Search Results (3,263)

The pancreas is an organ with two functions: endocrine and exocrine. The proper functioning of the pancreas depends on many factors. One of these is trace elements—precise control of trace element homeostasis is important for both the endocrine and exocrine parts. This review provides a comprehensive summary of current knowledge regarding the role of trace elements: iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in pancreatic physiology and their influence on the pathogenesis of key diseases of this organ, such as diabetes (DM), acute (AP) and chronic pancreatitis (CP), autoimmune pancreatitis (AIP), and pancreatic cancer (PC). Trace elements, including Fe, Cu, Zn, Se, and Mn, play a fundamental role in maintaining endocrine and exocrine homeostasis, participating in insulin synthesis, stabilizing digestive enzymes, and the functioning of antioxidant systems. It has been demonstrated that disturbances in their concentrations lead to the activation of pathological molecular pathways, including oxidative stress, chronic inflammation, and beta-cell apoptosis. In the context of diabetes, excess Fe promotes ferroptosis, whilst exposure to heavy metals such as Cd, Pb, and Hg induces insulin resistance and pancreatic islet dysfunction. In the course of pancreatitis, elements such as Zn and Se exhibit protective potential by stabilizing tissue barriers, whereas toxic metals impair ion transport, exacerbating fibrotic processes. Furthermore, analysis of available data indicates a significant association between heavy metal accumulation and pancreatic carcinogenesis, driven by DNA damage and oncogene modulation. Understanding pancreatic metallomics opens new prospects for early diagnosis, environmental prevention, and the development of targeted therapeutic strategies that restore the body’s micronutrient balance. Full article

Background: Lentigo maligna (LM) represents melanoma in situ and predominantly affects elderly individuals, typically arising on chronically sun-exposed skin of the head and neck. Although LM is characterized by slow horizontal growth and generally favourable prognosis, progression to invasive lentigo maligna melanoma may occur, making timely and effective treatment essential. Surgical excision remains the standard of care; however, advanced age, comorbidities, lesion size, and cosmetic or functional considerations may limit surgical feasibility. Case presentation: We report the case of a 93-year-old woman with no prior history of skin cancer who presented with a gradually enlarging pigmented lesion on the forehead. Clinical examination revealed an irregularly pigmented macule measuring 25 × 27 mm. Multiple mapping biopsies confirmed melanoma in situ of the lentigo maligna type, with adnexal extension and no evidence of dermal invasion. Given the patient’s advanced age and lesion location, a non-surgical approach was selected. Topical imiquimod 5% cream was applied five times per week for 12 weeks to the visible lesion and to a 20 mm margin around it. The patient was monitored closely throughout the treatment. Local inflammatory reactions were mild to moderate, consisting mainly of erythema, crusting, and superficial erosion, without systemic adverse effects. At treatment completion, marked clinical improvement with near-complete resolution of pigmentation was observed. Follow-up dermoscopic evaluation demonstrated only minimal residual granular pigmentation. Post-treatment mapping biopsies confirmed complete histological clearance of atypical melanocytic cells. Conclusions: This case illustrates that topical imiquimod may serve as a safe and effective alternative to surgery in carefully selected elderly patients with lentigo maligna. Close clinical follow-up and histological confirmation of clearance are essential to ensure treatment success and durable outcomes. Full article

Pain is a multidimensional experience arising from the integration of nociceptive signals with affective, cognitive and behavioral processes. In Alzheimer’s disease (AD), pain assessment remains challenging, as reduced self-reported pain is frequently observed despite exposure to potentially painful conditions, suggesting altered processing rather than its absence. Emerging evidence indicates that pain in AD is characterized by a disruption of coordination among sensory detection, affective experience and clinical expression. Within this framework, nociceptive input may remain partially preserved, while its integration into emotionally meaningful and behaviorally coherent responses is compromised. Clinical studies report reduced self-report alongside observable indicators of discomfort, including agitation, withdrawal and affective disturbances. In parallel, preclinical models demonstrate preserved reflexive responses but altered affective-motivational processing. These alterations are associated with neuroinflammatory processes, synaptic dysfunction, large-scale network disconnection and changes in neuromodulatory systems involved in affective pain regulation, ultimately disrupting the integration of nociceptive signals within limbic and cortical networks. Taken together, this review integrates clinical and preclinical evidence to characterize pain in AD as a disruption of multilevel integration linking nociception, affective processing and clinical expression, with important implications for pain assessment strategies that extend beyond self-report to incorporate behavioral and translational approaches. Full article

Complicated community-acquired pneumonia (cCAP) remains a major cause of morbidity in children. Although pneumococcal conjugate vaccines (PCVs) have reduced invasive disease, severe complications such as empyema and lung abscess persist. A retrospective analysis was conducted on 69 children treated at the University Children’s Hospital Belgrade between 2019 and 2024. Data included demographic characteristics, pneumococcal vaccination status, and radiologically confirmed complications. Patients were classified by residence and vaccination status. Statistical analysis included chi-square (χ²) tests, odds ratios (ORs) with 95% confidence intervals, and multivariable logistic regression. Pleuropneumonia and pleural effusion were the most frequent complications, while empyema and lung abscess were the most severe. Both occurred significantly more often in unvaccinated children (p = 0.0054 and p = 0.0027). Multivariable analysis confirmed vaccination as an independent protective factor against empyema (adjusted OR = 0.19, 95% CI 0.06–0.61). No significant regional differences were observed after accounting for vaccination status. Vaccination showed a strong protective effect against empyema and lung abscess (OR = 0.24 and 0.04, respectively). Unvaccinated children had significantly longer hospital stays, indicating a more severe clinical course. Prolonged hospitalization was associated with intensified antibiotic therapy, reflecting underlying disease severity. Lack of pneumococcal vaccination is strongly associated with severe complications in children with cCAP. Maintaining high PCV coverage remains essential, alongside early recognition and timely management of pleural disease. Full article

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a promising strategy for refractory cardiac arrest, enabling the restoration of systemic perfusion when conventional resuscitation fails. However, uncertainties remain regarding patient selection, timing and implementation. Methods: A narrative review of experimental data, clinical studies, randomized trials and international recommendations was performed. Particular emphasis was placed on the interplay between physiological mechanisms, real-world organizational models and decision-making processes. Results: ECPR can restore effective circulation, preserve end organ perfusion and serve as a bridge to definitive etiologic treatment, with the potential to improve survival and neurological outcomes in highly selected patients. However, its effectiveness is strongly dependent on rapid deployment, structured systems of care and multidisciplinary coordination. Significant challenges remain, including in relation to the heterogeneity of protocols, high resource utilization, complications with extracorporeal support and the complexity of post-resuscitation management. Furthermore, ECPR fundamentally alters traditional resuscitation paradigms, introducing ethical dilemmas related to patient selection, prognostication and the allocation of limited resources. Conclusions: ECPR represents a transition from procedure-based resuscitation to system-based extracorporeal support. Its clinical benefit is contingent upon timely implementation within optimized organizational frameworks and integration with definitive treatment pathways. Future research should focus on refining selection criteria, standardizing care pathways and addressing ethical sustainability challenges to ensure appropriate and effective use of this evolving technology. Full article

Background: Women with abnormal uterine bleeding (AUB) is reported in 10–30% of women and is a significant cause of iron deficiency anemia (IDA), with long-term effects on women’s quality of life. This retrospective study looked at the underlying causes of AUB and the contributory factors that required blood transfusions. Objectives: This study aimed to identify the treatable causes of AUB in patients who needed blood transfusion and parenteral iron in the reproductive age group and provide appropriate treatment to these underlying pathologies. Methods: A retrospective study was conducted in reproductive age group women with anemia due to AUB over a period of 10 years from January 2013 to December 2022. All women with significant uterine bleeding, who required blood transfusion were included in this study. Women with pregnancy, and hemolytic anemia, were excluded from the study. Results: During the study period 266 women needed blood transfusion for AUB. The mean age was 37.66 ± 11.4 years, mean parity 3, mean body mass index (BMI): 29.4 ± 8.9 kg/m², and most reported regular cycles. The most common etiology of AUB was uterine fibroids in 37.9% followed by ovulatory dysfunction in 15%. The mean hemoglobin was at 5.7 ± 1.14 gm/L, mean ferritin was 11.01 ± 21.88 ng/mL, mean number of blood transfusion was 2.83 ± 1.2 at first presentation and about 24% needed further transfusions. About 70% of them preferred oral hormonal treatment. Surgical management was required in about 35% of patients. Conclusion: The main cause of AUB was leiomyoma and anovulation. The morbidity of blood transfusion was easily avoidable in these women. Full article

(1) Background: The role of baseline humoral immunization in bone regeneration remains unclear. This study assessed the relationship between baseline serological immunization, graft type, photobiomodulation (PBM), and histological outcomes after maxillary sinus floor augmentation. (2) Methods: This exploratory secondary analysis included 20 adults undergoing lateral maxillary sinus lifting. Patients were allocated according to graft type (allogeneic or xenogeneic) and postoperative protocol (with or without adjunctive PBM). Before surgery, serum samples were analyzed for anti-HLA class I, anti-HLA class II, and anti-MICA antibodies. After approximately 6 months, bone core biopsies were collected. Histological evaluation focused on inflammatory cell infiltrates (ICI). (3) Results: Baseline antibody positivity was detected in 35.0% of patients for anti-HLA class I, 55.0% for anti-HLA class II, and 45.0% for anti-MICA. Histological findings were generally favorable. ICI scores were low, with 65.0% of samples scoring 0 and 35.0% scoring 1. A nominal positive correlation was observed between anti-HLA class I NBG ratio and ICI; however, this finding did not remain statistically significant after correction for multiple comparisons. Exploratory PBM subgroup estimates were directionally different but were based on very small subgroups and should not be interpreted as evidence of effect modification. (4) Conclusions: The findings suggest a possible hypothesis-generating link between baseline humoral sensitization and mild local inflammatory infiltrates, which requires validation in larger, prospectively powered studies with predefined histological and immunological endpoints. Full article

Prostate cancer (PCa) is one of the leading causes of cancer-related morbidity and mortality in men worldwide, and early detection remains crucial for ensuring effective treatment and improving patient outcomes. In this context, the development of non-invasive, accurate, and cost-effective screening strategies is of paramount importance. One particularly promising and innovative approach is the analysis of volatile organic compounds (VOCs), a field known as volatolomics. VOCs, which are metabolic by products released by the body, reflect underlying biochemical processes and offer a valuable, non-invasive source of diagnostic information. Recent advances have highlighted the potential of VOC profiling in PCa detection. A variety of biological systems have demonstrated remarkable sensitivity and specificity in recognizing disease-associated VOC signatures. Notably, trained dogs, selected invertebrates, and artificial sensing platforms have all shown the ability to identify PCa-related olfactory patterns. Among technological approaches, electronic noses (eNoses), which combine chemical sensor arrays with pattern recognition algorithms such as neural networks, represent a rapidly evolving diagnostic tool. Together, these biologically inspired and technology-driven strategies are reshaping the landscape of cancer diagnostics. They offer a compelling foundation for the development of rapid, non-invasive, and clinically translatable methods for PCa detection. This narrative review summarizes recent advances in using VOCs for PCa diagnosis and evaluates the reproducibility and clinical robustness of these approaches, focusing on challenges such as standardizing sampling, storage, and analysis, small cohort sizes, and the need for external validation and regulatory integration. Full article

CD47 is a transmembrane protein that possesses the ability to inhibit macrophage phagocytosis, enabling immune system evasion. While CD47 overexpression is associated with a poor prognosis in solid malignancies, data on its prognostic significance in lymphomas are inconsistent. This study aimed to evaluate the clinical and prognostic significance of CD47 expression in patients with large B-cell lymphoma (LBCL). In this study biopsy specimens from 146 patients diagnosed with LBCL and treated with immunochemotherapy were analyzed. CD47 expression was assessed using standard immunohistochemical methods. A high level of CD47 expression was detected in 30 (20.5%) patients. High CD47 expression was more frequently observed in patients with high β2-microglobulin levels and extranodal disease compared to nodal LBCL. No significant difference in CD47 expression was observed between gastrointestinal LBCL and other extranodal localizations. CD47 positivity had no significant influence on progression-free survival (PFS) and overall survival (OS); however, a trend toward shorter PFS and OS was noted (p = 0.099 and p = 0.149, respectively). The median PFS and OS were 27 and 37 months, respectively, in patients with high CD47 expression, while the median PFS and OS were not reached in the group of CD47 negative patients. Although CD47 expression was not an independent predictor of survival, the magnitude and direction of the observed hazard ratios suggest a potentially clinically meaningful effect. Full article

Hard-to-heal wounds pose a significant challenge in clinical practice due to the fact that the conventional treatments used are not always effective. For this reason, it is necessary to design alternatives to achieve an adequate resolution. In this context, a new Advanced Therapy product was produced in a Good Manufactured Practices Facility in the setting of a clinical trial authorised for the European Medicines Agency (EUCT 2023-505017-25-02). Briefly, an autologous plasma scaffold containing bone marrow mononuclear cells was applied to a 63-year-old male patient who presented a non-healing wound despite two months of self-care and three months of primary care treatment. After cleaning the affected area, a single-dose plasma scaffold with embedded bone marrow mononuclear cells was applied over the wound. Six weeks after treatment, the wound exhibited remarkable healing with complete closure as evidenced by follow-up assessments at different time points. Quality of life measures significantly improved, aligning with clinical findings, and no adverse effects were observed. While further studies are needed, the issues presented in this case report show the promising results obtained forthe first patient included in the trial and treated with this innovative alternative, which supports the potential of mononuclear cells combined with plasma as a therapeutic option for chronic wounds. Full article

Artificial intelligence (AI) is increasingly transforming gastrointestinal endoscopy by supporting lesion detection, lesion characterization, quality assessment, and clinical risk prediction. Hemostatic decision-making represents a particularly complex field for AI integration, as therapeutic decisions are often made rapidly in the presence of active bleeding, impaired visualization, unstable patients, and variable lesion accessibility. This review critically examines the current evidence for AI-assisted decision-making in gastrointestinal endoscopy and endoscopic hemostasis, with emphasis on gastrointestinal bleeding, prediction of hemostatic therapy requirements, bleeding-risk stratification, rebleeding prediction, transfusion support, and post-procedural monitoring. Available studies suggest that machine learning and deep learning models may outperform conventional scoring systems in selected retrospective or validation cohorts, improve recognition of high-risk lesions, support less experienced endoscopists, and contribute to more individualized management of non-variceal bleeding, variceal bleeding, and capsule endoscopy findings. However, prospective interventional evidence remains sparse, and most available models are limited by retrospective design, single-center datasets, incomplete external validation, black-box decision-making, heterogeneous reporting, workflow barriers, and uncertain cost-effectiveness. AI should therefore be regarded as an adjunctive decision-support tool rather than an autonomous replacement for clinical judgment. Its future value will depend on prospective multicenter validation, explainability, real-time usability, regulatory clarity, post-deployment surveillance, and evidence of improved patient-centered outcomes before widespread implementation in emergency endoscopy practice. Full article

Patellar tendinopathy is a chronic musculoskeletal condition characterized by localized pain and functional impairment. This systematic review and exploratory meta-analysis aimed to synthesize current evidence on the effectiveness of percutaneous electrolysis (PE), combined with eccentric exercise, for improving functional performance in individuals with patellar tendinopathy. Following PRISMA guidelines and registration in PROSPERO (CRD420251233971), comprehensive searches were performed in Cochrane Library, PEDro, PubMed, ScienceDirect, Scopus, and Web of Science databases. Only two randomized controlled trials, published between 2016 and 2021, met the eligibility criteria and were included in the quantitative synthesis. Functional capacity recorded using the Victorian Institute of Sport Assessment-Patella (VISA-P) scale was the primary outcome. Both included studies presented some concerns regarding risk of bias. The pooled random-effects meta-analysis (REML estimation with Hartung–Knapp–Sidik–Jonkman adjustment) revealed no statistically significant difference favoring PE over control interventions (Hedges’ g = –0.10; 95% CI: –2.69 to 2.50; p = 0.72). Statistical heterogeneity was nominally low (I² = 0%), although this metric is uninformative with only two studies. Between-group differences in both studies were below the minimal clinically important difference for the VISA-P scale. The certainty of evidence according to the GRADE framework was rated as very low. Given the extremely limited evidence base, these findings should be considered strictly exploratory. The very low certainty of evidence precludes definitive conclusions regarding the comparative effectiveness of PE. Larger, adequately powered randomized trials with standardized protocols and long-term follow-up are needed. Full article

Purpose: Ganglion cysts of the temporomandibular joint (TMJ) are uncommon periarticular lesions and may be diagnostically challenging because symptoms are often nonspecific. When these lesions arise posterior to the joint, they can produce otologic complaints through dynamic narrowing of the external auditory canal (EAC). Herein, we report on a histologically confirmed TMJ ganglion cyst causing position-dependent hearing loss and review the relevant literature. Case description: A 72-year-old woman presented with a 3-year history of bilateral preauricular pain, left-sided tinnitus, left aural fullness, and near-complete hearing loss in the left ear when the mandible was closed in occlusion. Clinical examination showed marked narrowing of the left EAC with mandibular closure. Magnetic resonance imaging demonstrated bilateral anterior disc displacement with reduction and a posterior meniscal cyst associated with the left TMJ. The lesion was excised using a preauricular approach. Results: Intraoperatively, the cyst was adherent to the posterior aspect of the TMJ disc and retrodiscal tissues and was noted to obstruct the EAC in the closed-mouth position. Gross examination showed a cystic structure measuring 2.4 × 2.1 × 1.0 cm which contained gelatinous material, while histopathology confirmed that the structure was a ganglion cyst. The patient’s hearing improved substantially by 4 months after surgery and had returned to normal 2 years later, with no clinical evidence of recurrence. Conclusions: Posterior TMJ ganglion cysts should be considered in patients with fluctuating otologic symptoms that vary with mandibular movement. MRI is valuable for diagnosis and surgical planning, and open excision can provide durable symptom resolution. Full article

Folliculitis decalvans (FD) and dissecting cellulitis of the scalp (DCS) are neutrophilic primary cicatricial alopecias characterized by chronic inflammation and irreversible hair loss, with distinct pathogenic mechanisms that make accurate diagnosis essential for appropriate management. This narrative review aims to provide a comprehensive overview of systemic therapeutic options for FD and DCS, to evaluate their efficacy in relation to underlying disease mechanisms, and to explore emerging targeted treatments. A literature search was conducted in PubMed/MEDLINE using relevant keywords related to neutrophilic cicatricial alopecias and therapeutic strategies, including studies reporting clinical outcomes in FD and DCS. Available evidence indicates that conventional therapies remain the cornerstone of management: antibiotics are typically first-line in FD, while isotretinoin represents the mainstay of treatment in DCS and a key option in refractory FD; however, these approaches are often associated with partial responses and frequent relapses. Biologic agents, particularly TNF-α inhibitors, have shown consistent benefit in refractory cases, while IL-17/23 and JAK inhibitors are supported by limited but emerging data. Overall, treatment response appears to reflect underlying pathogenic differences between FD and DCS, underscoring the importance of a tailored, mechanism-based approach. Further studies are needed to establish standardized treatment algorithms and confirm long-term efficacy and safety. Full article

Diabetes mellitus is a chronic and increasingly prevalent metabolic disorder characterized by persistent hyperglycemia, resulting from defects in insulin secretion, insulin action, or both. Despite the availability of pharmacological agents that effectively manage blood glucose levels, many are associated with adverse effects, limited efficacy over time, and high costs. Consequently, there is growing interest in alternative therapies, especially those derived from traditional medicinal plants, that have long been employed in various cultures for managing diabetes. Recent advances in phytochemistry have identified bioactive plant secondary metabolites with promising antidiabetic properties. This review aims to provide a comprehensive overview of plant-derived compounds that exhibit inhibitory activity against key diabetes-related enzymes, including α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl peptidase-4 (DPP-4). These enzymes play critical roles in glucose metabolism and insulin signaling pathways. The review highlights the structural diversity of these natural inhibitors, their mechanisms of action, and their effectiveness in preclinical models. Understanding the molecular interactions and pharmacological profiles of these metabolites may facilitate the development of safer and more effective antidiabetic agents. Full article