Parental influence and perceptions on youth single sport specialization: a systematic review.

OBJECTIVE: To evaluate the role of parental influence on youth SSS and to characterize parental perceptions of SSS. DATA SOURCES: Embase.com, Ovid-Medline All, CINAHL Plus, APA PsycInfo, Scopus, Web of Science, and PubMed Central (PMC) since database inception. STUDY SELECTION: Primary studies that assessed reasons for youth SSS that included parental influence as a factor and/or studies that investigated the nature or extent of parental influence on SSS were included. DATA EXTRACTION: A single author extracted data, focusing on definitions and measures of SSS and parental influence, findings concerning primary reasons for SSS, any quantitative or qualitative findings on the extent of parental influence on SSS, and findings concerning various associations between parental influence, SSS, and other themes. DATA SYNTHESIS: 61 articles were assessed in total, with 23 meeting criteria for inclusion. Parental influence plays a limited direct role in SSS, accounting for approximately 10.6% of the overall influence. Athlete self-influence or self-enjoyment of sport was found to be the predominant reason to pursue SSS, accounting for 82.3% of the overall influence. However, parents indirectly influence SSS by modulating athlete motivation and providing financial, practical, and emotional support. CONCLUSIONS: Athlete self-motivation primarily drives SSS directly, while parents indirectly influence SSS by modulating athlete self-motivation and offering financial, practical, and emotional support. Misconceptions persist regarding parental perceptions of SSS-related injury risks, scholarship attainment, and athletic development. Communication with parents regarding the risks associated with SSS and their role in monitoring their children's sports participation is crucial for mitigating adverse outcomes in youth athletes.

A Meta-Analysis of Surgical Outcomes in 25727 Patients Undergoing Anterior Cervical Discectomy and Fusion or Anterior Cervical Corpectomy and Fusion for Cervical Deformity.

STUDY DESIGN: Systematic Review. OBJECTIVES: To evaluate which cervical deformity correction technique between anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) produces better clinical, radiographic, and operative outcomes. METHODS: We conducted a meta-analysis comparing studies involving ACDF and ACCF. Adult patients with either original or previously treated cervical spine deformities were included. Two independent reviewers categorized extracted data into clinical, radiographic, and operative outcomes, including complications. Clinical assessments included patient-reported outcomes; radiographic evaluations examined C2-C7 Cobb angle, T1 slope, T1-CL, C2-7 SVA, and graft stability. Surgical measures included surgery duration, blood loss, hospital stay, and complications. RESULTS: 26 studies (25727 patients) met inclusion criteria and were extracted. Of these, 14 studies (19077 patients) with low risk of bias were included in meta-analysis. ACDF and ACCF similarly improve clinical outcomes in terms of JOA and NDI, but ACDF is significantly better at achieving lower VAS neck scores. ACDF is also more advantageous for improving cervical lordosis and minimizing the incidence of graft complications. While there is no significant difference between approaches for most surgical complications, ACDF is favorable for reducing operative time, intraoperative blood loss, and length of hospital stay. CONCLUSIONS: While both techniques benefit cervical deformity patients, when both techniques are feasible, ACDF may be superior with respect to VAS neck scores, cervical lordosis, graft complications and certain perioperative outcomes. Further studies are recommended to address outcome variability and refine surgical approach selection.

A scoping review of geriatric emergency medicine research transparency in diversity, equity, and inclusion reporting.

INTRODUCTION: The intersection of ageism and racism is underexplored in geriatric emergency medicine (GEM) research. METHODS: We performed a scoping review of research published between January 2016 and December 2021. We included original emergency department-based research focused on falls, delirium/dementia, medication safety, and elder abuse. We excluded manuscripts that did not include (1) original research data pertaining to the four core topics, (2) older adults, (3) subjects from the United States, and (4) for which full text publication could not be obtained. The primary objective was to qualitatively describe reporting about older adults' social identities in GEM research. Secondary objectives were to describe (1) the extent of inclusion of minoritized older adults in GEM research, (2) GEM research about health equity, and (3) feasible approaches to improve the status quo of GEM research reporting. RESULTS: After duplicates were removed, 3277 citations remained and 883 full-text articles were reviewed, of which 222 met inclusion criteria. Four findings emerged. First, race and ethnicity reporting was inconsistent. Second, research rarely provided a rationale for an age threshold used to define geriatric patients. Third, GEM research more commonly reported sex than gender. Fourth, research commonly excluded older adults with cognitive impairment and speakers of non-English primary languages. CONCLUSION: Meaningful assessment of GEM research inclusivity is limited by inconsistent reporting of sociodemographic characteristics, specifically race and ethnicity. Reporting of sociodemographic characteristics should be standardized across different study designs. Strategies are needed to include in GEM research older adults with cognitive impairment and non-English primary languages.

Restoration of respiration in high cervical spinal cord injury via phrenic nerve reinnervation: illustrative case.

BACKGROUND: Traumatic high cervical spinal cord injury (SCI) can result in a devastating loss of functional respiration, leaving patients permanently dependent on mechanical ventilation. Nerve transfer is a promising reinnervation strategy that has the potential to restore connectivity in paralyzed distal muscles. The spinal accessory nerve (SAN) remains functional in most cases after high cervical SCI and can serve as a donor to reinnervate the phrenic nerve (PN), thereby improving diaphragmatic function. OBSERVATIONS: Information regarding thorough physical, electrodiagnostic, and pulmonary assessments to establish candidacy for nerve transfer, as well as the surgical procedure, was summarized with an illustrative case. The patient demonstrated improvement in pulmonary function testing but did not achieve independent respiration. A systematic literature review identified 3 studies with 9 additional patients who had undergone SAN-to-PN transfer. The nerve transfer meaningfully restored diaphragmatic function, improving pulmonary function tests and reducing ventilator dependency. LESSONS: Respiratory dependency significantly impacts the quality of life of patients with a high cervical SCI. The use of the lower SAN motor branch for PN transfer is safe and does not result in a meaningful downgrade in trapezius function. Outcomes following this procedure are promising but heterogeneous, indicating a need for significant innovation and improvement for future therapies. https://thejns.org/doi/10.3171/CASE24236.

A systematic review/meta-analysis of prevalence and incidence rates illustrates systemic underrepresentation of individuals racialized as Asian and/or Asian-American in ADRD research.

We investigate Alzheimer's disease and related dementia (ADRD) prevalence, incidence rate, and risk factors in individuals racialized as Asian and/or Asian-American and assess sample representation. Prevalence, incidence rate, risk factors, and heterogeneity of samples were assessed. Random-effects meta-analysis was conducted, generating pooled estimates. Of 920 records across 14 databases, 45 studies were included. Individuals racialized as Asian and/or Asian-American were mainly from Eastern and Southern Asia, had higher education, and constituted a smaller sample relative to non-Hispanic white cohorts. The average prevalence was 10.9%, ranging from 0.4% to 46%. The average incidence rate was 20.03 (12.01-33.8) per 1000 person-years with a range of 75.19-13.59 (12.89-14.33). Risk factors included physiological, genetic, psychological, behavioral, and social factors. This review underscores the systemic underrepresentation of individuals racialized as Asian and/or Asian-American in ADRD research and the need for inclusive approaches accounting for culture, language, and immigration status. HIGHLIGHTS: There is considerable heterogeneity in the prevalence of ADRD among studies of Asian-Americans. There is limited data on group-specific risk factors for ADRD among Asian-Americans. The average prevalence of (ADRD) among Asian-Americans was found to be 7.4%, with a wide range from 0.5% to 46%.

A scoping review of racial, ethnic, socioeconomic, and geographic disparities in the outcomes of older adults with cancer.

INTRODUCTION: Cancer health disparities are widespread. Nevertheless, the disparities in outcomes among diverse survivors of cancer ages 65 years and older ("older") have not been systematically evaluated. METHODS: We conducted a scoping review of original research articles published between January 2016 and September 2023 and indexed in Medline (Ovid), Embase, Scopus, and CINAHL databases. We included studies evaluating racial, ethnic, socioeconomic disadvantaged, geographic, sexual and gender, and/or persons with disabilities disparities in treatment, survivorship, and mortality among older survivors of cancer. We excluded studies with no a priori aims related to a health disparity, review articles, conference proceedings, meeting abstracts, studies with unclear methodologies, and articles in which the disparity group was examined only as an analytic covariate. Two reviewers independently extracted data following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis reporting guidelines. RESULTS: After searching and removing duplicates, 2573 unique citations remained and after screening 59 articles met the inclusion criteria. Many investigated more than one health disparity, and most focused on racial and ethnic (n = 44) or socioeconomic (n = 25) disparities; only 10 studies described geographic disparities, and none evaluated disparities in persons with disabilities or due to sexual and gender identity. Research investigating disparities in outcomes among diverse older survivors of cancer is increasing gradually-68% of eligible articles were published between 2020 and 2023. Most studies focused on the treatment phase of care (n = 28) and mortality (n = 26), with 16 examined disparities in survivorship, symptoms, or quality of life. Most research was descriptive and lacked analyses of potential underlying mechanisms contributing to the reported disparities. CONCLUSION: Little research has evaluated the effect of strategies to reduce health disparities among older patients with cancer. This lack of evidence perpetuates cancer inequities and leaves the cancer care system ill equipped to address the unique needs of the rapidly growing and increasingly diverse older adult cancer population.

How does weight gain since the age of 18 years affect breast cancer risk in later life? A meta-analysis.

Early life factors are important risk factors for breast cancer. The association between weight gain after age 18 and breast cancer risk is inconsistent across previous epidemiologic studies. To evaluate this association, we conducted a meta-analysis according to PRISMA guidelines and the established inclusion criteria. We performed a comprehensive literature search using Medline (Ovid), Embase, Scopus, Cochrane Library, and ClinicalTrials.gov to identify relevant studies published before June 3, 2022. Two reviewers independently reviewed the articles for final inclusion. Seventeen out of 4,725 unique studies met the selection criteria. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS), and all were of moderate to high quality with NOS scores ranging from 5 to 8. We included 17 studies (11 case-control, 6 cohort) in final analysis. In case-control studies, weight gain after age 18 was associated with an increased risk of breast cancer (odds ratio [OR] = 1.25; 95% CI = 1.07-1.48), when comparing the highest versus the lowest categories of weight gain. Menopausal status was a source of heterogeneity, with weight gain after age 18 associated with an increased risk of breast cancer in postmenopausal women (OR = 1.53; 95% CI = 1.40-1.68), but not in premenopausal women (OR = 1.01; 95% CI = 0.92-1.12). Additionally, a 5 kg increase in weight was positively associated with postmenopausal breast cancer risk (OR = 1.12; 95%CI = 1.05-1.21) in case-control studies. Findings from cohort studies were identical, with a positive association between weight gain after age 18 and breast cancer incidence in postmenopausal women (relative risk [RR] = 1.30; 95% CI = 1.09-1.36), but not in premenopausal women (RR = 1.06; 95% CI = 0.92-1.22). Weight gain after age 18 is a risk factor for postmenopausal breast cancer, highlighting the importance of weight control from early adulthood to reduce the incidence of postmenopausal breast cancer.

Implications of Preoperative Depression for Lumbar Spine Surgery Outcomes: A Systematic Review and Meta-Analysis.

Importance: Comorbid depression is common among patients with degenerative lumbar spine disease. Although a well-researched topic, the evidence of the role of depression in spine surgery outcomes remains inconclusive. Objective: To investigate the association between preoperative depression and patient-reported outcome measures (PROMs) after lumbar spine surgery. Data Sources: A systematic search of PubMed, Cochrane Database of Systematic Reviews, Embase, Scopus, PsychInfo, Web of Science, and ClinicalTrials.gov was performed from database inception to September 14, 2023. Study Selection: Included studies involved adults undergoing lumbar spine surgery and compared PROMs in patients with vs those without depression. Studies evaluating the correlation between preoperative depression and disease severity were also included. Data Extraction and Synthesis: All data were independently extracted by 2 authors and independently verified by a third author. Study quality was assessed using Newcastle-Ottawa Scale. Random-effects meta-analysis was used to synthesize data, and I2 was used to assess heterogeneity. Metaregression was performed to identify factors explaining the heterogeneity. Main Outcomes and Measures: The primary outcome was the standardized mean difference (SMD) of change from preoperative baseline to postoperative follow-up in PROMs of disability, pain, and physical function for patients with vs without depression. Secondary outcomes were preoperative and postoperative differences in absolute disease severity for these 2 patient populations. Results: Of the 8459 articles identified, 44 were included in the analysis. These studies involved 21 452 patients with a mean (SD) age of 57 (8) years and included 11 747 females (55%). Among these studies, the median (range) follow-up duration was 12 (6-120) months. The pooled estimates of disability, pain, and physical function showed that patients with depression experienced a greater magnitude of improvement compared with patients without depression, but this difference was not significant (SMD, 0.04 [95% CI, -0.02 to 0.10]; I2 = 75%; P = .21). Nonetheless, patients with depression presented with worse preoperative disease severity in disability, pain, and physical function (SMD, -0.52 [95% CI, -0.62 to -0.41]; I2 = 89%; P < .001), which remained worse postoperatively (SMD, -0.52 [95% CI, -0.75 to -0.28]; I2 = 98%; P < .001). There was no significant correlation between depression severity and the primary outcome. A multivariable metaregression analysis suggested that age, sex (male to female ratio), percentage of comorbidities, and follow-up attrition were significant sources of variance. Conclusions and Relevance: Results of this systematic review and meta-analysis suggested that, although patients with depression had worse disease severity both before and after surgery compared with patients without depression, they had significant potential for recovery in disability, pain, and physical function. Further investigations are needed to examine the association between spine-related disability and depression as well as the role of perioperative mental health treatments.

The effect of digital health interventions on postpartum depression or anxiety: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to examine the effect of digital health interventions compared with treatment as usual on preventing and treating postpartum depression and postpartum anxiety. DATA SOURCES: Searches were conducted in Ovid MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. STUDY ELIGIBILITY REQUIREMENTS: The systematic review included full-text randomized controlled trials comparing digital health interventions with treatment as usual for preventing or treating postpartum depression and postpartum anxiety. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors independently screened all abstracts for eligibility and independently reviewed all potentially eligible full-text articles for inclusion. A third author screened abstracts and full-text articles as needed to determine eligibility in cases of discrepancy. The primary outcome was the score on the first ascertainment of postpartum depression or postpartum anxiety symptoms after the intervention. Secondary outcomes included screening positive for postpartum depression or postpartum anxiety --as defined in the primary study --and loss to follow-up, defined as the proportion of participants who completed the final study assessment compared with the number of initially randomized participants. For continuous outcomes, the Hedges method was used to obtain standardized mean differences when the studies used different psychometric scales, and weighted mean differences were calculated when studies used the same psychometric scales. For categorical outcomes, pooled relative risks were estimated. RESULTS: Of 921 studies originally identified, 31 randomized controlled trials-corresponding to 5532 participants randomized to digital health intervention and 5492 participants randomized to treatment as usual-were included. Compared with treatment as usual, digital health interventions significantly reduced mean scores ascertaining postpartum depression symptoms (29 studies: standardized mean difference, -0.64 [95% confidence interval, -0.88 to -0.40]; I2=94.4%) and postpartum anxiety symptoms (17 studies: standardized mean difference, -0.49 [95% confidence interval, -0.72 to -0.25]; I2=84.6%). In the few studies that assessed screen-positive rates for postpartum depression (n=4) or postpartum anxiety (n=1), there were no significant differences between those randomized to digital health intervention and treatment as usual. Overall, those randomized to digital health intervention had 38% increased risk of not completing the final study assessment compared with those randomized to treatment as usual (pooled relative risk, 1.38 [95% confidence interval, 1.18-1.62]), but those randomized to app-based digital health intervention had similar loss-to-follow-up rates as those randomized to treatment as usual (relative risk, 1.04 [95% confidence interval, 0.91-1.19]). CONCLUSION: Digital health interventions modestly, but significantly, reduced scores assessing postpartum depression and postpartum anxiety symptoms. More research is needed to identify digital health interventions that effectively prevent or treat postpartum depression and postpartum anxiety but encourage ongoing engagement throughout the study period.

A Systematic Review of the State of Neurosurgical Disparities Research: Past, Present, and Future.

BACKGROUND: The social determinants of health, which influence healthcare access, patient outcomes, and population-level burden of disease, contribute to health disparities experienced by marginalized patient populations. In the present study, we sought to evaluate the landscape of health disparities research within neurosurgery. METHODS: Embase, Ovid-MEDLINE, Scopus, Web of Science, Cochrane Library, and ProQuest Dissertations databases were queried for original research on health disparities regarding access to, outcomes of, and/or postoperative management after neurosurgical procedures in the United States. RESULTS: Of 883 studies screened, 196 were included, of which 144 had a neurosurgery-affiliated author. We found a significant increase in the number of neurosurgical disparities reports beginning in 2010, with only 10 studies reported before 2010. Of the included studies, 3.1% used prospective methods and 63.8% used data from national registries. The disparities analyzed were racial/ethnic (79.6%), economic/socioeconomic (53.6%), gender (18.9%), and disabled populations (0.5%), with 40.1% analyzing multiple or intersecting disparities. Of the included reports, 96.9% were in phase 1 (detecting phase of disparities research), with a few studies in phase 2 (understanding phase), and none in phase 3 (reducing phase). The spine was the most prevalent subspecialty evaluated (34.2%), followed by neuro-oncology (19.9%), cerebrovascular (16.3%), pediatrics (10.7%), functional (9.2%), general neurosurgery (5.1%), and trauma (4.1%). Senior authors with a neurosurgical affiliation accounted for 79.2% of the reports, 93% of whom were academically affiliated. CONCLUSIONS: Although a recent increase has occurred in neurosurgical disparities research within the past decade, most studies were limited to the detection of disparities without understanding or evaluating any interventions for a reduction in disparities. Future research in neurosurgical disparities should incorporate the latter 2 factors to reduce disparities and improve outcomes for all patients.

Intraoperative Computed Tomography Use in Orbital Fracture Repair: A Systematic Review and Meta-Analysis.

Background: Intraoperative computed tomography (CT) allows surgeons to make adjustments during orbital fracture repair that may impact postoperative outcomes. Learning/Study Objectives: To determine the impact of intraoperative CT use on intraoperative revision and surgical outcomes for orbital fracture repair. Methods: A systematic review was performed in concordance with the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines: the population was patients undergoing orbital fracture repair; intervention was use of intraoperative CT; comparison was patients not undergoing intraoperative CT; and outcomes were intraoperative revision rate, postoperative complications, and secondary revision surgeries. Meta-analysis was performed on the rate of intraoperative revision. Results: The search criteria yielded 790 articles, 377 were eligible for review, and 20 articles met criteria for analysis. In 19, intraoperative imaging led to immediate surgical corrections, with a random pooled effect size of 0.27 (0.20-0.35). Six studies reported secondary revision surgery rates (range 0-10.5%), and six studies reported postoperative complication rates (range 10-30%). Conclusions: Intraoperative imaging helps surgeons make precise, real-time adjustments in 27% of orbital fracture repair cases, which may improve surgical outcomes; however, more research is needed to investigate its impact on health care costs, operating time, and radiation exposure.

Endovascular treatment of dural arteriovenous fistulas involving the vein of Galen: a single-center cohort and meta-analysis.

BACKGROUND: Dural arteriovenous fistulas (dAVFs) draining into the vein of Galen (VoG) are complex lesions that often necessitate treatment to minimize the risk of rupture and relieve symptoms. These lesions can be treated with open surgical resection, radiosurgery, or endovascular embolization. Unfortunately, endovascular treatment of dAVFs involving the VoG has not been robustly assessed across large patient cohorts. To meet this need, we performed a retrospective review of dAVFs involving the VoG at our center, and included these in a meta-analysis to identify the safety and efficacy of endovascular embolization, as well as describing current treatment trends for this disease. METHODS: Consecutive patients with dAVFs involving the VoG treated at a single center were identified from a prospective database and retrospectively reviewed. A literature search was conducted with defined search criteria, and eligible studies were included alongside our cohort in a meta-analysis. Rates of complete dAVF treatment and clinical complications were pooled across studies with a random effects model and reported with a 95% CI. RESULTS: Five dAVFs involving the VoG were treated endovascularly at our center during the study period. In this series, 80% of treatments led to complete occlusion of the fistula while no patients had clinical complications. Onyx was used for all treatments. In our meta-analysis, the overall rate of complete occlusion was 72.0% (95% CI 59.8% to 84.1%) and the overall rate of clinical complications was 10.0% (95% CI 4.7% to 15.3%). CONCLUSIONS: Endovascular approaches for dAVFs involving the VoG are technically feasible, but carry a risk of clinical complications. Future work should identify optimal endovascular embolic agents.

Evaluating the state of non-invasive imaging biomarkers for traumatic brain injury.

Non-invasive imaging biomarkers are useful for prognostication in patients with traumatic brain injury (TBI) at high risk for morbidity with invasive procedures. The authors present findings from a scoping review discussing the pertinent biomarkers. Embase, Ovid-MEDLINE, and Scopus were queried for original research on imaging biomarkers for prognostication of TBI in adult patients. Two reviewers independently screened articles, extracted data, and evaluated risk of bias. Data was synthesized and confidence evaluated with the linked evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. Our search yielded 3104 unique citations, 44 of which were included in this review. Study populations varied in TBI severity, as defined by Glasgow Coma Scale (GCS), including: mild (n=9), mild and moderate (n=3), moderate and severe (n=7), severe (n=6), and all GCS scores (n=17). Diverse imaging modalities were used for prognostication, predominantly computed tomography (CT) only (n=11), magnetic resonance imaging (MRI) only (n=9), and diffusion tensor imaging (DTI) (N=9). The biomarkers included diffusion coefficient mapping, metabolic characteristics, optic nerve sheath diameter, T1-weighted signal changes, cortical cerebral blood flow, axial versus extra-axial lesions, T2-weighted gradient versus spin echo, translocator protein levels, and trauma imaging of brainstem areas. The majority (93%) of studies identified that the imaging biomarker of interest had a statistically significant prognostic value; however, these are based on a very low to low level of quality of evidence. No study directly compared the effects on specific TBI treatments on the temporal course of imaging biomarkers. The current literature is insufficient to make a strong recommendation about a preferred imaging biomarker for TBI, especially considering GRADE criteria revealing low quality of evidence. Rigorous prospective research of imaging biomarkers of TBI is warranted to improve the understanding of TBI severity.

Repeated measures of mammographic density and texture to evaluate prediction and risk of breast cancer: a systematic review of the methods used in the literature.

PURPOSE: It may be important for women to have mammograms at different points in time to track changes in breast density, as fluctuations in breast density can affect breast cancer risk. This systematic review aimed to assess methods used to relate repeated mammographic images to breast cancer risk. METHODS: The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021. Eligibility criteria included published articles in English describing the relationship of change in mammographic features with risk of breast cancer. Risk of bias was assessed using the Quality in Prognostic Studies tool. RESULTS: Twenty articles were included. The Breast Imaging Reporting and Data System and Cumulus were most commonly used for classifying mammographic density and automated assessment was used on more recent digital mammograms. Time between mammograms varied from 1 year to a median of 4.1, and only nine of the studies used more than two mammograms. Several studies showed that adding change of density or mammographic features improved model performance. Variation in risk of bias of studies was highest in prognostic factor measurement and study confounding. CONCLUSION: This review provided an updated overview and revealed research gaps in assessment of the use of texture features, risk prediction, and AUC. We provide recommendations for future studies using repeated measure methods for mammogram images to improve risk classification and risk prediction for women to tailor screening and prevention strategies to level of risk.

The function of histone methylation and acetylation regulators in GBM pathophysiology.

Glioblastoma (GBM) is the most common and lethal primary brain malignancy and is characterized by a high degree of intra and intertumor cellular heterogeneity, a starkly immunosuppressive tumor microenvironment, and nearly universal recurrence. The application of various genomic approaches has allowed us to understand the core molecular signatures, transcriptional states, and DNA methylation patterns that define GBM. Histone posttranslational modifications (PTMs) have been shown to influence oncogenesis in a variety of malignancies, including other forms of glioma, yet comparatively less effort has been placed on understanding the transcriptional impact and regulation of histone PTMs in the context of GBM. In this review we discuss work that investigates the role of histone acetylating and methylating enzymes in GBM pathogenesis, as well as the effects of targeted inhibition of these enzymes. We then synthesize broader genomic and epigenomic approaches to understand the influence of histone PTMs on chromatin architecture and transcription within GBM and finally, explore the limitations of current research in this field before proposing future directions for this area of research.

Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and meta-analysis.

Introduction: NRAS mutations are common in melanoma and confer a worse prognosis. Although most patients with metastatic melanoma receive immune checkpoint inhibitors (ICIs), the impact of NRAS mutational status on their efficacy remains under debate. Methods: We performed a comprehensive literature search across several large databases. Inclusion criteria were trials, cohorts, and large case series that analyzed the primary outcome of objective response rate by NRAS mutational status in patients with melanoma treated with any line of ICI. At least two reviewers independently screened studies using Covidence software, extracted data, and assessed risk of bias. Standard meta-analysis was performed in R with sensitivity analysis and tests for bias. Results: Data on 1770 patients from ten articles were pooled for meta-analysis, and the objective response rate to ICIs was calculated to compare NRAS-mutant and NRAS-wildtype melanoma. The objective response rate was 1.28 (95% confidence interval: 1.01-1.64). Sensitivity analysis identified the study by Dupuis et al. with influential impact on the pooled effect size and heterogeneity, favoring NRAS-mutant melanoma. Discussion: In this meta-analysis evaluating the impact of NRAS mutational status on objective response to ICIs in metastatic melanoma, NRAS-mutant cutaneous melanoma demonstrated an increased likelihood of partial or complete tumor response, relative to NRAS-wildtype cutaneous melanoma. Genomic screening for NRAS mutations in patients with metastatic melanoma may improve predictive ability when initiating ICIs.

Efficacy of Postpartum Pharmacologic Thromboprophylaxis: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of pharmacologic venous thromboembolism (VTE) prophylaxis in postpartum patients. DATA SOURCES: On February 21, 2022, a literature search was conducted on Embase.com , Ovid-Medline All, Cochrane Library, Scopus, and ClinicalTrials.gov using terms postpartum period AND thromboprophylaxis AND antithrombin medications including heparin and low molecular weight heparin. METHODS OF STUDY SELECTION: Studies that evaluated the outcome of VTE among postpartum patients exposed to pharmacologic VTE prophylaxis with or without a comparator group were eligible for inclusion. Studies of patients who received antepartum VTE prophylaxis, studies in which this prophylaxis could not be definitively ruled out, and studies of patients who received therapeutic dosing of anticoagulation for specific medical problems or treatment of VTE were excluded. Titles and abstracts were independently screened by two authors. Relevant full-text articles were retrieved and independently reviewed for inclusion or exclusion by two authors. TABULATION, INTEGRATION, AND RESULTS: A total of 944 studies were screened by title and abstract, and 54 full-text studies were retrieved for further evaluation after 890 studies were excluded. Fourteen studies including 11,944 patients were analyzed: eight randomized controlled trials (8,001 patients) and six observational studies (3,943 patients). Among the eight studies with a comparator group, there was no difference in the risk of VTE between patients who were exposed to postpartum pharmacologic VTE prophylaxis and those who were unexposed (pooled relative risk 1.02, 95% CI 0.29-3.51); however, six of eight studies had no events in either the exposed or unexposed group. Among the six studies without a comparator group, the pooled proportion of postpartum VTE events was 0.00, likely due to five of six studies having no events. CONCLUSION: The current literature provided an insufficient sample size to conclude whether postpartum VTE rates differ between those exposed to postpartum pharmacologic prophylaxis and those unexposed, given the rarity of VTE events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022323841.

A call for clinical trial globalization in Alzheimer's disease and related dementia.

BACKGROUND: The burden of Alzheimer's disease and related dementia (ADRD) is projected to disproportionally impact low-middle-income countries (LMICs). However, there is a systematic under-representation of LMICs in ADRD clinical trial platforms. METHODS: We aimed to determine the global distribution of ADRD clinical trials and identify existing barriers for conducting clinical trials in LMICs. Primary data sources to identify trial distribution in LMICs included ClinicalTrials.gov and the International Trials Registry Platform. An additional systematic review and expert consensus interviews were conducted to identify barriers for conducting clinical trials in LMICs. FINDINGS: Among 1237 disease-modifying therapies tested in ADRD clinical trials, only 11.6% have been or are conducted in emerging economies (upper-middle income [9.6%] and low-middle income [2.0%]). We identified several limitations for trial implementation including a lack of financial resources, low industry presence, regulatory obstacles, and operational barriers INTERPRETATION: Although LMICs bear the greatest burden of ADRD globally, substantial development of clinical trial platforms to address this inequity and health disparity is lacking.