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Although mutations in DNA are the best-studied source of neoantigens that determine response to immune checkpoint blockade, alterations in RNA splicing within cancer cells could similarly result in neoepitope production. However, the endogenous antigenicity and clinical potential of such splicing-derived epitopes have not been tested. Here, we demonstrate that pharmacologic modulation of splicing via specific drug classes generates bona fide neoantigens and elicits anti-tumor immunity, augmenting checkpoint immunotherapy. Splicing modulation inhibited tumor growth and enhanced checkpoint blockade in a manner dependent on host T cells and peptides presented on tumor MHC class I. Splicing modulation induced stereotyped splicing changes across tumor types, altering the MHC I-bound immunopeptidome to yield splicing-derived neoepitopes that trigger an anti-tumor T cell response in vivo. These data definitively identify splicing modulation as an untapped source of immunogenic peptides and provide a means to enhance response to checkpoint blockade that is readily translatable to the clinic.
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Neoplasias/genética , Neoplasias/imunologia , Splicing de RNA/genética , Animais , Apresentação de Antígeno/efeitos dos fármacos , Apresentação de Antígeno/imunologia , Antígenos de Neoplasias/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Epitopos/imunologia , Etilenodiaminas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hematopoese/efeitos dos fármacos , Hematopoese/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia , Inflamação/patologia , Camundongos Endogâmicos C57BL , Peptídeos/metabolismo , Isoformas de Proteínas/metabolismo , Pirróis/farmacologia , Splicing de RNA/efeitos dos fármacos , Sulfonamidas/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
PURPOSE: Iatrogenic neurologic deficits adversely affect patient outcomes following brain tumor resection. Motor evoked potential (MEP) monitoring allows surgeons to assess the integrity of motor-eloquent areas in real-time during tumor resection to lessen the risk of iatrogenic insult. We retrospectively associate intraoperative transcranial and direct cortical MEPs (TC-MEPs, DC-MEPs) to early and late post-operative motor function to prognosticate short- and long-term motor recovery in brain tumor patients undergoing surgical resection in peri-eloquent regions. METHODS: We reviewed 121 brain tumor patients undergoing craniotomies with DC-MEP and/or TC-MEP monitoring. Motor function scores were recorded at multiple time-points up to 1 year postoperatively. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated at each time point. RESULTS: The sensitivity, specificity, PPV, and NPV of TC-MEP in the immediate postoperative period was 17.5%, 100%, 100%, and 69.4%, respectively. For DC-MEP monitoring, the respective values were 25.0%, 100%, 100%, and 68.8%. By discharge, sensitivity had increased for both TC-MEP and DC MEPs to 43.8%, and 50.0% respectively. Subset analysis on patients without tumor recurrence/progression at long term follow-up (n = 62 pts, 51.2%) found that all patients with stable monitoring maintained or improved from preoperative status. One patient with transient intraoperative TC-MEP loss and permanent DC-MEP loss suffered a permanent deficit. CONCLUSION: Brain tumor patients who undergo surgery with intact MEP monitoring and experience new postoperative deficits likely suffer transient deficits that will improve over the postoperative course in the absence of disease progression.
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Neoplasias Encefálicas , Potencial Evocado Motor , Humanos , Potencial Evocado Motor/fisiologia , Prognóstico , Estudos Retrospectivos , Recidiva Local de Neoplasia , Neoplasias Encefálicas/cirurgia , Doença IatrogênicaRESUMO
PURPOSE: We systematically reviewed the current landscape of hippocampal-avoidance radiotherapy, focusing specifically on rates of hippocampal tumor recurrence and changes in neurocognitive function. METHODS: PubMed was queried for studies involving hippocampal-avoidance radiation therapy and results were screened using PRISMA guidelines. Results were analyzed for median overall survival, progression-free survival, hippocampal relapse rates, and neurocognitive function testing. RESULTS: Of 3709 search results, 19 articles were included and a total of 1611 patients analyzed. Of these studies, 7 were randomized controlled trials, 4 prospective cohort studies, and 8 retrospective cohort studies. All studies evaluated hippocampal-avoidance whole brain radiation treatment (WBRT) and/or prophylactic cranial irradiation (PCI) in patients with brain metastases. Hippocampal relapse rates were low (overall effect size = 0.04; 95% confidence interval [0.03, 0.05]) and there was no significant difference in risk of relapse between the five studies that compared HA-WBRT/HA-PCI and WBRT/PCI groups (risk difference = 0.01; 95% confidence interval [- 0.02, 0.03]; p = 0.63). 11 out of 19 studies included neurocognitive function testing. Significant differences were reported in overall cognitive function and memory and verbal learning 3-24 months post-RT. Differences in executive function were reported by one study, Brown et al., at 4 months. No studies reported differences in verbal fluency, visual learning, concentration, processing speed, and psychomotor speed at any timepoint. CONCLUSION: Current studies in HA-WBRT/HA-PCI showed low hippocampal relapse or metastasis rates. Significant differences in neurocognitive testing were most prominent in overall cognitive function, memory, and verbal learning. Studies were hampered by loss to follow-up.
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Neoplasias Encefálicas , Recidiva Local de Neoplasia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Irradiação Craniana/efeitos adversos , Irradiação Craniana/métodos , Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Hipocampo/patologiaRESUMO
BACKGROUND: As endoscopic transsphenoidal approaches are more routinely selected for progressively larger pituitary adenomas with parasellar extension, understanding potential anatomical factors that limit resection and contribute to complications is becoming increasingly important for tailoring a surgical approach. This study aimed to reevaluate existing predictive tools for resectability in pituitary adenomas specifically with suprasellar extension, and furthermore identify any additional measurable features that may be more useful in preoperative planning. METHODS: A single-center retrospective chart review of adult patients who underwent endoscopic transsphenoidal surgery for pituitary adenomas with suprasellar extension from 2015 to 2020 was performed. Preoperative MRIs were systematically assessed to assign a Knosp classification, a Zurich Pituitary Score (ZPS), and for dimensional measurements of the suprasellar aspect of the lesions. Univariate comparisons and multivariate regression models were employed to assess the influence of these factors on extent of resection and postoperative complications. RESULTS: Of the 96 patients with suprasellar pituitary adenomas who underwent endoscopic transsphenoidal surgery, 74 patients (77%) had a gross total resection (GTR). Neither Knosp grade nor ZPS score, even when dichotomized, demonstrated an association with GTR (Knosp 3A-4 versus Knosp 0-2, p = 0.069; ZPS III-IV versus ZPS I-II, p = 0.079). Multivariate regression analysis identified suprasellar anterior-posterior tumor diameter (SSAP) as the only significant predictor of extent of resection in this cohort (OR 0.951, 95% CI 0.905-1.000, p = 0.048*). A higher SSAP also had the strongest association with intraoperative CSF leaks (p = 0.0012*) and an increased overall rate of postoperative complications (p = 0.002*). Further analysis of the regression model for GTR suggested an optimal cut point value for SSAP of 23.7 mm, above which predictability for failing to achieve GTR carried a sensitivity of 89% and a specificity of 41%. CONCLUSIONS: This study is unique in its examination of endoscopic transsphenoidal surgical outcomes for pituitary adenomas with suprasellar extension. Our findings suggest that previously established grading systems based on lateral extension into the cavernous sinus lose their predictive value in lesions with suprasellar extension and, more specifically, with increasing suprasellar anterior-posterior diameter.
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Adenoma , Neoplasias Hipofisárias , Adulto , Humanos , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Estudos Retrospectivos , Resultado do Tratamento , Endoscopia/métodos , Complicações Pós-Operatórias , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Adenoma/patologiaRESUMO
PURPOSE: 5-aminolevulinic acid (5-ALA) has demonstrated its utility as an intraoperative imaging adjunct during fluorescence guided resection of malignant gliomas. However, literature regarding 5-ALA-guided resection for brain metastases is limited. We conducted a systematic review to evaluate the efficacy of 5-ALA fluorescence for resection of metastatic brain tumors. METHODS: PubMed was queried for studies involving 5-ALA and brain metastases, and results were screened following PRISMA guidelines. Articles related to 5-ALA and brain metastasis were further assessed based on inclusion and exclusion criteria and results were analyzed for 5-ALA fluorescence rates stratified by tumor primary sites and histological subtypes. RESULTS: Of 421 identified search results, 10 studies were included and a total of 631 patients analyzed. Of these studies, 60% were retrospective in design. The reported rates of 5-ALA fluorescence in included brain metastases ranged from 27.6 to 86.9%, with variability across and within tumor types. No studies concluded improved operative outcomes or survival outcomes related to 5-ALA use. CONCLUSIONS: Current studies regarding 5-ALA fluorescence in brain metastases are limited and do not confirm efficacy for improving extent of resection or post-operative survival. Fluorescence is variable across and within tumor types. Further studies are necessary to evaluate whether specific tumors may benefit from 5-ALA FGS or if changes in delivery protocols or fluorescence quantification may affect intraoperative utility.
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Neoplasias Encefálicas , Glioma , Cirurgia Assistida por Computador , Humanos , Ácido Aminolevulínico , Estudos Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Glioma/patologia , Neuronavegação/métodos , Cirurgia Assistida por Computador/métodosRESUMO
PURPOSE: Terminated clinical trials are an inefficient use of financial, patient, and administrative resources. We reviewed ClinicalTrials.gov for completed and terminated clinical trials for glioblastoma multiforme (GBM) and compared reported characteristics of completed and terminated trials to identify factors associated with early trial termination. METHODS: ClinicalTrials.gov was queried to identify all completed and terminated GBM-related clinical trials. Trial characteristics were examined and the reason for trial termination was determined. Univariate analysis by Pearson's chi-square and a multivariate logistic regression were performed to identify independent predictors of early trial termination. RESULTS: We identified 886 completed and terminated GBM-related trials between 2003 and 2020. Of these, 175 (19.8%) were terminated prior to completion. The most common reason for termination was participant accrual difficulties, accounting for 63 (36.0%) terminated trials. Trial termination was associated with trials that reported a primary purpose of diagnosis relative to treatment (OR = 2.952, p = 0.001). CONCLUSION: Early termination of clinical trials investigating interventions for the treatment of GBM is associated with diagnostic trials relative to therapeutic trials. Patient accrual difficulties are the most commonly identified reason for early trial termination. Predictors of trial termination should be considered when designing GBM-related clinical trials to minimize the odds of early trial termination.
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Glioblastoma , Glioblastoma/terapia , Humanos , Modelos Logísticos , Projetos de PesquisaRESUMO
We conducted a case-control study of 18 US transplant recipients with Rhodococcus infection and 36 matched controls. The predominant types of infection were pneumonia and bacteremia. Diabetes mellitus and recent opportunistic infection were independently associated with disease. Outcomes were generally favorable except for 1 relapse and 1 death.
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Infecções por Actinomycetales/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Oportunistas/microbiologia , Transplante de Órgãos/efeitos adversos , Rhodococcus , Infecções por Actinomycetales/tratamento farmacológico , Infecções por Actinomycetales/microbiologia , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Humanos , Hospedeiro Imunocomprometido , Imunossupressores , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Transplantados , Adulto JovemRESUMO
Surgical site infections (SSIs) after liver transplantation (LT) are associated with an increased risk of graft loss and death. The incidence of SSIs after LT and their risk factors have been determined for first LT but not for second LT. The importance of reporting the incidence of SSIs risk-stratified by first LT versus second LT is not known. All patients undergoing second LT at a single institution between 2003 and 2011 (n = 152) were reviewed. The Kaplan-Meier method was used to estimate the cumulative SSI incidence. Relative risks (RRs) and 95% confidence intervals (CIs) from Cox proportional hazards regression models were used to evaluate associations of potential risk factors with SSIs after second LT. Thirty-one patients developed SSIs (6 superficial SSIs, 1 deep SSI, and 24 organ/space SSIs). The cumulative incidence of SSIs 30 days after LT was 20.8% (95% CI = 14%-27%), which was slightly but not significantly higher than the previously reported incidence of SSIs after first LT at our institution between 2003 and 2008 (16%, RR = 1.32, 95% CI = 0.90-1.93, P = .16). Units of transfused red blood cells [RR (doubling) = 1.38, 95% CI = 1.02-1.86, P = .04] and hepaticojejunostomy (RR = 2.22, 95% CI = 1.05-4.72, P = .04) were the only factors associated with SSIs after second LT in single-variable analysis. The associations weakened in a multivariate analysis (P = .07 and P = .07, respectively), potentially because of the correlation of red blood cell transfusions and hepaticojejunostomy (P = .08). In conclusion, the incidence of SSIs after second LT was slightly higher but not significantly different than the published incidence of SSIs (16%) after first LT at the same institution. Significant independent risk factors for SSIs after second LT were not identified. Risk stratification for retransplantation may not be necessary when the incidence of SSIs after LT is being reported.
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Transplante de Fígado/efeitos adversos , Reoperação/efeitos adversos , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transfusão de Eritrócitos , Feminino , Seguimentos , Humanos , Incidência , Jejunostomia , Estimativa de Kaplan-Meier , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Análise de Regressão , Reoperação/métodos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
As invasive mucormycosis (IM) numbers rise, clinicians suspect prior voriconazole worsens IM incidence and severity, and believe combination anti-fungal therapy improves IM survival. To compare the cumulative incidence (CI), severity and mortality of IM in eras immediately before and after the commercial availability of voriconazole all IM cases from 1995 to 2011 were analysed across four risk-groups (hematologic/oncologic malignancy (H/O), stem cell transplantation (SCT), solid organ transplantation (SOT) and other), and two eras, E1 (1995-2003) and E2, (2004-2011). Of 101 IM cases, (79 proven, 22 probable): 30 were in E1 (3.3/year) and 71 in E2 (8.9/year). Between eras, the proportion with H/O or SCT rose from 47% to 73%, while 'other' dropped from 33% to 11% (P = 0.036). Between eras, the CI of IM did not significantly increase in SCT (P = 0.27) or SOT (P = 0.30), and patterns of anatomic location (P = 0.122) and surgical debridement (P = 0.200) were similar. Significantly more patients received amphotericin-echinocandin combination therapy in E2 (31% vs. 5%, P = 0.01); however, 90-day survival did not improve (54% vs. 59%, P = 0.67). Since 2003, the rise of IM reflects increasing numbers at risk, not prior use of voriconazole. Frequent combination of anti-fungal therapy has not improved survival.
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Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Equinocandinas/uso terapêutico , Mucormicose/tratamento farmacológico , Voriconazol/uso terapêutico , Adulto , Idoso , Anfotericina B/história , Antifúngicos/história , Quimioterapia Combinada/história , Equinocandinas/história , Feminino , Fungos/classificação , Fungos/genética , Fungos/isolamento & purificação , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Mucormicose/epidemiologia , Mucormicose/microbiologia , Mucormicose/mortalidade , Estados Unidos/epidemiologia , Voriconazol/história , Adulto JovemRESUMO
BACKGROUND: Functional magnetic resonance imaging (fMRI) has transformed our understanding of brain's functional architecture, providing critical insights into neurological diseases. This scoping review synthesizes the current landscape of fMRI applications across various neurological domains, elucidating the evolving role of both task-based and resting-state fMRI in different settings. METHODS: We conducted a comprehensive scoping review following the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews guidelines. Extensive searches in Medline/PubMed, Embase, and Web of Science were performed, focusing on studies published between 2003 and 2023 that utilized fMRI to explore functional connectivity and regional activation in adult patients with neurological conditions. Studies were selected based on predefined inclusion and exclusion criteria, with data extracted. RESULTS: We identified 211 studies, covering a broad spectrum of neurological disorders including mental health, movement disorders, epilepsy, neurodegeneration, traumatic brain injury, cerebrovascular accidents, vascular abnormalities, neurorehabilitation, neuro-critical care, and brain tumors. The majority of studies utilized resting-state fMRI, underscoring its prominence in identifying disease-specific connectivity patterns. Results highlight the potential of fMRI to reveal the underlying pathophysiological mechanisms of various neurological conditions, facilitate diagnostic processes, and potentially guide therapeutic interventions. CONCLUSIONS: fMRI serves as a powerful tool for elucidating complex neural dynamics and pathologies associated with neurological diseases. Despite the breadth of applications, further research is required to standardize fMRI protocols, improve interpretative methodologies, and enhance the translation of imaging findings to clinical practice. Advances in fMRI technology and analytics hold promise for improving the precision of neurological assessments and interventions.
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BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a perioperative model of care aimed at optimizing postoperative rehabilitation and reducing hospital length of stay (LOS). Decreasing LOS avoids hospital-acquired complications, reduces cost of care, and improves patient satisfaction. Given the lack of ERAS protocols for endoscopic endonasal transsphenoidal surgery (EETS) resection of pituitary adenomas, a systematic review of EETS was performed to compile patient outcomes and analyze factors that may lead to increased LOS, reoperation, and readmission rates with the intention to contribute to the development of a successful ERAS protocol for EETS. METHODS: The authors performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines-based systematic review of the literature. Information was extracted regarding patient LOS, surgery complications, and readmission/reoperation rates. Pearson's correlations to LOS and reoperation/readmission rates were performed with variables normalized to the number of participants. Statistical significance was set at P value <0.05. RESULTS: Fourteen studies were included, consisting of 2083 patients. The most common complications were cerebrospinal fluid leaks (37%) and postoperative diabetes insipidus (DI) (9%). Transient DI was significantly correlated with shorter LOS. Functional pituitary adenomas were significantly correlated with lower readmission rates while nonfunctional pituitary adenomas were correlated with higher readmission rates. No other factor was found to be significantly correlated with a change in LOS or reoperation rate. CONCLUSIONS: EETS may be an ideal candidate for the development of ERAS cranial protocols. While our data largely supports the safe implementation of shortened LOS protocols in EETS, our findings highlight the importance of transient DI and nonfunctional pituitary adenomas management when formulating ERAS protocols.
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Adenoma , Recuperação Pós-Cirúrgica Melhorada , Tempo de Internação , Neuroendoscopia , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/cirurgia , Adenoma/cirurgia , Tempo de Internação/estatística & dados numéricos , Neuroendoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Readmissão do Paciente/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Procedimentos Neurocirúrgicos/métodosRESUMO
PURPOSE: Direct-wave (D-wave) neuromonitoring is a direct measure of corticospinal tract integrity that detects potential injury during spinal cord surgery. Epidural placement of electrodes used for D-wave measurements can result in high electrical impedances resulting in substantial signal noise that can compromise signal interpretation. Subdural electrode placement may offer a solution. METHODS: Medical records for consecutive patients with epidural and subdural D-wave monitoring were reviewed. Demographic and clinical information including preoperative and postoperative motor strength were recorded. Neuromonitoring charts were reviewed to characterize impedances and signal amplitudes of D-waves recorded epidurally (before durotomy) and subdurally (following durotomy). Nonparametric statistics were used to compare epidural and subdural D-waves. RESULTS: Ten patients (50% women, median age 50.5 years) were analyzed, of which five patients (50%) were functionally independent (modified McCormick grade ≤ II) preoperatively. D-waves were successfully acquired by subdural electrodes in eight cases and by epidural electrodes in three cases. Subdural electrode placement was associated with lower impedance values ( P = 0.011) and a higher baseline D-wave amplitude ( P = 0.007) relative to epidural placement. No association was observed between D-wave obtainability and functional status, and no adverse events relating to subdural electrode placement were encountered. CONCLUSIONS: Subdural electrode placement allows successful D-wave acquisition with accurate monitoring, clearer waveforms, and a more optimal signal-to-noise ratio relative to epidural placement. For spinal surgeries where access to the subdural compartment is technically safe and feasible, surgeons should consider subdural placement when monitoring D-waves to optimize clinical interpretation.
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INTRODUCTION: Artificial intelligence (AI) has become increasingly used in neurosurgery. Generative pretrained transformers (GPTs) have been of particular interest. However, ethical concerns regarding the incorporation of AI into the field remain underexplored. We delineate key ethical considerations using a novel GPT-based, human-modified approach, synthesize the most common considerations, and present an ethical framework for the involvement of AI in neurosurgery. METHODS: GPT-4, ChatGPT, Bing Chat/Copilot, You, Perplexity.ai, and Google Bard were queried with the prompt "How can artificial intelligence be ethically incorporated into neurosurgery?". Then, a layered GPT-based thematic analysis was performed. The authors synthesized the results into considerations for the ethical incorporation of AI into neurosurgery. Separate Pareto analyses with 20% threshold and 10% threshold were conducted to determine salient themes. The authors refined these salient themes. RESULTS: Twelve key ethical considerations focusing on stakeholders, clinical implementation, and governance were identified. Refinement of the Pareto analysis of the top 20% most salient themes in the aggregated GPT outputs yielded 10 key considerations. Additionally, from the top 10% most salient themes, 5 considerations were retrieved. An ethical framework for the use of AI in neurosurgery was developed. CONCLUSIONS: It is critical to address the ethical considerations associated with the use of AI in neurosurgery. The framework described in this manuscript may facilitate the integration of AI into neurosurgery, benefitting both patients and neurosurgeons alike. We urge neurosurgeons to use AI only for validated purposes and caution against automatic adoption of its outputs without neurosurgeon interpretation.
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Inteligência Artificial , Neurocirurgia , Inteligência Artificial/ética , Humanos , Neurocirurgia/ética , Procedimentos Neurocirúrgicos/ética , Procedimentos Neurocirúrgicos/métodos , NeurocirurgiõesRESUMO
BACKGROUND: Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores measure patient experience and perspectives on care. Novel health information technologies facilitate communication between patients and healthcare teams. Playback Health is a health information technology that incorporates multimedia for providers to communicate health information to patients, their support network, and their healthcare teams. We hypothesized implementing Playback Health may enhance patient perspectives on care. METHODS: HCAHPS scores were obtained retrospectively from a neurosurgical practice located in a metropolitan area between 2020 and 2022 for seven providers. Of these, four providers utilized Playback Health, and three did not. Individual providers' scores were compared between domains using two tailed t-tests at a significance level of p < 0.05. RESULTS: Playback Health use was associated with higher HCAHPS scores across varying domains from 2020 through 2022 as well as overall scores. In 2020, the mean overall score of HCAHPS users was higher than non-users (89.65 vs. 87.28, p = 0.0095). In 2021, again higher mean overall scores were observed in users as compared to non-users (89.11 vs. 87.79, p 0.0266). In 2022, Playback Health users maintained higher scores across communication domains and overall scores (p < 0.00001). Comparisons within domains between Playback Health users and non-users revealed no domains in which non-users had a significantly higher score than users. CONCLUSION: The addition of Playback Health multimedia health information technology was associated with improved patient satisfaction scores. When used as an adjunct to existing patient care, multimedia health information technologies may improve patient perceived care.
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Saúde Digital , Satisfação do Paciente , Humanos , Estudos Retrospectivos , Inquéritos e Questionários , TecnologiaRESUMO
BACKGROUND AND OBJECTIVES: Intraoperative neurophysiological monitoring plays a pivotal role in modern neurosurgery, aiding in real-time assessment of eloquent neural structures to mitigate iatrogenic neural injury. This study represents the largest retrospective series to date in monitoring corticospinal tract integrity during intracranial surgery with transcranial motor-evoked potentials (TCMEPs), focusing on the influence of demographic factors, comorbidities, and preoperative motor deficits on the reliability of intraoperative neurophysiological monitoring. While the impact of patient-specific factors affecting TCMEP monitoring in spine surgery is well-documented, similar insights for intracranial surgery are lacking. METHODS: A total of 420 craniotomy patients were retrospectively analyzed from electronic medical records from December 2017 to February 2023, excluding patients without preoperative Medical Research Council scores or medical histories. Using intrinsic hand muscles as a robust data set, 840 hand TCMEPs acquired during intracranial surgery were assessed. Demographic and clinical factors, including preoperative motor scores, were analyzed to identify associations with TCMEP acquisition and amplitude. Nonparametric statistics and multivariate regression analysis were employed. RESULTS: TCMEPs were successfully acquired in 734 (87.7%) patient hands, even in the presence of preoperative motor deficits in 13.9% of total patient hands. Preoperative motor scores did not predict the ability to acquire baseline TCMEPs (P = .6). Notably, older age (P < .001) and hypertension (P = .01) were independent predictors of lower TCMEP acquisition rates. Preoperative motor scores significantly influenced TCMEP amplitudes, with higher scores correlating with higher amplitudes (1771 [SD = 1550] eve vs 882 [SD = 856] µV, P < .0001). Older age (P < .001) and chronic kidney disease (P = .04) were also associated with reduced TCMEP amplitudes. CONCLUSION: Our investigation into TCMEPs during intracranial surgery demonstrated a notably high acquisition rate in hand muscles, irrespective of preoperative motor deficits. Preoperative motor scores reliably correlated with TCMEP amplitudes in a linear fashion while advanced age and renal disease emerged as independent predictors of lower TCMEP amplitudes.
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Background: Although deep brain stimulation (DBS) has established uses for patients with movement disorders and epilepsy, it is under consideration for a wide range of neurologic and neuropsychiatric conditions. Objective: To review successful and unsuccessful DBS clinical trials and identify factors associated with early trial termination. Methods: The ClinicalTrials.gov database was screened for all studies related to DBS. Information regarding condition of interest, study aim, trial design, trial success, and, if applicable, reason for failure was collected. Trials were compared and logistic regression was utilized to identify independent factors associated with trial termination. Results: Of 325 identified trials, 79.7% were successful and 20.3% unsuccessful. Patient recruitment, sponsor decision, and device issues were the most cited reasons for termination. 242 trials (74.5%) were interventional with 78.1% successful. There was a statistically significant difference between successful and unsuccessful trials in number of funding sources (p = 0.0375). NIH funding was associated with successful trials while utilization of other funding sources (academic institutions and community organizations) was associated with unsuccessful trials. 83 trials (25.5%) were observational with 84.0% successful; there were no statistically significant differences between successful and unsuccessful observational trials. Conclusion: One in five clinical trials for DBS were found to be unsuccessful, most commonly due to patient recruitment difficulties. The source of funding was the only factor associated with trial success. As DBS research continues to grow, understanding the current state of clinical trials will help design successful future studies, thereby minimizing futile expenditures of time, cost, and patient engagement.
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In May of 2022, the World Health Organization declared a worldwide Mpox virus (MPXV) outbreak. Due to the widespread implementation of vaccination protocols and heightened awareness among the general population, there has been a notable decline in the incidence of Mpox (formerly known as Monkeypox) cases since March 2023. Nevertheless, it is crucial to remember that Mpox has the potential to impact multiple physiological systems in humans, encompassing the cardiovascular, gastrointestinal, ear/nose/throat, and ocular systems. The mortality rate of the Mpox disease is comparatively lower than that of smallpox. However, it is essential to note that this disease can still lead to significant systemic consequences. The specific pathophysiological mechanisms by which the virus affects various physiological systems are now being investigated. Direct inoculation through mucosal damage or intranasal exposure, direct viral toxicity, and lymphatic transmission via the seminal fluid are all viable hypotheses. The prompt recognition of such complications is crucial to decrease morbidity and mortality.
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Objective: Deep brain stimulation (DBS) allows for direct electrical stimulation of neural circuitry and recording of local field potentials (LFPs). A bibliometric analysis can be implemented to identify studies that have shaped a research field and influenced future study; however, no such analysis investigating the implementation of LFPs in DBS has been performed. The objective of the present study was to identify the most highly cited articles pertaining to DBS LFPs to identify and evaluate the research that has contributed the most to this growing field. Methods: The Science Citation Index of the Web of Science was implemented to identify the top 84 most cited articles pertaining to DBS LFPs. Information regarding the publication, including author information and study aims, was extracted. Results: The most highly cited articles had had a mean of 109 citations and had been published between 2002 and 2019, with a mode in 2016. The articles had predominantly investigated the subthalamic nucleus (68% of clinical studies) in humans (83.8% of clinical studies). The studies of humans had recruited a mean of 12.5 subjects. Most of the identified articles (56.0%) had reported class III clinical evidence. Conclusions: The implementation of DBS LFPs is a novel field that is rapidly growing. However, a need exists for more studies with larger patient cohorts and more randomized controlled trials to further elucidate the benefits of this technology. These results will allow for the identification and recognition of the most influential studies pertaining to DBS LFPs, appreciation of the current and future research trends, and inform us regarding areas warranting further investigation.
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Sonodynamic therapy (SDT) has emerged as an encouraging noninvasive technique that uses ultrasound to activate targeted agents to induce antitumor effects for the treatment of glioma. With extensive variation in the types of sonosensitizers, protocols for sonication, and model systems, a comprehensive overview of existing preclinical data on the efficacy of SDT in glioma treatment is warranted. Here, we conduct a systematic review of preclinical and early clinical literature on implementing SDT to treat in vitro and in vivo models of glioma. Our findings suggest that coupling sonosensitizers such as 5-aminolevulinic acid, hematoporphyrin monomethyl ether, and sinoporphyrin sodium with focused ultrasound induces robust cytotoxic activity in tumor cells (in vitro and in vivo). These effects are likely mediated by the oxidative stress induced by reactive oxygen species production, apoptotic signaling cascades, and intracellular calcium overload. Future research is needed to better understand the biochemical and mechanistic properties of SDT, and ongoing trials may help elucidate the clinical feasibility of glioma treatment with optimized sonically activated treatments.
Assuntos
Antineoplásicos , Glioma , Terapia por Ultrassom , Humanos , Terapia por Ultrassom/métodos , Glioma/terapia , Glioma/tratamento farmacológico , Ácido Aminolevulínico/farmacologia , Apoptose , Espécies Reativas de Oxigênio , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Linhagem Celular TumoralRESUMO
Neuromonitoring is commonly used in neurosurgery and allows intraoperative assessment of functional pathways in the brain during surgery. Monitoring alerts can guide surgical decision making in real-time allowing surgeons to mitigate or avoid potential iatrogenic injury and subsequent postoperative neurologic sequelae that may result from cerebral ischemia or malperfusion. Here we present a case of a patient undergoing a right pterional craniotomy for the resection of a tumor which crosses midline with multimodal intraoperative neuromonitoring including somatosensory evoked potentials, transcranial motor evoked potentials, and visual evoked potentials. During the final portion of tumor resection, arterial bleeding was noted of unknown origin shortly followed by loss of right lower extremity motor evoked potential recordings. Motor evoked potential recordings in the right upper, and left upper and lower extremities were stable, as well as all somatosensory evoked potentials and visual evoked potentials. This distinct pattern of right lower extremity motor-evoked potential loss suggested compromise of the contralateral anterior cerebral artery and guided the surgeons to a rapid intervention. The patient awoke from surgery with moderate postoperative weakness in the affected limb that resolved to preoperative status by postoperative day 2, and back to normal strength prior to three-month follow-up. In this case the neuromonitoring data suggested compromise to the contralateral anterior cerebral artery which guided the surgeons to investigate and identify the site of vascular injury. The present case reinforces the utility of neuromonitoring in emergent surgical situations to guide surgical decision making.