Search Results (19,165)

Recurrence of Takotsubo syndrome (TS) is the most significant challenge in the long-term follow-up of patients with TS. We present the case of a 40-year-old woman with a history of two acute coronary syndromes and myocarditis who was hospitalized in our clinic due to Takotsubo syndrome. Left ventriculography demonstrated the rare mid-ventricular variant of Takotsubo syndrome. Based on a carefully obtained medical history, it was established that all previous coronary events, as well as the current TS episode, had been preceded by psychological stress. Following an additional review of the patient’s medical records and application of the InterTAK score, we concluded that the previous incidents may have been episodes of TS and that the patient had now experienced her fourth episode of Takotsubo syndrome. Full article

Iron is essential for normal cellular function, but its dysregulation is increasingly recognized as a key factor in colorectal tumorigenesis. This review provides an integrated overview of iron-related biomarkers across the full spectrum of colorectal neoplasia, from preneoplastic lesions to advanced colorectal cancer (CRC). Evidence suggests that alterations in iron metabolism begin early, at the level of colorectal adenomas, where increased iron uptake and impaired export contribute to local iron accumulation and oxidative stress. As lesions progress to carcinoma, this imbalance becomes more pronounced, leading to expansion of the intracellular labile iron pool and supporting tumor growth, metabolic adaptation, and genomic instability. At the systemic level, patients often exhibit reduced circulating iron despite preserved or elevated ferritin levels, reflecting inflammation-driven functional iron deficiency. This pattern is largely mediated by dysregulation of the hepcidin–ferroportin axis. In this context, transferrin saturation and soluble transferrin receptor may provide a more accurate assessment of iron availability than ferritin alone. At the tissue level, increased expression of iron import proteins and impaired iron export promote intracellular iron retention. Excess iron further contributes to reactive oxygen species generation, leading to damage of DNA, lipids, and proteins. Clinically, iron-related biomarkers show variable diagnostic performance but may offer prognostic value. Integrating systemic and tissue biomarkers could improve risk stratification and support personalized approaches across the CRC continuum. Full article

Background/Objectives: Sarcoidosis is a multisystem inflammatory disease characterized by heterogeneous clinical manifestations and variable disease severity. Hematological inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red cell distribution width (RDW), and systemic immune-inflammation index (SII), have recently attracted attention as accessible indicators of systemic inflammation in sarcoidosis. This study aimed to evaluate radiological stage, symptom burden, pulmonary function parameters, and hematological markers in patients with sarcoidosis. Methods: This retrospective multicenter cohort study included histopathologically confirmed sarcoidosis patients from 10 centers. Demographic characteristics, clinical manifestations, pulmonary function test parameters, serum angiotensin-converting enzyme (ACE) levels, and hematological inflammatory markers (MPV, RDW, NLR, PLR, SII) were evaluated. Patients were categorized according to radiological stage (stage 0–I vs. stage II–IV), symptomatic status, and symptom burden (<3 vs. ≥3 symptoms). Results: Among 458 patients included in the study, stage I (47.8%) and stage II (46.9%) disease were the predominant radiological presentations. Patients with stage II–IV disease were older and demonstrated significantly lower forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and diffusing capacity for carbon monoxide (DLCO) values together with higher serum ACE levels compared with stage 0–I disease. Dyspnea, weight loss, and extrapulmonary involvement were more frequent in stage 2–4 disease. No significant associations were observed between radiological stage and NLR, PLR, or SII values. MPV and RDW values differed significantly between symptomatic and asymptomatic patients. Patients with ≥3 symptoms demonstrated significantly lower pulmonary function parameters together with statistically significant higher NLR, PLR, and SII values. In multivariate analyses, only the SII demonstrated an independent association with a high symptom burden. Conclusions: Serum ACE levels were associated with advanced radiological stage, whereas hemogram-derived inflammatory indices, particularly the NLR, PLR, and SII, were associated with symptom burden rather than radiological stage in sarcoidosis and may reflect symptomatic inflammatory activity. Full article

Background: Transient elastography (TE) is widely used for noninvasive assessment of liver fibrosis. In patients undergoing hemodialysis, however, liver stiffness measurements (LSM) may be affected by rapid intradialytic changes in volume status, venous congestion, and other non-fibrotic determinants. We prospectively evaluated peridialytic variability in liver stiffness and the concordance of serum fibrosis indices with elevated LSM in patients receiving maintenance hemodialysis. Methods: In this prospective paired pilot study, 45 adults on maintenance hemodialysis underwent LSM and controlled attenuation parameter (CAP) assessments immediately before and after a dialysis session; paired data were available for 41 patients. The Fibrosis-4 index (FIB-4) and the aspartate aminotransferase-to-platelet ratio index (APRI) were calculated from routine laboratory values. Paired comparisons, correlation analyses, and receiver operating characteristic curves were used to assess within-patient changes and the ability of serum indices to identify elevated pre-dialysis liver stiffness (LSM ≥ 8 kPa). Because no histologic or imaging reference standard for fibrosis was available, these analyses were interpreted as evidence of concordance with elevated LSM rather than as diagnostic accuracy for liver fibrosis. Results: Median LSM was 7.1 kPa (interquartile range [IQR] 5.2–12.1) pre-dialysis and 7.7 kPa (IQR 5.8–12.2) post-dialysis, with no significant paired change (median ΔLSM −0.2 kPa [IQR −1.1 to 1.2]; p = 0.898). However, the proportion with LSM ≥ 8 kPa increased from 36.6% to 46.3%, with 4 of 41 patients (9.8%) newly exceeding the threshold. CAP values showed no significant paired change (p = 0.511). Intradialytic weight loss was not associated with ΔLSM (rho = −0.13, p = 0.44). FIB-4 and APRI showed poor correlation with LSM and limited concordance with elevated LSM (area under the curve 0.553 and 0.578, respectively, with wide confidence intervals). Conclusions: In this exploratory hemodialysis cohort, cohort-level median LSM did not change significantly after dialysis, but clinically relevant individual-level reclassification occurred in approximately 10% of patients. Measurement timing may alter LSM-based classification, underscoring the need for dialysis-specific validation of LSM thresholds and noninvasive assessment strategies. Full article

Sarcoidosis is a multisystem disease characterised by a heterogeneous clinical presentation and variable disease course. Despite low mortality, the burden of sarcoidosis extends beyond organ involvement, with many patients reporting significant impairment in quality of life (QoL). Fatigue, chronic cough, and small fibre neuropathy (SFN) are among the most prevalent and debilitating symptoms reported by patients, often demonstrating poor correlation with conventional markers of disease activity and frequently persisting despite apparent disease control. This review examines the impact of sarcoidosis on QoL and highlights the limitations of traditional assessment tools, including imaging and pulmonary function testing, in capturing the full extent of disease burden. The role of patient-reported outcome measures (PROMs) is discussed, including generic instruments and sarcoidosis-specific tools such as the King’s Sarcoidosis Questionnaire (KSQ), Sarcoidosis Health Questionnaire (SHQ), and Sarcoidosis Assessment Tool (SAT), alongside symptom-specific measures targeting fatigue, neuropathic symptoms, and cough. Current and emerging management strategies aimed at improving QoL are reviewed, including immunosuppressive therapies, biologic agents, and non-pharmacological interventions. Despite increasing recognition of QoL as a key outcome, its integration into clinical trials remains inconsistent. Incorporating PROMs into routine clinical practice and research is essential to enable comprehensive assessment and support patient-centred care. Greater emphasis on QoL outcomes may improve therapeutic decision-making and overall disease management in sarcoidosis. Full article

Background/Objectives: Predicting how fast a patient with Alzheimer’s disease will decline over the next year remains a challenge. Existing blood transcriptomic studies have not established whether probe selection is reproducible, whether the signal is transcriptional or reflects immune cell shifts, or whether they generalise across platforms. Methods: We applied five steps to 96 ADNI-GO whole-blood microarray samples (Affymetrix HG-U219; 12-month MMSE change): PyImpetus Markov Blanket selection, Elastic Net with leave-one-out cross-validation (LOOCV), SHAP attribution, MCP-counter cell-type deconvolution, and cross-platform mapping into AddNeuroMed (GSE63060, n = 329, Illumina). Feature selection preceded cross-validation without constituting data leakage. Results: The same six probes emerged across four independent runs (Jaccard J = 0.214, p = 0.03): AQP7, RPS5, CHD2, SNX5, ASS1, and an uncharacterised chr12q15 transcript. The panel achieved LOOCV MAE = 1.388 and R² = 0.247, outperforming the full-probe baseline by 14.9%. All probes survived immune cell correction with signs intact. SNX5 replicated in AddNeuroMed (r = −0.170, p = 0.002). Conclusions: The exploratory six-probe blood RNA panel predicts 12-month cognitive decline (LOOCV R² = 0.247) with transcriptional origin confirmed by cell-type deconvolution and cross-platform evidence for SNX5. External testing in ADNI-2 (n = 91, R² = −0.222) showed that generalisation depends on visit-timepoint matching, indicating clinical utility cannot yet be claimed and defining conditions for prospective validation. Code and a research prototype tool are publicly available. Full article

Background/Objectives: Cardiac troponin I (TnI) is the reference biomarker for detecting myocardial injury. Saliva has recently emerged as a potential non-invasive diagnostic fluid; however, evidence regarding the clinical utility of salivary TnI remains limited. This study aimed to compare serum and salivary TnI concentrations in patients undergoing cardiac surgery and to evaluate their relationship during the perioperative period. Methods: A prospective longitudinal observational study included 54 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass and cardioplegic arrest. Serum and unstimulated saliva samples were collected 18–20 h before surgery, 18–20 h after surgery, and 42–44 h after surgery. TnI concentrations were measured using a high-sensitivity chemiluminescent immunoassay. Salivary pH, salivary flow rate, renal function, and fluid balance were also recorded. Results: Significant perioperative changes in TnI concentrations were observed in both serum and saliva (p < 0.001). Median salivary TnI increased from 3.0 ng/L preoperatively to 9.2 ng/L at 18–20 h postoperatively and decreased to 6.4 ng/L at 42–44 h. Median serum TnI increased from 10.2 ng/L to 2593.1 ng/L and subsequently decreased to 1204.5 ng/L. Despite similar temporal trends, no significant correlation was found between serum and salivary TnI concentrations at any time point. Ischemic time was positively associated with postoperative serum TnI concentrations (ρ = 0.347, p = 0.01), whereas no such association was observed for salivary TnI. Salivary TnI concentrations were not significantly associated with salivary flow rate or pH. Conclusions: Salivary TnI concentrations increased significantly following cardiac surgery, indicating measurable perioperative changes within the salivary compartment. However, no significant association was observed between salivary and serum TnI concentrations under the conditions investigated in this study. Therefore, the present findings do not support the use of salivary TnI as a surrogate marker of circulating troponin concentrations. Further analytical validation of high-sensitivity troponin assays in saliva and additional clinical studies are required before definitive conclusions regarding the biological significance and potential clinical utility of salivary troponin measurements can be made. Full article

Background/Objectives: Keratoconus (KC) is a chronic disease that causes progressive corneal thinning and steepening, thereby negatively impacting visual acuity. Although corneal topography and keratometry are the primary measures to diagnose KC, access to these methods can be limited by various factors. To address these limitations, this study evaluates a novel low-cost deep-learning algorithm that infers keratometric categories from smartphone-assisted Placido ring photographs. Methods: Development utilized 1240 healthy control eye images and 188 K1-labeled KC images for pretraining, without using their K1 labels. A Variational Autoencoder with KL divergence regularization (AutoEncoderKL) was trained on this pool; its encoder generated latent features for KC images (n = 535). A held-out set (n = 70) with Pentacam keratometry was labeled by K1 into <40 D, 40–47 D, and >47 D. An ensemble classifier chosen via grid search and cross-validation used the encoder features. Performance was assessed for accuracy, precision, recall, and F1-score. Results: The model achieved 91% accuracy across all classes. Precision of the model was 0.77 (<40 D), 0.98 (40–47 D), and 0.86 (>47 D); recall was 0.83, 0.91, and 1.00; and F1-scores were 0.80, 0.94, and 0.92, respectively. Notably, the model achieved perfect recall for the >47 D K1 category. Conclusions: A smartphone-assisted Placido ring imaging approach was able to predict K1-based keratometric categories without requiring tomographic or keratometric measurements as model inputs at inference. These findings provide preliminary proof-of-concept for the potential use of smartphone-assisted Placido ring images as a low-cost approach for K1-based stratification. Larger externally validated studies across different sites, devices, operators, printed Placido discs, acquisition conditions, and patient populations are required before clinical utility can be assessed. Full article

Background/Objectives: Abnormal vaginal discharge (AVD) is a common complaint among women of reproductive age, often involving multiple, overlapping etiologies, most commonly bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), aerobic vaginitis (AV), and sexually transmitted infections (STIs). We aimed to evaluate a syndromic diagnostic approach by developing qPCR-derived dysbiosis indices for BV, VVC, and AV, subsequently comparing their performance against established reference methods and clinician-assigned diagnoses. Methods: Vaginal swabs were collected in a case–control design from 74 symptomatic and 64 asymptomatic women at two clinics in Slovenia. Commercial qPCR assays quantified the microbial species associated with AVD. Relative abundances were integrated into novel dysbiosis indices. Diagnostic performance was validated against the Nugent scoring system (for BV), semiquantitative Candida culture with clinical symptoms (for VVC), and Hay–Ison criteria (for AV). Results: In this internally validated study, dysbiosis indices demonstrated high agreement with their respective reference tests and outperformed clinician-assigned diagnoses across all three conditions. The syndromic approach further revealed that mixed etiologies were frequent, leading to a diagnostic resolution for this patient subset. Conclusions: qPCR-based microbial dysbiosis indices offer a robust alternative to microscopy, particularly in settings where microscopy is not routinely performed. This method improves the accuracy of AVD evaluation and supports more targeted clinical management. Full article

Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. This significant burden necessitates effective early identification of pregnancies at high-risk for preeclampsia. Accurate prediction is essential in order to develop and optimize preventive strategies. The evolution of preeclampsia screening has progressed from a traditional checklist-based approach to individualized, multivariable models. The first-trimester triple test, which was developed by the Fetal Medicine Foundation (FMF), represents this advancement. It utilizes Bayes’ theorem to calculate patient-specific risks by integrating maternal factors, mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor. This model, called “first trimester FMF triple test”, has undergone successful internal and external validation for the prediction of preterm preeclampsia. To ensure the reliability of biomarker measurements and achieve an optimal screening performance, it is essential to implement standardized measurement protocols and rigorous quality control processes in biomarker testing. The triple test could also be utilized in the 2nd and 3rd trimester, and the addition of biomarkers such as soluble fms-like tyrosine kinase-1 further improves risk stratification assessment and continued surveillance of high-risk pregnancies. Full article

Background: Active surveillance (AS) criteria in prostate cancer (PCa) are expanding to include selected patients with intermediate-risk features. This multicenter retrospective study aimed to validate a proposed risk group (RG) classification for predicting unfavorable pathology (UP) in radical prostatectomy specimens among patients eligible for AS under expanded criteria. Methods: Patients from three Andalusian university hospitals who met the AS criteria, defined as prostate-specific antigen (PSA) ≤ 20 ng/mL, International Society of Urological Pathology (ISUP) ≤ 2, and clinical stage ≤ cT2, were included. The patients were stratified into five RGs according to PSA density, Prostate Imaging Reporting and Data System score (PI-RADS), and clinical stage. UP was defined as ≥pT3a and/or pN+ and/or ISUP grade ≥ 3. Results: A total of 244 patients were analyzed. The median age was 63 years, the median PSA 5.98 ng/mL, and the median PSA density was 0.14 ng/cc. UP was identified in 47.1% of radical prostatectomy specimens, increasing progressively across RGs from 20.8% to 93.3%. Each incremental RG was associated with a higher risk of UP, with an odds ratio of 2.14 and moderate predictive accuracy, as reflected by an area under the curve of 0.70. Conclusions: The proposed RG classification showed moderate predictive capacity for UP and may improve risk stratification in intermediate-risk patients considered for AS. Full article

Systemic chronic active Epstein–Barr virus disease (sCAEBV) is a rare and potentially fatal disorder characterized by inflammatory manifestations and organ infiltration by EBV-infected T- or NK-cells. Although [¹⁸F]FDG PET/CT has limited utility for assessing the disease activity of sCAEBV, [¹¹C]acetate PET/CT has not previously been evaluated in this setting. We therefore conducted this exploratory retrospective study to assess the utility of sequentially performed [¹¹C]acetate and [¹⁸F]FDG PET/CT in sCAEBV. Five patients diagnosed with sCAEBV according to the criteria of the Research Group on Measures against Intractable Diseases, Ministry of Health, Labour and Welfare of Japan (consistent with the 2017 WHO classification) and assessed between July 2017 and December 2018 were included; patients younger than 20 years were excluded. Each patient underwent both [¹¹C]acetate and 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomography/computed tomography (PET/CT) on the same day. The maximum and mean standardized uptake values (SUVmax and SUVmean) of the liver and spleen and the liver-to-spleen ratio (LSR) were correlated with laboratory parameters, including alanine aminotransferase (ALT) and lactate dehydrogenase (LDH), using Spearman’s rank correlation coefficient. The LSR was compared between active and inactive cases using the Mann–Whitney U test. Twenty-one lymph node regions were assessed in each patient, and the SUVmax of detected lesions was measured. The detection rate of lymph node lesions between the two tracers was compared using McNemar’s test, and the SUVmax of lymph node lesions was compared between the two tracers and between active and inactive cases using the Mann–Whitney U test. All statistical analyses were performed using R version 4.5.3 (R Foundation for Statistical Computing, Vienna, Austria), and a p-value < 0.05 was considered statistically significant. Five patients (three men and two women; mean age 31.8 years, range 21–39 years) were included. [¹¹C]acetate PET/CT showed significant negative correlations between spleen SUV and liver enzymes (AST, ALT, and LDH), and significant positive correlations between the LSR and all five liver enzymes tested (AST, ALT, LDH, γGTP, and ALP) (Spearman’s rank correlation coefficient; p < 0.05 for all). No significant correlations were observed with [¹⁸F]FDG PET/CT. The LSR on [¹¹C]acetate PET/CT was numerically higher in active cases than in inactive cases, though this difference was not statistically significant (0.88 ± 0.02 vs. 0.61 ± 0.02; p = 0.20, Mann–Whitney U test). Lymph node lesion detectability did not differ significantly between the two tracers (16 vs. 12 regions; p = 0.13, McNemar’s test). In this pilot study, [¹¹C]acetate PET/CT spleen SUV showed significant negative correlations with liver enzymes (AST, ALT, and LDH), and the LSR showed significant positive correlations with all measured liver enzymes, suggesting that [¹¹C]acetate PET/CT reflects both hepatic and splenic involvement in sCAEBV. [¹¹C]acetate PET/CT may therefore serve as a novel imaging biomarker for assessing disease activity in sCAEBV, warranting further investigation in larger cohorts. Full article

Background/Objectives: Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease that may progress to cirrhosis and liver failure if not diagnosed early. Although liver biopsy remains the reference standard for fibrosis assessment, its invasive nature limits routine use. This study aimed to compare the diagnostic performance of ultrasound-based microvascular imaging (MVI), transient elastography (TE), and serum fibrosis indices (APRI and FIB-4) in patients with biopsy-confirmed AIH. Methods: Fifty-five patients with probable or definite AIH according to IAIHG criteria were included in the study. All patients underwent liver biopsy, and fibrosis stage was assessed using the METAVIR system. TE and MVI examinations were performed, and APRI and FIB-4 scores were calculated. Diagnostic performance was evaluated using AUROC, sensitivity, and specificity. Spearman correlation and logistic regression analyses were additionally performed. Results: The mean age of the patients was 49.2 years, and most patients were women. Cirrhosis was present in 58.2% of the cohort. TE demonstrated high diagnostic accuracy, whereas FIB-4 showed moderate performance and APRI demonstrated limited utility. MVI achieved the highest diagnostic performance, with AUROC values of 0.99 for significant fibrosis and 0.97 for cirrhosis. MVI showed the strongest correlation with histological fibrosis stage (r = 0.916, p < 0.001), followed by TE (r = 0.907, p < 0.001). MVI was strongly associated with histologically confirmed cirrhosis (OR 16.7, 95% CI 2.36–118.2, p = 0.004). Conclusions: MVI demonstrates diagnostic performance comparable to TE and may represent a promising adjunctive non-invasive imaging biomarker for fibrosis assessment in AIH. Larger multicenter studies are required for external validation before routine clinical implementation. Full article

Background/Objectives: Although ultrasound-guided fine-needle aspiration biopsy with suction (FNA-S) is preferred for evaluating thyroid nodules, the capillary technique (FNA-C) is also used. However, the diagnostic performance of both techniques remains unclear. Our objective was to compare the diagnostic performance of FNA-S versus FNA-C for thyroid nodules. Methods: This retrospective, observational, exploratory, single-center pilot evaluation study was conducted at a tertiary hospital from January 2023 to June 2024. A total of 157 ultrasound-guided FNA biopsies were prospectively analyzed, comprising 71 FNA-S and 86 FNA-C procedures. Clinical, ultrasound, and cytological parameters were evaluated to compare the rates of non-diagnostic samples (Bethesda I) and the necessity for repeat punctures. Bivariate analyses and multivariate logistic regression were conducted. Results: Both techniques exhibited comparable rates of non-diagnostic samples (28.17% for FNA-S and 27.91% for FNA-C; p = 0.220) and repetition rates (38.03% for FNA-S and 43.02% for FNA-C; p = 0.637). The only factors significantly associated with sample adequacy, regardless of techniques employed, were the location and composition of the nodule. Conclusions: Ultrasound-guided FNA-S and FNA-C yield similar diagnostic performance for biopsy of thyroid nodules. The choice may depend on operator preference and nodule characteristics. Full article

Methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) has emerged as a valuable diagnostic, prognostic, and therapeutic biomarker in modern oncologic pathology, primarily serving as a surrogate for CDKN2A/B homozygous deletion due to their close genomic proximity at chromosome 9p21. This review aims to systematically evaluate the clinical utility, diagnostic accuracy, and technical limitations of MTAP IHC across a diverse spectrum of human malignancies, while contextualizing its role within current molecular testing algorithms. We first examine the established diagnostic and grading performance of MTAP loss in central nervous system neoplasms and thoracic tumors, particularly malignant pleural mesothelioma, followed by an analysis of its emerging prognostic value in gastrointestinal, cutaneous, and genitourinary malignancies. Furthermore, we discuss the therapeutic implications of MTAP deficiency, focusing on the biological consequences of methylthioadenosine accumulation and the resulting synthetic vulnerabilities in the PRMT5/MAT2A pathway. By synthesizing diagnostic precision, prognostic relevance, and translational therapeutic insights, this review provides a comprehensive framework for integrating MTAP IHC into routine surgical pathology workflows and personalized oncology. Full article