Search Results (16,115)

Obesity is a major global health challenge strongly associated with increased cardiometabolic morbidity and mortality. In men, obesity is characterized by a predominance of visceral adiposity, which is metabolically active and closely linked to systemic inflammation, hormonal dysregulation, and adverse cardiovascular outcomes. Despite its clinical relevance, male obesity remains underrecognized as a distinct pathophysiological condition. This study aimed to analyze the inflammatory mechanisms underlying male obesity and their relationship with cardiometabolic risk. A structured narrative review was conducted based on a PICo-guided research question, with literature searches performed in PubMed/MEDLINE, Scopus, Web of Science, Embase, and ScienceDirect, covering publications from 2015 to 2026. Studies focusing on male obesity, inflammatory pathways, and cardiometabolic outcomes were included. Evidence indicates that visceral adipose tissue acts as an active endocrine organ, releasing pro-inflammatory cytokines such as TNF-α and IL-6, contributing to chronic low-grade inflammation. This inflammatory state is associated with insulin resistance (IR), endothelial dysfunction, and oxidative stress, mediated by intracellular pathways including NF-κB and JNK. Additionally, adipokine imbalance, characterized by reduced adiponectin and increased leptin levels, further exacerbates metabolic and vascular impairment. Hormonal alterations, particularly reduced testosterone levels, play a key role in amplifying visceral fat accumulation and inflammation, creating a bidirectional relationship between hypogonadism and metabolic dysfunction. Clinically, these mechanisms highlight the importance of integrating inflammatory biomarkers, body composition assessment, and hormonal evaluation into the management of male obesity. Emerging therapies, including GLP-1 receptor agonists and immunometabolic interventions, offer promising strategies for reducing cardiometabolic risk. In conclusion, male obesity represents a complex, inflammation-driven condition requiring a comprehensive and mechanism-based approach to improve clinical outcomes and guide future therapeutic developments. Full article

Over the last years, incretin receptor agonists—including glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RA) and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide—have dramatically improved the management of type 2 diabetes, overweight and obesity. However, as the use of incretin receptor agonists continues to increase worldwide, micronutrient deficiencies—including iron deficiency—have emerged as newly recognized adverse effects of these drugs. The present article aims to discuss recent preliminary observational evidence on the potential relationship between incretin receptor agonist-based therapies and the development of iron deficiency and iron deficiency anemia (IDA), as well as the potential mechanisms by which incretin receptor agonists may affect iron homeostasis. Potential mechanisms and factors underlying the development of iron deficiency and IDA in patients treated with incretin receptor agonist-based therapies include inadequate dietary iron intake (due to incretin receptor agonist-mediated reduction in food intake and/or gastrointestinal adverse effects of incretin receptor agonists), low dietary variety, monotonous diets, and changes in food preferences, as well as impairment of intestinal iron absorption (due to delayed gastric emptying, reduced small intestinal motility and/or decreased gastric acid secretion caused by incretin receptor agonists). Moreover, vitamin B2 (riboflavin) deficiency and changes in gut microbiota composition are hypothetical mechanisms that may partly explain iron deficiency in patients treated with incretin receptor agonists, although these hypotheses require confirmation through mechanistic studies. Even though iron deficiency and IDA currently appear to be uncommon adverse effects of incretin receptor agonist-based therapies, clinicians should be aware of the possibility of their occurrence to ensure appropriate prevention and management of these nutritional complications. Nevertheless, future prospective studies are certainly needed to better establish the causal relationship between the initiation of incretin receptor agonist-based therapies and the development of iron deficiency/IDA, as well as the exact mechanisms underlying the potential development of these nutritional complications in patients treated with incretin receptor agonists. Meanwhile, the prescription of incretin receptor agonists should not be unjustifiably restricted by the possible and modest risk of iron deficiency and IDA in patients with one or more approved indications for therapeutic use of these agents. Since no established guidelines currently exist for the prevention and management of iron deficiency and IDA in patients treated with incretin receptor agonists, we herein propose practical strategies to address these possible nutritional complications of incretin receptor agonist-based therapies. These proposed strategies should only be regarded as practical clinical approaches deriving from the existing recommendations for the prevention and management of iron deficiency and IDA, although their cost-effectiveness for the prevention and management of incretin receptor agonist-associated iron deficiency/IDA should be appropriately assessed in future clinical trials. Full article

The gut–microbiota–brain axis (GMBA), an intricate network connecting the gastrointestinal (GI) tract and the brain, plays a pivotal role in maintaining overall health and influencing disease processes. The human gut microbiota, comprising over 3000 bacterial species, regulates immune responses, hormonal signals, and metabolite production, maintaining homeostasis under normal conditions. Dysbiosis, or microbial imbalance, has been linked to various central nervous system (CNS) disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and autism spectrum disorder (ASD). Given the growing interest in this topic and the limited effectiveness of current therapeutic strategies for managing patients with AD, the purpose of the current narrative review is to analyze the pathophysiological role of the GMBA in the pathogenesis of AD and assess potential therapeutic strategies targeting the GMBA, particularly the microbiome and its metabolites. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science to identify clinical studies, experimental research, and review articles examining the GMBA in health and AD, as well as related therapeutic strategies. The search terms included “Alzheimer’s disease”, “neuroinflammation”, “amyloid-beta”, “tau”, “gut–brain axis”, “microbiome”, “short-chain fatty acids”, “probiotics”, “prebiotics”, and “fecal microbiota transplantation”. In AD, altered gut microbiota composition is associated with neuroinflammation, neurodegeneration, and exacerbation of disease progression. Probiotics have shown potential in enhancing cognitive function and reducing neuroinflammation by modulating microbiota composition and influencing brain-derived neurotrophic factor (BDNF) levels. Prebiotics, through their impact on gut microbiota and metabolite production, also offer therapeutic promise by improving cognitive function and mitigating neuroinflammation. With its historical and modern applications, fecal microbiota transplantation (FMT) may represent a potential strategy for addressing dysbiosis and its neurological implications. This manuscript focuses on GMBA and its effects on neuroinflammation, neurodegeneration, and CNS health while emphasizing the need for further research into microbiome-based therapies and the gut–brain relationship in patients with AD. Full article

Lateral epicondylitis (LE), commonly referred to as tennis elbow, remains a frequent cause of lateral elbow pain, yet its optimal management and risk profile are still debated. Therefore, this review aimed to summarize current evidence on its definition, diagnosis, and treatment while addressing common misconceptions. A non-systematic review of major medical databases, including PubMed, Cochrane Library, and Google Scholar, was conducted using predefined inclusion criteria to identify relevant review articles. The analyzed literature highlights that LE is primarily diagnosed clinically and managed through a spectrum of conservative and interventional approaches. Evidence suggests that structured physiotherapy and load modification remain the cornerstones of treatment, while modalities such as platelet-rich plasma and autologous blood injections may offer longer-term benefits compared with corticosteroids, which are effective mainly for short-term symptom relief. In contrast, interventions such as acupuncture and shock wave therapy show limited or inconsistent efficacy. Identified risk factors include female sex, smoking history, repetitive or forceful manual work, and higher cardiovascular risk burden. Overall, conservative management should be the first-line approach, with biologic therapies considered in refractory cases and surgery reserved as a last option; however, further high-quality randomized controlled trials are required to establish optimal treatment algorithms and clarify long-term outcomes. Full article

The advent of transcatheter aortic valve implantation (TAVI) has redefined the treatment of aortic stenosis over the last two decades, evolving from a therapy reserved for patients that were deemed to be of prohibitive surgical risk to the standard of care for a large group of patients presenting with symptomatic disease. With improvements in technology, operator and institutional experience and longer-term outcome data, recent guidelines have supported the broadening of indications to low-risk and asymptomatic patients in addition to other pathologies including the management of failed surgical bioprosthetic valves and aortic regurgitation. The rapid developments in the field have resulted in a rapid expansion of TAVI. The focus has moved from the technical aspects of the procedure itself that are now well established to the lifetime management of patients with aortic stenosis, particularly younger patients with regard to valve durability, planning for a further intervention after TAVI and associated considerations including future coronary access. Beyond aortic stenosis, TAVI technology is also increasingly being utilized for the management of failed surgical bioprostheses, bicuspid valve disease, aortic incompetence and mitral/tricuspid disease and these represent future areas of focus in the field. Full article

Objective: To report a rare case of bilateral iris metastasis from small cell lung carcinoma (SCLC) and systematically review the literature on SCLC-associated iris metastases, with emphasis on clinical presentation, management, and outcomes. Materials and Methods: A systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, ScienceDirect, Scopus, and Web of Science were comprehensively searched on 10 July 2025. Eligible studies included English-language reports of iris metastasis originating from SCLC in human subjects. Case report: A 58-year-old woman with previously treated SCLC developed bilateral iris metastases one year after complete remission of the primary tumor. Ophthalmic examination revealed whitish-gray, vascularized iris masses with iridocorneal angle involvement, associated with secondary angle-closure glaucoma and markedly elevated intraocular pressure (48 mm Hg) in the left eye. Cyclocryotherapy, preceded by systemic and topical antiglaucoma therapy, resulted in pain relief and a reduction in intraocular pressure; the patient died four months later due to pneumonia. Results (Systematic Review): Seventeen studies comprising 17 patients were included; the median age was 60 years, and 64.7% were male. The median interval from SCLC diagnosis to ocular presentation was 4 months, although iris metastasis was occasionally the initial or concurrent manifestation of disease. The most common presenting features were visual impairment (58.8%), ocular pain (41.2%), and elevated intraocular pressure (41.2%), while iris neovascularization (35.3%) and synechiae (29.4%) were also frequent. Bilateral involvement was reported in only one previous case. Treatment approaches were heterogeneous and included antiglaucoma therapy, systemic chemotherapy, local radiotherapy, anti-VEGF therapy, and enucleation. Among patients with available follow-up (n = 12), 58.3% died within a median follow-up of 7.5 months. Conclusions: Bilateral iris metastasis from SCLC is rare and may occur as a manifestation of recurrent disease after remission. It is an aggressive condition characterized by nonspecific ocular symptoms, variable management, and poor survival, underscoring the importance of early recognition and the need for evidence-based diagnostic and therapeutic strategies. Full article

Food allergy is an increasingly prevalent global health condition characterized by immune-mediated reactions to dietary antigens and a substantial clinical burden. Growing understanding of IgE-mediated mechanisms has highlighted the central role of type 2 inflammation, effector-cell activation, and impaired immune regulation. These advances have prompted the development of disease-modifying therapies beyond allergen avoidance. This narrative review summarizes recent advances in the therapeutic management of IgE-mediated food allergy. A structured PubMed search was performed to identify clinical trials, randomized studies, and meta-analyses published within the last five years. Both allergen-specific and non-allergen-specific interventions were evaluated. Current evidence supports oral immunotherapy as the most effective strategy for increasing reaction thresholds and inducing desensitization in peanut, milk, and egg allergies. However, safety concerns remain, and sustained unresponsiveness after treatment discontinuation is achieved inconsistently. Sublingual and epicutaneous immunotherapy show improved safety but lower efficacy. Modified allergen approaches, including baked milk and processed peanut products, may improve tolerability and facilitate immune modulation in selected patients. Biologic therapies, particularly anti-IgE agents, demonstrate efficacy both alone and when combined with immunotherapy. Emerging approaches include peptide vaccines, DNA immunization, microbiome-targeted interventions, and early dietary modulation. These strategies may improve durable immune tolerance through personalized, mechanism-based therapeutic approaches. Future progress will depend on optimizing safety, identifying predictive biomarkers, and integrating multimodal approaches to achieve durable immune tolerance. Full article

Pancreatic cancer (PC) remains one of the malignancies with the most unfavorable prognosis and limited treatment options. The lack of biomarkers for early diagnosis and the asymptomatic nature of the disease contribute to delays in diagnosis and high mortality rates. In recent years, the role of the human microbiota in cancer biology has become increasingly significant, and the oral microbiota in particular has been found to be involved in the pathogenesis and prognosis of several neoplasms. This review summarizes the current evidence relating the salivary microbiota to PC in three key areas: screening and diagnostic potential, pathophysiology and tumor progression, as well as presenting prognostic implications and potential influence on therapy. With regard to early diagnosis, it has been reported that patients with PC have reduced levels of Neisseria elongata (N. elongata) and Streptococcus mitis (S. mitis) and elevated levels of Granulicatella adiacens. Several studies have shown that bacteria present in the saliva can migrate from the oral cavity to pancreatic tissue via hematogenous or enteric routes, where they may actively contribute to tumor development and progression. In particular, it has been shown that Porphyromonas gingivalis (P. gingivalis) and Veillonella atypica (V. atypica) translocate from the mouth to pancreatic tumors, promoting carcinogenesis by inducing a pro-inflammatory tumor microenvironment. Furthermore, some studies have identified certain species associated with prognosis and response to PC treatment. Despite the encouraging results, differences in study methodology, the lack of standardized methods and the scarcity of longitudinal data currently hinder clinical application. Large-scale, multi-omics prospective studies are needed to clarify causality and validate their clinical utility. Overall, the salivary microbiota represents a promising and non-invasive tool for improving early diagnosis, understanding prognosis and enhancing the management of PC. Full article

Background: Appropriateness of diagnostic test prescriptions represents a critical component of quality care in pediatric allergology, directly influencing diagnostic accuracy, therapeutic decisions, healthcare resource utilization, and patient outcomes. A multidisciplinary expert panel was convened to develop evidence-based clinical recommendations addressing the appropriate use of specialist consultations and diagnostic investigations in children with asthma, allergic rhinoconjunctivitis, and vernal keratoconjunctivitis (VKC). Methods: Clinical questions were formulated using the PICO framework and prioritized through structured expert consensus. Systematic literature reviews were conducted across major databases, and the certainty of evidence was assessed using the GRADE methodology. Results: Specialist evaluation emerged as a key determinant of improved diagnostic precision, optimization of treatment strategies, and reduction of inappropriate therapies. In asthma, spirometry, FeNO measurement, and allergy testing contributed to enhanced diagnostic accuracy and better control. In allergic rhinoconjunctivitis, allergological assessment supported diagnosis and the selection of immunotherapy, with demonstrated benefits on symptoms and quality of life. For VKC, multidisciplinary specialist involvement facilitated early diagnosis, personalized management, and prevention of complications. Conclusions: Although the overall certainty of evidence ranged from moderate to low, consistent clinical benefits supported consensus-based recommendations. Implementation of these recommendations may improve care quality, promote equitable access to diagnostic resources, and reduce unnecessary healthcare utilization. Full article

Introduction: Vancomycin is a widely used antibiotic in Outpatient Parenteral Antimicrobial Therapy (OPAT) services. The objective of this systematic review was to evaluate the published literature on the efficacy and safety outcomes of outpatient vancomycin therapy. Methods: A systematic search was performed in Embase, Medline ALL, the Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials from database inception until 20 March 2026. Both randomized controlled trials and non-randomized studies published in peer-reviewed journals were included. Study quality was assessed using the Newcastle–Ottawa Scale. Results: A total of 75 studies were included. Clinical success rates of 40.9% to 100% were reported. Reported adverse event (AE) rates ranged widely from 5.7% to 85.7%. Comparative studies suggest a higher risk of nephrotoxicity during intermittent infusion compared to continuous infusion. Reported line-related AE ranged from 1.1% to 5.7% and readmission risks associated with vancomycin use were inconsistent across studies. Conclusions: This systematic review shows that vancomycin is an effective agent to use in OPAT setting, however its use is associated with a risk of adverse events. The findings of this study underscore the need for a dedicated multidisciplinary OPAT team to ensure proper follow-up and tailored vancomycin management in the outpatient setting. Full article

The oncocytic variant of adrenocortical carcinoma (OACC) represents an exceptional type of adrenal malignancy, with heterogenous presentation. Currently, the genetic and molecular spectrum remains an open matter. A 20-year-old adult was accidentally found with a 7.2 cm adrenal tumor and underwent an open right adrenalectomy with OACC confirmation. Post-adrenalectomy positron emission tomography/computed tomography was negative. Immunohistochemistry was positive for calretin, inhibin, steroidogenic factor 1; Ki67 of 20%. Microsatellite instability was 7.61. Lin–Weiss–Bisceglia score showed 2 major criteria [mitoses 6/50 HPF + positive atypical mitoses], the reticuline algorithm (disrupted reticuline network + mitoses 6/50 HPF) was consistent for a malignant behavior, the Helsinki score was of 48. Next generation sequencing identified a likely pathogenic variant of CEL gene (heterozygote, c.539-2A>G) in peripheral blood and two pathogenic variants in the tumor: exon 48, NF1 gene [c.7159_7164del p.(N2387_F2388del)] and exon 6, TP53 gene [c.596delG p.(G199Efs*48)]. Polycystic ovary syndrome type A has been diagnosed as teenager with no phenotype change before the tumor detection. After surgery, oocyte retrieval and cryopreservation upon ovarian stimulation protocol (OSP) was performed before starting mitotane therapy. To the best of our knowledge, this is a novel genetic configuration in OACC with an impact on prognosis to be determined. Hyperandrogenemia stands on a dual source (potential CEL-driven insulin resistance for the ovary and OACC-originating for the adrenal glands). Also, this is the first case to receive OSP in OACC, noting that a tailored multidisciplinary management is mandatory. Full article

Background: We aim to estimate the variation in the prevalence of chronic kidney disease (CKD) in patients from a Brazilian cardiologic center. Methods: The outpatient serum creatinine level and urine albumin–creatinine ratio (UACR) in samples from patients ≥18 years old between 2014 and 2023 were evaluated. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m². Participants were categorized into low-, moderate-, high- or very high-risk groups according to the CKD heatmap, which combines eGFR with UACR results. Results: The mean number of adults with serum creatinine results per year was 36,477 ± 7239, and the mean number of those with UACR results was 16,870 ± 4310. The age- and sex-adjusted prevalence of participants with CKD increased significantly (from 20% to 31%; R² = 0.853; p < 0.001), as was the prevalence of individuals in the high or very high CKD risk groups (14% to 21%; R² = 0.945; p < 0.001). The cumulative incidence of CKD during the study period was 21.7% and was higher in females and in older age groups. Conclusions: The roughly 50% increase in the laboratory-based CKD prevalence over 10 years underscores the need for healthcare services to adapt to managing a population with growing complexity and a heightened risk of requiring kidney replacement therapy. Full article

Male reproductive health has experienced an unprecedented decline over the past five decades, characterized by substantial reductions in sperm count and testosterone levels. This review provides a comprehensive synthesis of current evidence on the global decline in sperm count and testosterone levels, examining epidemiological trends, underlying mechanisms, environmental drivers, and clinical implications. Sperm concentration declined by 51.6% globally between 1973 and 2018, with an accelerating trajectory post-2000 (from 1.16% to 2.64% per year). Concurrently, multiple independent studies document an age-independent secular decline in testosterone, averaging 1–2% per year across diverse populations. The etiology is multifactorial, involving endocrine-disrupting chemicals (bisphenol A, phthalates, pesticides, dioxins), lifestyle factors (obesity, sedentary behavior, smoking, heat exposure), and disruption of the hypothalamic–pituitary–gonadal axis. At the cellular level, mechanisms include Sertoli and Leydig cell dysfunction, oxidative stress, mitochondrial impairment, and sperm DNA fragmentation. Integrated clinical management combining lifestyle optimization, antioxidant therapy, and targeted endocrine interventions is essential. Prevention through environmental policy and public health initiatives represents the most promising long-term strategy. Full article

Fatigue and muscle wasting are common clinical manifestations of inherited and acquired neuromuscular disorders, including peripheral neuropathies, neuromuscular junction disorders, and myopathies. These conditions encompass a wide disease spectrum with variable prognoses, making accurate diagnosis essential for appropriate management. Congenital myasthenic syndromes (CMSs) are rare, inherited disorders characterized by impaired neuromuscular transmission. Although symptoms often begin in infancy or early childhood, later onset during adolescence or adulthood is increasingly recognized. Clinical phenotypes vary according to the underlying molecular defect, but fatigable weakness predominantly affecting axial and proximal limb muscles is a hallmark feature. We report an adolescent male who developed progressive proximal muscle weakness and wasting over several years, resulting in significant functional impairment. Initial evaluation suggested limb–girdle muscular dystrophy. However, comprehensive investigations, including whole-exome sequencing, identified a heterozygous CHRNB1 mutation consistent with postsynaptic CMS. Targeted pharmacological therapy led to clinical improvement. This case highlights the importance of considering CMS in patients presenting with limb–girdle weakness and underscores the value of genetic testing in establishing an accurate diagnosis and guiding treatment. Full article

Mucopolysaccharidosis (MPS) are a group of inherited lysosomal storage genetic disorders that affect the body’s ability to break down glycosaminoglycans (GAGs) due to the deficiency of required enzymes. This leads to depositions of these GAGs in various tissues and organs resulting in multi-systemic manifestations including pulmonary and sleep related issues. In recent years, there have been significant advancements in therapeutic options and supportive management which have led to the overall improvement in respiratory care, culminating in improved quality of life for MPS patients. Management of pulmonary and sleep disorders in mucopolysaccharidosis requires a multidisciplinary approach due to the multi-systemic affectation of the genetic disorders. Therapeutic options such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) have yielded varying success in mitigating respiratory complications. Emerging treatments such as gene therapies have shown exciting and promising results thus far. Supportive therapies such as airway clearance, regular vaccination and use of positive airway pressure devices are also essential. Pre-operative airway and anesthesia planning is critical to mitigate peri-operative and post-operative complications. Early diagnosis, close monitoring and a patient focused individualized approach are essential for respiratory optimization and overall improvement in clinical outcomes. This review article aims to discuss these advancements in a comprehensive format, making it accessible to medical providers who care for this subset of patients. Full article