ChatGPT and neurosurgical education: A crossroads of innovation and opportunity.

Large language models (LLM) have been promising recently in the medical field, with numerous applications in clinical neuroscience. OpenAI's launch of Generative Pre-trained Transformer 3.5 (GPT-3.5) in November 2022 and its successor, Generative Pre-trained Transformer 4 (GPT 4) in March 2023 have garnered widespread attention and debate surrounding natural language processing (NLP) and LLM advancements. Transformer models are trained on natural language datasets to predict and generate sequences of characters. Using internal weights from training, they produce tokens that align with their understanding of the initial input. This paper delves into ChatGPT's potential as a learning tool in neurosurgery while contextualizing its abilities for passing medical licensing exams and neurosurgery written boards. Additionally, possibilities for creating personalized case presentations and study material are discussed alongside ChatGPT's capacity to optimize the research workflow and perform a concise literature review. However, such tools need to be used with caution, given the possibility of artificial intelligence hallucinations and other concerns such as user overreliance, and complacency. Overall, this opinion paper raises key points surrounding ChatGPT's role in neurosurgical education.

Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma.

Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making.

Preoperative Corticosteroids Reduce Diagnostic Accuracy of Stereotactic Biopsies in Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Despite general acceptance that corticosteroid therapy (CST) should be withheld before biopsy for suspected primary central nervous system lymphoma (PCNSL), there remains conflicting evidence surrounding the precise impact of preoperative CST on the histopathological diagnosis. The objective of this systematic review and meta-analysis was to describe and quantify the effects of preoperative CST on the diagnostic accuracy of biopsies for PCNSL. METHODS: Primary articles were screened from Ovid MEDLINE, Embase, Web of Science, and Scopus databases. Meta-analysis was performed for immunocompetent patients with histologically confirmed PCNSL. Subgroup and regression analyses were performed to assess the effects of biopsy type, CST duration, dose, and preoperative taper on the diagnostic accuracy. In addition, the sensitivity of cerebrospinal fluid (CSF) analyses for PCNSL was assessed. RESULTS: Nineteen studies, comprising 1226 patients (45% female; mean age: 60.3 years), were included. Preoperative CST increased the risk of nondiagnostic biopsy with a relative risk (RR) of 2.1 (95% CI: 1.1-4.1). In the stereotactic biopsy subgroup, the RR for nondiagnostic biopsy was 3.0 (95% CI: 1.2-7.5). CST taper, duration, and dose did not significantly influence diagnostic biopsy rates. The sensitivity of CSF cytology, including flow cytometry, for PCNSL was 8.0% (95% CI: 6.0%-10.7%). CONCLUSION: Our results suggest that preoperative CST reduces the diagnostic yield of stereotactic biopsies for PCNSL. We found no evidence that tapering CST before biopsy improves diagnostic rates. CSF analysis currently has a poor sensitivity for the diagnosis of PCNSL.

Corrigendum: Grade 3 Meningioma Survival and Recurrence Outcomes in an International Multicenter Cohort.

[This corrects the article DOI: 10.1055/s-0044-1779888.].

Molecular prognostication in grade 3 meningiomas and p16/MTAP immunohistochemistry for predicting CDKN2A/B status.

Background: The World Health Organization 2021 classification introduces molecular grading criteria for anaplastic meningiomas, including TERT promoter (TERTp) mutations and CDKN2A/B homozygous deletion. Additional adverse prognostic factors include H3K27me3 and BAP1 loss. The aim of this study was to explore whether these molecular alterations stratified clinical outcomes in a single-center cohort of grade 3 meningiomas. Additionally, we examined whether p16 and MTAP immunohistochemistry can predict CDKN2A/B status. Methods: Clinical and histopathological information was obtained from the electronic medical records of grade 3 meningiomas resected at a tertiary center between 2007 and 2020. Molecular testing for TERTp mutations and CDKN2A/B copy-number status, methylation profiling, and immunohistochemistry for H3K27me3, BAP1, p16, and methylthioadenosine phosphorylase (MTAP) were performed. Predictors of survival were identified by Cox regression. Results: Eight of 15 cases demonstrated elevated mitotic index (≥20 mitoses per 10 consecutive high-power fields), 1 tumor exhibited BAP1 loss, 4 harbored TERTp mutations, and 3 demonstrated CDKN2A/B homozygous deletion. Meningiomas with TERTp mutations and/or CDKN2A/B homozygous deletion showed significantly reduced survival compared to anaplastic meningiomas with elevated mitotic index alone. Immunohistochemical loss of p16 and MTAP demonstrated high sensitivity (67% and 100%, respectively) and specificity (100% and 100%, respectively) for predicting CDKN2A/B status. Conclusions: Molecular alterations of grade 3 meningiomas stratify clinical outcomes more so than histologic features alone. Immunohistochemical loss of p16 and MTAP show promise in predicting CDKN2A/B status.

Grade 3 meningioma survival and recurrence outcomes in an international multicenter cohort.

OBJECTIVE: Grade 3 meningioma represents a rare meningioma subtype, for which limited natural history data are available. The objective of this study was to identify demographics and pathologic characteristics, clinical and functional status outcomes, and prognostic factors in an international cohort of grade 3 meningioma patients. METHODS: Clinical and histopathological data were collected for patients treated at 7 sites across North America and Europe between 1991 and 2022. RESULTS: A total of 103 patients (54% female, median age 65 [IQR 52, 72] years) were included. Sixty-seven (65%) patients had de novo grade 3 lesions, whereas 29 (28%) had malignant transformations of lower-grade meningiomas. All patients underwent initial resection of their tumor. Patients were followed for a median of 46 (IQR 24, 108) months, during which time there were 65 (73%) recurrences and 50 (49%) deaths. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 66% (95% CI 56%-77%) and 37% (95% CI 28%-48%), respectively. Age ≥ 65 years and male sex were independent predictors of worse OS and PFS in multivariate regression analysis, while postoperative radiotherapy was independently associated with improved OS. Karnofsky Performance Status (KPS) remained stable relative to baseline over 5 years postdiagnosis among participants who were alive at the end of the follow-up period. CONCLUSIONS: This large multicenter study provides insight into the longitudinal outcomes of grade 3 meningioma, with respect to recurrence, survival, and functional status. This study affirms the survival benefit conferred by radiotherapy in this population and suggests good functional status outcomes for patients surviving to 5 years postoperatively.

Exploring sex differences for acute ischemic stroke clinical, imaging and thrombus characteristics in the INTERRSeCT study.

Women, especially following menopause, are known to have worse outcomes following acute ischemic stroke. One primary postulated biological mechanism for worse outcomes in older women is a reduction in the vasculoprotective effects of estrogen. Using the INTERRseCT cohort, a multicentre international observational cohort studying recanalization in acute ischemic stroke, we explored the effects of sex, and modifying effects of age, on neuroradiological predictors of recanalization including robustness of leptomeningeal collaterals, thrombus burden and thrombus permeability. Ordinal regression analyses were used to examine the relationship between sex and each of the neuroradiological markers. Further, we explored both multiplicative and additive interactions between age and sex. All patients (n = 575) from INTERRseCT were included. Mean age was 70.2 years (SD: 13.1) and 48.5% were women. In the unadjusted model, female sex was associated with better collaterals (OR 1.37, 95% CIs: 1.01-1.85), however this relationship was not significant after adjusting for age and relevant comorbidities. There were no significant interactions between age and sex. In a large prospective international cohort, we found no association between sex and radiological predictors of recanalization including leptomeningeal collaterals, thrombus permeability and thrombus burden.

Efficacy of Antithrombotic Therapy and Risk of Hemorrhagic Complication in Blunt Cerebrovascular Injury Patients with Concomitant Injury: A Systematic Review.

BACKGROUND: The risk-benefit balance of antithrombotic therapy administration for blunt cerebrovascular injuries (BCVI) patients with concomitant injuries at high risk for bleeding is an ongoing therapeutic conundrum for trauma clinicians. We performed a systematic review to assess the reported efficacy and safety of treatment in this population with respect to prevention of ischemic stroke and risk of hemorrhagic complications. STUDY DESIGN: A systematic electronic literature search of MEDLINE, EMBASE, Cochrane Library, and Web of Science databases was performed from January 1, 1996 to December 31, 2021. Studies were included if they reported treatment-stratified clinical outcomes after antithrombotic therapy in BCVI patients with concomitant injuries at high risk of bleeding into a critical site. Data were extracted from selected studies by two independent reviewers, including the main outcomes of interest were BCVI-related ischemic stroke rates and rates of hemorrhagic complications. RESULTS: Of the 5,999 studies reviewed, 10 reported on the effects of treating BCVI patients with concurrent traumatic injuries and were included for review. In the pooled data, among patients with BCVI and concomitant injury who received any form of antithrombotic therapy, the BCVI-related stroke rate was 7.6%. The subgroup of patients who did not receive therapy had an overall BCVI-related stroke rate of 34%. The total rate of hemorrhagic complications in the treated population was 3.4%. CONCLUSIONS: In BCVI patients with concomitant injuries at high risk for bleeding, antithrombotic use reduces the risk of ischemic strokes with a low reported risk of serious hemorrhagic complications.

Malignant transformation of adult-onset pilocytic astrocytoma to diffuse leptomeningeal glioneuronal tumor within the thoracic spine: a case report and review of the literature.

We describe a 31-year-old male who presented with progressive myelopathy from a thoracic pilocytic astrocytoma (PA). Following multiple recurrences and resections, 10 years after his index surgery, pathology revealed diffuse leptomeningeal glioneuronal tumor (DLGNT) with high-grade features. We discuss his clinical course, management, histopathological findings, and present a comprehensive review of spinal PA undergoing malignant transformation in adults and adult-onset spinal DLGNT. To our knowledge, we present the first reported case of adult-onset spinal PA malignant transformation to DLGNT. Our case adds to the paucity of clinical data characterizing such transformations and highlights the importance of developing novel management paradigms.

Three-month Practice Effect of the National Institutes of Health Toolbox Cognition Battery in Young Healthy Adults.

The National Institutes of Health Toolbox-Cognition Battery (NIHTB-CB) is a tablet-based cognitive assessment intended for individuals with neurological diseases of all ages. NIHTB-CB practice effects (PEs), however, need clarification if this measure is used to track longitudinal change. We explored the test-retest PEs on NIHTB-CB performance at 3 months in young healthy adults (n = 22). We examined corrected T-scores normalized for demographic factors and calculated PEs using Cohen's d. There were significant PEs for all NIHTB-CB composite scores and on 4/7 subtests. This work suggests the need to further assess NIHTB-CB PEs as this may affect the interpretation of study results incorporating this battery.

Non-contrast-enhancing subdural empyema: illustrative case.

BACKGROUND: Subdural empyema (SDE) is a life-threatening intracranial infection that, without timely surgical intervention and appropriate antibiotic treatment, is inevitably fatal. SDE is classically recognized on brain imaging as a subdural collection surrounded by a contrast-enhancing ring. OBSERVATIONS: The authors describe the case of a 41-year-old male with clinical features consistent with SDE but without any contrast enhancement on multiple computed tomography scans obtained more than 48 hours apart. Given the high clinical suspicion for SDE, a craniotomy was performed that demonstrated frank pus that eventually grew Streptococcus pyogenes. LESSONS: This case demonstrates that SDE may present without ring enhancement on contrast-enhanced imaging. In critically ill patients with a high clinical suspicion for SDE despite lack of contrast enhancement, we demonstrate that exploratory burr holes or craniotomy can provide diagnostic confirmation and source control.

Health State Utility Values in People With Stroke: A Systematic Review and Meta-Analysis.

Background Health state utility values are commonly used to provide summary measures of health-related quality of life in studies of stroke. Contemporaneous summaries are needed as a benchmark to contextualize future observational studies and inform the effectiveness of interventions aimed at improving post-stroke quality of life. Methods and Results We conducted a systematic search of the literature using Medline, EMBASE, and Web of Science from January 1995 until October 2020 using search terms for stroke, health-related quality of life, and indirect health utility metrics. We calculated pooled estimates of health utility values for EQ-5D-3L, EQ-5D-5L, AQoL, HUI2, HUI3, 15D, and SF-6D using random effects models. For the EQ-5D-3L we conducted stratified meta-analyses and meta-regression by key subgroups. We screened 14 251 abstracts and 111 studies met our inclusion criteria (sample size range 11 to 12 447). EQ-5D-3L was reported in 78% of studies (study n=87; patient n=56 976). The pooled estimate for EQ-5D-3L at ≥3 months following stroke was 0.65 (95% CI, 0.63-0.67), which was ≈20% below population norms. There was high heterogeneity (I2>90%) between studies, and estimates differed by study size, case definition of stroke, and country of study. Women, older individuals, those with hemorrhagic stroke, and patients prior to discharge had lower pooled EQ-5D-3L estimates. Conclusions Pooled estimates of health utility for stroke survivors were substantially below population averages. We provide reference values for health utility in stroke to support future clinical and economic studies and identify subgroups with lower healthy utility. Registration URL: https://www.crd.york.ac.uk/prospero/. Unique Identifier: CRD42020215942.

Survival and Recurrence Outcomes Following Adjuvant Radiotherapy for Grade 2 Intracranial Meningiomas: 13-Year Experience in a Tertiary-Care Center.

OBJECTIVE: We sought to evaluate overall survival (OS) and local recurrence (LR) in patients with grade 2 meningiomas treated with adjuvant radiotherapy compared to surgery alone at time of diagnosis. METHODS: All patients at the authors' institution between 2007 and 2020 were retrospectively reviewed. OS, LR, and treatment toxicities were assessed. Sensitivity analyses were performed for patients with initial gross total resection (GTR) and subtotal resection (STR). Kaplan-Meier analyses and log-rank test for significance were used to compare surgery alone and adjuvant radiotherapy groups. RESULTS: We included 189 patients with mean age 57.4 ± 14.6 years. Patients were 64% female, and median follow-up was 64 (interquartile range: 20-96) months. At initial treatment, 21 patients received adjuvant radiotherapy and 168 received surgery alone. There was no significant difference for OS (hazard ratio = 1.3 [95% confidence interval 0.4-4.5], P = 0.92) overall or when limited to GTR (P = 0.38) or STR (P = 0.85). There was no significant difference in LR overall (P = 0.75) or when restricted to GTR (P = 0.77) or STR (P = 0.20). No patient had radiotherapy stopped or altered because of side effects; however, 71.4% reported tolerable side effects during the treatment period and 14.3% reported chronic side effects persisting longer than 12 months post treatment. CONCLUSIONS: In a large retrospective cohort, we found no survival or local recurrence benefit to adjuvant radiotherapy in treatment of grade 2 meningiomas. Sensitivity analysis limited to initial GTR and STR also failed to demonstrate any OS or LR benefit with adjuvant radiotherapy. In our experience, there is limited utility to upfront adjuvant radiotherapy following initial surgical resection in the treatment of grade 2 meningiomas.

The impact of brain invasion criteria on the incidence and distribution of WHO grade 1, 2, and 3 meningiomas.

BACKGROUND: In 2016 brain invasion was added as a standalone diagnostic criterion for Grade 2 meningiomas in the WHO Classification of Brain Tumors. The aim of this study was to compare the incidence and distribution of meningiomas, and agreement, between the 2007 and 2016 WHO criteria. METHODS: All cases of intracranial meningiomas diagnosed between 2007 and 2020 at a tertiary care academic hospital were identified. The incidence of each meningioma grade in the WHO 2007 and WHO 2016 cohorts were compared. Additionally, each case in the 2007 cohort was re-graded according to the WHO 2016 criteria to determine the intra-class correlation (ICC) between criteria. RESULTS: Of 814 cases, 532 (65.4%) were in the 2007 WHO cohort and 282 (34.6%) were in the 2016 WHO cohort. There were no differences in the distribution of meningioma grades between cohorts (P = .11). Incidence rates were: 75.0% vs. 75.2% for Grade 1, 22.7% vs. 24.5% for Grade 2, and 2.3% vs. 0.4% for Grade 3, for the 2007 and 2016 cohorts, respectively. Upon re-grading, 21 cases (3.9%) were changed. ICC between original and revised grade was 0.92 (95% CI: 0.91-0.93). Amongst Grade 2 meningiomas with brain invasion, 75.8% had three or more atypical histologic features or an elevated mitotic index. CONCLUSIONS: Including brain invasion as a standalone diagnostic criterion for Grade 2 meningiomas had minimal impact on the incidence of specific meningioma grade tumors. There is strong agreement between the 2007 and 2016 WHO criteria, likely due to cosegregation of grade elevating features.

Delayed coil migration into oropharynx following endovascular coiling of a traumatic carotid cavernous fistula: management considerations.

Carotid-cavernous fistulas (CCFs) are abnormal vascular shunts between the carotid artery and the cavernous sinus. A 37-year-old male presented with a traumatic CCF and basal skull fracture extending through the medial wall of the cavernous sinus and sphenoid sinus. The CCF was treated with endovascular coiling. Three months after this procedure, he was found to have coil migration through the traumatic sphenoid defect into the pharynx. He underwent urgent endonasal endoscopic surgery to disconnect and remove the extruded coil. Post-operative coil migration is a rare but serious complication following endovascular treatment of traumatic CCF.

Determinants of Leptomeningeal Collateral Status Variability in Ischemic Stroke Patients.

BACKGROUND: Collateral status is an indicator of a favorable outcome in stroke. Leptomeningeal collaterals provide alternative routes for brain perfusion following an arterial occlusion or flow-limiting stenosis. Using a large cohort of ischemic stroke patients, we examined the relative contribution of various demographic, laboratory, and clinical variables in explaining variability in collateral status. METHODS: Patients with acute ischemic stroke in the anterior circulation were enrolled in a multi-center hospital-based observational study. Intracranial occlusions and collateral status were identified and graded using multiphase computed tomography angiography. Based on the percentage of affected territory filled by collateral supply, collaterals were graded as either poor (0-49%), good (50-99%), or optimal (100%). Between-group differences in demographic, laboratory, and clinical factors were explored using ordinal regression models. Further, we explored the contribution of measured variables in explaining variance in collateral status. RESULTS: 386 patients with collateral status classified as poor (n = 64), good (n = 125), and optimal (n = 197) were included. Median time from symptom onset to CT was 120 (IQR: 78-246) minutes. In final multivariable model, male sex (OR 1.9, 95% CIs [1.2, 2.9], p = 0.005) and leukocytosis (OR 1.1, 95% CIs [1.1, 1.2], p = 0.001) were associated with poor collaterals. Measured variables only explained 44.8-53.0% of the observed between-patient variance in collaterals. CONCLUSION: Male sex and leukocytosis are associated with poorer collaterals. Nearly half of the variance in collateral flow remains unexplained and could be in part due to genetic differences.

Evaluating High-Functioning Young Stroke Survivors with Cognitive Complaints.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is a commonly used cognitive outcome in stroke trials. However, it may be insufficiently sensitive to detect impairment in high-functioning stroke survivors. The National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB-CB), a 30-min comprehensive tablet-based cognitive assessment, may be a better choice to characterize cognitive issues in this cohort. METHODS: We compared MoCA and NIHTB-CB performance in young stroke survivors (18-55 years) with excellent functional outcomes (modified Rankin Scale 0-1) reporting subjective cognitive complaints to that of age-matched healthy controls. We recruited 53 stroke survivors and 53 controls. We performed a sensitivity analysis in those participants with normal MoCA scores (≥26). RESULTS: Median MoCA scores were not significantly different between stroke survivors (27.0 vs. 28.0) and healthy controls. Mean T scores for NIHTB-CB fluid (44.9 vs. 54.2), crystallized (53.8 vs. 60.0), and total cognition (49.1 vs. 58.4) components were significantly lower in stroke survivors compared to healthy controls (p < 0.001 for all). In participants scoring within normal range (≥26) on the MoCA, NIHTB-CB scores for all components remained significantly lower in stroke survivors. CONCLUSIONS: In young stroke survivors with excellent functional outcomes and subjective cognitive complaints, the NIHTB-CB, but not the MoCA, was able to detect differences in cognitive performance between stroke survivors and healthy controls. The NIHTB-CB may be a suitable outcome measure for cognition in clinical trials examining higher-functioning young stroke survivors.

Health-Related Quality of Life Among Patients With Acute Ischemic Stroke and Large Vessel Occlusion in the ESCAPE Trial.

Background and Purpose: Endovascular thrombectomy (EVT) reduces 90-day disability in patients following acute ischemic stroke due to large vessel occlusion. Patient-reported outcome measures after EVT, such as health-related quality of life and specific functional domains, are less well described. Methods: We report outcomes on the EuroQol-5D (EQ-5D) from the ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) randomized controlled trial at 90 days after stroke. Death was assigned an index value of 0 for EQ-5D. We used quantile regression to evaluate the association between EVT and EQ-5D index scores and logistic regression for the association between EVT and symptom-free status among 90-day survivors for each EQ-5D dimension (self-care, usual activities, mobility, pain/discomfort, and anxiety/depression), assessing for modification by age or sex and adjusting for baseline factors including stroke severity, affected hemisphere, and receipt of alteplase. Lastly, the association between severe disability at 90 days and EQ-5D was evaluated with assessment for modification by EVT, age, and sex. Results: There were 165 patients randomized to EVT and 150 patients randomized to control. Median EQ-5D was significantly higher for those who received EVT compared with best medical management (0.80 versus 0.60; P<0.001). After accounting for the greater number of deaths in the elderly, there was evidence of modification of treatment effect by age, with older age associated with a larger effect size difference in EQ-5D with EVT. Those receiving EVT had higher odds of symptom-free status in self-care, usual activities, mobility for those aged 60 to 79 years, and pain/discomfort for women, but there was no association with anxiety/depression. Severe disability at 90 days was associated with lower EQ-5D in older compared with younger individuals, and the association was not modified by EVT. Conclusions: Patients treated with EVT report substantially improved health-related quality of life, with relatively greater impact in older individuals and observed benefit across multiple dimensions.

Incomplete Subacute Transverse Myelitis Following Vaccination With Pfizer-BioNTech COVID-19 mRNA Vaccine: A Case Report.

In response to the coronavirus disease 2019 (COVID-19) pandemic, rapid development, clinical testing, and regulatory approval of vaccines occurred. The tozinameran COVID-19 vaccine is the first mRNA vaccine approved for use in humans. Transverse myelitis is a rare inflammatory disorder of the spinal cord that is associated with traditional vaccinations. There are rare case reports describing an association between mRNA vaccines and transverse myelitis. Herein, we describe a case of transverse myelitis following mRNA vaccination. A healthy 26-year-old woman developed saddle anesthesia, numbness, and allodynia in the S1-S4 distribution within three days of receiving the first dose of tozinameran COVID-19 vaccine. She had decreased sensation to pinprick, temperature, and light touch in S1-S4 distribution and a positive Rhomberg test. An MRI brain and spine demonstrated a short segment T2 hyperintense and diffusely enhancing lesion at T5. Cerebrospinal fluid studies demonstrated pleocytosis and elevated IgG index. A five-day course of IV methylprednisolone resulted in minimal improvements in her symptoms. Stage III clinical trials may be underpowered to detect more rare adverse effects such as transverse myelitis. Therefore, it is imperative to have ongoing surveillance and reporting of adverse events associated with COVID-19 vaccines to ensure transparency with regard to potential risks to patients obtaining the vaccine and algorithms in place for detection and urgent treatment if required. Nonetheless, the safety and efficacy of vaccination against COVID-19 are well established and greatly outweigh any potential risks associated with the vaccine. Given the individual, societal, and global health benefits of vaccination we strongly advocate for ongoing vaccinations against COVID-19.