%, the two corresponding threshold HU values resulted in low specificity of 31.3% and sensitivity of 50.8%. Subgroup analysis of patients with negative myelograms showed poorer performance in discriminating SIH+ from SIH- (AUC 0.62). In this subgroup, using similar test criteria of sensitivity >90% or specificity >90 resulted in low specificities and sensitivities, at 26.0% and 37.5% respectively. CONCLUSIONS: We found a statistically significant positive association between RCE and SIH diagnosis during early-phase CTM, however clinically useful thresholds based on cutoff values for renal HU resulted in poor sensitivities or specificities, with substantial false positives or false negatives, respectively. Thus, while we confirmed statistically significant differences in RCE in the ≤30 min time period, in keeping with prior investigations of more delayed time periods, overlap in renal attenuation values prevented the development of clinically useful threshold value for discriminating SIH+ from SIH-patients. ABBREVIATIONS: SIH = spontaneous intracranial hypotension; RCE = renal contrast excretion; CTM = CT myelography; CVF = CSF-venous fistula; ICHD-3 = international classification of headache disorders third edition; CKD = chronic kidney disease.

Longitudinal Use Patterns of Technology Subtypes During the Transition Into Early Adolescence: Results From the Adolescent Brain Cognitive Development Study.

PURPOSE: Adolescents encounter a complex digital environment, yet existing data on youth technology use rarely differentiates technology subtypes. This study maps the evolution and intricacies of youth engagement with technology subtypes. METHODS: N = 11,868 participants in the Adolescent Brain Cognitive Development study followed from ages ∼9/10 to ∼13/14. We examined youths' self-reported hours per day (hr/day) of technology subtypes: TV/Movies, video games, YouTube, social media, video chat, and texting. We used descriptive statistics and multilevel logistic regression to assess cross-sectional and longitudinal use patterns of technology subtypes, agreement between child and parent reports on the child's technology use, and associations between each technology subtype and sociodemographics (child's biological sex, parent education, income, and marital status). RESULTS: At age 9/10, ∼75% of youth reported minimal (<30 min/day) social technology use (social media, video chat, texting) and up to ∼1.5 hr/day of TV, video games, and YouTube. By age 13/14, TV trajectories were converging to >2 hr/day, but social technology trajectories "fanned out" into a wide range of usage rates. Child and parent reports were weakly correlated (rs range: 0.13-0.29). Using child-reported hours of technology use, increases in the subject-specific odds of using a technology >2 hr/day ranged from 25% (YouTube; 95% CI: 1.16-1.35) to 234% (social media; 95% CI: 3.14-3.55). Compared with males, females had ∼100-200% greater odds of >2 hr/day of social technologies, but ∼40-80% reduced odds of >2 hr/day of video games and YouTube. Higher parent education and income predicted significantly lower odds of >2 hr/day of use - regardless of technology subtype. DISCUSSION: Distributions of youths' self-reported technology engagement are highly contingent on technology subtype, age, and biological sex. Future research on youth development and technology may benefit from considering youths' varied digital experiences.

Disability Ethics and Education in the Age of Artificial Intelligence: Identifying Ability Bias in ChatGPT and Gemini.

OBJECTIVE: To identify and quantify ability bias in generative artificial intelligence large language model chatbots, specifically OpenAI's ChatGPT and Google's Gemini. DESIGN: Observational study of language usage in generative artificial intelligence models. SETTING: Investigation-only browser profile restricted to ChatGPT and Gemini. PARTICIPANTS: Each chatbot generated 60 descriptions of people prompted without specified functional status, 30 descriptions of people with a disability, 30 descriptions of patients with a disability, and 30 descriptions of athletes with a disability (n = 300). MAIN OUTCOME MEASURE: Generated descriptions produced by the models were parsed into words that were linguistically analyzed into favorable qualities or limiting qualities. RESULTS: Both large language models significantly underestimated disability in a population of people, and linguistic analysis showed that people, patients, and athletes with a disability were generated as having significantly fewer favorable qualities and significantly more limitations when compared to people without a disability in both ChatGPT and Gemini. CONCLUSION: Generative artificial intelligence chatbots demonstrate quantifiable ability bias and often exclude people with disabilities in their responses. Ethical use of these generative large language model chatbots in medical systems should recognize this limitation, and further consideration should be taken in developing equitable artificial intelligence technologies.

Malassezia responds to environmental pH signals through the conserved Rim/Pal pathway.

During mammalian colonization and infection, microorganisms must be able to rapidly sense and adapt to changing environmental conditions including alterations in extracellular pH. The fungus-specific Rim/Pal signaling pathway is one process that supports microbial adaptation to alkaline pH. This cascading series of interacting proteins terminates in the proteolytic activation of the highly conserved Rim101/PacC protein, a transcription factor that mediates microbial responses that favor survival in neutral/alkaline pH growth conditions, including many mammalian tissues. We identified the putative Rim pathway proteins Rim101 and Rra1 in the human skin colonizing fungus Malassezia sympodialis. Gene deletion by transconjugation and homologous recombination revealed that Rim101 and Rra1 are required for M. sympodialis growth at higher pH. In addition, comparative transcriptional analysis of the mutant strains compared to wild-type suggested mechanisms for fungal adaptation to alkaline conditions. These pH-sensing signaling proteins are required for optimal growth in a murine model of atopic dermatitis, a pathological condition associated with increased skin pH. Together, these data elucidate both conserved and phylum-specific features of microbial adaptation to extracellular stresses.IMPORTANCEThe ability to adapt to host pH has been previously associated with microbial virulence in several pathogenic fungal species. Here we demonstrate that a fungal-specific alkaline response pathway is conserved in the human skin commensal fungus Malassezia sympodialis (Ms). This pathway is characterized by the pH-dependent activation of the Rim101/PacC transcription factor that controls cell surface adaptations to changing environmental conditions. By disrupting genes encoding two predicted components of this pathway, we demonstrated that the Rim/Pal pathway is conserved in this fungal species as a facilitator of alkaline pH growth. Moreover, targeted gene mutation and comparative transcriptional analysis support the role of the Ms Rra1 protein as a cell surface pH sensor conserved within the basidiomycete fungi, a group including plant and human pathogens. Using an animal model of atopic dermatitis, we demonstrate the importance of Ms Rim/Pal signaling in this common inflammatory condition characterized by increased skin pH.

PanIN and CAF transitions in pancreatic carcinogenesis revealed with spatial data integration.

This study introduces a new imaging, spatial transcriptomics (ST), and single-cell RNA-sequencing integration pipeline to characterize neoplastic cell state transitions during tumorigenesis. We applied a semi-supervised analysis pipeline to examine premalignant pancreatic intraepithelial neoplasias (PanINs) that can develop into pancreatic ductal adenocarcinoma (PDAC). Their strict diagnosis on formalin-fixed and paraffin-embedded (FFPE) samples limited the single-cell characterization of human PanINs within their microenvironment. We leverage whole transcriptome FFPE ST to enable the study of a rare cohort of matched low-grade (LG) and high-grade (HG) PanIN lesions to track progression and map cellular phenotypes relative to single-cell PDAC datasets. We demonstrate that cancer-associated fibroblasts (CAFs), including antigen-presenting CAFs, are located close to PanINs. We further observed a transition from CAF-related inflammatory signaling to cellular proliferation during PanIN progression. We validate these findings with single-cell high-dimensional imaging proteomics and transcriptomics technologies. Altogether, our semi-supervised learning framework for spatial multi-omics has broad applicability across cancer types to decipher the spatiotemporal dynamics of carcinogenesis.

Immune checkpoint inhibitors as subsequent treatment in older adults with non-small cell lung cancer and synchronous brain metastases.

Background: Immune checkpoint inhibitors (ICIs) have become the mainstay treatment for non-small cell lung cancer (NSCLC). However, there is a lack of studies assessing ICIs as subsequent treatment in older adults with NSCLC and brain metastasis (BM). This retrospective cohort study compared the real-world survival of older patients with NSCLC and BM at diagnosis [synchronous BM (SBM)] previously treated with chemotherapy receiving ICI versus chemotherapy as subsequent treatment. Methods: Patients with NSCLC and SBM ≥65 years previously treated with chemotherapy were identified using the SEER-Medicare database (2010-2019). Patients receiving new chemotherapy and/or Food and Drug Administration (FDA)-approved ICIs as second/third-line treatment were included, excluding those ever-receiving targeted therapies. Each ICI patient was matched to one chemotherapy patient by time to subsequent treatment (within ±30 days) from diagnosis. Overall survival (OS) time was measured from the start of subsequent treatment to death, censored at disenrollment from Medicare Part A/B, enrollment in Part C, or end of study (December 31, 2019), whichever came first. OS curves were estimated and compared using the Kaplan-Meier (KM) method and log-rank test. Hazard ratio (HR) was estimated using a multivariable-adjusted Cox proportional hazards model. Results: Matched cohorts included 546 patients [273 in each group; median age 71 (range, 65-87) years]. ICI patients were older, more likely non-Hispanic, with squamous cell carcinoma, and liver metastasis compared to chemotherapy. KM estimated better survival in ICI than chemotherapy {median survival: 209 days [95% confidence interval (CI): 160-275] vs. 155 days (95% CI: 135-187); log-rank P<0.001}. ICI was associated with a lower adjusted hazard of death [HR =0.63; 95% CI: 0.52-0.75; P<0.001] compared to subsequent chemotherapy treatment. Conclusions: In this population-based study of older patients with NSCLC and SBM previously treated with chemotherapy, subsequent treatment with ICI was associated with improved survival compared to chemotherapy.

DNA-PKcs Inhibition Improves Sequential Gene Insertion of the Full-Length CFTR cDNA in Airway Stem Cells.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although many people with CF (pwCF) are treated using CFTR modulators, some are non-responsive due to their genotype or other uncharacterized reasons. Autologous airway stem cell therapies, in which the CFTR cDNA has been replaced, may enable a durable therapy for all pwCF. Previously, CRISPR-Cas9 with two AAVs was used to sequentially insert two halves of the CFTR cDNA and an enrichment cassette into the CFTR locus. However, the editing efficiency was <10% and required enrichment to restore CFTR function. Further improvement in gene insertion may enhance cell therapy production. To improve CFTR cDNA insertion in human airway basal stem cells (ABCs), we evaluated the use of the small molecules AZD7648 and ART558 which inhibit non-homologous end joining (NHEJ) and micro-homology mediated end joining (MMEJ). Adding AZD7648 alone improved gene insertion by 2-3-fold. Adding both ART558 and AZD7648 improved gene insertion but induced toxicity. ABCs edited in the presence of AZD7648 produced differentiated airway epithelial sheets with restored CFTR function after enrichment. Adding AZD7648 did not increase off-target editing. Further studies are necessary to validate if AZD7648 treatment enriches cells with oncogenic mutations.

Customized passive-dynamic ankle-foot orthoses can improve walking economy and speed for many individuals post-stroke.

BACKGROUND: Passive-dynamic ankle-foot orthoses (PD-AFOs) are often prescribed to address plantar flexor weakness during gait, which is commonly observed after stroke. However, limited evidence is available to inform the prescription guidelines of PD-AFO bending stiffness. This study assessed the extent to which PD-AFOs customized to match an individual's level of plantar flexor weakness influence walking function, as compared to No AFO and their standard of care (SOC) AFO. METHODS: Mechanical cost-of-transport, self-selected walking speed, and key biomechanical variables were measured while individuals greater than six months post-stroke walked with No AFO, with their SOC AFO, and with a stiffness-customized PD-AFO. Outcomes were compared across these conditions using a repeated measures ANOVA or Friedman test (depending on normality) for group-level analysis and simulation modeling analysis for individual-level analysis. RESULTS: Twenty participants completed study activities. Mechanical cost-of-transport and self-selected walking speed improved with the stiffness-customized PD-AFOs compared to No AFO and SOC AFO. However, this did not result in a consistent improvement in other biomechanical variables toward typical values. In line with the heterogeneous nature of the post-stroke population, the response to the PD-AFO was highly variable. CONCLUSIONS: Stiffness-customized PD-AFOs can improve the mechanical cost-of-transport and self-selected walking speed in many individuals post-stroke, as compared to No AFO and participants' standard of care AFO. This work provides initial efficacy data for stiffness-customized PD-AFOs in individuals post-stroke and lays the foundation for future studies to enable consistently effective prescription of PD-AFOs for patients post-stroke in clinical practice. TRIAL REGISTRATION: NCT04619043.

Student experiences with a molecular biotechnology course containing an interactive 3D immersive simulation and its impact on motivational beliefs.

The development and use of virtual laboratories to augment traditional in-person skills training continues to grow. Virtual labs have been implemented in a number of diverse educational settings, which have many purported benefits including their adaptability, accessibility, and repeatability. However, few studies have evaluated the impact of virtual laboratories outside of academic achievement and skills competencies, especially in biotechnology. In this study, an interdisciplinary team of content experts, video game researchers, instructional designers, and assessment experts developed a 3D immersive simulation designed to teach novice scientists the technical skills necessary to perform sterile mammalian cell culture technique. Unique to the simulation development process is the recreation of an immersive experience through the capture of details in the real-world lab where participants have the freedom of choice in their actions, while receiving immediate feedback on their technical skills as well as procedural execution. However, unlike an in-person laboratory course, students are able to iterate and practice their skills outside of class time and learn from their mistakes. Over the course of two semesters, we used a mixed-methods study design to evaluate student attitudes towards the simulation and their science motivational beliefs. Students' self-efficacy and science identity were assessed after engaging with the simulation prior to the physical laboratory. Our results show that students' science identity remained unchanged while their science self-efficacy increased. Furthermore, students had positive perceptions of the benefits of the virtual simulation. These data suggest that the virtual cell culture simulation can be a useful pedagogical training tool to support students' motivational beliefs that is both accessible and easy to implement.

Immunologic Predictors of Vaccine Responsiveness in Patients With Lymphoma and Chronic Lymphocytic Leukemia.

Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. Severe acute respiratory syndrome coronavirus 2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic messenger RNA vaccine response in retrospective and prospective cohorts with lymphoma and chronic lymphocytic leukemia, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active treatment, but nonresponse was also common within observation and posttreatment groups. Total immunoglobulin A and immunoglobulin M correlated with successful vaccine response. In individuals treated with anti-CD19-directed chimeric antigen receptor-modified T cells, nonresponse was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to individualize vaccine timing.

Well-Being and Leadership Within the Emergency Department.

Description This article looks at well-being and the role of leadership from the perspective of emergency medicine. The importance of leadership within the emergency department (ED), emergency medicine writing at large, and the prevention of burnout and compassion fatigue cannot be overstated. This article looks at the need for more research and measured interventions within the ED. It also highlights some measures that could be taken to help improve well-being from a leadership perspective to improve patient safety and outcomes within the ED.