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.

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.

Letter to the editor: A prospective cohort study on perioperative percutaneous balloon compression for trigeminal neuralgia: safety and efficacy analysis.

This study evaluated the safety and efficacy of Percutaneous Balloon Compression (PBC) for managing Trigeminal Neuralgia (TN) during the perioperative period in 400 patients. The results indicated no significant difference in postoperative pain relief between male and female patients, although female patients experienced more complications. PBC demonstrated effectiveness regardless of prior treatment, such as PBC, Microvascular Decompression (MVD), or Radiofrequency Thermocoagulation (RFT). Despite its efficacy, PBC has drawbacks, including an increased risk of complications in females and challenges in achieving standardized compression parameters. Compared to other surgical techniques for TN, PBC offers advantages in minimally invasive intervention, but has limitations, particularly in recurrent TN after MVD or RFT. While promising, the lack of standardized protocols and focus on short-term outcomes limits the generalizability of the findings. In conclusion, PBC represents a significant advancement in TN management, providing high initial pain relief rates with minimal invasiveness. However, further research is necessary to standardize procedures, address complications, and evaluate the long-term efficacy for a comprehensive understanding of its role in TN treatment.

Preoperative anxiety management in pediatric patients: a systemic review and meta-analysis of randomized controlled trials on the efficacy of distraction techniques.

Background: This study addresses the pervasive issue of heightened preoperative anxiety in healthcare, particularly among pediatric patients. Recognizing the various sources of anxiety, we explored both pharmacological and nonpharmacological interventions. Focusing on distraction techniques, including active and passive forms, our meta-analysis aimed to provide comprehensive insights into their impact on preoperative anxiety in pediatric patients. Methods: Following the PRISMA and Cochrane guidelines, this meta-analysis and systematic review assessed the efficacy of pharmaceutical and distraction interventions in reducing pain and anxiety in pediatric surgery. This study was registered on PROSPERO (CRD42023449979). Results: This meta-analysis, comprising 45 studies, investigated pharmaceutical interventions and distraction tactics in pediatric surgery. Risk of bias assessment revealed undisclosed risks in performance and detection bias. Distraction interventions significantly reduced preoperative anxiety compared to control groups, with notable heterogeneity. Comparison with Midazolam favored distraction techniques. Subgroup analysis highlighted varied efficacies among distraction methods, with a notable reduction in anxiety levels. Sensitivity analysis indicated stable results. However, publication bias was observed, suggesting a potential reporting bias. Conclusion: Our study confirms distraction techniques as safe and effective for reducing pediatric preoperative anxiety, offering a valuable alternative to pharmacological interventions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=449979, PROSPERO [CRD42023449979].

Letter to the editor: fully endoscopic microvascular decompression for hemifacial spasm: a clinical study and analysis.

This article presents a comprehensive analysis of microvascular decompression (MVD) surgery as a treatment option for hemifacial spasm (HFS). Beginning with a thorough literature review, it explores the historical context, prevalence, and underlying mechanisms of HFS, laying a robust foundation for discussing MVD. Various surgical techniques, from traditional microscopic to fully endoscopic approaches, are described, along with their procedural nuances and advantages. Clinical data, including patient demographics and surgical success rates, substantiate the efficacy of MVD in alleviating HFS symptoms. The discussion of postoperative complications provides valuable insights into practical challenges. However, limitations such as single-center design, lack of robust statistical analysis, and absence of comparative data between endoscopic and microscopic approaches diminish the article's potential impact. Recommendations for multicenter collaborations, enhanced statistical analyses, comparative studies, and discussions on surgical training could significantly enhance the article's contribution to neurosurgery practice.

Letter to the Editor: Ross procedure: Valve function, clinical outcomes and predictors after 25 years' follow-up.

The following letter presents a critique of the study titled "Ross procedure: valve function, clinical outcomes and predictors after 25 years' follow-up," recently published in your esteemed journal. This study provides a comprehensive analysis of the long-term outcomes of the Ross procedure, focusing on survival rates and incidence of valve dysfunction over a 25-year period. Despite revealing excellent overall survival rates and promising outcomes in pediatric patients, concerns regarding valvular failure and reintervention are underscored. While acknowledging limitations, such as sample size and observational biases, this study highlights the significance of surgeon experience in mitigating adverse outcomes. This critique emphasizes the study's contribution to understanding the efficacy and challenges of the Ross procedure, advocating further research to optimize patient outcomes.

Accuracy of MRI in Detecting 1p/19q Co-deletion Status of Gliomas: A Single-Center Retrospective Study.

Background Oligodendrogliomas, rare brain tumors in the frontal lobe's white matter, are reshaped by molecular markers like isocitrate dehydrogenase mutations and 1p/19q co-deletion, influencing treatment outcomes. Despite the initial indolence, these tumors pose a significant risk, with a median survival of 10-12 years. Non-invasive alternatives, such as magnetic resonance imaging (MRI) for assessing T2-fluid-attenuated inversion recovery (FLAIR) mismatch and calcifications, provide insights into molecular subtypes and aid prognosis. Our study explored these features to predict the oligodendroglioma status and refine patient management to improve outcomes. Methods In this retrospective study, patient data identified patients with suspected central nervous system tumors undergoing MRI, revealing low-grade gliomas. Surgical biopsy and 1p/19q fluorescence in situ hybridization confirmed the co-deletion status. MRI was used to assess various morphological features. Statistical analyses included x2 tests, Fisher's exact tests, Kruskal-Wallis tests, and binary logistic regression models, with significance set at p < 0.05. Results Seventy-three patients (median age, 37 years) were stratified according to 1p/19q co-deletion. Most (61.6%) were 18-40 years old and mostly male (67.1%). Co-deletion cases, primarily frontal lobe lesions (67.6%), were unilateral (88.2%), with 55.9% non-circumscribed margins and 58.8% ill-defined contours. Smooth contrast enhancement and no necrosis were observed in 48.1% of 1p/19q co-deletion cases. Logistic regression analysis showed a significant association between ill-defined/irregular contours and 1p/19q co-deletion. Fisher's exact test confirmed this but raised concerns about the small sample size influencing the conclusions. Conclusions This study established a significant link between glioma tumor contour characteristics, particularly irregular and ill-defined contours, and the likelihood of 1p/19q co-deletion. Our findings underscore the clinical relevance of using tumor contours in treatment decisions and prognosis assessments.

Effectiveness of gamma knife radiosurgery in the management of trigeminal neuralgia associated with multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Trigeminal neuralgia (TN) is a chronic condition characterized by intense facial pain akin to electric shocks, often associated with the trigeminal nerve. It can be either idiopathic or secondary, with multiple sclerosis (Ms) being a significant contributing factor. Non-responsive patients may opt for minimally invasive procedures, such as gamma knife radiosurgery (GKRS), which offers precise, non-invasive treatment and is frequently chosen as a primary approach. This meta-analysis evaluates the long-term efficacy of GKRS in TN management in Ms patients. METHODS: We conducted a focused search across various databases. Inclusion criteria encompassed studies with ≥ 30 patients using GKRS for TN in Ms, reporting pertinent clinical outcomes. Primary outcomes assessed GKRS efficacy through Barrow Neurological Institute Pain scores. Secondary outcomes encompassed bothersome numbness, facial numbness, and recurrence. Data analysis employed OpenMeta, random effect models, and odds ratios with 95% confidence intervals. Heterogeneity was assessed using I2 statistics. RESULTS: Fourteen studies with 752 cases of GKRS for TN were included. Regarding the outcomes, 83% of patients experienced a positive initial pain response, while the overall treatment success rate was 51%. Additionally, 19.6% of patients reported facial numbness, 4.1% experienced bothersome numbness, and 40% faced recurrence. The odds ratio for positive initial pain response was 0.83 (95% CI, 0.76-0.89), while for treatment success, it was 0.51 (95% CI, 0.379-0.639). Facial numbness had an odds ratio of 0.196 (95% CI, 0.130-0.262), bothersome numbness had an odds ratio of 0.041 (95% CI, 0.013-0.069), and recurrence had an odds ratio of 0.403 (95% CI, 0.254-0.551). CONCLUSIONS: In conclusion, treating trigeminal neuralgia in multiple sclerosis patients remains challenging. GKRS shows promise, but customized treatment approaches tailored to individual patient characteristics are urgently needed to address the unique challenges of this condition.

Current and Emerging Treatments for Urothelial Carcinoma: A Focus on Enfortumab Vedotin.

Urothelial carcinoma is a common malignancy that affects the urinary system, with bladder cancer being the most prevalent form. Although the management of early-stage disease has seen significant improvements, the treatment of locally advanced and metastatic urothelial carcinoma remains challenging. Over the past decade, there has been an explosion in the number of therapies available for the treatment of advanced disease, with immune checkpoint inhibitors and antibody-drug conjugates leading the way. Enfortumab vedotin is an antibody-drug conjugate that targets Nectin-4, a protein that is overexpressed in urothelial carcinoma cells. In clinical trials, it has shown promising outcomes for the treatment of advanced urothelial carcinoma that has progressed after chemotherapy or immunotherapy. The US Food and Drug Administration has granted expedited approval for enfortumab vedotin in the treatment of advanced urothelial carcinoma. This review provides an overview of the current and emerging treatments for urothelial carcinoma, with a particular focus on enfortumab vedotin. We discuss the mechanisms of action, clinical efficacy, safety, and ongoing research of enfortumab vedotin, along with the current landscape of other approved therapies and promising agents in development. The aim of this review is to provide a comprehensive and up-to-date summary of the available treatment options for urothelial carcinoma, including their limitations and future prospects.