Search Results (2,318)

Background: Follicular lymphoma (FL) is the second most common B-cell lymphoma in Western countries, typically presenting as an indolent disease with prolonged overall survival. Despite favorable initial responses to therapy, most patients experience relapse, and early progression is associated with poor outcomes. Methods: This guideline provides evidence-based recommendations from the Spanish GELTAMO group on the diagnosis, staging, treatment, and follow-up of FL. A systematic literature review was conducted, and recommendations were graded according to the GRADE system. Results: Histopathological diagnosis should be based on excisional biopsy. PET-CT is recommended for staging and response evaluation. For localized disease, involved-site radiotherapy (ISRT) remains the treatment of choice. In asymptomatic patients with advanced-stage disease and low tumor burden, a watch-and-wait approach is appropriate, although rituximab monotherapy is also acceptable. For advanced-stage disease with high tumor burden, immunochemotherapy with anti-CD20 antibodies (rituximab or obinutuzumab) combined with CHOP, CVP, or bendamustine is recommended, followed by maintenance therapy. Management of relapsed disease is tailored based on tumor burden, treatment history, and timing of relapse. Although novel immunotherapies (CAR-T therapy and bispecific antibodies) are emerging as promising options, autologous stem cell therapies may still be a valid option in young patients with early relapse who are sensitive to immunochemotherapy. Conclusions: FL is a heterogeneous disease requiring individualized management strategies. Recent advances in immunotherapy and molecular diagnostics are reshaping the therapeutic landscape. These updated GELTAMO recommendations aim to provide practical guidance for optimal FL management in clinical practice. Full article

The management of rheumatoid arthritis (RA) has undergone several practice-defining evolutions, beginning with the approval of low-dose methotrexate and continuing through the introduction of numerous disease-modifying antirheumatic drugs (DMARDs). With increasing capability to target pro-inflammatory pathways, successive therapeutics have carried the promise of improved disease control for patients with RA; however, many patients still fail to meet treatment objectives, leading to the recognition of clinical phenotypes that remain therapeutically challenging under the current treat-to-target standard of care, including preclinical inflammatory arthritis, late-onset RA, and treatment-resistant RA. Precision medicine approaches are beginning to characterize the pathogenesis of RA in such populations, and to inform effective tailoring of DMARD therapy to individual patients. Simultaneously, observational data derived from clinical practice are increasingly being used to understand the risks and benefits of long-term DMARD therapy under real-world conditions of use, with registries and other observational sources confirming long-term effectiveness, revising safety profiles, and estimating the costs of treatment for approved therapies. Together, these strategies offer opportunities to address unmet needs in the care of patients with RA. In this review of peer-reviewed clinical and translational research in RA, we identify several clinical phenotypes that demonstrate inadequate response to guideline-directed therapy and review frontiers in clinical research in RA emerging over the last decade, highlighting the use of precision medicine and real-world evidence-based approaches to advance individualized, patient-centered care. Full article

Rheumatoid nodules are the most common extra-articular manifestation of rheumatoid arthritis. Long-term immunomodulatory therapies, including corticosteroids, used in the management of rheumatoid arthritis are associated with a higher risk of infections. Leishmaniasis is a neglected protozoal infection that may arise in these patients. Cutaneous presentation is the most common and is characterized by a wide spectrum of clinical manifestations and courses, depending on the interplay between species involved and the host’s immune response. Here, we report the rare and intriguing case of a patient with long-standing rheumatoid arthritis, chronically treated with systemic prednisone, whose rheumatoid nodules were colonized by Leishmania major. In this context, therapeutic strategies must be tailored to species and patient factors. This report expands the differential diagnosis of rheumatoid nodule, highlighting the importance of considering opportunistic infections in exuberant presentations, particularly in immunosuppressed patients coming from or travelling in endemic regions. Intracellular pathogens may exploit the localized immunological niche represented by the rheumatoid nodule of an immunocompromised host to survive and replicate undisturbed. It also underscores the value of the clinico-pathological correlation and the importance of integrating molecular analyses to identify unexpected microorganisms that can be hidden by concomitant disease, avoiding misdiagnosis, ensuring timely treatment, and improving patients outcomes. Full article

Background/Objectives: Trigeminal Neuralgia (TN) is a chronic neuropathic condition characterized by sudden, severe facial pain. Anticonvulsants are the cornerstone of pharmacological management, yet comparative evidence based on pharmacological class remains scarce. This systematic review aimed to evaluate the efficacy and safety of anticonvulsants in TN, stratified by their mechanism of action. Methods: A systematic search in PubMed, Scopus and Web of Science was conducted following PRISMA 2020 guidelines. Studies employing a pharmacological approach including human patients with TN, published in English since 2000, were included. Risk of bias was assessed using the Cochrane RoB 2, the ROBINS-I and the ROBINS-E tools, according to the study design. Results: Out of 922 initial records, 12 studies met the eligibility criteria. Sodium channel inhibitors showed high efficacy but frequent adverse effects, particularly hyponatremia and central nervous system symptoms. Calcium channel modulators offered a more favorable safety profile. Combination therapies showed benefits, levetiracetam and topiramate were moderately effective and well tolerated. Although the evidence has limitations, anticonvulsants continue to be the primary treatment for TN. Sodium-channel blockers demonstrate strong efficacy, whereas alternative agents generally provide superior tolerability. Conclusions: These findings support selecting drugs according to their underlying mechanisms of action. Equally important is tailoring therapy to pain phenotype and patient characteristics, balancing mechanism with tolerability and efficacy. Full article

Objective: This study aimed to design and clinically evaluate a bespoke cosmetic formulation tailored to individual skin characteristics and user preferences, focusing on hydration and barrier recovery in mature, therapy-affected skin. In addition, this study aimed to explore the feasibility and short-term outcomes of a structured, biometry-driven personalization approach applied within a single-subject case study design. Materials and Methods: A personalized dermato-cosmetic formulation incorporating melatonin, astaxanthin, low-molecular-weight hyaluronic acid, allantoin, yarrow oil (Achillea millefolium), lecithin, cholesterol, and arginine was developed based on objective biophysical assessment of the skin. A clinical case evaluation was conducted in a male subject over 55 years of age (Fitzpatrick phototype III) presenting persistent xerosis and dehydration following completed oncologic therapy. Quantitative skin biometry was performed at baseline and after 28 days of daily application, assessing hydration at six anatomical sites, sebum secretion, pigmentation and erythema indices, elasticity, and stratum corneum turnover and scaling. Results: After 28 days, sebum secretion increased by more than 100%, indicating partial restoration of the lipid barrier. Hyperpigmented areas decreased from 7.2% to 2.3%, while skin elasticity improved from 25% to 44%. A reduction of 8% in the erythema index suggested decreased vascular reactivity. Hydration levels improved consistently across all evaluated sites, and epidermal renewal was enhanced, as evidenced by reduced scaling and smoother skin surface. The melanin index remained stable throughout the study period. Conclusions: This pilot evaluation shows that bespoke cosmetic formulations, customized to individual skin biometry and preferences, can yield measurable improvements in hydration, barrier repair, elasticity, pigmentation uniformity, and epidermal renewal within 28 days, even in skin compromised by previous oncologic therapy. Given the single-subject nature of this pilot evaluation, these findings cannot be generalized to broader populations but rather highlight the importance of personalization and objective skin assessment in guiding individualized dermato-cosmetic formulation strategies. Personalized dermato-cosmetology using objective biophysical assessment may be a promising future strategy for effective, consumer-centered skincare. Full article

Background: Beyond the direct COVID-19 effects, the pandemic’s broader impact on vulnerable groups, such as patients with systemic sclerosis (SSc), is particularly concerning, especially regarding any resulting increase in overall mortality due to healthcare access disruptions. We aimed to determine excess all-cause mortality in SSc patients before and during the pandemic. Methods: We examined mortality data from Thailand’s Ministry of Public Health database for adults with SSc (ICD-10: M34). According to the WHO methodology, a negative binomial distribution model was used to estimate the expected number of deaths using pre-pandemic data (1 January 2015–31 December 2019). We evaluated actual versus expected deaths during the pandemic (1 January 2020 to 31 December 2022), defining excess mortality as the difference between observed and projected deaths under normal conditions. Results: The total number of all-cause deaths in Thailand was 2,325,384 in the pre-pandemic period and 1,634,121 during the pandemic period. The mortality rate among patients with SSc was 3693 before and 3107 during the pandemic. Of those with SSc, 1785 of the deceased were female, and the observed mortality was significantly lower than expected, with an excess death count of −368 (95% CI: −459 to −277), as well as in males with an excess death count of −123 (95% CI: −198 to −48). However, younger SSc patients (aged 18–29 years) experienced significantly higher excess mortality, with an excess death count of 11 (95% CI: 4–18). Conclusions: During the COVID-19 pandemic, neither sex had significantly higher SSc mortality; however, mortality in younger SSc patients increased significantly compared to pre-pandemic levels, underscoring the need for tailored therapies. Full article

Cardiovascular disease (CVD) is increasingly recognized as a significant comorbidity in people living with HIV (PWH), contributing to increased morbidity and mortality. Epidemiological studies indicate that PWH have a 1.2–2-fold higher risk of myocardial infarction (MI) and other CVD events compared to HIV-negative individuals. While the mechanisms underlying HIV-associated CVD are not fully understood, they are likely to include a combination of cardiovascular-related adverse effects of HIV medications, vascular dysfunction caused by HIV-induced monocyte activation, and cytokine secretion, in addition to existing comorbidities and lifestyle choices. This comprehensive review examines the complex relationship between HIV infection and CVD, highlighting key pathophysiological mechanisms such as chronic immune activation, inflammation, endothelial dysfunction, and the role of antiretroviral therapy (ART) in promoting cardiovascular risk. Alongside conventional risk factors such as smoking, hypertension, and dyslipidemia, HIV-specific elements, especially metabolic abnormalities associated with ART, significantly contribute to the development of CVD. Prevention strategies are crucial, focusing on the early identification and management of cardiovascular risk factors as well as optimizing ART regimens to minimize adverse metabolic effects. Clinical guidelines now recommend routine cardiovascular risk assessment in PWH, emphasizing aggressive management tailored to their unique health profiles. However, challenges exist in fully understanding the cardiovascular outcomes in this population. Future research directions include exploring the role of inflammation-modulating therapies and refining sustainable prevention strategies to mitigate the growing burden of CVD in PWH. Full article

Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) coexist in 40–60% of cases and mutually reinforce each other through adverse electrical, cellular, and functional remodelling. There is considerable overlap in signs and symptoms, and diagnosis may be challenging due to nonspecific clinical presentations and chronic course. AF is clearly linked with worsening morbidity and mortality in HFpEF with higher rates of HF hospitalizations, HF progression, stroke, systemic embolism, and all-cause death. Optimal management of HFpEF-AF patients requires aggressive treatment of comorbidities and risk factor modification. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated consistent benefit with respect to HF hospitalizations, symptoms and exercise haemodynamics, and potential to reduce AF burden. Gastric inhibitory polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) agonists, mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and statins may provide benefit in selected phenotypes, though evidence remains heterogeneous. A rhythm control strategy in the early clinical course of HFpEF might be a reasonable strategy to improve symptoms and delay both AF and HFpEF disease progression. Catheter ablation appears to improve exercise haemodynamics and quality of life, and observational data suggest it may reduce mortality and HF hospitalization, though current evidence is inconsistent and not yet definitive. Emerging device-based and molecular therapies could represent promising avenues for future research. Overall, early detection of AF, comprehensive risk-factor modification, and tailored rhythm-control strategies are central to improving outcomes in the HFpEF-AF overlap syndrome. Full article

The past decade has witnessed an unprecedented transformation in breast cancer management, driven by parallel advances in targeted therapies, immunomodulation, drug-delivery technologies, and molecular diagnostic tools. This review summarizes the key achievements of 2015–2025, encompassing all major biological subtypes of breast cancer as well as technological innovations with substantial clinical relevance. In hormone receptor-positive (HR+)/HER2− disease, the integration of CDK4/6 inhibitors, modulators of the PI3K/AKT/mTOR pathway, oral Selective Estrogen Receptor Degraders (SERDs), and real-time monitoring of Estrogen Receptor 1 (ESR1) mutations has enabled clinicians to overcome endocrine resistance and dynamically tailor treatment based on evolving molecular alterations detected in circulating biomarkers. In HER2-positive breast cancer, treatment paradigms have been revolutionized by next-generation antibody–drug conjugates, advanced antibody formats, and technologies facilitating drug penetration across the blood–brain barrier, collectively improving systemic and central nervous system disease control. The most rapid progress has occurred in triple-negative breast cancer (TNBC), where synergistic strategies combining selective cytotoxicity via Antibody-Drug Conjugates (ADCs), DNA damage response inhibitors, immunotherapy, epigenetic modulation, and therapies targeting immunometabolic pathways have markedly expanded therapeutic opportunities for this historically challenging subtype. In parallel, photodynamic therapy has emerged as an investigational and predominantly local phototheranostic approach, incorporating nanocarriers, next-generation photosensitizers, and photoimmunotherapy capable of inducing immunogenic cell death and modulating antitumor immune responses. A defining feature of the past decade has been the surge in patent-driven innovation, encompassing multispecific antibodies, optimized ADC architectures, novel linker–payload designs, and advanced nanotechnological and photoactive delivery systems. By integrating data from clinical trials, molecular analyses, and patent landscapes, this review illustrates how multimechanistic, biomarker-guided therapies supported by advanced drug-delivery technologies are redefining contemporary precision oncology in breast cancer. The emerging therapeutic paradigm underscores the convergence of targeted therapy, immunomodulation, synthetic lethality, and localized immune-activating approaches, charting a path toward further personalization of treatment in the years ahead. Full article

Background: Cardiovascular implications in systemic lupus erythematosus (SLE) are common and varied, including impacts on the pericardium, myocardium, valves, coronary arteries, and conduction system; all of these could be potential substrates or triggers of cardiac arrhythmias by interfering with disease severity and specific medication. Therefore, this narrative review aimed to assess the cardiac involvement in SLE underlying, mainly, cardiac arrhythmias. Methods: We analyzed studies, published between 2015 and 2025 on PubMed, which explore cardiovascular involvement with a focus on arrhythmias in SLE from the perspectives of epidemiology, underlying mechanisms, diagnostic techniques, and the impact of standard and biologic therapies. Results: The cardiac manifestation of LES (lupus pericarditis, lupus myocarditis, Libman–Sacks endocarditis, coronary artery disease, coronary vasculitis or myocardial fibrosis) represents a substrate for arrhythmia risk. These substrates, in association with other arrhythmias mechanisms considered as triggers or conduction abnormalities, determined arrhythmogenic conditions in these patients. In addition to structural heart disease, arrhythmias in SLE are caused by ongoing inflammation, immune system irregularities, microvascular problems, autonomic imbalance, oxidative stress, and side effects from treatments. Despite this complex background, arrhythmias are often overlooked and not routinely investigated in SLE care. Data that show how disease-modifying drugs may affect arrhythmias are limited and inconsistent, highlighting significant gaps in knowledge. Cardiac arrhythmias are a significant but, as yet, insufficiently underrecognized aspect of SLE, with serious implications for prognosis. Conclusions: Systemic lupus erythematosus causes cardiovascular involvement that is associated with arrhythmias through various and complexes mechanisms, mainly related to direct cardiovascular structural damage, systemic inflammation or specific therapies. Data on arrhythmias secondary to cardiovascular damage in patients with SLE in the literature are limited. Therefore, early detection of electrical issues, regular cardiovascular evaluation in high-risk patients, and careful management of treatment effects are vital. A coordinated, multidisciplinary cardio-rheumatology approach is essential to improving arrhythmia detection, tailoring treatments, and ultimately decreasing cardiovascular complications and deaths in SLE patients. Full article

Artificial Intelligence (AI) is a computer science that focuses on developing systems and machines capable of performing tasks that typically require human cognitive abilities. It has widespread applications in medical diagnostics. Its use has led to rapid advancements in diagnostic methodology, enabling the analysis of large datasets. The major applications of AI in medical diagnostics include personalized treatment based on patient genetics, preventive measures, and medical image analysis. AI is employed to analyse genomic data and biomarkers, aiding in the precise tailoring of therapies to individual patient needs. It could also be employed in modern dentistry in the near future, helping to achieve higher efficiency and accuracy in diagnosis and treatment planning. AI may be utilized in screening for oral mucosa lesions and to discriminate between oral potentially malignant disorders and cancers from benign lesions. The potential advantages of AI include high speed and accuracy in the diagnostic process, as well as relatively low costs. The aim of this review was to present the potential applications of AI methods in the diagnosis of selected mucocutaneous diseases. A literature review focuses on oral lichen planus, recurrent aphthous stomatitis, and oral and laryngeal leukoplakia. Full article

Background: Lentiviral vectors (LVs) show promise as gene therapy tools for brain tumors, but optimal envelope protein choices for different tumor types have not been determined. Methodology: This study evaluated three pseudotyped LV variants—VSV-GP, FuG-B2, and LCMV-GP—across diverse brain tumor cell lines including glioblastoma (GBM), diffuse intrinsic pontine glioma (DIPG), medulloblastoma, and metastatic brain cancers. Results: VSV-GP and FuG-B2 pseudotypes significantly outperformed LCMV-GP across most tumor types. Both VSV-GP and FuG-B2 demonstrated high transduction efficiency in GBM and DIPG cells, though some cell lines displayed selective preferences for one pseudotype over the other. Medulloblastoma cells were challenging to transduce, with only VSV-GP achieving substantial efficacy. Metastatic brain cancers showed distinct tropism patterns: melanoma metastases were preferentially transduced by the FuG-B2 pseudotype, while lung metastases showed preference for the VSV-GP pseudotype. Conclusions: These findings suggest envelope protein selection should be tailored to specific brain tumor types. VSV-GP appears most suitable for medulloblastoma and lung metastases, FuG-B2 for melanoma metastases, and both for GBM and DIPG gene therapy applications. The study provides crucial guidance for translating lentiviral gene therapy to clinical applications, supporting personalized treatment strategies based on tumor-specific vector tropism profiles. Full article

Spinal cord injury (SCI) remains one of the most formidable challenges in regenerative medicine, often resulting in permanent loss of motor, sensory, and autonomic function. Cell-based therapies offer a promising path toward repair by providing donor neurons and glia capable of integrating into host circuits, modulating the injury environment, and restoring function. Early studies employing fetal neural tissue and neural progenitor cells (NPCs) have demonstrated proof-of-principle for survival, differentiation, and synaptic integration. More recently, pluripotent stem cell (PSC)-derived donor populations and engineered constructs have expanded the therapeutic repertoire, enabling precise specification of interneuron subtypes, astrocytes, and oligodendrocytes tailored to the injured spinal cord. Advances in genetic engineering, including CRISPR-based editing, trophic factor overexpression, and immune-evasive modifications, are giving rise to next-generation donor cells with enhanced survival and controllable integration. At the same time, biomaterials, pharmacological agents, activity-based therapies, and neuromodulation strategies are being combined with transplantation to overcome barriers and promote long-term recovery. In this review, we summarize progress in designing and engineering donor cells and tissues for SCI repair, highlight how combination strategies are reshaping the therapeutic landscape, and outline opportunities for next-generation approaches. Together, these advances point toward a future in which tailored, multimodal cell-based therapies achieve consistent and durable restoration of spinal cord function. Full article

Background: Parasitic skin-related conditions represent a frequent and evolving challenge in human dermatology, as they often mimic other dermatoses, and are increasingly complicated by therapeutic resistance. With this study, we aimed to provide a practical, clinician-oriented overview of our experience, contextualising it within the current literature. Materials and Methods: We conducted a retrospective, single-centre observational study, reporting a case series of 88 patients diagnosed with parasitic or arthropod-related skin infestations at the San Raffaele Hospital Dermatology Unit (Milan) between 2019 and 2024, and integrated a concise narrative review of contemporary evidence on diagnosis, non-invasive imaging and management. For each case, we documented clinical presentation, dermoscopic or reflectance confocal microscopy (RCM) findings, and treatment response. Non-invasive tools (dermoscopy, videodermoscopy, RCM) were used when appropriate. Results: The spectrum of conditions included flea bites, bed bug bites, cutaneous larva migrans, subcutaneous dirofilariasis, Dermanyssus gallinae dermatitis, pediculosis, tick bites (including Lyme disease), myiasis, scabies, and cutaneous leishmaniasis. One case of eosinophilic dermatosis of haematologic malignancy was also considered due to its possible association with arthropod bites. Non-invasive imaging was critical in confirming suspected infestations, particularly in ambiguous cases or when invasive testing was not feasible. Several cases highlighted suspected therapeutic resistance: a paediatric pediculosis and three adult scabies cases required systemic therapy after standard regimens failed, raising concerns over putative resistance to permethrin and pyrethroids. In dirofilariasis, the persistence of filarial elements visualised by RCM justified the extension of antiparasitic therapy despite prior surgical removal. Conclusions: Our findings underline that accurate diagnosis, early intervention, and tailored treatment remain essential for the effective management of cutaneous infestations. The observed vast spectrum of isolated parasites reflects broader health and ecological dynamics, including zoonotic transmission, international mobility, and changing environmental conditions. At the same time, diagnostic delays, inappropriate treatments, and neglected parasitic diseases continue to pose significant risks. To address these challenges, clinicians should remain alert to atypical presentations, and consider a multidisciplinary approach including the consultation with parasitologists and veterinarians, as well as the incorporation of high-resolution imaging and alternative therapeutic strategies into their routine practice. Full article

Lymph node evaluation is a central determinant of oncologic quality in the surgical management of non-small-cell lung cancer (NSCLC). Accurate assessment of hilar and mediastinal lymph nodes underpins pathologic staging, informs postoperative treatment decisions, and remains essential for prognostic stratification and assessment of resection completeness. Although international guidelines provide clear recommendations, real-world data consistently demonstrate substantial variability in lymph node staging practices, with inadequate evaluation frequently observed across institutions and surgical settings. Insufficient nodal assessment, manifested as the omission of mediastinal staging, limited station sampling, or low lymph node yield, is associated with reduced nodal upstaging, inappropriate omission of adjuvant therapy, higher recurrence rates, and inferior long-term survival. Contemporary guidance from major societies, including the National Comprehensive Cancer Network, European Society of Thoracic Surgeons, International Association for the Study of Lung Cancer, and the Commission on Cancer, has increasingly converged on a station-based definition of adequacy, emphasizing systematic evaluation of both N1 and N2 nodal stations rather than reliance on absolute node counts alone. In parallel, preoperative mediastinal staging algorithms have evolved toward routine use of endobronchial and esophageal ultrasound as first-line invasive modalities, reserving surgical mediastinoscopy for selected high-risk or inconclusive cases. Evidence from randomized trials, population-level databases, and meta-analyses indicates that thorough nodal assessment improves staging accuracy and survival, while recent data support the selective use of lobe-specific or tailored lymphadenectomy in carefully staged, low-risk early disease. Finally, emerging quality improvement interventions, including standardized specimen handling, operative checklists, and multidisciplinary feedback mechanisms, have demonstrated measurable improvements in guideline adherence and patient outcomes. This narrative review integrates contemporary evidence and guideline recommendations to outline a practical framework for implementing reliable, high-quality lymph node staging in modern lung cancer surgery. Full article