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BACKGROUND AND OBJECTIVES: Studying malpractice claims is important to improve quality of health care and patient safety and to educate the individual healthcare providers. The objective of this study was to describe characteristics of neurosurgical claims in the Netherlands. METHODS: A nationwide retrospective observational study of neurosurgery-related claims closed by Centramed and MediRisk, 2 major insurance companies in the Netherlands, was performed. Relevant data, including type of neurosurgical pathology, theme and category of the claim, type and severity of injury, outcome, and financial burden, were extracted from anonymized claim files. The estimated annual risk was used to determine the risk for claims by adjusting for the number of annually practicing neurosurgeons in the Netherlands. RESULTS: A total of 388 claims against neurosurgeons were closed between 2007 and 2021. Liability was denied in a slight majority of claims (n = 230; 59%). The total burden during this period was 6 165 000 (amount paid out to patients: 5 497 000). The estimated annual risk per Dutch neurosurgeon for a claim was 15.5%, meaning 1 claim per 6.5 years. The case-level analysis of 238 available anonymized claims revealed that most claims were related to spinal pathology (81.5%), followed by cranial pathology (10.9%) and peripheral nerve (7.6%). The motivations for filing claims were mostly related to alleged surgical (56.3%) or diagnostic errors (22.3%). Most of these claims were denied (151/238; 63.4%), and fewer were settled (42/238; 17.6%), sustained (31/238; 13.0%), or closed without final decision (14/238; 5.9%). CONCLUSION: Neurosurgery-related malpractice claims primarily involved spinal pathology and were mostly related to alleged treatment errors. Most claims did not result in compensation because there seemed to be no liability or culpable injury. However, the annual risk for a claim for Dutch neurosurgeons is considerable.
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OBJECTIVE: Chronic subdural hematoma (CSDH) is a common neurological condition and is typically treated with burr hole craniostomy. Nevertheless, conservative treatment may lead to spontaneous hematoma resolution in some patients. This study aims to describe the characteristics of patients who were treated conservatively without the eventual need for additional treatment. METHODS: Data were retrospectively collected from patients who were primarily treated conservatively in three hospitals in the Netherlands from 2008 to 2018. The Primary outcome was the nonnecessity of additional treatment within 3 months after the initial CSDH diagnosis. We used univariable and multivariable logistic regression analyses to identify factors associated with not receiving additional treatment. RESULTS: In this study, 83 patients were included and 61 patients (73%) did not receive additional treatment within 3 months. Upon first presentation, the patients had a Markwalder Grading Scale score (MGS) of 0 (n = 5, 6%), 1 (n = 43, 52%), and 2 (n = 35, 42%). Additional treatment was less often received by patients with smaller hematoma volumes (adjusted odds ratio [aOR] 0.78 per 10 mL; 95% confidence interval [CI] 0.64-0.92). Patients using antithrombotic medication also received less additional treatment, but this association was not significant (aOR 2.02; 95% CI 0.61-6.69). CONCLUSIONS: Three quarters of the initially conservatively treated CSDH patients do not receive additional management. Typically, these patients have smaller hematoma volumes. Further, prospective research is needed to distinguish which patients require surgical intervention and in whom primary conservative treatment suffices.
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Tratamento Conservador , Hematoma Subdural Crônico , Humanos , Hematoma Subdural Crônico/terapia , Masculino , Feminino , Tratamento Conservador/métodos , Estudos Retrospectivos , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Países BaixosRESUMO
PURPOSE: IDH-mutant glioma are classified as oligodendroglioma or astrocytoma on the basis of 1p19q-codeletion. Whether prognostic factors are similar between these tumor types is not well understood. EXPERIMENTAL DESIGN: Retrospective cohort study. Molecular characterization was performed with targeted next-generation sequencing. Tumor volumes were calculated using semi-automatic 3D segmentation on all pre- and postoperative MRI-scans. Overall survival was assessed with Cox proportional hazards model. RESULTS: 383 patients with newly diagnosed IDH-mutant glioma were followed-up for a median of 7.2 years. Grade 3 and grade 4 patients had significantly lower Karnofsky performance, with tumors having more contrast-enhancement. Patients also received more aggressive post-surgery treatment. Postoperative tumor volume is significantly and independently associated with survival (HR per cm3 1.19, 95% CI 1.03 - 1.39) in IDH-mutant glioma. Separate analysis of oligodendroglioma and astrocytoma showed a significant association of postoperative tumor volume in astrocytoma, but not in oligodendroglioma. Higher age and histological tumor grade were associated with worse survival in patients with oligodendroglioma, but not with astrocytoma. CONCLUSIONS: Our data support an initial strategy of extensive resection in both oligodendroglioma and astrocytoma patients. Other important prognostic factors differ between these tumor types, urging researchers and clinicians to keep treating these tumors as separate entities.
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BACKGROUND: Craniosynostosis, a congenital condition characterized by the premature fusion of cranial sutures, necessitates objective methods for evaluating cranial morphology to enhance patient treatment. Current subjective assessments often lead to inconsistent outcomes. This study introduces a novel, quantitative approach to classify craniosynostosis and measure its severity. METHODS: An artificial neural network was trained to classify normocephalic, trigonocephalic, and scaphocephalic head shapes based on a publicly available dataset of synthetic 3D head models. Each 3D model was converted into a low-dimensional shape representation based on the distribution of normal vectors, which served as the input for the neural network, ensuring complete patient anonymity and invariance to geometric size and orientation. Explainable AI methods were utilized to highlight significant features when making predictions. Additionally, the Feature Prominence (FP) score was introduced, a novel metric that captures the prominence of distinct shape characteristics associated with a given class. Its relationship with clinical severity scores was examined using the Spearman Rank Correlation Coefficient. RESULTS: The final model achieved excellent test accuracy in classifying the different cranial shapes from their low-dimensional representation. Attention maps indicated that the network's attention was predominantly directed toward the parietal and temporal regions, as well as toward the region signifying vertex depression in scaphocephaly. In trigonocephaly, features around the temples were most pronounced. The FP score showed a strong positive monotonic relationship with clinical severity scores in both scaphocephalic (ρ = 0.83, p < 0.001) and trigonocephalic (ρ = 0.64, p < 0.001) models. Visual assessments further confirmed that as FP values rose, phenotypic severity became increasingly evident. CONCLUSION: This study presents an innovative and accessible AI-based method for quantifying cranial shape that mitigates the need for adjustments due to age-specific size variations or differences in the spatial orientation of the 3D images, while ensuring complete patient privacy. The proposed FP score strongly correlates with clinical severity scores and has the potential to aid in clinical decision-making and facilitate multi-center collaborations. Future work will focus on validating the model with larger patient datasets and exploring the potential of the FP score for broader applications. The publicly available source code facilitates easy implementation, aiming to advance craniofacial care and research.
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BACKGROUND AND OBJECTIVES: Guideline recommendations for surgical management of traumatic epidural hematomas (EDHs) do not directly address EDHs that co-occur with other intracranial hematomas; the relative rates of isolated vs nonisolated EDHs and guideline adherence are unknown. We describe characteristics of a contemporary cohort of patients with EDHs and identify factors influencing acute surgery. METHODS: This research was conducted within the longitudinal, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury cohort study which prospectively enrolled patients with traumatic brain injury from 65 hospitals in 18 European countries from 2014 to 2017. All patients with EDH on the first scan were included. We describe clinical, imaging, management, and outcome characteristics and assess associations between site and baseline characteristics and acute EDH surgery, using regression modeling. RESULTS: In 461 patients with EDH, median age was 41 years (IQR 24-56), 76% were male, and median EDH volume was 5 cm3 (IQR 2-20). Concomitant acute subdural hematomas (ASDHs) and/or intraparenchymal hemorrhages were present in 328/461 patients (71%). Acute surgery was performed in 99/461 patients (21%), including 70/86 with EDH volume ≥30 cm3 (81%). Larger EDH volumes (odds ratio [OR] 1.19 [95% CI 1.14-1.24] per cm3 below 30 cm3), smaller ASDH volumes (OR 0.93 [95% CI 0.88-0.97] per cm3), and midline shift (OR 6.63 [95% CI 1.99-22.15]) were associated with acute surgery; between-site variation was observed (median OR 2.08 [95% CI 1.01-3.48]). Six-month Glasgow Outcome Scale-Extended scores ≥5 occurred in 289/389 patients (74%); 41/389 (11%) died. CONCLUSION: Isolated EDHs are relatively infrequent, and two-thirds of patients harbor concomitant ASDHs and/or intraparenchymal hemorrhages. EDHs ≥30 cm3 are generally evacuated early, adhering to Brain Trauma Foundation guidelines. For heterogeneous intracranial pathology, surgical decision-making is related to clinical status and overall lesion burden. Further research should examine the optimal surgical management of EDH with concomitant lesions in traumatic brain injury, to inform updated guidelines.
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The axons of neocortical pyramidal neurons are frequently myelinated. Heterogeneity in the topography of axonal myelination in the cerebral cortex has been attributed to a combination of electrophysiological activity, axonal morphology, and neuronal-glial interactions. Previously, we showed that axonal segment length and caliber are critical local determinants of fast-spiking interneuron myelination. However, the factors that determine the myelination of individual axonal segments along neocortical pyramidal neurons remain largely unexplored. Here, we used structured illumination microscopy to examine the extent to which axonal morphology is predictive of the topography of myelination along neocortical pyramidal neurons. We identified critical thresholds for axonal caliber and interbranch distance that are necessary, but not sufficient, for myelination of pyramidal cell axons in mouse primary somatosensory cortex (S1). Specifically, we found that pyramidal neuron axonal segments with a caliber < 0.24 µm or interbranch distance < 18.10 µm are rarely myelinated. Moreover, we further confirmed that these findings in mice are similar for human neocortical pyramidal cell myelination (caliber < 0.25 µm, interbranch distance < 19.00 µm), suggesting that this mechanism is evolutionarily conserved. Taken together, our findings suggest that axonal morphology is a critical correlate of the topography and cell-type specificity of neocortical myelination.
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Neocórtex , Células Piramidais , Humanos , Animais , Camundongos , Axônios , Bainha de Mielina , InterneurôniosRESUMO
BACKGROUND: The health-related quality of life (HRQoL) and cognition are important indicators for the quality of survival in patients with high-grade glioma (HGG). However, data on long-term survivors and their caregivers are scarce. We aim to investigate the interaction between cognition and HRQoL in long-term survivors, their caregivers' evaluations, and the effect on caregiver strain and burden. METHODS: 21 long-term HGG (8 WHO grade III and 13 WHO grade IV) survivors (survival ≥ 5 years) and 15 caregivers were included. Cognition (verbal memory, attention, executive functioning, and language), HRQoL, anxiety and depression, caregiver strain, and caregiver burden were assessed with standardized measures. Questionnaires were completed by patients and/or their caregivers. RESULTS: Mean survival was 12 years (grade III) and 8 years (grade IV). Cognition was significantly impaired with a large individual variety. Patients' general HRQoL was not impaired but all functioning scales were deviant. Patient-proxy agreement was found in most HRQoL subscales. Three patients (14%) showed indications of anxiety or depression. One-third of the caregivers reported a high caregiver strain or a high burden. Test scores for attention, executive functioning, language, and/or verbal memory were correlated with perceived global health status, cognitive functioning, and/or communication deficits. Caregiver burden was not related to cognitive deficits. CONCLUSIONS: In long-term HGG survivors maintained HRQoL seems possible even when cognition is impaired in a large variety at the individual level. A tailored approach is therefore recommended to investigate the cognitive impairments and HRQoL in patients and the need for patient and caregiver support.
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Glioma , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Cuidadores/psicologia , Glioma/psicologia , Inquéritos e Questionários , Cognição , Sobreviventes/psicologiaRESUMO
OBJECTIVE: Intraoperative Doppler ultrasound imaging of human brain vasculature is an emerging neuro-imaging modality that offers vascular brain mapping with unprecedented spatiotemporal resolution. At present, however, access to the human brain using Doppler Ultrasound is only possible in this intraoperative context, posing a significant challenge for validation of imaging techniques. This challenge necessitates the development of realistic flow phantoms outside of the neurosurgical operating room as external platforms for testing hardware and software. An ideal ultrasound flow phantom should provide reference-like values in standardized topologies such as a slanted pipe, and allow for measurements in structures closely resembling vascular morphology of actual patients. Additionally, the phantom should be compatible with other clinical cerebrovascular imaging modalities. To meet these criteria, we developed and validated a versatile, multimodal MRI- and ultrasound Doppler phantom. METHODS: Our approach incorporates the latest advancements in phantom research using tissue-mimicking material and 3D-printing with water-soluble resin to create wall-less patient-specific lumens, compatible for ultrasound and MRI. RESULTS: We successfully produced three distinct phantoms: a slanted pipe, a y-shape phantom representing a bifurcating vessel and an arteriovenous malformation (AVM) derived from clinical Digital Subtraction Angiography (DSA)-data of the brain. We present 3D ultrafast power Doppler imaging results from these phantoms, demonstrating their ability to mimic complex flow patterns as observed in the human brain. Furthermore, we showcase the compatibility of our phantom with Magnetic Resonance Imaging (MRI). CONCLUSION: We developed an MRI- and Doppler Ultrasound-compatible flow-phantom using customizable, water-soluble resin prints ranging from geometrical forms to patient-specific vasculature.
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Imageamento por Ressonância Magnética , Imagens de Fantasmas , Ultrassonografia Doppler , Humanos , Imageamento por Ressonância Magnética/métodos , Ultrassonografia Doppler/métodos , Circulação Cerebrovascular/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Desenho de EquipamentoRESUMO
With increasing interest in 3D photogrammetry, diverse methods have been developed for craniofacial shape analysis in craniosynostosis patients. This review provides an overview of these methods and offers recommendations for future studies. A systematic literature search was used to identify publications on 3D photogrammetry analyses in craniosynostosis patients until August 2023. Inclusion criteria were original research reporting on 3D photogrammetry analyses in patients with craniosynostosis and written in English. Sixty-three publications that had reproducible methods for measuring cranial, forehead, or facial shape were included in the systematic review. Cranial shape changes were commonly assessed using heat maps and curvature analyses. Publications assessing the forehead utilized volumetric measurements, angles, ratios, and mirroring techniques. Mirroring techniques were frequently used to determine facial asymmetry. Although 3D photogrammetry shows promise, methods vary widely between standardized and less conventional measurements. A standardized protocol for the selection and documentation of landmarks, planes, and measurements across the cranium, forehead, and face is essential for consistent clinical and research applications.
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Oncolytic virus (OV) clinical trials have demonstrated remarkable efficacy in subsets of patients with glioblastoma (GBM). However, the lack of tools to predict this response hinders the advancement of a more personalized application of OV therapy. In this study, we characterize an ex vivo co-culture system designed to examine the immune response to OV infection of patient-derived GBM neurospheres in the presence of autologous peripheral blood mononuclear cells (PBMCs). Co-culture conditions were optimized to retain viability and functionality of both tumor cells and PBMCs, effectively recapitulating the well-recognized immunosuppressive effects of GBM. Following OV infection, we observed elevated secretion of pro-inflammatory cytokines and chemokines, including interferon γ, tumor necrosis factor α, CXCL9, and CXCL10, and marked changes in immune cell activation markers. Importantly, OV treatment induced unique patient-specific immune responses. In summary, our co-culture platform presents an avenue for personalized screening of viro-immunotherapies in GBM, offering promise as a potential tool for future patient stratification in OV therapy.
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Glioblastoma , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Leucócitos Mononucleares/patologia , ImunoterapiaRESUMO
Glioma patients often suffer from deficits in language and executive functioning. Performance in verbal fluency (generating words within one minute according to a semantic category-category fluency, or given letter-letter fluency) is typically impaired in this patient group. While both language and executive functioning play a role in verbal fluency, the relative contribution of both domains remains unclear. We aim to retrospectively investigate glioma patients' performance on verbal and nonverbal fluency and to explore the influence of language and executive functioning on verbal fluency. Sixty-nine adults with gliomas in eloquent areas underwent a neuropsychological test battery (verbal fluency, nonverbal fluency, language, and executive functioning tests) before surgery (T1) and a subgroup of 31 patients also at three (T2) and twelve months (T3) after surgery. Preoperatively, patients were impaired in all verbal fluency tasks and dissociations were found based on tumour location. In contrast, nonverbal fluency was intact. Different language and executive functioning tests predicted performance on category fluency animals and letter fluency, while no significant predictors for category fluency professions were found. The longitudinal results indicated that category fluency professions deteriorated after surgery (T1-T2, T1-T3) and that nonverbal fluency improved after surgery (T1-T3, T2-T3). Verbal fluency performance can provide information on different possible underlying deficits in language and executive functioning in glioma patients, depending on verbal fluency task selection. Efficient task (order) selection can be based on complexity. Category fluency professions can be selected to detect more permanent long-term deficits.
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Glioma , Comportamento Verbal , Adulto , Humanos , Estudos Retrospectivos , Idioma , Função Executiva , Glioma/complicações , Glioma/cirurgia , Testes NeuropsicológicosRESUMO
BACKGROUND: Standardized Mortality Ratios (SMRs) are case-mix adjusted mortality rates per hospital and are used to evaluate quality of care. However, acute care is increasingly organized on a regional level, with more severe patients admitted to specialized hospitals. We hypothesize that the current case-mix adjustment insufficiently captures differences in case-mix between non-specialized and specialized hospitals. We aim to improve the SMR by adding proxies of disease severity to the model and by calculating a regional SMR (RSMR) for acute cerebrovascular disease (CVD) and myocardial infarction (MI). METHODS: We used data from the Dutch National Basic Registration of Hospital Care. We selected all admissions from 2016 to 2018. SMRs and RSMRs were calculated by dividing the observed in-hospital mortality by the expected in-hospital mortality. The expected in-hospital mortality was calculated using logistic regression with adjustment for age, sex, socioeconomic status, severity of main diagnosis, urgency of admission, Charlson comorbidity index, place of residence before admission, month/year of admission, and in-hospital mortality as outcome. RESULTS: The IQR of hospital SMRs of CVD was 0.85-1.10, median 0.94, with higher SMRs for specialized hospitals (median 1.12, IQR 1.00-1.28, 71%-SMR > 1) than for non-specialized hospitals (median 0.92, IQR 0.82-1.07, 32%-SMR > 1). The IQR of RSMRs was 0.92-1.09, median 1.00. The IQR of hospital SMRs of MI was 0.76-1.14, median 0.98, with higher SMRs for specialized hospitals (median 1.00, IQR 0.89-1.25, 50%-SMR > 1 versus median 0.94, IQR 0.74-1.11, 44%-SMR > 1). The IQR of RSMRs was 0.90-1.08, median 1.00. Adjustment for proxies of disease severity mostly led to lower SMRs of specialized hospitals. CONCLUSION: SMRs of acute regionally organized diseases do not only measure differences in quality of care between hospitals, but merely measure differences in case-mix between hospitals. Although the addition of proxies of disease severity improves the model to calculate SMRs, real disease severity scores would be preferred. However, such scores are not available in administrative data. As a consequence, the usefulness of the current SMR as quality indicator is very limited. RSMRs are potentially more useful, since they fit regional organization and might be a more valid representation of quality of care.
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Infarto do Miocárdio , Humanos , Mortalidade Hospitalar , Hospitais , Hospitais Especializados , HospitalizaçãoRESUMO
BACKGROUND: This study evaluated the health-related quality of life (HR-QoL) in patients with sagittal synostosis (SS), and the influence of frequent headaches and surgical techniques on the HR-QoL. METHOD: Patients with SS aged 8 to 18 years were invited to participate between June 2016 and February 2017. The Child Health Questionnaire was used to assess the HR-QoL. A detailed questionnaire was used to assess the severity of headache symptoms. The control group consisted of 353 school children aged 5 to 14 years. RESULTS: In all, 95 parents of patients with SS were invited to participate, of whom 68 (71.6%) parents completed the CHQ-PF50. The mean age of the participating patients was 12.4 years (10.8 to 14.2). The Psychosocial- and Physical summary of the patients with SS was similar to the general population. In the distinct CHQ scales, "Family cohesion" ( P =0.02) was higher, and "Mental health" ( P =0.05) was lower compared with the general population. The type and timing of surgery did not affect the HR-QoL. Thirty-two patients (47.1%) reported having headache complaints at least once a month. The CHQ scores of SS patients with frequent headaches had a significantly lower score of mild to large effect than those without headaches. CONCLUSION: Patients with SS have a slightly lower to similar HR-QoL compared with the general population. In all, 47.1% of SS patients have frequent headaches, resulting in lower average HR-QoL. The type and timing of surgery did not affect the results. Clinicians should be aware of lower HR-QoL in some subgroups of patients with SS.
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Craniossinostoses , Qualidade de Vida , Humanos , Criança , Adolescente , Nível de Saúde , Inquéritos e Questionários , Cefaleia , Craniossinostoses/cirurgiaRESUMO
BACKGROUND: Patient-derived glioma stem-like cells (GSCs) have become the gold-standard in neuro-oncological research; however, it remains to be established whether loss of in situ microenvironment affects the clinically-predictive value of this model. We implemented a GSC monolayer system to investigate in situ-in vitro molecular correspondence and the relationship between in vitro and patient response to temozolomide (TMZ). METHODS: DNA/RNA-sequencing was performed on 56 glioblastoma tissues and 19 derived GSC cultures. Sensitivity to TMZ was screened across 66 GSC cultures. Viability readouts were related to clinical parameters of corresponding patients and whole-transcriptome data. RESULTS: Tumour DNA and RNA sequences revealed strong similarity to corresponding GSCs despite loss of neuronal and immune interactions. In vitro TMZ screening yielded three response categories which significantly correlated with patient survival, therewith providing more specific prediction than the binary MGMT marker. Transcriptome analysis identified 121 genes related to TMZ sensitivity of which 21were validated in external datasets. CONCLUSION: GSCs retain patient-unique hallmark gene expressions despite loss of their natural environment. Drug screening using GSCs predicted patient response to TMZ more specifically than MGMT status, while transcriptome analysis identified potential biomarkers for this response. GSC drug screening therefore provides a tool to improve drug development and precision medicine for glioblastoma.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Biomarcadores , DNA/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
INTRODUCTION: Clarifying the effect of music on pain endurance in an experimental design could aid in how music should be applied during both surgical and non-surgical interventions. This study aims to investigate the effect of music on pain endurance and the involvement of the sympathetic adrenomedullary axis (SAM) and the hypothalamic-pituitary-adrenocortical axis (HPA). MATERIALS AND METHODS: In this randomized controlled trial all participants received increasing electric stimuli through their non-dominant index finger. Participants were randomly assigned to the music group (M) receiving a 20-minute music intervention or control group (C) receiving a 20-minute resting period. The primary outcome was pain endurance, defined as amount milliampere tolerated. Secondary outcomes included anxiety level, SAM-axis based on heart rate variability (HRV) and salivary alpha-amylase, and HPA-axis activity based on salivary cortisol. RESULTS: In the intention-to-treat analysis, the effect of music on pain tolerance did not statistically differ between the M and C group. A significant positive effect of music on pain endurance was noted after excluding participants with a high skin impedance (p = 0.013, CI 0.35; 2.85). Increased HRV was observed in the M-group compared to the C-group for SDNN (B/95%CI:13.80/2.22;25.39, p = 0.022), RMSSD (B/95%CI:15.97/1.64;30.31, p = 0.032), VLF (B/95%CI:212.08/60.49;363.67, p = 0.008) and HF (B/95%CI:821.15/150.78;1491.52, p = 0.0190). No statistical significance was observed in other secondary outcomes. CONCLUSIONS: The effect of the music intervention on pain endurance was not statistically significant in the intention-to-treat analysis. The subgroup analyses revealed an increase in pain endurance in the music group after correcting for skin impedance, which could be attributed to increased parasympathetic activation.
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Musicoterapia , Música , Humanos , Dor , Frequência Cardíaca/fisiologia , Limiar da Dor , Ansiedade/terapiaRESUMO
BACKGROUND: This Phase 1 study evaluates the intra- and peritumoral administration by convection enhanced delivery (CED) of human recombinant Bone Morphogenetic Protein 4 (hrBMP4) - an inhibitory regulator of cancer stem cells (CSCs) - in recurrent glioblastoma. METHODS: In a 3 + 3 dose escalation design, over four to six days, fifteen recurrent glioblastoma patients received, by CED, one of five doses of hrBMP4 ranging from 0·5 to 18 mg. Patients were followed by periodic physical, neurological, blood testing, magnetic resonance imaging (MRI) and quality of life evaluations. The primary objective of this first-in-human study was to determine the safety, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of hrBMP4. Secondary objectives were to assess potential efficacy and systemic exposure to hrBMP4 upon intracerebral infusion. RESULTS: Intra- and peritumoral infusion of hrBMP4 was safe and well-tolerated. We observed no serious adverse events related to this drug. Neither MTD nor DLT were reached. Three patients had increased hrBMP4 serum levels at the end of infusion, which normalized within 4 weeks, without sign of toxicity. One patient showed partial response and two patients a complete (local) tumor response, which was maintained until the most recent follow-up, 57 and 30 months post-hrBMP4. Tumor growth was inhibited in areas permeated by hrBMP4. CONCLUSION: Local delivery of hrBMP4 in and around recurring glioblastoma is safe and well-tolerated. Three patients responded to the treatment. A complete response and long-term survival occurred in two of them. This warrants further clinical studies on this novel treatment targeting glioblastoma CSCs. TRIAL REGISTRATION: ClinicaTrials.gov identifier: NCT02869243.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Qualidade de Vida , Proteína Morfogenética Óssea 4/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Encefálicas/patologia , Dose Máxima TolerávelRESUMO
BACKGROUND: The role of glucocorticoids without surgical evacuation in the treatment of chronic subdural hematoma is unclear. METHODS: In this multicenter, open-label, controlled, noninferiority trial, we randomly assigned symptomatic patients with chronic subdural hematoma in a 1:1 ratio to a 19-day tapering course of dexamethasone or to burr-hole drainage. The primary end point was the functional outcome at 3 months after randomization, as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]). Noninferiority was defined by a lower limit of the 95% confidence interval of the odds ratio for a better functional outcome with dexamethasone than with surgery of 0.9 or more. Secondary end points included scores on the Markwalder Grading Scale of symptom severity and on the Extended Glasgow Outcome Scale. RESULTS: From September 2016 through February 2021, we enrolled 252 patients of a planned sample size of 420; 127 were assigned to the dexamethasone group and 125 to the surgery group. The mean age of the patients was 74 years, and 77% were men. The trial was terminated early by the data and safety monitoring board owing to safety and outcome concerns in the dexamethasone group. The adjusted common odds ratio for a lower (better) score on the modified Rankin scale at 3 months with dexamethasone than with surgery was 0.55 (95% confidence interval, 0.34 to 0.90), which failed to show noninferiority of dexamethasone. The scores on the Markwalder Grading Scale and Extended Glasgow Outcome Scale were generally supportive of the results of the primary analysis. Complications occurred in 59% of the patients in the dexamethasone group and 32% of those in the surgery group, and additional surgery was performed in 55% and 6%, respectively. CONCLUSIONS: In a trial that involved patients with chronic subdural hematoma and that was stopped early, dexamethasone treatment was not found to be noninferior to burr-hole drainage with respect to functional outcomes and was associated with more complications and a greater likelihood of later surgery. (Funded by the Netherlands Organization for Health Research and Development and others; DECSA EudraCT number, 2015-001563-39.).
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Craniectomia Descompressiva , Dexametasona , Glucocorticoides , Hematoma Subdural Crônico , Idoso , Feminino , Humanos , Masculino , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Drenagem/efeitos adversos , Drenagem/métodos , Escala de Resultado de Glasgow , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Hematoma Subdural Crônico/tratamento farmacológico , Hematoma Subdural Crônico/cirurgiaRESUMO
OBJECTIVES: Delirium is a serious complication following neurosurgical procedures. We hypothesise that the beneficial effect of music on a combination of delirium-eliciting factors might reduce delirium incidence following neurosurgery and subsequently improve clinical outcomes. DESIGN: Prospective randomised controlled trial. SETTING: Single centre, conducted at the neurosurgical department of the Erasmus Medical Center, Rotterdam, the Netherlands. PARTICIPANTS: Adult patients undergoing craniotomy were eligible. INTERVENTIONS: Patients in the intervention group received preferred recorded music before, during and after the operation until day 3 after surgery. Patients in the control group were treated according to standard of clinical care. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was presence or absence of postoperative delirium within the first 5 postoperative days measured with the Delirium Observation Screening Scale (DOSS) and, in case of a daily mean score of 3 or higher, a psychiatric evaluation with the latest Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Secondary outcomes included anxiety, heart rate variability (HRV), depth of anaesthesia, delirium severity and duration, postoperative complications, length of stay and location of discharge. RESULTS: We enrolled 189 patients (music=95, control=94) from July 2020 through September 2021. Delirium, as assessed by the DOSS, was less common in the music (n=11, 11.6%) than in the control group (n=21, 22.3%, OR:0.49, p=0.048). However, after DSM-5 confirmation, differences in delirium were not significant (4.2% vs 7.4%, OR:0.47, p=0.342). Moreover, music increased the HRV (root mean square of successive differences between normal heartbeats, p=0.012). All other secondary outcomes were not different between groups. CONCLUSION: Our results support the efficacy of music in reducing the incidence of delirium after craniotomy, as found with DOSS but not after DSM-5 confirmation, substantiated by the effect of music on preoperative autonomic tone. Delirium screening tools should be validated and the long-term implications should be evaluated after craniotomy. TRIAL REGISTRATION NUMBER: Trialregister.nl: NL8503 and ClinicalTrials.gov: NCT04649450.
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Delírio , Música , Neurocirurgia , Adulto , Humanos , Estudos Prospectivos , Delírio/etiologia , Delírio/prevenção & controle , Delírio/diagnóstico , Procedimentos Neurocirúrgicos/efeitos adversosRESUMO
INTRODUCTION: We performed a systematic review and meta-analysis on the incidence of secondary tethered spinal cord (TSC) between prenatal and postnatal closure in patients with MMC. The objectives was to understand the incidence of secondary TSC after prenatal surgery for MMC compared to postnatal surgery for MMC. MATERIAL AND METHODS: On May 4, 2023, a systematic search was conducted in Medline, Embase, and the Cochrane Library to gather relevant data. Primary studies focusing on repair type, lesion level, and TSC were included, while non-English or non-Dutch reports, case reports, conference abstracts, editorials, letters, comments, and animal studies were excluded. Two reviewers assessed the included studies for bias risk, following PRISMA guidelines. TSC frequency in MMC closure types was determined, and the relationship between TSC occurrence and closure technique was analyzed using relative risk and Fisher's exact test. Subgroup analysis revealed relative risk differences based on study designs and follow-up periods. A total of ten studies, involving 2,724 patients, were assessed. Among them, 2,293 patients underwent postnatal closure, while 431 received prenatal closure for the MMC defect. In the prenatal closure group, TSC occurred in 21.6% (n = 93), compared to 18.8% (n = 432) in the postnatal closure group. The relative risk (RR) of TSC in patients with prenatal MMC closure versus postnatal MMC closure was 1.145 (95%CI 0.939 to 1.398). Fisher's exact test indicated a statistically non-significant association (p = 0.106) between TSC and closure technique. When considering only RCT and controlled cohort studies, the overall RR for TSC was 1.308 (95%CI 1.007 to 1.698) with a non-significant association (p = .053). For studies focusing on children up until early puberty (maximum 12 years follow-up), the RR for tethering was 1.104 (95%CI 0.876 to 1.391), with a non-significant association (p = 0.409). CONCLUSION AND DISCUSSION: This review found no significant increase in relative risk of TSC between prenatal and postnatal closure in MMC patients, but a trend of increased TSC in the prenatal group. More long-term data on TSC after fetal closure is needed for better counseling and outcomes in MMC.
Assuntos
Meningomielocele , Humanos , Feminino , Gravidez , Meningomielocele/cirurgia , Feto , Procedimentos Neurocirúrgicos/métodos , Incidência , Medula EspinalRESUMO
This study aimed to assess the reliability and agreement of automated head measurements using 3-dimensional (3D) photogrammetry in young children. Specifically, the study evaluated the agreement between manual and automated occipitofrontal circumference (OFC) measurements (n = 264) obtained from 3D images of 188 patients diagnosed with sagittal synostosis using a novel automated method proposed in this study. In addition, the study aimed to determine the interrater and intrarater reliability of the automatically extracted OFC, cephalic index, and volume. The results of the study showed that the automated OFC measurements had an excellent agreement with manual measurements, with a very strong regression score ( R2 = 0.969) and a small mean difference of -0.1 cm (-0.2%). The limits of agreement ranged from -0.93 to 0.74 cm, falling within the reported limits of agreement for manual OFC measurements. High interrater and intrarater reliability of OFC, cephalic index, and volume measurements were also demonstrated. The proposed method for automated OFC measurements was found to be a reliable alternative to manual measurements, which may be particularly beneficial in young children who undergo 3D imaging in craniofacial centers as part of their treatment protocol and in research settings that require a reproducible and transparent pipeline for anthropometric measurements. The method has been incorporated into CraniumPy, an open-source tool for 3D image visualization, registration, and optimization, which is publicly available on GitHub ( https://github.com/T-AbdelAlim/CraniumPy ).