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1.
Child Maltreat ; : 10775595241252350, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733155

ABSTRACT

It is not known how school closure affected child maltreatment. We conducted a retrospective cohort, linear mixed-models study of 133 counties (comprising 8,582,479 children) in Virginia between 2018 and 2021. Exposure was the opening of schools at least 2 days a week. Outcomes were referrals and incidence of child maltreatment reported to the Department of Social Services. In 2020-2021, there were descriptively more referrals (in-person: 50.9 per 10,000 [95% CI: 47.9, 54.0]; virtual: 45.8 per 10,000 [95% CI: 40.7, 50.9]) and incidence (in-person: 3.7 per 10,000 [95% CI: 3.3, 4.2]; virtual: 2.9 per 10,000 [95% CI: 2.3, 3.5]) of child maltreatment in counties with in-person schooling, though these differences did not reach statistical significance. The referral rate variations (between pandemic and pre-pandemic eras) of counties with in-person schooling was significantly greater than rate changes in counties with virtual schooling during the summer period. There were no differences in incidence in any quarter. Higher poverty within a county was associated with both higher referrals and incidence. Our findings suggest that child maltreatment is driven primarily by underlying differences in counties (namely, poverty) rather than the type of schooling children receive.

2.
Cancers (Basel) ; 16(9)2024 May 05.
Article in English | MEDLINE | ID: mdl-38730736

ABSTRACT

BACKGROUND: Awake craniotomy (AC) is recommended for the resection of tumors in eloquent areas. It is traditionally performed under monitored anesthesia care (MAC), which relies on hypnotics and opioids. Hypnosis-assisted AC (HAAC) is an emerging technique that aims to provide psychological support while reducing the need for pharmacological sedation and analgesia. We aimed to compare the characteristics and outcomes of patients who underwent AC under HAAC or MAC. METHODS: We retrospectively analyzed the clinical, anesthetic, surgical, and neuropsychological data of patients who underwent awake surgical resection of eloquent brain tumors under HAAC or MAC. We used Mann-Whitney U tests, Wilcoxon signed-rank tests, and repeated-measures analyses of variance to identify statistically significant differences at the 0.05 level. RESULTS: A total of 22 patients were analyzed, 14 in the HAAC group and 8 in the MAC group. Demographic, radiological, and surgical characteristics as well as postoperative outcomes were similar. Patients in the HAAC group received less remifentanil (p = 0.047) and propofol (p = 0.002), but more dexmedetomidine (p = 0.025). None of them received ketamine as a rescue analgesic. Although patients in the HAAC group experienced higher levels of perioperative pain (p < 0.05), they reported decreasing stress levels (p = 0.04) and greater levels of satisfaction (p = 0.02). CONCLUSION: HAAC is a safe alternative to MAC as it reduces perioperative stress and increases overall satisfaction. Further research is necessary to assess whether hypnosis is clinically beneficial.

3.
Acta Neurochir (Wien) ; 166(1): 133, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38472426

ABSTRACT

PURPOSE: Intrathecal vasoactive drugs have been proposed in patients with aneurysmal subarachnoid hemorrhage (aSAH) to manage cerebral vasospasm (CV). We analyzed the efficacy of intracisternal nicardipine compared to intraventricular administration to a control group (CG) to determine its impact on delayed cerebral ischemia (DCI) and functional outcomes. Secondary outcomes included the need for intra-arterial angioplasties and the safety profile. METHODS: We performed a retrospective analysis of prospectively collected data of all adult patients admitted for a high modified Fisher grade aSAH between January 2015 and April 2022. All patients with significant radiological CV were included. Three groups of patients were defined based on the CV management: cisternal nicardipine (CN), ventricular nicardipine (VN), and no intrathecal nicardipine (control group). RESULTS: Seventy patients met the inclusion criteria. Eleven patients received intracisternal nicardipine, 18 intraventricular nicardipine, and 41 belonged to the control group. No cases of DCI were observed in the CN group (p = 0.02). Patients with intracisternal nicardipine had a reduced number of intra-arterial angioplasties when compared to the control group (p = 0.03). The safety profile analysis showed no difference in complications across the three groups. Intrathecal (ventricular or cisternal) nicardipine therapy improved functional outcomes at 6 months (p = 0.04) when compared to the control group. CONCLUSION: Administration of intrathecal nicardipine for moderate to severe CV reduces the rate of DCI and improved long-term functional outcomes in patients with high modified Fisher grade aSAH. This study also showed a relative benefit of cisternal over intraventricular nicardipine, thereby reducing the number of angioplasties performed in the post-treatment phase. However, these preliminary results should be confirmed with future prospective studies.


Subject(s)
Brain Ischemia , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Adult , Humans , Nicardipine , Subarachnoid Hemorrhage/complications , Retrospective Studies , Prospective Studies , Brain Ischemia/drug therapy , Cerebral Infarction , Vasospasm, Intracranial/etiology
5.
J Pers Med ; 14(2)2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38392620

ABSTRACT

Our study explores the integration of three-dimensional (3D) virtual reality (VR) and 3D printing in neurosurgical preoperative planning. Traditionally, surgeons relied on two-dimensional (2D) imaging for complex neuroanatomy analyses, requiring significant mental visualization. Fortunately, nowadays advanced technology enables the creation of detailed 3D models from patient scans, utilizing different software. Afterwards, these models can be experienced through VR systems, offering comprehensive preoperative rehearsal opportunities. Additionally, 3D models can be 3D printed for hands-on training, therefore enhancing surgical preparedness. This technological integration transforms the paradigm of neurosurgical planning, ensuring safer procedures.

6.
ERJ Open Res ; 10(1)2024 Jan.
Article in English | MEDLINE | ID: mdl-38410700

ABSTRACT

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

7.
Cancer Cell ; 42(3): 378-395.e10, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38242126

ABSTRACT

Brain metastasis (BrM) is a common malignancy, predominantly originating from lung, melanoma, and breast cancers. The vasculature is a key component of the BrM tumor microenvironment with critical roles in regulating metastatic seeding and progression. However, the heterogeneity of the major BrM vascular components, namely endothelial and mural cells, is still poorly understood. We perform single-cell and bulk RNA-sequencing of sorted vascular cell types and detect multiple subtypes enriched specifically in BrM compared to non-tumor brain, including previously unrecognized immune regulatory subtypes. We integrate the human data with mouse models, creating a platform to interrogate vascular targets for the treatment of BrM. We find that the CD276 immune checkpoint molecule is significantly upregulated in the BrM vasculature, and anti-CD276 blocking antibodies prolonged survival in preclinical trials. This study provides important insights into the complex interactions between the vasculature, immune cells, and cancer cells, with translational relevance for designing therapeutic interventions.


Subject(s)
Brain Neoplasms , Breast Neoplasms , Melanoma , Mice , Animals , Humans , Female , Brain Neoplasms/pathology , Brain/metabolism , Breast Neoplasms/pathology , Transcription Factors/metabolism , Tumor Microenvironment , B7 Antigens
8.
NPJ Digit Med ; 7(1): 1, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38172429

ABSTRACT

Dementia is a common medical condition in the ageing population, and cognitive intervention is a non-pharmacologic strategy to improve cognitive functions. This meta-analysis evaluated the benefits of computerized cognitive training (CCT) on memory functions in individuals with MCI or dementia. The study was registered prospectively with PROSPERO under CRD42022363715 and received no funding. The search was conducted on MEDLINE, Embase, and PsycINFO on Sept 19, 2022, and Google Scholar on May 9, 2023, to identify randomized controlled trials that examined the effects of CCT on memory outcomes in individuals with MCI or dementia. Mean differences and standard deviations of neuropsychological assessment scores were extracted to derive standardized mean differences. Our search identified 10,678 studies, of which 35 studies were included. Among 1489 participants with MCI, CCT showed improvements in verbal memory (SMD (95%CI) = 0.55 (0.35-0.74)), visual memory (0.36 (0.12-0.60)), and working memory (0.37 (0.10-0.64)). Supervised CCT showed improvements in verbal memory (0.72 (0.45-0.98)), visual memory (0.51 (0.22-0.79)), and working memory (0.33 (0.01-0.66)). Unsupervised CCT showed improvement in verbal memory (0.21 (0.04-0.38)) only. Among 371 participants with dementia, CCT showed improvement in verbal memory (0.64 (0.02-1.27)) only. Inconsistency due to heterogeneity (as indicated by I2 values) is observed, which reduces our confidence in MCI outcomes to a moderate level and dementia outcomes to a low level. The results suggest that CCT is efficacious on various memory domains in individuals with MCI. Although the supervised approach showed greater effects, the unsupervised approach can improve verbal memory while allowing users to receive CCT at home without engaging as many healthcare resources.

9.
J Neurophysiol ; 131(2): 338-359, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38230872

ABSTRACT

Complex locomotor patterns are generated by combination of muscle synergies. How genetic processes, early sensorimotor experiences, and the developmental dynamics of neuronal circuits contribute to the expression of muscle synergies remains elusive. We shed light on the factors that influence development of muscle synergies by studying subjects with spinal muscular atrophy (SMA, types II/IIIa), a disorder associated with degeneration and deafferentation of motoneurons and possibly motor cortical and cerebellar abnormalities, from which the afflicted would have atypical sensorimotor histories around typical walking onset. Muscle synergies of children with SMA were identified from electromyographic signals recorded during active-assisted leg motions or walking, and compared with those of age-matched controls. We found that the earlier the SMA onset age, the more different the SMA synergies were from the normative. These alterations could not just be explained by the different degrees of uneven motoneuronal losses across muscles. The SMA-specific synergies had activations in muscles from multiple limb compartments, a finding reminiscent of the neonatal synergies of typically developing infants. Overall, while the synergies shared between SMA and control subjects may reflect components of a core modular infrastructure determined early in life, the SMA-specific synergies may be developmentally immature synergies that arise from inadequate activity-dependent interneuronal sculpting due to abnormal sensorimotor experience and other factors. Other mechanisms including SMA-induced intraspinal changes and altered cortical-spinal interactions may also contribute to synergy changes. Our interpretation highlights the roles of the sensory and descending systems to the typical and abnormal development of locomotor modules.NEW & NOTEWORTHY This is likely the first report of locomotor muscle synergies of children with spinal muscular atrophy (SMA), a subject group with atypical developmental sensorimotor experience. We found that the earlier the SMA onset age, the more the subjects' synergies deviated from those of age-matched controls. This result suggests contributions of the sensory/corticospinal activities to the typical expression of locomotor modules, and how their disruptions during a critical period of development may lead to abnormal motor modules.


Subject(s)
Muscle, Skeletal , Muscular Atrophy, Spinal , Child , Infant , Infant, Newborn , Humans , Muscle, Skeletal/physiology , Electromyography , Walking/physiology , Motor Neurons/physiology
10.
J Am Board Fam Med ; 36(6): 892-904, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38092433

ABSTRACT

BACKGROUND: Primary care is the foundation of health care, resulting in longer lives and improved equity. Primary care was the frontline of the COVID-19 pandemic public response and essential for access to care. Yet primary care faces substantial structural and systemic challenges. As part of a longitudinal analysis to track the capacity and health of primary care, we surveyed every primary care practice in Virginia in 2018 and again in 2022. METHODS: Surveys were emailed or mailed up to 6 times and nonresponders received a phone call. Questions assessed organizational characteristics, scope of care, capacity, and organizational stress in the prior year. From respondents, 39 clinicians, nurses, staff, administrators, and practice managers were interviewed. RESULTS: 526 out of 2296 primary care practices (23% response rate) completed the survey, with broad representation across geography, ownership, and payer mix. Compared with 2018, in 2022 there were increases in practices owned by health systems (25% vs 43%, P < .0001) and average percent of patients with Medicaid per practice (12% vs 22%, P < .0001). The percent of practices reporting any major stressor increased from 34% to 53% (P < .0001). The main increased stress was losing a clinician, with 13% of practices in 2018 versus 42% in 2022 reporting losing a clinician (P < .0001). CONCLUSIONS: Primary care practices are resilient and continue to serve their communities, including a broad scope of services and care for underserved people. However, the COVID-19 pandemic caused significant stress. With an increase in clinicians leaving clinical practice, we anticipate worsening access to primary care.


Subject(s)
COVID-19 , Medicaid , United States/epidemiology , Humans , Ownership , Pandemics , Primary Health Care , COVID-19/epidemiology
11.
Oper Neurosurg (Hagerstown) ; 26(3): 301-308, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37878474

ABSTRACT

BACKGROUND AND OBJECTIVES: The extradural anterior petrosal approach (EAPA) can present a challenge because it deals with critical structures in a narrow, confined corridor. It is associated with several potential approach-related risks including temporal lobe and venous injuries. Tentorial peeling has the potential to largely eliminate these risks during the approach and may offer more options for tailoring the dural opening to the anatomic region that one wants to expose. METHODS: Anatomic dissections of five adult injected non-formalin-fixed cadaveric heads were performed. Anterior petrosectomy with intertentorial approach (APIA) through a tentorial peeling was completed. Step-by-step documentation of the cadaveric dissections and diagrammatic representations are presented along with an illustrative case. RESULTS: Tentorial peeling separates the tentorium into a temporal tentorial leaf and posterior fossa tentorial leaf, adding a fourth dural layer to the three classic ones described during a standard EAPA. This opens out the intertentorial space and offers more options for tailoring the dural incisions specific to the pathology being treated. This represents a unique possibility to address brainstem or skull base pathology along the mid- and upper clivus with the ability to keep the entire temporal lobe and basal temporal veins covered by the temporal tentorial leaf. The APIA was successfully used for the resection of a large clival chordoma in the illustrative case. CONCLUSION: APIA is an interesting modification to the classic EAPA to reduce the approach-related morbidity. The risk reduction achieved is by eliminating the exposure of the temporal lobe while maintaining the excellent access to the petroclival region. It also provides several options to tailor the durotomies based on the localization of the lesion.


Subject(s)
Neurosurgical Procedures , Skull Base Neoplasms , Adult , Humans , Craniotomy , Skull Base/surgery , Skull Base Neoplasms/surgery , Cadaver
12.
Matern Child Health J ; 28(5): 798-803, 2024 May.
Article in English | MEDLINE | ID: mdl-37991589

ABSTRACT

PURPOSE: Women and children continue to miss preventive visits. Which neighborhood factors predict inadequate prenatal care (PNC) and well-child visit (WCV) attendance remain unclear. DESCRIPTION: In a retrospective case-control study at Virginia Commonwealth University Health System, mothers with less than 50% adherence or initiation after 5 months gestation were eligible as cases and those with ≥ 80% adherence and initiation before 5 months were eligible as controls. Children in the lowest quintile of adherence were eligible as cases and those with ≥ 80% of adherence were eligible as controls. Cases and controls were randomly selected at a 1:2 ratio and matched on birth month. Covariates were derived from the 2018 American Community Survey. A hotspot was defined as a zip code tabulation area (ZCTA) with a proportion of controls less than 0.66. ZCTAs with fewer than 5 individuals were excluded. Weighted quantile regression was used to determine which covariates were most associated with inadequate attendance. ASSESSMENT: We identified 38 and 35 ZCTAs for the PNC and WCV analyses, respectively. Five of 11 hotspots for WCV were also hotspots for PNC. Education and income predicted 51% and 34% of the variation in missed PNCs, respectively; language, education and transportation difficulties explained 33%, 29%, and 17% of the variation in missed WCVs, respectively. Higher proportions of Black residents lived in hotspots of inadequate PCV and WCV attendance. CONCLUSION: Neighborhood-level factors performed well in predicting inadequate PCV and WCV attendance. The disproportionate impact impact of inadequate PCV and WCV in neighborhoods where higher proportions of Black people lived highlights the potential influence of systemic racism and segregation on healthcare utilization.


Subject(s)
Prenatal Care , Residence Characteristics , Humans , Pregnancy , Female , Retrospective Studies , Case-Control Studies , Income
13.
Article in English | MEDLINE | ID: mdl-38082572

ABSTRACT

Distance running related injuries are common, and many ailments have been associated with faulty posture. Conventional measurement of running kinematics requires sophisticated motion capture system in laboratory. In this study, we developed a wearable solution to accurately predict lower limb running kinematics using a single inertial measurement unit placed on the left lower leg. The running data collected from participants was used to train a model using long short-term memory (LSTM) neural networks with an inter-subject approach that predicted lower limb kinematics with an average accuracy of 80.2%, 85.8%, and 69.4% for sagittal hip, knee and ankle joint angles respectively for the ipsilateral limb. A comparable accuracy range was observed for the contralateral limb. The average RMSE (root mean squared error) of sagittal hip, knee and ankle were 8.76°, 13.13°, and 9.67° respectively for the ipsilateral limb. Analysis of contralateral limb kinematics was performed. The model established in this study can be used as a monitoring device to track essential running kinematics in natural running environments. Besides, the wearable solution can be an integral part of a real-time gait retraining biofeedback system for injury prevention and rehabilitation.


Subject(s)
Gait , Lower Extremity , Humans , Biomechanical Phenomena , Knee Joint , Neural Networks, Computer
14.
Brain Sci ; 13(11)2023 Nov 11.
Article in English | MEDLINE | ID: mdl-38002540

ABSTRACT

Aneurysmal subarachnoid hemorrhage (aSAH) provokes a cascade reaction that is responsible for early and delayed brain injuries mediated by intracranial hypertension, hydrocephalus, cerebral vasospasm (CV), and delayed cerebral ischemia (DCI), which result in increased morbidity and mortality. During open microsurgical repair, cisternal access is achieved essentially to gain proximal vascular control and aneurysm exposition. Cisternostomy also allows brain relaxation, removal of cisternal clots, and restoration of the CSF dynamics through the communication between the anterior and posterior circulation cisterns and the ventricular system, with the opening of the Membrane of Liliequist and lamina terminalis, respectively. Continuous postoperative CSF drainage through a cisternal drain (CD) is a valuable option for treating acute hydrocephalus and intracranial hypertension. Moreover, it efficiently removes the blood and toxic degradation products, with a potential benefit on CV, DCI, and shunt-dependent hydrocephalus. Finally, the CD is an effective pathway to administer vasoactive, fibrinolytic, and anti-oxidant agents and shows promising results in decreasing CV and DCI rates while minimizing systemic effects. We performed a comprehensive review to establish the adjuvant role of cisternostomy and CD performed in cases of direct surgical repair for ruptured intracranial aneurysms and their role in the prevention and treatment of aSAH complications.

15.
Sports Biomech ; : 1-10, 2023 Nov 13.
Article in English | MEDLINE | ID: mdl-37955262

ABSTRACT

Trail runners have been reported to be more injury prone than road runners. Limited past studies have examined the difference in the running biomechanics between the two groups of runners. More importantly, the effect of surface inclination has not been fully investigated. Hence, this study examined the effect of surface inclination on running biomechanics in trail and road runners. Twenty trails and 20 road runners were recruited in this study. Trail runners appeared to be more experienced and had longer training distance per week (p < 0.001) compared to road runners. All participants ran at a self-selected pace on an instrumented treadmill in three inclination conditions (i.e., level, +10% uphill and -10% downhill) in a random order. Vertical average loading rate (VALR), vertical instantaneous loading rate (VILR) and footstrike angle (FSA) were measured using established methods. Trail runners experienced greater VILR (p = 0.039, Cohen's d = 2.9) with a greater FSA (p = 0.002, Cohen's d = 1.1) during downhill running than road runners. No significant differences in VALR, VILR and FSA were found between the two groups during level and uphill running. Our findings provide potential biomechanical rationale to explain a higher injury incidence among trail runners.

16.
AJPM Focus ; 2(3): 100102, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37790667

ABSTRACT

Introduction: There were more than 100,000 fatal drug overdoses in the U.S. in 2021 alone. In recent years, there has been a shift in opioid mortality from predominantly White rural communities to Black urban communities. This study aimed to identify the Virginia communities disproportionately affected by the overdose crisis and to better understand the systemic factors contributing to disparities in opioid mortality. Methods: Using the state all-payer claims database, state mortality records, and census data, we created a multivariate model to examine the community-level factors contributing to racial disparities in opioid mortality. We used generalized linear mixed models to examine the associations between socioecologic factors and fatal opioid overdoses, opioid use disorder diagnoses, opioid-related emergency department visits, and mental health diagnoses. Results: Between 2015 and 2020, racial disparities in mortality widened. In 2020, Black males were 1.5 times more likely to die of an opioid overdose than White males (47.3 vs 31.6 per 100,000; p<0.001). The rate of mental health disorders strongly correlated with mortality (ß=0.53, p<0.001). Black individuals are not more likely to be diagnosed with opioid use disorder (ß=0.01, p=0.002) or with mental health disorders (ß= -0.12, p<0.001), despite higher fatal opioid overdoses. Conclusions: There are widening racial disparities in opioid mortality. Untreated mental health disorders are a major risk factor for opioid mortality. Findings show pathways to address inequities, including early linkage to care for mental health and opioid use disorders. This analysis shows the use of comprehensive socioecologic data to identify the precursors to fatal overdoses, which could allow earlier intervention and reallocation of resources in high-risk communities.

17.
Neurosurg Rev ; 46(1): 287, 2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37897519

ABSTRACT

Perioptic meningiomas, defined as those that are less than 3 mm from the optic apparatus, are challenging to treat with stereotactic radiosurgery (SRS). Tumor control must be weighed against the risk of radiation-induced optic neuropathy (RION), as both tumor progression and RION can lead to visual decline. We performed a systematic review and meta-analysis of single fraction SRS and hypofractionated radiosurgery (hfRS) for perioptic meningiomas, evaluating tumor control and visual preservation rates. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we reviewed articles published between 1968 and December 8, 2022. We retained 5 studies reporting 865 patients, 438 cases treated in single fraction, while 427 with hfRS. For single fraction SRS, the overall rate of tumor control was 95.1%, with actuarial rates at 5 and 10 years of 96% and 89%, respectively; tumor progression was 7.7%. The rate of visual stability was 90.4%, including visual improvement in 29.3%. The rate of visual decline was 9.6%, including blindness in 1.2%. For hfRS, the overall rate of tumor control was 95.6% (range 92.1-99.1, p < 0.001); tumor progression was 4.4% (range 0.9-7.9, p = 0.01). Overall rate of visual stability was 94.9% (range 90.9-98.9, p < 0.001), including visual improvement in 22.7% (range 5.0-40.3, p = 0.01); visual decline was 5.1% (range 1.1-9.1, p = 0.013). SRS is an effective and safe treatment option for perioptic meningiomas. Both hypofractionated regimens and single fraction SRS can be considered.


Subject(s)
Meningeal Neoplasms , Meningioma , Radiosurgery , Humans , Meningeal Neoplasms/radiotherapy , Meningeal Neoplasms/surgery , Meningeal Neoplasms/pathology , Meningioma/radiotherapy , Meningioma/surgery , Meningioma/pathology , Optic Nerve , Treatment Outcome
18.
Cell ; 186(21): 4546-4566.e27, 2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37769657

ABSTRACT

Neutrophils are abundant immune cells in the circulation and frequently infiltrate tumors in substantial numbers. However, their precise functions in different cancer types remain incompletely understood, including in the brain microenvironment. We therefore investigated neutrophils in tumor tissue of glioma and brain metastasis patients, with matched peripheral blood, and herein describe the first in-depth analysis of neutrophil phenotypes and functions in these tissues. Orthogonal profiling strategies in humans and mice revealed that brain tumor-associated neutrophils (TANs) differ significantly from blood neutrophils and have a prolonged lifespan and immune-suppressive and pro-angiogenic capacity. TANs exhibit a distinct inflammatory signature, driven by a combination of soluble inflammatory mediators including tumor necrosis factor alpha (TNF-ɑ) and Ceruloplasmin, which is more pronounced in TANs from brain metastasis versus glioma. Myeloid cells, including tumor-associated macrophages, emerge at the core of this network of pro-inflammatory mediators, supporting the concept of a critical myeloid niche regulating overall immune suppression in human brain tumors.

19.
Milbank Q ; 101(4): 1191-1222, 2023 12.
Article in English | MEDLINE | ID: mdl-37706227

ABSTRACT

Policy Points The increasing political polarization of states reached new heights during the COVID-19 pandemic, when response plans differed sharply across party lines. This study found that states with Republican governors and larger Republican majorities in legislatures experienced higher death rates during the COVID-19 pandemic-and in preceding years-but these associations often lost statistical significance after adjusting for the average income and health status of state populations and for the policy orientations of the states. Future research may help clarify whether the higher death rates in these states result from policy choices or have other explanations, such as the tendency of voters with lower incomes or poorer health to elect Republican candidates. CONTEXT: Increasing polarization of states reached a high point during the COVID-19 pandemic, when the party affiliation of elected officials often predicted their policy response. The health consequences of these divisions are unclear. Prior studies compared mortality rates based on presidential voting patterns, but few considered the partisan orientation of state officials. This study examined whether the partisan orientation of governors or legislatures was associated with mortality outcomes during the COVID-19 pandemic. METHODS: Data on deaths and the partisan orientation of governors and legislators were obtained from the Centers for Disease Control and Prevention and the National Conference of State Legislatures, respectively. Linear regression was used to measure the association between Republican representation (percentage of seats held) in legislatures and (1) age-adjusted, all-cause mortality rates (AAMRs) in 2015-2021 and (2) excess death rates during three phases of the COVID-19 pandemic, controlling for median household income, the prevalence of four risk factors (obesity, chronic obstructive pulmonary disease, heart attack, stroke), and state policy orientation. Associations between excess death rates and the governor's party were also examined. FINDINGS: States with Republican governors or greater Republican representation in legislatures experienced higher AAMRs during 2015-2021, lower excess death rates during Phase 1 of the COVID-19 pandemic (weeks ending March 28, 2020, through June 13, 2020), and higher excess death rates in Phases 2 and 3 (weeks ending June 20, 2020, through April 30, 2022; p < 0.05). Most associations lost statistical significance after adjustment for control variables. CONCLUSIONS: Mortality was higher in states with Republican governors and greater Republican legislative representation before and during much of the pandemic. Observed associations could be explained by the adverse effects of policy choices, reverse causality (e.g., popularity of Republican candidates in states with lower socioeconomic and health status), or unmeasured factors that predominate in states with Republican leaders.


Subject(s)
COVID-19 , Humans , United States/epidemiology , State Government , Pandemics , Politics , Voting
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