Search Results (1,220)

Background and Clinical Significance: Acquired angioedema (AAE) is a rare and potentially life-threatening condition characterized by acquired deficiency of C1-inhibitor (C1-INH) resulting in hyperactivation of the classical complement pathway. AAE occurs in association with malignancies or autoimmune diseases. Infectious triggers are rarely encountered, and the underlying mechanisms have yet to be completely clarified. Case Presentation: This case involves a previously healthy 19-year-old male who was admitted with Mycoplasma pneumonia and oral ulcers, subsequently developing unilateral facial angioedema. Laboratory studies demonstrated reduced C4, decreased levels and activity of C1-INH, and reduced C1q, all consistent with acquired C1-INH deficiency. These findings were attributed to the presence of cold agglutinins, which are frequently observed in Mycoplasma pneumoniae infections. Following treatment with icatibant, a bradykinin B2 receptor antagonist, the patient’s angioedema resolved rapidly. An exhaustive workup found no evidence of underlying systemic disorders, and the patient did not experience any angioedema attacks following resolution of the infection. Conclusions: The presence of cold agglutinins, commonly associated with Mycoplasma infections, can precipitate a decline in C1-INH levels, resulting in complement pathway dysregulation. This disruption leads to an excess of bradykinin, followed by increased vascular permeability and localized edema. Full article

Individuals with severe mental illness face a substantially higher risk of suicide compared with the general population, with drug overdose representing one of the most common and potentially lethal methods. This narrative review explores toxidromes frequently encountered in psychiatric populations, such as opioid, anticholinergic, and serotonergic toxicity, highlighting the clinical presentation in intentional overdose. Emphasis is placed on clinical recognition, antidote-based treatment, and systems-level strategies for the prevention of lethal overdose. We conducted a comprehensive literature search of PubMed, Google Scholar, and Web of Science for English-language articles using combinations of the following keywords: mental disorders; persons with psychiatric disorders; drug overdose; poisoning; serotonin syndrome; neuroleptic malignant syndrome; anticholinergic agents/poisoning; cholinergic antagonists/poisoning; psychotropic drugs/adverse effects; substance-related disorders; drug-related side effects and adverse reactions; polypharmacy; suicide, attempted; emergency service, hospital. By embedding toxidrome awareness into routine emergency and psychiatric practice, we aim to expedite treatment and improve patient outcomes. Full article

Background: Patients with hematological malignancies undergo intensive treatments, endure prolonged hospitalizations, and face the stress of a life-threatening diagnosis, placing them at high risk for developing post-traumatic stress disorder (PTSD) and related trauma symptoms. Methods: This narrative review synthesizes findings from PubMed-indexed studies examining the prevalence, clinical features, and consequences of PTSD in patients with hematological malignancies. A separate focused search was also conducted to identify PTSD studies in patients undergoing hematopoietic stem cell transplantation, which is a population recognized as being at high psychological risk. Results: Evidence indicates that a substantial proportion of these patients develop full or subthreshold PTSD. Key contributing factors include treatment intensity, fear of relapse, and extended hospital stays. PTSD symptoms are linked to reduced treatment adherence, diminished quality of life, and poorer clinical outcomes. Conclusions: Psychiatric care plays a critical role in addressing PTSD in this population. Routine trauma-informed screening, access to evidence-based pharmacologic and psychotherapeutic interventions, and close interdisciplinary collaboration with hematology teams are essential to improving patient outcomes. Full article

Background/Objectives: Gallstone disease, a prevalent and costly digestive system disorder, is influenced by multifactorial risk factors, some of which may predispose to malignancy. This study aims to evaluate the association between gallstone disease and malignancy using advanced machine learning (ML) algorithms. Methods: A dataset comprising approximately 1000 patients was analyzed, employing six ML methods: random forests (RFs), support vector machines (SVMs), multi-layer perceptron (MLP), MLP with PyTorch 2.3.1 (MLP_PT), naive Bayes (NB), and Tabular Prior-data Fitted Network (TabPFN). Comparative performance was assessed using Pearson correlation, sensitivity, specificity, Kappa, receiver operating characteristic (ROC), area under curve (AUC), and accuracy metrics. Results: Our results revealed that age, body mass index (BMI), and history of HRT were the most significant predictors of malignancy. Among the ML models, TabPFN emerged as the most effective, achieving superior performance across multiple evaluation criteria. Conclusions: This study highlights the potential of leveraging cutting-edge ML methodologies to uncover complex relationships in clinical datasets, offering a novel perspective on gallstone-related malignancy. By identifying critical risk factors and demonstrating the efficacy of TabPFN, this research provides actionable insights for predictive modeling and personalized patient management in clinical practice. Full article

Background: Autoimmune diseases and other immune-mediated disorders are associated with an increased risk of malignancy, influenced by chronic inflammation, immune dysregulation, and treatment-related factors. Clarifying cancer risk patterns across specific conditions is essential to improve clinical vigilance and inform screening practices. Objective: The aim of this study was to synthesise current evidence on the association between autoimmune and immune-mediated diseases and cancer, with a focus on practical implications for clinicians. Methods: Recent cohort studies, meta-analyses, and expert consensus documents were analysed to describe cancer epidemiology, pathogenic mechanisms, high-risk phenotypes, and treatment considerations across major autoimmune diseases and other immune-mediated conditions. The review covers idiopathic inflammatory myopathies, Sjögren’s syndrome, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, ANCA-associated vasculitis, giant cell arteritis, polymyalgia rheumatica, sarcoidosis, mixed connective tissue disease, IgG4-related disease, VEXAS syndrome, and eosinophilic fasciitis. Special attention was given to identifying warning features for underlying malignancy and evaluating cancer screening strategies. Results: The magnitude and distribution of cancer risk vary across diseases. In some conditions such as dermatomyositis, systemic sclerosis or Sjögren’s syndrome, increased risk is well established, particularly for haematological and certain solid tumours. However, tumour patterns may differ across populations, and findings are not always consistent. Distinct clinical and serological features help stratify individual cancer risk and may guide the intensity of screening. The first years after disease onset often represent a window of higher vulnerability, during which intensified surveillance may be warranted in selected patients. Conclusions: Cancer risk in autoimmune diseases should be assessed on an individual basis. Awareness of disease-specific risk factors and clinical warning signs supports early recognition of malignancy and informs screening decisions in routine practice. Full article

Background: chordomas are characterized as locally aggressive yet infrequently metastasizing malignant neoplasms of bone, primarily arising in the axial skeleton, with a notable prevalence in the sacral region. En bloc resection is recognized as the standard treatment for sacral chordoma; however, its feasibility is not universally guaranteed. Therefore, definitive proton, carbon ion, or photon therapy is often utilized as an alternative to surgical intervention or as a (neo-)adjuvant measure in conjunction with surgery, owing to their role in enhancing local control. Methods: a search of PubMed yielded 127 articles, with 18 that were ultimately included in the review. This review aims to systematically evaluate clinical outcomes and complications associated with hadron therapy in cases of sacral chordomas. The review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, including publication dates up to January 2025. Results: data extraction showed promising outcomes for patients treated with hadron therapy alone or when hadron therapy was used as an adjuvant for surgery, even if complications are described. The 5-year overall survival estimated from evaluating 10 of 18 articles was 82.4%, although some articles reported different results in shorter follow-up periods. Skin ulceration and pain were described in 323 (29%) and 186 (16%) patients, respectively. Chronic complications reported were sacral fractures, metastasis, rectal disorders, urinary disorders, and peripheral motor and sensory neuropathy. Conclusions: hadron therapy represents a highly effective and promising treatment for sacral chordomas. In cases of inoperable tumors, it has demonstrated outcomes comparable to surgery while significantly reducing treatment-related morbidity. Hadron therapy is also viable as adjuvant therapy and provides superior outcomes for patients who undergo surgery with positive margins compared to those treated with surgery alone, improving local control and overall prognosis. Full article

Oral leukoplakia (OL) is the most common potentially malignant oral disorder, with variable risk of progression to oral squamous cell carcinoma (OSCC). This study evaluated the chemopreventive and immunomodulatory potential of Artemisinin (ART) and Rubus occidentalis (RO), alone or combined (ARO), in a 4NQO-induced murine model. Mice received 4NQO (100 µg/mL) in drinking water, and treatments began at week 8. Animals were euthanized at weeks 12 and 16 for histological, apoptotic (caspases-3, -8, -9; calreticulin), inflammatory (IL-1β, IL-10, HMGB1), and immune (CD8, CD68, CD56, IFN-γ, GM-CSF) marker analyses. RO-treated animals showed delayed malignant transformation, with no carcinomas at week 16 and increased expression of caspase-9, calreticulin, HMGB1, IFN-γ, and GM-CSF, indicating transient activation of antitumor immune responses. ART-treated mice showed increased CD68 and reduced CD56 expression, suggesting an immunosuppressive profile and higher carcinoma incidence. The ARO combination did not improve outcomes beyond ART alone. These findings support the immunomodulatory and pro-apoptotic effects of RO in delaying OL progression, highlighting its chemopreventive potential. ART showed limited benefit under current conditions, warranting further investigation into dose optimization and synergistic strategies. Full article

Asbestos-related diseases (ARDs), including malignant mesothelioma, asbestos-related lung cancer, and asbestosis, are known for their long latency periods and poor prognoses. Although the physical effects of ARDs have been widely studied, limited research has examined the psychological burden faced by affected individuals. This study investigated depressive and anxiety symptoms among 275 patients officially recognized as asbestos victims in Korea. Mental health was assessed using the Korean version of the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and the Hospital Anxiety and Depression Scale (HADS). The analysis revealed that the mean ± standard deviation of depression and anxiety levels among patients with asbestos-related diseases were 8.06 ± 6.27 for PHQ-9, 6.02 ± 5.64 for GAD-7, 7.09 ± 5.44 for HADS-A, and 8.41 ± 5.47 for HADS-D. Patients with asbestosis had higher levels of depressive and anxiety symptoms than those with malignant mesothelioma or lung cancer, with symptom severity increasing alongside asbestosis grade. When compared with national data from the 2020–2021 Korea National Health and Nutrition Examination Survey (KNHANES), PHQ-9 and GAD-7 scores among ARD patients, particularly those with Grade 1 asbestosis, were higher than the scores reported for all major cancer types. These findings highlight the substantial psychological distress experienced by individuals with ARDs and emphasize the urgent need for targeted mental health interventions in this population. Full article

Oral squamous cell carcinoma (OSCC) is a malignancy with a poor prognosis, and early diagnosis is essential for improving patient survival and quality of life. This study aimed to develop a non-invasive screening method based on salivary gene expression and microbiome analysis. Unstimulated saliva samples were collected from patients with OSCC, patients with oral potentially malignant disorders, and healthy controls. Microbiome profiling was performed using 16S ribosomal RNA gene sequencing. The OSCC group showed a significant increase in Fusobacterium and Bacteroidetes and a decrease in Streptococcus. LEfSe analysis indicated microbial changes associated with disease progression. Receiver operating characteristic analysis demonstrated high diagnostic accuracy when multiple bacterial species were combined. An increase in Fusobacteria was also associated with a higher risk of recurrence. Gene expression analysis revealed that NUS1, RCN1, CPLANE1, and CCL20 were significantly upregulated in OSCC, as confirmed by qRT-PCR and tissue expression data. Notably, CCL20 expression positively correlated with Fusobacterium abundance. These findings suggest that integrated analysis of the salivary microbiome and gene expression may offer a useful non-invasive approach for early OSCC detection and disease monitoring. Furthermore, we integrated current evidence from the literature to provide a comprehensive overview. Full article

Multiple myeloma (MM) is a malignant plasma cell disorder that evolves from precursor conditions including monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Understanding the biological continuum and the molecular drivers of disease progression is crucial for early diagnosis and risk-adapted therapy. Recent advances in next-generation sequencing have identified recurrent mutations in the RAS/MAPK, TP53, and MYC pathways, along with epigenetic alterations that contribute to clonal evolution and therapeutic resistance. Novel diagnostic tools including minimal residual disease (MRD) assessment, gene expression profiling, and advanced imaging have improved risk stratification. Therapeutically, the integration of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has dramatically improved patient outcomes. In parallel, emerging immunotherapies such as CAR-T cells, bispecific T-cell engagers, and antibody–drug conjugates are expanding treatment options, especially in relapsed or refractory settings. Future directions aim to personalize treatment using genomics, target the tumor microenvironment, and leverage synthetic lethality and epigenetic vulnerabilities. This review highlights the evolving landscape of plasma cell disorders from molecular pathogenesis to cutting-edge therapeutic innovations, emphasizing the need for precision medicine approaches to improve survival and quality of life for patients with MM and its precursors. Full article

Background/Objectives: The goal of this research was to determine the prevalence and distribution of the oro-maxillofacial pathologies in patients with diabetes mellitus and to determine the correlation between diabetes mellitus and oro-maxillofacial disorders. Methods: The retrospective study group consisted of 6868 patients (mean age 49.84 ± 22.79 years) admitted in Oral and Maxillofacial Surgery Department between 2018 and 2024. Qualitative data were analyzed by Chi-square (χ²) test. Odds Ratio (OR) and Relative Risk (RR) were measured for each oro-maxillofacial pathology. Quantitative data were analyzed by Student’s T-test. Results: Among patients with diabetes mellitus (DM), the estimated risk of malignant tumors was 5.29 times higher (RR = 5.29; p = 0.001) compared to the non-DM group, with 15.0% of diabetic patients affected, versus 1.4% in the non-diabetic group. The probability of periodontal disease in diabetic patients was 4.66 times higher (RR = 4.66; p = 0.001), affecting 5.5% of the DM group, compared to only 0.6% in the non-DM group. Diabetic patients had a likelihood 3.53 times higher (RR = 3.53; p = 0.001) of developing apical periodontitis, with 5.3% of the DM group affected, in contrast to 1.0% of the non-DM group. The presence of root remnants was 1.43 times more likely (RR = 1.43; p = 0.001) in diabetic patients, with 9.0% of the DM group affected, compared to 6.1% in the non-DM group. Conclusions: The strong correlation between diabetes and oral pathologies, particularly malignancies and periodontal disease, underscores the need for early screening, preventive care, and targeted management strategies for diabetic patients. Full article

Oral cancer (OC) constitutes a significant health problem globally. There is an urgent need to develop novel biomarkers for OC diagnosis. This meta-analysis aimed to analyze the potential of salivary lactate dehydrogenase (LDH), matrix metalloproteinase-9 (MMP-9), and chemerin as OC biomarkers. The meta-analysis was conducted according to the PRISMA statement guidelines and registered in PROSPERO (CRD420251045968). PubMed, Embase, Scopus, and Web of Science databases were thoroughly searched up to 18 April 2025. After screening, thirty-three articles were included in the meta-analysis based on the random-effects model. The meta-analysis revealed a significantly elevated LDH level in OC patients compared with controls (SMD = 4.592, 95% CI: 3.580–5.605, p < 0.001) and with oral potentially malignant disorders (OPMD) (SMD = 2.416, 95% CI: 1.474–3.358, p < 0.001). For poorly versus well-differentiated OC, significantly higher LDH levels were observed in poorly differentiated tumors (SMD = 6.158, 95% CI: 0.739–11.576, p = 0.027). For MMP-9, there was a significant increase in OC compared with controls and a borderline-significant difference compared with OPMD (SMD = 1.507, 95% CI: 0.644–2.369, p = 0.001; SMD = 1.626, 95% CI: −0.097–3.350, p = 0.064, respectively). In comparing poorly versus well-differentiated OC, MMP-9 levels were significantly increased in poorly differentiated tumors (SMD = 1.790, 95% CI: 0.643–2.937, p = 0.003). Chemerin levels were significantly elevated in OC versus controls (SMD = 3.905, 95% CI: 3.210–4.600, p < 0.001) and OPMD (SMD = 1.605, 95% CI: 1.139–2.071, p < 0.001). In conclusion, these findings support the potential use of LDH, MMP-9, and chemerin as adjunctive biomarkers in diagnosing and stratifying OC. Full article

The areca nut (AN) is chewed by approximately 600 million people worldwide. Among AN chewers, ~5% develop oral submucosal fibrosis (OSF), a progressive fibrotic disorder of the oral cavity. OSF is characterized by subepithelial fibrosis and mucosal rigidity, leading to restricted mouth opening, difficulty in mastication, deglutition, and speech. These impairments severely compromise oral hygiene and routine dental care, diminishing patients’ quality of life. At least 4% of OSF patients develop oral cancer. The prevalence of OSF correlates with AN chewing, particularly when accompanied by other risk factors such as tobacco use. The International Agency for Research on Cancer has identified chronic chemical and mechanical irritation of the oral mucosa from AN chewing as a major cause of OSF. The active chemical ingredients of AN include alkaloids such as arecoline, flavonoids, and tannins. Of these, arecoline is considered the most potent fibrogenic agent. In vitro, arecoline induces cultured fibroblasts to differentiate into highly contractile α-smooth muscle actin (α-SMA)-expressing myofibroblasts, the effector cells of fibrosis, and to express profibrotic markers and mediators, including transforming growth factor-β 1 (TGF-β1) and cellular communication network factor 2 (CCN2), which is associated with malignant progression of OSF. In vivo, mice exposed to AN extract or arecoline show submucosal collagen accumulation and myofibroblast differentiation, concomitant with upregulated pro-fibrotic gene (TGF-β1, Col1A1, α-SMA) expression. Although myofibroblasts can be seen in OSF patient-derived samples, substantial disease heterogeneity exists, which has thus far hindered the generation of high-quality data necessary to gain insights into underlying mechanisms and disease progression. Consequently, treatment options for OSF are limited and primarily symptomatic. Collectively, evidence from human and animal studies establishes OSF as an AN-induced fibrotic disorder and underscores the urgent need for mechanism-focused research to identify reliable diagnostic markers and therapeutic targets to address its growing global burden. Full article

Chimeric antigen receptor (CAR) T cell immunotherapy has changed the landscape of B cell hematological malignancies’ management, while it has recently shown promising results in the treatment of refractory autoimmune rheumatic disorders (ARDs). Targeting B cell antigens such as CD19 and BCMA, CAR-T cell therapy can induce sustained remission by the elimination of autoreactive B cell populations resistant to the standard of care treatment options. Clinical data from case reports and small case series demonstrate profound clinical responses in ARDs, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), rheumatoid arthritis (RA), antiphospholipid syndrome (APS), and primary Sjögren’s syndrome (pSS). Treatment outcomes include reduced disease activity, normalization of serologic markers, improved organ function, and drug-free remission, even after B cell reconstitution. Additionally, toxicities, primarily limited to mild cytokine release syndrome (CRS), were generally manageable with supportive care. Encouraging preliminary results have led to the development of several ongoing clinical trials investigating CAR-T cell therapy across multiple ARDs and patient populations, including pediatric patients. This review summarizes the current clinical experience and provides a comprehensive overview of ongoing clinical trials exploring CAR-T cell immunotherapy for ARDs. Full article

Background: Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle triggered by certain anesthetic agents. While Ryanodine Receptor 1 (RYR1) and Calcium Voltage-Gated Channel Subunit Alpha1 S (CACNA1S) are well-established susceptibility genes, the complete genetic basis of MH remains unclear, particularly in Asian populations. Methods: We conducted gene panel testing targeting 24 calcium-related genes in 338 individuals from 247 Japanese families with suspected or confirmed MH. Variants were analyzed on a gene-by-gene basis, and their pathogenicity was assessed using in silico prediction tools. Additionally, patients were classified into subgroups based on the results of the calcium-induced calcium release (CICR) assay and the Clinical Grading Scale (CGS) score. Results: Candidate pathogenic variants were identified in 118 families (48.2%), including 73 (29.8%) in RYR1, 16 (6.5%) in CACNA1S, and 62 (25.3%) in other genes. Among CICR-positive families, RYR1 and CACNA1S variants were detected in 42.0% and 5.3% of cases, respectively. In individuals with high CGS scores (Ranks 5–6), RYR1 and CACNA1S variants were observed in 56.0% and 12.0%, respectively. Variants in other genes such as STAC3, CASQ1, ATP2A1, ASPH, HRC and TRPV1 were also detected. Conclusions: Our findings confirm the predominant role of RYR1 and CACNA1S in MH susceptibility in the Japanese population and highlight additional candidate genes that may contribute to the condition. Broader genetic screening and functional validation studies are warranted to further elucidate the polygenic nature of MH. Full article