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Meningioma surgery in patients ≥70 years of age: clinical outcome and validation of the SKALE score
(2021)
Along with increasing average life expectancy, the number of elderly meningioma patients has grown proportionally. Our aim was to evaluate whether these specific patients benefit from surgery and to investigate a previously published score for decision-making in meningioma patients (SKALE). Of 421 patients who underwent primary intracranial meningioma resection between 2009 and 2015, 71 patients were ≥70 years of age. We compared clinical data including World Health Organization (WHO) grade, MIB-1 proliferation index, Karnofsky Performance Status Scale (KPS), progression free survival (PFS) and mortality rate between elderly and all other meningioma patients. Preoperative SKALE scores (Sex, KPS, ASA score, location and edema) were determined for elderly patients. SKALE ≥8 was set for dichotomization to determine any association with outcome parameters. In 71 elderly patients (male/female 37/34) all data were available. Postoperative KPS was significantly lower in elderly patients (p < 0.0001). Pulmonary complications including pneumonia (10% vs. 3.2%; p = 0.0202) and pulmonary embolism (12.7% vs. 6%; p = 0.0209) occurred more frequently in our elderly cohort. Analyses of the Kaplan Meier curves revealed differences in three-month (5.6% vs. 0.3%; p = 0.0033), six-month (7% vs. 0.3%; p = 0.0006) and one-year mortality (8.5% vs. 0.3%; p < 0.0001) for elderly patients. Statistical analysis showed significant survival benefit in terms of one-year mortality for elderly patients with SKALE scores ≥8 (5.1 vs. 25%; p = 0.0479). According to our data, elderly meningioma patients face higher postoperative morbidity and mortality than younger patients. However, resection is reasonable for selected patients, particularly when reaching a SKALE score ≥ 8.
Background: Dysphagia is a common and severe symptom of traumatic brain injury (TBI) affecting up to 78% of patients. It is associated with pneumonia, increased morbidity and mortality. Although subdural hematoma (SDH) accounts for over 50% of TBI, the occurrence of dysphagia in this subtype has not been investigated. This study investigates the overall frequency, clinical predictors of dysphagia and functional outcome of patients with SDH associated dysphagia.
Methods: All patients presenting in author ́s institution between 2007 and 2020 with SDH were included in the study. Patients with SDH and clinical suspicion for dysphagia received a clinical swallowing assessment by a speech and language pathologist (SLP). Furthermore the severity of dysphagia was rated according to swallowing disorder scale.Functional outcome was evaluated by Glasgow outcome scale (GOS).
Results: Of 545 patients with SDH, 71 patients had dysphagia (13%). The prevalence of dysphagia was significantly lower in the surgical arm compared to the conservative arm (11.8% vs 21.8%; OR 0.23; p=0.02). Independent predictors for dysphagia were GCS <13 at admission (p<0.001; OR 4.17), cardiovascular disease (p=0.002; OR 2.29) and pneumonia (p=0.002; OR 2.88) whereas operation was a protective factor (p<0.001; OR 0.2). All patients with dysphagia improved significantly under SLP treatment from initial diagnosis to hospital discharge (p<0.01). However, patients with most severe grade of dysphagia showed no significant improvement during the clinical course. Patients with dysphagia had significantly worse outcome (GOS 1-3) compared to those without dysphagia (48.8% vs 26.4%; p<0.001).
Conclusion: Dysphagia is a frequent symptom in SDH and the early identification of dysphagia is crucial regarding initiation of treatment and functional outcome. Surgery is effective in preventing dysphagia and should be considered in high-risked patients.
Background: The most frequent therapy of hydrocephalus is the implantation of ventriculoperitoneal shunts for diverting cerebrospinal fluid from the ventricles into the peritoneum. We compared two adjustable valves, the proGAV and proGAV 2.0, for complications which resulted in revision operations.
Methods: Four hundred patients who underwent primary shunt implantation between 2014 and 2020 were analyzed for overall revision rate, one-year revision rate, revision free survival and overall survival observing patient age group, gender, etiology of hydrocephalus, implantation site, prior diversion of cerebrospinal fluid and cause of revision.
Results: All data were available of all 400 patients (female/male 208/192). Overall, 99 patients underwent revision surgery after primary implantation. ProGAV valve was implanted in 283 patients, proGAV 2.0 in 117 patients. There was no significant difference between the two shunt valves concerning revision rate (p=0.8069), one-year revision rate (p=0.9077), revision free survival (p=0.6921) and overall survival (p=0.3232). Furthermore, regarding one-year revision rate, we observed no significant difference between the two shunt valves in pediatric patients (40.7% vs 27.6%; p=0.2247). Revision operation had to be performed more frequently in pediatric patients (46.6% vs 24.8%; p=0.0093) with a significant higher number of total revisions with proGAV than proGAV 2.0 (55.9% vs. 27.6%; p=0.0110) most likely due to longer follow up in the proGAV -group.
Conclusion: According to the target variables we analyzed, aside from lifetime revision rate in pediatric patients there is no significant difference between the two shunt valves. From our subjective point of view, implantation of the newer proGAV 2.0 valve is preferable due to higher adjustment comfort for both patients and physicians.
Background: The extent of preoperative peritumoral edema in glioblastoma (GBM) has been negatively correlated with patient outcome. As several ongoing studies are investigating T-cell based immunotherapy in GBM, we conducted this study to assess whether peritumoral edema with potentially increased intracranial pressure, disrupted tissue homeostasis and reduced local blood flow has influence on immune infiltration and affects survival.
Methods: A volumetric analysis of preoperative imaging (gadolinium enhanced T1 weighted MRI sequences for tumor size and T2 weighted sequences for extent of edema (including the infiltrative zone, gliosis etc.) was conducted in 144 patients using the BrainlabÒ software. Immunohistochemical staining was analyzed for lymphocytic- (CD 3+) and myeloid (CD15+) tumor infiltration. A retrospective analysis of patient-, surgical-, and molecular characteristics was performed using medical records.
Results: The edema to tumor ratio was neither associated with progression-free nor overall survival (p=0.90, p=0.74). However, GBM patients displaying IDH-1 wildtype had significantly higher edema to tumor ratio than patients displaying an IDH-1 mutation (p=0.01). Immunohistopathological analysis did not show significant differences in lymphocytic or myeloid tumor infiltration (p=0.78, p=0.74) between these groups.
Conclusion: In our cohort, edema to tumor ratio had no significant correlation with immune infiltration and outcome. However, patients with an IDH-1wildtype GBM had a significantly higher edema to tumor ratio compared to their IDH-1 mutated peer group. Further studies are necessary to elucidate the underlying mechanisms.
Background: Research on chronic subdural hematoma (cSDH) management has primarily focused on potential recurrence after surgical evacuation. Herein, we present a novel postoperative/non-invasive treatment that includes a supervised Valsalva maneuver (SVM), which may serve to reduce SDH recurrence. Accordingly, the aims of the study were to investigate the effects of SVM on SDH recurrence rates and functional outcomes.
Methods: A prospective study was conducted from December 2016 until December 2019 at the Goethe University Hospital Frankfurt. Of the 204 adult patients with surgically treated cSDH who had subdural drains placed, 94 patients were assigned to the SVM group and 82 patients were assigned to the control group. The SVM was performed by having patients blow into a self-made SVM device at least two times/h for 12 h/day. The primary end-point was SDH recurrence rate, while secondary outcomes were morbidity and functional outcomes at 3 months of follow-up.
Results: SDH recurrence was observed in 16 of 94 patients (17%) in the SVM group, which was a significant reduction as compared with the control group, which had 24 of 82 patients (29.3%; p = 0.05) develop recurrent SDHs. Further, the infection rate (e.g., pneumonia) was significantly lower in the SVM group (1.1%) than in the control group (13.4%; p < 0.001; odds ratio [OR] 0.1). At the 3-month follow-up, 85 of 94 patients (90.4%) achieved favorable outcomes in the SVM group compared with 62 of 82 patients (75.6%) in the control group (p = 0.008; OR 3.0). Independent predictors for favorable outcome at follow-up were age (OR 0.9) and infection (OR 0.2).
Conclusion: SVM appears to be safe and effective in the post-operative management of cSDHs, reducing both recurrence rates and infections after surgical evacuation, thereby resulting in favorable outcomes at follow-up.
Background: Epileptic seizures are common clinical features in patients with acute subdural hematoma (aSDH); however, diagnostic feasibility and therapeutic monitoring remain limited. Surface electroencephalography (EEG) is the major diagnostic tool for the detection of seizures but it might be not sensitive enough to detect all subclinical or nonconvulsive seizures or status epilepticus. Therefore, we have planned a clinical trial to evaluate a novel treatment modality by perioperatively implanting subdural EEG electrodes to diagnose seizures; we will then treat the seizures under therapeutic monitoring and analyze the clinical benefit.
Methods: In a prospective nonrandomized trial, we aim to include 110 patients with aSDH. Only patients undergoing surgical removal of aSDH will be included; one arm will be treated according to the guidelines of the Brain Trauma Foundation, while the other arm will additionally receive a subdural grid electrode. The study's primary outcome is the comparison of incidence of seizures and time-to-seizure between the interventional and control arms. Invasive therapeutic monitoring will guide treatment with antiseizure drugs (ASDs). The secondary outcome will be the functional outcome for both groups as assessed via the Glasgow Outcome Scale and modified Rankin Scale both at discharge and during 6 months of follow-up. The tertiary outcome will be the evaluation of chronic epilepsy within 2-4 years of follow-up.
Discussion: The implantation of a subdural EEG grid electrode in patients with aSDH is expected to be effective in diagnosing seizures in a timely manner, facilitating treatment with ASDs and monitoring of treatment success. Moreover, the occurrence of epileptiform discharges prior to the manifestation of seizure patterns could be evaluated in order to identify high-risk patients who might benefit from prophylactic treatment with ASDs.
Trial registration: ClinicalTrials.gov identifier no. NCT04211233.
Background: The angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact of long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and functionally important endothelial lncRNAs.
Methods: Epigenetically controlled lncRNAs in human umbilical vein endothelial cells were searched by exon-array analysis after knockdown of the histone demethylase JARID1B. Molecular mechanisms were investigated by RNA pulldown and immunoprecipitation, mass spectrometry, microarray, several knockdown approaches, CRISPR-Cas9, assay for transposase-accessible chromatin sequencing, and chromatin immunoprecipitation in human umbilical vein endothelial cells. Patient samples from lung and tumors were studied for MANTIS expression.
Results: A search for epigenetically controlled endothelial lncRNAs yielded lncRNA n342419, here termed MANTIS, as the most strongly regulated lncRNA. Controlled by the histone demethylase JARID1B, MANTIS was downregulated in patients with idiopathic pulmonary arterial hypertension and in rats treated with monocrotaline, whereas it was upregulated in carotid arteries of Macaca fascicularis subjected to atherosclerosis regression diet, and in endothelial cells isolated from human glioblastoma patients. CRISPR/Cas9-mediated deletion or silencing of MANTIS with small interfering RNAs or GapmeRs inhibited angiogenic sprouting and alignment of endothelial cells in response to shear stress. Mechanistically, the nuclear-localized MANTIS lncRNA interacted with BRG1, the catalytic subunit of the switch/sucrose nonfermentable chromatin-remodeling complex. This interaction was required for nucleosome remodeling by keeping the ATPase function of BRG1 active. Thereby, the transcription of key endothelial genes such as SOX18, SMAD6, and COUP-TFII was regulated by ensuring efficient RNA polymerase II machinery binding.
Conclusion: MANTIS is a differentially regulated novel lncRNA facilitating endothelial angiogenic function.
Purpose: In patients with pyogenic spondylodiscitis, surgery is considered the treatment of choice to conduct proper debridement, stabilise the spine and avoid extended bed rest, which in turn is a risk factor for complications such as deep vein thrombosis and pulmonary embolism. Methods: We conducted a retrospective clinical study with analysis of a group of 99 patients who had undergone treatment for pyogenic discitis at our institution between June 2012 and August 2017. Included parameters were age, sex, disease pattern, the presence of deep vein thrombosis, resuscitation, in-hospital mortality, present anticoagulation, preexisting comorbidities, tobacco abuse, body mass index, microbiological germ detection and laboratory results. Results: Among the analysed cohort, 12% of the treated patients for pyogenic spondylodiscitis suffered from a radiologically confirmed pulmonary embolism. Coronary heart disease (p < 0.01), female sex (p < 0.01), anticoagulation at admission (p < 0.01) and non-O blood type (p < 0.001) were associated with development of pulmonary embolism. Pulmonary embolism was significantly associated with resuscitation (p < 0.005) and deep vein thrombosis (p < 0.001). Neurosurgery was not associated with increased risk for pulmonary embolism compared to conservative-treated patients (p > 0.05). Conclusion: Surgery for pyogenic spondylodiscitis was not associated with an elevated risk of pulmonary embolism in our analysis. However, we describe several risk factors for pulmonary embolism in this vulnerable cohort. Prospective studies are necessary to improve prevention and postoperative management in patients with pyogenic spondylodiscitis.
Glioblastoma (GBM) is a cancer type with high thrombogenic potential and GBM patients are therefore at a particularly high risk for thrombotic events. To date, only limited data on anticoagulation management after pulmonary embolism (PE) in GBM is available and the sporadic use of DOACs remains off-label. A retrospective cohort analysis of patients with GBM and postoperative, thoracic CT scan confirmed PE was performed. Clinical course, follow-up at 6 and 12 months and the overall survival (OS) were evaluated using medical charts and neuroradiological data. Out of 584 GBM patients, 8% suffered from postoperative PE. Out of these, 30% received direct oral anticoagulants (DOACs) and 70% low-molecular-weight heparin (LMWH) for therapeutic anticoagulation. There was no significant difference in major intracranial hemorrhage (ICH), re-thrombosis, or re-embolism between the two cohorts. Although statistically non-significant, a tendency to reduced mRS at 6 and 12 months was observed in the LMWH cohort. Furthermore, patients receiving DOACs had a statistical benefit in OS. In our analysis, DOACs showed a satisfactory safety profile in terms of major ICH, re-thrombosis, and re-embolism compared to LMWH in GBM patients with postoperative PE. Prospective, randomized trials are urgent to evaluate DOACs for therapeutic anticoagulation in GBM patients with PE.
Background: Glioblastoma (GBM) is a cancer type with high thrombogenic potential and GBM patients are therefore at a particularly high risk for thrombotic events. To date only limited data on anticoagulation management after pulmonary embolism (PE) in GBM is available and the sporadic use of DOACs remains off-label.
Methods: A retrospective cohort analysis of patients with GBM and postoperative, thoracic CT-scan confirmed, PE was performed. Clinical course, follow-up at 6 and 12 months and the overall survival (OS) were evaluated using medical charts and neuroradiological data.
Results: Out of 584 GBM patients, 8% suffered from postoperative PE. Out of theses, 30% received direct oral anticoagulants (DOACs) and 70% low-molecular-weight heparin (LMWH) for therapeutic anticoagulation. There was no significant difference in major intracranial hemorrhage (ICH), re-thrombosis or re-embolism between the two cohorts. Although statistically non-significant, a tendency to reduced mRS at 6- and 12 months was observed in the LMWH cohort. Furthermore, patients receiving DOACs had a statistical benefit in OS.
Conclusion: In our analysis DOACs showed a satisfactory safety profile in terms of major ICH, re-thrombosis and re-embolism compared to LMWH in GBM patients with postoperative PE. Prospective, randomized trials are urgent to evaluate DOACs for therapeutic anticoagulation in GBM patients with PE.
