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1.
Cancers (Basel) ; 16(6)2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38539447

RESUMO

Serpins are serine proteinase inhibitors, with several serpins being overexpressed in cancer cells. Thus, we aim to analyze the single-nucleotide polymorphism (SNP) of Serpinb11 and its association with GBM survival. A cohort of 63 GBM patients recruited from King Abdullah University Hospital in Jordan underwent polymorphism analysis and overall survival (OS) assessments. The Cancer Genome Atlas (GBM) cohort was useful for validation. We constructed a risk score using the principal component analysis for the following Serpin genes: Serpinb3, Serpinb5, Serpinb6, Serpinb11, and Serpinb12, and patients were grouped into high- vs. low-risk groups based on the median cutoff. Univariable Cox models were used to study the survival outcomes. We identified a significant association between rs4940595 and survival. In the TCGA cohort, Serpinb3 alterations showed worse OS. Univariable Cox showed worse PFS outcomes with higher SERPINB5 and SERPINB6 expression. A Serpin B 5-gene risk score showed a trend towards worse PFS in the high-risk group. Upregulated DEGs showed GO enrichment in cytokine regulation and production, positive regulation of leukocyte activation, and the MAPK cascade. The high-risk group showed a significantly higher infiltration of M2 macrophages and activated mast cells. Our findings showed a significant role of the Serpin B family in GBM survival in the Jordanian population.

2.
Cancers (Basel) ; 16(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339384

RESUMO

Glioblastoma (GBM) represents a profoundly aggressive and heterogeneous brain neoplasm linked to a bleak prognosis. Hypoxia, a common feature in GBM, has been linked to tumor progression and therapy resistance. In this study, we aimed to identify hypoxia-related differentially expressed genes (DEGs) and construct a prognostic signature for GBM patients using multi-omics analysis. Patient cohorts were collected from publicly available databases, including the Gene Expression Omnibus (GEO), the Chinese Glioma Genome Atlas (CGGA), and The Cancer Genome Atlas-Glioblastoma Multiforme (TCGA-GBM), to facilitate a comprehensive analysis. Hypoxia-related genes (HRGs) were obtained from the Molecular Signatures Database (MSigDB). Differential expression analysis revealed 41 hypoxia-related DEGs in GBM patients. A consensus clustering approach, utilizing these DEGs' expression patterns, identified four distinct clusters, with cluster 1 showing significantly better overall survival. Machine learning techniques, including univariate Cox regression and LASSO regression, delineated a prognostic signature comprising six genes (ANXA1, CALD1, CP, IGFBP2, IGFBP5, and LOX). Multivariate Cox regression analysis substantiated the prognostic significance of a set of three optimal signature genes (CP, IGFBP2, and LOX). Using the hypoxia-related prognostic signature, patients were classified into high- and low-risk categories. Survival analysis demonstrated that the high-risk group exhibited inferior overall survival rates in comparison to the low-risk group. The prognostic signature showed good predictive performance, as indicated by the area under the curve (AUC) values for one-, three-, and five-year overall survival. Furthermore, functional enrichment analysis of the DEGs identified biological processes and pathways associated with hypoxia, providing insights into the underlying mechanisms of GBM. Delving into the tumor immune microenvironment, our analysis revealed correlations relating the hypoxia-related prognostic signature to the infiltration of immune cells in GBM. Overall, our study highlights the potential of a hypoxia-related prognostic signature as a valuable resource for forecasting the survival outcome of GBM patients. The multi-omics approach integrating bulk sequencing, single-cell analysis, and immune microenvironment assessment enhances our understanding of the intricate biology characterizing GBM, thereby potentially informing the tailored design of therapeutic interventions.

3.
World Neurosurg ; 182: e344-e359, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38013108

RESUMO

OBJECTIVE: The differential diagnosis for postoperative back pain is broad, and conventional imaging modalities are not always conclusive. Therefore, we performed a systematic review of the literature and present case studies describing the use of single-photon emission CT (SPECT)/CT or positron emission tomography (PET)/CT in the diagnosis of back pain following spine surgery. METHODS: A systematic review was conducted according to PRISMA guidelines across 5 databases. Relevant keywords included PET/CT, bone SPECT/CT, and pseudarthrosis. The studies were assessed for diagnostic accuracy of the imaging technologies. RESULTS: A total of 2,444 studies were screened, 91 were selected for full-text review, and 21 were ultimately included. Six retrospective studies investigated the use of SPECT/CT with a total sample size of 309 patients. Two of these studies used SPECT/CT to predict screw loosening in over 50% of patients. Eight studies examined the use of 18-fluoride sodium fluoride (18F-NaF) PET/CT. Among these studies, measures of diagnostic accuracy varied but overall demonstrated the ability of 18F-NaF PET/CT to detect screw loosening and pseudarthrosis. Seven studies examined 18F-fluorodeoxyglucose (FDG) PET/CT and supported its utility in the diagnosis of postoperative infections in the spine. CONCLUSIONS: PET/CT and SPECT/CT are useful in the evaluation of postoperative pain of the spine, especially in patients for whom conventional imaging modalities yield inconclusive results. More diagnostic accuracy studies with strong reference standards are needed to compare hybrid imaging to conventional imaging.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Pseudoartrose , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons/métodos , Dor Pós-Operatória/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Dor nas Costas , Fluordesoxiglucose F18 , Sensibilidade e Especificidade
4.
Int J Mol Sci ; 24(22)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38003507

RESUMO

Glioblastoma is the most common malignant primary central nervous system tumor and one of the most debilitating cancers. The prognosis of patients with glioblastoma remains poor, and the management of this tumor, both in its primary and recurrent forms, remains suboptimal. Despite the tremendous efforts that are being put forward by the research community to discover novel efficacious therapeutic agents and modalities, no major paradigm shifts have been established in the field in the last decade. However, this does not mirror the abundance of relevant findings and discoveries made in preclinical glioblastoma research. Hence, developing and utilizing appropriate preclinical models that faithfully recapitulate the characteristics and behavior of human glioblastoma is of utmost importance. Herein, we offer a holistic picture of the evolution of preclinical models of glioblastoma. We further elaborate on the commonly used in vitro and vivo models, delving into their development, favorable characteristics, shortcomings, and areas of potential improvement, which aids researchers in designing future experiments and utilizing the most suitable models. Additionally, this review explores progress in the fields of humanized and immunotolerant mouse models, genetically engineered animal models, 3D in vitro models, and microfluidics and highlights promising avenues for the future of preclinical glioblastoma research.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Animais , Camundongos , Humanos , Glioblastoma/patologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Modelos Animais de Doenças
5.
Cancers (Basel) ; 15(15)2023 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-37568705

RESUMO

Medulloblastoma is the most common malignant pediatric brain tumor and is associated with significant morbidity and mortality in the pediatric population. Despite the use of multiple therapeutic approaches consisting of surgical resection, craniospinal irradiation, and multiagent chemotherapy, the prognosis of many patients with medulloblastoma remains dismal. Additionally, the high doses of radiation and the chemotherapeutic agents used are associated with significant short- and long-term complications and adverse effects, most notably neurocognitive delay. Hence, there is an urgent need for the development and clinical integration of targeted treatment regimens with greater efficacy and superior safety profiles. Since the adoption of the molecular-based classification of medulloblastoma into wingless (WNT) activated, sonic hedgehog (SHH) activated, group 3, and group 4, research efforts have been directed towards unraveling the genetic, epigenetic, transcriptomic, and proteomic profiles of each subtype. This review aims to delineate the progress that has been made in characterizing the neurodevelopmental and molecular features of each medulloblastoma subtype. It further delves into the implications that these characteristics have on the development of subgroup-specific targeted therapeutic agents. Furthermore, it highlights potential future avenues for combining multiple agents or strategies in order to obtain augmented effects and evade the development of treatment resistance in tumors.

6.
Oper Neurosurg (Hagerstown) ; 25(6): 482-488, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37578266

RESUMO

BACKGROUND AND OBJECTIVES: Robot-assisted pedicle screw placement is associated with greater accuracy, reduced radiation, less blood loss, shorter hospital stays, and fewer complications than freehand screw placement. However, it can be associated with longer operative times and an extended training period. We report the initial experience of a surgeon using a robot system at an academic medical center. METHODS: We retrospectively reviewed all patients undergoing robot-assisted pedicle screw placement at a single tertiary care institution by 1 surgeon from 10/2017 to 05/2022. Linear regression, analysis of variance, and cumulative sum analysis were used to evaluate operative time learning curves. Operative time subanalyses for surgery indication, number of levels, and experience level were performed. RESULTS: In total, 234 cases were analyzed. A significant 0.19-minute decrease in operative time per case was observed (r = 0.14, P = .03). After 234 operations, this translates to a reduction in 44.5 minutes from the first to last case. A linear relationship was observed between case number and operative time in patients with spondylolisthesis (-0.63 minutes/case, r = 0.41, P < .001), 2-level involvement (-0.35 minutes/case, r = 0.19, P = .05), and 4-or-more-level involvement (-1.29 minutes/case, r = 0.24, P = .05). This resulted in reductions in operative time ranging from 39 minutes to 1.5 hours. Continued reductions in operative time were observed across the learning, experienced, and expert phases, which had mean operative times of 214, 197, and 146 minutes, respectively ( P < .001). General proficiency in robot-assisted surgery was observed after the 20th case. However, 67 cases were required to reach mastery, defined as the inflection point of the cumulative sum curve. CONCLUSION: This study documents the long-term learning curve of a fellowship-trained spine neurosurgeon. Operative time significantly decreased with more experience. Although gaining comfort with robotic systems may be challenging or require additional training, it can benefit surgeons and patients alike with continued reductions in operative time.


Assuntos
Parafusos Pediculares , Robótica , Humanos , Curva de Aprendizado , Duração da Cirurgia , Estudos Retrospectivos
7.
J Neurosurg Case Lessons ; 6(2)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37458340

RESUMO

BACKGROUND: Synthetic computed tomography (sCT) can be created from magnetic resonance imaging (MRI) utilizing newer software. sCT is yet to be explored as a possible alternative to routine CT (rCT). In this study, rCT scans and MRI-derived sCT scans were obtained on a cadaver. Morphometric analysis was performed comparing the 2 scans. The ExcelsiusGPS robot was used to place lumbosacral screws with both rCT and sCT images. OBSERVATIONS: In total, 14 screws were placed. All screws were grade A on the Gertzbein-Robbins scale. The mean surface distance difference between rCT and sCT on a reconstructed software model was -0.02 ± 0.05 mm, the mean absolute surface distance was 0.24 ± 0.05 mm, and the mean absolute error of radiodensity was 92.88 ± 10.53 HU. The overall mean tip distance for the sCT versus rCT was 1.74 ± 1.1 versus 2.36 ± 1.6 mm (p = 0.24); mean tail distance for the sCT versus rCT was 1.93 ± 0.88 versus 2.81 ± 1.03 mm (p = 0.07); and mean angular deviation for the sCT versus rCT was 3.2° ± 2.05° versus 4.04°± 2.71° (p = 0.53). LESSONS: MRI-based sCT yielded results comparable to those of rCT in both morphometric analysis and robot-assisted lumbosacral screw placement in a cadaver study.

8.
Int J Spine Surg ; 17(S2): S18-S25, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37321646

RESUMO

Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are well-recognized challenges of surgery for adult spinal deformity (ASD). Multiple risk factors have been identified for PJK/PJF, including osteoporosis, frailty, neurodegenerative disease, obesity, and smoking. Several surgical techniques to mitigate risk of PJK/PJF have been identified; however, patient optimization is also critical. This review summarizes the data behind these 5 risk factors (osteoporosis, frailty, neurodegenerative disease, obesity, and smoking) and details the related recommendations for patients undergoing surgery for ASD.

9.
Neurosurgery ; 93(2): 462-472, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36921234

RESUMO

BACKGROUND: Patients undergoing surgical procedures for spinal tumors are vulnerable to major adverse events (AEs) and death in the postoperative period. Shared decision making and preoperative optimization of outcomes require accurate risk estimation. OBJECTIVE: To develop and validate a risk index to predict short-term major AEs after spinal tumor surgery. METHODS: Prospectively collected data from multiple medical centers affiliated with the American College of Surgeons National Surgical Quality Improvement Program from 2006 to 2020 were reviewed. Multiple logistic regression was used to assess sociodemographic, tumor-related, and surgery-related factors in the derivation cohort. The spinal tumor surgery risk index (STSRI) was built based on the resulting scores. The STSRI was internally validated using a subgroup of patients from the American College of Surgeons National Surgical Quality Improvement Program database and externally validated using a cohort from a single tertiary center. RESULTS: In total, 14 982 operations were reviewed and 4556 (16.5%) major AEs occurred within 30 days after surgery, including 209 (4.5%) deaths. 22 factors were independently associated with major AEs or death and were included in the STSRI. Using the internal and external validation cohorts, the STSRI produced an area under the curve of 0.86 and 0.82, sensitivity of 80.1% and 79.7%, and specificity of 74.3% and 73.7%, respectively. The STSRI, which is freely available, outperformed the modified frailty indices, the American Society of Anesthesiologists classification, and the American College of Surgeons risk calculator. CONCLUSION: In patients undergoing surgery for spinal tumors, the STSRI showed the highest predictive accuracy for major postoperative AEs and death compared with other current risk predictors.


Assuntos
Neoplasias da Medula Espinal , Neoplasias da Coluna Vertebral , Humanos , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Neoplasias da Medula Espinal/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Coluna Vertebral/cirurgia
10.
Cancers (Basel) ; 15(4)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36831418

RESUMO

Novel therapeutic and diagnostic methods are sorely needed for gliomas, which contribute yearly to hundreds of thousands of cancer deaths worldwide. Despite the outpouring of research efforts and funding aimed at improving clinical outcomes for patients with glioma, the prognosis for high-grade glioma, and especially glioblastoma, remains dire. One of the greatest obstacles to improving treatment efficacy and destroying cancer cells is the safe delivery of chemotherapeutic drugs and biologics to the tumor site at a high enough dose to be effective. Over the past few decades, a burst of research has leveraged nanotechnology to overcome this obstacle. There has been a renewed interest in adapting previously understudied dendrimer nanocarriers for this task. Dendrimers are small, highly modifiable, branched structures featuring binding sites for a variety of drugs and ligands. Recent studies have demonstrated the potential for dendrimers and dendrimer conjugates to effectively shuttle therapeutic cargo to the correct tumor location, permeate the tumor, and promote apoptosis of tumor cells while minimizing systemic toxicity and damage to surrounding healthy brain tissue. This review provides a primer on the properties of dendrimers; outlines the mechanisms by which they can target delivery of substances to the site of brain pathology; and delves into current trends in the application of dendrimers to drug and gene delivery, and diagnostic imaging, in glioma. Finally, future directions for translating these in vitro and in vivo findings to the clinic are discussed.

11.
Oper Neurosurg (Hagerstown) ; 24(3): 262-267, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36656065

RESUMO

BACKGROUND: Microvascular decompression (MVD) using a retrosigmoid approach is a highly effective, open-surgical procedure for neurovascular conflict in the posterior fossa, although there is a risk of postoperative cerebrospinal fluid (CSF) leak. OBJECTIVE: To identify factors associated with postoperative CSF leakage after MVD. METHODS: We retrospectively reviewed all patients who underwent MVDs at our institution from 2007 to 2020. Patient demographics, clinical diagnoses, and procedural characteristics were recorded and compared. Factors leading to CSF leak were analyzed using χ 2 , univariate, and multivariate regression. RESULTS: Of 1011 patients who underwent MVDs, 37 (3.7%) presented with postoperative CSF leaks. In univariate analysis, the use of Cranios/Norian to obliterate the air cells was protective against CSF leak ( P = .01). Craniotomies ( P = .002), the use of dural substitutes such as Durepair ( P = .04), dural onlays such as DuraGen ( P = .04), muscle/fascia ( P = .03), and titanium mesh cranioplasty >5 cm ( P = .03) were associated with CSF leak. On multivariate analysis, only the presence of craniotomies ( P = .04) and nonprimary dural closure ( P = .03) were significant risk factors for CSF leak. When excluding the 34 (3.4%) patients who underwent a craniotomy, the lack of primary dural closure still remained significantly associated with postoperative CSF leak ( P = .04). CONCLUSION: Our results represent one of the largest series of posterior fossa surgeries for a uniform indication in North America. Our study demonstrates increased risk for postoperative CSF leak when craniotomies are performed and when primary dural closure is not established. Given the small sample of patients who received a craniotomy, however, future studies corroborating this finding should be performed.


Assuntos
Cirurgia de Descompressão Microvascular , Humanos , Estudos Retrospectivos , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Craniotomia/efeitos adversos , Craniotomia/métodos
13.
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
14.
Spine (Phila Pa 1976) ; 48(3): 180-188, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36190990

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim was to investigate the accuracy of pedicle screw placement by freehand technique and to compare revision surgery rates among three different imaging verification pathways. SUMMARY OF BACKGROUND DATA: Studies comparing different imaging modalities in freehand screw placement surgery are limited. MATERIALS AND METHODS: A single-institution retrospective chart review identified adult patients who underwent freehand pedicle screw placement in the thoracic, lumbar or sacral levels. Patients were stratified into three cohorts based on the intraoperative imaging modality used to assess the accuracy of screw position: intraoperative X-rays (cohort 1); intraoperative O-arm (cohort 2); or intraoperative computed tomography (CT)-scan (cohort 3). Postoperative CT scans were performed on all patients in cohorts 1 and 2. Postoperative CT scan was not required in cohort 3. Screw accuracy was assessed using the Gertzbein-Robbins grading system. RESULTS: A total of 9179 pedicle screws were placed in the thoracic or lumbosacral spine in 1311 patients. 210 (2.3%) screws were identified as Gertzbein-Robbins grades C-E on intraoperative/postoperative CT scan, 137 thoracic screws, and 73 lumbar screws ( P <0.001). Four hundred and nine patients underwent placement of 2754 screws followed by intraoperative X-ray (cohort 1); 793 patients underwent placement of 5587 screws followed by intraoperative O-arm (cohort 2); and 109 patients underwent placement of 838 screws followed by intraoperative CT scan (cohort 3). Postoperative CT scans identified 65 (2.4%) and 127 (2.3%) malpositioned screws in cohorts 1 and 2, respectively. Eleven screws (0.12%) were significantly malpositioned and required a second operation for screw revision. Nine patients (0.69%) required revision operations: eight of these patients were from cohort 1 and one patient was from cohort 2. CONCLUSION: When compared to intraoperative X-ray, intraoperative O-arm verification decreased the revision surgery rate for malpositioned screws from 0.37% to 0.02%. In addition, our analysis suggests that the use of intraoperative O-arm can obviate the need for postoperative CT scans.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Cirurgia Assistida por Computador , Adulto , Humanos , Estudos Retrospectivos , Imageamento Tridimensional/métodos , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Fusão Vertebral/métodos
15.
Cancers (Basel) ; 14(19)2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36230843

RESUMO

Glioblastoma (GBM) is an aggressive primary astrocytoma associated with short overall survival. Treatment for GBM primarily consists of maximal safe surgical resection, radiation therapy, and chemotherapy using temozolomide. Nonetheless, recurrence and tumor progression is the norm, driven by tumor stem cell activity and a high mutational burden. Focused ultrasound (FUS) has shown promising results in preclinical and clinical trials for treatment of GBM and has received regulatory approval for the treatment of other neoplasms. Here, we review the range of applications for FUS in the treatment of GBM, which depend on parameters, including frequency, power, pulse duration, and duty cycle. Low-intensity FUS can be used to transiently open the blood-brain barrier (BBB), which restricts diffusion of most macromolecules and therapeutic agents into the brain. Under guidance from magnetic resonance imaging, the BBB can be targeted in a precise location to permit diffusion of molecules only at the vicinity of the tumor, preventing side effects to healthy tissue. BBB opening can also be used to improve detection of cell-free tumor DNA with liquid biopsies, allowing non-invasive diagnosis and identification of molecular mutations. High-intensity FUS can cause tumor ablation via a hyperthermic effect. Additionally, FUS can stimulate immunological attack of tumor cells, can activate sonosensitizers to exert cytotoxic effects on tumor tissue, and can sensitize tumors to radiation therapy. Finally, another mechanism under investigation, known as histotripsy, produces tumor ablation via acoustic cavitation rather than thermal effects.

16.
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
17.
Cancers (Basel) ; 14(15)2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35954407

RESUMO

Glioblastoma (GBM) is an aggressive tumor of the central nervous system categorized by the World Health Organization as a Grade 4 astrocytoma. Despite treatment with surgical resection, adjuvant chemotherapy, and radiation therapy, outcomes remain poor, with a median survival of only 14-16 months. Although tumor regression is often observed initially after treatment, long-term recurrence or progression invariably occurs. Tumor growth, invasion, and recurrence is mediated by a unique population of glioblastoma stem cells (GSCs). Their high mutation rate and dysregulated transcriptional landscape augment their resistance to conventional chemotherapy and radiation therapy, explaining the poor outcomes observed in patients. Consequently, GSCs have emerged as targets of interest in new treatment paradigms. Here, we review the unique properties of GSCs, including their interactions with the hypoxic microenvironment that drives their proliferation. We discuss vital signaling pathways in GSCs that mediate stemness, self-renewal, proliferation, and invasion, including the Notch, epidermal growth factor receptor, phosphatidylinositol 3-kinase/Akt, sonic hedgehog, transforming growth factor beta, Wnt, signal transducer and activator of transcription 3, and inhibitors of differentiation pathways. We also review epigenomic changes in GSCs that influence their transcriptional state, including DNA methylation, histone methylation and acetylation, and miRNA expression. The constituent molecular components of the signaling pathways and epigenomic regulators represent potential sites for targeted therapy, and representative examples of inhibitory molecules and pharmaceuticals are discussed. Continued investigation into the molecular pathways of GSCs and candidate therapeutics is needed to discover new effective treatments for GBM and improve survival.

18.
World Neurosurg ; 166: e504-e510, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35842175

RESUMO

OBJECTIVES: Microvascular decompression (MVD) has grown as a first-line surgical intervention for severe facial pain from trigeminal neuralgia and/or hemifacial spasm. We sought to examine the safety and cost-benefits of discharging patients with MVD within 1 day of admission. METHODS: We retrospectively reviewed patients undergoing MVD at our institution from 2008 to 2020. Patients were sorted by 1 day, 2 days, or >2 days until discharge and by year from 2008 to 2013, 2014 to 2018, or 2019 to 2020. Patient presenting characteristics, intraoperative measures, and complications were documented. Statistical differences were calculated by one-way analysis of variance and χ2 analyses. RESULTS: Our cohort included 976 patients undergoing MVD, with 231 (23.6%) between 2008 and 2013, 517 (52.9%) between 2014 and 2018, and 228 (23.3%) between 2019 and 2020. Over time, postoperative admission rates to the critical care unit, total inpatient hospital admission times, and Barrow Neurological Institute scores at first follow-up decreased. Postoperative complications, including cerebrospinal fluid leak, decreased significantly. In addition, patients discharged within 1 day of admission incurred a total hospital cost of $26,689, which was $3588 lower than patients discharged within more than 1 day of admission, P < 0.0001. Discharging carefully selected patients who are appropriate for discharge within 1 day of admission could translate to a potential cost-savings of $255,346 per year in our clinical practice. CONCLUSIONS: In our experience, MVDs are a safe, elective intervention. Our findings suggest that postoperative day 1 discharge in patients with an uncomplicated postoperative course may be safe while improving hospital resource use.


Assuntos
Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo , Redução de Custos , Espasmo Hemifacial/complicações , Espasmo Hemifacial/cirurgia , Humanos , Pacientes Internados , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Neuralgia do Trigêmeo/complicações , Neuralgia do Trigêmeo/cirurgia
19.
J Vis Exp ; (183)2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35604202

RESUMO

The present protocol describes a standardized paradigm for rodent brain tumor resection and tissue preservation. In clinical practice, maximal tumor resection is the standard-of-care treatment for most brain tumors. However, most currently available preclinical brain tumor models either do not include resection, or utilize surgical resection models that are time-consuming and lead to significant postoperative morbidity, mortality, or experimental variability. In addition, performing resection in rodents can be daunting for several reasons, including a lack of clinically comparable surgical tools or protocols and the absence of an established platform for standardized tissue collection. This protocol highlights the use of a multi-functional, non-ablative resection device and an integrated tissue preservation system adapted from the clinical version of the device. The device applied in the present study combines tunable suction and a cylindrical blade at the aperture to precisely probe, cut, and suction tissue. The minimally invasive resection device performs its functions via the same burr hole used for the initial tumor implantation. This approach minimizes alterations to regional anatomy during biopsy or resection surgeries and reduces the risk of significant blood loss. These factors significantly reduced the operative time (<2 min/animal), improved postoperative animal survival, lower variability in experimental groups, and result in high viability of resected tissues and cells for future analyses. This process is facilitated by a blade speed of ~1,400 cycles/min, which allows the harvesting of tissues into a sterile closed system that can be filled with a physiologic solution of choice. Given the emerging importance of studying and accurately modeling the impact of surgery, preservation and rigorous comparative analysis of regionalized tumor resection specimens, and intra-cavity-delivered therapeutics, this unique protocol will expand opportunities to explore unanswered questions about perioperative management and therapeutic discovery for brain tumor patients.


Assuntos
Neoplasias Encefálicas , Roedores , Animais , Encéfalo/cirurgia , Neoplasias Encefálicas/cirurgia , Humanos , Microcirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Técnicas Estereotáxicas
20.
Clin Spine Surg ; 35(9): 383-387, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35552292

RESUMO

STUDY DESIGN: This was a systematic review of the literature. OBJECTIVE: The aim was to examine the contemporary demographics, etiological factors, treatment options and outcomes of spinal epidural lipomatosis (SEL) in adults. SUMMARY OF BACKGROUND DATA: SEL is primarily seen in obese patients as well as those on steroid therapy. Much regarding the etiology and treatment outcomes of SEL is unknown. METHODS: We reviewed Ovid MEDLINE, PubMed, SCOPUS, and Google Scholars databases from 1990 through August 2020 to identify cases of SEL. Data collected included patient characteristics, disease associations, level of pathology, treatment, and clinical outcomes. RESULTS: Ninety articles (145 individual cases) were included in the analysis. The median age was 54 years and 79% were males. Obesity-associated SEL constituted the largest proportion (52%) of our cohort. 22% of SEL cases were related to steroid use, while 26% cases were considered to be idiopathic. Lumbosacral SEL was the most frequently reported level of disease (68.9%), followed by the thoracic level (26.2%). The mean age of cases who underwent surgical intervention was 55 years, as compared with 48 years in those who received conservative management ( P =0.03). 95% of patients reported some degree of symptomatic improvement regardless of the treatment modality. Logistic regression suggested a possible superior outcome associated with those undergoing surgical treatment. CONCLUSION: In contrast to historical comparisons, contemporary articles support that obesity has become the major contributing factor for SEL. Logistic regression of the existing cases suggests that there may be a role for surgical intervention in select patients.


Assuntos
Espaço Epidural , Lipomatose , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espaço Epidural/patologia , Lipomatose/complicações , Lipomatose/patologia , Lipomatose/cirurgia , Imageamento por Ressonância Magnética , Obesidade/complicações , Esteroides , Resultado do Tratamento
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