Search Results (448)

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic review aimed to analyze the study design, characteristics, and timing of the treatments administered—including the type of systemic chemotherapy, intraperitoneal agents used in PIPAC, and interval between administrations—as well as the clinical outcomes, safety profile, and overall methodological quality of the available literature on bidirectional treatment for peritoneal metastases. Methods: A systematic literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to April 2025. Studies were included if they reported clinical outcomes of patients undergoing bidirectional treatment. Data extraction focused on survival, response assessment (PRGS, PCI), adverse events, systemic and intraperitoneal regimens, treatment interval, and study methodology. Results: A total of 22 studies involving 1015 patients (742 treated with bidirectional therapy) were included. Median overall survival ranged from 2.8 to 19.6 months, with the most favorable outcomes observed in gastric and colorectal cancer cohorts. PRGS improvement after multiple PIPAC cycles was reported in >80% of evaluable cases. High-grade adverse events (CTCAE ≥ 3) occurred in up to 17% of patients in most studies, with only one study reporting treatment-related mortality. However, methodological quality was generally moderate, with considerable heterogeneity in treatment protocols, response criteria, systemic regimens, and toxicity attribution. Conclusions: Bidirectional therapy with PIPAC and systemic chemotherapy appears to be a feasible and potentially effective strategy for selected patients with peritoneal metastases. Despite encouraging outcomes, definitive conclusions are limited by the retrospective nature and heterogeneity of available studies. Prospective standardized trials are needed to confirm efficacy, clarify patient selection, and optimize treatment protocols. Full article

Cutaneous and oral mucosal adverse events (AEs) are among the most common non-hematologic toxicities observed during breast cancer treatment. These complications arise across various therapeutic modalities including chemotherapy, targeted therapy, hormonal therapy, radiotherapy, and immunotherapy. Although often underrecognized compared with systemic side effects, dermatologic and mucosal toxicities can severely impact the patients’ quality of life, leading to psychosocial distress, pain, and reduced treatment adherence. In severe cases, these toxicities may necessitate dose reductions, treatment delays, or discontinuation, thereby compromising oncologic outcomes. The growing use of precision medicine and novel targeted agents has broadened the spectrum of AEs, with some therapies linked to distinct dermatologic syndromes and mucosal complications such as mucositis, xerostomia, and lichenoid reactions. Early detection, accurate classification, and timely multidisciplinary management are essential for mitigating these effects. This review provides a comprehensive synthesis of current knowledge on cutaneous and oral mucosal toxicities associated with modern breast cancer therapies. Particular attention is given to clinical presentation, underlying pathophysiology, incidence, and evidence-based prevention and management strategies. We also explore emerging approaches, including nanoparticle-based delivery systems and personalized interventions, which may reduce toxicity without compromising therapeutic efficacy. By emphasizing the integration of dermatologic and mucosal care, this review aims to support clinicians in preserving treatment adherence and enhancing the overall therapeutic experience in breast cancer patients. The novelty of this review lies in its dual focus on cutaneous and oral complications across all major therapeutic classes, including recent biologic and immunotherapeutic agents, and its emphasis on multidisciplinary, patient-centered strategies. Full article

Background: Patients with resected stage IIB and IIC melanoma are at high risk of recurrence and distant metastasis, despite surgical treatment. The recent emergence of immune checkpoint inhibitors (ICIs) has led to their evaluation in the adjuvant setting for early-stage disease. This review aims to synthesize current evidence regarding adjuvant immunotherapy for stage IIB/IIC melanoma, explore emerging strategies, and highlight key challenges and future directions. Methods: We conducted a comprehensive literature review of randomized clinical trials, observational studies, and relevant mechanistic and biomarker research on adjuvant therapy in stage IIB/IIC melanoma. Particular focus was placed on pivotal trials evaluating PD-1 inhibitors (KEYNOTE-716 and CheckMate 76K), novel vaccine and targeted therapy trials, mechanisms of resistance, immune-related toxicity, and biomarker development. Results: KEYNOTE-716 and CheckMate 76K demonstrated significant improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with pembrolizumab and nivolumab, respectively, compared to placebo. However, no definitive overall survival benefit has yet been shown. Adjuvant immunotherapy is linked to immune-related adverse events, including permanent endocrinopathies. Emerging personalized approaches, such as circulating tumor DNA monitoring and gene expression profiling, may enhance patient selection, but remain investigational. Conclusions: Adjuvant PD-1 blockade offers clear RFS benefits in high-risk stage II melanoma, but optimal patient selection remains challenging, due to uncertain overall survival benefit and toxicity concerns. Future trials should integrate biomarker-driven approaches to refine therapeutic decisions and minimize overtreatment. Full article

Background: Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of severe aortic valve stenosis (AS). Balloon post-dilatation (PD) remains an important procedural step to optimize valve function by resolving incomplete valve expansion, which may lead to paravalvular regurgitation and other potentially adverse effects. There are only limited data on the predictors, incidence, and clinical impact of PD during TAVI. Methods: This retrospective, single-center study analyzed 585 patients who underwent TAVI (2016–2022). Pre-procedural evaluations included transthoracic echocardiography and CT angiography to assess key parameters, including the aortic valve calcium score (AVCS); aortic valve calcium density (AVCd); aortic valve maximal systolic transvalvular flow velocity (AV Vmax); and aortic valve mean systolic pressure gradient (AV MPG). We identified imaging predictors of PD and evaluated associated clinical outcomes by analyzing procedural endpoints (according to VARC-3 criteria) and long-term survival. Results: PD was performed on 67 out of 585 patients, with elevated AV Vmax (OR: 1.424, 95% CI: 1.039–1.950; p = 0.028) and AVCd (OR: 1.618, 95% CI: 1.227–2.132; p = 0.001) emerging as a significant independent predictor for PD in TAVI. Kaplan–Meier survival analysis revealed no significant differences in short- and mid-term survival between patients who underwent PD and those who did not. Interestingly, patients requiring PD exhibited a lower incidence of adverse events regarding major vascular complications, permanent pacemaker implantations and stroke. Conclusions: The study highlights AV Vmax and AVCd as key predictors of PD. Importantly, PD was not associated with increased procedural adverse events and did not predict adverse events in this contemporary cohort. Full article

Background/Objectives: Acne vulgaris is a widespread, chronic inflammatory skin condition that significantly impacts patients’ quality of life. Although oral isotretinoin remains the most effective treatment, recent evidence suggests that H₁-antihistamines such as desloratadine and levocetirizine may enhance acne therapy. This study assesses whether combining H₁-antihistamines to isotretinoin enhances treatment efficacy in acne vulgaris compared to isotretinoin alone. Methods: Our analysis included 10 randomized controlled trials involving 675 patients collectively, predominantly from Asia and the Middle East. Data were extracted by two independent reviewers, with discrepancies resolved by a third. Risk of bias was assessed using the Cochrane RoB 2 tool. Analyses were performed using RevMan 5.4 with random-effects models, and heterogeneity was evaluated via I² and Q tests. Sensitivity analyses were conducted to assess result robustness. Results: Combination therapy with isotretinoin and desloratadine showed a significantly greater reduction in GAGS (Global Acne Grading Scale) score by week 12 (p < 0.00001; MD 2.68, 95% CI 1.60 to 3.75; I² = 0%) while earlier timepoints showed non-significant or borderline results. For inflammatory lesions, significant improvements with desloratadine emerged at weeks 4, 8, and 12 after excluding an influential outlier, with low heterogeneity and consistent direction of effect. Non-inflammatory lesions did not differ significantly at weeks 4 or 8. At week 12, a significant reduction was seen in the desloratadine subgroup (OR 2.61, p = 0.003, I² = 11%) and in overall pooled analysis (OR 2.77, p < 0.0001, I² = 2%). Among side effects, acne flare-ups, pruritus, and cheilitis were significantly reduced in the desloratadine group, as well as in pooled analysis. Xerosis did not consistently differ between groups. Overall, desloratadine improved tolerability and reduced mucocutaneous adverse events more than levocetirizine. Conclusions: Current evidence suggests that combining oral antihistamines with isotretinoin may offer therapeutic benefits in acne management, particularly in enhancing tolerability and potentially improving clinical outcomes, as reflected by significant reductions in GAGS scores and mucocutaneous adverse effects such as cheilitis, pruritus, and acne flare-ups. Full article

Axial truncal dystonia can present as either flexion or extension, often with a tendency toward lateral movement. Flexion dystonia is more common and may represent a clinical spectrum associated with parkinsonism. In contrast, extensor trunk dystonia is less frequent and exhibits a diverse range of causes. In this paper, we reviewed the literature on axial extensor trunk dystonia. We identified 11 studies involving 49 patients, of which only 10 had idiopathic trunk dystonia. Treatment with botulinum neurotoxin A (BoNT/A) emerged as the most effective therapy; however, many studies did not provide detailed descriptions of the treatment (4/11) and follow-up periods were not specified or short term (up to one–two years). We present four new, well-documented patients with the idiopathic form of extensor trunk dystonia who were treated with BoNT/A with moderate to significant effect according to Global Clinical Impression scale (GCI) and Burke-Fahn-Marsden (BFM) dystonia scale. These cases include long-term follow-up for three patients, all without any adverse events. While the diagnostic process and treatment can be challenging, we recommend using BoNT/A with adjusted doses tailored to the appropriate muscle groups as a first-line treatment. 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: Immune checkpoint inhibitors have significantly transformed the treatment paradigm of advanced melanoma, leading to substantial improvements in survival outcomes. However, this therapeutic success is accompanied by a spectrum of treatment-related adverse events, some of which are increasingly recognised as enduring and non-reversible. Whilst early-onset immune-related toxicities have been well characterized, late-onset toxicities, often emerging in patients with long-term disease control, remain understudied and are frequently overlooked. Methods: To address this knowledge gap, we conducted a retrospective multicentre study in three UK tertiary referral centres, exploring immune-related adverse events in 246 patients with melanoma who received immune checkpoint inhibitors in the advanced setting. We defined late-onset immune-related adverse events as those occurring at least 3 months after the last cycle of immune checkpoint inhibitors. Results: Although most patients experienced early-onset toxicity, almost 15% of patients developed late-onset immune-related adverse events, including skin rash, colitis, hepatitis, and arthritis, among others. These were often challenging to manage and necessitated the use of systemic steroids. Up to 2% of patients presented ultra-late-onset toxicities, defined as those events occurring at least 12 months after treatment completion. Conclusions: This study provides valuable insights into the characteristics of late-onset immune-related adverse events. To further advance our understanding of these late-onset toxicities, dedicated prospective studies are needed to assess risk factors associated with their development and their impact on quality of life. Additionally, translational research focused on finding predictive biomarkers is essential to identify patients at a higher risk of developing delayed adverse events and to understand how best to manage them. Full article

Background and Objectives: Type 2 diabetes (T2D) is a global health burden with increasing prevalence, necessitating effective management strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as beneficial therapies, promoting both glycemic control and weight loss, yet real-world data on sex differences in response are limited. This study aimed to investigate sex-based differences in glycemic and weight outcomes, as well as adverse effects, in T2D patients treated with GLP-1 RAs at a single diabetes center. Materials and Methods: In this retrospective analysis, 114 patients (58.8% men) with T2D who were initiated on GLP-1 RA therapy between 2015 and 2023 were evaluated. Data on HbA1c, BMI, and adverse events were collected at baseline and 3, 6, and 12 months post-treatment initiation. Results: Our findings indicated a statistically significant HbA1c reduction (from 8.6% at GLP-1 RA initiation to 6.9% at 12 months in men (p < 0.001) and from 8.4% at initiation to 7.0% at 12 months after GLP-1 RA initiation (p < 0.001) in women). By 12 months, a significantly greater proportion of women compared to men achieved ≥ 5% (51.1% vs. 28.4%, p = 0.019) and ≥10% weight loss (29.8% vs. 9.0%, p = 0.006), with both differences reaching statistical significance. A statistically significant difference in weight loss in mean weight change and percent weight change in men vs. women was observed from month 6 of therapy. Conclusions: These findings underscore the effectiveness of GLP-1 RAs in improving glycemic control and weight loss in a real-world setting and suggest that women may experience greater weight reduction. Understanding these differences could inform personalized treatment strategies for optimized outcomes in T2D management. Full article

Chronic Coronary Syndrome (CCS) significantly impacts quality of life and increases the risk of adverse cardiovascular events, remaining the leading cause of mortality worldwide. The use of sensor technology in medicine is emerging as a promising approach to enhance the management and monitoring of patients across a wide range of diseases. Recent advancements in engineering and nanotechnology have enabled the development of ultra-small devices capable of collecting data on critical physiological parameters. Several sensors integrated in wearable and implantable devices, instruments for exhaled gas analysis, smart stents and tools capable of real time biochemical analysis have been developed, and some of them have demonstrated to be effective in CCS management. Their application in CCS could provide valuable insights into disease progression, ischemic events, and patient responses to therapy. Moreover, sensor technologies can support the personalization of treatment plans, enable early detection of disease exacerbations, and facilitate prompt interventions, potentially reducing the need for frequent hospital visits and unnecessary invasive diagnostic procedures such as coronary angiography. This review explores sensor integration in CCS care, highlighting technological advances, clinical potential, and implementation challenges. Full article

Background: Total neoadjuvant therapy (TNT) has emerged as a promising strategy for locally advanced rectal cancer (LARC). By administering both chemoradiotherapy (CRT) and systemic chemotherapy (CHT) pre-surgery, TNT is associated with improved disease-free survival (DFS), reduced distant metastases, and higher pathological complete response (pCR) rates. Materials and Methods: This study included patients with LARC who received various TNT schedules: induction chemotherapy (iCHT), consolidation chemotherapy (cCHT), or a combination of both (sandwichCHT). We analyzed treatment adherence, toxicity, and pathological response. Local and distant disease recurrence, as well as survival outcomes, were also evaluated. Results: Between May 2021 and January 2025, 70 patients received TNT. Treatment included iCHT (41%), sandwichCHT (49%), and cCHT (10%). Most patients (94%) received long-course radiotherapy (LCRT). Overall, TNT was well tolerated, with grade 2 gastrointestinal toxicity during CRT being the most common frequent adverse event (33%). Disease progression during TNT was noted in five patients (7%); three of these patients were receiving chemotherapy, while two underwent surgical resection of the primary tumor. A watch-and-wait strategy was adopted for five patients (7%) following TNT. Surgical procedures performed included anterior resection (92%), abdominoperineal resection (7%), and local excision (1%). Pathological assessment revealed an overall pCR rate of 30%. With a median follow-up of 17 months, no patients experienced local recurrence. Post-surgery, 10 patients (17%) developed disease progression. The median DFS was 14.7 months. Five patients (7%) died during the follow-up period, with only one death attributed to causes other than disease progression. Conclusions: In this cohort of LARC patients, TNT demonstrated favorable tolerability and encouraging short-term efficacy. Full article

Epilepsy remains a major therapeutic challenge, with approximately one-third of patients experiencing drug-resistant epilepsy (DRE) despite the availability of multiple antiseizure medications (ASMs). This review aims to evaluate emerging ASMs—cenobamate, fenfluramine, ganaxolone, ezogabine (retigabine), and perampanel—with a focus on their mechanisms of action, pharmacological profiles, and potential role in precision medicine. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science to identify preclinical and clinical studies evaluating the pharmacodynamics, pharmacokinetics, efficacy, and safety of the selected ASMs. Relevant trials, reviews, and mechanistic studies were reviewed to synthesize the current understanding of their application in DRE and specific epilepsy syndromes. Each ASM demonstrated unique mechanisms targeting hyperexcitability, including the modulation of γ-aminobutyric acid receptor A (GABA-A) receptors, sodium and potassium channels, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptors), and serotonin systems. These mechanisms correspond with specific pathophysiological features in syndromes such as Dravet and Lennox–Gastaut. Evidence from clinical trials supports their use as adjunctive therapies with generally favorable tolerability, though adverse events and variable efficacy profiles were noted. The mechanistic diversity of these emerging ASMs supports their value in personalized epilepsy management, particularly in treatment-resistant cases. While the promise of precision medicine is evident, further studies are required to address challenges related to long-term safety, cost, and equitable access. Full article

Background and Objective: Benign prostatic hyperplasia (BPH) and urethral stricture (US) are common causes of lower urinary tract symptoms in ageing men, often requiring repeated interventions. Conventional treatments of US, such as urethrotomy and mechanical dilation, have high recurrence rates. The Optilume drug-coated balloon catheter system, which combines mechanical dilation with paclitaxel delivery, has emerged as a minimally invasive alternative. This systematic review assesses its efficacy and safety in the management of BPH and US. Methods: A systematic search of PubMed was conducted for studies published between August 2020 and October 2023. Eligible studies included randomised controlled trials (RCTs), cohort studies, and case reports evaluating Optilume’s therapeutic effects. Key outcomes analysed included symptom relief, urinary flow improvement, recurrence rates, and adverse events. Results: Seven studies met the inclusion criteria, including five on US and two on BPH. The ROBUST trial series demonstrated sustained improvements in urinary flow rates and symptom scores in US patients over follow-up periods of up to four years. The EVEREST-1 and PINNACLE trials reported significant symptom relief and preserved sexual function in BPH patients, with a favourable safety profile and minimal complications. Conclusions: Optilume appears to be a promising alternative to conventional endoscopic treatments for US and BPH, offering durable symptom relief with a low complication rate. Further long-term studies are required to confirm its efficacy and cost-effectiveness in routine clinical practice. Full article

Background: Carfilzomib (CFZ) is a proteasome inhibitor with known cardiotoxic effects used in multiple myeloma (MM) treatment. Cardio-oncology guidelines recommend cardiovascular risk assessment via echocardiography. Left atrial strain (LAS) is not yet included as a marker of cardiotoxicity, but it is emerging as a potential indicator of cardiac dysfunction. Objective: This study evaluates LAS as a predictor of CFZ-related hypertensive cardiovascular adverse events (CVAEs) in MM patients, with or without prior hypertension. Methods: A total of 125 MM patients treated with CFZ at the Hypertension Center, “Città della Salute e della Scienza” in Turin, were enrolled. Baseline assessments included transthoracic echocardiography for LAS analysis via Philips QLAB software. Results: During CFZ therapy, 52% of patients experienced hypertensive events. LAS conduit was significantly impaired in those who experienced CVAEs (−16.20 [−20.75; −12.65] vs. −20.80 [−26.30; −15.40], p = 0.006) and LAS conduit > −22 acted as a predictor of hypertensive adverse events in the normotensive population (OR 2.37 [1.02; 5.50]). Conclusion: These findings indicate that alterations in LAS conduit are linked to an increased risk of hypertensive adverse events during CFZ treatment. Incorporating LAS measurement into cardiovascular risk assessments may improve personalized risk stratification for MM patients, especially those without pre-existing hypertension. Full article