The bleeding risk and outcome of pregnant women harboring intracranial arteriovenous malformations are still unclear, and no consensus has been achieved on management timing and strategy.
We searched ...PubMed, MEDLINE, and EMBASE from 1990 to 2022 for studies evaluating the bleeding risk and the outcome of women with intracranial arteriovenous malformations. Our primary end point was the hemorrhage rate. The secondary end points were pregnancy outcome and treatment safety for the mother and the fetus.
Nine studies reporting on 2426 women were included. The overall hemorrhage rate in untreated women was 2.6%. The rate of first bleeding during pregnancy and postpartum was greater than the respective fertile period in unpregnant women (11% vs. 6.7%). The risk of first bleeding was greater in the II and III trimesters (4.5% and 2.9%), while was lower during delivery and puerperium (0.1% and 0.2%). The majority of the women did not report any complications after pregnancy and early postpartum death occurred in 4.1% of cases. The overall miscarriage rate was 12.4%.
Women harboring intracranial arteriovenous malformations appear to have a greater risk of hemorrhage during pregnancy. There is an increased bleeding risk in the later stages of gestation, whereas delivery and puerperium are less risky phases. Outcomes are relatively good for the mother, with low rates of mortality and unfavorable sequelae, but there is a risk of miscarriage for the fetus. Intervention should be undertaken prophylactically before pregnancy or during early gestation if possible. For pregnant women who deferred treatment, multidisciplinary management is advised.
Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients remains poor. Immunotherapy ...has recently emerged as a potential treatment option. The aim of this systematic review is to assess the current strategies and future perspectives of the GBM immunotherapy strategies. A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 3 September 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to “glioblastomas,” “immunotherapies,” and “treatment.” The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of immunotherapies for the treatment of gliomas in human subjects. A total of 1588 papers are initially identified. Eligibility is confirmed for 752 articles, while 655 are excluded for various reasons, including irrelevance to the research topic (627), insufficient method and results details (12), and being case-series or cohort studies (22), systematic literature reviews, or meta-analyses (3). All the studies within the systematic review were clinical trials spanning from 1995 to 2023, involving 6383 patients. Neuro-oncology published the most glioma immunotherapy-related clinical trials (15/97, 16%). Most studies were released between 2018 and 2022, averaging nine publications annually during this period. Adoptive cellular transfer chimeric antigen receptor (CAR) T cells were the primary focus in 11% of the studies, with immune checkpoint inhibitors (ICIs), oncolytic viruses (OVs), and cancer vaccines (CVs) comprising 26%, 12%, and 51%, respectively. Phase-I trials constituted the majority at 51%, while phase-III trials were only 7% of the total. Among these trials, 60% were single arm, 39% double arm, and one multi-arm. Immunotherapies were predominantly employed for recurrent GBM (55%). The review also revealed ongoing clinical trials, including 9 on ICIs, 7 on CVs, 10 on OVs, and 8 on CAR T cells, totaling 34 trials, with phase-I trials representing the majority at 53%, and only one in phase III. Overcoming immunotolerance, stimulating robust tumor antigen responses, and countering immunosuppressive microenvironment mechanisms are critical for curative GBM immunotherapy. Immune checkpoint inhibitors, such as PD-1 and CTLA-4 inhibitors, show promise, with the ongoing research aiming to enhance their effectiveness. Personalized cancer vaccines, especially targeting neoantigens, offer substantial potential. Oncolytic viruses exhibited dual mechanisms and a breakthrough status in the clinical trials. CAR T-cell therapy, engineered for specific antigen targeting, yields encouraging results, particularly against IL13 Rα2 and EGFRvIII. The development of second-generation CAR T cells with improved specificity exemplifies their adaptability.
Parkinson's disease (PD) is the second most prevalent neurodegenerative condition after Alzheimer's disease and it represents one of the fastest emerging neurological diseases worldwide. PD is ...usually diagnosed after the third decade of life with symptoms like tremors at rest and muscle stiffness. Rapid Eye Movement sleep behavioral disorder (RBD) is another disorder that is caused by a loss of typical muscle relaxation during sleep with a lot of motor activity. Usually, RBD is strongly associated with PD. Recent studies have demonstrated that PD reduces the life expectancy of patients to 10 and 20 years after being diagnosed. In addition, delayed diagnosis and treatment of these neurological disorders have significant socio-economic impacts on patients, their partners and on the general public. Often, it is not clear about PD associated financial burdens both in low and high-income countries. On the other hand, PD triggers neurological variations that affect differences in the dopamine transporter (DAT) and in glucose metabolism. Therefore, positron emission tomography (PET) using specific DAT radiotracers and fluorine-18 labeled desoxyglucose (FDG) has being considered a key imaging technique that could be applied clinically for the very early diagnosis of RBD and in PD. However, a few myths about PET is that it is very expensive. Here, we looked at the cost of treatment of PD and RBD in relation to early PET imaging. Our finding suggests that PET imaging might also be a cost sparing diagnostic option in the management of patients with PD and RBD, not only for first world countries as it is the case now but also for the third world countries. Therefore, PET is a cost-effective imaging technique for very early diagnostic of RBD and PD.
•Early diagnosis of neurological disorders crucial for socioeconomic impact.•PET imaging aids in detecting REM Sleep Behavior Disorder (RBD) and Parkinson's Disease (PD) early.•RBD precedes PD, making it a strong predictor for early diagnosis.•Cost analysis shows PET imaging's potential cost-effectiveness in PD diagnosis.•Advocacy for wider PET availability globally to improve early diagnosis and treatment.
High-grade glial tumors (HGGs) exhibit aggressive growth patterns and high recurrence rates. The prevailing treatment approach comprises radiation therapy (RT), chemotherapy (CMT), and surgical ...resection. Despite the progress made in traditional treatments, the outlook for patients with HGGs remains bleak. Tumor metabolism is emerging as a potential target for glioma therapies, a promising approach that harnesses the metabolism to target tumor cells. However, the efficacy of therapies targeting the metabolism of HGGs remains unclear, compelling a comprehensive review. This study aimed to assess the outcome of present trials on HGG therapies targeting metabolism. A comprehensive search of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted until November 2023. The search method used pertinent Medical Subject Heading (MeSH) terminologies and keywords referring to "high-grade gliomas", "metabolism", "target therapies", "monoclonal antibodies", "overall survival", and "progression-free survival". The review analyzed studies that focused on therapies targeting the metabolism of HGGs in human subjects. These studies included both randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs). Out of 284 articles identified, 23 trials met the inclusion criteria and were thoroughly analyzed. Phase II trials were the most numerous (62%). Targeted metabolic therapies were predominantly used for recurrent HGGs (67%). The most common targeted pathways were the vascular endothelial growth factor (VEGF, 43%), the human epidermal growth factor receptor (HER, 22%), the platelet-derived growth factor (PDGF, 17%), and the mammalian target of rapamycin (mTOR, 17%). In 39% of studies, the subject treatment was combined with CMT (22%), RT (4%), or both (13%). The median OS widely ranged from 4 to 26.3 months, while the median PFS ranged from 1.5 to 13 months. This systematic literature review offers a thorough exploration of the present state of metabolic therapies for HGGs. The multitude of targeted pathways underscores the intricate nature of addressing the metabolic aspects of these tumors. Despite existing challenges, these findings provide valuable insights, guiding future research endeavors. The results serve as a foundation for refining treatment strategies and enhancing patient outcomes within the complex landscape of HGGs.
Cinnamic acid is a known allelochemical that affects seed germination and plant root growth and therefore influences several metabolic processes. In the present work, we evaluated its effects on ...growth, indole-3-acetic acid (IAA) oxidase and cinnamate 4-hydroxylase (C4H) activities and lignin monomer composition in soybean (Glycine max) roots. The results revealed that exogenously applied cinnamic acid inhibited root growth and increased IAA oxidase and C4H activities. The allelochemical increased the total lignin content, thus altering the sum and ratios of the p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) lignin monomers. When applied alone or with cinnamic acid, piperonylic acid (PIP, a quasi-irreversible inhibitor of C4H) reduced C4H activity, lignin and the H, G, S monomer content compared to the cinnamic acid treatment. Taken together, these results indicate that exogenously applied cinnamic acid can be channeled into the phenylpropanoid pathway via the C4H reaction, resulting in an increase in H lignin. In conjunction with enhanced IAA oxidase activity, these metabolic responses lead to the stiffening of the cell wall and are followed by a reduction in soybean root growth.
L-3,4-Dihydroxyphenylalanine (L-DOPA) is an allelochemical released by roots of velvet bean (
Mucuna pruriens
) that affects the growth of several plant species. However, its mechanism of action is ...inconclusive. In this work, we compared the effects of L-DOPA (0.01–1.0 mmol L
−1
) and of aqueous extracts (300, 1200, and 3000 mg L
−1
) of velvet bean on growth and photosynthesis (gas exchange and chlorophyll
a
fluorescence) of soybean (
Glycine max
). Overall, the results showed that both L-DOPA and aqueous extracts of velvet bean reduced the growth, leaf area, photosynthetic rate (A), stomatal conductance (g
s
), transpiration (E), and quantum yield of electron flow through photosystem II (PSII) in vivo (Φ
F
). In addition, L-DOPA and aqueous extracts increased the internal CO
2
concentration (Ci) and the leaf wax and trichome density on the leaf surface, while the maximum quantum yield of PSII (F
v
/F
m
) was not changed. These results suggest that the reduction of A should not be related exclusively to the stomatal closure, but also to limitations of the carbon metabolism, as indicated by the increase of Ci and decrease of Φ
F
. Briefly, we concluded that soybean growth inhibition by L-DOPA and aqueous extracts of velvet bean is due to the combination of damage in the root meristem and reduction in A.
To better define the overall performance of the current radiomics-based models for the discrimination of pediatric posterior fossa tumors.
A comprehensive literature search of the databases PubMed, ...Ovid MEDLINE, Ovid EMBASE, Web of Science, and Scopus was designed and conducted by an experienced librarian. We estimated overall sensitivity (SEN) and specificity (SPE). Event rates were pooled across studies using a random-effects meta-analysis, and the χ
test was performed to assess the heterogeneity.
Overall SEN and SPE for differentiation between MB, PA, and EP were found to be promising, with SEN values of 93% (95% CI = 0.88-0.96), 83% (95% CI = 0.66-0.93), and 85% (95% CI = 0.71-0.93), and corresponding SPE values of 87% (95% CI = 0.82-0.90), 95% (95% CI = 0.90-0.98) and 90% (95% CI = 0.84-0.94), respectively. For MB, there is a better trend for LR classifiers, while textural features are the most used and the best performing (ACC 96%). As for PA and EP, a synergistic employment of LR and NN classifiers, accompanied by geometrical or morphological features, demonstrated superior performance (ACC 94% and 96%, respectively).
The diagnostic performance is high, making radiomics a helpful method to discriminate these tumor types. In the forthcoming years, we expect even more precise models.
Numerous radiomics-based models have been proposed to discriminate between central nervous system (CNS) gliomas and primary central nervous system lymphomas (PCNSLs). Given the heterogeneity of the ...existing models, we aimed to define their overall performance and identify the most critical variables to pilot future algorithms.
A systematic review of the literature and a meta-analysis were conducted, encompassing 12 studies and a total of 1779 patients, focusing on radiomics to differentiate gliomas from PCNSLs. A comprehensive literature search was performed through PubMed, Ovid MEDLINE, Ovid EMBASE, Web of Science, and Scopus databases. Overall sensitivity (SEN) and specificity (SPE) were estimated. Event rates were pooled using a random-effects meta-analysis, and the heterogeneity was assessed using the χ2 test.
The overall SEN and SPE for differentiation between CNS gliomas and PCNSLs were 88% (95% CI = 0.83 - 0.91) and 87% (95% CI = 0.83 - 0.91), respectively. The best-performing features were the ones extracted from the Gray Level Run Length Matrix (GLRLM; ACC 97%), followed by those obtained from the Neighboring Gray Tone Difference Matrix (NGTDM; ACC 93%), and shape-based features (ACC 91%). The 18F-FDG-PET/CT was the best-performing imaging modality (ACC 97%), followed by the MRI CE-T1W (ACC 87% - 95%). Most studies applied a cross-validation analysis (92%).
The current SEN and SPE of radiomics to discriminate CNS gliomas from PCNSLs are high, making radiomics a helpful method to differentiate these tumor types. The best-performing features are the GLRLM, NGTDM, and shape-based features. The 18F-FDG-PET/CT imaging modality is the best-performing, while the MRI CE-T1W is the most used.
Despite significant advances in understanding the molecular pathways of glioma, translating this knowledge into effective long-term solutions remains a challenge. Indeed, gliomas pose a significant ...challenge to neurosurgical oncology because of their diverse histopathological features, genetic heterogeneity, and clinical manifestations. Relevant sections: This study focuses on glioma complexity by reviewing recent advances in their management, also considering new classification systems and emerging neurosurgical techniques. To bridge the gap between new neurosurgical approaches and standards of care, the importance of molecular diagnosis and the use of techniques such as laser interstitial thermal therapy (LITT) and focused ultrasound (FUS) are emphasized, exploring how the integration of molecular knowledge with emerging neurosurgical approaches can personalize and improve the treatment of gliomas.
The choice between LITT and FUS should be tailored to each case, considering factors such as tumor characteristics and patient health. LITT is favored for larger, complex tumors, while FUS is standard for smaller, deep-seated ones. Both techniques are equally effective for small and superficial tumors. Our study provides clear guidance for treating pediatric low-grade gliomas and highlights the crucial roles of LITT and FUS in managing high-grade gliomas in adults. This research sets the stage for improved patient care and future developments in the field of neurosurgery.
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