Search Results (1,250)

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

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: This systematic review investigates the role of virtual reality (VR)-based multisensory cognitive training in cognitive function, executive function and wayfinding ability among people diagnosed with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Methods: The review was carried out using PRISMA guidelines. PubMed, Scopus, Embase, and Google Scholar were searched up from inception to February 2025 using terms related to MCI, AD, VR, and cognitive functions. Studies were included if they involved participants with MCI or early AD, used VR-based training, collected baseline data, and reported cognitive outcomes. Results: Nine studies with MCI were included, but no eligible studies focused on AD. Seven out of nine eligible studies in MCI reported significant improvements in global cognitive function (MoCA, CERAD-K, MMSE). Some studies showed improvements in executive function (EXIT-25, TMT-A/B, and SCWT), while others found no significant differences. One study reported improved depression/mental status (GDS, MOSES, QoL-AD). Just one study reported improvement in functional ability (IADL). One study reported enhanced cognition and reduced discomfort (SSQ). VR programs were generally well-tolerated, with no significant adverse events reported. Conclusions: VR shows promise for improving cognitive function in MCI. VR also showed potential benefits in executive function and psychological outcomes like depression and quality of life, though consistency varied. Full article

Secukinumab (SEC) is a recombinant, fully human monoclonal antibody that is selective for interleukin-17A (IL-17A). SEC may increase the risk of developing infections such as oral herpes and oral candidiasis. The aim of this case report and literature review was to describe chronic hyperplastic candidiasis (CHC) in a patient with psoriasis (PsO) and psoriatic arthritis (PsA) treated with SEC. CHC is a rare and atypical clinical entity. A definitive diagnosis requires biopsy of the oral mucosa for histopathological diagnosis (PHD). The differential diagnosis includes hairy tongue, hairy leukoplakia, oral lichen planus (OLP), oral lichenoid reaction (OLR), leukoplakia, frictional keratosis, morsication, oral psoriasis, syphilis, and oral lesions associated with coronavirus disease (COVID-19). In addition to the usual factors (xerostomia, smoking, antibiotics, vitamin deficiency, immunosuppression, comorbidities), the new biological therapies/immunotherapies are a predisposing factor for oral candidiasis. The therapeutic approach must be multidisciplinary and in consultation with a clinical immunologist. Dentists and specialists (oral medicine, dermatologists, rheumatologists) must be familiar with the oral adverse events of the new biological therapies. Simultaneous monitoring of patients by clinical immunology and oral medicine specialists is crucial for timely diagnosis and therapeutic intervention to avoid possible adverse events and improve quality of life (QoL). Full article

Background: Knee osteoarthritis (KOA) is a prevalent degenerative joint disease that can greatly affect quality of life in middle-aged and elderly individuals. Nutritional supplements are increasingly used for KOA due to their low risk, but direct comparative evidence on their efficacy and safety remains scarce. This study aimed to systematically compare the effectiveness and safety of seven common nutritional supplements for KOA. Methods: A systematic review and network meta-analysis were conducted following PRISMA guidelines. Embase, PubMed, and the Cochrane Library were searched through December 2024 for randomized controlled trials (RCTs) evaluating use of eggshell membrane, vitamin D, Boswellia, curcumin, ginger, krill oil, or collagen, versus placebo, in adults with KOA. Primary outcomes included changes in scores for WOMAC pain, stiffness and function, and pain visual analog scale (VAS). Adverse events were also assessed. Bayesian network meta-analyses estimated ranking probabilities for each intervention. Results: In total, 39 RCTs (42 studies; 4599 patients) were included. Compared with placebo, Boswellia showed significant improvements in WOMAC pain (mean difference [MD] = 10.58, 95% CI: 6.45 to 14.78, p < 0.05), stiffness (MD = 9.47, 95% CI: 6.39 254 to 12.74, p < 0.05), function (MD = 14.00, 95% CI: 7.74 to 20.21, p < 0.05), and VAS pain (MD = 17.26, 95% CI: 8.06 to 26.52, p < 0.05). Curcumin, collagen, ginger, and krill oil also demonstrated benefits in some outcomes. No supplement was associated with increased adverse events compared to placebo. Bayesian rankings indicated Boswellia had the highest probability of being most effective for pain and stiffness, with krill oil and curcumin showing potential for function improvement. Conclusions: Nutritional supplements, particularly Boswellia, appear to be effective and well-tolerated for improving KOA symptoms and function. These results suggest that certain supplements may be useful as part of non-pharmacological KOA management. However, further large-scale, well-designed randomized controlled trials (RCTs) are needed to confirm these findings, particularly those that include more standardized dosages and formulations, as well as to evaluate their long-term efficacy. Full article

Background/Objectives: Cannabidiol (CBD) is a non-intoxicating cannabinoid touted for a variety of medical benefits, including alleviation of anxiety. While legalization of hemp-derived products in the United States (containing ≤0.3% delta-9-tetrahydrocannabinol [d9-THC] by weight) has led to a rapid increase in the commercialization of hemp-derived CBD products, most therapeutic claims have not been substantiated using clinical trials. This trial aimed to assess the impact of 6 weeks of treatment with a proprietary hemp-derived, full-spectrum, high-CBD sublingual solution similar to those available in the marketplace in patients with anxiety. Methods: An open-label pilot clinical trial (NCT04286594) was conducted in 12 patients with at least moderate levels of anxiety. Patients self-administered a hemp-derived, high-CBD sublingual solution twice daily during the 6-week trial (target daily dose: 30 mg/day CBD). Clinical change over time relative to baseline was assessed for anxiety, mood, sleep, and quality of life, as well as changes in cognitive performance on measures of executive function and memory. Safety and tolerability of the study product were also evaluated. Results: Patients reported significant reductions in anxiety symptoms over time. Concurrent improvements in mood, sleep, and relevant quality of life domains were also observed, along with stable or improved performance on all neurocognitive measures. Few side effects were reported, and no serious adverse events occurred. Conclusions: These pilot findings provide initial support for the efficacy and tolerability of the hemp-derived, high-CBD product in patients with moderate-to-severe levels of anxiety. Double-blind, placebo-controlled studies are indicated to obtain robust data regarding efficacy and tolerability of these types of products for anxiety. Full article

Context: Many patients at the end of life receive antibiotics to alleviate symptoms and improve quality of life; however, clear guidelines supporting decision making about the use of antibiotics are still lacking. Objectives: This study aimed to evaluate the benefits and harms of antibiotic use among patients under a palliative care community support team in Portugal. Methods: An observational, cross-sectional, retrospective study was conducted on 249 patients who died over a two-year period, having been followed for at least 30 days prior to their death. Data included patient demographics, clinical diagnoses, antibiotic prescriptions, and symptomatic outcomes. The effects of commonly prescribed antibiotics—amoxicillin + clavulanic acid, cefixime, ciprofloxacin, and levofloxacin—were compared using statistical analyses to assess survival, symptom intensity, and functional scales. Results: Adverse events, primarily infections and secretions, occurred in 57.8% of cases, with 33.7% receiving antibiotics. No significant difference in survival was observed across the antibiotic groups (p = 0.990). Symptom intensity significantly reduced after 72 h of treatment (p < 0.05), with ciprofloxacin demonstrating the greatest symptom control. The Palliative Outcome Scale decreased uniformly, with higher scores associated with amoxicillin + clavulanic acid (p = 0.004). The Palliative Performance Scale declined post-treatment, with significant changes noted for cefixime and ciprofloxacin (p < 0.05). Conclusions: Antibiotics may improve symptom control and quality of life in the end-of-life stage. While second-line antibiotics may offer additional benefits, the heterogeneity of the sample and limited adverse effect data underscore the need for further research to guide appropriate prescription practices in palliative care. Full article

Background: Mobile health applications have emerged as a novel tool to support secondary prevention after myocardial infarction (MI) or percutaneous coronary intervention (PCI). However, the impact of app-based interventions on clinically meaningful outcomes such as hospital readmissions remains uncertain. Objective: To systematically evaluate the effectiveness of smartphone app-based interventions in reducing unplanned hospital readmissions among post-MI/PCI patients. Methods: A systematic search of PubMed was conducted for randomized controlled trials published between January 2020 and April 2025. Eligible studies evaluated smartphone apps designed for secondary cardiovascular prevention and reported on unplanned hospital readmissions. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup analyses were performed based on follow-up duration and user adherence. Results: Four trials encompassing 827 patients met inclusion criteria. App-based interventions were associated with a significant reduction in unplanned hospital readmissions compared to standard care (RR 0.45; 95% CI: 0.23–0.89; p = 0.0219). Greater benefits were observed in studies with longer follow-up durations and higher adherence rates. Improvements in patient-reported outcomes, including health-related quality of life, were also documented. Heterogeneity was moderate. Major adverse cardiovascular events (MACEs) were reported in only two studies and were not analyzed due to inconsistent definitions and low event rates. Conclusions: Smartphone applications for post-MI/PCI care are associated with reduced unplanned hospital readmissions and improved patient-reported outcomes. These tools may play a meaningful role in future cardiovascular care models, especially when sustained engagement and personalized features are prioritized. Full article

Hurricanes and flooding events substantially elevate indoor fungal spore levels, which have been associated with increased risks of developing childhood asthma and other adverse respiratory outcomes. Although environmental fungal compositions following major hurricanes have been well characterized, the fungal communities within the nasal cavity (i.e., the nasal mycobiome) of exposed individuals remain unexplored. We collected nasal swab samples from infants following Hurricane Maria in San Juan, Puerto Rico, during two periods (March to August 2018 and February to September 2019). We processed a total of 58 samples (26 from the first year and 32 from the second year post-Hurricane Maria) and performed internally transcribed spacer (ITS) rRNA gene sequencing to characterize and compare the infant nasal mycobiome between the two groups. Although alpha-diversity did not differ significantly, beta-diversity analyses revealed significantly different fungal compositions between the two groups (p <0.01). Infants exposed during the first year post-Hurricane Maria had significantly higher abundances of Alternaria, Eutypella, Schizophyllum, and Auricularia, compared to infants from the second year. Alternaria was also more prevalent in the first-year than in the second-year infants (42% vs. 9%, p = 0.01). Our study provides evidence linking early-life hurricane exposures to elevated risks of developing childhood asthma. 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

Breast cancer (BC) is the most prevalent malignancy in women worldwide. Despite most cases being diagnosed in the early stages, patients typically require a multimodal treatment approach. This typically involves a combination of surgery, radiotherapy, systemic treatments (including chemotherapy or immunotherapy), targeted therapy, and endocrine therapy, depending on the disease subtype and the risk of recurrence. Moreover, patients with BC and germline mutations in the breast cancer genes 1 or 2 (BRCA1/BRCA2), (gBRCAm), who are typically young women, often require more aggressive therapeutic interventions. These mutations present unique characteristics that necessitate a distinct treatment approach, potentially influencing the side effect profiles of patients with BC. Regardless of the clear benefit observed with these treatments in terms of reduced recurrence and mortality rates, long-term, treatment-related adverse events occur that negatively affect the health-related quality of life (HRQoL) of BC survivors. Thus, long-term adverse events need to be factored into the treatment decision algorithm of patients with early BC (eBC). Physical, functional, emotional, and psychosocial adverse events can occur and represent a significant concern and a challenge for clinicians, patients, and their families. This review article provides an overview of the various long-term adverse events that patients with eBC may experience, including their associated risk factors, as well as management and prevention strategies. We also explore the evidence of the long-term impact of treatment on the HRQoL of patients with gBRCAm. By providing a comprehensive overview of current evidence and recommendations regarding patients’ HRQoL, we aim to equip clinicians with scientific and clinical knowledge and provide guidance to optimize care and improve long-term outcomes. 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: Providing appropriate treatment for pediatric patients after traffic accidents remains a significant challenge. Furthermore, limited studies have validated the long-term effectiveness and safety of integrative Korean medicine treatment (IKMT) based on follow-up periods of 6 months or longer for pediatric patients. Methods: A retrospective chart review was conducted, focused on children aged 0–6 years who visited one of seven Korean medicine hospitals after traffic accident injuries and received IKMT between 1 January 2019 and 30 June 2023. The primary outcome was the Numeric Rating Scale (NRS) scores of chief complaints, and the secondary outcomes were quality of life, adverse events, and satisfaction with IKMT. Statistical analyses were conducted using paired t-tests and descriptive statistics, with a significance level of 5%. Results: Sixty-four participants were included in the retrospective chart review, and fifty-seven guardians responded to the surveys (mean age: 4.84 ± 1.26 years; mean duration of treatment: 19.20 ± 25.38 days). Among the immediate symptoms after the accidents, flashbacks and intrusive symptoms as well as nightmares and crying were the most common (50.9%). Following treatment, the NRS scores for flashbacks and intrusive symptoms and for nightmares and crying showed meaningful improvements from the time right after the accidents to the survey period. Follow-up confirmed that quality of life scores on all dimensions corresponded with those of healthy children. Nine adverse events were reported, and the participants fully recovered without the need for additional treatment. Furthermore, 91.2% of the survey respondents were satisfied with IKMT. Conclusions: IKMT was effective and safe for alleviating the post-accident symptoms in infants and young children aged 0–6 years involved in traffic accidents. 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

Artificial intelligence (AI) and machine learning (ML) are increasingly transforming the landscape of cosmetic formulation, enabling the development of safer, more effective, and personalized products. This article explores how AI-driven predictive modeling is applied across various components of cosmetic products, including surfactants, polymers, fragrances, preservatives, antioxidants, and prebiotics. These technologies are employed to forecast critical properties such as texture, stability, and shelf-life, optimizing both product performance and user experience. The integration of computational toxicology and ML algorithms also allows for early prediction of skin sensitization risks, including the likelihood of adverse events such as allergic contact dermatitis. Furthermore, AI models can support efficacy assessment, bridging formulation science with dermatological outcomes. The article also addresses the ethical, regulatory, and safety challenges associated with AI in cosmetic science, underlining the need for transparency, accountability, and harmonized standards. The potential of AI to reshape dermocosmetic innovation is vast, but it must be approached with robust oversight and a commitment to user well-being. Full article