Search Results (478)

This comprehensive review examines the role of septoplasty in the pediatric population, emphasizing its therapeutic significance in relieving nasal obstruction and facilitating normal craniofacial growth. Despite the evident advantages of septoplasty, its application in young patients remains a subject of ongoing debate. This issue is primarily characterized by concerns regarding the still-developing immaturity of nasal cartilage, potential intraoperative and postoperative risks, and the current absence of robust data on long-term outcomes following septoplasty. Common complications such as bleeding, septal perforation, saddle nose deformity, and persistent nasal obstruction are reported in the literature; however, many studies lack long-term follow-up data on the incidence of these adverse events and revision rates, which may be higher compared to adult populations, often leading to the need for secondary surgical interventions. Strict inclusion criteria and comprehensive patient selection are paramount to maximize therapeutic success while minimizing complications. Current evidence suggests that appropriately indicated septoplasty can improve airway patency, support optimal facial development, and reduce the risk of secondary sinonasal pathology. There is a significant necessity for additional prospective, large-scale studies to establish standardized therapeutic guidelines and management strategies for this specific population, thereby ensuring effective and evidence-based pediatric otolaryngologic care. Full article

Post-craniotomy pain is common yet often sub-optimally managed because systemic opioids can obscure postoperative neurologic examinations. The superficial cervical plexus block (SCPB) has, therefore, emerged as a targeted regional anesthesia option for occipital craniotomies. The SCPB targets the C2–C4 nerves to anesthetize the occipital scalp region, covering the lesser occipital nerve territory that lies within typical posterior scalp incisions. Clinical evidence shows the block is effective in reducing acute postoperative pain after occipital craniotomy and diminishes opioid requirements. Studies have demonstrated successful and long-lasting analgesia, reductions in 24-h opioid consumption, and a lower incidence of severe pain. Moreover, the technique exhibits a low complication rate and is safer than a deep cervical plexus block because the injection remains superficial and avoids critical vascular and neural structures. When delivered under ultrasound guidance, major adverse events are exceedingly rare. By reducing opioid use, the SCPB can help reduce postoperative complications, allowing earlier neurological assessments and fewer opioid-related side effects. Incorporation of the SCPB into multimodal analgesia regimens can, therefore, accelerate postoperative recovery by providing regionally focused, opioid-sparing pain control without clinically significant sedation. Overall, current data support the SCPB as a dependable, well-tolerated, and clinically practical approach for managing post-craniotomy pain in patients undergoing occipital approaches. In this narrative review, we will discuss the mechanism of action and anatomy, the clinical application, safety and tolerability, patient outcomes, and emerging future directions of the superficial cervical plexus block and how it mitigates post-occipital craniotomy pain. Full article

Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP). Despite its significant health and socioeconomic impact, earlier obesity medications, such as fenfluramine, sibutramine, and orlistat, fell short of expectations due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) has revolutionized obesity management. These agents demonstrate unprecedented efficacy, achieving 15–25% mean weight loss in clinical trials, alongside reducing major adverse cardiovascular events by 20% and T2D incidence by 72%. Emerging therapies, including oral GLP-1 agonists and triple-receptor agonists (e.g., retatrutide), promise enhanced tolerability and muscle preservation, potentially bridging the efficacy gap with bariatric surgery. However, challenges persist. High costs, supply shortages, and unequal access pose significant barriers to the widespread implementation of obesity treatment, particularly in low-resource settings. Gastrointestinal side effects and long-term safety concerns require close monitoring, while weight regain after medication discontinuation emphasizes the need for ongoing adherence and lifestyle support. This review highlights the transformative potential of incretin-based therapies while advocating for policy reforms to address cost barriers, equitable access, and preventive strategies. Future research must prioritize long-term cardiovascular outcome trials and mitigate emerging risks, such as sarcopenia and joint degeneration. A multidisciplinary approach combining pharmacotherapy, behavioral interventions, and systemic policy changes is critical to curbing the obesity epidemic and its downstream consequences. Full article

Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study assessed vedolizumab’s safety in a real-world cohort and supported the detection of potential safety signals. Methods: A retrospective chart review was conducted on adult IBD patients treated with vedolizumab at a tertiary center in the Republic of Serbia between October 2021 and August 2022. Data included demographics, AEs, and newly reported extraintestinal manifestations (EIMs). Exposure-adjusted incidence rates were calculated per 100 patient-years (PYs). Disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) was performed to identify safety signals, employing reporting odds ratios (RORs) and proportional reporting ratios (PRRs) for AEs also observed in the cohort. Prior IBD therapies and reasons for discontinuation were evaluated. Results: A total of 107 patients (42.1% Crohn’s disease, 57.9% ulcerative colitis) were included, with a median vedolizumab exposure of 605 days. There were 92 AEs (56.51/100 PYs), most frequently infections (23.95/100 PYs), gastrointestinal disorders (4.30/100 PYs), and skin disorders (4.30/100 PYs). The most frequently reported preferred terms (PTs) included COVID-19, COVID-19 pneumonia, nephrolithiasis, and nasopharyngitis. Arthralgia (12.90/100 PYs) was the most frequent newly reported EIM. No discontinuations due to vedolizumab AEs occurred. FAERS analysis revealed potential signals for events not listed in prescribing information but observed in the cohort: nephrolithiasis, abdominal pain, diarrhea, malaise, cholangitis, gastrointestinal infection, blood pressure decreased, weight decreased, female genital tract fistula, respiratory symptom, and appendicectomy. Most patients had received three prior therapies, often stopping one due to AEs. Conclusions: Vedolizumab demonstrated a favorable safety profile in the IBD cohort. However, FAERS-identified signals, such as nephrolithiasis, gastrointestinal infections, and decreased blood pressure, warrant further investigation in larger, more diverse populations. Full article

Background: Advanced and recurrent vulvar squamous cell carcinoma (VSCC) presents a major therapeutic challenge with limited treatment options and poor outcomes. Immune checkpoint inhibitors (ICIs) have shown efficacy in other HPV-associated malignancies, but their role in VSCC remains poorly defined due to the rarity of the disease and limited clinical trial data. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines and registered in PROSPERO (CRD420251067565). A comprehensive literature search identified prospective clinical trials evaluating ICIs in patients with advanced, unresectable, recurrent, or metastatic VSCC. The primary outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Risk of bias was assessed using the MINORS tool. Meta-analyses were performed using random-effects models, with subgroup analyses based on PD-L1 status and treatment regimens (monotherapy vs. combination therapy). Results: Six non-randomized single-arm trials involving 181 patients were included. The pooled ORR was 21%, with higher response rates observed in combination therapy (46%) compared to monotherapy (11%), though not statistically significant. Median PFS and OS were 2.2 months and 6.4 months, respectively. ORRs were similar between PD-L1-positive and PD-L1-negative subgroups. A safety analysis showed treatment-related adverse events (AEs) in 73% of patients and grade ≥ 3 AEs in 23%. The incidence of treatment-related death was 3%. Conclusions: ICIs demonstrate modest but durable efficacy and an acceptable safety profile in advanced VSCC. The current evidence supports their use in selected patients. However, response variability and the lack of reliable predictive biomarkers, such as PD-L1 or HPV status, underscore the need for biomarker-driven clinical trials and improved patient selection strategies. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that significantly affects patients’ quality of life. Dupilumab, a monoclonal antibody targeting interleukin (IL)-4 receptor alpha (IL-4Rα), has been the standard biologic therapy for moderate-to-severe AD. This review compares dupilumab with tralokinumab—a promising alternative that selectively neutralizes IL-13—by examining their distinct mechanisms, clinical efficacy, safety profiles, and practical considerations. While both biologics are highly effective, pivotal monotherapy trials indicate numerically higher efficacy rates for dupilumab. Regarding safety, while long-term data show comparable rates of serious adverse events, dupilumab is associated with a higher incidence of both conjunctivitis and injection-site reactions. Key practical differences include dupilumab’s broader indications and approval for infants (≥6 months), versus tralokinumab’s flexible maintenance dosing and notable efficacy in head and neck AD. By highlighting these key distinctions, this review aims to support personalized treatment selection in AD. However, no direct head-to-head clinical trials have yet compared dupilumab and tralokinumab, and the available evidence is based on indirect comparisons from separate pivotal studies. Full article

Background: The treatment options for HER2-negative metastatic breast cancer include targeted therapies, cytotoxic chemotherapies, and immunotherapy. However, limited specificity and inevitable resistance highlight the need for novel agents. Antibody–drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), represent a breakthrough by selectively delivering cytotoxic agents to tumor cells, potentially improving the therapeutic index. Despite demonstrated efficacy, ADCs present toxicity profiles similar to conventional chemotherapy, alongside unique adverse events. In clinical practice, oncologists may face scenarios where both T-DXd and SG are treatment options in HER2-negative mBC. To enable shared decision-making, it is crucial to present a comprehensive overview that includes both efficacy data and detailed toxicity profiles. Our objective was to provide a pooled and informative synthesis of toxicities from pivotal studies, including graphical representations, to support informed, patient-centered medical decisions. Methods: We reviewed safety data from phase 3 clinical trials in HER2-negative mBC: DESTINY-Breast04/DESTINY-Breast06 for T-DXd and ASCENT/TROPICS-02 for SG. Adverse event (AE) profiles, including frequency and severity, were extracted, and weighted means were calculated. Emerging ADCs such as datopotamab deruxtecan and patritumab deruxtecan were considered to contextualize future therapeutic decisions. Results: Tables, bar plots and radar plots were generated. T-DXd demonstrated high rates of nausea (69.2%), fatigue (47.2%), and neutropenia (35.6%), with 52.7% experiencing grade ≥ 3 AEs. Notably, pneumonitis occurred in 10.7%, with grade ≥ 3 in 2.6%. SG showed a distinct AE profile, with higher incidences of neutropenia (67.1%), with grade ≥ 3 in 51.3%, and diarrhea (60.8%). Conclusions: The choice between ADCs in HER2-negative metastatic BC when both T-DXd and SG are treatment options should consider toxicity profiles to optimize patient-centered treatment strategies. Tailoring ADC selection based on individual tolerance and preferences is critical for shared decision-making, and future research should focus on assessing the utility and acceptability of such clinical tools to guide treatment selection. Full article

Background/Objectives: Nivolumab is a key therapy for advanced-stage melanoma; however, limited data are available from Asian populations comparing the efficacy and side effects of four dosing regimens: 3 mg/kg every 2 weeks (3mg/kgQ2W), 2 mg/kg every 3 weeks (2mg/kgQ3W), 240 mg every 2 weeks (240mgQ2W), and 480 mg every 4 weeks (480mgQ4W). This retrospective study evaluated Japanese patients with advanced melanoma treated with various nivolumab regimens to assess the impact of dosing interval and dosage on treatment efficacy and immune-related adverse events (irAEs). Methods: We reviewed the records of 153 participants with stage IV melanoma who received nivolumab monotherapy between February 2012 and December 2024 at Shizuoka Cancer Center. Patients were categorized by nivolumab regimen, dosing interval, and dose per body weight. We then compared treatment efficacy and incidence of irAEs across groups. Results: No significant differences were observed in objective response rate (ORR), progression-free survival (PFS), overall survival (OS), or irAE incidence between the 240mgQ2W and 480mgQ4W groups. Similar results were observed in the 3mg/kgQ2W and 2mg/kgQ3W groups. However, participants who received nivolumab within 3 weeks exhibited a significantly higher ORR than those who received nivolumab more than 3 weeks. No significant differences were found in PFS or OS. Conclusions: The administration of nivolumab at shorter intervals may provide short-term benefits in Japanese patients with advanced melanoma. However, long-term efficacy and side effects did not differ significantly across the studied nivolumab regimens. Full article

Background: Coronary heart disease (CHD) remains the most prevalent pathology within the circulatory system. Among its chronic complications, ischemic mitral valve regurgitation (IMR) is observed in approximately 15% of patients with sustained myocardial ischemia. The presence of this complex valvular defect significantly increases both overall mortality and the incidence of adverse cardiovascular events. Notably, the presence of moderate to severe mitral regurgitation in patients undergoing surgical revascularization has been shown to double the risk of death. Despite the well-established etiology of IMR, data regarding the efficacy of surgical interventions and the determinants of postoperative outcomes remain inconclusive. Methods: The objective of the present study was to evaluate both early and long-term outcomes of surgical treatment of mitral regurgitation in patients undergoing coronary artery bypass grafting (CABG) due to ischemic heart disease. Particular attention was given to the influence of the severity of regurgitation, left ventricular ejection fraction (LVEF), and the dimensions of the left atrium (LA) and left ventricle (LV) on the postoperative prognosis. An additional aim was to identify preoperative risk factors associated with increased postoperative mortality and morbidity. A retrospective analysis was conducted on 421 patients diagnosed with ischemic mitral regurgitation who underwent concomitant mitral valve surgery and CABG. Exclusion criteria included emergent and urgent procedures as well as non-ischemic etiologies of mitral valve dysfunction. Results: The study cohort comprised 34.9% women and 65.1% men, with the mean age of 65.7 years (±7.57). A substantial proportion (76.7%) of patients were aged over 60 years. More than half (51.5%) presented with severe heart failure symptoms, classified as NYHA class III or IV, while over 70% were categorized as CCS class II or III. Among the surgical procedures performed, 344 patients underwent mitral valve repair, and 77 patients required mitral valve replacement. Additionally, 119 individuals underwent concomitant tricuspid valve repair. Short-term survival was significantly affected by the presence of hypertension, prior cerebrovascular events, and chronic kidney disease. In contrast, hypertension and chronic obstructive pulmonary disease were identified as significant predictors of adverse late-term outcomes. Conclusions: Interestingly, neither the preoperative severity of mitral regurgitation nor the echocardiographic measurements of LA and LV dimensions were found to significantly influence surgical outcomes. The perioperative risk, as assessed by the EuroSCORE II (average score: 10.0%), corresponded closely with observed mortality rates following mitral valve repair (9.9%) and replacement (10.4%). Notably, the need for concomitant tricuspid valve surgery was associated with an elevated mortality rate (12.4%). Furthermore, the preoperative echocardiographic evaluation of LA regurgitation severity, as well as LA and LV dimensions, did not exhibit a statistically significant impact on either early or long-term surgical outcomes. However, a reduced LVEF was correlated with increased long-term mortality. The presence of advanced clinical symptoms and the necessity for tricuspid valve repair were independently associated with a poorer late-term prognosis. Importantly, the annual mortality rate observed in the late-term follow-up of patients who underwent surgical treatment of ischemic mitral regurgitation was lower than rates reported in the literature for patients managed conservatively. The EuroSCORE II scale proved to be a reliable and precise tool in predicting surgical risk and outcomes in this patient population. Full article

Background/Objectives: Patients with peripheral artery disease (PAD) have a heightened risk of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and death. Despite this, limited progress has been made in identifying reliable biomarkers to prognosticate such outcomes. Circulating growth factors, known to influence endothelial function and the progression of atherosclerosis, may hold prognostic value in this context. The objective of this research was to evaluate a broad range of blood-based growth factors to investigate their potential as predictors of MACE in patients diagnosed with PAD. Methods: A total of 465 patients with PAD were enrolled in a prospective cohort study. Baseline plasma levels of five different growth factors were measured, and participants were monitored over a two-year period. The primary outcome was the occurrence of MACE within those two years. Comparative analysis of protein levels between patients who did and did not experience MACE was performed using the Mann–Whitney U test. To assess the individual prognostic significance of each protein for predicting MACE within two years, Cox proportional hazards regression was performed, adjusting for clinical and demographic factors including a history of coronary and cerebrovascular disease. Subgroup analysis was performed to assess the prognostic value of these proteins in females, who may be at higher risk of PAD-related adverse events. Net reclassification improvement (NRI), integrated discrimination improvement (IDI), and area under the receiver operating characteristic curve (AUROC) were calculated to assess the added value of significant biomarkers to model performance for predicting 2-year MACE when compared to using demographic/clinical features alone. Kaplan–Meier curves stratified by IGFBP-1 tertiles compared using log-rank tests and Cox proportional hazards analysis were used to assess 2-year MACE risk trajectory based on plasma protein levels. Results: The average participant age was 71 years (SD 10); 31.1% were female and 47.2% had diabetes. By the end of the two-year follow-up, 18.1% (n = 84) had experienced MACE. Of all proteins studied, only insulin-like growth factor-binding protein 1 (IGFBP-1) showed a significant elevation among patients who suffered MACE versus those who remained event-free (20.66 [SD 3.91] vs. 13.94 [SD 3.80] pg/mL; p = 0.012). IGFBP-1 remained a significant independent predictor of 2-year MACE occurrence in the multivariable Cox analysis (adjusted hazard ratio [HR] 1.57, 95% CI 1.21–1.97; p = 0.012). Subgroup analyses revealed that IGFBP-1 was significantly associated with 2-year MACE occurrence in both females (adjusted HR 1.52, 95% CI 1.16–1.97; p = 0.015) and males (adjusted HR 1.04, 95% CI 1.02–1.22; p = 0.045). Incorporating IGFBP-1 into the clinical risk prediction model significantly enhanced its predictive performance, with an increase in the AUROC from 0.73 (95% CI 0.71–0.75) to 0.79 (95% CI 0.77–0.81; p = 0.01), an NRI of 0.21 (95% CI 0.07–0.36; p = 0.014), and an IDI of 0.041 (95% CI 0.015–0.066; p = 0.008), highlighting the prognostic value of IGFBP-1. Kaplan–Meier analysis showed an increase in the cumulative incidence of 2-year MACE across IGFBP-1 tertiles. Patients in the highest IGFBP-1 tertile experienced a significantly higher event rate compared to those in the lowest tertile (log-rank p = 0.008). In the Cox proportional hazards analysis, the highest tertile of IGFBP-1 was associated with increased 2-year MACE risk compared to the lowest tertile (adjusted HR 1.81; 95% CI: 1.31–2.65; p = 0.001). Conclusions: Among the growth factors analyzed, IGFBP-1 emerged as the sole biomarker independently linked to the development of MACE over a two-year span in both female and male PAD patients. The addition of IGFBP-1 to clinical features significantly improved model predictive performance for 2-year MACE. Measuring IGFBP-1 levels may enhance risk stratification and guide the intensity of therapeutic interventions and referrals to cardiovascular specialists, ultimately supporting more personalized and effective management strategies for patients with PAD to reduce systemic vascular risk. Full article

Background: Septoplasty is a widely performed surgical procedure to correct nasal septal deviations and improve respiratory function. One of its most significant complications is septal perforation, which can severely impact the patient’s quality of life. This study evaluates the use of bovine pericardium grafts to enhance mucosal healing, thereby reducing the risk of postoperative septal perforation in cases with intraoperative bilateral mucosal defects. Methods: A retrospective study was conducted on patients who underwent septoplasty between January 2018 and January 2025 in whom bovine pericardium grafts were interposed due to the presence of bilateral opposing mucosal defects. Epidemiological and surgical variables were recorded, and outcomes and complications were analyzed. Results: Out of the 4151 septoplasties performed, 30 cases (0.72%) required bovine pericardium interposition. The mean patient age was 42.87 years. Postoperative absence of septal perforation was confirmed in 90% of cases, with only three postoperative perforations, all asymptomatic and approximately 2 mm in size. Complications were recorded in three patients (10%), all of which were resolved with conservative treatment and without sequelae. Conclusions: For the first time in routine surgical practice, bovine pericardium emerges as a viable option for preventing postoperative septal perforation in cases with bilateral opposing mucosal defects. With a high closure rate and a low incidence of adverse events, this material represents a promising tool in septal surgery. Full article

Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by the increased production of monoclonal immunoglobulin. Patients with MM are at high risk of suffering from disease-related complications. Osteolytic bone disease is one of the most common disease-related complications, resulting in chronic pain and skeletal pathologies that contribute significantly to high morbidity and mortality rates among MM patients. In addition to standard anti-MM therapy, management of disease-related sequelae is integral to improving quality of life in MM patients. Bisphosphates have long been the mainstay treatment for patients with myeloma bone disease (MBD) due to their ability to reduce the incidence of skeletal-related adverse events. However, in recent years, a deeper understanding of the complex biology and pathophysiology associated with myeloma bone disease has led to the development of novel therapies that have the potential to improve MM patient management and outcomes. This narrative review uses the most recent extant publications to review all such advancements. It aims to summarize evidence-based strategies for the management of myeloma bone disease and therapy-associated adverse events whilst highlighting current guidelines on optimal bisphosphonate use and providing an overview of promising new agents currently in clinical development. Full article

The global aging population has led to a growing incidence of malignancies, including metastatic non-small-cell lung cancer (mNSCLC). Immunosenescence may affect the efficacy of immune checkpoint inhibitors (ICIs). The prognostic role of age in ICI-treated mNSCLC remains uncertain. Objectives: This study aims to assess whether age independently influences survival, response, and toxicity in mNSCLC patients treated with ICIs, and to examine potential interactions with clinical factors. Methods: In this retrospective cohort study, 105 patients with mNSCLC treated with ICIs were enrolled. Patients were stratified into four groups based on age quartiles. Clinical, pathological, and treatment data were collected. Survival outcomes were analyzed using Kaplan–Meier curves, ROC curve and multivariable Cox regression models adjusted for confounders. Interaction and restricted cubic spline analyses were performed to explore age-related effects. The p < 0.05 was considered as statistically significant. Results: The median age was 60.8 years. Clinical benefit—defined as objective response rate (51.4%) and disease control rate (86.6%)—did not significantly differ across age quartiles (p = 0.551 and p = 0.257, respectively). Median overall survival also did not differ significantly (p = 0.2853). Cox regression and spline modeling demonstrated no independent association between chronological age and all-cause mortality (Model 3: HR = 1.00, 95% CI: 0.95–1.04, p = 0.889). However, interaction analyses revealed that poor ECOG performance status (p = 0.001), longer duration of ICI treatment (p < 0.0001), and low PD-L1 expression (p = 0.017) were stronger predictors of mortality in older patients. Age was associated with increased immune-related adverse events and higher Charlson Comorbidity Index scores, suggesting the need for age-specific management strategies. Conclusions: Age alone does not predict survival in mNSCLC patients receiving ICIs. However, functional status, treatment duration and PD-L1 expression may modify age-related outcomes. Full article

Introduction: In the past decade, chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment of relapsed refractory multiple myeloma (RRMM) and lymphoma, but it is associated with significant cardiovascular adverse effects. We aim to analyze the incidence, patterns, and outcomes of cardiac events in RRMM and lymphoma patients undergoing CAR-T therapy utilizing the FDA Adverse Event Reporting System (FAERS) database, paving the way for future research and being more vigilant in treating high-risk populations. Methods: We conducted a retrospective post-marketing pharmacovigilance inquiry using the FDA Adverse Event Reporting System (FAERS) database and the Medical Dictionary for Regulatory Activities (MEDRA). We examined the adverse effects associated with CAR-T and TCE since their FDA approval in US and non-US populations (accessed 5 January 2024), and we analyzed the incidence of cardiac events related to six CAR-T products: Idecabtagene vicleucel, Ciltacabtagene autoleucel, Axicabtagene ciloleucel, Tisagenlecleucel, Lisocabtagene maraleucel, and Brexucabtagene autoleucel since FDA approval. Cardiotoxicities were assessed, including coronary artery disease (CAD), myocardial infarction (MI), arrhythmia, heart failure, and hypotension. Results: Out of 12,949 adverse events, we identified 675 (5.2%) cardiac events irrespective of severity. Almost 440 (65%) cardiac events were associated with cytokine release syndrome (CRS). The most common cardiotoxic event was atrial fibrillation (122), followed by the development of heart failure (113), ventricular arrhythmia (108), hypotension (87), and bradyarrhythmia (41). The mortality rate was highest among Brexucabtagene autoleucel recipients (n = 26, 2.3%), followed by Tisagenlecleucel (n = 71, 2.1%) and Lisocabtagene maraleucel (n = 10, 2.1%). Conclusions: CAR-T therapy can result in fatal adverse events due to its cardiotoxic properties. Timely monitoring, such as screening echocardiography and electrocardiograms, can help identify the at-risk population and allow for early intervention—particularly in patients with high baseline cardiovascular risk or previous exposure to cardiotoxic agents—thereby improving outcomes by enabling risk stratification and supportive management. Full article

Objective: The SHARON (Short course RadiatiON therapy for palliative treatment) Bone trial is a phase III randomized non-inferiority multicentric study comparing symptom relief for complicated bone metastases (BMs) achieved through hypofractionated accelerated palliative radiotherapy (RT) to a standard RT regimen. Methods: Eligible participants were adults with ECOG PS ≤ 3 who were referred for palliative RT for painful BMs. Patients were assigned to receive either 30 Gy delivered in 10 daily fractions or 20 Gy in 4 fractions over two consecutive days. The primary outcome was pain relief one month post-treatment. Pain relief and adverse events were also evaluated at 2, 3, 6, and 12 months after RT. This trial was registered at clinicaltrials.gov (NCT03503682). Results: Between February 2018 and November 2021, 83 patients were enrolled (30 Gy: 41; 20 Gy: 42). In the standard RT group, five patients did not complete the prescribed RT, while none in the experimental arm discontinued treatment (p = 0.026). Due to early mortality, the primary endpoint was evaluable in 73 patients (35 and 38 in the standard and experimental arms, respectively). The rate of complete pain response at one month was 22.9% and 28.9% in the 30 Gy and 20 Gy arms, respectively (p: 0.571). The overall pain response rates, which included complete and partial responses, were 74.3% and 78.9% in the 30 Gy and 20 Gy arms, respectively (p = 0.638), when considering at least a 2-point reduction in the numerical rating scale. In both arms, 4.8% of patients experienced Grade >2 toxicity. Conclusions: Administering 20 Gy in four fractions twice a day is non-inferior to the standard 30 Gy delivered in 10 fractions for pain relief in the context of complicated BMs. Furthermore, this regimen demonstrated comparable safety in terms of acute toxicity, with a lower incidence of definitive interruptions of radiotherapy. Full article