Utilization of carbonated calcium phosphate cement for contouring cranioplasty in patients with syndromic craniosynostosis.

PURPOSE: Carbonated calcium phosphate (CCP) cement is an alloplastic material which has been increasingly utilized for cranioplasty reconstruction; however, there is a paucity of data investigating its use in patients with syndromic craniosynostosis. The purpose of this study was to characterize our institutional experience with CCP cement for secondary contouring cranioplasty in these patients to establish safety and aesthetic efficacy. METHODS: Patients with syndromic craniosynostosis undergoing cranioplasty with CCP cement from 2009 to 2022 were retrospectively reviewed for prior medical and surgical history, cranioplasty size, cement usage, and postoperative complications. Aesthetic ratings of the forehead region were quantified using the Whitaker scoring system at three timepoints: preoperative (T1), < 6 months postoperative (T2), and > 1 year postoperative (T3). RESULTS: Twenty-one patients were included. Age at surgery was 16.2 ± 2.8 years, forehead cranioplasty area was 135 ± 112 cm2, and mass of cement was 17.2 ± 7.8 g. Patients were followed for 3.0 ± 3.1 years. Whitaker scores decreased from 1.9 ± 0.4 at T1 to 1.4 ± 0.5 at T2 (p = 0.005). Whitaker scores at T2 and T3 were not significantly different (p = 0.720). Two infectious complications (9.5%) were noted, one at 4.5 months postoperatively and the other at 23 months, both requiring operative removal of CCP cement. CONCLUSION: Our results suggest that aesthetic forehead ratings improve after CCP contouring cranioplasty and that the improvement is sustained in medium-term follow-up. Complications were uncommon, suggesting that CCP is relatively safe though longer-term follow-up is needed before reaching definitive conclusions.

Craniosynostosis in primary metabolic bone disorders: a single-institution experience.

PURPOSE: The incidence of metabolic bone diseases in pediatric neurosurgical patients is rare. We examined our institutional experience of metabolic bone diseases along with a review of the literature in an effort to understand management for this rare entity. METHODS: Retrospective review of the electronic medical record database was performed to identify patients with primary metabolic bone disorders who underwent craniosynostosis surgery between 2011 and 2022 at a quaternary referral pediatric hospital. Literature review was conducted for primary metabolic bone disorders associated with craniosynostosis. RESULTS: Ten patients were identified, 6 of whom were male. The most common bone disorders were hypophosphatemic rickets (n = 2) and pseudohypoparathyroidism (n = 2). The median age at diagnosis of metabolic bone disorder was 2.02 years (IQR: 0.11-4.26), 2.52 years (IQR: 1.24-3.14) at craniosynostosis diagnosis, and 2.65 years (IQR: 0.91-3.58) at the time of surgery. Sagittal suture was most commonly fused (n = 4), followed by multi-suture craniosynostosis (n = 3). Other imaging findings included Chiari (n = 1), hydrocephalus (n = 1), and concurrent Chiari and hydrocephalus (n = 1). All patients underwent surgery for craniosynostosis, with the most common operation being bifronto-orbital advancement (n = 4). A total of 5 patients underwent reoperation, 3 of which were planned second-stage surgeries and 2 of whom had craniosynostosis recurrence. CONCLUSIONS: We advocate screening for suture abnormalities in children with primary metabolic bone disorders. While cranial vault remodeling is not associated with a high rate of postoperative complications in this patient cohort, craniosynostosis recurrences may occur, and parental counseling is recommended.

Sensitivity and specificity of self-reported psychiatric diagnoses amongst patients treated for opioid use disorder.

BACKGROUND: Patients with opioid use disorder (OUD) frequently present with comorbid psychiatric illnesses which have significant implications for their treatment outcomes. Notably, these are often identified by self-report. Our study examined the sensitivity and specificity of self-reported psychiatric diagnoses against a structured diagnostic interview in a cohort of patients receiving outpatient pharmacological treatment for OUD. METHODS: Using cross-sectional data from adults receiving outpatient opioid agonist treatment for OUD in clinics across Ontario, Canada, we compared participants' self-reported psychiatric diagnoses with those identified by the Mini Neuropsychiatric Interview (MINI) Version 6.0 administered at the time of study entry. Sensitivity and specificity were calculated for self-report of psychiatric diagnoses. RESULTS: Amongst a sample of 683 participants, 24% (n = 162) reported having a comorbid psychiatric disorder. Only 104 of these 162 individuals (64%) reporting a comorbidity met criteria for a psychiatric disorder as per the MINI; meanwhile, 304 (75%) participants who self-reported no psychiatric comorbidity were in fact identified to meet MINI criteria for a psychiatric disorder. The sensitivity and specificity for any self-reported psychiatric diagnoses were 25.5% (95% CI 21.3, 30.0) and 78.9% (95% CI 73.6, 83.6), respectively. CONCLUSIONS: Our findings raise questions about the utility of self-reported psychiatric comorbidity in patients with OUD, particularly in the context of low sensitivity of self-reported diagnoses. Several factors may contribute to this including remittance and relapse of some psychiatric illnesses, underdiagnosis, and the challenge of differentiating psychiatric and substance-induced disorders. These findings highlight that other methods should be considered in order to identify comorbid psychiatric disorders in patients with OUD.

Quantitating Endosomal Escape of a Library of Polymers for mRNA Delivery.

Endosomal escape is a key step for intracellular drug delivery of nucleic acids, but reliable and sensitive methods for its quantitation remain an unmet need. In order to rationally optimize the mRNA transfection efficiency of a library of polymeric materials, we designed a deactivated Renilla luciferase-derived molecular probe whose activity can be restored only in the cytosol. This probe can be coencapsulated with mRNA in the same delivery vehicle, thereby accurately measuring its endosomal escape efficiency. We examined a library of poly(amine-co-ester) (PACE) polymers with different end groups using this probe and observed a strong correlation between endosomal escape and transfection efficiency (R2 = 0.9334). In addition, we found that mRNA encapsulation efficiency and endosomal escape, but not uptake, were determinant factors for transfection efficiency. The polymers with high endosomal escape/transfection efficiency in vitro also showed good transfection efficiency in vivo, and mRNA expression was primarily observed in spleens after intravenous delivery. Together, our study suggests that the luciferase probe can be used as an effective tool to quantitate endosomal escape, which is essential for rational optimization of intracellular drug delivery systems.

Targeting ß-catenin in hepatocellular cancers induced by coexpression of mutant ß-catenin and K-Ras in mice.

Recently, we have shown that coexpression of hMet and mutant-ß-catenin using sleeping beauty transposon/transposase leads to hepatocellular carcinoma (HCC) in mice that corresponds to around 10% of human HCC. In the current study, we investigate whether Ras activation, which can occur downstream of Met signaling, is sufficient to cause HCC in association with mutant-ß-catenin. We also tested therapeutic efficacy of targeting ß-catenin in an HCC model. We show that mutant-K-Ras (G12D), which leads to Ras activation, cooperates with ß-catenin mutants (S33Y, S45Y) to yield HCC in mice. Affymetrix microarray showed > 90% similarity in gene expression in mutant-K-Ras-ß-catenin and Met-ß-catenin HCC. K-Ras-ß-catenin tumors showed up-regulation of ß-catenin targets like glutamine synthetase (GS), leukocyte cell-derived chemotaxin 2, Regucalcin, and Cyclin-D1 and of K-Ras effectors, including phosphorylated extracellular signal-regulated kinase, phosphorylated protein kinase B, phosphorylated mammalian target of rapamycin, phosphorylated eukaryotic translation initiation factor 4E, phosphorylated 4E-binding protein 1, and p-S6 ribosomal protein. Inclusion of dominant-negative transcription factor 4 at the time of K-Ras-ß-catenin injection prevented HCC and downstream ß-catenin and Ras signaling. To address whether targeting ß-catenin has any benefit postestablishment of HCC, we administered K-Ras-ß-catenin mice with EnCore lipid nanoparticles (LNP) loaded with a Dicer substrate small interfering RNA targeting catenin beta 1 (CTNNB1; CTNNB1-LNP), scrambled sequence (Scr-LNP), or phosphate-buffered saline for multiple cycles. A significant decrease in tumor burden was evident in the CTNNB1-LNP group versus all controls, which was associated with dramatic decreases in ß-catenin targets and some K-Ras effectors, leading to reduced tumor cell proliferation and viability. Intriguingly, in relatively few mice, non-GS-positive tumors, which were evident as a small subset of overall tumor burden, were not affected by ß-catenin suppression. CONCLUSION: Ras activation downstream of c-Met is sufficient to induce clinically relevant HCC in cooperation with mutant ß-catenin. ß-catenin suppression by a clinically relevant modality is effective in treatment of ß-catenin-positive, GS-positive HCCs. (Hepatology 2017;65:1581-1599).

Modeling a human hepatocellular carcinoma subset in mice through coexpression of met and point-mutant ß-catenin.

Hepatocellular cancer (HCC) remains a significant therapeutic challenge due to its poorly understood molecular basis. In the current study, we investigated two independent cohorts of 249 and 194 HCC cases for any combinatorial molecular aberrations. Specifically we assessed for simultaneous HMET expression or hMet activation and catenin ß1 gene (CTNNB1) mutations to address any concomitant Met and Wnt signaling. To investigate cooperation in tumorigenesis, we coexpressed hMet and ß-catenin point mutants (S33Y or S45Y) in hepatocytes using sleeping beauty transposon/transposase and hydrodynamic tail vein injection and characterized tumors for growth, signaling, gene signatures, and similarity to human HCC. Missense mutations in exon 3 of CTNNB1 were identified in subsets of HCC patients. Irrespective of amino acid affected, all exon 3 mutations induced similar changes in gene expression. Concomitant HMET overexpression or hMet activation and CTNNB1 mutations were evident in 9%-12.5% of HCCs. Coexpression of hMet and mutant-ß-catenin led to notable HCC in mice. Tumors showed active Wnt and hMet signaling with evidence of glutamine synthetase and cyclin D1 positivity and mitogen-activated protein kinase/extracellular signal-regulated kinase, AKT/Ras/mammalian target of rapamycin activation. Introduction of dominant-negative T-cell factor 4 prevented tumorigenesis. The gene expression of mouse tumors in hMet-mutant ß-catenin showed high correlation, with subsets of human HCC displaying concomitant hMet activation signature and CTNNB1 mutations. CONCLUSION: We have identified cooperation of hMet and ß-catenin activation in a subset of HCC patients and modeled this human disease in mice with a significant transcriptomic intersection; this model will provide novel insight into the biology of this tumor and allow us to evaluate novel therapies as a step toward precision medicine. (Hepatology 2016;64:1587-1605).

Memory systems modulate crosslinguistic influence on third language morphosyntactic acquisition.

Previous studies on crosslinguistic influence (CLI) on third language (L3) morphosyntactic acquisition have provided support for competing theories about the source(s) of CLI. The present study aimed to test if both L1 and L2 can be the source of CLI, and whether they influence L3 learning in similar or different ways. In particular, we aimed to add to our knowledge of the neural correlates of CLI by conducting an exploratory EEG study to investigate how L1 and L2 CLI affect L3 neural processing. Predictions based on the D/P model, which posited different memory systems sustaining L1 and L2, were tested. The findings confirmed both L1-sourced and L2-sourced facilitation on L3 morphosyntactic acquisition. Specifically, we suggest that L1-similarity showed a consolidating effect on L3 implicit knowledge and neurocognitive internalization, whereas L2-similarity contributed to enhanced L3 metalinguistic knowledge. This preliminary study is the first to investigate the neurocognitive mechanisms underlying CLI in L3 learning by natural language learners.

Home Care Workers Providing Person-Centered Care to People With Dementia.

Person-centered care for people living with dementia has been associated with improved functional ability and quality of life, yet little is known about person-centered care in the home settings. Our objective was to explore home care worker perspectives on providing person-centered care for their clients living with dementia. Using secondary qualitative analysis of 22 semi-structured interviews with home care workers, we identified themes related to the Dementia Initiative's person-centered dementia care framework (Initiative, 2013). We found that home care workers acknowledged their client's personhood while also advocating for their needs. However, home care workers encountered barriers to providing person-centered care, including role limitations and challenging dynamics with other home care workers and family caregivers. This analysis can inform further approaches to better integrate home care workers in person-centered healthcare teams and improve how the needs of people living with dementia are identified and met in the home.

Public Perception of the Tobacco 21 Amendment on Twitter in the United States: Observational Study.

BACKGROUND: Following the signing of the Tobacco 21 Amendment (T21) in December 2019 to raise the minimum legal age for the sale of tobacco products from 18 to 21 years in the United States, there is a need to monitor public responses and potential unintended consequences. Social media platforms, such as Twitter (subsequently rebranded as X), can provide rich data on public perceptions. OBJECTIVE: This study contributes to the literature using Twitter data to assess the knowledge and beliefs of T21. METHODS: Twitter data were collected from November 2019 to February 2021 using the Twitter streaming application programming interface with keywords related to vaping or e-cigarettes, such as "vape," "ecig," etc. The temporal trend of the T21 discussion on Twitter was examined using the mean number of daily T21-related tweets. Inductive methods were used to manually code the tweets into different sentiment groups (positive, neutral, and negative) based on the attitude expressed toward the policy by 3 coders with high interrater reliability. Topics discussed were examined within each sentiment group through theme analyses. RESULTS: Among the collected 3197 tweets, 2169 tweets were related to T21, of which 444 tweets (20.5%) showed a positive attitude, 736 (33.9%) showed a negative attitude, and 989 (45.6%) showed a neutral attitude. The temporal trend showed a clear peak in the number of tweets around January 2020, following the enactment of this legislation. For positive tweets, the most frequent topics were "avoidance of further regulation" (120/444, 27%), "Enforce T21" (110/444, 24.8%), and "health benefits" (81/444, 18.2%). For negative tweets, the most frequent topics were "general disagreement or frustration" (207/736, 28.1%) and "will still use tobacco" (188/736, 25.5%). Neutral tweets were primarily "public service announcements (PSA) or news posts" (782/989, 79.1%). CONCLUSIONS: Overall, we find that one-third of tweets displayed a negative attitude toward T21 during the study period. Many were frustrated with T21 and reported that underage consumers could still obtain products. Social media data provide a timely opportunity to monitor public perceptions and responses to regulatory actions. Continued monitoring can inform enforcement efforts and potential unintended consequences of T21.

Recurrent and Concurrent Prediction of Longitudinal Progression of Stargardt Atrophy and Geographic Atrophy.

Stargardt disease and age-related macular degeneration are the leading causes of blindness in the juvenile and geriatric populations, respectively. The formation of atrophic regions of the macula is a hallmark of the end-stages of both diseases. The progression of these diseases is tracked using various imaging modalities, two of the most common being fundus autofluorescence (FAF) imaging and spectral-domain optical coherence tomography (SD-OCT). This study seeks to investigate the use of longitudinal FAF and SD-OCT imaging (month 0, month 6, month 12, and month 18) data for the predictive modelling of future atrophy in Stargardt and geographic atrophy. To achieve such an objective, we develop a set of novel deep convolutional neural networks enhanced with recurrent network units for longitudinal prediction and concurrent learning of ensemble network units (termed ReConNet) which take advantage of improved retinal layer features beyond the mean intensity features. Using FAF images, the neural network presented in this paper achieved mean (± standard deviation, SD) and median Dice coefficients of 0.895 (± 0.086) and 0.922 for Stargardt atrophy, and 0.864 (± 0.113) and 0.893 for geographic atrophy. Using SD-OCT images for Stargardt atrophy, the neural network achieved mean and median Dice coefficients of 0.882 (± 0.101) and 0.906, respectively. When predicting only the interval growth of the atrophic lesions with FAF images, mean (± SD) and median Dice coefficients of 0.557 (± 0.094) and 0.559 were achieved for Stargardt atrophy, and 0.612 (± 0.089) and 0.601 for geographic atrophy. The prediction performance in OCT images is comparably good to that using FAF which opens a new, more efficient, and practical door in the assessment of atrophy progression for clinical trials and retina clinics, beyond widely used FAF. These results are highly encouraging for a high-performance interval growth prediction when more frequent or longer-term longitudinal data are available in our clinics. This is a pressing task for our next step in ongoing research.

A Cross-Sectional Analysis of Interventional Clinical Trials in High-Grade Glioma Therapy.

High-grade glioma is the most frequent and lethal primary tumor of the central nervous system. Despite advances in surgical, pharmacological, and cell-directed therapies, there have been no updates to the standard of care in over a decade. This cross-sectional study analyzes patient and trial data from 201 interventional trials completed between 2010 and 2023, encompassing 18,563 participants. Although we found that all trials reported participant age and sex, only 52% of trials reported participant demographics, resulting in 51% of total participant demographics being unreported. The majority of studies did not report ethnicity, with approximately 60% of participants unreported. Additionally, males were significantly underrepresented in trials, comprising 60% of participants despite representing 75% of glioblastoma patients. Improved demographic reporting has been observed since 2011; however, it is inconsistent. Furthermore, we cataloged the geographic diversity of trials across the United States and found significant coverage deserts in relatively rural, but highly affected, areas such as Montana and Maine. We found a wider distribution of trials in both urban and wealthier regions, which indicates extensive coverage gaps and decreased access to participation for patients of a lower socioeconomic status.

Magnetic Resonance Imaging-Guided Frameless Stereotactic Injections of the Bilateral Cerebellar Dentate Nuclei in Nonhuman Primates: Technical Note.

BACKGROUND AND OBJECTIVES: Nonhuman primates (NHPs) are important preclinical models for evaluating therapeutics because of their anatomophysiological similarities to humans, and can be especially useful for testing new delivery targets. With the growing promise of cell and gene therapies for the treatment of neurological diseases, it is important to ensure the accurate and safe delivery of these agents to target structures in the brain. However, a standard guideline or method has not been developed for stereotactic targeting in NHPs. In this article, we describe the safe use of a magnetic resonance imaging-guided frameless stereotactic system to target bilateral cerebellar dentate nuclei for accurate, real-time delivery of viral vector in NHPs. METHODS: Seventeen rhesus macaques (Macaca mulatta) underwent stereotactic surgery under real-time MRI guidance using the ClearPoint® system. Bilateral cerebellar dentate nuclei were targeted through a single parietal entry point with a transtentorial approach. Fifty microliters of contrast-impregnated infusate was delivered to each dentate nucleus, and adjustments were made as necessary according to real-time MRI monitoring of delivery. Perioperative clinical outcomes and postoperative volumes of distribution were recorded. RESULTS: All macaques underwent bilateral surgery successfully. Superficial pin site infection occurred in 4/17 (23.5%) subjects, which resolved with antibiotics. Two episodes of transient neurological deficit (anisocoria and unilateral weakness) were recorded, which did not require additional postoperative treatment and resolved over time. Volume of distribution of infusate achieved satisfactory coverage of target dentate nuclei, and only 1 incidence (2.9%) of cerebrospinal fluid penetration was recorded. Mean volume of distribution was 161.22 ± 39.61 mm3 (left, 173.65 ± 48.29; right, 148.80 ± 23.98). CONCLUSION: MRI-guided frameless stereotactic injection of bilateral cerebellar dentate nuclei in NHPs is safe and feasible. The use of this technique enables real-time modification of the surgical plan to achieve adequate target coverage and can be readily translated to clinical use.

The effect of chronic kidney disease on short-term single-level lumbar fusion outcomes.

INTRODUCTION: Chronic kidney disease (CKD) has an increasing global prevalence and has previously been associated with increased complications and morbidity after spine surgery. Understanding the isolated effect of CKD on short-term patient outcomes is critical for optimizing perioperative risk management and healthcare utilization. OBJECTIVE: The aim of this study is to utilize coarsened exact matching (CEM) to analyze the isolated effect of CKD on short-term patient outcomes in single-level posterior lumbar fusion surgery. METHODS: A retrospective analysis of 4680 consecutive patients undergoing single-level, posterior-only lumbar fusion was performed. Univariate logistic regression comparing the odds of outcomes in patients with CKD (n=40) to patients without medical comorbidities (n=2329) was performed. CEM was then employed to match patients with CKD to those without any comorbidities 1:1 on ten patient characteristics known to affect neurosurgical outcomes. Primary outcomes included intraoperative complications, length of stay, discharge disposition, and 30-day Emergency Department (ED) visits, readmissions, reoperations, and mortality. RESULTS: In a univariate logistic regression, CKD was associated with increased risk of 30-day ED visits (OR=3.53, p=0.003) but not complication, discharge disposition, or 30-day readmissions or reoperations. Between otherwise exactly matched patients (n=72), CKD similarly remained associated with an increased risk of 30-day ED visits (OR=7.00, p=0.034) and not with other outcomes. CONCLUSION: Between otherwise exactly matched patients undergoing single-level posterior lumbar fusion, CKD was related to increased risk of 30-day ED utilization but not other markers indicative of inferior surgical outcomes. Further study must investigate the reasons for increased ED visitation and implement risk-mitigation strategies for these patients.

Zebrafish models of human-duplicated gene SRGAP2 reveal novel functions in microglia and visual system development.

Recent expansion of duplicated genes unique in the Homo lineage likely contributed to brain evolution and other human-specific traits. One hallmark example is the expansion of the human SRGAP2 family, resulting in a human-specific paralog SRGAP2C . Introduction of SRGAP2C in mouse models is associated with altering cortical neuronal migration, axon guidance, synaptogenesis, and sensory-task performance. Truncated, human-specific SRGAP2C heterodimerizes with the full-length ancestral gene product SRGAP2A and antagonizes its functions. However, the significance of SRGAP2 duplication beyond neocortex development has not been elucidated due to the embryonic lethality of complete Srgap2 knockout in mice. Using zebrafish, we showed that srgap2 knockout results in viable offspring that phenocopy "humanized" SRGAP2C larvae. Specifically, human SRGAP2C protein interacts with zebrafish Srgap2, demonstrating similar Srgap2 functional antagonism observed in mice. Shared traits between knockout and humanized zebrafish larvae include altered morphometric features (i.e., reduced body length and inter-eye distance) and differential expression of synapse-, axogenesis-, vision-related genes. Through single-cell transcriptome analysis, we further observed a skewed balance of excitatory and inhibitory neurons that likely contributes to increased susceptibility to seizures displayed by Srgap2 mutant larvae, a phenotype resembling SRGAP2 loss-of-function in a child with early infantile epileptic encephalopathy. Single-cell data also pointed to strong microglia expression of srgap2 with mutants exhibiting altered membrane dynamics and likely delayed maturation of microglial cells. srgap2 -expressing microglia cells were also detected in the developing eye together with altered expression of genes related to axogenesis and synaptogenesis in mutant retinal cells. Consistent with the perturbed gene expression in the retina, we found that SRGAP2 mutant larvae exhibited increased sensitivity to broad and fine visual cues. Finally, comparing the transcriptomes of relevant cell types between human (+ SRGAP2C ) and non-human primates (- SRGAP2C ) revealed significant overlaps of gene alterations with mutant cells in our zebrafish models; this suggests that SRGAP2C plays similar roles altering microglia and the visual system in modern humans. Together, our functional characterization of zebrafish Srgap2 and human SRGAP2C in zebrafish uncovered novel gene functions and highlights the strength of cross-species analysis in understanding the development of human-specific features.

Treatment of critical bleeding events in patients with immune thrombocytopenia: a protocol for a systematic review and meta-analysis.

BACKGROUND: Critical bleeding events in adults and children with ITP are medical emergencies; however, evidence-based treatment protocols are lacking. Due to the severe thrombocytopenia, (typically platelet count less than 20 × 109/L), a critical bleed portends a high risk of death or disability. We plan to perform a systematic review and meta-analysis of treatments for critical bleeding in patients with ITP that will inform evidence-based recommendations. METHODS: Literature searches will be conducted in four electronic databases: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. Eligible studies will be randomized controlled trials or observational studies that enrolled patients with ITP describing one or more interventions for the management of critical bleeding. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation will be conducted independently and in duplicate using Covidence and Excel. Outcomes will be pooled for meta-analysis where appropriate or summarized descriptively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology will be used to evaluate the certainty of the evidence. Primary outcomes of interest will include frequency of critical bleeds, mortality and bleeding-related mortality, bleeding resolution, platelet count, and disability. DISCUSSION: Evidence-based treatments for critical bleeding in patients with ITP are needed to improve patient outcomes and standardize care in the emergency setting. SYSTEMATIC REVIEW REGISTRATION: CRD42020161206.

Preoperative stereotactic radiosurgery for cerebral metastases: safe, effective, and decreases steroid dependency.

OBJECTIVE: Preoperative stereotactic radiosurgery (SRS) is emerging as a viable alternative to standard postoperative SRS. Studies have suggested that preoperative SRS provides comparable tumor control and overall survival (OS) and may reduce the incidence of leptomeningeal disease (LMD) and adverse radiation effects (AREs). It is unknown, however, if preoperative SRS remains effective in cohorts including large brain metastases (> 14 cm3) or if preoperative SRS affects steroid taper/immunotherapy. Here, the authors report the results of a phase 2 single-arm trial assessing a prospectively acquired series of 26 patients who underwent preoperative SRS, without a volumetric cutoff, compared with a propensity score-matched concurrent cohort of 30 patients who underwent postoperative SRS to address these salient questions. METHODS: Demographics, oncological history, surgical details, and outcomes were collected from the medical records. Coprimary endpoints were local tumor control (LTC) and a composite outcome of LTC, ARE, and LMD. Additional outcomes were OS, steroid taper details, and immunotherapy resumption. For survival analyses, cohorts were propensity score matched. RESULTS: Preoperative and postoperative SRS patients were comparable in terms of age, sex, Karnofsky Performance Status score, oncological history, and operative details. Gross tumor volume (GTV) was significantly higher in the preoperative group (median 12.2 vs 5.3 cm3, p < 0.001). One-year LTC (preoperative SRS: 77.2% vs postoperative SRS: 82.5%, p = 0.61) and composite outcome (68.3% vs 72.7%, p = 0.38) were not significantly different between the groups. In multivariable analysis, preoperative SRS did not have a significant effect on LTC (HR 1.57 [95% CI 0.38-6.49], p = 0.536) or the composite outcome (HR 1.18 [95% CI 0.38-3.72], p = 0.771), although the confidence intervals were large. The median OS (preoperative SRS: 17.0 vs postoperative SRS: 14.0 months, p = 0.61) was not significantly different. Rates of LMD were nonsignificantly lower in the preoperative SRS group (3.8% vs 16.7%, p = 0.200). Greater GTV volume was associated with prolonged (> 10 days) steroid taper (OR 1.24 [95% CI 1.04-1.55], p = 0.032). However, in multivariable analysis, preoperative SRS markedly reduced the steroid taper length (OR 0.13 [95% CI 0.02-0.61], p = 0.016). Time to immunotherapy was shorter in the preoperative SRS group (36 [IQR 26, 76] vs OR 228 [IQR 129, 436] days, p = 0.02). CONCLUSIONS: Compared with postoperative SRS, preoperative SRS is a safe and effective strategy in the management of cerebral metastases of all sizes and provides comparable tumor control without increased adverse effects. Notably, preoperative SRS enabled rapid steroid taper, even in larger tumors. Future studies should specifically examine the interaction of preoperative SRS with steroid usage and resumption of systemic therapies and the subsequent effects on systemic progression and OS.

Is It Reasonable to Expect Students and Trainees to Internalize Equity as a Core Professional Value When Teaching and Learning Occurs in Segregated Settings?

Training in a segregated health care system means that health professions students and trainees learn bias and experience helplessness and burnout if they wish to-but cannot-rectify segregated care. When racial segregation is built into training environments, many students and trainees quickly internalize which patients are de facto deemed more worthy of care. Students and trainees who recognize this feature of their professional training as dysfunctional and as an ethical and equity problem need support when reporting inequities and advocating for desegregated health systems. By supporting such efforts, faculty and organizations can help desegregate health care, minimize iatrogenic harm from bias, motivate health equity, and promote equitable access to quality health service delivery.

Public Perceptions and Discussions of Premium Cigars on Reddit.

Introduction: While premium cigars have similar addictive, toxic, and carcinogenic constituents as other cigars and cigarettes, about 1% of the US adults reported premium cigar use from 2010 to 2019. This study aimed to understand public perceptions and discussions of premium cigars on Reddit, one of the most popular social media platforms. Methods: Using keywords such as "premium cigar", we extracted 2,238 Reddit posts from Reddit Archive between July 2019 and June 2021. Among them, 1,626 posts were related to premium cigars. By employing the inductive approach, we manually coded each Reddit post on premium cigars to understand public perceptions and discussions of premium cigars by summarizing them into different topics and subtopics. Results: Longitudinal analysis showed that the number of Reddit posts on premium cigars increased since June 2020. Content analysis showed that among Reddit posts related to premium cigars, the most popular topic is "Information sharing" (75.72%), in which Reddit users shared their perceptions about premium cigars, asked for advice, and provided some recommendations about premium cigars. Over one-quarter of posts (27.17%) are sharing user experiences of premium cigars (such as taste). Nearly one-fifth (18.99%) of posts are discussing the affordability of premium cigars. In addition, 7.87% of posts are discussing legal/policy issues related to premium cigars, and 6.82% of posts are related to the health risks of premium cigars compared to cigarettes. Conclusions: Public perceptions including misperceptions, user experiences, and affordability related to premium cigars have been actively discussed on Reddit.

Public perceptions of the FDA's marketing authorization of Vuse on Twitter/X.

Introduction: On October 12, 2021, the FDA issued its first marketing granted orders for Vuse, the e-cigarette product by R.J. Reynolds Vapor Company. The public perceptions and reactions to the FDA's Vuse authorization are prevalent on social media platforms such as Twitter/X. We aim to understand public perceptions of the FDA's Vuse authorization in the US using Twitter/X data. Methods: Through the Twitter/X streaming API (Application Programming Interface), 3,852 tweets between October 12, 2021, and October 23, 2021, were downloaded using the keyword of Vuse. With the elimination of retweets, irrelevant tweets, and tweets from other countries, the final dataset consisted of 523 relevant tweets from the US. Based on their attitudes toward the FDA authorization on Vuse, these tweets were coded into three major categories: positive, negative, and neutral. These tweets were further manually classified into different categories based on their contents. Results: There was a large peak on Twitter/X mentioning FDA's Vuse authorization on October 13, 2021, just after the authorization was announced. Of the 523 US tweets related to FDA's Vuse authorization, 6.12% (n=32) were positive, 26.77% (n=140) were negative, and 67.11% (n=351) were neutral. In positive tweets, the dominant subcategory was Cessation Claims (n=18, 56.25%). In negative tweets, the topics Health Risk (n=43, 30.71%), Criticize Authorization (n=42, 30.00%), and Big Tobacco (n=40, 38.57%) were the major topics. News (n=271, 77.21%) was the most prevalent topic among neutral tweets. In addition, tweets with a positive attitude tend to have more likes. Discussion: Public perceptions and discussions on Twitter/X regarding the FDA's Vuse authorization in the US showed that Twitter/X users were more likely to show a negative than a positive attitude with a major concern about health risks.

Care Disruptions and End-Of-Life Care Experiences Among Home-Based Primary Care Patients During the COVID-19 Pandemic in New York City: A Retrospective Chart Review.

Background: Research on deaths during COVID-19 has largely focused on hospitals and nursing homes. Less is known about medically complex patients receiving care in the community. We examined care disruptions and end-of-life experiences of homebound patients receiving home-based primary care (HBPC) in New York City during the initial 2020 COVID-19 surge. Methods: We conducted a retrospective chart review of patients enrolled in Mount Sinai Visiting Doctors who died between March 1-June 30, 2020. We collected patient sociodemographic and clinical data and analyzed care disruptions and end-of-life experiences using clinical notes, informed by thematic and narrative analysis. Results: Among 1300 homebound patients, 112 (9%) died during the study period. Patients who died were more likely to be older, non-Hispanic white, and have dementia than those who survived. Thirty percent of decedents had confirmed or probable COVID-19. Fifty-eight (52%) were referred to hospice and 50 enrolled. Seventy-three percent died at home. We identified multiple intersecting disruptions in family caregiving, paid caregiving, medical supplies and services, and hospice care, as well as hospital avoidance, complicating EOL experiences. The HBPC team responded by providing clinical, logistical and emotional support to patients and families. Conclusion: Despite substantial care disruptions, the majority of patients in our study died at home with support from their HBPC team as the practice worked to manage care disruptions. Our findings suggest HBPC's multi-disciplinary, team-based model may be uniquely suited to meet the needs of the most medically and socially vulnerable older adults at end of life during public health emergencies.