Medicina, Volume 61, Issue 6 (June 2025) – 140 articles

Background and Objectives: This study aimed to evaluate the effects of hard, soft, and semi-soft splints on TMJ vibrations in bruxers with JVA and to compare them with data obtained from asymptomatic individuals. Materials and Methods: A total of 64 individuals were divided into four subgroups: control (n = 15); and hard (n = 17), soft (n = 16), and semi-soft (n = 16) splints. Electrovibratography records from all individuals included in the study before and after the 3-month splint treatment were obtained with the Biopak^® System. Joint vibration analysis was used to evaluate TMJ sounds. Data normality was examined with the Kolmogorov–Smirnov and Levene tests. The significance of the differences was investigated by One-Way ANOVA and by the Kruskal–Wallis test. Conover’s multiple comparison test was used in post hoc tests. (ClinicalTrials.gov identifier: NCT06893744, on 24 March 2025, titled; Effects of Different Occlusal Splints). Results: After 3 months of treatment, for I < 300 Hz right opening, the control group was statistically lower than both semi-soft (p < 0.001) and hard (p < 0.001) splint groups. The difference between semi-soft and hard splints in post-treatment I < 300 Hz right opening is not statistically significant. After 3 months of treatment compared with the beginning, the increases in left-opening Ti (p = 0.004), I < 300 Hz (p = 0.004), and PA (p = 0.007) values in the soft splint group were statistically significant. Conclusions: All three kinds of splints improved clinical symptoms and complaints of bruxers. For joint vibrations in bruxers, hard and semi-soft splints are more beneficial than soft splints. Full article

Background and Objectives: Indeterminate thyroid nodules (Bethesda III and IV) are a common clinical entity that present a diagnostic challenge due to their intermediate risk of malignancy. This study aimed to evaluate the role of ultrasound in risk stratification and malignancy prediction to support clinical decision-making and reduce unnecessary surgical interventions. Materials and Methods: This retrospective multicenter cohort study included patients aged ≥18 years who underwent thyroid surgery between 2016 and 2022 at four centers in the Eastern Province of Saudi Arabia. Only nodules with indeterminate cytology (Bethesda III or IV) were included. Data collected included demographic characteristics, thyroid function, ultrasound features, cytology results, and histopathological findings. Results: A total of 679 patients with 733 nodules were reviewed. Of these, 206 patients with 223 indeterminate nodules were included (median age: 42 years; 88.3% female). The overall malignancy rate was 46.6%. Independent predictors of malignancy included solid hypoechoic composition (OR = 2.26, p = 0.012), microcalcifications (OR = 3.07, p = 0.002), lymph node involvement (OR = 2.43, p = 0.021), American Thyroid Association (ATA) intermediate to high suspicion category (OR = 1.9, p = 0.018), and Thyroid Imaging Reporting and Data Systems (TI-RADS) categories 4–5 (OR = 2.3, p = 0.003). Solid hypoechoic nodules showed 82.3% specificity and 63.0% positive predictive value (PPV); microcalcifications demonstrated 84.1% specificity and 68.4% PPV; lymph node involvement had 87.6% specificity and 68.9% PPV. The ATA and TI-RADS classifications showed higher sensitivity (63.5% and 68.0%, respectively), but lower specificity (53.1% and 52.8%, respectively). Conclusions: Ultrasound features, particularly solid hypoechoic composition, microcalcifications, and lymph node involvement, as well as ATA and TI-RADS classifications, were independent predictors of malignancy in indeterminate thyroid nodules. Although ATA and TI-RADS offered higher sensitivity, individual features demonstrated greater specificity and PPV. These findings support the use of ultrasound risk stratification to guide surgical decisions in high-risk cases and suggest that additional diagnostic evaluation may be appropriate for low-risk nodules. Full article

Background and Objectives: Robotic surgery represents one of the most significant innovations in the field of surgery, offering new opportunities for the treatment of complex pathologies that require greater accuracy and precision. It is a technology that has become widely used in general, urologic, gynecologic, and cardio-thoracic surgery, but has a limited evidence in the head and neck region. This review explores the use of robotic surgery in orbital pathology, focusing on its applications, benefits, and limitations. Materials and Methods: A cross-sectional search method was performed in multiple databases to answer the following question: “What are the applications of robotic surgery in the management of orbital pathologies?” Studies were carefully reviewed by two simultaneous researchers, and, in case of disagreement, a third researcher was engaged. Care was taken to identify the surgical hardware (robotic station) used to perform the surgical procedure. Results: Out of 491 records, eight studies met the inclusion criteria. These included cadaveric, preclinical, in vitro, and early clinical investigations assessing robotic approaches for fronto-orbital advancement, tumor resection, orbital decompression, and other surgical procedures such as lacrimal gland dissection and biopsy, medial and lateral orbital wall dissections, enucleation, and lid-sparing orbital exenteration. The robotic systems evaluated included the Da Vinci Xi, Da Vinci SP, Medineering Robotic Endoscope Guiding System, and a modular multi-arm concentric tube robot, each with specific advantages and limitations. Conclusions: Robotic surgery provides significant advantages for orbital pathologies such as improved precision, visualization, and tissue preservation, with reduced complications and faster recovery, although some limitations still exist. Future advancements, such as smaller instruments and AI integration, promise to improve outcomes, making robotic surgery more effective in treating orbital conditions. Full article

Background and Objectives: Acute decompensated heart failure (ADHF) leads to significant impairments in exercise capacity and functional outcomes. This study aimed to evaluate the feasibility and effectiveness of integrating early phase I cardiac rehabilitation with a multidisciplinary heart failure post-acute care (HF-PAC) program to improve functional capacity in patients hospitalized for ADHF, assessed by serial cardiopulmonary exercise testing (CPET). Materials and Methods: We conducted a prospective cohort study at a medical center in Taiwan. Patients hospitalized for ADHF between February 2017 and March 2023 who completed inpatient and six-month follow-up CPET were enrolled. The rehabilitation protocol included supervised aerobic and resistance training during hospitalization, followed by outpatient multidisciplinary care. The primary outcome was the change in peak oxygen uptake (peak VO₂) over six months. Results: A total of 90 patients were included (74.4% male, mean age 58.4 ± 14.7 years). Peak VO₂ significantly improved from 11.57 ± 3.33 to 13.99 ± 4.2 mL/kg/min (p < 0.001). Significant improvements were also observed in 6 min walk distance, anaerobic threshold, heart rate recovery, oxygen uptake efficiency slope, and left ventricular ejection fraction. Conclusions: Early integration of phase I cardiac rehabilitation with multidisciplinary HF-PAC is feasible and enhances exercise capacity in patients with ADHF. Serial CPET provides an objective evaluation of functional recovery and may guide rehabilitation strategies in this high-risk population. Full article

Background and Objectives: The therapeutic effect of para-aortic lymphadenectomy in patients with clinically para-aortic node-negative diseases remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared with pelvic lymphadenectomy alone in patients with clinically FIGO stage IIIC1 high-grade endometrial cancer. Materials and Methods: We retrospectively reviewed patients with clinically FIGO stage IIIC1 high-grade endometrial cancer in the period between January 2000 and December 2020 at two tertiary centers. The patients were stratified according to type of lymphadenectomy and subgroup analyses performed. Kaplan–Meier analysis and a Cox proportional-hazards model were used to evaluate survival outcomes. Results: A total of 56 patients were identified. Of these patients, 18 underwent pelvic lymphadenectomy alone and 38 underwent combined pelvic and para-aortic lymphadenectomy. After staging surgery, 34 (60.7%) patients had pathologically confirmed lymph node metastases. Within a median follow-up of 57.5 months, there were no significant differences in recurrence-free survival (RFS) and overall survival (OS) between the two groups. In subgroup analyses, the node- and lymphovascular space invasion (LVSI)-positive patients characterized by grade 3 endometrioid histologic type (p = 0.010) or negative peritoneal washing cytology (p = 0.035) had an RFS benefit from combined pelvic and para-aortic lymphadenectomy. Conclusions: The addition of para-aortic lymphadenectomy to pelvic lymphadenectomy did not improve survival in patients with clinically FIGO IIIC1 endometrial cancer. However, para-aortic lymphadenectomy may have RFS benefit for patients with grade 3 endometrioid histologic type and positive LVSI. Full article

Background and Objectives: Community-acquired pneumonia (CAP) remains a major health burden worldwide, with high morbidity and mortality, particularly among older adults and those with comorbidities. This study aimed to evaluate the etiological factors of CAP and to investigate systemic inflammatory markers (IL-6, IL-8, IFN-γ, and G-CSF) in blood samples collected from CAP patients to identify which markers could be targets for potential etiological, clinical, and therapeutic interventions. Materials and Methods: A prospective study was conducted in 41 patients with confirmed CAP hospitalised during the winter season of 2024–2025. Clinical, demographic, and laboratory data were collected at admission and seven days later. Serum IL-6, IL-8, IFN-γ, and G-CSF concentrations were measured using a multiplex assay. Results: Aetiology was identified in 87.8% of cases, with typical bacterial pathogens being more prevalent among older, smoking patients, while atypical pathogens were more common among younger, non-smoking patients. Hospitalisation and increased inflammatory markers were associated with older age. After seven days of treatment, significant decreases in IL-6, IFN-γ, and G-CSF concentrations were observed. IFN-γ levels were significantly higher in patients with atypical aetiology. Higher concentrations of IL-8 and G-CSF were associated with hospitalisation. IL-6 levels were positively correlated with age, C-reactive protein (CRP), and pneumonia severity index (PSI) scores. Conclusions: Systemic inflammatory markers, especially IL-6, IL-8, IFN-γ, and G-CSF, may be valuable tools in managing generalised pneumonia. They can help to differentiate etiologically, assess disease severity, and make treatment decisions. Full article

High-risk pregnancies (HRPs) constitute a significant global health issue due to their strong association with increased maternal and neonatal morbidity and mortality. Although pregnancy is generally characterized by positive expectations, the presence of maternal comorbidities, gestational complications, or adverse socioeconomic and environmental conditions can markedly elevate the probability of unfavorable outcomes. HRPs contribute disproportionately to complications such as preterm birth, fetal growth restriction, low birth weight, and congenital anomalies, which are key determinants of neonatal mortality and long-term developmental and health challenges. A broad spectrum of risk factors as well as insufficient prenatal care, underscores the complex nature of HRPs. These conditions necessitate a multidisciplinary management approach encompassing early risk identification, continuous monitoring, and individualized interventions. The neonatal prognosis in such contexts is strongly influenced by gestational age at delivery, birth weight, the standard of neonatal care, and the underlying etiological factors driving preterm or complicated deliveries. Preventive strategies including comprehensive prenatal screening, systematic antenatal follow-up, and timely referral to specialized perinatal care centers are essential for reducing the burden of HRPs. Furthermore, addressing social determinants of health—such as low socioeconomic status and limited access to healthcare—is critical for optimizing maternal and neonatal outcomes. This review consolidates current evidence on the epidemiology, etiological factors, and clinical implications of high-risk pregnancies, emphasizing the necessity of an integrative, preventive, and multidisciplinary framework to mitigate adverse neonatal outcomes and improve long-term health trajectories. Full article

Background: Despite advances in chemotherapy and supportive care, pancreatic ductal adenocarcinoma (PDAC) continues to carry a dismal prognosis, with a five-year survival rate of approximately 13%. While immunotherapy has revolutionized treatment for several malignancies, its efficacy in PDAC remains limited. Recent research has shifted focus toward integrating immunotherapy with chemotherapy, radiation, and targeted therapies in an effort to overcome therapeutic resistance and improve outcomes. Ongoing clinical trials are actively investigating these multimodal strategies. Materials and Methods: A systematic search was conducted using PubMed and ScienceDirect to identify relevant studies published in the past six years. Search terms included “pancreatic adenocarcinoma immunotherapy,” “pancreatic cancer treatments,” and “combination treatments for pancreatic adenocarcinoma.” Only English-language articles were included. Results: A total of 126 articles were initially identified through the database search. After a full-text screening, 48 articles were deemed potentially relevant. Following a rigorous review, 11 studies met the inclusion criteria and were selected for analysis. These studies included randomized controlled trials, non-randomized controlled trials, and retrospective studies. Meta-analyses and case reports were excluded. Articles that failed to meet the inclusion criteria were excluded, primarily due to the absence of relevant data addressing the main objective of this review. Conclusions: Combination strategies with immunotherapy and chemotherapy offer modest survival gains in metastatic settings, yet efforts in resectable and borderline resectable disease have fallen short. These outcomes reflect the profound immunosuppressive forces of the PDAC microenvironment. A new era of treatment must move beyond broad immunotherapeutic applications toward a precision-driven model. Molecular markers, such as KRAS mutations and circulating tumor DNA (ctDNA) profiles, are beginning to illuminate paths for personalized therapy selection. Future progress will depend on biomarker-guided clinical trials, a deeper understanding of immune resistance mechanisms, and bold innovation at the intersection of immunology and tumor biology. Full article

Background and Objectives: Venous thromboembolism (VTE) is a serious complication frequently encountered in cancer patients and is associated with high morbidity. In patients undergoing cancer treatment—particularly those receiving chemotherapy—VTE increases treatment-related complications and has a direct impact on mortality. The development of VTE in oncology patients varies depending on cancer type, treatment protocols, and individual patient characteristics. The Khorana Risk Score (KRS) is a validated risk assessment tool used to estimate the risk of VTE development in patients receiving chemotherapy. KRS provides risk estimations based on the patient’s clinical features, cancer type, and treatment process. This study aims to investigate the prognostic value of the Khorana Risk Score in predicting VTE development and overall survival in patients with metastatic gastric cancer. Materials and Methods: This retrospective study used data from 337 metastatic gastric cancer patients who presented to Kartal Dr. Lütfi Kırdar City Hospital between January 2012 and June 2024. Patients were categorized into intermediate- and high-risk groups according to the Khorana Risk Score. The study’s primary endpoints were the development of VTE and overall survival. Results: There was no statistically significant difference in VTE incidence (p = 0.27) or overall survival (11.9 months vs. 11.5 months, p = 0.23) between patients in the intermediate- and high-risk groups. Conclusions: These results indicate that the Khorana Risk Score is insufficient in predicting VTE development in patients with metastatic gastric cancer and has a weak association with overall survival outcomes. In conclusion, this study demonstrates the KRS’s inadequacy in predicting VTE and survival outcomes in patients with metastatic gastric cancer, highlighting the need for more tailored approaches. Full article

Background and Objectives: This study investigated the frequency and clinical significance of subclinical but substantial peripheral arterial disease (PAD), identified using PAD evaluation, including pulse volume recording/ankle–brachial index (PVR/ABI), transcutaneous oxygen pressure (TcpO2), and skin perfusion pressure (SPP) tests in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 54 patients with PAD evaluation results at or after AAV diagnosis. PVR/ABI and/or TcpO2 and/or SPP were performed on the same day. Abnormal PVR/ABI, TcpO2, and SPP were defined as PVR/ABI < 0.97, TcpO2 < 40 mmHg, and SPP < 50 mmHg, respectively. Poor outcomes included all-cause mortality, end-stage kidney disease (ESKD), cerebrovascular accidents, and acute coronary syndrome after PAD evaluation. Results: The median age of the 54 patients was 67 years, and 48.1% were male. In total, 3 of 54 patients (5.6%), 6 of 16 (37.5%), and 6 of 23 (26.1%) had abnormal PVR/ABI, TcpO2, and SPP, respectively. The concordance rate between abnormal PVR/ABI and abnormal TcpO2 or SPP was very low. Among the 54 patients, 5 (9.3%) died, and 2 (3.7%) progressed to ESKD. Abnormal SPP was significantly associated with cutaneous and renal manifestations at the time of PAD evaluation and had the potential to predict progression to ESKD during follow-up in patients with AAV. Conclusions: This study is the first to reveal the clinical usefulness of PAD evaluation: abnormal SPP may have the potential to identify subclinical but substantial PAD and can predict simultaneous kidney involvement as well as future progression to ESKD in patients with AAV. Full article

Background/Objectives: This study aimed to evaluate the relationship between sirtuin family members (SIRT1, SIRT3, and SIRT6) and Wnt/β-catenin pathways with inflammation during the rejection process following kidney transplantation, as well as to explore their potential roles as candidate biomarkers. Materials and Methods: Blood samples were collected from 35 kidney transplant rejection patients and 30 healthy controls. The gene expression levels of SIRT1, SIRT3, SIRT6, and Wnt/β-catenin pathway components were measured using real-time PCR, and miRNA and lncRNA expression levels were analyzed. Statistical analyses were performed using SPSS version 23. Results: Significant alterations in SIRT1, SIRT3, and SIRT6 expression levels were observed in rejection patients, suggesting their potential role in disease pathogenesis and as therapeutic biomarkers. Key altered genes included hsa-miR-34c-1, hsa-miR-122b-5b, MALAT1, HOTAIR, LINC00473, TUG, PVT1, SIRT1, SIRT3, SIRT6, WNT1, TCF-LEF, LRP, AXIN1, IL1B, IL6, and IFNB1, all showing significant changes. However, no significant differences were found for miRNAs such as hsa-miR-21-2, hsa-miR-155-5p, and hsa-miR-200b-3p. SIRT1 expression was significantly decreased in the cellular rejection group, with a more pronounced reduction in these patients. Significant differences in SIRT1 expression were observed with interstitial inflammation and glomerulitis. Increased inflammation severity correlated with decreased SIRT1 and increased TCF-LEF, TUG, and miR-21 levels, while tubulitis severity was associated with elevated TCF-LEF and miR-155 expression. Conclusions: Along with the activation of Wnt/β-catenin pathways and increased levels of certain miRNAs and long non-coding RNAs (lncRNAs) associated with TCF-LEF transcription factors, the observed decrease in SIRT1 expression may be related to the severity of inflammation and tubulitis. These findings suggest that SIRT1, Wnt/β-catenin pathways, and non-coding RNAs play a role in the rejection process following kidney transplantation and could be considered as potential biomarkers or therapeutic target candidates for future research. Full article

Background and Objectives: Acute infections among elite athletes are predominantly attributed to upper respiratory tract pathogens. From a practical standpoint, medical personnel responsible for the healthcare of professional football players should be aware of this and develop infection prevention strategies. This pilot study aimed to investigate the prevalence of respiratory infections in football players using multiplex rapid diagnostic tests targeting four respiratory pathogens. Materials and Methods: The mean age of the participants was 32.76 ± 10.96 years. Among the participants, 32 were professional football players, with a mean age of 26.5 years, SD + 5.3, and 18 were members of staff, with a mean age of 44.3 years, SD + 8.6. In the present study, participants were followed up over a period of 6 months (from October 2024 to March 2025). Results: Among the participants and among a total of 1078 tests, 10 tests were found to be positive. We recorded a proportion of 0.46% for Flu-A, 0.27% for Flu-B, 0.18% for SARS-CoV-2, and 0 positive tests for RSV and adenovirus. There were six days of absence for players and staff and the proportion of total absenteeism was calculated as 3.7%. Univariate analysis revealed no statistically significant difference in infection risk between staff and players (odds ratio: 0.3795; 95% confidence interval: 0.07843–1.735). Conclusions: The multiplex rapid diagnostic test platform has a demonstrated ease of use and appears to be a reliable and safe method for distinguishing contagious symptomatic individuals from non-contagious individuals in occupational settings. Early identification of respiratory infections facilitates improved clinical management, thereby enhancing the quality of care for both athletes and supporting staff. Full article

Background and Objectives: The common cold (acute rhinopharyngitis) and acute rhinosinusitis are highly prevalent conditions that significantly impact quality of life, often leading to nasal congestion, inflammation, and discomfort. Given the growing demand for non-pharmacological treatment options, particularly for vulnerable populations such as children and pregnant women, alternative therapies are increasingly being explored. NESOSPRAY HE-C, a nasal spray formulated with a glycerol-based filmogenic solution, acts by forming a protective osmotic film on the nasal mucosa. This mechanism facilitates mechanical cleansing, enhances decongestion, and reduces inflammation while preserving mucosal integrity. Its purely topical and mechanical mode of action provides a non-systemic alternative for symptom management. Materials and Methods: This randomized, double-blind, parallel-group clinical trial evaluated the efficacy and safety of NESOSPRAY HE-C (n = 29) compared to a placebo nasal spray (n = 26) in patients aged ≥ 3 years diagnosed with the common cold or acute rhinosinusitis. Participants had a baseline Rhinosinusitis Symptom Severity Score (RSSS) of ≥25/50. Treatment consisted of administering 2–3 sprays per nostril, four times daily, every 4 to 6 h, for up to 8 days or until symptom resolution. The primary outcomes included changes in total RSSS, Wisconsin Upper Respiratory Symptom Survey (WURSS) score, and individual symptom scores (rhinorrhea, nasal congestion, cough, poor sleep, facial pain, and fever). Safety assessments included adverse event monitoring and treatment tolerability, with subgroup analyses performed for children and pregnant women. Results: Baseline demographics were comparable between the treatment groups. NESOSPRAY HE-C demonstrated a significantly greater reduction in total RSSS from Day 3 onward (p = 0.0008), with sustained superiority through Day 8 (p < 0.0001). Significant improvements in rhinorrhea and nasal congestion were observed within 2 h of administration (p = 0.0089), while reductions in cough (p = 0.0052), poor sleep (p = 0.0005), and facial pain (p = 0.0111) emerged by Day 3. Fever reduction was most pronounced on Days 6 (p = 0.0001) and 8 (p = 0.0312), indicating a delayed but significant effect. In terms of the WURSS score, NESOSPRAY HE-C showed a significant improvement from Day 1, with a greater reduction in symptom severity compared to placebo. This trend of greater improvement continued through Day 8. The treatment was well tolerated, with no reports of serious adverse events or allergic reactions. Efficacy was consistent across all subgroups, including children, pregnant women, and adults. Conclusions: NESOSPRAY HE-C provides rapid and sustained symptom relief for the common cold and acute rhinosinusitis, serving as a safe and effective non-pharmacological alternative to conventional treatments. By leveraging its osmotic action and barrier-forming properties, it facilitates mechanical cleansing, enhances decongestion, and reduces inflammation while preserving mucosal integrity. Additionally, by forming a protective film on the nasal mucosa, it protects against future irritations, further supporting its role as a valuable therapeutic option, particularly for individuals seeking non-systemic symptom management. Full article

Background: Acute appendicitis (AA) is a common surgical emergency worldwide. Over the past few decades, diagnostic imaging has become a cornerstone in the identification of acute appendicitis, significantly contributing to the reduction in unnecessary laparotomies and associated healthcare costs. This study aimed to investigate the influence of serum and spot urine 5-hydroxyindoleacetic acid (5-HIAA) levels, as well as other established clinical and biochemical parameters on the diagnosis of acute appendicitis. Methods: This prospective study was conducted between January and November 2023, evaluating 97 patients diagnosed with acute appendicitis. Serum and spot urine 5-HIAA levels, level of white blood cell (WBC), neutrophils, lymphocytes, platelets, C-reactive protein (CRP), and Alvarado score were analyzed. Patients were further allocated to subgroups based on their Alvarado scores, the onset time of the symptoms, and pathological findings to statistically assess the relationship between the parameters. Results: The mean age of the patients was 34.6 ± 14.8 years. Of the patients, 57 (58.8%) were male, and 40 (41.2%) were female. Spot urine 5-HIAA levels exhibited statistically significant variation among different symptom onset time groups, with elevated levels observed in patients presenting within the first 12 h of symptom onset (p < 0.001). Neutrophil counts were significantly different among Alvarado score groups (p < 0.001), whereas CRP levels significantly increased with the onset time of the symptoms (p < 0.001). Conclusions: Increased spot urine 5-HIAA is supportive of the diagnosis of AA in patients presenting within the first 12 h of symptom onset. Hematological parameters, especially CRP, may provide more reliable information regarding disease severity and progression. Full article

Background and Objectives: The assessment of HER2 status in invasive breast carcinomas (IBCs) is critical for determining treatment strategies. The aim of this study was to evaluate the FICTION technique as a potential method for assessing HER2 status and to compare it with the standard sequential immunohistochemistry (IHC)–in situ hybridization (ISH) assays. Materials and Methods: This study included 49 patients diagnosed with invasive breast carcinomas. HER2 status was assessed using both IHC+FISH and FICTION techniques, and the results were compared. Results: Comparative analysis demonstrated an 83.67% categorical agreement between IHC and IF using the ASCO/CAP system. The percentage of cells showing any degree of HER2 protein expression was higher with IF (73.77%) than with IHC (60.71%) (p = 0.00026). The in situ hybridization assays showed an excellent agreement, with a 90% or higher concordance. The concordance of the ASCO/CAP group classification of cases using both ISH assays (FICTION and standard FISH) was high (85, 7%). Agreement was 100% for the final classification of cases (Her2 positive/negative). Conclusions: We compared standard tests for Her2 protein expression and the gene copy number with a modified FICTION protocol. The study showed moderate agreement between IHC and IF for Her2 protein and excellent agreement between FISH and FICTION ISH for the gene copy number. Final Her2 status was unaffected by low IF IHC concordance. Optimizing the FICTION protocol could improve results. Combining protein and gene assays may enhance IBC patient stratification. Full article

Background and Objectives: The gut–liver axis plays a crucial role in the development of post-surgical infections. Surgery-induced dysbiosis can lead to increased bacterial translocation, impairing the liver’s detoxification capacity and negatively affecting surgical outcomes. Following liver surgery, approximately a third of the patients develop bacterial infections, with a high risk of bacteremia or even sepsis-related liver failure and death. The potential advantages of administering pro- or synbiotics before/after surgery remain a topic of discussion. Therefore, a systematic review of randomized clinical trials comparing patients with and without supplementation and their outcomes and effects after liver resection (LR) or liver transplantation (LT) was conducted. Materials and Methods: A computer-based search of electronic databases was conducted to gather randomized controlled trials (RCTs) that focused on probiotic/synbiotic use during the perioperative period for liver surgery patients. Two researchers independently screened the studies, extracted the data, evaluated the risk of bias, and performed a meta-analysis using RevMan Web. Results: Our research revealed 19 relevant randomized controlled studies that included a total of 1698 patients on the perioperative use of pro-/symbiotic administration in liver surgery. Eight studies were performed on liver transplantation (LT), and 11 studies were performed for liver resection (LR). The results of the meta-analysis demonstrated that the probiotic group exhibited lower rates of postoperative infectious complications (OR = 0.34; 95%CI 0.25 to 0.45; p < 0.0001), hospital stay duration (SMD = −0.13; 95%CI −0.25 to −0.00; p = 0.05), lower serum endotoxin levels (SMD = −0.39%CI −0.59 to −19; p < 0.0001), and white blood cell counts (SMD = −SMD = −0.35; 95%CI −0.56 to −0.13; p = 0.002) compared to the control group. Further, with regard to liver function, we observed significant postoperative differences in alanine aminotransferase (ALT)-levels (SMD = −0.46; 95%CI −0.63 to −0.29; p < 0.0001), aspartate aminotransferase (AST) levels (SMD = −0.53; 95%CI −0.71 to −0.34; p < 0.0001), bilirubin levels (SMD = −0.35; 95%CI −0.50 to −0.19; p < 0.0001), and international ratio (INR) levels (SMD = −0.1; 95%CI −0.12 to −0.08; p ≤ 0.0001), favoring the symbiotic group compared to the control group. Conclusions: The use of pro-/synbiotics during the perioperative period reduces the risk of postoperative infections, support postoperative liver function, and recovery and shortens hospital stays for liver surgery patients. However, they do not appear to particularly aid in inflammation reduction. Full article

Background and Objectives: Myasthenia Gravis (MG) comprises an autoimmune disorder marked by muscle weakness and fatigue. MG has been associated with comorbid conditions, including dyslipidemia (DL), which may exacerbate the clinical burden of MG and impact the overall quality of life. Materials and Methods: This systematic review and meta-analysis aimed to assess the prevalence of DL in patients with MG. Following PRISMA guidelines, a comprehensive search was conducted in the MEDLINE, Scopus, and Google Scholar databases. Primary outcomes included the pooled prevalence of DL in MG patients, and the relative risk of DL compared to healthy controls. Results: Nineteen studies involving 98,947 MG patients were analyzed. The pooled prevalence of DL was 23.64% (95% CI: 17.01–30.98). The relative risk of DL in MG patients versus controls was 1.13 (95% CI: 0.53–2.41), indicating no significant increase. Meta-regression revealed a positive correlation between DL prevalence and MG onset age (β = 0.02, p < 0.001), with a 2% rise in DL prevalence per 1-year increase in onset age. Regional subgroup analysis showed a statistical trend of higher DL prevalence in the USA (33.02%) compared to Asia (19.89%) and Europe (17.5%). Conclusions: This study found that approximately one in four MG patients has comorbid DL, with MG onset age significantly influencing DL prevalence. These findings highlight the need for personalized management strategies and evaluations (e.g., statins, LP(a) levels). Further research is warranted to elucidate the pathophysiological links between MG and DL. Full article

Background and Objectives: This scoping review aimed to identify and synthesize current evidence on the clinical applications of artificial intelligence (AI) in periodontology, focusing on its potential to improve diagnosis, treatment planning, and patient care. Materials and Methods: A comprehensive literature search was conducted using electronic databases including PubMed-MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science™ Core Collection. Studies were included if they met predefined PICO criteria relating to AI applications in periodontology. Due to the heterogeneity of study designs, imaging modalities, and outcome measures, a scoping review approach was employed rather than a systematic review. Results: A total of 6394 articles were initially identified and screened. The review revealed a significant interest in utilizing AI, particularly convolutional neural networks (CNNs), for various periodontal applications. Studies demonstrated the potential of AI models to accurately detect and classify alveolar bone loss, intrabony defects, furcation involvements, gingivitis, dental biofilm, and calculus from dental radiographs and intraoral images. AI systems often achieved diagnostic accuracy, sensitivity, and specificity comparable to or exceeding that of dental professionals. Various CNN architectures and methodologies, including ensemble models and task-specific designs, showed promise in enhancing periodontal disease assessment and management. Conclusions: AI, especially deep learning techniques, holds considerable potential to revolutionize periodontology by improving the accuracy and efficiency of diagnostic and treatment planning processes. While challenges remain, including the need for further research with larger and more diverse datasets, the reviewed evidence supports the integration of AI technologies into dental practice to aid clinicians and ultimately improve patient outcomes. Full article

Background and Objectives: Sarcopenia is a major risk factor for falls in older adults. The 2023 Korean Working Group on Sarcopenia (KWGS) introduced revised definitions, including functional sarcopenia, which considers low strength and performance despite normal muscle mass. This study investigated the prevalence of sarcopenia, severe sarcopenia, and functional sarcopenia using the KWGS criteria and their association with fall risk by sex and fall frequency. Materials and Methods: A cross-sectional analysis was conducted using data from 2061 community-dwelling Korean adults aged 70–84 years who participated in the Korean Frailty and Aging cohort study. Sarcopenia was classified based on muscle mass, grip strength, and four physical performance tests. Fall experiences in the past year were categorized as ≥1, ≥2, and ≥4 falls. Logistic regression analyses were performed separately according to sex to evaluate the association between sarcopenia definition and fall risk. Results: The prevalence of sarcopenia and severe sarcopenia was 32.9% and 10.1% in men and 21.5% and 5.0% in women, respectively. Functional sarcopenia was more prevalent in women (10.5%) than in men (5.1%). In men, sarcopenia (defined using gait speed) was associated with fall risk across all thresholds (odds ratio [OR] = 2.28 for ≥1 fall; OR = 5.64 for ≥4 falls). In women, sarcopenia (defined using gait speed) was associated with ≥1 fall (OR = 1.72), while functional sarcopenia (defined using gait speed and timed up-and-go test) was associated with frequent falls (OR = 3.79–3.87). Conclusions: The 2023 KWGS guidelines revealed sex-specific differences in the prevalence of sarcopenia and highlighted gait speed as a key predictor of fall risk in men, whereas functional sarcopenia was more prevalent in women. Limitations include the cross-sectional design and use of self-reported fall data, which may be subject to recall bias. Full article

Background and Objectives: Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of global morbidity and mortality. The cardiometabolic index (CMI) has been shown to be associated with metabolic disorders and mortality in general populations, but its role in ASCVD-specific mortality risk remains unexplored. Materials and Methods: This cohort study was based on the National Health and Nutrition Examination Survey (NHANES). Weighted Cox proportional hazards models were fitted to estimate the associations between CMI and mortality. Restricted cubic splines were used to explore nonlinear relationships. Subgroup analyses were used to investigate potential differences among specific ASCVD patients. Results: A total of 2157 patients with ASCVD were included. Over a median 83-month follow-up, 887 all-cause and 300 cardiovascular deaths occurred. Each unit increase in CMI was associated with an 11.3% increased risk of all-cause mortality (HR = 1.113, 95% CI: 1.112–1.115) and a 6.4% increased risk of cardiovascular mortality (HR = 1.064, 95% CI: 1.062–1.065). There was a nonlinear J-shaped relationship between CMI and all-cause mortality, while the risk of cardiovascular mortality increased linearly with increasing CMI. Conclusions: These findings underscore the importance of monitoring and managing CMI in patients with ASCVD in clinical practice and suggest that optimizing CMI levels may help reduce the risk of death and improve the long-term prognosis of patients. Full article

Neuropathic pain resulting from injury to the somatosensory nervous system affects approximately 6.9–10% of the general population and significantly impacts quality of life. Common presentations include burning, stabbing, tingling, or electrical sensations, occurring spontaneously or through hyperalgesia or allodynia. Treatment approaches follow a tiered system. First-line therapies include gabapentinoids (e.g., gabapentin, pregabalin), which target voltage-gated calcium channels; tricyclic antidepressants (e.g., amitriptyline, nortriptyline); and serotonin-norepinephrine reuptake inhibitors such as duloxetine. Second-line options encompass topical agents (e.g., 5% lidocaine, 8% capsaicin), opioid-like medications (e.g., tramadol, tapentadol), and adjunctive therapies including psychological therapies and lifestyle interventions. For refractory cases, third-line treatments include NMDA receptor antagonists (e.g., ketamine, dextromethorphan), cannabinoids, and botulinum toxin type A, though these have more limited clinical evidence. Procedural interventions such as spinal cord stimulation and transcutaneous electrical nerve stimulation provide alternatives when pharmacological approaches fail. Despite advances in treatment options, many patients remain undertreated, highlighting the need for individualized, multimodal approaches and continued research into the complex pathophysiology of neuropathic pain conditions. Full article

Background and Objectives: Due to the rare focus on ureteral cancer survival analyses, this study investigates post-surgery cancer-specific survival (CSS) rates, along with prognostic factors affecting these outcomes. It aims to enhance understanding of disease progression and determinants of patient survival and develop a nomogram for reference. Materials and Methods: This research undertook a retrospective analysis of ureteral cancer patients who received surgical intervention from 2010 to 2017, utilizing data from the Surveillance, Epidemiology, and End Results database. The primary endpoint was survival, with 1-, 3-, and 5-year CSS rates calculated using the Kaplan–Meier method. Initial univariate Cox proportional hazards analyses identified factors impacting survival, with those yielding a p-value under 0.05 progressing to multivariate Cox regression analysis to ascertain significant prognostic indicators. Results: The investigation encompassed 2277 patients diagnosed with ureteral cancer. CSS rates at 1, 3, and 5 years post-surgery were observed at 88.2%, 68.1%, and 60.3%, respectively. Multivariate analyses identified age, staging of tumor, node and metastasis, and the application of radiotherapy as significant prognostic indicators for CSS. Based on these factors, a post-surgical nomogram for CSS was developed. Conclusions: The survival outcomes for ureteral cancer are not yet satisfactory. Age and stage emerge as pivotal prognostic elements, significantly impacting CSS following surgery. Recognizing these factors is essential for clinicians, as they offer critical insights that inform treatment strategies and patient management. Full article

Background and Objectives: Obesity is a health condition that significantly augments the risk of several chronic diseases and is a major public health concern. In Italy, this phenomenon has highly increased in the last few decades, raising alarm about both NHS sustainability and population health. We investigate whether and to what extent obesity impacts three different categories of outcomes, namely healthcare consumption, quality of life and the presence of relevant comorbidities. Materials and Methods: We use data from the European Health Interview Survey, 2019, a micro dataset that displays more than 45,000 observations, providing detailed information on the health status and healthcare access, demographics and socioeconomic characteristics among Italian individuals aged 15 and over. We first provide a descriptive analysis of the socioeconomic gradient of obesity, and then we implement propensity score matching to detect the effects of this condition on healthcare use, quality of life and comorbidities. To the best of our knowledge, this is the first empirical paper to jointly consider the healthcare consumption, declared comorbidities and quality of life of Italian obese individuals. Results: The findings show that obese individuals consume more health services, have a lower quality of life and present a higher rate of comorbidities compared to non-obese individuals with the same observable characteristics. We also find that obesity is rooted in socioeconomic drivers, with richer and more educated individuals being less likely to present with this condition. Conclusions: The findings call for policy measures aimed at monitoring and contrasting the rising phenomenon of obesity in Italy, with a tailored approach across socioeconomic groups. Full article

Background and Objectives: Tuberculosis (TB) is one of the most common infectious diseases in developing countries. The resistance of the causative agent, Mycobacterium tuberculosis, to two or more first-line anti-TB drugs results in multidrug-resistant (MDR) TB, posing a serious challenge to the control of TB worldwide. This study was designed to determine the changes in drug resistance over time in TB strains isolated from patients in all departments of Uludağ University Hospital in western Türkiye. Materials and Methods: We retrospectively analyzed 104,598 clinical samples sent to our laboratory for the investigation of the presence of TB between 1996 and 2023. BACTEC 460 TB, BACTEC MGIT 960 culture systems and Löwenstein–Jensen medium were used for the culture of these samples. The susceptibility of M. tuberculosis complex strains grown in culture to isoniazid (INH) (0.1 μg/mL), rifampicin (RIF) (1.0 μg/mL), ethambutol (ETB) (5.0 μg/mL) and streptomycin (SM) (1.0 μg/mL) antibiotics was studied according to the manufacturer’s recommendation. Results: Out of 104,598 patient samples, 2752 (2.6%) were culture-positive, and the susceptibility test results of 1869 of these were analyzed. Of the isolates, 358 (19.2%) were found to be resistant to at least one first-line drug, i.e., INH, RIF, ETB, or SM. In addition, 2.9% were resistant to two or more first-line drugs. Conclusions: Drug susceptibility testing is essential to ensure the optimal treatment and control of drug-resistant TB strains. This study highlights the value of ongoing efforts to control tuberculosis drug resistance in the fight against this disease. Full article

Early recognition and timely treatment of sepsis and septic shock is vital. Despite appropriate management, mortality and morbidity rates remain high. In recent years, many of the research efforts have been directed towards finding novel biomarkers that would rapidly identify, classify and risk-stratify the severity of sepsis in order to achieve prompt and targeted treatment of patients with sepsis and septic shock. Among these biomarkers, adrenomedullin (ADM) in the form of the biologically active fragment (bio-ADM) and dipeptidyl peptidase 3 (DPP3) have recently been in the spotlight. The aim of this narrative review is to summarize current evidence on these two novel biomarkers regarding their clinical utility in diagnosis, prognosis, treatment monitoring and therapy guidance of sepsis and septic shock in the emergency department (ED) and in the intensive care unit (ICU) setting. Bio-ADM seems to be a promising biomarker with respect to the overall management of sepsis (diagnosis, severity prediction, prognosis and treatment monitoring and guidance). On the other hand, DPP3 appears to be useful mainly for sepsis prognosis and for predicting sepsis-induced acute kidney injury. Given their potential clinical utility in sepsis management, the use of these two novel biomarkers, in conjunction with established biomarkers and clinical scores, could lead to the application of refined integrated protocols in the ED and the ICU, which could promptly and effectively inform clinical decision-making in patients presenting with sepsis or septic shock. Full article

Background and Objectives: Ectopic pregnancy (EP) is a potentially life-threatening condition and the leading cause of maternal mortality in the first trimester. Although both surgical and medical approaches are effective, selection criteria for Methotrexate (MTX) treatment remain inconsistent across international guidelines. Additionally, limited data on long-term reproductive outcomes are available. Materials and Methods: We conducted a single-center retrospective cohort study of 107 patients diagnosed with tubal EP and treated at the Obstetrics and Gynecology Unit of the University Hospital of Parma between 2019 and 2023. MTX (50 mg/m²) was offered to patients with β-hCG < 5000 mIU/mL, sac diameter < 40 mm, and no embryonic cardiac activity or hemoperitoneum; others underwent salpingectomy. Treatment outcomes, predictors of MTX success, and fertility outcomes were analyzed. Results: Medical treatment was offered to 36 patients (33.6%), with an overall success rate of 72%: in total, 20 resolved after a single dose and 6 after a second dose. Surgical conversion was necessary in 10 patients. The remaining 71 patients (66.4%) underwent primary salpingectomy. Initial β-hCG levels and gestational age did not significantly predict MTX failure (p 0.14 and 0.73, respectively), whereas gestational sac diameter was identified as a reliable predictor of treatment success (p = 0.01). In particular, a gestational sac maximum diameter of <2 cm emerged as a positive factor for MTX success (OR 1.13, 95% CI: 1.1–1.3, p = 0.04). Among the 50 patients with follow-up data, 68% achieved a term live birth, with no significant difference between the MTX (52.9%) and surgical (75.8%) groups (p 0.12). Most of the pregnancies (90%) occurred spontaneously, while only 10% required assisted reproductive technologies. Conclusions: MTX is a safe and effective treatment for tubal EP when patients are appropriately selected. Gestational sac diameter appears to be a reliable predictor of success. Both medical and surgical treatments yielded comparable reproductive outcomes, supporting individualized care models that prioritize fertility preservation. Full article

Lichen planus (LP) is a chronic inflammatory disorder affecting approximately 1% of the population. It presents with a wide range of clinical manifestations, mainly involving the skin, mucosal surfaces, and skin appendages, and is often characterized by a relapsing course and variable response to treatment. Although several therapeutic strategies are available, many are off-label and show limited efficacy in resistant forms. Increasing evidence points to the central role of the JAK/STAT signaling pathway in the immunopathogenesis of LP, with cytokines such as interferon-gamma and interleukin-21 playing key roles in sustaining chronic inflammation. Based on this rationale, Janus kinase (JAK) inhibitors have recently been proposed as potential therapeutic agents in LP. This review explores the biological basis for their use and systematically summarizes the existing clinical evidence on the use of JAK inhibitors in cutaneous, mucosal, appendageal, and nail variants of LP. The preliminary data suggests favorable outcomes in many patients with difficult-to-treat disease, with an acceptable safety profile. Further prospective trials are needed to establish their definitive role in the management of LP. Full article

Background and Objectives: Chronic respiratory diseases, such as COPD, cystic fibrosis, and post-COVID-19, are frequently accompanied by psychological distress and physical impairment. As a non-pharmacological intervention, progressive muscle relaxation (PMR) may benefit these patients psychologically and physiologically. This systematic review aimed to evaluate the effects of PMR on anxiety, depression, fatigue, sleep quality, dyspnea, and pulmonary function in patients with COPD, CF, and COVID-19. Materials and Methods: Following PRISMA guidelines, a comprehensive search was conducted across PubMed, Scopus, Web of Science, MEDLINE, Cochrane, SpringerLink, and ClinicalTrials.gov. Eligible studies assessed PMR in adult patients with COPD, CF, or COVID-19. Psychological and physical outcomes were extracted, and methodological quality and risk of bias were evaluated using standardized tools. Results: A total of 32 studies were included in the analysis. PMR was consistently associated with reductions in anxiety, depression, fatigue, and sleep-related distress, particularly in patients with COPD and COVID-19. Some also reported improvements in dyspnea and mild pulmonary function tests, but these were more variable. Only one study evaluated PMR in patients with cystic fibrosis, providing the first clinical data for this group. Interventions were predominantly short-term, with significant variation in design, duration, and methodology, and the risk of bias was often moderate or high. Conclusions: PMR is a helpful strategy in treating chronic respiratory diseases, particularly for reducing psychological distress and improving sleep. However, the evidence is limited by methodological variations and lack of long-term follow-up. Rigorous research is needed to support clinical application, particularly in cystic fibrosis. Full article

The Phosphoinositide Specific-Phospholipase C (PI-PLC) family of enzymes plays a crucial role in various cellular processes by catalyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] into inositol 1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG), which are essential messengers mediating critical intracellular signaling pathways. Herein, we carry out a comprehensive analysis of the structure, function, regulation, and implications of the PI-PLC family enzymes in both physiological and pathological contexts. More specifically, we discuss the structural features of PI-PLCs, elucidating their conserved domains and catalytic mechanisms. Furthermore, we explore the multifaceted roles of PI-PLCs in signal transduction, cellular homeostasis, and membrane dynamics, whilst highlighting the intricate regulatory mechanisms governing their activity such as protein–protein interactions, post-translational modifications, and lipid modulation. Lastly, we assess the involvement of PI-PLCs in various diseases, such as cancer, neurological disorders, immune dysregulation, and male infertility, emphasizing their potential as therapeutic targets. Full article