Δευτέρα 8 Μαρτίου 2021

Novel Focal Therapeutic Hypothermia Device for Treatment of Acute Neurologic Injury: Large Animal Safety and Efficacy Trial

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0040-1721818

Objective Therapeutic hypothermia is a potentially powerful and controversial clinical tool for neuroprotection following acute neurologic pathology, particularly vascular injury. Indeed, therapeutic hypothermia remains a standard of care for postcardiac arrest ischemia and acute neonatal hypoxic-ischemic encephalopathy, improving both survival and outcomes. Although therapeutic hypothermia remains promising for cellular and systems-based neuronal protection in other neurologic injury states, the systemic side effects have limited clinical utility, confounded analysis of potential neurologic benefits, and precluded the completion of meaningful clinical trials. Methods To address such limitations, we developed and tested a novel, minimally invasive, neurocritical care device that employs continuous circulation of cold saline through the pharyngeal region to deliver focal cerebrovascular cooling. We conducted a preclinical safety and efficacy trial in six adult porcine animals to assess the validity and functionality of the NeuroSave device, and assess cooling potential following middle cerebral artery occlusion (n = 2). Results NeuroSave consistently lowered brain parenchymal temperature by a median of 9°C relative to core temperature within 60 minutes of initiation, including in ischemic cerebral parenchyma. The core body temperature experienced a maximal reduction of 2°C, or 5% of body temperature, with no associated adverse effects identified. Conclusion The present study uses a large animal preclinical model to demonstrate the safety and efficacy of a novel, noninvasive device for the induction of robust and systemically safe hypothermia within the brain.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Vision Deterioration and Hydrocephalus: Rare Presentations of Vestibular Schwannoma and Evolution of Management

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10-1055-s-0041-1725032_200310-1.jpg

J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1725032

Introduction The incidence of vestibular schwannoma is reported as 12 to 54 new cases per million per year, increasing over time. These patients usually present with unilateral sensorineural hearing loss, tinnitus, or vertigo. Rarely, these patients present with symptoms of hydrocephalus or vision changes. Objective The study aimed to evaluate the surgical management of vestibular schwannoma at a single institution and to identify factors that may contribute to hydrocephalus, papilledema, and the need for pre-resection diversion of cerebrospinal fluid. Patients and Methods A retrospective review examining the data of 203 patients with vestibular schwannoma managed with surgical resection from May 2008 to May 2020. We stratified patients into five different groups to analyze: tumors with a diameter of ≥40 mm, clinical evidence of hydrocephalus, and of papilledema, and patients who underwent pre-resection cerebrospinal fluid (CSF) diversion. Results From May 2008 to May 2020, 203 patients were treated with surgical resection. Patients with tumors ≥40 mm were more likely to present with visual symptoms (p < 0.001). Presentation with hydrocephalus was associated with larger tumor size (p < 0.001) as well as concomitant visual symptoms and papilledema (p < 0.001). Patients with visual symptoms presented at a younger age (p = 0.002) and with larger tumors (p < 0.001). Conclusion This case series highlights the rare presentation of vision changes and hydrocephalus in patients with vestibular schwannoma. We recommend urgent CSF diversion for patients with visual symptoms and hydrocephalus, followed by definitive resection. Further, vision may still deteriorate even after CSF diversion and tumor resection.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Relationship between Signal Intensity of the Labyrinth and Cochleovestibular Testing and Morphologic Features of Vestibular Schwannoma

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10-1055-s-0041-1725035_200362-1.jpg

J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1725035

Objectives The aim of this article was to evaluate the relationship between signal intensity of the labyrinth and vestibulocochlear function and morphologic features of vestibular schwannoma (VS). Design Cross-sectional Study. Setting Tertiary referral center. Participants Fifty-four patients with sporadic, untreated VS. Main Outcome Measure Signal intensity of the cochlea and vestibule (SIRc and SIRv: signal intensity of cochlea/vestibule compared with cerebellar signal intensity; AURc and AURv: SIRc/SIRv of the affected side compared with the unaffected side) in 1.5T T2-weighted images was correlated with size (Hannover classification), cystic status, distance from the fundus of the internal auditory canal, video head impulse test (vHIT), and audiometry. Results Signal intensity of the vestibule was higher than that of the cochlea (p < 0.01). Large tumors had lower SIRc than smaller tumors (p = 0.03); Hannover T1 tumors had higher SIRc (p < 0.01), SIRv (p < 0.01), AURc (p < 0.01) and AURv (p < 0.01) than the rest; heterogenous and cystic tumors had higher SIRv than solid large tumors (p = 0.02); superior vestibular nerve pattern on vHIT had higher SIRv and AURv than inferior vestibular nerve and mixed patterns (p = 0.03 and 0.004, respectively); and there was a weak correlation between AURv and speech discrimination (r = 0.33, p = 0.04). Conclusion A more abnormal signal intensity of the labyrinth is associated with larger size and solid status of VS. There was a positive relationship between signal intensity of the labyrinth and speech discrimination scores on audiogram.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Κυριακή 7 Μαρτίου 2021

Relationship between tumor cell infiltration and 5-aminolevulinic acid fluorescence signals after resection of MR-enhancing lesions and its prognostic significance in glioblastoma

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Abstract

Purpose

This study investigated the degree of tumor cell infiltration in the tumor cavity and ventricle wall based on fluorescent signals of 5-aminolevulinic acid (5-ALA) after removal of the magnetic resonance (MR)-enhancing area and analyzed its prognostic significance in glioblastoma.

Methods

Twenty-five newly developed isocitrate dehydrogenase (IDH)-wildtype glioblastomas with complete resection both of MR-enhancing lesions and strong purple fluorescence on resection cavity were retrospectively analyzed. The fluorescent signals of 5-ALA were divided into strong purple, vague pink, and blue colors. The pathologic findings were classified into massively infiltrating tumor cells, infiltrating tumor cells, suspicious single-cell infiltration, and normal-appearing cells. The pathological findings were analyzed according to the fluorescent signals in the resection cavity and ventricle wall.

Results

There was no correlation between fluorescent signals and infiltrating tumor cells in the resection cavity (p = 0.199) and ventricle wall (p = 0.704) after resection of the MR-enhancing lesion. The median progression-free survival (PFS) and median overall survival (OS) were 12.5 (± 2.1) and 21.1 (± 3.5) months, respectively. In univariate analysis, the presence of definitive infiltrating tumor cells in the resection cavity and ventricle wall was significantly related to the PFS (p = 0.002) and OS (p = 0.027). In multivariate analysis, the absence of definitive infiltrating tumor cells improved PFS (hazard ratio: 0.184; 95% CI: 0.049–0.690, p = 0.012) and OS (hazard ratio: 0.124; 95% CI: 0.015–0.998, p = 0.050).

Conclusions

After resection both of the MR-enhancing lesions and strong purple fluorescence on resection cavity, there was no correlation between remnant fluorescent signals and infiltrating tumor cells. The remnant definitive infiltrating tumor cells in the resection cavity and ventricle wall significantly influenced the prognosis of patients with glioblastoma. Aggressive surgical removal of infiltrating tumor cells may improve their prognosis.

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Patterns of treatment failure in patients with prostate cancer treated with 76–80 Gy radiotherapy to the prostate and seminal vesicles ± hormonotherapy

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Abstract

Purpose

To assess the pattern of treatment failure in patients with prostate cancer (PCa) treated with radiotherapy (76–80 Gy) ± hormone therapy (HT). We also evaluated the influence of treatment failure on survival outcomes.

Methods

Retrospective study of patients with PCa (n = 302) treated with radiotherapy (RT) ± HT at our centre between November 1999 and July 2007. The mean patient age was 70.2 years (range 51–87). Distribution by NCCN risk group was low (n = 80, 26.5%), intermediate (n = 86, 28.5%), high (n = 77, 25.5%), and very high (n = 49, 16.2%). Most patients (n = 273, 90.4%) received IMRT at a dose of 76–80 Gy. HT was administered in 237 patients (78.5%), in most cases (n = 167, 55.3%) for < 7 months

Results

Survival rates at 10 years were: overall survival (OS), 64.3%; biochemical disease-free survival, 83.9%; disease-free survival, 92.5%; and metastasis-free survival (MFS), 94.3%. Biochemical failure (BF) was observed in 55 cases (18.2%), 32 of whom subsequently developed clinical recurrence: metastasis (n = 17, 5.6%), local failure (n = 11, 3.6%), and regional failure (n = 4, 1.3%). The cause of death (n = 159) was intercurrent disease in 115 cases (72.3%), second cancer in 27 (17.0%), and PCa in 17 (10.7%). Biochemical failure-free survival ≤ 24 months was significantly associated with worse OS and MFS (p = 0.0001). Late genitourinary and gastrointestinal toxicity grade ≥ 3 (RTOG) was observed in 18 (6.0%) and 7 (2.3%) patients, respectively.

Conclusions

The main type of treatment failure after 76–80 Gy of radiotherapy ± HT is local or metastatic. In all cases, biochemical failure occurred prior to treatment failure. BF within 24 months of treatment completion was significantly associated with worse OS and MFS.

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Influence of glioblastoma contact with the subventricular zone on survival and recurrence patterns

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Abstract

Background

There is growing evidence that the subventricular zone (SVZ) may be involved in both the initiation and progression of glioblastoma (GB). We aimed to assess tumor proximity to the SVZ as a potential prognostic factor in GB.

Method

Retrospective study of 133 patients diagnosed with primary GB who underwent surgery followed by temozolomide-based chemoradiation between 2010 and 2016. All lesions were classified according to their anatomic relation with the SVZ. We determined the effect of tumor contact with the SVZ on progression-free survival (PFS), overall survival (OS), type, and patterns of recurrence.

Results

At a median follow-up of 18.6 months (95% CI 15.9–21.2), PFS and OS were 7.5 (95% CI 6.7–8.3) and 13.9 (95% CI 10.9–16.9) months, respectively. On the univariate analyses, initial contact with the SVZ was a factor for poor prognosis for both PFS (6.1 vs. 8.7 months; p = 0.006) and OS (10.6 vs. 17.9 months; p = 0.037). On the multivariate analysis, tumor contact with the SVZ remained statistically significant for PFS, but not OS. Patients with SVZ-contacting tumors presented a higher rate of aggressive clinical progression (30.9% vs. 11.3%; p = 0.007) and contralateral relapse patterns (23.4% vs. 9.1%; p = 0.048).

Conclusions

Our results suggest that glioblastoma contact with the SVZ appears to be an independent prognostic factor for poor PFS. The presence of an SVZ-contacting tumor was associated with more aggressive recurrences and a higher rate of contralateral relapses. These findings suggest that this variable may be a new prognostic factor in glioblastoma.

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SMARCA4 promotes benign skin malignant transformation into melanoma through Adherens junction signal transduction

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Abstract

Purpose

Melanoma is a malignant skin tumor, and its incidence is rising. To explore the specific differences in benign and malignant melanoma at the genetic level, we performed a series of bioinformatics analyses, including differential gene analysis, co-expression analysis, enrichment analysis, and regulatory prediction.

Methods

The microarray data of benign and malignant melanocytes were downloaded from GEO, and 1917 differential genes were obtained by differential analysis (p < 0.05). Weighted gene co-expression network analysis obtained three functional barrier modules. The essential genes of each module are SMARTA4, HECA, and C1R.

Results

The results of the enrichment analysis showed that the dysfunctional module gene was mainly associated with RNA splicing and Adherens junction. Through the pivotal analysis of ncRNA, it was found that miR-448, miR-152-3p, and miR-302b-3p essentially regulate three modules, which we consider to be critical regulators. In the pivot analysis of TF, more control modules include ARID3A, E2F1, E2F3, and E2F8.

Conclusions

We believe that the regulator (miR-448, miR-152-3p, miR-302b-3p) regulates the expression of the core gene SMARCA4, which in turn affects the signal transduction of the Adherens junction. It eventually leads to the deterioration of benign skin spasms into melanoma.

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