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2.
Pharmacol Ther ; 259: 108667, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38763321

RESUMEN

This review critically examines the evolving landscape of chimeric antigen receptor (CAR) T-cell therapy in treating solid tumors, with a particular focus on the metabolic challenges within the tumor microenvironment. CAR T-cell therapy has demonstrated remarkable success in hematologic malignancies, yet its efficacy in solid tumors remains limited. A significant barrier is the hostile milieu of the tumor microenvironment, which impairs CAR T-cell survival and function. This review delves into the metabolic adaptations of cancer cells and their impact on immune cells, highlighting the competition for nutrients and the accumulation of immunosuppressive metabolites. It also explores emerging strategies to enhance CAR T-cell metabolic fitness and persistence, including genetic engineering and metabolic reprogramming. An integrated approach, combining metabolic interventions with CAR T-cell therapy, has the potential to overcome these constraints and improve therapeutic outcomes in solid tumors.


Asunto(s)
Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , Microambiente Tumoral , Humanos , Neoplasias/terapia , Neoplasias/inmunología , Inmunoterapia Adoptiva/métodos , Animales , Microambiente Tumoral/inmunología , Receptores Quiméricos de Antígenos/inmunología , Linfocitos T/inmunología
3.
Neuro Oncol ; 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38581292

RESUMEN

BACKGROUND: Survival is variable in patients with glioblastoma IDH wild-type (GBM), even after comparable surgical resection of radiographically-detectable disease, highlighting the limitations of radiographic assessment of infiltrative tumor anatomy. The majority of post-surgical progressive events are failures within 2cm of the resection margin, motivating supramaximal resection strategies to improve local control. However, which patients benefit from such radical resections remains unknown. METHODS: We developed a predictive model to identify which IDH wild-type GBM are amenable to radiographic gross total resection (GTR). We then investigated whether GBM survival heterogeneity following GTR is correlated with microscopic tumor burden a by analyzing tumor cell content at the surgical margin with a rapid qPCR-based method for detection of TERT promoter mutation. RESULTS: Our predictive model for achievable GTR, developed on retrospective radiographic and molecular data of GBM patients undergoing resection, had an AUC of 0.83, sensitivity of 62%, and specificity of 90%. Prospective analysis of this model in 44 patients found 89% of patients were correctly predicted to achieve a RV<4.9cc. Of the 44 prospective patients undergoing rapid qPCR TERT promoter mutation analysis at the surgical margin, 7 had undetectable TERT mutation, of which 5 also had a gross total resection (RV<1cc). In these 5 patients at 30 months follow up, 75% showed no progression, compared to 0% in the group with TERT mutations detected at the surgical margin (p=0.02). CONCLUSIONS: These findings identify a subset of patients with GBM that may derive local control benefit from radical resection to undetectable molecular margins.

4.
Clin Toxicol (Phila) ; 62(3): 174-182, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38683030

RESUMEN

INTRODUCTION: Despite known contraindications, benzodiazepines are frequently prescribed for older adults. This study utilizes poison control center data on benzodiazepine-involved cases aged 50 and above to compare the characteristics of suspected suicide attempt with other intentional misuse cases. We also examined associations of major medical outcomes (major effect/death) with demographic characteristics and other co-used substances in each group. METHODS: The study employed data from the America's Poison Center National Poison Data System from 2015-2022. Descriptive statistics and binary logistic regression models were used. RESULTS: Of the benzodiazepine-poisoning cases of intentional misuse (n = 93,245), 85 percent were suicide attempts and 15 percent were other intentional misuses. Reports to poisons centers showed a decline from 2019-2022 when compared to 2015-2016. However, the likelihood of a reported suicide attempt, compared to other intentional misuse, was greater in 2019-2022 compared to 2015-2016 and among those who co-used antidepressants, anxiolytics, atypical antipsychotics, other benzodiazepines, other analgesics, anticonvulsants, and alcohol. The odds of major effect/death in both groups were also greater in 2019-2022, with suicide attempt cases in advanced ages showing higher odds. The co-use of antidepressants, prescription opioids, atypical antipsychotics, anticonvulsants, and other analgesics were associated with a higher likelihood of major effect/death in both exposure groups. For instance, adjusted odds ratios for co-used prescription opioids were 2.20 (95 percent confidence intervals: 2.09-2.31) among suicide attempt cases and 3.51 (95 percent confidence intervals: 3.10-3.97) among other intentional misuse cases. DISCUSSION: Healthcare providers need to screen for suicidal ideation among benzodiazepine users, with special attention to an increased risk of suicide attempt among those who co-use antidepressants and opioids and to decreasing adverse outcomes in all misuse cases. Assessments of underlying mental health and substance use problems and medication regimens to minimize polypharmacy and drug interactions are needed to reduce adverse outcomes. CONCLUSIONS: Though the numbers of benzodiazepine-involved suicide attempt and other intentional misuse cases reported to United States poison centers decreased in recent years, the likelihood of major medical effect/death among these cases have increased.


Asunto(s)
Benzodiazepinas , Centros de Control de Intoxicaciones , Intento de Suicidio , Humanos , Benzodiazepinas/envenenamiento , Centros de Control de Intoxicaciones/estadística & datos numéricos , Masculino , Femenino , Estados Unidos/epidemiología , Anciano , Persona de Mediana Edad , Intento de Suicidio/estadística & datos numéricos , Anciano de 80 o más Años , Sobredosis de Droga/epidemiología , Intoxicación/epidemiología
5.
Curr Treat Options Oncol ; 25(5): 628-643, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38649630

RESUMEN

OPINION STATEMENT: Immunotherapy for glioblastoma (GBM) remains an intensive area of investigation. Given the seismic impact of cancer immunotherapy across a range of malignancies, there is optimism that harnessing the power of immunity will influence GBM as well. However, despite several phase 3 studies, there are still no FDA-approved immunotherapies for GBM. Importantly, the field has learned a great deal from the randomized studies to date. Today, we are continuing to better understand the disease-specific features of the microenvironment in GBM-as well as the exploitable antigenic characteristic of the tumor cells themselves-that are informing the next generation of immune-based therapeutic strategies. The coming phase of next-generation immunotherapies is thus poised to bring us closer to treatments that will improve the lives of patients with GBM.


Asunto(s)
Neoplasias Encefálicas , Inmunoterapia , Microambiente Tumoral , Humanos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/inmunología , Inmunoterapia/métodos , Microambiente Tumoral/inmunología , Glioblastoma/terapia , Glioblastoma/inmunología , Terapia Combinada/métodos , Resultado del Tratamiento , Manejo de la Enfermedad , Ensayos Clínicos como Asunto
6.
Gerontol Geriatr Med ; 10: 23337214241241397, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38525486

RESUMEN

In this study, based on the 2022 National Health and Aging Trend Study (N = 5,593, age 65+), we examined direct associations between moderate and vigorous physical exercise (PE) and depressive/anxiety symptoms as well as bothersome pain and sleep problems. We then examined if the association between PE and depressive/anxiety symptoms would be partially mediated by the effects of PE on bothersome pain and sleep problems. Results from a path model showed that controlling for sociodemographic and health statuses, PE was negatively associated with depressive/anxiety symptoms and bothersome pain, but it was not significantly associated with sleep problems. The mediation analysis showed that 10% of the total effects of PE on depressive/anxiety symptoms was indirect effects of PE on bothersome pain. This study is important as it examined the associations among PE, pain, sleep, and depression/anxiety in community-dwelling older adults in their natural environments. Healthcare and social service providers for older adults need to emphasize the importance and benefits of PE for older adults' physical and mental health. Easy access to venues for PE is also important.

7.
J Gerontol Soc Work ; 67(3): 349-368, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38451780

RESUMEN

Using the 2018-2021 National Health Interview Survey data, we examined the associations between healthcare cost burden and depressive/anxious feelings in older adults. Nearly12% reported healthcare cost burden and 18% daily/weekly depressive/anxious feelings. Healthcare cost burden was higher among women, racial/ethnic minorities, those with chronic illnesses, mobility impairment, and those with Medicare Part D, but lower among individuals with Medicare-Medicaid dual eligibility, Medicare Advantage, VA/military insurance, and private insurance. Daily/weekly depressive/anxious feelings was higher among healthcare cost burden reporters. The COVID-19 pandemic-related medical care access problems were also associated with a higher risk of reporting healthcare cost burden and depression/anxiety.


Asunto(s)
Medicare , Pandemias , Humanos , Femenino , Anciano , Estados Unidos/epidemiología , Autoinforme , Costos de la Atención en Salud
8.
Blood Cell Ther ; 7(1): 10-13, 2024 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-38486827

RESUMEN

The use of cell therapy for clinical applications has seen a dramatic increase in recent years, primarily in oncology, especially with the use of chimeric antigen receptor (CAR) T-cell therapies. However, there are some barriers to the widespread adoption of CAR-T cell therapies globally, primarily because of the high cost of manufacturing these cells and clinical infrastructure considerations. We reviewed the different strategies adopted across Asia to implement CAR-T cell therapy and found that these included patient assistance programs, close engagement with funders, cost-effectiveness studies, on-site manufacturing of CAR-T cells, and joint ventures between local partners and foreign pharmaceutical companies. Although on-site manufacturing can reduce the cost of genetic engineering and expansion, it does not address many other hidden costs and quality considerations. Future growth in large-scale regional manufacturing, facilitated by cutting-edge science and innovation, could reduce costs through economies of scale and facilitate the eagerly needed global access.

9.
N Engl J Med ; 390(14): 1290-1298, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38477966

RESUMEN

In this first-in-human, investigator-initiated, open-label study, three participants with recurrent glioblastoma were treated with CARv3-TEAM-E T cells, which are chimeric antigen receptor (CAR) T cells engineered to target the epidermal growth factor receptor (EGFR) variant III tumor-specific antigen, as well as the wild-type EGFR protein, through secretion of a T-cell-engaging antibody molecule (TEAM). Treatment with CARv3-TEAM-E T cells did not result in adverse events greater than grade 3 or dose-limiting toxic effects. Radiographic tumor regression was dramatic and rapid, occurring within days after receipt of a single intraventricular infusion, but the responses were transient in two of the three participants. (Funded by Gateway for Cancer Research and others; INCIPIENT ClinicalTrials.gov number, NCT05660369.).


Asunto(s)
Receptores ErbB , Glioblastoma , Inmunoterapia Adoptiva , Receptores de Antígenos de Linfocitos T , Receptores Quiméricos de Antígenos , Humanos , Linfocitos T CD8-positivos/metabolismo , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Glioblastoma/terapia , Glioblastoma/patología , Inmunoterapia Adoptiva/efectos adversos , Recurrencia Local de Neoplasia/terapia , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/uso terapéutico , Receptores Quiméricos de Antígenos/uso terapéutico
10.
J Neurosurg Case Lessons ; 7(9)2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38408351

RESUMEN

BACKGROUND: 5-Aminolevulinic acid (5-ALA) fluorescence-guided surgery is a well-established technique for resecting high-grade gliomas. However, its application in meningiomas, especially those previously treated with radiation therapy, remains under investigation. OBSERVATIONS: A 48-year-old female with recurrent anaplastic meningioma, World Health Organization grade 3, underwent a right-sided craniotomy using off-label 5-ALA as a surgical adjunct. The patient had previously undergone brachytherapy seed implantation (20 × cesium 131) for tumor management. During the surgery, a large fluorescent tumor mass adjacent to the brachytherapy-treated area was resected, and the prior brachytherapy seeds were removed. Interestingly, the surrounding brain tissue in the irradiated area showed robust 5-ALA fluorescence. Pathological examination confirmed that the fluorescent brain tissue was nonneoplastic and associated with lymphocyte and macrophage infiltration. LESSONS: This case report presents unique 5-ALA fluorescence in nonneoplastic tissue following brachytherapy, which was found during the resection of recurrent anaplastic meningioma. This phenomenon may reflect an intricate interplay among radiation therapy, immune cells, the tumor microenvironment, and 5-ALA metabolism. Given that false-positive findings in fluorescence-guided surgery can lead to unnecessary tissue resection and increased surgical morbidity, further research is warranted to elucidate the mechanisms underlying this phenomenon and its implications for meningioma surgery.

11.
Clin Gerontol ; : 1-13, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38372144

RESUMEN

OBJECTIVES: To examine correlates of the changes in technology use among older adults and the associations of depression/anxiety symptoms with technology use changes. METHODS: We used the 2019-2021 U.S. National Health and Aging Trends Study (N = 3,063; age 70+). We fitted multinomial logistic regression models to examine: (1) correlates of never use and discontinued use versus use of email/texting and the internet during the 3-year study period; and (2) associations of past-month depression/anxiety symptoms in 2021 with use and discontinued use versus never use of email/texting and social network site (SNS). RESULTS: The findings show age, socioeconomic, and health barriers to technology use. Email/texting and SNS use in 2021, compared to never use in all 3 years, was associated with a lower likelihood of moderate/severe depression/anxiety symptoms in 2021 (RRR = 0.54, 95% CI = 0.37-0.81 for email/texting use; RRR = 0.56, 95% CI = 0.33-0.97 for SNS use). Video calls with family/friends were not associated with depression/anxiety symptoms. CONCLUSIONS: The findings expand the existing knowledge base regarding potential impact of technology use on mental health beyond the early months of the COVID-19 pandemic. CLINICAL IMPLICATIONS: More concerted efforts are warranted to help older adults' technology uptake and continued use and to promote mental health benefits of technology use.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38372825

RESUMEN

Analyzing the 2021 National Survey on Drug Use and Health data with generalized linear models, we examined: (1) COVID pandemic-related and other correlates of mental health treatment use and unmet perceived treatment need among U.S. adults who experienced serious suicidal thoughts (N = 3,177); and (2) correlates of self-reported reasons for not receiving treatment. We found that 61% used any mental health treatment, and 48% of users and 37% of nonusers reported perceived treatment need. Significant correlates of treatment use were demographic factors, insurance, major depressive disorder, and illicit drug use disorder. Significant correlates of perceived treatment need were age 18-34, some college education, and major depressive episode. Perceived negative effect of the COVID pandemic on mental health was a significant factor for both treatment use and perceived need. The most frequent reasons for not getting treatment were the cost of treatment or lack of insurance and stigma-related concerns.

13.
Neurosurg Focus ; 56(2): E2, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38301244

RESUMEN

OBJECTIVE: Several studies have compared the immune microenvironment of isocitrate dehydrogenase (IDH)-wildtype glioma versus IDH-mutant glioma. The authors sought to determine whether histological tumor progression in a subset of IDH-mutant glioma was associated with concomitant alterations in the intratumoral immune microenvironment. METHODS: The authors performed bulk RNA sequencing on paired and unpaired samples from patients with IDH-mutant glioma who underwent surgery for tumor progression across multiple timepoints. They compared patterns of differential gene expression, overall inflammatory signatures, and transcriptomic measures of relative immune cell proportions. RESULTS: A total of 55 unique IDH-mutant glioma samples were included in the analysis. The authors identified multiple genes associated with progression and higher grade across IDH-mutant oligodendrogliomas and astrocytomas. Compared with lower-grade paired samples, grade 4 IDH-mutant astrocytomas uniquely demonstrated upregulation of VEGFA in addition to counterproductive alterations in inflammatory score reflective of a more hostile immune microenvironment. CONCLUSIONS: Here, the authors have provided a transcriptomic analysis of a progression cohort for IDH-mutant glioma. Compared with lower-grade tumors, grade 4 astrocytomas displayed alterations that may inform the timing of antiangiogenic and immune-based therapy as these tumors progress.


Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Isocitrato Deshidrogenasa/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Regulación hacia Arriba , Mutación/genética , Glioma/genética , Glioma/patología , Astrocitoma/genética , Microambiente Tumoral/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
14.
Cancer Discov ; 14(6): 1106-1131, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38416133

RESUMEN

Recent clinical trials have highlighted the limited efficacy of T cell-based immunotherapy in patients with glioblastoma (GBM). To better understand the characteristics of tumor-infiltrating lymphocytes (TIL) in GBM, we performed cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing with paired V(D)J sequencing, respectively, on TILs from two cohorts of patients totaling 15 patients with high-grade glioma, including GBM or astrocytoma, IDH-mutant, grade 4 (G4A). Analysis of the CD8+ TIL landscape reveals an enrichment of clonally expanded GZMK+ effector T cells in the tumor compared with matched blood, which was validated at the protein level. Furthermore, integration with other cancer types highlights the lack of a canonically exhausted CD8+ T-cell population in GBM TIL. These data suggest that GZMK+ effector T cells represent an important T-cell subset within the GBM microenvironment and may harbor potential therapeutic implications. SIGNIFICANCE: To understand the limited efficacy of immune-checkpoint blockade in GBM, we applied a multiomics approach to understand the TIL landscape. By highlighting the enrichment of GZMK+ effector T cells and the lack of exhausted T cells, we provide a new potential mechanism of resistance to immunotherapy in GBM. This article is featured in Selected Articles from This Issue, p. 897.


Asunto(s)
Linfocitos T CD8-positivos , Glioblastoma , Linfocitos Infiltrantes de Tumor , Humanos , Glioblastoma/inmunología , Glioblastoma/terapia , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias Encefálicas/inmunología , Microambiente Tumoral/inmunología
15.
Clin Cancer Res ; 30(9): 1859-1877, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38393682

RESUMEN

PURPOSE: Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target antigen expression, antigen escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated by cancer-associated fibroblasts (CAF), which may contribute to the limited efficacy of mesothelin-directed CAR T cells in early-phase clinical trials. To provide a more favorable TME for CAR T cells to target pancreatic ductal adenocarcinoma (PDAC), we generated T cells with an antimesothelin CAR and a secreted T-cell-engaging molecule (TEAM) that targets CAF through fibroblast activation protein (FAP) and engages T cells through CD3 (termed mesoFAP CAR-TEAM cells). EXPERIMENTAL DESIGN: Using a suite of in vitro, in vivo, and ex vivo patient-derived models containing cancer cells and CAF, we examined the ability of mesoFAP CAR-TEAM cells to target PDAC cells and CAF within the TME. We developed and used patient-derived ex vivo models, including patient-derived organoids with patient-matched CAF and patient-derived organotypic tumor spheroids. RESULTS: We demonstrated specific and significant binding of the TEAM to its respective antigens (CD3 and FAP) when released from mesothelin-targeting CAR T cells, leading to T-cell activation and cytotoxicity of the target cell. MesoFAP CAR-TEAM cells were superior in eliminating PDAC and CAF compared with T cells engineered to target either antigen alone in our ex vivo patient-derived models and in mouse models of PDAC with primary or metastatic liver tumors. CONCLUSIONS: CAR-TEAM cells enable modification of tumor stroma, leading to increased elimination of PDAC tumors. This approach represents a promising treatment option for pancreatic cancer.


Asunto(s)
Complejo CD3 , Endopeptidasas , Proteínas Ligadas a GPI , Inmunoterapia Adoptiva , Mesotelina , Neoplasias Pancreáticas , Receptores Quiméricos de Antígenos , Microambiente Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Animales , Ratones , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Microambiente Tumoral/inmunología , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Complejo CD3/inmunología , Complejo CD3/metabolismo , Proteínas Ligadas a GPI/inmunología , Proteínas Ligadas a GPI/metabolismo , Línea Celular Tumoral , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/inmunología , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/metabolismo , Serina Endopeptidasas/inmunología , Serina Endopeptidasas/metabolismo , Adenocarcinoma/inmunología , Adenocarcinoma/terapia , Adenocarcinoma/patología
16.
J Ment Health ; 33(1): 84-91, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37578139

RESUMEN

BACKGROUND: A significant portion of suicides are precipitated by interpersonal relationship problems. AIMS: To examine demographic and clinical correlates of any intimate partner conflicts (IPC) and other interpersonal conflicts (OPC) as suicide precipitants. METHODS: We analyzed data on 92,805 (72,628 male; 20,177 female) adult suicide decedents from the 2017 to 2019 U.S. National Violent Death Reporting System, using multinomial and binary logistic regression models. We included case examples from coroners/medical examiner (CME) and law enforcement (LE) agency reports. RESULTS: Of all decedents, 23.6% had IPC and 8.0% had OPC as a suicide precipitant. Compared to those without any relationship conflict, those who had IPC or OPC were younger and more likely to have had previous suicide attempt(s), alcohol/other substance use problems, and job/finance/housing and legal problems. Compared to those with OPC, those with IPC were more likely to be male and Hispanic and had higher odds of previous suicide attempt, depression diagnosis, alcohol problems, and more acute crises. CME/LE reports showed distress of divorce/break-up, other life stressors, prior suicide attempt(s), alcohol/other substance involvement, and/or loss of family support. CONCLUSIONS: Access to behavioral health treatment for those at risk of suicide in the face of IPC or OPC is essential for suicide prevention.


Asunto(s)
Homicidio , Violencia , Adulto , Humanos , Masculino , Femenino , Estados Unidos , Causas de Muerte , Intento de Suicidio , Prevención del Suicidio
17.
Neurosurg Focus ; 55(5): E12, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37913538

RESUMEN

OBJECTIVE: Racial and socioeconomic disparities in neuro-oncological care for patients with brain tumors remain underexplored. This study aimed to analyze county-level disparities in glioblastoma (GBM) care in the United States, focusing on access to surgery and the use of adjuvant temozolomide chemotherapy and radiation therapy. METHODS: Using repeated cross-sectional data from the Surveillance, Epidemiology, and End Results 17 database; the Area Health Resources File; and the American Community Survey, from 2010 to 2019, the authors performed multivariate regression analyses to understand the associations between county-level racial and socioeconomic characteristics, as well as the rates of surgery performed, delays in surgery, and use of adjuvant chemotherapy and radiation therapy for newly diagnosed GBM. RESULTS: In total, 29,609 GBM patients from 602 different US counties over a decade were included in this study. Counties with lower rates of surgery for GBM were associated with a higher percentage of Black residents (coefficient [CE] -0.001, 95% CI -0.002 to 0; p < 0.05) and being located in the Midwest (CE -0.132, 95% CI -0.195 to -0.069; p < 0.001) or West (CE -0.127, 95% CI -0.189 to -0.065; p < 0.001) relative to the Northeast. Counties with delayed surgical treatment were more likely to lack neurosurgeons (adjusted OR [aOR] 2.52, 95% CI 1.77-3.60; p < 0.001), have a higher percentage of Black residents (aOR 1.011, 95% CI 1.00-1.02; p < 0.05), and be located in the Midwest (aOR 3.042, 95% CI 1.12-8.24; p < 0.05) or West (aOR 3.175, 95% CI 1.12-8.97 p < 0.05). Counties with high rates of adjuvant radiation therapy were less likely to have higher percentages of Black residents (aOR 0.987, 95% CI 0.980-0.995; p < 0.01) and uninsured individuals (aOR 0.962, 95% CI 0.937-0.987; p < 0.01). CONCLUSIONS: Counties without neurosurgeons and those with a higher percentage of Black patients have delays in surgical care and demonstrate lower overall rates of surgery and adjuvant therapy for GBM. This study underscores the need for targeted interventions and policies that address structural barriers in healthcare access, improve equitable distribution of the neurosurgery workforce, and ensure timely and comprehensive GBM care to all populations.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Humanos , Estados Unidos/epidemiología , Glioblastoma/epidemiología , Glioblastoma/cirugía , Estudios Transversales , Factores Socioeconómicos , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/cirugía , Recursos en Salud
18.
Antibodies (Basel) ; 12(4)2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37987252

RESUMEN

This review explores the evolving landscape of antibody-based therapies in neuro-oncology, in particular, immune checkpoint inhibitors and immunomodulatory antibodies. We discuss their mechanisms of action, blood-brain barrier (BBB) penetration, and experience in neuro-oncological conditions. Evidence from recent trials indicates that while these therapies can modulate the tumor immune microenvironment, their clinical benefits remain uncertain, largely due to challenges with BBB penetration and tumor-derived immunosuppression. This review also examines emerging targets such as TIGIT and LAG3, the potential of antibodies in modulating the myeloid compartment, and tumor-specific targets for monoclonal antibody therapy. We further delve into advanced strategies such as antibody-drug conjugates and bispecific T cell engagers. Lastly, we explore innovative techniques being investigated to enhance antibody delivery, including CAR T cell therapy. Despite current limitations, these therapies hold significant therapeutic potential for neuro-oncology. Future research should focus on optimizing antibody delivery to the CNS, identifying novel biological targets, and discovering combination therapies to address the hostile tumor microenvironment.

19.
Front Public Health ; 11: 1255519, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38026395

RESUMEN

Background and aims: A majority of older adult suicide decedents used firearms. In this study, we focused on suicide decedents age 75+ who disclosed their suicidal intent within a month of their injury/death to examine demographic and clinical characteristics associated with firearm use and firearm access restriction attempts by their family members. Methods: The 2017-2019 U.S. National Violent Death Reporting System provided data (N = 1,734 suicidal intent disclosers; 1,476 males and 258 females; 21.4% of decedents age 75+). Generalized linear model (GLM) for a Poisson distribution with a log link was used to examine firearm use risk factors. Firearm access restriction attempts by decedents' family members were examined based on coroner/medical examiner and law enforcement (CME/LE) reports. Results: Nearly three quarters of disclosers disclosed their intent to family members, and 82.9% of males and 27.5% of females used firearms. GLM results showed males, non-Hispanic white people, and residents in the South and West regions had higher likelihood of firearm use. CME/LE reports of 140 out of 1,294 firearm decedents included narratives related to firearm restriction attempts or lack thereof. Firearm access restrictions were not attempted in 65 cases because family members did not take suicidal intent disclosure seriously or because decedents promised no self-harm. Partial or complete removal of firearms in 75 cases were not effective as decedents had hidden a firearm or purchased a new one. Others used different lethal methods. Implications: The findings indicate a need for: (a) training family members of older adults who are at risk of suicide in effective means safety/access restriction and strategies to prevent means substitution; (b) more comprehensive legislative reforms reducing access to firearms by those at risk of suicide; and (c) more comfort and palliative care and counseling for psychosocial risk factors.


Asunto(s)
Armas de Fuego , Suicidio , Masculino , Femenino , Humanos , Anciano , Ideación Suicida , Suicidio/psicología , Factores de Riesgo , Violencia
20.
Cureus ; 15(9): e45603, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37868464

RESUMEN

Cryptococcal meningitis is a life-threatening fungal infection of the central nervous system. It primarily affects immunocompromised individuals, particularly those with advanced HIV/AIDS, but can occur in people of all ages. Risk factors include solid organ transplantation, hematological malignancies, immunosuppressive medications, and primary immunodeficiency disorders. We describe a case of a 68-year-old male with atypical risk factors for cryptococcal meningitis who presented acutely delirious with a negative diagnostic workup aside from a positive cerebrospinal fluid (CSF) meningitis screen reporting Cryptococcus neoformans/gattii. While the rate of lumbar puncture (LP) in the ED has drastically decreased over the years, we emphasize the importance of considering its diagnostic value in emergency department settings in patients with atypical presentations.

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