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1.
Int J Mol Sci ; 24(3)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36768342

RESUMO

Primary CNS neoplasms are responsible for considerable mortality and morbidity, and many therapies directed at primary brain tumors have proven unsuccessful despite their success in preclinical studies. Recently, the tumor immune microenvironment has emerged as a critical aspect of primary CNS neoplasms that may affect their malignancy, prognosis, and response to therapy across patients and tumor grades. This review covers the tumor microenvironment of various primary CNS neoplasms, with a focus on glioblastoma and meningioma. Additionally, current therapeutic strategies based on elements of the tumor microenvironment, including checkpoint inhibitor therapy and immunotherapeutic vaccines, are discussed.


Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Glioblastoma , Neoplasias , Humanos , Imunoterapia/métodos , Microambiente Tumoral , Glioblastoma/patologia , Terapia Combinada , Neoplasias do Sistema Nervoso Central/terapia , Neoplasias Encefálicas/patologia
2.
J Neurosurg ; 138(1): 270-275, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35523261

RESUMO

OBJECTIVE: Internal neurolysis (IN) and intraoperative glycerin rhizotomy (ioGR) are emerging surgical options for patients with trigeminal neuralgia without neurovascular contact. The objective of this study was to compare the neurological outcomes of patients who underwent IN with those of patients who underwent ioGR. METHODS: The authors retrospectively reviewed all patients who underwent IN or ioGR for trigeminal neuralgia at our institution. Patient demographic characteristics and immediate postoperative outcomes, as well as long-term neurological outcomes, were compared. RESULTS: Of 1044 patients who underwent open surgical treatment for trigeminal neuralgia, 56 patients underwent IN and 91 underwent ioGR. Of these 147 patients, 37 had no evidence of intraoperative neurovascular conflict. All patients who underwent IN and 96.7% of patients who underwent ioGR had immediate postoperative pain relief. At last follow-up, patients who underwent IN had lower Barrow Neurological Institute (BNI) pain intensity scores (p = 0.05), better BNI facial numbness scores (p < 0.01), and a greater degree of pain improvement (p = 0.05) compared with those who underwent ioGR. Patients who underwent IN also had significantly lower rates of symptomatic pain recurrence (p < 0.01) at last follow-up over an average of 9.5 months. CONCLUSIONS: IN appears to provide patients with a greater degree of pain relief, lower rates of facial numbness, and lower rates of pain recurrence compared with ioGR. Future prospective studies will better characterize long-term pain recurrence and outcomes.


Assuntos
Radiocirurgia , Neuralgia do Trigêmeo , Humanos , Neuralgia do Trigêmeo/cirurgia , Glicerol , Resultado do Tratamento , Estudos Retrospectivos , Rizotomia , Estudos Prospectivos , Hipestesia , Dor/cirurgia
3.
Acad Pediatr ; 23(4): 790-799, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36122826

RESUMO

BACKGROUND AND OBJECTIVES: As the coronavirus disease 2019 (COVID-19) pandemic evolves and vaccines become available to children, pediatricians must navigate vaccination discussions in the setting of rapidly changing vaccine recommendations and approvals. We developed and evaluated an educational curriculum for pediatricians to improve their knowledge about COVID-19 vaccines and confidence in communicating with patients and families about COVID-19 vaccines. METHODS: Five institutions collaborated to develop an online educational curriculum. Utilizing the collaboration's multidisciplinary expertise, we developed a 3-module curriculum focused on the SARS-CoV-2 virus and vaccine basics, logistics and administration of COVID-19 vaccine, and COVID-19 vaccine communication principles. Surveys administered to clinician participants before and after completion of the curriculum assessed knowledge and confidence; a follow-up survey 1 month after the post-survey assessed persistence of initial findings. RESULTS: A total of 152 pediatric providers participated; 72 completed both pre- and post-surveys. The median knowledge score improved from the pre-survey to the post-survey (79%-93%, P < .001). There was an increase in providers' confidence after completing the curriculum, which persisted in the follow-up survey. In the post-survey, 98% of participants had had the opportunity to discuss the COVID-19 vaccine with patients, and most clinicians reported that the modules decreased apprehension some or significantly. CONCLUSIONS: This project demonstrates rapid and feasible deployment of a curriculum providing up-to-date information to front-line clinicians responsible for having complex conversations about COVID-19 vaccine decision-making. Clinicians who completed this curriculum had sustained increased confidence and decreased levels of apprehension when discussing the COVID-19 vaccine.


Assuntos
COVID-19 , Vacinas , Humanos , Criança , Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Currículo , Pediatras
4.
Cell Rep ; 41(11): 111799, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36493786

RESUMO

Although vaccination efforts have expanded, there are still gaps in our understanding surrounding the immune response to SARS-CoV-2. Measuring IgG Fc glycosylation provides insight into an infected individual's inflammatory state, among other functions. We set out to interrogate bulk IgG glycosylation changes from SARS-CoV-2 infection and vaccination, using plasma from mild or hospitalized COVID-19 patients, and from vaccinated individuals. Inflammatory glycans are elevated in hospitalized COVID-19 patients and increase over time, while mild patients have anti-inflammatory glycans that increase over time, including increased sialic acid correlating with RBD antibody levels. Vaccinated individuals with low RBD antibody levels and low neutralization have the same IgG glycan traits as hospitalized COVID-19 patients. In addition, a small vaccinated cohort reveals a decrease in inflammatory glycans associated with peak IgG concentrations and neutralization. This report characterizes the bulk IgG glycome associated with COVID-19 severity and vaccine responsiveness and can help guide future studies into SARS-CoV-2 protective immunity.


Assuntos
COVID-19 , Vacinas , Humanos , Formação de Anticorpos , Glicosilação , SARS-CoV-2 , Imunoglobulina G , Anticorpos Antivirais
5.
J Neurol Surg B Skull Base ; 83(6): 635-645, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36393884

RESUMO

Objective While predictive analytic techniques have been used to analyze meningioma postoperative outcomes, to our knowledge, there have been no studies that have investigated the utility of machine learning (ML) models in prognosticating outcomes among skull base meningioma patients. The present study aimed to develop models for predicting postoperative outcomes among skull base meningioma patients, specifically prolonged hospital length of stay (LOS), nonroutine discharge disposition, and high hospital charges. We also validated the predictive performance of our models on out-of-sample testing data. Methods Patients who underwent skull base meningioma surgery between 2016 and 2019 at an academic institution were included in our study. Prolonged hospital LOS and high hospital charges were defined as >4 days and >$47,887, respectively. Elastic net logistic regression algorithms were trained to predict postoperative outcomes using 70% of available data, and their predictive performance was evaluated on the remaining 30%. Results A total of 265 patients were included in our final analysis. Our cohort was majority female (77.7%) and Caucasian (63.4%). Elastic net logistic regression algorithms predicting prolonged LOS, nonroutine discharge, and high hospital charges achieved areas under the receiver operating characteristic curve of 0.798, 0.752, and 0.592, respectively. Further, all models were adequately calibrated as determined by the Spiegelhalter Z -test ( p >0.05). Conclusion Our study developed models predicting prolonged hospital LOS, nonroutine discharge disposition, and high hospital charges among skull base meningioma patients. Our models highlight the utility of ML as a tool to aid skull base surgeons in providing high-value health care and optimizing clinical workflows.

6.
World Neurosurg ; 167: e1291-e1298, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36113711

RESUMO

OBJECTIVE: Effective therapies for acute pain management in trigeminal neuralgia (TN) are limited. We aimed to investigate the role of steroids in TN patients experiencing acute pain flares. METHODS: We retrospectively reviewed patients presenting to the emergency department of a tertiary care institution between 2014 and 2020 for acute TN pain flares. Patients were divided into those who received steroids versus those who did not. Presenting characteristics, admission and surgical intervention rates, Barrow Neurological Institute pain scores, pain recurrence rates, and surgical intervention within 6 months of discharge were obtained for each patient. RESULTS: Our cohort comprised 151 patients, of whom 40 (26.5%) received steroids before admission and/or discharge. These patients were less likely to undergo surgical intervention to treat acute pain (P = 0.023). Specifically, patients receiving steroids were less likely to undergo combined glycerin and radiofrequency rhizotomy compared with patients not receiving steroids (P = 0.012). Frequency and dosage of opioid administration did not differ between groups. The steroids group demonstrated a lower average Barrow Neurological Institute pain score on discharge compared with the no steroids group (P = 0.013). Patients receiving steroids for acute pain management were less likely to undergo surgical intervention within 6 months of discharge than patients who did not receive steroids (P = 0.033). CONCLUSIONS: Steroid administration in patients with acute TN pain flares may reduce the likelihood of surgical intervention both during admission and within 6 months of discharge. Future prospective studies should examine the efficacy of steroids as an adjunctive medication in acute TN pain management.


Assuntos
Dor Aguda , Radiocirurgia , Neuralgia do Trigêmeo , Humanos , Manejo da Dor , Neuralgia do Trigêmeo/tratamento farmacológico , Neuralgia do Trigêmeo/cirurgia , Resultado do Tratamento , Estudos Prospectivos , Estudos Retrospectivos , Esteroides/uso terapêutico
7.
Spinal Cord Ser Cases ; 8(1): 66, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35831274

RESUMO

INTRODUCTION: Post-traumatic syringomyelia is an uncommon complication after traumatic spinal cord injury. This case study details our decision-making and surgical approach for a patient with symptomatic post-traumatic syringomyelia after sustaining a gunshot wound. CASE PRESENTATION: A 24-year-old man with past medical history of distant American Spinal Injury Association Impairment Grade B spinal cord injury due to ballistic injury developed delayed post-traumatic syringomyelia, resulting in unilateral sensory loss and left upper extremity weakness. CT and MR imaging revealed a syrinx spanning his cervical and thoracic spine causing significant spinal cord compression. To relieve achieve decompression and restore CSF flow dynamics, we performed a bony extradural decompression, bullet fragment extraction, spinal cord untethering, and midline myelotomy. Postoperatively, the patient demonstrated clinical and radiographical improvement. DISCUSSION: Post-traumatic syringomyelia is potentially morbid sequalae of spinal cord injuries. Suspicion for post-traumatic syringomyelia should be maintained in patients with delayed, progressive neurologic deficits. In this setting, surgical intervention may require extradural and intradural procedures to mitigate neural compression along the dilated central canal by the syrinx.


Assuntos
Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Siringomielia , Ferimentos por Arma de Fogo , Adulto , Humanos , Masculino , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/cirurgia , Traumatismos da Coluna Vertebral/complicações , Siringomielia/diagnóstico por imagem , Siringomielia/etiologia , Siringomielia/cirurgia , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/cirurgia , Adulto Jovem
8.
Front Oncol ; 12: 892004, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35712492

RESUMO

No portion of this manuscript has previously been presented. Meningiomas, the most common primary intracranial tumors, are histologically categorized by the World Health Organization (WHO) grading system. While higher WHO grade is generally associated with poor clinical outcomes, a significant subset of grade I tumors recur or progress, indicating a need for more reliable models of meningioma behavior. Several groups have developed risk scores based on molecular or immunologic characteristics. These classification schemes show promise, with several models preliminarily demonstrating similar or superior accuracy to WHO grading. Improved understanding of immune system recognition and targeting of meningioma subtypes is necessary to advance the predictive power, as well as develop new therapies. Here, we characterize meningioma molecular drivers, predictive of recurrence and progression, and describe specific aspects of the immune response to meningiomas while highlighting critical questions and ongoing research. Relevant manuscripts of interest were identified using a systematic approach and synthesized into this focused review. Finally, we summarize the ongoing and completed clinical trials for immunotherapy in meningiomas and offer perspective on future directions.

9.
J Neurooncol ; 159(1): 103-115, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35716311

RESUMO

INTRODUCTION: Although immunosuppression is a known characteristic of glioma, no previous large studies have reported peripheral blood immune cell profiles prior to patient surgery and chemoradiation. This report describes blood immune cell characteristics and associated variables prior to surgery among typical glioma patients seen at a large University practice. METHODS: We analyzed pre-surgery blood samples from 139 glioma patients diagnosed with a new or recurrent grade II/III glioma (LrGG, n = 64) or new glioblastoma (GBM, n = 75) and 454 control participants without glioma. Relative cell fractions of CD4, CD8, B-cells, Natural Killer cells, monocytes, and neutrophils, were estimated via a validated deconvolution algorithm from blood DNA methylation measures from Illumina EPIC arrays. RESULTS: Dexamethasone use at time of blood draw varied by glioma type being highest among patients with IDH wild-type (wt) GBM (75%) and lowest for those with oligodendroglioma (14%). Compared to controls, glioma patients showed statistically significant lower cell fractions for all immune cell subsets except for neutrophils which were higher (all p-values < 0.001), in part because of the higher prevalence of dexamethasone use at time of blood draw for IDHwt GBM. Patients who were taking dexamethasone were more likely to have a low CD4 count (< 200, < 500), increased neutrophils, low absolute lymphocyte counts, higher total cell count and higher NLR. CONCLUSION: We show that pre-surgery blood immune profiles vary by glioma subtype, age, and more critically, by use of dexamethasone. Our results highlight the importance of considering dexamethasone exposures in all studies of immune profiles and of obtaining immune measures prior to use of dexamethasone, if possible.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Adulto , Neoplasias Encefálicas/genética , Dexametasona/uso terapêutico , Glioma/genética , Humanos , Isocitrato Desidrogenase/genética , Recidiva Local de Neoplasia
10.
Crit Care Med ; 50(9): 1380-1393, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35686911

RESUMO

OBJECTIVES: The standard-of-care for postoperative care following elective craniotomy has historically been ICU admission. However, recent literature interrogating complications and interventions during this postoperative ICU stay suggests that all patients may not require this level of care. Thus, hospitals began implementing non-ICU postoperative care pathways for elective craniotomy. This systematic review aims to summarize and evaluate the existing literature regarding outcomes and costs for patients receiving non-ICU care after elective craniotomy. DATA SOURCES: A systematic review of the PubMed database was performed following PRISMA guidelines from database inception to August 2021. STUDY SELECTION: Included studies were published in peer-reviewed journals, in English, and described outcomes for patients undergoing elective craniotomies without postoperative ICU care. DATA EXTRACTION: Data regarding study design, patient characteristics, and postoperative care pathways were extracted independently by two authors. Quality and risk of bias were evaluated using the Oxford Centre for Evidence-Based Medicine Levels of Evidence tool and Risk Of Bias In Non-Randomized Studies-of Interventions tool, respectively. DATA SYNTHESIS: In total, 1,131 unique articles were identified through the database search, with 27 meeting inclusion criteria. Included articles were published from 2001 to 2021 and included non-ICU inpatient care and same-day discharge pathways. Overall, the studies demonstrated that postoperative non-ICU care for elective craniotomies led to length of stay reduction ranging from 6 hours to 4 days and notable cost reductions. Across 13 studies, 53 of the 2,469 patients (2.1%) intended for postoperative management in a non-ICU setting required subsequent care escalation. CONCLUSIONS: Overall, these studies suggest that non-ICU care pathways for appropriately selected postcraniotomy patients may represent a meaningful opportunity to improve care value. However, included studies varied greatly in patient selection, postoperative care protocol, and outcomes reporting. Standardization and multi-institutional collaboration are needed to draw definitive conclusions regarding non-ICU postoperative care for elective craniotomy.


Assuntos
Craniotomia , Unidades de Terapia Intensiva , Procedimentos Cirúrgicos Eletivos , Humanos , Tempo de Internação , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório
11.
Indian J Urol ; 38(2): 121-127, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35400877

RESUMO

Introduction: COVID-19 pandemic is associated with secondary opportunistic fungal infections. These have an aggressive course with a high mortality rate. We present our experience of seven cases of post-COVID-19 fungal pyelonephritis. Methods: An observational study over a period of 8 months of May to December 2021 was carried out at our tertiary care hospital, including all patients with features of fungal pyelonephritis in post-COVID-19 setting. The patient demographics, details of previous COVID-19 infection, details of present admission and management were collected. The endpoints were either discharge from the hospital or death. Results: Seven patients were included. Mean age of presentation was 42 years (range: 20-63 years, standard deviation ± 14.2). Male-to-female ratio was 6:1. One patient was diabetic. Two patients were asymptomatic, one had mild infection, and four patients had severe COVID-19 infection as per National Institute of Health criteria. In the present admission, all patients had symptomatic pyelonephritis with laboratory parameters showing elevated D dimer, C reactive protein, and total leukocyte counts. In all seven patients, ultrasound of kidney ureter bladder region showed bulky kidney, color Doppler showed main renal arterial thrombosis in two patients, segmental arterial thrombosis in another patient. Computed tomography scan was suggestive of changes of pyelonephritis in all patients with multiple renal hypodense areas. All patients required nephrectomy with biopsy suggestive of changes of necrotizing fungal inflammation. Three patients expired. Conclusion: Management of post-COVID-19 fungal pyelonephritis should be aggressive and suspicious laboratory and imaging findings should be treated by early nephrectomy.

12.
Neurocrit Care ; 37(Suppl 2): 259-266, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35314969

RESUMO

Heterogeneity is recognized as a major barrier in efforts to improve the care and outcomes of patients with traumatic brain injury (TBI). Even within the narrower stratum of moderate and severe TBI, current management approaches do not capture the complexity of this condition characterized by manifold clinical, anatomical, and pathophysiologic features. One approach to heterogeneity may be to resolve undifferentiated TBI populations into endotypes, subclasses that are distinguished by shared biological characteristics. The endotype paradigm has been explored in a range of medical domains, including psychiatry, oncology, immunology, and pulmonology. In intensive care, endotypes are being investigated for syndromes such as sepsis and acute respiratory distress syndrome. This review provides an overview of the endotype paradigm as well as some of its methods and use cases. A conceptual framework is proposed for endotype research in moderate and severe TBI, together with a scientific road map for endotype discovery and validation in this population.


Assuntos
Lesões Encefálicas Traumáticas , Síndrome do Desconforto Respiratório , Sepse , Lesões Encefálicas Traumáticas/terapia , Humanos
13.
Oper Neurosurg (Hagerstown) ; 22(5): 262-268, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35315836

RESUMO

BACKGROUND: The utility of arterial lines in microvascular decompression (MVD) is not well described. OBJECTIVE: To examine the safety and costs of arterial lines compared with noninvasive blood pressure (NIBP) monitoring in MVDs. METHODS: We retrospectively reviewed patients undergoing MVD from 2012 to 2020. Patients were grouped by procedure date from 2012 to 2014 and 2015 to 2020, reflecting our institution's decreasing trend in arterial line placement around 2014 to 2015. Patient features, intraoperative characteristics, and postoperative complications were collected for all cases. Statistical differences were evaluated using chi-squared analyses and t-tests. RESULTS: Eight hundred fifty-eight patients underwent MVDs, with 204 between 2012 and 2014 and 654 between 2015 and 2020. Over time, the frequency of arterial line placement decreased from 64.2% to 30.1%, P < .001. Arterial lines involved 11 additional minutes of preincision time, P < .001. Patients with arterial lines required both increased doses and costs of vasoactive medications intraoperatively. Patients receiving arterial lines demonstrated no significant differences in complications compared with patients with NIBP monitoring. On average, patients with arterial lines incurred $802 increased costs per case compared with NIBP monitoring. CONCLUSION: NIBP monitoring in MVDs provides neurologically and hemodynamically safe outcomes compared with invasive blood pressure monitoring. For patients without significant cardiopulmonary risk factors, NIBP monitoring may be a cost-effective alternative in MVDs.


Assuntos
Cirurgia de Descompressão Microvascular , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/métodos , Humanos , Monitorização Fisiológica/métodos , Estudos Retrospectivos
14.
Bioresour Technol ; 351: 127023, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35307523

RESUMO

Screening of suitable microbe-nutrient combination and prediction of oil recovery at the initial stage is essential for the success of Microbial Enhanced Oil Recovery (MEOR) technique. However, experimental and physics-based modelling approaches are expensive and time-consuming. In this study, Physics Informed Machine Learning (PIML) framework was developed to screen and predict oil recovery at a relatively lesser time and cost with limited experimental data. The screening was done by quantifying the influence of parameters on oil recovery from correlation and feature importance studies. Results revealed that microbial kinetic, operational and reservoir parameters influenced the oil recovery by 50%, 32.6% and 17.4%, respectively. Higher oil recovery is attained by selecting a microbe-nutrient combination having a higher ratio of value between biosurfactant yield and microbial yield parameters, as they combinedly influence the oil recovery by 27%. Neural Network is the best ML model for MEOR application to predict oil recovery (R2≈0.99).


Assuntos
Petróleo , Aprendizado de Máquina , Nutrientes , Óleos , Física , Tensoativos
15.
Nat Commun ; 13(1): 688, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35115515

RESUMO

Disparities in SARS-CoV-2 genomic surveillance have limited our understanding of the viral population dynamics and may delay identification of globally important variants. Despite being the most populated country in Africa, Nigeria has remained critically under sampled. Here, we report sequences from 378 SARS-CoV-2 isolates collected in Oyo State, Nigeria between July 2020 and August 2021. In early 2021, most isolates belonged to the Alpha "variant of concern" (VOC) or the Eta lineage. Eta outcompeted Alpha in Nigeria and across West Africa, persisting in the region even after expansion of an otherwise rare Delta sub-lineage. Spike protein from the Eta variant conferred increased infectivity and decreased neutralization by convalescent sera in vitro. Phylodynamic reconstructions suggest that Eta originated in West Africa before spreading globally and represented a VOC in early 2021. These results demonstrate a distinct distribution of SARS-CoV-2 lineages in Nigeria, and emphasize the need for improved genomic surveillance worldwide.


Assuntos
COVID-19/virologia , SARS-CoV-2/classificação , SARS-CoV-2/genética , Adolescente , Adulto , África Ocidental , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/diagnóstico , COVID-19/epidemiologia , Criança , Pré-Escolar , Feminino , Genoma Viral , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Nigéria/epidemiologia , Filogenia , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Adulto Jovem
16.
Chemosphere ; 287(Pt 4): 132298, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34610539

RESUMO

In recent years, the piezophotocatalytic mechanism had been intensively recognized as a potential and promising route to sewage treatment. Here we report the piezoelectric effect improved heterogeneous photocatalysis of g-C3N4/Ag/ZnO (g-CN/A/Z) tricomponent in rhodomine B (RhB) degradation. Initially, the nanomaterials were characterized for their physico-chemical and optoelectronic properties using analytical techniques such as x-ray diffraction (XRD), scanning & transmission electron microscopes (SEM & TEM), UV-vis spectrophotometer and photoluminescence spectroscopy (PL). In addition, the photoelectrochemical activity of determining the photocurrent density and electrochemical impendence response were also been conducted. The catalytic properties of the tricomponent, g-CN/A/Z was studied with the degradation of RhB with visible photons irradiation and ultrasonication. In piezophotocatalysis, degradation up to 89% of RhB was achieved with 1.26 folds synergetic effect on par to the photocatalysis and piezocatalysis.


Assuntos
Óxido de Zinco , Catálise , Luz , Difração de Raios X
17.
J Neurosurg ; 136(2): 379-388, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34388730

RESUMO

OBJECTIVE: Immune checkpoint inhibitors such as anti-programmed cell death protein 1 (anti-PD-1) have shown promise for the treatment of cancers such as melanoma, but results for glioblastoma (GBM) have been disappointing thus far. It has been suggested that GBM has multiple mechanisms of immunosuppression, indicating a need for combinatorial treatment strategies. It is well understood that GBM increases glutamate in the tumor microenvironment (TME); however, the significance of this is not well understood. The authors posit that glutamate upregulation in the GBM TME is immunosuppressive. The authors utilized a novel glutamate modulator, BHV-4157, to determine synergy between glutamate modulation and the well-established anti-PD-1 immunotherapy for GBM. METHODS: C57BL/6J mice were intracranially implanted with luciferase-tagged GL261 glioma cells. Mice were randomly assigned to the control, anti-PD-1, BHV-4157, or combination anti-PD-1 plus BHV-4157 treatment arms, and median overall survival was assessed. In vivo microdialysis was performed at the tumor site with administration of BHV-4157. Intratumoral immune cell populations were characterized with immunofluorescence and flow cytometry. RESULTS: The BHV-4157 treatment arm demonstrated improved survival compared with the control arm (p < 0.0001). Microdialysis demonstrated that glutamate concentration in TME significantly decreased after BHV-4157 administration. Immunofluorescence and flow cytometry demonstrated increased CD4+ T cells and decreased Foxp3+ T cells in mice that received BHV-4157 treatment. No survival benefit was observed when CD4+ or CD8+ T cells were depleted in mice prior to BHV-4157 administration (p < 0.05). CONCLUSIONS: In this study, the authors showed synergy between anti-PD-1 immunotherapy and glutamate modulation. The authors provide a possible mechanism for this synergistic benefit by showing that BHV-4157 relies on CD4+ and CD8+ T cells. This study sheds light on the role of excess glutamate in GBM and provides a basis for further exploring combinatorial approaches for the treatment of this disease.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Animais , Camundongos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Ácido Glutâmico , Imunoterapia/métodos , Camundongos Endogâmicos C57BL , Microambiente Tumoral
18.
J Neurosurg ; 136(1): 56-66, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34087798

RESUMO

OBJECTIVE: Non-small cell lung cancer (NSCLC) is the most common primary tumor to develop brain metastasis. Prognostic markers are needed to better determine survival after neurosurgical resection of intracranial disease. Given the importance of mutation subtyping in determining systemic therapy and overall prognosis of NSCLC, the authors examined the prognostic value of mutation status for postresection survival of patients with NSCLC brain metastasis. METHODS: The authors retrospectively analyzed all cases of NSCLC brain metastasis with available molecular testing data that were resected by a single surgeon at a single academic center from January 2009 to February 2019. Mutation status, demographic characteristics, clinical factors, and treatments were analyzed. Association between predictive variables and overall survival after neurosurgery was determined with Cox regression. RESULTS: Of the included patients (n = 84), 40% were male, 76% were smokers, the mean ± SD Karnofsky Performance Status was 85 ± 14, and the mean ± SD age at surgery was 63 ± 11 years. In total, 23%, 26%, and 4% of patients had EGFR, KRAS, and ALK/ROS1 alterations, respectively. On multivariate analysis, survival of patients with EGFR (HR 0.495, p = 0.0672) and KRAS (HR 1.380, p = 0.3617) mutations were not significantly different from survival of patients with wild-type (WT) tumor. However, the subgroup of patients with EGFR mutation who also received tyrosine kinase inhibitor (TKI) therapy had significantly prolonged survival (HR 0.421, p = 0.0471). In addition, postoperative stereotactic radiosurgery (HR 0.409, p = 0.0177) and resected tumor diameter < 3 cm (HR 0.431, p = 0.0146) were also significantly associated with prolonged survival, but Graded Prognostic Assessment score ≤ 1.0 (HR 2.269, p = 0.0364) was significantly associated with shortened survival. CONCLUSIONS: Patients with EGFR mutation who receive TKI therapy may have better survival after resection of brain metastasis than patients with WT tumor. These results may inform counseling and decision-making regarding the appropriateness of resection of NSCLC brain metastasis.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Tomada de Decisão Clínica , Análise Mutacional de DNA , Receptores ErbB/sangue , Feminino , Humanos , Avaliação de Estado de Karnofsky , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/sangue , Proteínas Proto-Oncogênicas/sangue , Proteínas Proto-Oncogênicas p21(ras)/sangue , Estudos Retrospectivos , Fumar/efeitos adversos , Análise de Sobrevida
19.
J Proteome Res ; 21(1): 274-288, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34878788

RESUMO

Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multiparametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We applied Ig-MS to plasma from subjects with severe and mild COVID-19 and immunized subjects after two vaccine doses, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, that could use other antigens of interest to gauge immune responses to vaccination, pathogens, or autoimmune disorders.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Espectrometria de Massas , Glicoproteína da Espícula de Coronavírus/genética
20.
World Neurosurg ; 159: e130-e138, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34896348

RESUMO

OBJECTIVE: A need exists to better understand the prognostic factors that influence high-value care outcomes after meningioma surgery. The goal of the present study was to develop predictive models to determine the patients at risk of experiencing an extended hospital length of stay (LOS), nonroutine discharge disposition, and/or a 90-day hospital readmission after non-skull base meningioma resection. METHODS: In the present study, we analyzed the data from 396 patients who had undergone surgical resection of non-skull base meningiomas at a single institution between January 1, 2005 and December 31, 2020. The Mann-Whitney U test was used for bivariate analysis of the continuous variables and the Fisher exact test for bivariate analysis of the categorical variables. A multivariate analysis was conducted using logistic regression models. RESULTS: Most patients had had a falcine or parasagittal meningioma (66.2%), with the remainder having convexity (31.8%) or intraventricular (2.0%) tumors. Nonelective surgery (P < 0.0001) and an increased tumor volume (P = 0.0022) were significantly associated with a LOS >4 days on multivariate analysis. The independent predictors of a nonroutine discharge disposition included male sex (P = 0.0090), nonmarried status (P = 0.024), nonelective surgery (P = 0.0067), tumor location within the parasagittal or intraventricular region (P = 0.0084), and an increased modified frailty index score (P = 0.039). Hospital readmission within 90 days was independently associated with nonprivate insurance (P = 0.010) and nonmarried status (P = 0.0081). Three models predicting for a prolonged LOS, nonroutine discharge disposition, and 90-day readmission were implemented in the form of an open-access, online calculator (available at: https://neurooncsurgery3.shinyapps.io/non_skull_base_meningiomas/). CONCLUSIONS: After external validation, our open-access, online calculator could be useful for assessing the likelihood of adverse postoperative outcomes for patients undergoing surgery of non-skull base meningioma.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Tempo de Internação , Masculino , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Readmissão do Paciente , Estudos Retrospectivos
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