Search Results (28,571)

Background: The prognostic significance of histological transformation (HT) in treatment-naive diffuse large B-cell lymphoma (DLBCL) remains controversial. This study aimed to evaluate the clinical outcomes and failure patterns of treatment-naive transformed DLBCL (trDLBCL) compared with de novo DLBCL using a large-scale cohort. Methods: We retrospectively analyzed 1735 consecutively enrolled treatment-naive DLBCL patients (118 trDLBCL and 1617 de novo). Propensity score matching (PSM) was performed to balance baseline characteristics. Survival outcomes were assessed using Kaplan–Meier and Cox proportional hazards models. Subgroups were defined by pathology (t-FL vs. t-MZL) and pattern: concurrent (synchronous indolent lymphoma and DLBCL components at diagnosis)vs. pure transformation (DLBCL occurring as the sole histology in patients with a prior history of untreated indolent lymphoma). Results: In the overall cohort, trDLBCL was associated with significantly inferior progression-free survival (PFS) compared with de novo disease and remained an independent adverse prognostic factor in multivariable analysis (HR 1.754, p < 0.001). These findings were confirmed in a 1:1 propensity score-matched cohort (108 pairs), where trDLBCL continued to show worse PFS (p < 0.01), while overall survival (OS) was comparable (p = 0.99). Within trDLBCL patients, the underlying indolent subtype (t-FL vs. t-MZL) did not significantly affect survival (PFS p = 0.17, OS p = 0.35), whereas “pure transformation” was associated with markedly inferior PFS (p = 0.005) and OS (HR 2.56, p = 0.02) compared with concurrent transformation. Failure pattern analysis revealed a higher risk of early progression in trDLBCL (POD24: 30.56% vs. 18.52%; OR 1.94, 95% CI: 1.05–3.56), whereas central nervous system (CNS) involvement was low and comparable between groups (2.78% vs. 0.93%, p = 0.62). Conclusions: Treatment-naive trDLBCL is associated with inferior PFS driven by early progression, whereas OS is comparable due to effective salvage therapies. Pure transformation appeared to define a higher-risk subgroup with inferior disease control, supporting the need for future prospective studies to evaluate risk-adapted frontline, consolidation, or maintenance strategies. Full article

Background/Objectives: Congenital heart malformations (CHDs) are not rare diseases, and, in many cases, their pathogenic mechanisms are well established. Several conotruncal defects are associated with genetic syndromes such as DiGeorge syndrome and RASopathies, reflecting shared developmental pathways affecting cardiac outflow tract formation. However, even common CHDs may occur within complex syndromic contexts, making early diagnosis essential for optimal management. This review aims to provide a unifying framework linking ciliary dysfunction to CHD phenotypes. Methods: We performed an integrative narrative review of genetic, experimental, and developmental studies focusing on the role of primary and motile cilia in cardiac morphogenesis. Particular attention was given to signaling pathways regulated by cilia and their contribution to disease phenotypes. Results: Emerging evidence indicates that primary and motile cilia act as central regulators of cardiac development, integrating morphogen gradients and mechanical cues into transcriptional programs. Dysfunctions in ciliary structure or signaling are increasingly recognized as important contributors to selected complex CHD phenotypes, particularly in syndromic forms and laterality-associated defects. This cilia-centered model may help explain part of the phenotypic heterogeneity observed in CHD and highlights shared mechanisms across distinct clinical entities. Conclusions: Understanding cilia-dependent mechanisms provides a unifying conceptual framework linking genetic defects to disrupted morphogenesis. This perspective may refine disease interpretation and support future development of precision diagnostics and pathway-informed therapeutic strategies in CHD. Full article

Background/Objectives: Erythroderma is a rare but potentially life-threatening dermatological emergency characterised by generalised erythema and scaling involving more than 80% of the total body surface area. Erythroderma is associated with significant morbidity and mortality due to systemic complications and diverse underlying aetiologies. Methods: In this narrative review, PubMed was searched up to February 2026. Studies were screened for relevance to emergency physicians, with emphasis on epidemiology, diagnostic approach, and acute management. Non-English publications and conference abstracts were excluded. A total of 122 sources were included in the final synthesis. Results: Erythroderma most commonly results from exacerbation of pre-existing inflammatory dermatoses, drug reactions, infections, or cutaneous T-cell lymphoma. Clinical presentation includes diffuse erythema and scaling affecting ≥80–90% of body surface area, often accompanied by pruritus, systemic symptoms, and signs of organ dysfunction. Systemic complications arise from cutaneous barrier failure and include fluid imbalance, thermoregulatory dysfunction, cardiovascular strain, protein loss, and secondary infection. Initial emergency department management prioritises supportive care, fluid and nutritional optimisation, restoration of skin barrier function, and assessment for organ dysfunction. While a definitive aetiological diagnosis is not always immediately required, certain conditions—particularly severe drug reactions and infectious causes such as staphylococcal scalded skin syndrome—necessitate urgent targeted intervention. Conclusions: Erythroderma represents a syndromic emergency requiring systematic evaluation and early supportive management. Prompt recognition of high-risk aetiologies and timely dermatology referral are essential to optimise outcomes and reduce morbidity and mortality. Full article

The transition from relapsing–remitting multiple sclerosis (RRMS) to secondary-progressive multiple sclerosis (SPMS) represents an ambiguous transition period characterized by diagnostic delays and a shifting therapeutic window. While inflammatory relapses are well-managed, the underlying neurodegeneration often remains undetected until substantial disability has accrued. This review evaluated the shift from traditional metrics, such as the Expanded Disability Status Scale (EDSS), toward more sensitive, multimodal monitoring strategies. We described characteristic MRI findings in SPMS and addressed the impact of comorbidities that frequently confound the diagnosis of disease transition. Furthermore, we evaluated the predictive potential of emerging fluid biomarkers and gut microbial signatures in identifying the early RRMS-to-SPMS transition. Finally, we described the current therapeutic landscape and emerging immunomodulatory interventions. Diagnosing SPMS remains a clinical challenge due to comorbidities and the lack of a singular definitive marker. Moving toward high-sensitivity imaging and molecular biomarkers is essential for the early initiation of treatments and improved patient outcomes. Full article

Cervical cancer remains a major global health challenge, particularly in low- and middle-income countries, where access to screening, vaccination, and timely treatment may be limited. Cervical cytology has played an important historical role in prevention, but it is labor-intensive, time-consuming, and subject to observer variability and limited sensitivity. In many contemporary screening programs, HPV testing is now used as the primary screening test, while cytology is used mainly for the triage of HPV-positive women. In recent years, artificial intelligence (AI), particularly deep learning (DL), has shown considerable potential in medical image analysis and computer-aided diagnosis. This review summarizes current applications of AI in cervical cytology and related diagnostic workflows, including automated and assisted slide screening, liquid-based cytology, the triage of equivocal or HPV-positive cases, and colposcopy support. Across these settings, AI-assisted systems may improve efficiency, standardization, and diagnostic consistency, and may reduce workload in resource-constrained environments. However, the evidence is heterogeneous, and important challenges remain, including the need for large and diverse datasets, prospective validation, regulatory approval, digital infrastructure, workflow integration, and the resolution of ethical and legal issues. AI should therefore be regarded as a promising adjunct to human expertise rather than a replacement in cervical cytology and related clinical diagnostic pathways. Full article

Patient health knowledge graphs provide a means for high-quality and interoperable clinical data representation, while graph neural networks are a key enabler in order to learn their underlying relationships for downstream prediction tasks. In this work, we propose a sequential graph neural network (SeqGNN) framework that models patient visit trajectories for multiple binary clinical tasks, namely diagnosis, readmission, and mortality prediction. The proposed architecture integrates temporal dynamics with graph-based representations that enhances patient-level embeddings. Focusing on patients at the risk of Heart Failure (HF), our methodology achieves comparatively high accuracy and precision-versus-recall tradeoffs on highly heterogeneous graphs and imbalanced labeled data. We additionally quantify the uncertainty concerning each clinical decision making task and, compared with the state-of-the-art, show that AUROC and AUPRC scores reliably improve for onset diagnosis in particular, as high as 93.1 and 79.1 respectively. Our experiments conducted on real-world data from an intensive care unit demonstrate the potential for sequential representation learning over patient health knowledge graphs that can be provided for high-precision decision-making in clinical settings. Full article

Basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPPD) crystals drive the degenerative and inflammatory pathways that lead to crystal arthropathy. Although recent classification criteria and imaging recommendations have improved standardisation for CPPD disease, it remains underdiagnosed in practice. In contrast, BCP disease lacks validated classification criteria and standardised diagnostic descriptors, limiting translational research and clinical recognition. Accurate diagnoses are limited by varied reference standards, operator-dependent techniques, and the absence of validated bedside tools. As the population ages and the burden of crystal disease rises, there will be increased demand for reliable diagnostic tools in clinical practice. This review summarises current and emerging diagnostic tools for identifying BCP and CPPD, with emphasis on bridging the diagnostic gap from research to routine care. Polarised light microscopy remains a highly specific test for the diagnosis of CPPD but is limited by inter-observer variability and access to polarising light microscopes. Imaging tools such as ultrasound, conventional radiography, computed tomography (CT) and dual-energy CT can identify CPPD, although performance varies by anatomical site, disease stage and technical parameters. Ultrasound is a useful bedside tool for identifying BCP disease, whereas CT and DECT also have diagnostic utility but lack validation for routine use. Emerging technologies such as computational polarised light microscopy and Raman spectroscopy are promising techniques, but require further research to evidence their use in clinical practice. Development of clear diagnostic reference standards, classification criteria for BCP disease, and evidence-based multimodal diagnostic pathways are essential to bridge the gap between research and routine clinical diagnosis. Full article

Background: Prostate cancer is a heterogeneous disease with variable clinical outcomes. If localized, the patient may be cured. However, prostate cancer is lethal if recurrence/progression to metastatic castrate resistant disease occurs. Thus, there is an unmet need to further understand the molecular underpinnings of this progression. Epidemiologic studies show that increased risk of developing and dying from prostate cancer has been associated with elevated serum IGF-1 levels, hyperinsulinemia and metabolic syndrome. Alterations in insulin pathway genes, such as PTEN, FOXO, and PIK3CA, are mutated in up to 32%, 15%, and 11% of localized prostate tumors, respectively. We aimed to further characterize expression of insulin pathway genes in localized prostate cancers in an effort to (1) provide insights into potential mechanisms of progression to metastatic disease and (2) try to further enrich for those prostate tumors that portend worse survival outcomes. Methods: Using the multi-institutional Oncology Research Information Exchange Network (ORIEN) database, gene expression data was analyzed from localized prostate cancer tumors. The raw counts were first normalized, and 176 genes related to the insulin receptor and its downstream pathways were then subset and used for clustering using the non-negative matrix factorization (NMF). The NMF cluster analysis was performed in an attempt to separate gene expression into two groups. Gene Set Enrichment Analysis (GSEA) was then performed between the two groups that had been separated by cluster analysis to determine homology between other GSEA sets. Kaplan–Meier curves were used to assess median overall survival. Cox analysis was performed to generate the adjusted KM curve. Mediation analysis was conducted to determine the relationship between cluster status, TN stage, and survival. Results: Cluster analysis revealed two distinct groups of insulin gene expression, cluster 1 (n = 96) and cluster 2 (n = 337). Compared with cluster 2, cluster 1 consisted of decreased expression of PTEN (p < 0.001) and PIK3R1 (p < 0.001), along with increases in the expression of AKT1 (p < 0.001), IRS1/2 (p < 0.001), FASN (p < 0.001), IGFBP2 (p < 0.001), and MTOR (p < 0.001). GSEA analysis revealed changes in lipid metabolism and WNT secretion pathways in cluster 1. Cluster 2 GSEA showed pathway changes related to DNA damage repair and testosterone. Patient characteristics between clusters differed significantly in the T and N stages of tumor but not in other ways. In unadjusted analysis, median overall survival was estimated at 117 months and 232 months for cluster 1 and cluster 2, respectively (p < 0.05). The proportion of patients who went on to develop metastases (p < 0.05) or need chemotherapy (p < 0.05) was increased in cluster 1 compared to cluster 2. Repeat survival analysis adjusted for confounders (T stage, N stage, age at diagnosis, pathologic grade) showed no difference in survival between clusters. Mediation analysis showed that the contribution of cluster status to survival was independent of T or N stage. Conclusions: A subset of localized prostate cancer patients demonstrated linked insulin pathway changes that are consistent with prior studies describing a pattern of insulin dysregulation. Though the group characterized by insulin dysregulation initially showed worse survival outcomes, this difference disappeared when controlling for confounders. Though baseline differences in tumor stage seemed to most readily explain the difference in survival between clusters, mediation analysis showed that the effect of cluster status on survival was independent of tumor stage. This suggests that other confounders, such as pathologic grade or baseline age, may explain the survival difference. 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

Ketosis is a prevalent metabolic disorder in early-lactation dairy cows, significantly affecting animal health, milk production, and farm profitability. Developing accurate and non-invasive methods for early risk detection is therefore of critical importance. In this study, a hybrid optimization framework integrating an Improved Whale Migration Algorithm (IWMA) with a Light Gradient Boosting Machine (LightGBM) is proposed to predict ketosis risk based on the milk fat-to-protein ratio (F/P) using Dairy Herd Improvement (DHI) records. The proposed IWMA enhances optimization performance through cubic chaotic initialization, elite opposition-based learning, and a Cauchy–Gaussian hybrid mutation strategy, enabling improved global exploration and convergence stability. A dataset comprising 25,155 DHI records collected from multiple commercial dairy farms over seven months was used for model development and evaluation. Experimental results demonstrate that the IWMA–LightGBM model achieves a classification accuracy of 0.8997 and a mean squared error of 0.289, consistently outperforming six benchmark optimization methods. Feature analysis identifies Herd Within Index (WHI), Energy Corrected Milk (ECM), Days in Milk (DIM), Milk Urea Nitrogen, and Foremilk as key predictors associated with metabolic risk. Overall, the proposed approach provides a robust and effective non-invasive solution for early-stage metabolic risk screening at the herd level, offering practical value for precision dairy management. It should be noted that the model is intended for risk assessment rather than clinical diagnosis of ketosis. Full article

Background: Pulmonary arterial hypertension is a rare but life-threatening condition in children, with hereditary forms often being linked to mutations in genes such as bone morphogenetic protein receptor type 2 (BMPR2), caveolin 1 (CAV1), and potassium channel subfamily K member 3 (KCNK3). Among these, CAV1 mutations are associated with severe disease phenotypes, though cases resulting from de novo heterozygous CAV1 mutations with multi-system involvement remain rarely reported. The CAV1 mutation (c.424C > T, p.Q142X) disrupts caveolin-1 function, leading to dysregulated pulmonary vascular remodeling and multi-system abnormalities. Methods: This was a retrospective case study of a pediatric patient with hereditary PAH. The patient was followed at our hospital from initial presentation until death. Clinical data were collected from medical records, including physical examinations, laboratory tests, echocardiography, chest X-ray, computed tomography pulmonary angiography (CTPA), and genetic analysis. The patient was treated sequentially with various PAH-targeted medications. This report also includes a review of the relevant literature on CAV1-associated PAH. Results: A female aged 3 years and 11 months was diagnosed with hereditary PAH associated with a de novo heterozygous CAV1 mutation (c.424C > T, p.Q142X). Both parents underwent genetic testing and were negative for the mutation, confirming its de novo origin. Clinical manifestations included special facial features, congenital telangiectasia, cutis marmorata (marbled skin), congenital cataract, hereditary lipodystrophy, and severe PAH. The patient presented with progressive exercise intolerance, syncope, and worsening dyspnea over nine years. Echocardiography revealed pulmonary hypertension with an estimated pulmonary artery systolic pressure of 69–105 mmHg, right heart enlargement, right ventricular hypertrophy, and moderate tricuspid regurgitation. Blood and urine metabolic screenings were normal. A chest X-ray showed progressive enlargement of the cardiac silhouette and bulging of the pulmonary artery segment. CTPA demonstrated pulmonary hypertension, secondary right heart dysfunction, decompensated right ventricular function, and mosaic perfusion in both lungs, suggestive of small arterial branch occlusion. Right heart catheterization was declined by the parents. Thus, the diagnosis of PAH was established based on clinical, echocardiographic, CTPA, and genetic findings. The patient was hospitalized four times and lost to follow-up from 2017 to 2023. She received sequential treatment with digoxin, hydrochlorothiazide, tadalafil, ambrisentan, selexipag, and treprostinil. Despite these therapies, pulmonary artery pressure continued to rise with progressive clinical deterioration. The patient ultimately died at 13 years of age due to a pulmonary hypertensive crisis and multiple organ failure following a severe episode of gastroenteritis. Conclusions: Despite aggressive treatment with multiple targeted reduced pulmonary artery pressure drug therapies, managing hereditary PAH caused by CAV1 mutations in children remains a significant challenge, with a high mortality rate. Early genetic diagnosis, regular follow-up, and individualized treatment are crucial. It requires the joint efforts of patients, parents, and healthcare providers. Full article

The incidence of cancer during pregnancy is rising, yet scientific understanding and clinical management remain underdeveloped. Delayed diagnoses, limited therapeutic options, and lack of safety data exacerbate the clinical challenges of treating cancer during pregnancy. Further, the biology of gestational cancers is poorly understood due to the scarcity of model systems and mechanistic studies. This manuscript presents a multidisciplinary perspective from a group of researchers and clinicians to evaluate the current state of pregnancy-associated cancers, identify unmet clinical and biological questions, and propose strategies to improve diagnosis, treatment, and maternal–fetal outcomes. Full article

Diabetes mellitus (DM) is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The most common types—type 1 and type 2 diabetes—have different etiologies and pathophysiological mechanisms. Type 1 diabetes (T1DM) results from autoimmune destruction of the insulin-producing pancreatic β-cells, leading to the development of absolute insulin deficiency, whereas in type 2 diabetes (T2DM), impaired carbohydrate metabolism is primarily caused by insulin resistance and relative insulin deficiency. Current diagnostic criteria do not allow for the detection of the disease at the preclinical stage. MicroRNA (miRNA) influences post-translational regulation of gene expression by inhibiting mRNA translation and also promotes mRNA degradation. The aim of this review is to summarize current evidence on the role of microRNAs in the pathogenesis of T1DM and T2DM and to evaluate their potential as early diagnostic biomarkers and therapeutic targets. It is demonstrated that T1DM and T2DM exhibit altered expression of specific microRNAs involved in β-cell apoptosis, autoimmune inflammation, and insulin signaling. In T1DM, key miRNAs include miR-21, miR-25, miR-146a, and miR-375, which reflect β-cell destruction and the autoimmune process. In T2DM, critical roles are played by miR-9, miR-29, miR-34a, miR-103/107, miR-126, miR-143, and miR-375, which regulate insulin secretion, lipid metabolism, and tissue insulin sensitivity. Particular attention is given to microRNAs whose expression changes several years before clinical disease onset (miR-15a, miR-126, miR-375), offering opportunities for early diagnosis. Data are presented on circulating miRNAs in stable biological fluids (blood, urine). It should be emphasized, however, that the proposed microRNA panel currently represents only a potential diagnostic tool. This panel requires further validation and confirmation by clinicians in large-scale prospective studies and does not yet claim to be ready for routine clinical use. Nevertheless, the development of such a universal microRNA panel, followed by thorough clinical evaluation, has promising biomedical potential, which will not only allow for the diagnosis of diabetes at an early stage but also identify new therapeutic targets for personalized medicine. 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

Background and Clinical Significance: This case highlights the management of chronic extensor carpi ulnaris (ECU) tenosynovitis in a patient exposed to non-traditional wrist-loading activities. Exercise therapy rehabilitation is well established in shoulder and knee tendinopathies, although it remains less well described for wrist tendinopathies beyond De Quervain’s disease. Moreover, the patient’s active engagement in non-traditional, wrist-intensive sports such as handstands, slacklining, and yoga may have contributed to the development and persistence of chronic extensor carpi ulnaris (ECU) tenosynovitis. Unlike more common ECU injuries observed in tennis or golf players, this case demonstrates how ECU tenosynovitis can develop in less conventional sports. It adds to the scientific literature by showing that chronic ECU tenosynovitis can be effectively managed through non-surgical rehabilitation tailored to the specific needs of the patient, in particular by using exercise therapy. Case Presentation: The patient presented with chronic left wrist pain, especially during ulnar deviation and resisted ECU testing, following two traumatic events. Examination revealed limited range of motion caused by pain, particularly in flexion, extension, and both ulnar and radial deviations. Ultrasound imaging confirmed ECU tenosynovitis with mild inflammation of other wrist tendons and a small synovial cyst on radio-scapho-lunate level. ECU stability during forearm rotation was confirmed both clinically and by ultrasound.  The diagnosis of chronic ECU tenosynovitis was managed conservatively with a targeted rehabilitation program focused on isometric strengthening and progressive resistance exercises. Over one month, the patient demonstrated marked improvement in wrist strength, pain reduction, and functional capacity, allowing for a gradual return to sporting activities. Conclusions: The main takeaway from this case is that chronic ECU tenosynovitis can be successfully managed through individualized, conservative treatment based on exercise therapy. Early intervention, patient adherence, and rehabilitation tailored to the athlete’s specific demands are crucial for recovery, even in chronic cases, without the need for surgical intervention. Full article