Search Results (659)

Background and Clinical Significance: Arterial and venous thromboses are typically distinct clinical entities, each governed by unique pathophysiological mechanisms. The concurrent manifestation of both, particularly in the setting of massive pulmonary embolism (PE), is exceptionally rare and poses significant diagnostic and therapeutic challenges. Case Presentation: This report describes a 61-year-old male with well-controlled hypertension and type 2 diabetes who developed extensive thromboses involving deep vein thrombosis (DVT) of the right popliteal vein, arterial thrombosis of the left iliac artery, and massive PE. The patient was initially managed conservatively, in accordance with the European Society of Cardiology (ESC) 2019 Guidelines for Acute PE, using unfractionated heparin (UFH), low-molecular-weight heparin, a direct oral anticoagulant (DOAC), and adjunctive therapy. This approach was chosen due to the absence of hemodynamic instability. However, given failed percutaneous revascularization and persistent arterial occlusion, surgical thromboendarterectomy (TEA) was ultimately required. Post hoc genetic testing was prompted by the complex presentation in the absence of classical provoking factors—such as trauma, surgery, malignancy, or antiphospholipid syndrome—consistent with recommendations for selective thrombophilia testing in atypical or severe cases. The analysis revealed four thrombophilia-associated polymorphisms: heterozygous Factor V Leiden (FVL; R506Q genotype), Plasminogen Activator Inhibitor-1 (PAI-1; 4G/5G genotype), Methylenetetrahydrofolate reductase (MTHFR; c.677C > T genotype), and homozygous Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D; DD genotype). Conclusions: While each variant has been individually associated with thrombotic risk, their co-occurrence in a single patient with simultaneous arterial and venous thromboses has not, to our knowledge, been previously documented. This case underscores the potential for gene–gene interactions to amplify thrombotic risk, even in the presence of variants traditionally considered to confer only modest to moderate risk. It highlights the need for a multidisciplinary approach and raises questions regarding pharmacogenetics, anticoagulation, and future research into cumulative genetic risk in complex thrombotic phenotypes. Full article

Background: Autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), Sjögren’s syndrome, systemic sclerosis (SSc), and rheumatoid arthritis (RA), pose significant challenges during pregnancy and are associated with increased risks of adverse maternal and fetal outcomes, such as preeclampsia, fetal growth restriction (FGR), miscarriage, and preterm birth. The aim of this review is to synthesize recent evidence on pregnancy-related risks, preconception counseling, and therapeutic strategies for these conditions, with a particular focus on the importance of disease remission, pregnancy-compatible medications, and the selective use of biologics. Methods: A structured narrative review was conducted through a comprehensive PubMed search (2020–2025). Eligible studies addressed maternal–fetal outcomes, therapeutic approaches, and predictive factors in pregnant individuals with autoimmune rheumatic diseases. Results: Pregnancy outcomes have improved with early disease control and multidisciplinary care; however, major challenges persist. These include limited access to novel therapies, underrepresentation of diverse populations in clinical trials, and insufficient data on long-term neonatal outcomes. The strongest predictors of adverse outcomes remain disease activity at conception, specific autoantibody profiles, and systemic organ involvement. Conclusions: Optimal pregnancy outcomes for women with autoimmune rheumatic diseases require coordinated multidisciplinary care, the use of pregnancy-compatible medications, and achievement of prolonged disease remission prior to conception. Further research is needed to close existing knowledge gaps and ensure equitable, high-quality maternal–fetal care. Full article

Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, with cure rates exceeding 80% due to advancements in treatment protocols and supportive care. However, in children with Down syndrome (DS), ALL (DS-ALL) presents distinct genomic and clinical challenges. These include mutations in Janus kinase 2 (JAK2), neuroblastoma RAS viral oncogene homolog (NRAS), and E1A-binding protein p300 (EP300), as well as cytokine receptor-like factor 2 (CRLF2) rearrangements—such as P2RY8-CRLF2 fusion—and intrachromosomal amplification of chromosome 21 (iAMP21). These aberrations are associated with poor prognosis and increased risk of relapse. The objective of this study was to present a unique DS-ALL case with five concurrent high-risk genomic lesions and to contextualize its management in light of existing literature, emphasizing minimal residual disease (MRD)-guided therapy and supportive care. Case Report and Results: We present the case of a three-year-old boy with DS and B-cell ALL (B-ALL), in whom multiple high-risk genomic features co-occurred. Despite these adverse prognostic markers, the patient achieved complete remission following an intensive high-dose induction protocol. We also discuss therapeutic strategies that aim at balancing individualized treatment approaches with optimized supportive care to reduce toxicity and minimize relapse risk. Conclusions: This case underlines the importance of comprehensive molecular diagnostics, serial MRD monitoring, and personalized multidisciplinary care in DS-ALL. Full article

Background/Objectives: Generalized anxiety disorder (GAD) is one of the most commonly diagnosed anxiety disorders in primary care. The global lifetime prevalence of GAD is estimated at 3.7%, ranging from 1.6% in low-income countries to 5.0% in high-income countries, underscoring its widespread impact. Given the frequent co-occurrence of GAD with obesity, this association has important clinical implications, particularly for screening, prevention, and treatment strategies. The aim of this review is to identify potential biological mechanisms linking obesity and GAD, summarize the current state of knowledge in this area, and highlight existing research gaps, as well as directions for future research. Methods: This narrative review is based on the literature published between 2015 and 2025 concerning the co-occurrence of GAD and obesity, with a focus on potential shared mechanisms including HPA axis dysregulation, chronic inflammation, oxidative stress, insulin resistance, gut–brain axis and microbiota dysbiosis, sleep disturbance, and maladaptive eating behaviors. Results/Conclusions: A growing body of evidence suggests an important, albeit still ambiguously defined, relationship between obesity and GAD. GAD and obesity may reinforce each other, leading to a mutually reinforcing relationship. Despite growing interest, high-quality prospective and interventional studies focusing specifically on GAD are lacking. A potentially effective therapeutic approach should be integrated and multidisciplinary, combining psychological, pharmacological, and lifestyle interventions. It may also be beneficial for clinicians to consider routine assessment of anxiety in patients with obesity and, conversely, to monitor metabolic risk in individuals with GAD. Such an approach, targeting both mental and metabolic domains, holds promise for improving outcomes. Full article

The use of immune checkpoint inhibitors (ICIs) has increased exponentially in recent years, leading to a significant impact on cancer patient survival. However, their administration can trigger immune-mediated adverse effects, notably pulmonary toxicity, which is a potentially serious complication. ICI-induced pneumonitis has a variable incidence ranging from 5 to 19% and usually appears in the first few months of treatment. The diagnosis requires a high index of suspicion, especially in patients with risk factors (elderly male smokers with squamous cell lung cancer, previous respiratory or autoimmune disease, and receiving combination treatment with other ICIs or chemo-radiotherapy). Chest computed tomography (CT) is a key test, allowing the identification of different radiological patterns. This study can be completed with bronchoscopy with bronchoalveolar lavage (BAL) to rule out infection or tumour progression. In general terms, treatment is based on discontinuing the causative drug, with or without the initiation of systemic corticosteroids, escalating to immunosuppressants depending on the severity and/or refractoriness of the condition. This paper provides an updated narrative review of ICI pulmonary toxicity, addressing its pathophysiology, different types of lung damage, diagnostic and therapeutic algorithms, and the emerging role of biomarkers such as KL-6 or IL-6. This article emphasises the need for a multidisciplinary approach and further prospective studies to optimise the management and prognosis of this immune-mediated complication. Full article

Diabetes mellitus (DM) poses an increasingly high global health burden nowadays, while in adults, chronic kidney disease (CKD) associated with DM impacts 20–40% of those with the condition. Effective management of CKD in patients with diabetes necessitates a comprehensive, multidisciplinary approach. Numerous factors, including glomerular hyperfiltration, oxidative stress, inflammation, and hypoxia are linked to the advancement of diabetic kidney disease (DKD). Currently, no specific treatment for DKD has been established, prompting extensive exploration of new approaches. Renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter 2 inhibitors have demonstrated renoprotective effects in various human clinical trials. Additionally, glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists have been reported as effective in managing DKD, while new therapeutic candidates are also under investigation, such as soluble guanylate cyclase activators and aldosterone synthase inhibitors. Recent evidence has shown that treating diabetic nephropathy by reducing albuminuria levels and retarding its progression is a complex skill. The purpose of this review is to support the impressive results that appear in reducing albuminuria and the progression of diabetic nephropathy with early and intensive combination treatment compared to the recently emerged conventional monotherapy, with agents that act on different pathophysiological mechanisms. Full article

Background and Objectives: Transcatheter Aortic Valve Replacement (TAVR) has revolutionized the management of severe aortic stenosis (AS), offering a less invasive alternative to surgical replacement, which is particularly beneficial for elderly and high-risk populations. This narrative review aims to summarize current evidence regarding TAVR’s clinical outcomes, patient selection, the role of cardiac remodeling, and the impact of geriatric syndromes on procedural success. Materials and Methods: This review is based on a comprehensive analysis of the peer-reviewed literature indexed in major scientific databases. We included relevant studies addressing TAVR in older adults, focusing on cardiac biomarkers, imaging, patient stratification, and geriatric syndromes, such as frailty, delirium, and sarcopenia. Results: Evidence indicates that TAVR significantly improves survival and quality of life in elderly patients with severe AS. Advanced cardiac imaging and biomarkers contribute to improved risk stratification and post-procedural management. Geriatric syndromes are prevalent in this population and strongly influence clinical outcomes. Tailored prehabilitation and multidisciplinary approaches are increasingly recognized as critical components of TAVR care. Conclusions: TAVR is an effective and safe option for older adults with severe AS. Optimal outcomes depend not only on procedural expertise but also on recognizing and addressing the complex interplay between cardiac pathology and geriatric vulnerabilities. A holistic, patient-centered approach is essential to maximize the therapeutic benefits in this growing patient population. Full article

Optic pathway glioma (OPG) is a rare pediatric low-grade glioma, frequently associated with neurofibromatosis type 1 (NF–1), that presents unique therapeutic challenges due to its anatomical location and its potential to impair vision, endocrine function, and developmental trajectories. Current clinical management prioritizes a multidisciplinary, patient-specific approach aimed at tumor control while preserving long-term quality of life. Strategies vary based on clinical presentation, ranging from observation in asymptomatic cases to chemotherapy for progressive or symptomatic tumors. Surgical and radiation options are limited due to potential risks and complications. In recent years, advances in molecular characterization have guided the development of targeted therapies, particularly MEK inhibitors, which demonstrate encouraging efficacy and reduced toxicity profiles. In parallel, investigational therapies including immunotherapy and precision medicine-based approaches are under clinical evaluation. This review provides a synthesis of current standard practices, emerging targeted treatments, and ongoing clinical trials, drawing on relevant literature and expert consensus to inform clinicians and families about available therapeutic options. Literature discussed in this review was identified through a non-systematic search of published articles, clinical trial registries, and authoritative guidelines, with selection based on relevance, clinical significance, and contribution to understanding current and emerging management strategies for OPG. Full article

Background and Clinical Significance: Spinal arachnoid cysts are rare lesions that may become symptomatic through progressive spinal cord compression. We present a complex case of a thoracic extradural SAC in a 17-year-old male, managed through a stepwise, multidisciplinary approach. Case Presentation: The patient presented with progressive lower limb weakness, right knee paresthesia, and urinary hesitancy following physical exertion. MRI revealed a large posterior extradural SAC extending from T2–T3 to T8, with associated spinal cord compression. Initial management involved T8 laminectomy and cyst fenestration under intraoperative neurophysiological monitoring, with partial clinical improvement. However, early recurrence with pseudomeningocele formation prompted a second surgery, including external CSF drainage. Persistent cerebrospinal fluid (CSF) leakage led to targeted epidural blood patching, followed by temporary stabilization. Due to continued cyst enlargement and spinal cord compression, definitive surgical repair was undertaken: fistula clipping at T3 and embolization with platinum coils inside the cystic cavity, combined with a new blood patch. This novel technique resulted in radiological improvement and clinical stabilization. Conclusions: This case highlights the diagnostic and therapeutic challenges of managing symptomatic extradural SACs, particularly in young patients. Our experience underscores the utility of a staged approach involving surgical decompression, neuroimaging-guided interventions, and definitive dural repair. The combination of fistula clipping and coil embolization may offer a promising strategy for refractory cases, potentially reducing recurrence and preserving neurological function. Full article

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease (ILD) with poor prognosis and limited therapeutic options. The introduction of antifibrotic agents has improved survival outcomes in IPF patients, which has led to more frequent recognition of comorbidities, particularly lung cancer (LC). This review summarizes current evidence on the epidemiology and pathogenesis of LC in the context of IPF, with particular emphasis placed on shared molecular, cellular, genetic, and epigenetic alterations. Diagnostic approaches and available treatment modalities, including surgical, systemic, and radiation therapies, are outlined, and their limitations in patients with IPF-LC are discussed. Acute exacerbations (AEs), as a life-threatening complication influencing diagnostic and treatment strategies, are specifically addressed. Moreover, studies indicating a possible protective effect of antifibrotic agents against LC development in IPF are reviewed. Further research is warranted into the shared mechanisms of IPF and LC to identify novel therapeutic targets. Establishing standardized, multidisciplinary clinical guidelines is essential for optimizing patient management, reducing AE risk, and improving patient outcomes. Full article

Background/Objectives: The extension of euthanasia and physician-assisted suicide to individuals with mental disorders presents a profound ethical, clinical, and legal challenge. While increasingly accepted in some jurisdictions, their application in psychiatric contexts—particularly in cases of depression—raises concerns about diagnostic precision, therapeutic adequacy, and the validity of informed consent. This study examines two controversial Belgian cases to explore the complexities of euthanasia for psychological suffering. Methods: A qualitative case analysis was conducted through a qualitative analysis of publicly available media sources. The cases were examined through clinical, psychoanalytic, and medico-legal lenses to assess diagnostic clarity, treatment history, and ethical considerations. No access to official medical records was available. Case Presentation: The first case involved a young woman whose depressive symptoms were reportedly linked to trauma from a terrorist attack. The second concerned a middle-aged woman convicted of infanticide and later diagnosed with Major Depression. Discussion: In both cases, euthanasia was granted on the grounds of “irreversible psychological suffering.” However, the absence of detailed clinical documentation, potential unresolved trauma, and lack of psychodynamic assessment raised doubts about the robustness of the evaluations and the validity of informed consent. Conclusions: These findings highlight the need for a more rigorous, multidisciplinary, and ethically grounded approach to psychiatric euthanasia. This study underscores the importance of precise diagnostic criteria, comprehensive treatment histories, and deeper exploration of unconscious and existential motivations. Safeguarding clinical integrity and ethical standards is essential in end-of-life decisions involving mental illness. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by providing durable responses and a favorable safety profile, ushering in a new era of tumor immunotherapy. However, immune-related adverse events (irAEs) remain a significant clinical challenge. Among these, gastrointestinal irAEs, especially immune-related colitis (ir-colitis), can lead to serious complications if not promptly recognized and managed. Here, we present a case of grade 3 ir-colitis induced by the programmed cell death protein 1 (PD-1) inhibitor sintilimab in a 68-year-old woman with endometrial cancer. The patient developed severe acute diarrhea following ICI administration, which progressed despite initial antidiarrheal and antimicrobial treatments. A multidisciplinary team (MDT) involving gastroenterologists, oncologists, a pathologist, and a clinical pharmacist confirmed the diagnosis and implemented high-dose corticosteroid therapy, yielding significant clinical improvement. Importantly, this report highlights the mechanistic link between PD-1 blockade and ir-colitis pathogenesis, focusing on the dysregulation of the mucosal immune environment and its role in triggering colonic injury. In addition to the case description, we provide a comprehensive review of the literature and clinical guidelines, discussing risk factors, diagnostic approaches, therapeutic strategies, and long-term monitoring. By integrating insights from pharmacology, immunology, and clinical practice, this work emphasizes the importance of early detection, patient education, and MDT collaboration for optimizing therapeutic outcomes and advancing the understanding of ir-colitis in the context of ICI therapy. Full article

Objectives: Obesity has become a major health issue, with multifactorial etiologies involving lifestyle, genetic, and neuroendocrine mechanisms. Despite public health campaigns and lifestyle interventions, long-term weight loss is often difficult to achieve or sustain. This literature review aims to summarize current knowledge on the main molecular mechanisms that hinder weight loss and to summarize the newest therapeutic strategies targeting obesity. Methods: The literature review was conducted using PubMed, Scopus, and Web of Science databases, with a preference for peer-reviewed original articles, systematic reviews, and meta-analyses. Eligible studies were required to be published in the English language and within the last ten years (2015–2025), with the exception of historically significant publications. A total of 112 articles were included in our review. Results: Obesity is a complex, chronic, recurrent metabolic condition that requires personalized, multidisciplinary treatment approaches. In this review, we summarize the major molecular mechanisms underlying weight gain and weight maintenance in obesity. In this literature review, we address the metabolic memory and epigenetics that act through DNA and histone modifications and micro interfering RNAs, resulting in an energy imbalance that can be passed on to further generations. The dysfunction of adipose tissue contributes to chronic low-grade inflammation and insulin resistance, leading to more severe obesity. The ratio of white, beige, and brown adipocytes also plays an important role in regulating energy balance. Novel medical interventions offer promising results in attenuating these mechanisms against successful weight loss. Conclusions: Current interventions, including calorie restriction, physical activity, and pharmacological treatment together, may show great promise in combating obesity, but long-term efficacy and safety remain to be established. Full article

Pediatric obstructive sleep apnea (OSA) is a highly prevalent, multifactorial, and often underdiagnosed condition with significant consequences for cognitive and behavioral development. Early detection and timely multidisciplinary interventions are essential, particularly in children with craniofacial anomalies or syndromes associated with increased OSA risks, to prevent long-term complications. This narrative review explores the orthodontists’ role in the interdisciplinary management of pediatric OSA, focusing on early screening for craniofacial risk factors and implementing interceptive orthodontic interventions that support favorable airway development and growth modulation. Through early and frequent interaction with pediatric patients, orthodontists are well-positioned to identify clinical signs of airway-related abnormalities and craniofacial risk factors such as mandibular and maxillary retrognathism, maxillary constriction, and high-arched palatal vaults. Orthodontic interventions such as rapid maxillary expansion (RME), mandibular advancement, and myofunctional therapy may improve airway patency in selected cases. These approaches should be coordinated and integrated within the multidisciplinary team, including orthodontists, pediatricians, sleep specialists, ENT specialists, and speech-language pathologists. Furthermore, caregivers’ involvement and patients’ compliance are keys to success. Despite encouraging clinical observations, current evidence is limited by heterogeneity and a lack of long-term outcome data. Future research should prioritize well-designed prospective trials, explore the effectiveness of combined therapeutic strategies, and support the development of standard diagnostic protocols. Equally important is a stronger focus on early diagnosis and preventive measures to enhance patient outcomes and long-term treatment strategies. Integrating orthodontists into early OSA care is essential for optimizing outcomes and reducing long-term morbidity. Full article

Pain is a fundamental yet complex biological and psychosocial phenomenon. While acute pain serves as a defense mechanism, alerting the body to potential tissue damage, chronic pain loses this protective function and becomes a persistent, independent condition. Chronic pain in the elderly is particularly significant due to age-related changes in pain perception, a higher prevalence of comorbidities, and an increased susceptibility to pharmacological side effects. Diagnosing pain in older adults presents unique challenges owing to cognitive decline, multimorbidity, and impaired communication. This narrative review aims to summarize the current knowledge on chronic pain in the elderly, with a particular emphasis on diagnostic difficulties, therapeutic strategies, and the essential role of nurses in multidisciplinary management. Both objective scales and subjective assessment tools are essential for an accurate evaluation. Effective management requires a multidisciplinary approach that integrates individualized pharmacological and non-pharmacological therapies. Analgesic use must be tailored to account for altered pharmacokinetics and risks such as sedation or falls. Non-drug interventions, including physiotherapy and psychological techniques, are especially valuable in geriatric care. Nurses play a pivotal role in the recognition, assessment, and ongoing management of pain in this population. Developing age-appropriate, personalized strategies is essential for improving the quality of life in older adults living with chronic pain. Full article