Search Results (2,702)

Background/Objectives: Metabolic comorbidities and systemic inflammation are implicated in colon carcinogenesis, yet their relationship with acute obstructive presentation and early in-hospital course remains unclear. This study evaluated whether age, metabolic multimorbidity, and inflammatory–metabolic biomarkers are associated with obstruction severity and length of stay in a surgical colon cancer cohort. Methods: We analyzed 677 consecutive adults undergoing surgery for histologically confirmed colon cancer. Acute presentation was categorized as no obstruction, subocclusive syndrome, or frank obstruction. Predictors included age, comorbidity count (multimorbidity defined as ≥2), diabetes, hypertension, and preoperative biomarkers (C-reactive protein (CRP), lipids, glucose; neutrophil-to-lymphocyte ratio (NLR)/platelet-to-lymphocyte ratio (PLR)/C-reactive protein-to-albumin ratio (CAR)where available). Multivariable logistic and ordinal regression assessed obstructive presentation; linear regression assessed length of stay. Results: Subocclusion or obstruction occurred in 34.8% of patients. In multivariable logistic regression, age was independently associated with obstructive presentation (odds ratio (OR) 1.016 per year; 95% confidence interval (CI) 1.001–1.032), while comorbidity count and CRP were not. In an ordinal model, age increased the odds of more severe presentation (OR 1.018 per year), whereas diabetes was inversely associated (OR 0.573). Length of stay was independently associated only with presentation severity (β = −0.959 days per category). Correlations between inflammatory indices and length of stay were negligible. Conclusions: In this hospital-based surgical cohort, age showed a modest association with obstructive presentation, while metabolic multimorbidity and routine inflammatory markers provided limited discrimination for obstruction or early in-hospital resource use. Full article

Diabetic retinopathy (DR), a leading cause of vision loss in diabetic patients, involves complex pathological mechanisms including neurodegeneration, microvascular damage, inflammation, and oxidative stress. Recent studies have identified ferroptosis—a ferrodependent cell death mechanism—as playing a pivotal role in DR development. Existing evidence indicates that oxidative stress and mitochondrial dysfunction induced by hyperglycemia may contribute to retinal damage through the ferroptosis pathway in DR. Ferroptosis inhibitors such as Ferostatin-1 have demonstrated protective effects against DR in animal models. The core mechanisms of ferroptosis involve iron homeostasis imbalance and lipid peroxidation, with key regulatory pathways including GPX4-dependent and non-dependent mechanisms (such as FSP1-CoQ10). Within the signaling network, Nrf2 inhibits ferroptosis, p53 promotes it, while Hippo/YAP functions are environment-dependent. Non-coding RNAs and epigenetic modifications (e.g., DNA methylation and histone modifications) also participate in regulation. In DR, iron overload, GPX4 dysfunction, and p53 upregulation collectively induce ferroptosis in various types of retinal cells, making these pathways potential therapeutic targets. This review not only elaborates the role of iron metabolism imbalance and ferroptosis pathway in the occurrence and development of DR but also summarizes the new therapeutic approaches of DR targeting ferroptosis pathway. Investigating the relationship between ferroptosis and DR not only helps unravel its core pathophysiological mechanisms but also provides theoretical foundations for developing novel therapeutic approaches. Full article

Background/Objectives: Echocardiography is the reference standard for grading aortic stenosis (AS); however, it yields discordant severity estimates in up to 40% of patients. Multidetector computed tomography (MDCT)-derived methods for calculating aortic valve area (AVA) may improve diagnostic concordance, but their diagnostic performance, validation against invasive hemodynamics, and the influence of left ventricular outflow tract (LVOT) morphology on severity grading remain insufficiently investigated. Methods: We retrospectively analyzed 307 patients with normal-flow, high-gradient calcific AS who underwent echocardiography, MDCT, and cardiac catheterization. AVA was calculated using (1) echocardiographic LVOT diameter, (2) hybrid Doppler–MDCT planimetric LVOT area, and (3) corrected echocardiographic LVOT diameter (×1.13). Agreement, correlation, and diagnostic performance were assessed using Bland–Altman analysis, Pearson correlation, ROC analysis, and McNemar’s test. Subgroups defined by diagnostic concordance and MDCT-derived LVOT size were compared using ANOVA. Results: Hybrid AVA showed a strong correlation with echocardiographic AVA (r = 0.749, p < 0.001), with a mean difference of +0.11 ± 0.15 cm². Both methods demonstrated similar relationships with invasive and non-invasive hemodynamic markers of AS severity. When combined with echocardiography, the hybrid method increased concordant classification of severe AS by 8%. In contrast, corrected AVA performed significantly worse, leading to more discordant classifications. LVOT size was significantly associated with variability in AVA and Doppler velocity index, independent of flow status. Conclusions: Hybrid MDCT-derived AVA provides diagnostic performance equivalent to echocardiography and improves concordance in selected patients. LVOT size influences key echocardiographic parameters and may warrant tailored diagnostic thresholds. Full article

Background: Melasma is a chronic skin condition resulting from increased melanogenic activity, which induces a significant emotional impact on the patient’s quality of life. The efficacy of melasma treatments depends on individual response and on the chosen therapeutic approach, which may include topical skin-lightening agents, oral drugs, and chemical peels. Objectives: We aimed to evaluate the reported efficacy of treatment techniques on melasma control and patients’ quality of life through a systematic review and meta-analysis, as well as to investigate a putative relationship between melasma severity and quality of life. Methods: Following PRISMA guidelines, we collected data from PubMed, Scopus, and Embase databases. The eligibility criteria included studies that analyzed the quality of life through the Melasma Quality of Life (MELASQoL) scale from populations of patients suffering from melasma, scored by the Melasma Area Severity Index (MASI). Results: We retrieved 1296 records; those that did not meet the eligibility criteria and duplicates were excluded, resulting in 41 papers that underwent qualitative analysis (information synthesis), from which 23 papers containing 34 studies were included in the meta-analysis. The meta-analysis revealed a decrease in both MASI and MELASQoL scores following oral or topical treatment, as well as the chemical peeling procedure. Spearman correlation test showed a mild positive relationship between MASI and MELASQoL scores. Conclusions: This study provides evidence supporting oral and topical pharmacological treatments, as well as chemical peels, as effective interventions for melasma management. Despite high heterogeneity among studies and methodological limitations, all treatment modalities analyzed improved patients’ quality of life. Full article

Accurate multi-leaf collimator (MLC) motion prediction is a prerequisite for precise dose delivery in advanced techniques such as IMRT and VMAT. Traditional patient-specific quality assurance (QA) methods remain resource-intensive and prone to physical measurement uncertainties. This study aimed to develop machine learning (ML) models to predict delivered MLC positions using kinematic parameters extracted from DICOM-RT plans for the Elekta Versa HD system. A dataset comprising 200 patient plans was constructed by pairing planned MLC positions, velocities, and accelerations with corresponding delivered values parsed from unstructured trajectory logs. Four regression models, including linear regression (LR), were trained to evaluate the deterministic nature of the Elekta servo-mechanism. LR demonstrated superior prediction accuracy, achieving the lowest mean absolute error (MAE) of 0.145 mm, empirically confirming the fundamentally linear relationship between planned and delivered trajectories. Subsequent dosimetric validation using ArcCHECK measurements on 17 clinical plans revealed that LR-corrected plans achieved statistically significant improvements in gamma passing rates, with a mean increase of 2.24% under the stringent 1%/1 mm criterion (p < 0.001). These results indicate that the LR model successfully captures systematic mechanical signatures, such as inertial effects. This study demonstrates that a computationally efficient LR model can accurately predict Elekta MLC performance, providing a robust foundation for implementing ML-based virtual QA. This approach is particularly valuable for time-sensitive workflows like adaptive radiotherapy (ART), as it significantly reduces reliance on physical QA resources. Full article

TANGO2 deficiency disorder is a rare autosomal recessive disease (~100 cases reported worldwide). Despite being caused by loss-of-function variants in the TANGO2 gene, patients exhibit marked phenotypic variability, including intrafamilial differences among individuals carrying identical variants. To uncover potential modifier mechanisms influencing disease severity, we developed an integrative Systems biology framework, combining exome sequencing, transcriptomics, variant effect prediction, and Human Phenotype Ontology mapping. This approach was applied to two siblings carrying identical compound heterozygous TANGO2 variants but opposite clinical outcomes: one severely affected and one asymptomatic. Personalized protein–protein interaction networks and combined univariate and multivariate analyses were employed to maximize specificity in this single-family comparison. In the affected sibling, a cumulative burden of common APOB variants, together with altered VLDLR, NTN1, and LDHA expression, implicated disrupted lipid metabolism and neurodevelopmental pathways. The asymptomatic sibling harbored a potentially protective 3′-UTR variant in EP300 and no APOB variant burden, supporting enhanced post-transcriptional regulation within developmental biology networks. These findings highlight lipid metabolism as a key pathway in TANGO2 deficiency pathophysiology and suggest autophagy and mitophagy as additional modifier mechanisms influencing phenotypic variability. Our integrative multi-omics framework provides a valuable strategy for elucidating genotype-phenotype relationships in rare diseases and supports personalized therapeutic approaches. Full article

Background/Objectives: Low-income compared to high-income women have a higher incidence of and mortality from cervical cancer (CC) due to lower screening rates (under/never-screened). Home-based screening for CC via mailed “self-collection” for human papillomavirus (HPV) testing is an alternative to traditional, provider-collected screening that may be more acceptable to low-income women. Theoretically, adoption of a recent technology, in this case, mailed return of self-collection, is related to the Diffusion of Innovations concepts of advantages and complexity. The purpose of this study was to develop and psychometrically test scales to measure advantages and complexity of self-collection in a low-income, under/never-screened population. Methods: Low-income women (n = 168) were recruited in person from food pantries and online using Facebook in the Midwest U.S. After a baseline survey, women were mailed a self-collection kit. We assessed reliability with item analysis and Cronbach’s α and evaluated validity with exploratory factor analysis and t-tests, using mailed kit return as the independent variable. Results: Two scales were developed: (1) advantages (Cronbach’s α = 0.84), item–total correlation = 0.51 to 0.69, and (2) complexity (Cronbach’s α = 0.82), item–total correlation = 0.45 to 0.64. Exploratory factor analysis supported items factoring on their respective scales, and t-tests supported a relationship between each scale and mailed return of kits. Conclusions: Both the advantages and complexity scales demonstrated reliability and validity among low-income women. Future studies should evaluate these scales in a larger, more diverse population. Nurses could use these scales to assess preferences and difficulties associated with self-collection and aid patients with CC screening decision-making. Full article

Background: Aging is associated with progressive structural and functional changes in dentin, reducing its mechanical integrity and increasing vulnerability to damage. Among the most important regulators of dentin physiology are extracellular matrix proteins from the SIBLING family, including Dentin Matrix Protein 1 (DMP-1), Dentin Sialophosphoprotein (DSPP), and Osteopontin (OPN). These proteins are essential for dentin mineralization, collagen organization, and tissue remodeling. Despite their critical role, knowledge about their age-related distribution and correlation with dentin structure and morphology remains limited. Aim: To examine age-dependent changes in the expression of SIBLING proteins (DMP-1, DSPP, OPN) in human dentin and to evaluate their relationship with collagen structure and ultramorphology using polarized light microscopy (PLM), immunohistochemistry (IHC), and scanning electron microscopy (SEM). Materials and Methods: Ninety extracted human teeth were categorized into young (≤17 years), mature (18–50 years), and old (>51 years) groups. IHC was applied to detect protein distribution, PLM to assess collagen organization, and SEM to evaluate dentinal morphology. Results and Conclusions: Aging was associated with increased expression of DMP-1 and OPN and a reduction in DSPP, which is particularly evident in peritubular dentin. Older samples showed collagen disorganization, reduced birefringence, and extensive intratubular mineralization. These findings suggest that age-related alterations in SIBLING proteins contribute to structural changes in dentin, providing new insights relevant to dental care in elderly patients. Full article

Dysregulated T-cell-mediated immune responses are a hallmark of inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). MicroRNAs (miRNAs) regulate various biological processes and play a significant role in the pathophysiology of numerous diseases. In this study, we aim to clarify the relationship between dysregulated immune response and altered miRNA signatures in patients with IBD. Our goal is to identify differentially expressed miRNAs that could potentially serve as diagnostic markers to differentiate between CD and UC. To quantify circulating miRNAs, we employed small RNA sequencing. To describe immune dysregulation, we determined the levels of circulating T-cell-related cytokines and the distribution of T-cell subpopulations in both circulation and in tissue samples. Our analysis revealed that 14 miRNAs exhibited significant expression differences between IBD patients and control subjects. These miRNAs may also implicate pathways associated with colitis-related colorectal carcinogenesis, suggesting their value in early risk assessment. Furthermore, we found that five miRNAs demonstrated a strong ability to discriminate between CD and UC patients. Additionally, levels of IL-22 and IFN-γ were significantly elevated in individuals with IBD. Notably, miRNA levels showed strong correlations with cytokine levels and T-cell subset distribution in both blood and tissue samples, exhibiting disease-specific patterns. In conclusion, we identified differentially expressed miRNAs in IBD patient groups, and a subset of these miRNAs might exhibit diagnostic potential to distinguish between CD and UC. Analyzing miRNAs in the blood of IBD patients may provide valuable insights into the underlying immune dysfunction. Full article

Adrenocortical carcinoma (ACC) is a rare and aggressive cancer with limited treatment options, commonly managed with mitotane, which can cause serious side effects, including central hypothyroidism and dyslipidemia. This study aimed to evaluate the incidence, clinical features, and relationship between mitotane-induced central hypothyroidism and dyslipidemia in ACC patients, as well as to investigate mitotane’s direct toxic effects on thyroid cells. Thirty-eight ACC patients treated with mitotane for at least six months were monitored for thyroid function and lipid profiles. Central hypothyroidism developed in 50% of patients with normal baseline thyroid function, mostly women, who were at higher risk. Dyslipidemia occurred in 40% of patients, more frequently in men, and appeared earlier than hypothyroidism. In vitro experiments on rat thyroid cells demonstrated a dose-dependent toxic effect of mitotane on cell viability. No significant link was found between hypothyroidism and dyslipidemia risk. These findings reveal sex-specific susceptibilities to mitotane toxicity and provide novel evidence of direct mitotane-induced thyroid cell damage. This insight supports the need for careful thyroid and lipid profile monitoring during mitotane treatment and may inform the development of safer therapies for ACC. Full article

Against the backdrop of artificial intelligence (AI) empowering the medical industry, achieving symmetric coordination between patients and medical intelligent systems has emerged as a key factor in enhancing the efficacy of medical human–computer collaborative diagnosis. This study systematically identified the factors influencing the effectiveness of human–machine collaborative diagnosis in healthcare by combining literature analysis with expert interviews, based on the Socio-technical Systems Theory. It constructed a symmetric evaluation framework consisting of 19 indicators across four dimensions: user, technology, task, and environment. An integrated DEMATEL method incorporating symmetric logic was employed to quantitatively analyze the interdependent relationships among factors and identify 18 key factors. Subsequently, ISM was applied to analyze the dependency relationships between these key factors, thereby constructing a clear multi-level hierarchical structure model. Through hierarchical construction of a multi-level hierarchical structure model, four core paths driving diagnostic effectiveness were revealed. The research shows that optimizing user behavior mechanisms and technology adaptability and strengthening dynamic coordination strategies between tasks and the environment can effectively achieve the two-way symmetric mapping of the medical human–machine system from fuzzy decision-making to precise output. This has not only improved the efficacy of medical human–computer collaborative diagnosis, but also provided a theoretical basis and practical guidance for optimizing the practical application of medical human–computer collaborative diagnosis. Full article

The interplay between the oral and gut microbiota and systemic health has garnered significant attention in recent years, particularly concerning hematological malignancies. Multiple myeloma and other hematological cancers are characterized by immune dysfunction, creating a bidirectional relationship with microbial communities. Dysbiosis, defined as an imbalance in microbial composition, may influence disease progression, treatment response, and overall prognosis. This narrative review is based on a non-systematic search of PubMed and Scopus (2010–2024) using terms related to oral microbiota, gut microbiota, dysbiosis, hematological malignancies, multiple myeloma, immune modulation, and treatment-related complications. Studies were selected for relevance to pathogenesis, immune regulation, clinical implications, and therapeutic interactions. As this is a narrative review, no quantitative synthesis or formal grading of evidence strength was performed; findings are therefore interpreted qualitatively based on the available literature. The role of microbial-derived metabolites, their effects on immune modulation, and their potential as biomarkers for disease and treatment outcomes have been explored. Specific attention is given to the implications of dysbiosis in chemotherapy-induced complications, such as mucositis and infections, and emerging therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation. Additionally, the influence of anticancer therapies on microbial ecosystems has been highlighted and the bidirectional impact of host–microbe interactions in shaping disease trajectory has been discussed. Understanding these complex interactions could lead to novel diagnostic and therapeutic approaches, ultimately improving patient outcomes. This review aims to provide clinicians and researchers with a comprehensive overview of current knowledge and future perspectives on the role of oral and gut microbiota in the context of hematological malignancies. Full article

Background: Ibrutinib, a Bruton’s tyrosine kinase inhibitor (BTKi), has revolutionized the treatment of Chronic Lymphocytic Leukemia (CLL), yet hepatotoxicity remains a rare and poorly characterized adverse event. Case Presentation: We report the case of a 54-year-old man with progressive CLL and radiologically confirmed hepatic involvement who developed acute hepatocellular injury during ibrutinib monotherapy. Baseline liver tests showed mild abnormalities attributed to hepatic steatosis and leukemic infiltration. After approximately 10–12 weeks of ibrutinib (420 mg/day), transaminases markedly increased (ALT 660 U/L, AST 326 U/L), while bilirubin and synthetic function remained normal. Viral, autoimmune, and obstructive causes were excluded. Stepwise dose reductions to 140 mg/day provided limited benefit. The addition of prednisone (50 mg/day) led to rapid biochemical improvement. Ibrutinib was successfully re-escalated to 280 mg/day alongside venetoclax initiation, maintaining disease control without recurrence of liver injury. Discussion: The temporal relationship, exclusion of alternative causes, and corticosteroid responsiveness suggest an ibrutinib-induced liver injury, possibly exacerbated by pre-existing hepatic steatosis and leukemic infiltration. Conclusions: This case underscores the multifactorial pathogenesis of BTKi-related hepatotoxicity and highlights the potential role of corticosteroids in management. Prompt recognition, stepwise dose adjustment, and corticosteroid therapy may enable continued treatment and sustained disease control in selected patients. Full article

Background: To evaluate women’s satisfaction with gynecological services at a public referral facility, recognizing the importance of patient satisfaction in assessing healthcare quality. Methods: Patient satisfaction was assessed with a 52-item questionnaire, targeting women undergoing laparoscopy/laparotomy, operative and office hysteroscopy, hormonal diagnostics, and others. The impact of patient-specific and hospitalization-related variables on satisfaction indicators and the relationships between provider-specific factors, expectation fulfillment, and readmission willingness were analyzed. Additionally, the institution’s organizational culture was evaluated. Results: Analysis of 790 questionnaires revealed a median satisfaction score of 88.48% and scores of 92.31%, 89.42%, 88.18%, 88.33%, and 85% across groups, with the highest satisfaction for laparoscopy/laparotomy (p = 0.003). Expectation fulfillment and total satisfaction relied on devoted time and alternatives discussion (both p = 0.001 and <0.001, respectively), positively correlating with comprehension, sense of security, and information quality (all p < 0.001). Readmission willingness was affected by devoted time (p = 0.016) and alternatives discussion (p = 0.028), and positively correlated with sense of security (p = 0.01). Expectation fulfillment and total satisfaction for office hysteroscopy depended on ongoing information (both p < 0.001) and pain aspects, positively correlating with comprehension, communication, and security, but negatively with pain (all p < 0.001), without affecting readmission willingness. Significant correlations existed between patient-specific and hospitalization-related variables and satisfaction, expectation fulfillment, and readmission willingness. A hierarchical culture with clan orientation was identified. Conclusions: Women’s high satisfaction was primarily linked to information quality. Readmission willingness correlated with a sense of security. Communication was crucial during office hysteroscopy. Public healthcare setting did not affect staff attitudes. Clan-oriented hierarchical culture favored a sense of security. Full article

Epilepsy affects approximately 50 million people worldwide, with nearly one-third of patients experiencing inadequate seizure control with conventional anti-epileptic drugs. The GABAergic system, responsible for inhibitory neurotransmission in the central nervous system, represents a critical target for seizure management. GABA aminotransferase (GABA-T), the enzyme responsible for GABA catabolism, has emerged as a particularly attractive therapeutic target. Inhibition of GABA-T increases synaptic GABA availability, enhancing inhibitory neurotransmission and raising the seizure threshold. Vigabatrin, an irreversible GABA-T inhibitor, has demonstrated remarkable efficacy in specific epilepsy syndromes, particularly infantile spasms and refractory partial seizures. However, its clinical utility is tempered by the risk of irreversible visual field defects, necessitating careful patient selection and monitoring. This review examines the molecular biology of GABA-T, the mechanisms of action of its inhibitors, clinical applications, safety considerations, and emerging developments in this therapeutic area. We discuss the structure–function relationships of GABA-T, the pharmacology of vigabatrin and experimental inhibitors, clinical efficacy across various epilepsy syndromes, adverse effect profiles, and future directions including novel inhibitors with improved safety profiles. Understanding the role of GABA-T in epilepsy pathophysiology and the therapeutic potential of its inhibitors provides insights into rational drug design and personalized treatment strategies for epilepsy management. Full article