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1.
Front Psychol ; 14: 1136223, 2023.
Article in English | MEDLINE | ID: mdl-37151327

ABSTRACT

Introduction: Intramedullary spinal cord tumors (IMSCTs) are rare but clinically significant entities that may cause severe neurological decline with progressive pain and motor or sensory deterioration. Beyond the beneficial effects of surgical treatment and the long-term progression-free survival, neurological deficits may still persist after surgery, and information about the long-term patients' health-related quality of life (QoL) is still lacking. In this study, we investigate the patients' health perception 15 years after the surgery in an overall patients' wellbeing framework. Methods: Patients surgically treated for IMSCT over a period from 1996 to 2011 were selected. After a mean of 15 years from the surgery, patient's self-administered questionnaire on disability, pain, sleep quality, and QoL was collected and neurological postoperative evaluation at the chronic stage was reexamined. Results: Neurological deficits are reported in half of the patients in the postoperative chronic phase. After 15 years of surgery, half of the patients still report mild or severe disability grades associated with significantly higher pain and poor sleep and QoL. In accordance, the neurological condition measured at the chronic stage is significantly related not only to disease-specific symptoms (i.e., pain) but even to sleep quality complaints and poor QoL, measured at 15 years follow-up. Conclusions: Health-related QoL is an important secondary outcome in patients. Although the progression-free survival, worse postoperative neurological conditions could predict long-term sequelae reflecting patients' poor health perception. It suggests the importance of preserving patients' functional status and globally evaluating patients' wellbeing to handle disease-specific symptoms but even more general aspects of QoL.

2.
Int J Mol Sci ; 23(18)2022 Sep 06.
Article in English | MEDLINE | ID: mdl-36142158

ABSTRACT

Glioblastoma multiforme (GBM) is a fatal brain tumor without effective drug treatment. In this study, we highlight, for the first time, the contribution of chromatin remodeling gene Lysine (K)-specific demethylase 5C (KDM5C) in GBM via an extensive analysis of clinical, expression, and functional data, integrated with publicly available omic datasets. The expression analysis on GBM samples (N = 37) revealed two informative subtypes, namely KDM5CHigh and KDM5CLow, displaying higher/lower KDM5C levels compared to the controls. The former subtype displays a strong downregulation of brain-derived neurotrophic factor (BDNF)-a negative KDM5C target-and a robust overexpression of hypoxia-inducible transcription factor-1A (HIF1A) gene, a KDM5C modulator. Additionally, a significant co-expression among the prognostic markers HIF1A, Survivin, and p75 was observed. These results, corroborated by KDM5C overexpression and hypoxia-related functional assays in T98G cells, suggest a role for the HIF1A-KDM5C axis in the hypoxic response in this tumor. Interestingly, fluorescence-guided surgery on GBM sections further revealed higher KDM5C and HIF1A levels in the tumor rim niche compared to the adjacent tumor margin, indicating a regionally restricted hyperactivity of this regulatory axis. Analyzing the TCGA expression and methylation data, we found methylation changes between the subtypes in the genes, accounting for the hypoxia response, stem cell differentiation, and inflammation. High NANOG and IL6 levels highlight a distinctive stem cell-like and proinflammatory signature in the KDM5CHigh subgroup and GBM niches. Taken together, our results indicate HIF1A-KDM5C as a new, relevant cancer axis in GBM, opening a new, interesting field of investigation based on KDM5C as a potential therapeutic target of the hypoxic microenvironment in GBM.


Subject(s)
Brain Neoplasms , Glioblastoma , Brain Neoplasms/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Cell Line, Tumor , Chromatin/genetics , Gene Expression Regulation, Neoplastic , Glioblastoma/metabolism , Histone Demethylases/genetics , Histone Demethylases/metabolism , Humans , Hypoxia/genetics , Interleukin-6/metabolism , Lysine/metabolism , Oxygen/metabolism , Survivin/genetics , Transcription Factors/metabolism , Tumor Microenvironment/genetics
3.
Front Neurol ; 12: 640581, 2021.
Article in English | MEDLINE | ID: mdl-33716943

ABSTRACT

Objectives: Restrictive measures adopted during the COVID-19 pandemic, in order to limit contagion, have had a severe impact on mental health. The burden of lockdown has been particularly heavy on patients with chronic neurologic diseases such as People with Epilepsy (PwE). Our survey aims to describe the struggles and needs of Drug-Resistant (DR) PwE with implanted Vagal Nerve Stimulator (VNS) during the first wave of the COVID-19 lockdown in order to find strategies that help patients cope with present or future periods of restriction. Methods: We collected answers from 30 respondents who underwent an online survey including socio-demographic and clinical information and COVID-19-related information. Depression, anxiety symptoms, and sleep quality were investigated in patients through BDI II, GAD-7, and the PSQI scale. Results: In all, 46% of our sample reported an increase in the number of seizures; the entire sample complained of epilepsy-related issues (medication availability, VSN adjustments, anxiety, sleep disturbance); one out of three participants reported major epilepsy issues felt urgent; 30% had to postpone scheduled examination. Significantly higher scores for depression and anxiety scales were found in patients who perceived seizure frequency worsening and reported major epilepsy-related issues. Conclusion: Preliminary findings showed that the first lockdown influenced the clinical and psychological status of PwE and was related to seizures worsening. The lack of medical assistance and control on VNS therapy left patients to cope with the situation without a chance to contact a specialist. We discuss how a wider implementation of telemedicine programs could facilitate remote assistance of PwE with a VNS implant.

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