Epidemiology and patterns of gymnastics-related head & neck trauma injuries: A NEISS database study.

OBJECTIVE: To describe the epidemiology and patterns of gymnastics-related Head & Neck trauma injuries using the NEISS database from 2001 to 2020. STUDY DESIGN AND SETTING: Cross-sectional analysis of a national database. METHODS: Gymnastics-related ED visits between 2001 and 2020 were queried from the NEISS database. Bivariate chi-squared analyses were used to compare injury demographics, location, type, and disposition. Fracture location was identified using the narrative description of each case and were divided into subtypes for further analysis. RESULTS: 1455 gymnastics-related head and neck traumatic injuries were identified. The majority were in females (65.8%). The most common presenting age group was pediatric (≤18 years) (92.7%), and the largest racial group was Caucasian (51.5%). Of all location subtypes, facial injuries were the most common presenting injury type overall (45.2%). Regarding injury types, lacerations were most common (36.8%), followed by dental injury (30.7%) and fractures (21.2%). The most common location of head and neck fractures was the nose (45.8%), followed by cervical spine (16.7%) and orbit (13.3%). The majority (95.7%) of gymnastics-related head and neck traumatic injuries presenting to the ED were treated and discharged. CONCLUSION: This study characterizes gymnastics-related head and neck injuries which is a topic that is under-studied. The findings from this study are helpful for gymnasts and those who care for them including providers, coaches and guardians, and this data may help inform future guidelines for treatment and injury prevention.

Serum Neutralizing Antibody Titers 12 Months After Coronavirus Disease 2019 Messenger RNA Vaccination: Correlation to Clinical Variables in an Adult, US Population.

BACKGROUND: We studied whether comorbid conditions affect strength and duration of immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA vaccination in a US-based, adult population. METHODS: Sera (before and after BNT162b2 vaccination) were tested serially up to 12 months after 2 doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Postbooster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects, respectively. RESULTS: After completion of primary vaccine series, neutralizing antibody half maximal inhibitory concentration (IC50) values were high at 1 month (14-fold increase from prevaccination), declined at 6 months (3.3-fold increase), and increased at 1 month postbooster (41.5-fold increase). Three months postbooster, IC50 decreased in coronavirus disease (COVID)-naïve individuals (18-fold increase) and increased in prior COVID 2019 (COVID-19+) individuals (132-fold increase). Age >65 years (ß = -0.94, P = .001) and malignancy (ß = -0.88, P = .002) reduced strength of response at 1 month. Both neutralization strength and durability at 6 months, respectively, were negatively affected by end-stage renal disease ([ß = -1.10, P = .004]; [ß = -0.66, P = .014]), diabetes mellitus ([ß = -0.57, P = .032]; [ß = -0.44, P = .028]), and systemic steroid use ([ß = -0.066, P = .032]; [ß = -0.55, P = .037]). Postbooster IC50 was robust against WA-1 and B.1.617.2. Postbooster neutralization increased with prior COVID-19 (ß = 2.9, P < .0001), and malignancy reduced neutralization response (ß = -0.68, P = .03), regardless of infection status. CONCLUSIONS: Multiple clinical factors affect the strength and duration of neutralization response after primary series vaccination, but not the postbooster dose strength. Malignancy was associated with lower booster-dose response regardless of prior COVID infection, suggesting a need for clinically guided vaccine regimens.

Benefit of Extended Surveillance of Low-Risk Pancreatic Cysts After 5-Year Stability: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Low-risk branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) lacking worrisome features (WF) and high-risk stigmata (HRS) warrant surveillance. However, their optimal duration, especially among cysts with initial 5 years of size stability, warrants further investigation. We systematically reviewed the surveillance of low-risk BD-IPMNs and investigated the incidence of WF/HRS and advanced neoplasia, high-grade dysplasia, and pancreatic cancer during the initial (<5 years) and extended surveillance period (>5-years). METHODS: A systematic search (CRD42020117120) identified studies investigating long-term IPMN surveillance outcomes of low-risk IPMN among the Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until July 9, 2021. The outcomes included the incidence of WF/HRS and advanced neoplasia, disease-specific mortality, and surveillance-related harm (expressed as percentage per patient-years). The meta-analysis relied on time-to-event plots and used a random-effects model. RESULTS: Forty-one eligible studies underwent systematic review, and 18 studies were meta-analyzed. The pooled incidence of WF/HRS among low-risk BD-IPMNs during initial and extended surveillance was 2.2% (95% CI, 1.0%-3.7%) and 2.9% (95% CI, 1.0%-5.7%) patient-years, respectively, whereas the incidence of advanced neoplasia was 0.6% (95% CI, 0.2%-1.00%) and 1.0% (95% CI, 0.6%-1.5%) patient-years, respectively. The pooled incidence of disease-specific mortality during initial and extended surveillance was 0.3% (95% CI, 0.1%-0.6%) and 0.6% (95% CI, 0.0%-1.6%) patient-years, respectively. Among BD-IPMNs with initial size stability, extended surveillance had a WF/HRS and advanced neoplasia incidence of 1.9% (95% CI, 1.2%-2.8%) and 0.2% (95% CI, 0.1%-0.5%) patient-years, respectively. CONCLUSIONS: A lower incidence of advanced neoplasia during extended surveillance among low-risk, stable-sized BD-IPMNs was a key finding of this study. However, the survival benefit of surveillance among this population warrants further exploration through high-quality studies before recommending surveillance cessation with certainty.

Ophthalmologist Turnover in the United States: Analysis of Workforce Changes from 2014 through 2021.

PURPOSE: Physician turnover is costly to health care systems and affects patient experience due to discontinuity of care. This study aimed to assess the frequency of turnover by ophthalmologists and identify physician and practice characteristics associated with turnover. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Actively practicing United States ophthalmologists included in the Centers for Medicare and Medicaid Services Physician Compare and Physician and Other Supplier Public Use File between 2014 and 2021. METHODS: We collected data for each ophthalmologist that was associated with practice/institution and then calculated the rate of turnover both annually in each year window and cumulatively as the total proportion from 2014 to 2021. Multivariable logistic regression analysis was used to identify physician and practice characteristics associated with turnover. We also evaluated turnover characteristics surrounding the Coronavirus disease 2019 (COVID-19) pandemic. MAIN OUTCOME MEASURES: Ophthalmologist turnover, defined as a change of an ophthalmologist's National Provider Identifier practice affiliation from one year to the next. RESULTS: Of 13 264 ophthalmologists affiliated with 3306 unique practices, 34.1% separated from at least 1 practice between 2014 and 2021. Annual turnover ranged from 3.7% (2017) to 19.4% (2018), with an average rate of 9.4%. Factors associated with increased turnover included solo practice (adjusted odds ratio [aOR], 9.59), university affiliation (aOR, 1.55), practice location in the Northeast (aOR, 1.39), and practice size of 2 to 4 members (aOR, 1.21; P < 0.05 for all). Factors associated with decreased turnover included male gender (aOR, 0.87) and more than 5 years of practice: 6 to 10 years (aOR, 0.63), 11 to 19 years (aOR, 0.54), 20 to 29 years (aOR, 0.36), and ≥ 30 years (aOR, 0.18; P < 0.05 for all). In the initial year (2020) of the COVID-19 pandemic, annual turnover increased from 7.8% to 11.0%, then decreased to 8.7% in the postvaccine period (2021). CONCLUSIONS: One-third of United States ophthalmologists separated from at least 1 practice from 2014 through 2021. Turnover patterns differed by various physician and practice characteristics, which may be used to develop future strategies for workforce stability. Because administrative data cannot solely determine reasons for turnover, further investigation is warranted given the potential clinical and financial implications. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Patients with psychiatric illness report worse patient-reported outcomes and receive lower rates of autologous breast reconstruction.

Psychiatric well-being impacts on general satisfaction and quality of life. This study explored how the presence of psychiatric diagnoses affects patient-reported outcomes in breast reconstruction and on selection of reconstructive modality. Patients who received breast reconstruction at a tertiary hospital between 2013 and 2018 and completed the BREAST-Q survey were included. BREAST-Q module scores were compared between patients who had a psychiatric diagnosis at presentation and the remaining cohort using t tests. General linear models (GLMs) were used to control for confounding factors. A chi-squared test was used to assess the effect on reconstructive modality, and binary logistic regression was used to control for confounding factors. Of the 471 patients included, 93 (19.7%) had at least one psychiatric diagnosis. Cohorts did not differ significantly by age, BMI, race, ASA classification, or insurance status. Patients with a psychiatric diagnosis experienced a decrease in BREAST-Q scores for the Psychosocial Wellbeing (B = 9.16, P = .001) and Sexual Wellbeing (B = 9.29, P = .025) modules. On binary logistic regression, patients with a psychiatric diagnosis were less likely to receive autologous reconstruction compared with implant reconstruction (OR = 0.489, P = .010). The presence of psychiatric diagnoses is an independent predictor of decreased BREAST-Q. Furthermore, there is a significant disparity in modality of reconstruction given to patients with psychiatric diagnoses. Further study is needed to evaluate interventions to improve satisfaction among at-risk populations and evaluate the reason for low autologous reconstruction in this population.

Is Public Interest Associated with Real-World Management of Ankyloglossia?

OBJECTIVES: Assess the relationship between public interest in ankyloglossia as determined by internet search volume and real-world medical claims data. STUDY DESIGN: Retrospective Cohort Study. SETTING: This retrospective cohort study was conducted using claims data from the Merative™ Marketscan® Research Databases. The internet search data was collected from Google Trends. METHODS: Annual Google Trends data were compiled using search terms associated with "ankyloglossia" and "frenotomy" for the years 2011 to 2021. We obtained incidence of ankyloglossia diagnoses and frenotomy procedures in children under 12 months from Marketscan relative to all infants enrolled. We compared associations between search and incidence data among US states and over time. RESULTS: Google search correlated with ankyloglossia incidence (r = 0.4104, P = .0031) and with frenotomy incidence (r = 0.4062, P = .0034) per state. Ankyloglossia diagnoses increased with Google search index (coefficient = 0.336, 95% confidence interval [CI] 0.284, 0.388) and year (coefficient = 0.028, 95% CI 0.025, 0.031). Similarly, frenotomy procedures increased with Google search index (coefficient = 0.371, 95% CI 0.313, 0.429) and year (coefficient = 0.027, 95% CI 0.024, 0.030). CONCLUSIONS: Associations between online ankyloglossia search trends and both diagnosis and treatment rates, persist across US regions and timeframes. Internet search trends are pivotal in shaping pediatric health care decisions, driving clinical consensus, and disseminating evidence-based information.

Disruption Index in Otolaryngology: Uncovering a Bibliometric History of a Rapidly Evolving Field.

OBJECTIVES: As the volume of research publications in the field of otolaryngology has increased, so has the need to qualify articles through bibliometric analyses to identify the most important and impactful work in the field. Herein, we aim to identify the 100 most disruptive articles in ENT over a 60-year period and examine how disruption index (DI) compares with other bibliometrics in identifying impactful works in the field. METHODS: In this cross-sectional bibliometric analysis, articles published between 1954 and 2014 in commonly referenced otolaryngology-head and neck surgery (OHNS) journals were queried in PubMed. Publications were characterized by DI, journal, subspecialty discipline, and status as an impactful article in the field as determined by other bibliometrics such as citation count, the "Sleeping Beauty Index," and those derived by the modified Delphi process. RESULTS: Of the 122,094 articles queried, 67,561 (55.3%) had available citation count as well as disruption score data, meeting inclusion criteria. The most represented subspecialty disciplines within the top 100 most disruptive articles were Otology/Neurotology (28%), General (Comprehensive) (27%), Head and Neck Surgery (12%), and Laryngology (11%). Fifty percent of articles identified as Sleeping Beauties and impactful via modified Delphi approach had scores in the top 86th percentile. CONCLUSION: DI in otolaryngology can be appreciated as an added dimension to existing indices and can unearth seminal research, which serve as early foundations of evidence-based management in the field of OHNS today. LEVEL OF EVIDENCE: NA Laryngoscope, 134:629-636, 2024.

Trends in clinical trials for olfactory dysfunction in the COVID-19 era.

KEY POINTS: Nearly half of all olfactory dysfunction (OD) clinical trials since 2010 are COVID-19-related. COVID-19-related OD trials are published significantly faster than COVID-19-unrelated trials. High-quality clinical trials and publications are crucial to discovering effective treatments.

Epimorphic regeneration in the mammalian tympanic membrane.

Adult mammals are generally believed to have limited ability to regenerate complex tissues and instead, repair wounds by forming scars. In humans and across mammalian species, the tympanic membrane (TM) rapidly repairs perforations without intervention. Using mouse models, we demonstrate that the TM repairs itself through a process that bears many hallmarks of epimorphic regeneration rather than typical wound healing. Following injury, the TM forms a wound epidermis characterized by EGFR ligand expression and signaling. After the expansion of the wound epidermis that emerges from known stem cell regions of the TM, a multi-lineage blastema-like cellular mass is recruited. After two weeks, the tissue architecture of the TM is largely restored, but with disorganized collagen. In the months that follow, the organized and patterned collagen framework of the TM is restored resulting in scar-free repair. Finally, we demonstrate that deletion of Egfr in the epidermis results in failure to expand the wound epidermis, recruit the blastema-like cells, and regenerate normal TM structure. This work establishes the TM as a model of mammalian complex tissue regeneration.

Physician Turnover Among Otolaryngologists in the United States, 2014-2021.

Using publicly available Medicare data, we performed a retrospective cross-sectional analysis of separation between otolaryngologists and affiliated medical groups between 2014 and 2021. During this period, the cumulative turnover rate among otolaryngologists was 36.4%, with annual turnover rates ranging between 6.2%-10.2%. Otolaryngologist turnover rates varied by career stage and group size.

Adverse Events Associated With Bioabsorbable Nasal Implants: A MAUDE Database Analysis.

Bioabsorbable implants (eg, Latera) have recently been approved for addressing nasal valve collapse. The purpose of this study is to summarize adverse events and treatment sequelae associated with bioabsorbable nasal implants queried in the Manufacturer and User Facility Device Experience (MAUDE) database. Of the 26 device reports entered between March 2017 and April 2022, the most frequently reported complications included abscess (n = 13) and implant protrusion (n = 5). Other common symptoms reported greater than 1-year postimplantation included facial pain/discomfort (n = 3) and failure to absorb (n = 3). Management of adverse events included treatment with antibiotics (n = 9), steroid injections (n = 4), and explantation (n = 20). In 3 reports, adverse reactions required a biopsy of adjacent tissue for pathologic analysis. These findings suggest that further research is required to assess the potential long-term complications and optimize the management of bioabsorbable nasal implants. Furthermore, standardized reporting templates may improve the utility of the MAUDE database.

Single-cell analysis reveals inflammatory interactions driving macular degeneration.

Due to commonalities in pathophysiology, age-related macular degeneration (AMD) represents a uniquely accessible model to investigate therapies for neurodegenerative diseases, leading us to examine whether pathways of disease progression are shared across neurodegenerative conditions. Here we use single-nucleus RNA sequencing to profile lesions from 11 postmortem human retinas with age-related macular degeneration and 6 control retinas with no history of retinal disease. We create a machine-learning pipeline based on recent advances in data geometry and topology and identify activated glial populations enriched in the early phase of disease. Examining single-cell data from Alzheimer's disease and progressive multiple sclerosis with our pipeline, we find a similar glial activation profile enriched in the early phase of these neurodegenerative diseases. In late-stage age-related macular degeneration, we identify a microglia-to-astrocyte signaling axis mediated by interleukin-1ß which drives angiogenesis characteristic of disease pathogenesis. We validated this mechanism using in vitro and in vivo assays in mouse, identifying a possible new therapeutic target for AMD and possibly other neurodegenerative conditions. Thus, due to shared glial states, the retina provides a potential system for investigating therapeutic approaches in neurodegenerative diseases.

Emergency Department Presentations of Acute Primary Angle Closure in the United States from 2008 to 2017.

Purpose: Acute primary angle closure (APAC) is an ophthalmologic emergency. Nationwide data on the epidemiology and clinical characteristics of APAC are lacking despite the associated visual morbidity. Patients and Methods: A retrospective cross-sectional study using the Nationwide Emergency Department Sample (NEDS). The NEDS was queried by ICD-9/10 code for cases of APAC presenting to the United States emergency departments over a ten-year period from 2008 to 2017. All identified cases were included to produce nationally representative estimates. Linear regression and seasonality tests were used to identify trends. Reported outcomes include the incidence, demographics, seasonality, and economic impact of APAC regionally and nationwide. Results: A total of 23,203 APAC-related ED visits were identified. The mean (SD) and median ages were 58.8 (16.2) and 60 years, respectively. Females (59.4%, p < 0.01), those in the lowest income quartile (6983, 30.1%, p < 0.01), and those in the seventh decade of life (5599, 24.1%) presented more frequently with APAC. The incidence of ED presentations within each age group rose with age and increased significantly over the study period (p < 0.01). The Northeast region had the highest average incidence (0.93 per 100,000 population). Significant seasonal variation was seen regionally and nationally (p < 0.01), with the highest average incidence in December and lowest in April. Median inflation adjusted charge per ED visit was $2496.10, and the total inflation adjusted charges equaled $101.5 million. Conclusion: The incidence of APAC-related ED visits continues to rise in the United States. High-risk groups include women, individuals of low socioeconomic status, and those between ages 50 and 70. Significant seasonal and regional trends were observed in ED presentations of APAC.

Analysis of the Frequency, Characteristics, and Reasons for Termination of Spine-related Clinical Trials.

STUDY DESIGN: Cross-sectional analysis of completed and terminated spine-related clinical trials in the ClinicalTrials.gov registry. OBJECTIVE: The aim was to quantify completed and terminated spine-related clinical trials, assess reasons for termination, and determine predictors of termination by comparing characteristics of completed and terminated trials. SUMMARY OF BACKGROUND DATA: Clinical trials are key to the advancement of products and procedures related to the spine. Unfortunately, trials may be terminated before completion. ClinicalTrials.gov is a registry and results database maintained by the National Library of Medicine that catalogs trial characteristics and tracks overall recruitment status (eg, ongoing, completed, terminated) for each study as well as reasons for termination. Reasons for trial termination have not been specifically evaluated for spine-related clinical trials. METHODS: The ClinicalTrials.gov database was queried on July 20, 2021 for all completed and terminated interventional studies registered to date using all available spine-related search terms. Trial characteristics and reason for termination, were abstracted. Univariate and multivariate analyses were performed determine predictors of trial termination. RESULTS: A total of 969 clinical trials were identified and characterized (833 completed, 136 terminated). Insufficient rate of participant accrual was the most frequently reported reason for trial termination, accounting for 33.8% of terminated trials.Multivariate analysis demonstrated increased odds of trial termination for industry-sponsorship [odds ratio (OR)=1.59] relative to sponsorship from local groups, device studies (OR=2.18) relative to investigations of drug or biological product(s), and phase II (OR=3.07) relative to phase III studies ( P <0.05 for each). CONCLUSIONS: Spine-related clinical trials were found to be terminated 14% of the time, with insufficient accrual being the most common reason for termination. With significant resources put into clinical studies and the need to advance scientific objectives, predictors, and reasons for trial termination should be considered and optimized to increase the completion rate of trials that are initiated.

Clinical Variables Correlate with Serum Neutralizing Antibody Titers after COVID-19 mRNA Vaccination in an Adult, US-based Population.

Background: We studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population. Methods: Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 12 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 124 individuals; neutralizing titers were correlated to clinical variables with multivariate regression. Post-booster (third dose) effect was measured at 1 and 3 months in 72 and 88 subjects respectively. Results: After completion of primary vaccine series, neutralizing antibody IC50 values were high at one month (14-fold increase from pre-vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (41.5-fold increase). Three months post-booster, IC50 decreased in COVID-naïve individuals (18-fold increase) and increased in prior COVID-19+ individuals (132-fold increase). Age >65 years (ß=-0.94, p=0.001) and malignancy (ß=-0.88, p=0.002) reduced strength of response at 1 month. Both strength and durability of response at 6 months, respectively, were negatively impacted by end-stage renal disease [(ß=-1.10, p=0.004); (ß=-0.66, p=0.014)], diabetes mellitus [(ß=-0.57, p=0.032); (ß=-0.44, p=0.028)], and systemic steroid use [(ß=-0.066, p=0.032); (ß=-0.55, p=0.037)]. Post-booster IC50 was robust against WA-1 and B.1.617.2, but the immune response decreased with malignancy (ß =-0.68, p=0.03) and increased with prior COVID-19 (p-value < 0.0001). Conclusion: Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination, but not the post-booster dose strength. Prior COVID-19 infection enhances the booster-dose response except in individuals with malignancy, suggesting a need for clinically guiding vaccine dosing regimens. Summary: Multiple clinical factors impact the strength and duration of neutralization response post-primary series vaccination. All subjects, irrespective of prior COVID infection, benefited from a third dose. Malignancy decreased response following third dose, suggesting the importance of clinically guided vaccine regimens.

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis-A Systematic Review and Meta-Analysis.

Allogeneic hematopoietic cell transplant (allo-HCT) remains the only potentially curative therapeutic modality for patients with primary or secondary myelofibrosis (MF). However, many patients are considered ineligible for allo-HCT, and transplant-related mortality can be substantial. Data on the efficacy and safety of allo-HCT are mixed and largely derived from retrospective studies. We aimed to synthesize the available evidence on the safety and efficacy of allo-HCT in MF and to identify patient, disease, and transplant characteristics with prognostic impact on outcomes of patients with MF undergoing allo-HCT. For this systematic review and meta-analysis, Cochrane Library, Google Scholar, Ovid Medline, Ovid Embase, PubMed, Scopus, and Web of Science Core Collection were searched from inception to October 11, 2020, for studies on allo-HCT in MF. Random-effects models were used to pool response rates for the co-primary outcomes of 1-year, 2-year, and 5-year overall survival (OS). Rates of non-relapse mortality and acute and chronic graft-versus-host-disease (GVHD) were studied as secondary endpoints. Subgroup analyses on the effect of conditioning regimen intensity, baseline dynamic international prognostic scoring system (DIPSS) score, and patient age were performed. The study protocol has been registered on PROSPERO (CRD42020188706). Forty-three studies with 8739 patients were identified and included in this meta-analysis. Rates of 1-year, 2-year, and 5-year OS were 66.7% (95% confidence interval [CI], 63.5%-69.8%), 64.4% (95% CI, 57.6%-70.6%), and 55.0% (95% CI, 51.8%-58.3%), respectively. Rates of 1-year, 2-year, and 5-year nonrelapse mortality were 25.9% (95% CI, 23.3%-28.7%), 29.7% (95% CI, 24.5%-35.4%), and 30.5% (95% CI, 25.9%-35.5%), respectively. The combined rate of graft failure was 10.6% (95% CI, 8.9%-12.5%) with primary and secondary graft failure occurring in 7.3% (95% CI, 5.7%-9.4%) and 5.9% (95% CI, 4.3%-8.0%) of patients, respectively. Rates of acute and chronic graft-versus-host disease were 44.0% (95% CI, 39.6%-48.4%; grade III/IV: 15.2%) and 46.5% (95% CI, 42.2%-50.8%; extensive or moderate/severe: 26.1%), respectively. Subgroup analyses did not show any significant difference between conditioning regimen intensity (myeloablative versus reduced-intensity), median patient age, and proportion of DIPSS-intermediate-2/high patients. The quality of the evidence is limited by the absence of randomized clinical trials in the field and the heterogeneity of patient and transplant characteristics across included studies. Given the poor prognosis of patients not receiving transplants and in the absence of curative nontransplantation therapies, our results support consideration of allo-HCT for eligible patients with MF.

Preresidency Publication Productivity of U.S. Neurosurgery Interns.

BACKGROUND: Research experience is believed to be an important component of the neurosurgery residency application process. One measure of research productivity is publication volume. The preresidency publication volume of U.S. neurosurgery interns and any potential association between applicant publication volume and the match results of top-ranked residency programs have not been well characterized. OBJECTIVE: In this study, we sought to characterize the preresidency publication volume of U.S. neurosurgery residents in the 2018-2019 intern class using the Scopus database. METHODS: For each intern, we recorded the total number of publications, total number of first or last author publications, total number of neuroscience-related publications, mean number of citations per publication, and mean impact factor of the journal per publication. Preresidency publication volumes of interns at the top-25 programs (based on a composite ranking score according to 4 different ranking metrics) were compared with those at all other programs. RESULTS: We found that 82% of neurosurgery interns included in the analysis (190 interns from 95 programs) had at least 1 publication. The average number of publications per intern among all programs was 6 ± 0.63 (mean ± standard error of the mean). We also found that interns at top-25 neurosurgery residency programs tended to have a higher number of publications (8.3 ± 1.2 vs. 4.8 ± 0.7, P = 0.0137), number of neuroscience-related publications (6.8 ± 1.1 vs. 4.1 ± 0.7, P = 0.0419), and mean number of citations per publication (9.8 ± 1.7 vs. 5.7 ± 0.8, P = 0.0267) compared with interns at all other programs. CONCLUSIONS: Our results provide a general estimate of the preresidency publication volume of U.S. neurosurgery interns and suggest a potential association between publication volume and matching in the top-25 neurosurgery residency programs.

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated de novo mutation (p.Cys188Trp) in the GABAA receptor Cl- channel γ-1 subunit (GABRG1) exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na+ and Ca+ channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca2+ channel Cav3.2 (CACNA1H). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis.

Mutations disrupting neuritogenesis genes confer risk for cerebral palsy.

In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.

Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas.

OBJECTIVE: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts. METHODS: Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features. RESULTS: Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation. CONCLUSIONS: Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.