Medicina

Background and Objectives: Infant feeding practices play a crucial role in shaping the oral microbiome, modulating inflammatory responses, and maintaining epithelial health during the first year of life. Breastfeeding promotes the growth of beneficial bacteria and supports a diverse, stable microbial community. In contrast, formula feeding is associated with increased colonization by potentially pathogenic bacteria, such as Staphylococcus and Escherichia coli, which may elevate the risk of infections, oral diseases, and inflammation. This study investigates the effects of breastfeeding versus formula feeding on oral bacterial growth, epithelial cell integrity, and interleukin-17 (IL-17) expression in infants aged 1–12 months. Materials and Methods: A total of 60 infants (30 breastfed and 30 formula-fed) were recruited from pediatric clinics in the Qassim region. Microbial cultures quantified bacterial colony-forming units (CFUs), and epithelial cell morphology was assessed through the microscopic analysis of mucosal scrapings. IL-17 concentrations were quantified from the oral mucosa through enzyme-linked immunosorbent assay. Statistical analyses, including t-tests and chi-square tests, compared bacterial loads, IL-17 levels, and indicators of epithelial health between groups. Adjustment for potential confounders was achieved through multivariate statistical analysis. Results: Formula-fed infants showed significantly higher IL-17 levels than breastfed infants (p < 0.001), indicating a stronger pro-inflammatory profile. Breastfed infants exhibited lower inflammation, improved epithelial health, and reduced cellular debris compared to formula-fed infants, who had higher bacterial loads. A significant correlation was found between epithelial health and bacterial clustering, with clearer epithelial cells associated with lower bacterial colonization. Conclusions: Formula feeding was associated with increased salivary IL-17 levels, greater bacterial colonization, and compromised epithelial integrity, indicating a heightened pro-inflammatory state and potential vulnerability to mucosal irritation or infection. Breastfeeding appeared to confer protective effects by promoting healthier microbial balance, epithelial integrity, and reducing inflammatory responses. These findings underscore the immunological and microbial benefits of breastfeeding in supporting oral health during infancy. Full article

Background and Objectives: Anterior open-bite malocclusion remains a challenging orthodontic condition where achieving a positive overbite necessitates precise control of incisor extrusion and molar intrusion. With recent advances in clear aligner therapy—improved materials, attachment techniques and digital treatment planning—the potential for non-invasive treatment has increased. This scoping review systematically maps the evidence on the efficacy of clear aligners in treating anterior open bite among adult patients, outlines treatment protocols and highlights gaps in the literature. Materials and Methods: A systematic search was conducted in PubMed/Medline, Embase/ScienceDirect and Clarivate/Web of Science for literature published in English between January 2000 and December 2024. Studies involving adult patients treated with clear aligners (predominantly Invisalign^®) were included. A two-step screening process was applied, and data were charted according to pre-specified criteria. The review adheres to the PRISMA-ScR checklist guidelines. Results: From an initial pool of 802 articles, 30 met the inclusion criteria following duplicate removal and full-text screening. The evidence suggests that clear aligners can achieve measurable incisor extrusion and posterior intrusion when appropriate auxiliary techniques (e.g., attachments and mini screws) are used. However, digital treatment planning software may overestimate movement predictions, necessitating iterative refinement phases. Patient compliance, clinician expertise and technological limitations are key factors influencing outcomes. Conclusions: Clear aligner therapy represents a promising alternative to fixed appliances for anterior open-bite correction in adults, although challenges remain in achieving precise vertical control. Further high-quality randomized controlled trials and standardized outcome measures are needed to confirm long-term stability and efficacy. Full article

Background and Objectives: Breast cancer accounts for 12.5% of all new cancer cases in women worldwide. Early detection significantly improves survival rates, but traditional biomarkers like CA 15-3 and HER2 lack sensitivity and specificity, particularly for early-stage disease. Advances in metabolomics and machine learning, particularly explainable artificial intelligence (XAI), offer new opportunities for identifying robust biomarkers and improving diagnostic accuracy. This study aimed to identify and validate serum-based metabolic biomarkers for breast cancer using advanced metabolomic profiling techniques and a Light Gradient Boosting Machine (LightGBM) model. Additionally, SHapley Additive exPlanations (SHAP) were applied to enhance model interpretability and biological insight. Materials and Methods: The study included 103 breast cancer patients and 31 healthy controls. Serum samples underwent liquid and gas chromatography–time-of-flight mass spectrometry (LC-TOFMS and GC-TOFMS). Mutual Information (MI), Sparse Partial Least Squares (sPLS), Boruta, and Multi-Objective Feature Selection (MOFS) approaches were applied to the data for biomarker discovery. LightGBM, AdaBoost, and Random Forest were employed for classification and to identify class imbalance with the Synthetic Minority Oversampling Technique (SMOTE). SHAP analysis ranked metabolites based on their contribution to model predictions. Results: Compared to other feature selection approaches, the MOFS approach was more robust in terms of predictive performance, and metabolites identified by this method were used in subsequent analyses for biomarker discovery. LightGBM outperformed the AdaBoost and Random Forest models, achieving 86.6% accuracy, 89.1% sensitivity, 84.2% specificity, and an F1-score of 87.0%. SHAP analysis identified 2-Aminobutyric acid, choline, and coproporphyrin as the most influential metabolites, with dysregulation of these markers associated with breast cancer risk. Conclusions: This study is among the first to integrate SHAP explainability with metabolomic profiling, bridging computational predictions and biological insights for improved clinical adoption. This study demonstrates the effectiveness of combining metabolomics with XAI-driven machine learning for breast cancer diagnostics. The identified biomarkers not only improve diagnostic accuracy but also reveal critical metabolic dysregulations associated with disease progression. Full article

Background and Objectives: Military capability may be reduced in hot environments with individuals at risk of exertional heat stroke (EHS). Heat tolerance testing (HTT) can be used to indicate readiness to return to duty following EHS. HTT traditionally relies on rectal core temperature (T_re) assessment via a rectal probe. This study investigated the use of gastrointestinal core temperature (T_gi) as an alternative to T_re during HTT. A secondary aim was to compare physiological factors between heat-tolerant and heat-intolerant trials. Materials and Methods: Australian Defence Force personnel undergoing HTT following known or suspected heat stroke volunteered (n = 23 cases participating in 26 trials) along with 14 controls with no known heat illness history. Confusion matrices enabled comparison of HTT outcome based on T_gi and T_re. The validity of T_gi compared to T_re during HTT was assessed using correlation and bias. Comparisons between heat-tolerant and intolerant trials were performed using non-parametric tests. Results: Although T_gi correlated closely with T_re (Spearman’s rank correlation $\rho$ = 0.893; median bias 0.2 °C) there was no consistent pattern in the differences between measures. Importantly, the two measures only agreed on heat tolerance outcome in 80% of trials with T_gi failing to detect heat intolerance identified by T_re in 6 of 8 trials. If T_gi was relied upon for diagnostic outcome, return to duty may occur before full recovery. None of the assessed covariates were related to the difference between T_re and T_gi. In addition, resting heart rate and systolic blood pressure were significantly lower and body surface area to mass ratio significantly higher in heat-tolerant compared to intolerant trials. Conclusions: It is not recommended to rely on T_gi instead of T_re during HTT. Resting heart rate and systolic blood pressure findings point to the importance of aerobic exercise in conveying heat tolerance along with body composition. Full article

Background and Objectives: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition linked to substantial urogenital symptoms, notably sexual dysfunction. This meta-analysis sought to determine the overall prevalence of sexual dysfunction in men with CP/CPPS, considering the four primary categories: desire, arousal, orgasm, and pain disorders. Materials and Methods: A systematic literature review, following MOOSE guidelines, was performed across four electronic databases (PubMed, Embase, Web of Science, and Google Scholar) for the period from January 2000 to 2025. The review included observational studies reporting the prevalence of sexual dysfunction in men with CP/CPPS. Data extraction and quality assessment were conducted independently by two reviewers. A random-effects model was used to calculate the pooled prevalence estimates and 95% confidence intervals. Heterogeneity was evaluated using I², τ², and Chi-squared tests, while publication bias was assessed via funnel plot asymmetry and Egger’s test. Results: The meta-analysis incorporated data from 26 studies, representing a total of 20,127 participants. The pooled prevalence of overall sexual dysfunction was 59% (95% CI: 34–81%; I² = 98%) across six studies and 5333 participants. Pooled erectile dysfunction (ED) prevalence was 34% (95% CI: 26–42%; I² = 99%) across 24 studies with 20,127 participants, whereas pooled prevalence for premature ejaculation (PE) was 35% (95% CI: 22–49%; I² = 98%) across 10 studies with 13,686 participants. Significant heterogeneity was observed across all analyses (I² > 98%). Funnel plot analysis suggested potential asymmetry, but Egger’s test was non-significant (p = 0.7034). Conclusions: This meta-analysis confirms the high prevalence of sexual dysfunction, including ED and PE, in men with CP/CPPS, providing a comprehensive estimate of its burden. The substantial heterogeneity observed underscores the need for further research to identify contributing factors and develop targeted interventions. Full article

Background and Objectives: Vision uses about half of the pathways within the brain, and these anatomical structures are susceptible to injury in concussion. Authors have suggested that subconcussive head impacts, common in soccer, may disrupt visual function. The following study aimed to explore and compare quantitative pupillometry and Vestibular Ocular Motor Screening (VOMS) in female soccer athletes. Materials and Methods: Twenty-six Division 1 female soccer athletes (20.46 ± 2.36 years) received baseline quantitative pupillometry and VOMS measurements. Results: Of the 26 tested athletes, 3 (11.5%) had clinically significant pupillometry findings at baseline. The mean Neurological Pupil Index or NPi, a composite generated from pupillometry, did not vary: 3.9 ± 0.4 (right eye) and 4.0 ± 0.4 (left eye). No difference in NPi was observed compared to the VOMS score (p > 0.05). Kruskal–Wallis H tests were significant in the right eye for constriction percentage (χ²(2) = 17.843, p < 0.001, E² = 0.69) and minimum pupil size (χ²(2) = 7.976, p = 0.019, E² = 0.31). A post hoc Dunn test showed significant differences in constriction percentage and minimum pupil size between low NPi and high NPi groups (p < 0.05). One athlete sustained a concussion. NPi was measured within 24 h and was normal, but VOMS was not (total score = 4). Conclusions: The components of pupillometry need more investigation, and there is a need for agreement on concussion-specific cutoffs for quantitative pupillometry for concussion assessment. The lack of a relationship between quantitative pupillometry and VOMS suggests that these tools evaluate different constructs. Athletes with an NPi < 3.8 had significantly less constriction percentage and larger minimum pupil size than athletes with higher NPi scores. More research should be carried out to determine the usefulness of the NPi score, and perhaps researchers should consider individual pupillometry components. Full article

Cryptococcosis, an opportunistic fungal infection predominantly caused by Cryptococcus neoformans, is the third most common invasive fungal disease in solid organ transplant recipients. While well-characterized in adult kidney transplant (KT) patients, pediatric data remain sparse. This article compares clinical presentation, immune response, renal involvement, and management strategies of cryptococcosis between adult and pediatric KT recipients. In adults, the disease typically presents as cryptococcal meningitis or pulmonary infection, often complicated by delayed diagnosis and high mortality. In contrast, children frequently exhibit non-specific respiratory symptoms or disseminated disease, reflecting immune immaturity and increased susceptibility to hematogenous spread. Key immunopathological differences include impaired Th1 type responses, macrophage dysfunction, and variable complement activity across age groups. Management involves similar antifungal regimens such as liposomal amphotericin B, flucytosine, and fluconazole, but requires weight-based dosing and careful toxicity monitoring in pediatric patients. Early diagnosis through serum cryptococcal antigen screening, appropriate adjustment of immunosuppressive therapy, and coordinated multidisciplinary care are essential. The findings underscore the need for pediatric specific research and clinical vigilance, emphasizing tailored antifungal dosing and individualized immune management to improve outcomes in this vulnerable population. Full article

Background and Objectives: This study aimed to evaluate the influence of the angle and position of the tibial tunnel in the coronal and sagittal planes on short-term postoperative clinical outcomes following arthroscopic anterior cruciate ligament reconstruction (ACLR). Materials and Methods: This retrospective study included 40 patients who underwent anatomical ACLR between 1 January 2023 and 31 December 2023 and had a follow-up period of at least 4 months. The angle of the tibial tunnel on the AP radiograph and both the angle and anteroposterior position on the lateral radiograph were measured. Clinical evaluations were conducted using the Visual Analogue Scale (VAS), the International Knee Documentation Committee (IKDC) score, and the Lysholm Knee Score, along with measurements of knee flexion and extension, to assess short-term outcomes at 1, 2, and 4 months postoperatively. Results: In patients whose tibial tunnels were positioned at 40–50° in the coronal plane, Lysholm scores were significantly higher at the 2nd and 4th months compared to other angles. In the sagittal plane, a tunnel angle between 30° and 40° was associated with significantly increased IKDC scores at both the 2nd and 4th months. Additionally, tunnels with an anterior–posterior ratio of 0.4–0.6 in the sagittal plane were associated with limitations in flexion and extension at the 4th month. There was no significant difference in VAS scores between the groups. Conclusions: Our findings suggest that optimizing the tibial tunnel angle in both the coronal and sagittal planes may play a crucial role in early postoperative knee function. Specifically, tibial tunnels placed between 40° and 50° in the coronal plane and 30° and 40° in the sagittal plane were associated with higher functional scores. However, tunnels positioned with an anterior–posterior ratio of 0.4 to 0.6 were linked to greater joint motion limitation. These findings indicate that angular and positional optimization of the tibial tunnel may have contributed to improved functional recovery following ACL reconstruction. Full article

Background and Objectives: There have been a limited number of randomized controlled trials (RCTs) comparing pharmacopuncture therapy (PPT) and physical therapy (PT) for chronic knee pain. In this study, we assess the feasibility, safety, and preliminary effectiveness of PPT compared to PT in patients with chronic knee pain. Materials and Methods: This pilot study was designed as a two-arm, parallel RCT. Patients were recruited through in-hospital advertisements. Forty patients aged 19 to 70 with knee pain with a numeric rating scale (NRS) score of 5, persisting for >3 months, were randomized into the PPT or PT group. The type of PT solution or PT method was not determined in advance, leaving it to the clinician’s judgment. Treatment was administered twice weekly for 3 weeks with a 6-week follow-up. The primary outcome was the NRS score for knee pain, whereas the secondary outcomes were the visual analog scale (VAS), knee range of motion, Korean Western Ontario and McMaster (K-WOMAC), Patient Global Impression of Change, and five-level EuroQol five-dimension scores. Additionally, adherence, acceptability, dropout rate, and adverse events were measured to assess the feasibility of a follow-up main study. The protocol was registered at ClinicalTrials.gov (NCT06505681). Results: The PPT group showed significantly superior improvement compared with the PT group in the NRS (difference = −2.05, 95% confidence interval [CI]: −2.76 to −1.34), VAS (difference = −21.58, 95% CI: −29.42 to −13.74), and K-WOMAC scores (difference = −13.17, 95% CI: −21.67 to −4.67). Of the 55 patients who initially expressed interest in participation, 8 declined after receiving detailed information about this study. Among the forty enrolled participants, one patient in the PPT group dropped out, and one missed a single treatment session. Apart from these cases, all participants completed the assigned treatments and follow-up assessments, demonstrating high adherence. No serious adverse events were reported. Conclusions: PPT demonstrated excellent effectiveness in pain relief and functional improvement in these patients. Full article

Background and Objectives: The prognostic nutritional index (PNI), a marker reflecting both nutritional and immune status, has been associated with prognosis in various malignancies. However, evidence in metastatic castration-resistant prostate cancer (mCRPC), particularly from non-Asian populations, remains limited. This study aimed to evaluate the prognostic value of baseline PNI and to develop a blood-based prognostic model in mCRPC patients treated with abiraterone acetate (AA), enzalutamide (ENZA), or cabazitaxel (CABA). Materials and Methods: This retrospective study included mCRPC patients treated with AA, ENZA, or CABA before or after docetaxel. PNI was calculated as: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm³). Patients were classified into low-PNI (≤40.8) and high-PNI (>40.8) groups using the median PNI value. Survival outcomes were analyzed using Kaplan–Meier and Cox regression methods. Results: A total of 299 patients were analyzed: 133 (44.5%) received AA, 106 (35.5%) ENZA, and 60 (20.0%) CABA. Patients with high PNI had significantly longer median overall survival (OS; 30.2 vs. 12.6 months, p < 0.001), radiologic progression-free survival (rPFS; 13.5 vs. 6.7 months, p < 0.001), and PSA progression-free survival (PSA-PFS; 10.2 vs. 5.1 months, p < 0.001). These associations remained significant across all treatment subgroups. In multivariate analysis, prostate surgery (HR: 0.6), high PNI (HR: 0.5), PSA response (HR: 0.5), and elevated ALP (HR: 1.6) were independent predictors of OS. A prognostic model incorporating PNI, alkaline phosphatase, and anemia stratified patients into four risk groups with distinct OS: 49.1, 30.8, 18.8, and 9.1 months, respectively. Conclusions: This is the largest study to date in a non-Asian mCRPC population showing that baseline PNI is a strong, independent prognostic factor for survival. The proposed blood-based tool may aid in clinical risk stratification, pending prospective validation. Full article

Background and Objectives: Complete dentures remain a primary solution for oral rehabilitation in aging and medically compromised populations. The integration of digital workflows, regenerative materials, and smart technologies is propelling prosthodontics towards a new era, transcending the limitations of traditional static prostheses. Materials and Methods: This narrative review synthesizes historical developments, current practices, and future innovations in complete denture therapy. A comprehensive review of literature from PubMed, Scopus, and Web of Science (2000–2025) was conducted, with a focus on materials science, digital design, patient-centered care, artificial intelligence (AI), and sustainable fabrication. Results: Innovations in the field include high-performance polymers, CAD–CAM systems, digital impressions, smart sensors, and bioactive liners. Recent trends in the field include the development of self-monitoring prostheses, artificial intelligence (AI)-driven design platforms, and bioprinted regenerative bases. These advances have been shown to enhance customization, durability, hygiene, and patient satisfaction. However, challenges persist in terms of accessibility, clinician training, regulatory validation, and ethical integration of digital data. Conclusions: The field of complete denture therapy is undergoing a transition toward a new paradigm of prosthetics that are personalized, intelligent, and sustainable. To ensure the integration of these technologies into standard care, ongoing interdisciplinary research, clinical validation, and equitable implementation are imperative. Full article

Backgrounds and Objectives: This study aims to characterize the prevalence and severity of antidepressant-associated adverse drug events (ADEs) and to identify predictors strongly associated with serious adverse events (SAEs). Materials and Methods: Disproportionality analysis on antidepressant-related ADEs spontaneously reported to the Korea Adverse event Reporting System (KIDS KAERS DB) from 2014 to 2023 was performed. Multiple logistic regression was conducted to identify predictors associated with SAEs. Sensitivity analysis was performed to validate the overall findings and assess the robustness of associations across subgroups defined by completeness of demographic data (age and sex), elderly age-stratification, and causality assessment. The study protocol was approved by the Kyung Hee University institutional review board. Results: Among 21,103 antidepressant-related ADEs, duloxetine was the most etiologic medication, followed by amitriptyline and escitalopram. Fluoxetine is the only agent with a high likelihood of reporting SAEs. ADEs involving vascular (extracardiac) disorders (ROR 42.42, 95% CI 13.19–136.42) and liver and biliary system disorders (ROR 7.84, 95% CI 3.77–16.29) were most likely to be SAEs. The predictors associated with substantial increased SAE risk were fluoxetine use (OR 2.71, 95% CI 1.68–4.39), male sex (OR 1.48, 95% CI 1.11–1.98), and concomitant administration of antiparkinsonian treatment (OR 8.29, 95% CI 3.61–19.06) and antidementia treatment (OR 2.94, 95% CI 1.34–6.05). Sensitivity analyses demonstrated similar and consistent findings. However, reversed trends in the association between SOC-based ADEs and sex were observed in the sensitivity analysis restricted to cases with “certain” and “probable” causality. Conclusions: The type of antidepressant, concomitant medications, and sex are major predictors for SAE risk. Further controlled studies on the impact of comorbidities and polypharmacy on antidepressant-related SAEs are warranted. Full article

Background and Objectives: Fibrosis stage is the key histopathological determinant of liver-related outcomes in metabolic dysfunction-associated steatohepatitis (MASH); however, a reliable noninvasive method for predicting fibrosis stage remains an unmet need. This study aimed to develop an accurate, practical, and noninvasive tool for identifying “at-risk MASH patients”. Materials and Methods: Fifty-six patients with biopsy-confirmed MASH were prospectively enrolled and categorized into fibrosis stages using the NASH-CRN system. In addition to anthropometric and biochemical parameters, seven serum fibrosis biomarkers were evaluated across fibrosis stages. Binary logistic regression analysis was used to construct a scoring model for predicting ≥F2 fibrosis. The diagnostic performance of the proposed model was compared with established noninvasive tests (NITs) and magnetic resonance elastography (MRE) for detecting both ≥F2 and ≥F3 fibrosis. Results: The total metabolic syndrome score was the only variable that significantly distinguished between F1 and F2 stages (p = 0.039). Among the biomarkers, matrix metalloproteinase-1 (MMP-1) showed a significant difference across fibrosis groups (p = 0.009). The AST/ALT ratio was the most robust predictor for differentiating ≥F3 (p < 0.001). A scoring model integrating the total metabolic syndrome score, MMP-1, and AST/ALT ratio demonstrated superior diagnostic accuracy for identifying ≥F2 (AUROC 0.88, 95% CI 0.79–0.97) compared to other NITs and MRE, and strong performance for detecting ≥F3 (AUROC 0.95, 95% CI 0.90–1.00). Conclusions: Total metabolic syndrome score and MMP-1 are promising candidates for future approaches. Combining total metabolic syndrome score, MMP-1, and AST/ALT ratio might detect ≥F2 in MASH with higher diagnostic accuracy than other NITs and MRE. Full article

Background and Objectives: The use of antiseizure medications (ASMs) during pregnancy is critical to seizure control in women with epilepsy but raises concerns regarding the use of these drugs and their possible effect on the maternal serum biochemical markers used for second-trimester prenatal screening. The aim of this study was to assess the effect of ASMs on the levels of maternal serum alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG) assessed in the serum biomarker analyses part of second-trimester prenatal screening. Materials and Methods: This retrospective cohort study included 43 pregnant women in the ASM-exposed group (levetiracetam, lamotrigine, carbamazepine, or combined therapy) and 43 matched controls without medication use. Groups were matched based on maternal age, gravidity, parity, abortion history, gestational age at testing, body mass index, and smoking status with propensity score matching. Serum AFP, uE3, and hCG levels measured at 15–20 weeks of gestation were compared between groups. The incidence of fetal congenital anomalies or aneuploidies was also compared between groups. Results: Pregnant women in the ASM-exposed group had significantly higher maternal serum AFP (1.34 ± 0.42 vs. 1.01 ± 0.31 MoM; p < 0.001) and uE3 (1.28 ± 0.39 vs. 1.05 ± 0.34 MoM; p = 0.004) than the controls. However, hCG did not differ significantly between the groups (1.07 ± 0.46 vs. 1.01 ± 0.42 MoM; p = 0.523). Regarding the ASM subgroups (levetiracetam, lamotrigine, and carbamazepine), there were no significant differences in the serum biomarkers (p > 0.05). There was no significant difference between the ASM-exposed and control groups in terms of the incidence of congenital anomalies or aneuploidies (2.3% in the ASM-exposed group vs. 2.3% in the control group; p = 1.000). Conclusions: The use of ASMs during pregnancy significantly alters second-trimester maternal serum biochemical markers, including our primary concerns, AFP and uE3, which could cause inaccurate interpretations of second-trimester prenatal screening. Clinicians should carefully consider maternal medication exposure when interpreting these biochemical markers in pregnant women with epilepsy to prevent the misclassification of fetal risks and avoid unnecessary invasive procedures. Full article

Background and Objectives: Despite developments in cervical cancer (CC) treatment, an advanced stage is a poor prognostic factor. Cervical cancer is an immunogenic tumor in which viruses, like HPV, play a role in carcinogenesis. Therefore, systemic inflammatory markers (SIMs) may have prognostic value. Most studies on SIMs focus on the early stage by evaluating pretreatment levels. This study aims to evaluate the prognostic and predictive values of both pretreatment and post-treatment parameters at the advanced stage, as well as treatment efficacy after progression with first-line treatment. Materials and Methods: A total of 133 advanced-stage CC patients with progression on first-line platin–paclitaxel and bevacizumab were evaluated retrospectively. Demographic and histopathological characteristics were recorded along with treatment details. Pre-treatment baseline blood parameters and post-treatment follow-up values were recorded to calculate SIMs as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammatory response index (SIRI). Results: Median values for SIMs were accepted as cut-off values. Post-treatment values demonstrated stronger predictive power, with pre-treatment SIRI and NLR being significant only in univariate analysis, but not in multivariate analysis. High post-treatment SIRI (>2.1) was correlated with shorter overall survival (OS) and considered a poor prognostic factor. High post-treatment SIRI (>2.1), -SII (>746), and -PLR (>197) emerged as independent prognostic factors for progression-free survival (PFS). Their prognostic values were clearer in the whole population and the metachronous metastatic subgroup. Rechallenge of platinum-based chemotherapy was an option for those who had at least 6 months of PFS with first-line platinum-based chemotherapy. Bevacizumab addition to single-agent or combination regimens led to improved ORR as well. Conclusions: Post-treatment SIRI is a promising prognostic factor for OS, while post-treatment SIRI, SII, and PLR may serve as convenient SIMs for PFS. Platinum-based combination chemotherapy reinduction is a feasible second-line treatment strategy, especially with the addition of bevacizumab. Full article

Background and Objectives: Traditionally, we evaluate the size of a wound by using Opsite Flexigrid transparent film dressing, placing it over the wound, tracing the edges of the wound, and then calculating the area. However, this method is both time-consuming and subjective, often leading to varying results depending on the individual performing the assessment. In this study, our goal is to provide an objective method to calculate the wound size and solve variations in photo-taking distance caused by different medical practitioners or at different times, as these can lead to inaccurate wound size assessments. To evaluate this, we employed K-means clustering and used a QR code as a reference to analyze images of the same wound captured at varying distances, objectively quantifying the areas of 40 wounds. This study aims to develop an objective method for calculating the wound size, addressing variations in photo-taking distance that occur across different medical personnel or time points—factors that can compromise measurement accuracy. By improving consistency and reducing the manual workload, this approach also seeks to enhance the efficiency of healthcare providers. We applied K-means clustering for wound segmentation and used a QR code as a spatial reference. Images of the same wounds taken at varying distances were analyzed, and the wound areas of 40 cases were objectively quantified. Materials and Methods: We employed K-means clustering and used a QR code as a reference to analyze wound photos taken by different medical practitioners in the outpatient consulting room. K-means clustering is a machine learning algorithm that segments the wound region by grouping pixels in an image according to their color similarity. It organizes data points into clusters based on shared features. Based on this algorithm, we can use it to identify the wound region and determine its pixel area. We also used a QR code as a reference because of its unique graphical pattern. We used the printed QR code on the patient’s identification sticker as a reference for length. By calculating the ratio of the number of pixels within the square area of the QR code to its actual area, we applied this ratio to the detected wound pixel area, enabling us to calculate the wound’s actual size. The printed patient identification stickers were all uniform in size and format, allowing us to apply this method consistently to every patient. Results: The results support the accuracy of our algorithm when tested on a standard one-cent coin. The paired t-test comparing the first and second photos shot yielded a p-value of 0.370, indicating no significant difference between the two. Similarly, the t-test comparing the first and third photos shot produced a p-value of 0.179, also showing no significant difference. The comparison between the second and third photos shot resulted in a p-value of 0.547, again indicating no significant difference. Since all p-values are greater than 0.05, none of the test pairs show statistically significant differences. These findings suggest that the three randomly taken photo shots produce consistent results and can be considered equivalent. Conclusions: Our algorithm for wound area assessment is highly reliable, interchangeable, and consistently produces accurate results. This objective and practical method can aid clinical decision-making by tracking wound progression over time. Full article

Background and Objectives: Complications in wound healing present significant challenges in clinical settings. While platelet-rich plasma from human sources has been extensively used to aid wound recovery, allogeneic or xenogeneic platelet-derived products remain in the research phase. This study aimed to assess both the immunogenicity and therapeutic potential of xenogeneic porcine platelet lysate (pPL) in wound healing, using a rat model. Materials and Methods: Porcine platelet lysates with undetectable levels of antigens, including blood cells and complement factors, were engineered. Rat models simulating wound conditions were employed to investigate the effects of xenogeneic pPL on injured skin tissues. Histological assessments, including re-epithelialization, angiogenesis, and inflammatory cell response, were comprehensively conducted to evaluate the healing process. Results: The application of xenogeneic pPL on rat skin incisions significantly expedited the wound healing process. No rejection reaction was observed. Histological examinations of the xenogeneic pPL-treated wounds revealed enhanced re-epithelialization and angiogenesis compared to the wounds in control groups. Conclusions: These findings support the clinical promise of xenogeneic pPL as a feasible and effective agent for wound repair and tissue regeneration. This study suggests that its potential application in in vivo regeneration appears viable and promising. Full article

Background and Objectives: On 6 February 2023, two catastrophic earthquakes struck southeastern Türkiye, affecting over 13 million individuals and causing widespread destruction. While the physical damage was immediate, the psychological consequences—particularly posttraumatic stress disorder (PTSD) and depression—have proven long-lasting. This study aimed to evaluate the severity and course of PTSD symptoms among survivors and to examine the effectiveness of a telepsychiatry-based mental health intervention in a post-disaster setting. Materials and Methods: This naturalistic, observational study included 153 adult participants from the affected regions who underwent at least two telepsychiatry sessions between the first and sixth month post-disaster. Initial screening was conducted using the General Health Questionnaire (GHQ-12), and individuals scoring ≥ 13 were further assessed with the PTSD Checklist—Civilian Version (PCL-C) and the Beck Depression Inventory (BDI). Follow-up evaluations and pharmacological or psychoeducational interventions were offered as clinically indicated. Results: At the one-month follow-up, 94.4% of participants met the threshold for PTSD symptoms (PCL-C > 22) and 77.6% had severe depressive symptoms (BDI > 30). By the sixth month, PTSD symptoms had significantly decreased (mean PCL-C score reduced from 42.47 ± 12.22 to 33.02 ± 12.23, p < 0.001). Greater symptom reduction was associated with higher educational attainment and perceived social support, while prior trauma predicted poorer outcomes. Depression severity emerged as the strongest predictor of chronic PTSD. Conclusions: This study highlights the psychological burden following the 2023 earthquakes in Türkiye and demonstrates the feasibility and potential effectiveness of telepsychiatry in disaster mental health care. Integrating digital mental health services into disaster response systems may help reach vulnerable populations and improve long-term psychological recovery. Full article

Background and Objectives: The role of adenosine deaminase (ADA) in pulmonary tuberculosis (PTB) remains insufficiently defined in advanced forms of disease. Likewise, the systemic immune inflammatory index (SII) has not been validated in severe PTB. This 6-year prospective observational study aims to evaluate biomarker signatures of serum ADA and SII. Materials and Methods: According to the PTB case definition, 232 adult patients were divided into group 1, with a positive bacteriologic exam (n = 168), and group 2, without bacteriological confirmation (n = 64). ADA serum levels were compared by age, gender, nutritional status, morphologic and bacteriological pattern of PTB lesions, survival status, along with serum levels of other inflammatory biomarkers. All patients with comorbidities, interfering with the level of ADA, were excluded to avoid bias. Results: A total cohort of 208 PTB adults, aged 54.37 ± 14.365 years, included 156 males. The overall mortality was 11.53%. Death occurred after a mean interval of 1.63 ± 3.228 months after PTB diagnosis. ADA serum mean levels were 32.94 ± 9.146 IU/L, significantly higher in G1 (p = 0.002), in patients with delayed diagnosis of PTB (p = 0.000), with lung cavitation (p = 0.003), and death as a poor outcome (p ˂ 0.02). SII had a mean value of 1752.226 ± 2704.150, significantly increased in bacteriologically confirmed PTB cases (p = 0.018), delayed diagnosis (p = 0.002), cavitary advanced pulmonary tuberculosis (APT) (p = 0.002), and deceased (p = 0.003). Both an ADA cut-off elevated risk value of over 30 IU/L and SII of over 902 were fulfilled by 73 patients, with 2.10 higher risk of advanced PTB (p = 0.006) and 4.49 higher risk of mortality (p = 0.000). Conclusions: Serum ADA and SII are recommended as predictors of advanced and severe pulmonary TB. These findings indicate that ADA and SII, when elevated together, delineate a high-risk PTB phenotype with greater disease severity and early mortality. The combination offers a pragmatic, biomarker-based approach to risk stratification in PTB. Full article