Search Results (8,116)

Introduction: Major depressive disorder (MDD) is a common and often treatment-resistant condition, with many patients showing only partial or minimal response to standard therapies. Repetitive transcranial magnetic stimulation (rTMS) is a well-established, non-invasive treatment for depression, though individual response varies considerably. While demographic and clinical predictors have been explored, the impact of personality styles on rTMS outcomes remains underinvestigated. Herein, we aimed to explore whether personality styles influence treatment response to rTMS. Methods: This retrospective study included 63 in- and outpatients with depressive episodes treated with intermittent theta-burst stimulation (iTBS) between September 2020 and December 2022. Patients were assessed before and after treatment using the 21-item Hamilton Depression Rating Scale (HAMD-21) and the self-reported Major Depression Inventory (MDI). Personality styles were evaluated using the German Persönlichkeits-Stil-und-Störungs-Inventar (PSSI), a dimensional measure of 14 personality styles. Statistical analyses included paired-samples t-tests to assess symptom change and linear regression models to examine whether personality styles predicted treatment outcomes. Effect sizes were reported as Cohen’s d. Results: Patients showed a significant reduction in depressive symptoms following iTBS (HAMD-21: t(62) = 10.86, p < 0.001, d = 1.37. MDI: t(62) = 8.55, p < 0.001, d = 1.06). Stepwise regression for the MDI identified critical–negativistic (NT) and reserved–schizoid (SZ) styles as significant predictors, explaining approximately 16% of the variance (R² = 0.159, p = 0.007). When entered simultaneously in a regression model for the HAMD-21, these same traits also predicted symptom change, though the effect was smaller (R² = 0.108, p = 0.033). Higher scores of critical–negativistic (NT) style were associated with better improvement, whereas higher scores of reserved–schizoid (SZ) style were associated with less improvement. Conclusions: This study confirms the overall efficacy of rTMS in reducing depressive symptoms. While SZ and NT traits showed some predictive value for treatment response—particularly on self-reported outcomes—their influence was modest and inconsistent. Based on our findings, there is no reason why patients with depression and specific personality styles, or even comorbid personality disorders, should be denied rTMS treatment. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Radiomics and artificial intelligence (AI) have emerged as promising tools for quantitative imaging analysis and precision staging. This study aimed to evaluate the ability of an AI-based radiomics model to preoperatively predict tumor (T) and nodal (N) stage, lymphovascular invasion (LVI), and postoperative complications in patients with early-stage NSCLC. Material and Methods: This retrospective study included 51 consecutive patients who underwent anatomical lobectomy with systematic lymph node dissection between 2019 and 2024, at the Clinic for Thoracic Surgery of the University Clinical Center of Serbia. Quantitative imaging features were extracted from preoperative CT scans using the Lesion Scout with Auto ID module (syngo.via VB50 MM, Siemens Healthineers). Radiomics and clinical predictors were analyzed using regularized logistic regression (LASSO) with five-fold cross-validation. Model performance was assessed using AUC, accuracy, sensitivity, specificity, precision, and F1 score, and calibration was evaluated using the Hosmer–Lemeshow test. Groups were compared using parametric and non-parametric tests. Correlation between the variables was assessed using Spearman’s rank correlation coefficient. All p-values less than 0.05 were considered significant. Results: The AI-based model showed excellent performance for predicting the T component (training AUC = 0.89; test AUC = 0.86; F1 = 0.81) and acceptable calibration (p = 0.41). Nodal metastasis (OR = 0.108; 95% CI: 0.011–1.069; p = 0.057) and LVI (OR = 0.519; 95% CI: 0.139–1.937; p = 0.329) were not significantly predicted. Emphysema was identified as a significant independent predictor of postoperative complications (χ² = 5.13; p = 0.024). Conclusions: The AI-driven radiomics model demonstrated strong predictive ability for the T component and identified emphysema as a clinically relevant predictor of postoperative complications. Full article

Background: Invasive aspergillosis (IA) is a life-threatening infection in immunocompromised patients, including those with hematologic malignancies and hematopoietic stem cell transplants. While adult IA has been well characterized, data on pediatric populations remain limited, and potential age-related differences are often overlooked in current management guidelines. Methods: We conducted a retrospective matched cohort study at a tertiary cancer center, evaluating IA cases diagnosed over a 31-year period. Pediatric patients (≤18 years) with proven or probable IA were matched 1:3 with adult IA cases based on year of diagnosis, underlying disease, and history of hematopoietic cell transplantation. We compared demographics, clinical presentation, diagnostic modalities, microbiology, antifungal prophylaxis, and treatment approaches between the two groups. Results: The study included 34 pediatric and 102 matched adult IA cases. Pediatric patients were significantly more likely to present with neutropenia (p = 0.04) and sinus involvement (p = 0.048). Serum galactomannan testing was more often positive in pediatric patients (p = 0.027), whereas bronchoalveolar lavage galactomannan was more frequently positive in adults (p = 0.003). Differences in antifungal prophylactic regimens were also observed. Conclusions: Our findings underscore significant age-related variations in IA epidemiology, diagnostics, and management. These results support the development of age-specific diagnostic algorithms and antifungal strategies. Full article

Background: Human papillomavirus (HPV)-associated oral and oropharyngeal squamous cell carcinomas have risen dramatically in incidence over recent decades. Yet, unlike cervical neoplasia, there is no established screening paradigm for HPV-driven oropharyngeal dysplasia, as precursor lesions are often occult and are not easily accessible for examination. This drives an urgent need for non-invasive biomarkers to enable early detection, risk stratification, and timely intervention. Objective of this review is to highlight advances in liquid biopsy modalities, specifically saliva- and blood-based biomarkers—in the context of HPV-driven oral carcinogenesis—and to evaluate their utility in early cancer detection, prognostic, post-treatment surveillance, and recurrence monitoring. Methods: We performed a narrative review of PubMed-indexed studies (2015–2025) focusing on HPV-positive oral and oropharyngeal squamous cell carcinomas. and liquid biopsy analytes. Key sources were high-impact original studies and meta-analyses from 2020–2025 examining circulating tumor DNA (ctDNA), viral nucleic acids, circulating tumor cells (CTCs), extracellular vesicles (EVs), and related biomarkers in saliva and blood. Reported data on assay performance, biases, and validation were reviewed to highlight how oral cancer findings align with trends seen in other solid tumors. Results: In reviewing recent studies (2015–2025), we found consistent evidence that saliva best captures locoregional tumor signals while plasma circulating tumor HPV DNA (ctHPV DNA) reflects systemic disease, and that using both matrices improves detection over either alone. Dual-fluid testing will potentially enable earlier identification of molecular residual disease with clinically meaningful lead time before radiographic recurrence, supporting risk-adapted surveillance. Overall, literature favors standardized pre-analytics and combined saliva plus plasma workflows to enhance early detection and follow-up in HPV-positive oral and oropharyngeal squamous cell carcinomas. Conclusions: Liquid biopsy approaches offer promising tools for the early, non-invasive detection and real-time monitoring of HPV-associated oral cancers. Realizing their full clinical potential will require robust prospective validation and standardization of pre-analytical protocols. Integrating salivary and blood biomarkers into tailored surveillance programs may further support earlier intervention and improved patient outcomes, while potentially reducing reliance on unnecessary invasive procedures. Full article

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC) represent a distinct subgroup of head and neck squamous cell carcinoma (HNSCC) characterized by better prognosis and increased radiosensitivity compared to HPV-negative OPSCC. However, current diagnostic and monitoring methods, including tissue biopsies and imaging, are insufficient for precise risk stratification and early detection of recurrence, leading to challenges in treatment de-escalation and surveillance strategies. Circulating tumor HPV DNA (ctHPV-DNA) has emerged as a promising minimally invasive biomarker that offers tumor-specific detection and monitoring capabilities, potentially transforming the management of HPV-related OPSCC through early disease detection, treatment response assessment, recurrence surveillance stratification, and disease monitoring. Despite encouraging results from early clinical studies, current use is limited to trial settings. Large-scale prospective studies are needed to validate its clinical utility and determine whether early ctHPV-DNA testing can improve patient outcome while reducing treatment related morbidity. This review outlines the biological rationale, technological approaches, and current clinical evidence for ctHPV-DNA in HPV-related OPSCC, emphasizing its potential role in treatment monitoring and surveillance. Full article

LTP allergy and its accurate diagnosis remain a challenge in modern allergology. Patients sensitized to lipid transfer proteins (LTPs) present a wide range of symptoms, from mild manifestations—such as oral allergy syndrome, urticaria, and angioedema—to severe systemic reactions, including anaphylaxis. Oral food challenges (OFCs), the gold standard in food allergy diagnostics, are problematic in this group of patients due to the high risk of life-threatening reactions during the procedure. The basophil activation test (BAT), a functional assay based on flow cytometry, is a promising diagnostic tool that may benefit many food-allergic patients by reducing the need for OFCs. In 2023, BAT was incorporated into selected diagnostic pathways for food sensitization in the guidelines issued by the European Academy of Allergy and Clinical Immunology (EAACI). While many studies have investigated BAT in the context of peanut allergy, evidence regarding its application in LTP allergy remains limited. In this systematic review, we analyzed the currently available studies on the use of BAT in the diagnosis of LTP sensitization and evaluated its potential to supplement or even replace OFCs in specific clinical scenarios. Full article

Background: The SARS-CoV-2 pandemic raised concerns about severe asthma (SA) patients, especially those on biological therapy. While initial fears of increased risks diminished for the general asthma population, a subset of severe cases undergoing specific treatments continued to be closely monitored. Our study aimed to evaluate COVID-19 occurrence, asthma exacerbations, hospitalizations, and outcomes in severe asthma patients. Methods: This multicenter study gathered data from 237 adult severe asthma patients in Croatia and Serbia to assess COVID-19 impact compared to the general population. Participants received omalizumab, mepolizumab, benralizumab, or reslizumab. Data on demographics, clinical features, and COVID-19 were collected. COVID-19 symptoms and diagnostic testing were assessed as described. Results: No demographic differences were seen between COVID-19-positive and -negative groups, with eosinophilic asthma prevailing. Among patients with SA treated with biologics, the occurrence of COVID-19 did not differ significantly from that in the general population, and biologic therapy was not associated with more severe disease or higher mortality. Importantly, no meaningful differences were observed among different biologics regarding COVID-19 outcomes. Vaccination was associated with a reduction in severe cases and hospitalizations. Conclusions: Biologic therapy for severe asthma appears safe during the COVID-19 pandemic. Patients receiving biologics did not experience worse outcomes than the general population, and no biologic was linked to poorer COVID-19 prognosis. Vaccination further contributed to protection against severe disease. Full article

Endometriosis is a chronic condition characterized by the presence of endometrial-like tissue outside the uterine cavity. It affects ~10% of reproductive-aged individuals and is associated with dysmenorrhea and infertility. Although imaging modalities have improved diagnosis, laparoscopy is required in many cases, contributing to 4–11 years of diagnostic delay. Non-invasive biomarkers could improve diagnosis and clinical decision-making, yet no candidate has achieved sufficient accuracy for routine use. Galectins, a family of β-galactoside-binding lectins involved in angiogenesis, immune regulation, and fibrosis, have emerged as promising biomarkers. In this study, we measured serum Galectin-1 (Gal-1) concentrations in 80 women with endometriosis and 15 controls using ELISA at four time points. Preoperative Gal-1 levels were significantly higher in endometriosis patients, particularly in Stage III–IV disease. ROC analysis yielded a modest diagnostic performance (AUC 0.692; p = 0.011) with high sensitivity (91.3%) and excellent negative predictive value (96.8%) but low specificity (46.7%) at a study-derived threshold (>14.06 ng/mL). Longitudinally, Gal-1 levels decreased immediately after surgery and rose above baseline by one year, while no significant correlations with preoperative pain severity were observed. These findings suggest that serum Gal-1 alone is insufficient as a diagnostic test but may be useful for multi-marker strategies to improve early diagnosis. Full article

Pulmonary arterial hypertension (PAH) is a fatal disease with no cure. Until recently, most specific therapies for PAH had aimed at enhancing cyclic nucleotide (cAMP and cGMP) pathways, taking advantage of the vasorelaxant and antiproliferative properties of these key intracellular messengers. This process can be achieved by inhibiting phosphodiesterases (PDEs), which are intracellular enzymes responsible for cyclic nucleotide degradation. To date, only inhibitors of PDE type 5 (PDE5) have been approved for the treatment of PAH. Because the PDE superfamily comprises 11 families that encompass many variants, substantial experimental investigation has been conducted to assess the relevance of inhibiting other PDE families, aiming to offer therapeutic alternatives. This review synthesizes the main research work conducted on in vivo or ex vivo models, as well as on biological resources from patients. It helps provide evidence for the expression of PDE isoforms in the lung vasculature, as well as the efficacy and limitations of various pharmacological compounds tested for inhibiting pathological processes ongoing in the disease. Perspectives and suggestions for future research orientation are proposed. Full article

Background/Objectives: Pharmacogenetic variability plays a crucial role in determining both the efficacy and toxicity of chemotherapy for gastrointestinal cancers. However, data on allele frequencies and their clinical relevance in Russian populations remain scarce. Methods: We conducted a prospective observational study of 412 patients with gastrointestinal malignancies between 2020 and 2023. Pharmacogenetic testing was performed prior to the initiation of chemotherapy using real-time allele-specific PCR and microarray hybridization technology. Polymorphisms in the DPYD, UGT1A1, CYP2C8, CYP3A5, GSTP1, ERCC1, XPC, CDA, MTHFR, TYMS, and SLC31A1 genes were analyzed. Results: The frequency of most variants was consistent with those reported in European populations, reflecting the ethnic proximity of the studied cohort. Several clinically relevant variants were identified: DPYD rs2297595 occurred more frequently than in European cohorts, and UGT1A1 rs8175347 was observed at a higher prevalence, underscoring the potential risk of irinotecan-related neutropenia and diarrhea. CYP2C8 rs10509681 was present at frequencies comparable to European populations and is associated with an increased risk of taxane-induced peripheral neuropathy. Other markers (GSTP1, ERCC1, CDA, SLC31A1, MTHFR, TYMS) demonstrated variable associations with chemotherapy efficacy and toxicity, consistent with findings from previous international studies. Conclusions: This study provides the first comprehensive description of pharmacogenetic polymorphisms in a Russian cohort of patients with gastrointestinal cancers. Our findings confirm the clinical importance of DPYD and UGT1A1 testing and highlight additional variants of potential interest. Full article

Bladder cancer is a prevalent malignancy with high morbidity and mortality, particularly when diagnosed at an advanced stage. Early detection is critical, as it significantly improves prognosis and the patient’s outcomes. Bladder cancer also has a high recurrence rate, necessitating long-term surveillance. While cystoscopy remains the gold standard for diagnosis and monitoring, it is invasive and costly. Urine cytology, though widely used, has high specificity for detecting high-grade urothelial carcinoma but suffers from low sensitivity and limited effectiveness as a stand-alone diagnostic tool. Urinary biomarkers offer a promising, noninvasive alternative for early detection and disease surveillance. This review examines FDA-approved urinary biomarker tests, including NMP 22, UroVysion, and BTA, highlighting their clinical utility and limitations. Additionally, we explore emerging biomarkers such as DNA methylation assays, genomic alterations, and proteomic signatures as well as advanced technologies like next-generation sequencing and machine learning-based platforms. These innovations have the potential to enhance diagnostic accuracy, risk stratification, and recurrent monitoring, ultimately improving early detection and long-term disease management. By evaluating both established and emerging urinary biomarkers, this review aims to provide clinicians and researchers with insights into evolving tools for bladder cancer diagnosis and surveillance. Full article

Low back pain (LBP) is a highly prevalent musculoskeletal problem and a leading cause of disability worldwide. From a pathophysiological perspective, the contribution of inflammation to LBP is being increasingly recognized. In this literature review, we aim to provide an overview of the role of inflammation as a mediator of LBP while summarizing clinical studies investigating the potential role of anti-inflammatory treatments in the management of LBP. Although often controversial, the available evidence suggests an important role of inflammation in the pathogenesis of LBP, which can be further translated into novel therapeutic targets. Both anti-tumor necrosis factor (anti-TNF) and anti-nerve growth factor (anti-NGF) agents hold the potential of blocking inflammation and pain pathways in patients with chronic LBP. TNF inhibitors have been tested mostly in small trials with mixed results, and their long-term efficacy remains to be proven. Anti-NGF agents have demonstrated stronger and consistent efficacy in randomized controlled trials, but safety concerns compromise their widespread use. The potential role of other anti-inflammatory molecules is currently under investigation. Presently, the routine use of TNF or NGF inhibitors is not supported in radiculopathy or chronic LBP. However, novel anti-inflammatory therapies introduced in the rheumatology field appear to be promising for specific subsets of patients suffering from chronic, refractory LBP, with a complementary role as therapeutic tools, after the unsuccessful outcome of the conservative approach. Full article

Breast cancer remains a major global health challenge. In 2022, there were an estimated 2.3 million new cases and 670,000 deaths among women worldwide. Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer accounts for approximately 70% of breast cancer diagnoses. The treatment landscape for advanced HR+)/HER2− breast cancer has been transformed by the introduction of CDK4/6 inhibitors in the first-line setting. However, therapeutic strategies following progression on CDK4/6 inhibitors remain heterogeneous and uncertainty exists in their optimal integration in clinical practice. This review aims to systematically examine available second-line and subsequent treatment options for HR+/HER2− metastatic breast cancer after progression on CDK4/6 inhibitors, with a focus on biomarker-driven strategies and emerging therapies. The therapeutic landscape beyond CDK4/6 inhibitors includes targeted agents guided by actionable biomarkers as well as novel selective estrogen receptor degraders (SERDs). In biomarker-unselected populations, options include CDK4/6 continuation strategies, endocrine monotherapy in selected cases, and cytotoxic therapy. The integration of molecular testing via next-generation sequencing has become standard of care in guiding these decisions. However, overlapping molecular alterations and a lack of consensus on treatment sequencing pose significant challenges. Prognostic factors such as circulating tumor DNA dynamics may further refine treatment personalization. Post-CDK4/6 therapy in HR+/HER2− metastatic breast cancer is an evolving and increasingly complex area of practice. Optimal treatment selection should be tailored to both tumor biology and patient-specific factors, supported by molecular testing and high-quality evidence. Full article

Body image dissatisfaction, particularly related to breast appearance, plays an important role in cosmetic breast surgery (CBS) decisions and psychological wellbeing. However, existing measures are often lengthy, overlook healthy women considering CBS, and fail to adequately address the nipple–areola complex (NAC), a critical component of breast satisfaction. This study introduces the 12-item Breast Appearance Concerns Scale (BACS), a brief screening tool developed to address existing gaps and to document breast-specific body image concerns among women considering CBS. Data were collected from a diverse sample of 589 young adult women who completed the BACS along with measures of related constructs such as self-esteem and anxiety. Exploratory and confirmatory factor analyses supported a two-subscale structure: NAC Satisfaction and General Breast Satisfaction. The BACS total score demonstrated strong internal consistency (α = 0.785) and test–retest reliability (r = 0.741). Predictive validity analyses revealed that the General Breast Satisfaction subscale effectively distinguished women who had considered CBS from those who had not (classification accuracy = 72.1%). Receiver Operating Characteristic (ROC) analysis was conducted with the General Breast Satisfaction subscale to establish a preliminary cutoff score. This cutoff provides initial support for use of this subscale as a screening tool to help classify individuals based on their consideration of CBS. Although clinically important, the NAC subscale is still in an early stage of development and requires additional research before cutoff scores can be established to inform surgical decision-making and evaluate patient-reported satisfaction outcomes. Both subscales require further investigation in older populations and clinical settings to support their use as screening tools. These findings position the BACS as a promising screening tool for assessing breast-specific body image concerns, particularly general breast satisfaction, with potential applications in clinical, pre-surgical settings. Full article

Objective: The aim of this study was to evaluate whether Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) scores, the Systemic Immune-Inflammation Index (SII), and the Systemic Inflammatory Response Index (SIRI) can predict intensive care unit (ICU) or inpatient admissions in pediatric diabetic ketoacidosis (DKA) cases and to determine their sensitivity and specificity. Methods: This retrospective study included 39 pediatric patients (<18 years) diagnosed with DKA (pH < 7.3, HCO₃ < 15). HALP, SII, SIRI, and urine ketone values were collected from medical records. Statistical analyses included ROC curve analysis, correlation tests, and appropriate parametric or non-parametric comparisons to evaluate associations with 30-day outcomes. Results: The median age was 13 years (IQR: 8–15), 56.4% were male, and 64.1% required ICU monitoring. ICU patients had significantly lower pH (p = 0.005) and HCO₃ (p = 0.012) and significantly higher monocyte, SII, and SIRI values (all p ≤ 0.018). ROC analysis showed SIRI had the highest predictive power for ICU admission (cut-off: 3911; sensitivity: 76%; specificity: 85.7%), followed by SII. HALP scores did not demonstrate any value in assessingdisease severity for predicting ICU admission (AUC = 0.25). Conclusion: SIRI and SII are reliable predictors of ICU admission in pediatric DKA. HALP scores do not predict ICU admission and should not be considered a marker of disease severity. Incorporating SIRI and SII into clinical decision-making may improve early risk stratification. Prospective multicenter studies are warranted to validate these results. Full article