Focus on current and emerging treatment options for glioma: A comprehensive review.

This comprehensive review delves into the current updates and challenges associated with the management of low-grade gliomas (LGG), the predominant primary tumors in the central nervous system. With a general incidence rate of 5.81 per 100000, gliomas pose a significant global concern, necessitating advancements in treatment techniques to reduce mortality and morbidity. This review places a particular focus on immunotherapies, discussing promising agents such as Zotiraciclib and Lerapolturev. Zotiraciclib, a CDK9 inhibitor, has demonstrated efficacy in glioblastoma treatment in preclinical and clinical studies, showing its potential as a therapeutic breakthrough. Lerapolturev, a viral immunotherapy, induces inflammation in glioblastoma and displays positive outcomes in both adult and pediatric patients. Exploration of immunotherapy extends to Pembrolizumab, Nivolumab, and Entrectinib, revealing the challenges and variabilities in patient responses. Despite promising preclinical data, the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment, emphasizing the critical need to understand resistance mechanisms. The review also covers the success of radiation therapy in pediatric LGG, with evolving techniques, such as proton therapy, showing potential improvements in patient quality of life. Surgical treatment is discussed in the context of achieving a balance between preserving the patient's quality of life and attaining gross total resection, with the extent of surgical resection significantly influencing the survival outcomes. In addition to advancements in cancer vaccine development, this review highlights the evolving landscape of LGG treatment, emphasizing a shift toward personalized and targeted therapies. Ongoing research is essential for refining strategies and enhancing outcomes in the management of LGG.

Evaluating the Effectiveness and Safety of Evinacumab in Treating Hypercholesterolemia and Hypertriglyceridemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Cardiovascular disease remains a significant global health concern, with high low-density lipoprotein cholesterol (LDL-C) levels contributing to an increased risk. Familial hypercholesterolemia (FH) further complicates its management, necessitating additional lipid-lowering therapies. Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, has emerged as a potential treatment, particularly for patients with FH, by effectively reducing LDL-C and triglyceride levels. This meta-analysis aimed to evaluate the efficacy and safety of evinacumab across diverse patient populations. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, relevant randomized controlled trials (RCTs) were systematically retrieved from multiple databases until November 24, 2023. The inclusion criteria were studies comparing evinacumab (at doses of 5 and 15 mg) to placebo, with outcomes focusing on lipid levels and adverse events. Standardized protocols were employed for data extraction and quality assessment, and statistical analysis was conducted using RevMan software. RESULTS: Four RCTs, involving 270 patients, were included in the analysis. The analysis revealed significant reductions in lipid markers, particularly with the 15-mg dose of evinacumab, including triacylglycerols (standard mean difference [SMD] = -6.09, 95% confidence interval [CI] - 14.53 to 2.36, P = 0.16), total cholesterol (SMD = - 6.20, 95% CI - 11.53 to - 0.88, P = 0.02), high-density lipoprotein cholesterol (SMD = - 0.79, 95% CI - 1.27 to - 0.31, P = 0.001), LDL-C (SMD = - 4.58, 95% CI - 9.13 to - 0.03, P = 0.05), apolipoprotein (Apo) B (SMD = - 4.01, 95% CI - 7.53 to - 0.46, P = 0.03), and Apo C3 (SMD = - 7.67, 95% CI - 12.94 to - 2.41, P = 0.004). Adverse event analysis revealed no significant association, indicating good tolerability. CONCLUSION: High-dose evinacumab (15 mg) consistently demonstrated efficacy in reducing cholesterol and other lipid markers, with favorable tolerability. Further research is warranted to comprehensively assess its safety and clinical effectiveness, emphasizing the need for additional data to support its use in managing cardiovascular disease.

Evaluating the efficacy and safety of nivolumab and ipilimumab combination therapy compared to nivolumab monotherapy in advanced cancers (excluding melanoma): a systemic review and meta-analysis.

BACKGROUND: Nivolumab (Nivo) and ipilimumab (Ipi) have revolutionized cancer treatment by targeting different pathways. Their combination shows promising results in various cancers, including melanoma, but not all studies have demonstrated significant benefits. A meta-analysis was performed to assess the effectiveness and safety of Nivo-Ipi compared to Nivo alone in advanced cancer types (excluding melanoma). METHODS: Following PRISMA guidelines, we conducted a meta-analysis up to September 30, 2023, searching databases for randomized controlled trials (RCTs). We focused on advanced solid malignancies (excluding melanoma) with specific Nivo and Ipi dosing. Primary outcomes were overall survival (OS), progression-free survival (PFS), grades 3-4 adverse events (AEs), and treatment-related discontinuations. Secondary outcomes included specific adverse events. Statistical analysis in Review Manager included hazard ratio (HR) and risk ratio (RR), assessing heterogeneity (Higgins I2). RESULTS: Nine RCTs, involving 2152 patients covering various malignancies, were analyzed. The Nivo plus Ipi group exhibited a median OS of 12.3 months and a median PFS of 3.73 months, compared to monotherapy with 11.67 months and 3.98 months, respectively. OS showed no significant difference between Nivo and Ipi combination and Nivo alone (HR = 0.97, 95% CI: 0.88 to 1.08, p = 0.61). PFS had a slight improvement with combination therapy (HR = 0.91, 95% CI: 0.82 to 1.00, p = 0.04). Treatment-related cumulative grades 3-4 adverse events were higher with Nivo and Ipi (RR = 1.52, 95% CI: 1.30 to 1.78, p < 0.00001), as were treatment-related discontinuations (RR = 1.99, 95% CI: 1.46 to 2.70, p < 0.0001). Hepatotoxicity (RR = 2.42, 95% CI: 1.39 to 4.24, p = 0.002), GI toxicity (RR = 2.84, 95% CI: 1.44 to 5.59, p = 0.002), pneumonitis (RR = 2.29, 95% CI: 1.24 to 2.23, p = 0.008), dermatitis (RR = 2.96, 95% CI: 1.08 to 8.14, p = 0.04), and endocrine dysfunction (RR = 6.22, 95% CI: 2.31 to 16.71, p = 0.0003) were more frequent with Nivo and Ipi. CONCLUSIONS: Combining nivolumab and ipilimumab did not significantly improve overall survival compared to nivolumab alone in advanced cancers (except melanoma). However, it did show slightly better PFS at the cost of increased toxicity, particularly grades 3-4 adverse events. Specific AEs occurred more frequently in the combination group. Further trials are needed to fully assess this combination in treating advanced cancers.

Comparing equiosmolar hypertonic saline and mannitol for achieving brain relaxation in elective craniotomy patients: A systematic review and meta-analysis.

Background: This study strives to provide a current and thorough assessment of the comparative efficacy and safety between equiosmolar quantities of hypertonic saline (HS) and mannitol in facilitating brain relaxation for patients undergoing elective craniotomies. Methods: This systematic review and meta-analysis, following preferred reporting items for systematic reviews and meta-analyses guidelines, compared the efficacy and safety of equiosmolar concentrations of mannitol and HS in elective craniotomies. PubMed, Scopus, Cochrane Library, ScienceDirect, and Proquest databases were searched using keywords related to mannitol, HS, and craniotomy. Results were analyzed through a random-effects model using Mantel-Haenszel risk ratio and standard mean difference. P < 0.05 was considered significant. Results: Thirteen randomized controlled trials encompassing 965 patients (516 in the HS group and 448 in the mannitol group) were analyzed. The quality of studies was moderate-to-high, and no significant publication bias was observed. The primary outcome, brain relaxation, favored HS over mannitol without significant heterogeneity. Mannitol was associated with increased urine output compared to HS, irrespective of dose, with high heterogeneity. HS was linked to significantly reduced fluid input, confirmed by subgroup analysis with lower heterogeneity. No significant difference was found in serum osmolality between the two agents. Serum sodium (Na+) levels favored HS, whereas arterial blood Na+ levels also favored HS despite considerable heterogeneity. Maximum mean arterial pressure was higher with HS, but it displayed significant heterogeneity. Maximum central venous pressure showed no significant difference between the two agents, with moderate heterogeneity. Conclusion: HS appears more effective than mannitol in achieving brain relaxation, and it may offer advantages in fluid management and Na+ balance. Clinicians should consider these findings when selecting hyperosmotic agents for neurosurgical procedures. Further research is needed to address heterogeneity in certain outcomes and guide clinical practice.

Breakthroughs in Alzheimer's Research: A Path to a More Promising Future?

Background: Alzheimer's disease (AD) is a widespread neurodegenerative disorder with a significant global impact, affecting approximately 50 million individuals, and projections estimate that up to 152 million people will be affected by 2050. AD is characterized by beta-amyloid plaques and tau tangles in the brain, leading to cognitive decline. Summary: Recent research on AD has made significant strides, including the development of an "amyloid clock" biomarker that tracks AD progression through positron emission tomography (PET) scans. Surf4 and other genes have been discovered to play a role in regulating beta-amyloid toxicity, while inhibiting the enzyme hexokinase-2 has shown positive results in preclinical studies. New brain mapping techniques have identified early brain-based causes of cognitive changes in AD, and biomarkers such as neuronal pentraxin protein Nptx2 and astrocytic 7-subunit of the nicotinic acetylcholine receptors (7nAChRs) show potential for early detection. Other approaches, such as replenishing the enzyme Tip60, selectively degrading the modified protein p-p38 with PRZ-18002, and targeting the protein voltage-dependent anion channel-1 (VDAC1), have shown promise in enhancing cognitive function and preventing pathophysiological alterations linked to AD. Baseline blood samples and other biomarkers such as urine formic acid, p-tau 198, microRNAs, and glial fibrillary acidic protein (GFAP) have also been discovered for early detection and intervention of AD. Additionally, recent FDA approvals for medications such as aducanumab and lecanemab provide options for reducing AD symptoms and improving function, while clinical trials for dementia vaccines show promise for the nasal and beta-amyloid 40 vaccines as well as vaccinations targeting tau. Key Messages: These advancements in AD research, including biomarker discovery and the development of disease-modifying treatments, are crucial steps towards improving the lives of those affected by AD and finding a cure for this debilitating disease.

Neurosurgical Malpractice Litigation: A Systematic Review and Meta-Analysis.

BACKGROUND: Neurosurgery has 1 of the highest risks for medical malpractice claims. We reviewed the factors associated with neurosurgical malpractice claims and litigation in the United States and reported the outcomes through a systematic review of the literature. METHODS: We conducted a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines using the Medline, Embase, Cochrane, PubMed, and Google Scholar databases. We sought to identify pertinent studies containing information about medical malpractice claims and outcomes involving neurosurgeons in the United States. RESULTS: We identified 15 retrospective studies spanning from 2002 to 2023 that reviewed over 7890 malpractice claims involving practicing neurosurgeons in the United States. Disparities were evident in neurosurgical litigation, with 474 cases linked to brain-related surgeries and a larger proportion, 1926 cases, tied to spine surgeries. The most commonly filed claims were intraprocedural errors (37.4%), delayed diagnoses (32.1%), and failure to treat (28.8%). Less frequently filed claims included misdiagnosis or choice of incorrect procedure (18.4%), occurrence of death (17.3%), test misinterpretation (14.4%), failure to appropriately refer patients for evaluation/treatment (14.3%), unnecessary surgical procedures (13.3%), and lack of informed consent (8.3%). The defendant was favored in 44.3% of claims, while in 31.3% of lawsuits were dropped, 17.7% of verdicts favored the plaintiff, and 16.6% reached an out of court settlement. Only 3.5% of lawsuits found both parties liable. CONCLUSION: Neurosurgery is a high-risk specialty with 1 of the highest rates of malpractice claims. Spine claims had a significantly higher rate of filed malpractice claims, while cranial malpractice claims were associated with higher litigation compensation. Predictably, spinal cord injuries play a crucial role in predicting litigation. Importantly, nonsurgical treatments are also a common source of liability in neurosurgical practice.

Comment on: Severe pulmonary hypertension in pulmonary alveolar microlithiasis: A comprehensive literature review.

This letter commends the study "Severe pulmonary hypertension in pulmonary alveolar microlithiasis: A comprehensive literature review" for its thorough exploration of Pulmonary Alveolar Microlithiasis (PAM) and its association with pulmonary hypertension (PH). The study offers insights into PAM's genetics, clinical manifestations, diagnostic approaches, and treatment modalities. It highlights the importance of early diagnosis and management while discussing limitations such as its retrospective nature and small sample size. Despite these limitations, the study contributes significantly to understanding PAM and PH, emphasizing the need for larger prospective studies to validate findings and explore novel therapeutic avenues.

Comment on, "Systematic literature review and critical analysis of RDW in patients with aortic pathologies".

Recent medical research has explored Red Cell Distribution Width (RDW) as a potential biomarker for predicting adverse clinical outcomes in patients with aortic pathologies. The study "Systematic literature review and critical analysis of RDW in patients with aortic pathologies" conducted a pooled analysis of 704 patients, revealing a consistent association between elevated RDW levels and adverse clinical progression. While the study provides valuable insights into RDW's diagnostic and prognostic potential, limitations include the inclusion of a limited number of articles and the lack of direct comparison with established biomarkers or imaging techniques. Further research is needed to validate RDW's clinical utility and elucidate underlying biological mechanisms. RDW shows promise as a cost-effective marker for risk stratification and monitoring in clinical practice, but further validation and refinement are necessary for its full clinical impact in aortic diseases.

Comment on "Inclisiran siRNA technology in the management of dyslipidemia: A narrative review of clinical trials".

The study "Inclisiran siRNA technology in the management of dyslipidemia: A narrative review of clinical trials" evaluates inclisiran's efficacy and safety in reducing LDL cholesterol levels across diverse patient populations. Twelve clinical trials were reviewed, demonstrating consistent LDL-C reduction, even in statin intolerance or resistance cases, with sustained efficacy observed over various durations, some extending up to four years. Inclisiran exhibited a favorable safety profile, suggesting its potential as a well-tolerated treatment option. Despite promising findings, the limitations include the short duration of some trials and the exclusion of non-English language studies, warranting further research. Future studies should focus on the long-term safety and efficacy in diverse patient populations and explore the broader clinical implications of inclisiran. Although inclisiran shows promise in dyslipidemia management, comprehensive research is needed to understand its full potential in cardiovascular medicine.

Surgical strategies in acute subdural hematoma: a meta-analysis of decompressive craniectomy vs. craniotomy.

OBJECTIVE: Acute subdural hematoma (ASDH) stands as a significant contributor to morbidity after severe traumatic brain injuries (TBI). The primary treatment approach for patients experiencing progressive neurological deficits or notable mass effects is the surgical removal of the hematoma, which can be achieved through craniotomy (CO) or decompressive craniectomy (DC). Nevertheless, the choice between these two procedures remains a subject of ongoing debate and controversy. MATERIALS AND METHODS: We conducted a comprehensive literature review, utilizing prominent online databases and manually searching references related to craniotomy and craniectomy for subdural hematoma evacuation up to November 2023. Our analysis focused on outcome variables such as the presence of residual subdural hematoma, the need for revision procedures, and overall clinical outcomes. RESULTS: We included a total of 11 comparative studies in our analysis, encompassing 4269 patients, with 2979 undergoing craniotomy and 1290 undergoing craniectomy, meeting the inclusion criteria. Patients who underwent craniectomy displayed significantly lower scores on the Glasgow Coma Scale (GCS) during their initial presentation. Following surgery, the DC group exhibited a significantly reduced rate of residual subdural (P = 0.009). Additionally, the likelihood of a poor outcome during follow-up was lower in the CO group. Likewise, the mortality rate was lower in the CO group compared to the craniectomy group (OR 0.63, 95% CI 0.41-0.98, I2 = 84%, P = 0.04). CONCLUSION: Our study found that CO was associated with more favorable outcomes in terms of mortality, reoperation rate, and functional outcome while DC was associated with less likelihood of residual subdural hematoma. Upon further investigation of patient characteristics who underwent into either of these interventions, it was very clear that patients in DC cohort have more serious and low pre-op characteristics than the CO group. Nonetheless, brain herniation and advanced age act as independent factor for predicting the outcome irrespective of the intervention.