Search Results (29,183)

This study examined the distribution and disease associations of non-HLA-B*27 HLA-B alleles in Romanian spondyloarthritis (SpA) patients, aiming to address the underrepresentation of Eastern European populations in immunogenetic research. Methods: We analyzed 263 HLA-B*27-negative patients from Northeastern Romania fulfilling ASAS criteria. HLA-B genotyping was performed at two-digit resolution, and allele distributions were compared with two Romanian HLA-B*27-negative control groups (n = 335 and n = 1705 cases), using chi-square testing and logistic regression. Compared to controls, HLA-B*47 (p = 0.0007) and HLA-B*54 (p = 0.0013) were significantly enriched, while HLA-B*40 was underrepresented (p = 0.0287). Notably, HLA-B*54 was observed exclusively in axial SpA. Within the cohort, both HLA-B*13 and HLA-B*57 alleles were associated with psoriasis, while HLA-B*37 and HLA-B*41 alleles were clustered within the reactive arthritis group. The HLA-B*35 and HLA-B*18 alleles were the most frequently observed alleles across most clinical phenotypes. When comparing the frequency of HLA-B associations, the most common genotypes among SpA patients were B*08-B*18, B*13-B*35, and B*35-B*51. Notably, B*08-B*18 was more frequent in patients with radiographic sacroiliitis grade ≥ 2, while B*35-B*51 was more frequent in those with confirmed systemic inflammation, as indicated by elevated CRP or ESR levels. Analysis of peptide-binding patterns revealed a cluster of risk alleles, HLA-B*08, B*18, B*35, B*40, and B*54, sharing similar features, distinct from the canonical profile of B*27. These findings highlight the contribution of non-B*27 HLA-B alleles to SpA susceptibility in an Eastern European population and support the notion that HLA-B*27-negative SpA may represent a distinct clinical and immunological entity, driven by alternative pathogenic mechanisms. They also emphasize the importance of population-specific immunogenetic profiling and support expanding genetic characterization in HLA-B*27-negative patients. Full article

Background: Renal cell carcinoma (RCC) is a common malignancy with a rising global incidence. While cytoreductive nephrectomy (CRN) was historically a cornerstone in the management of metastatic RCC (mRCC), its role has been questioned following pivotal trials such as CARMENA and SURTIME. With the advent of immune checkpoint inhibitors (ICIs) and targeted therapies, the contemporary relevance of CRN coupled with first-line immunotherapy and targeted therapy combination regimens warrants re-evaluation. Methods: This retrospective cohort study utilized the TriNetX research network to identify patients aged 18–90 years diagnosed with mRCC between 2005 and 2024 who received first-line systemic therapies. Patients were stratified into two cohorts based on receipt of CRN status within one year of diagnosis. Propensity score matching (1:1) was done to adjust baseline characteristics. Kaplan–Meier survival analysis and Cox proportional hazards modeling were used to compare five-year overall survival between the groups. Results: Among 5960 eligible patients, 1776 (888 CRN matched to 888 who did not) formed the cohort of analysis. The CRN group demonstrated significantly higher five-year survival (57.7% vs. 45.0%, p < 0.0001) with a hazard ratio of 1.56 (95% CI: 1.33–1.83). Subgroup analyses showed consistent survival benefits across all four NCCN-recommended first-line regimens—Axitinib + Pembrolizumab: 64.0% (CRN) vs. 53.3% (no CRN), p = 0.01; Cabozantinib + Nivolumab: 50.1% vs. 40.4%, p = 0.004; Lenvatinib + Pembrolizumab: 37.4% vs. 22.8%, p = 0.012; Nivolumab + Ipilimumab: 56.4% vs. 46.1%, p = 0.005. Conclusions: In the era of modern immunotherapy and targeted agents, CRN remains associated with improved survival in patients with mRCC receiving NCCN-recommended first-line regimens. These findings support the continued evaluation of CRN as a component of multimodal therapy, particularly in patients with favorable risk profiles. Full article

Background/Objectives: Orbital reconstruction remains one of the most demanding procedures in maxillofacial surgery. It requires not only precise anatomical knowledge but also poses multiple intraoperative challenges. Limited surgical visibility—especially in transconjunctival or transcaruncular approaches—demands exceptional precision from the surgeon. At the same time, the complex anatomical structure of the orbit, its rich vascularization and innervation, and the risk of severe postoperative complications—such as diplopia, sensory deficits, impaired ocular mobility, or in the most serious cases, post-traumatic blindness due to nerve injury or orbital compartment syndrome—necessitate the highest level of surgical accuracy. In this context, patient-specific implants (PSIs), commonly fabricated from zirconium oxide or ultra-high-density polyethylene, have become invaluable. Within CAD-based reconstructive planning, especially for orbital implants, critical factors include the implant’s anatomical fit, passive stabilization on intact bony structures, and non-interference with orbital soft tissues. Above all, precise replication of the orbital dimensions is essential for optimal clinical outcomes. This study compares the morphological accuracy of orbital structures based on anthropometric measurements from 3D models generated from fan-beam computed tomography (FBCT) and cone-beam computed tomography (CBCT). Methods: A cohort group of 500 Caucasian patients aged 8 to 88 years was analyzed. 3D models of the orbits were generated from FBCT and CBCT scans. Anthropometric measurements were taken to evaluate the morphological accuracy of the orbital structures. The assessed parameters included orbital depth, orbital width, the distance from the infraorbital rim to the infraorbital foramen, the distance between the piriform aperture and the infraorbital foramen, and the distance from the zygomatico-orbital foramen to the infraorbital rim. Results: Statistically significant differences were observed between virtual models derived from FBCT and those based on CBCT in several key parameters. Discrepancies were particularly evident in measurements of orbital depth, orbital width, the distance from the infraorbital rim to the infraorbital foramen, the distance between the piriform aperture and the infraorbital foramen, and the distance from the zygomatico-orbital foramen to the infraorbital rim. Conclusions: The statistically significant discrepancies in selected orbital dimensions—particularly in regions of so-called thin bone—demonstrate that FBCT remains the gold standard in the planning and design of CAD/CAM patient-specific orbital implants. Despite its advantages, including greater accessibility and lower radiation dose, CBCT shows limited reliability in the context of orbital and infraorbital reconstruction planning. Full article

Background/Objectives: Osteoporosis remains a leading cause of morbidity in postmenopausal women, yet many high-risk individuals remain undiagnosed or untreated. This study aimed to assess the prevalence of osteoporosis and osteopenia, treatment patterns, and skeletal fragility indicators in a large cohort of postmenopausal women undergoing DXA screening. Methods: We analyzed data from 1669 postmenopausal women aged 40–89 years who underwent DXA evaluation. BMD status was categorized as normal, osteopenia, or osteoporosis. Treatment status was classified based on active antiosteoporotic therapy, calcium/vitamin D supplementation, hormonal therapy (historical use), or no treatment. Logistic regression models were used to explore independent predictors of osteoporosis and treatment uptake. Results: A total of 45.0% of women had osteoporosis and 43.5% had osteopenia. Despite this, 58.5% of the population, over half of women with osteoporosis, were not receiving any active pharmacologic treatment. Bisphosphonates were the most prescribed therapy (17.9%), followed by calcium/vitamin D supplements (20.6%). A prior history of fragility fractures and radiological bone lesions were significantly associated with lower BMD (p < 0.05). Historical hormone replacement therapy (HRT) use was not associated with current BMD (p = 0.699), but women with HRT use reported significantly fewer fractures (p < 0.001). In multivariate analysis, later menopause age and low BMD status predicted higher odds of receiving active treatment. Conclusions: Our findings highlight a substantial care gap in osteoporosis management, with treatment primarily initiated reactively in more severe cases. Improved screening and earlier intervention strategies are urgently needed to prevent fractures and reduce the long-term burden of osteoporosis. Full article

Background: This cross-sectional study examined the association between body mass index (BMI) and executive function (EF) in older adults, with a focus on the moderating role of attitudes toward own aging (ATOA). Method: A total of 431 community-dwelling elderly individuals from Yakumo Town and Kyoto City, Japan, participated between 2023 and 2024. EF was assessed using the Digit Cancellation Test (D-CAT), and ATOA was measured via a validated subscale of the Philadelphia Geriatric Center Morale Scale. Results: Multiple linear regression analyses adjusted for demographic and health covariates revealed a significant interaction between BMI and ATOA in the younger-old cohort. Specifically, higher BMI was associated with lower executive function only in individuals with lower ATOA scores. No such association was observed in those with more positive views on aging. Conclusions: These results indicate that positive psychological constructs, particularly favorable self-perceptions of aging, may serve as protective factors against the detrimental cognitive consequences of increased body mass index in younger-old populations. Full article

Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice. Full article

Background/Objective: This study explores a novel approach for diagnosing common middle ear pathologies using Pressure-Less Acoustic Immittance (PLAI™), a non-invasive alternative to conventional tympanometry. Methods: A total of 516 ear measurements were collected and stratified into three age groups: 0–3, 3–12, and 12+ years, reflecting key developmental stages. PLAI™-derived acoustic parameters, including resonant frequency, peak admittance, canal volume, and resonance peak frequency boundaries, were analyzed using Random Forest classifiers, with SMOTE addressing class imbalance and SHAP values assessing feature importance. Results: Age-specific models demonstrated superior diagnostic accuracy compared to non-stratified approaches, with macro F1-scores of 0.79, 0.84, and 0.78, respectively. Resonant frequency, ear canal volume, and peak admittance consistently emerged as the most informative features. Notably, age-based stratification significantly reduced false negative rates for conditions such as Otitis Media with Effusion and tympanic membrane retractions, enhancing clinical reliability. These results underscore the relevance of age-aware modeling in pediatric audiology and validate PLAI™ as a promising tool for early, pressure-free middle ear diagnostics. Conclusions: While further validation on larger, balanced cohorts is recommended, this study supports the integration of machine learning and acoustic immittance into more accurate, developmentally informed screening frameworks. Full article

Background/Objectives: Cognitive impairment in older adults has emerged as a growing public health concern, particularly in relation to COVID-19 infection and its associated neuropsychiatric symptoms. The identification of modifiable risk factors may contribute to the development of targeted preventive strategies. This study aimed to assess predictors of cognitive impairment in older adults with and without recent SARS-CoV-2 infection. Methods: A prospective cohort study was conducted from June 2023 to March 2024 at a tertiary hospital in western Mexico. Adults aged 65 years or older with confirmed SARS-CoV-2 infection within the previous six months, along with uninfected controls, were enrolled. Cognitive function (Mini-Mental State Examination), depression (PHQ-9), anxiety (Geriatric Anxiety Inventory), insomnia (Insomnia Severity Index), functional status (Katz Index and Lawton–Brody Scale), and laboratory markers were evaluated at baseline, three months, and six months. The primary outcome was cognitive impairment at six months. Independent predictors were identified using a multivariable generalized linear mixed-effects model. Results: Among the 111 participants, 20 (18.8%) developed cognitive impairment within six months. Low serum magnesium (adjusted risk ratio [aRR] 2.73; 95% CI 1.04–7.17; p = 0.041) and depression (aRR 5.57; 95% CI 1.88–16.48; p = 0.002) were independently associated with a higher risk. A significant synergistic among COVID-19, depression, and hypomagnesemia was observed (RR 44.30; 95% CI 9.52–206.21; p < 0.001), corresponding to the group with simultaneous presence of all three factors compared to the group with none. Conclusions: Depression and hypomagnesemia appear to be independent predictors of cognitive impairment in older adults with recent COVID-19 infection. These findings suggest potential targets for prevention and support the implementation of routine neuropsychiatric and biochemical assessments in this population. Full article

Background: Catheter ablation of the arrhythmogenic substrate has emerged as a promising therapeutic strategy for symptomatic Brugada syndrome (BrS). However, high-quality comparative evidence against conventional implantable cardioverter-defibrillator (ICD)-based management remains limited. Objectives: This meta-analysis aimed to evaluate the efficacy of catheter ablation in reducing ventricular fibrillation (VF) recurrence in symptomatic BrS compared to standard therapy. Methods: Medline, Cochrane Library, and Scopus were systematically searched through 1 June 2025. Study selection, data extraction, and quality assessment were independently conducted by three reviewers. Random-effects meta-analyses were used to pool risk estimates. Results: Three studies (two randomized controlled trials, one observational cohort; 130 symptomatic BrS patients) were included. Over a median follow-up of 3.9 years, catheter ablation was associated with a significantly lower risk of VF recurrence compared to standard therapy [risk ratio (RR) = 0.19, 95% confidence interval (CI) = (0.06, 0.60); I² = 36%, p for heterogeneity = 0.21], with no deaths reported in any group. A sensitivity analysis restricted to randomized trials confirmed similar findings in favor of ablation. Conclusions: Catheter ablation was associated with reduced VF recurrence compared to ICD therapy alone, supporting its potential role as first-line treatment in symptomatic BrS or as an alternative for patients who decline ICD implantation. Full article

Background: HIV-associated neurocognitive disorders (HANDs) continue to be a significant concern, despite the advancements in prognosis achieved through Combination Antiretroviral Therapy (cART). Neuropsychological assessment, recommended by international guidelines for HANDs diagnosis, can be resource-intensive. Brief screening tools, like the International HIV Dementia Scale (IHDS) and the Montreal Cognitive Assessment (MoCA), are crucial in facilitating initial evaluations. This study aims to assess the Italian IHDS (IHDS-IT) and evaluate its sensitivity and specificity in detecting cognitive impairment in HIV patients. Methods: This cross-sectional study involved 294 patients aged ≥30 years, evaluated at the Immunology Unit of the University of Cagliari. Cognitive function was assessed using the MoCA and IHDS. Laboratory parameters, such as CD4 nadir, current CD4 count, and HIV-RNA levels, were also collected. Statistical analyses included Spearman’s correlation, Receiver Operating Characteristic analysis, and the Youden J statistic to identify the optimal IHDS-IT cut-off for cognitive impairment detection. Results: The IHDS and MoCA scores showed a moderate positive correlation (Spearman’s rho = 0.411, p < 0.0001). ROC analysis identified an IHDS-IT cut-off of ≤9, yielding an Area Under the Curve (AUC) of 0.76, sensitivity of 71.7%, and specificity of 67.2%. At this threshold, 73.1% of patients with MoCA scores below 23 also presented abnormal IHDS scores, highlighting the complementary utility of both cognitive assessment instruments. Conclusions: The IHDS-IT exhibited fair diagnostic accuracy for intercepting cognitive impairment, with a lower optimal cut-off than previously reported. The observed differences may reflect this study cohort’s demographic and clinical characteristics, including advanced age and long-lasting HIV infection. Further, longitudinal studies are necessary to validate these findings and to confirm the proposed IHDS cut-off over extended periods. Full article

Background: RSV remains a leading cause of infant hospitalization worldwide, and the recently approved nirsevimab could represent an effective and safe prophylactic strategy to prevent severe infections in the general neonatal population. Objectives: We conducted a retrospective observational monocentric pilot study in a mixed preterm/term birth cohort to add real-world evidence of the efficacy and safety of nirsevimab in preventing severe RSV infection. Methods: We included a total of 2035 consecutive infants admitted to the Neonatal Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy, from November 2024 to April 2025. We evaluated 30-day safety profiles and season-wide RSV infection rates, and the outcomes were also compared to newborns’ birth rate in the two previous seasons (2022–2023 and 2023–2024). Results: After the introduction of nirsevimab, a lower RSV infection rate was reported compared to previous seasons, and no adverse effects were observed. Compared to previous seasons, the clinical outcomes were more favorable, as only one unvaccinated neonate with RSV infection required invasive ventilation. Conclusions: In this real-world analysis, we demonstrated a good short-term safety profile of nirsevimab, as well as a potentially high efficacy in the general neonatal population with lower RSV infection incidence. However, future studies are needed to better assess its long-term safety and season-wide efficacy. Full article

Background: Asprosin is a relatively recently discovered glucogenic adipokine secreted during fasting that plays an important role in various biochemical processes in the body, including those connected with obesity and insulin resistance. The aim of this exploratory study was to investigate the associations between selected hormonal, anthropometric, and lifestyle-related parameters and serum asprosin concentration. As studies concerning fertility and asprosin have so far been limited to men or women with PCOS, its role in the general female population remains largely unexplored. The direction of this exploration was thus pointed toward possible connections with female fertility. Methods: The case-control study group included 56 women of reproductive age (25–42 years), who were patients of the Reproductive Health Clinic and the Clinic of Endocrinology, Diabetology, and Internal Medicine of the Medical University of Białystok, Poland. The levels of selected hormones, including anti-Müllerian hormone (AMH), estradiol, sex hormone-binding globulin (SHBG), and testosterone, body composition parameters, and a lifestyle parameter—night fasting duration—were assessed to test their associations with serum asprosin concentration. Results: A weak negative correlation was found between AMH level and serum asprosin concentration, suggesting a potential link between asprosin and ovarian reserve. Furthermore, a moderate positive correlation was found between the percentage of total body water (TBW) and serum asprosin concentration. No significant associations were observed between the levels of the other tested hormones and serum asprosin concentration, or between body composition parameters or night fasting duration and serum asprosin concentration. The multivariate model designed in the study shows that AMH, TBW, and night fasting duration explain 23.4% of asprosin variability. Conclusions: Although the nature of the study is exploratory, the findings indicate that the role of asprosin in the female population—particularly its role in fertility—requires further research. Not only is the number of available studies on asprosin insufficient, but the results of this study partly contradict what is known about the hormone from previous studies, which were largely performed with male cohorts. In addition, the results of this study suggest that asprosin may indeed be involved in mechanisms related to female fertility, particularly those connected with ovarian reserve. Nevertheless, studies performed in larger, more homogeneous populations are necessary to confirm the role of asprosin in women, including its association with female fertility. Full article

Aim: Antibiotic de-escalation (ADE) is essential, but appears to be underperformed although being possible, which we refer to as a ‘missed opportunity’. We aimed to analyze the ADE missed opportunities in Gram-negative bloodstream infections (BSIs) in a setting with a high antimicrobial resistance profile. Methods: A retrospective, two-centered cohort study was performed from 1 January 2018 to 30 June 2019, including adults with mono- or polymicrobial Gram-negative BSIs. All ADE episodes and 30-day mortality were noted. Results/Discussion: Out of 273 BSIs (43 ADE vs. 230 no-ADE episodes), 101 were considered a ‘missed’ opportunity of ADE (36.9%, 101/273). In multivariate analysis, ADE opportunities were missed 4.4 times more (OR = 4.4; 95% CI 1.24–15.9) in the presence of hematological malignancy and 6.2 times more (OR = 6.2; 95% CI 1.76–22.2) in ESBL. Contrary to this, ADE opportunities were missed 0.24 times less (OR = 0.24; 95% CI 0.09–0.61) among patients with E. coli BSIs, and 0.17 less (OR = 0.17; 95% CI 0.05–0.67) if ertapenem was used as an empirical agent. The ADE missed opportunity group had a higher mortality rate, which is statistically significant in univariate analysis, but not in multivariate analysis. Conclusion: The presence of ESBL and hematological malignancy were the significant barriers to appropriate ADE practice in our study. A good stewardship program must address physician hesitation in ADE practice. Full article

Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic review aimed to analyze the study design, characteristics, and timing of the treatments administered—including the type of systemic chemotherapy, intraperitoneal agents used in PIPAC, and interval between administrations—as well as the clinical outcomes, safety profile, and overall methodological quality of the available literature on bidirectional treatment for peritoneal metastases. Methods: A systematic literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to April 2025. Studies were included if they reported clinical outcomes of patients undergoing bidirectional treatment. Data extraction focused on survival, response assessment (PRGS, PCI), adverse events, systemic and intraperitoneal regimens, treatment interval, and study methodology. Results: A total of 22 studies involving 1015 patients (742 treated with bidirectional therapy) were included. Median overall survival ranged from 2.8 to 19.6 months, with the most favorable outcomes observed in gastric and colorectal cancer cohorts. PRGS improvement after multiple PIPAC cycles was reported in >80% of evaluable cases. High-grade adverse events (CTCAE ≥ 3) occurred in up to 17% of patients in most studies, with only one study reporting treatment-related mortality. However, methodological quality was generally moderate, with considerable heterogeneity in treatment protocols, response criteria, systemic regimens, and toxicity attribution. Conclusions: Bidirectional therapy with PIPAC and systemic chemotherapy appears to be a feasible and potentially effective strategy for selected patients with peritoneal metastases. Despite encouraging outcomes, definitive conclusions are limited by the retrospective nature and heterogeneity of available studies. Prospective standardized trials are needed to confirm efficacy, clarify patient selection, and optimize treatment protocols. Full article

As the body of knowledge on feline mammary tumors (FMTs) continues to grow, their histological classification and grading systems have undergone revisions and updates to better reflect the biological behavior of these tumors. In this review, the historical evolution of these frameworks is traced and later revisited in the context of their prognostic relevance. Numerous studies have investigated clinicopathological prognostic factors in feline mammary carcinomas (FMCs); however, the heterogeneity in assessment methods, inclusion criteria for survival analysis, and the clinical endpoints considered can often complicate direct comparisons across different studies and may contribute to seemingly conflicting results. Furthermore, the small cohort size of many studies limits the robustness and transferability of their findings. This paper provides an updated overview of the epidemiological, clinical, and pathological prognostic factors of these tumors, while also highlighting current challenges, methodological limitations, and areas for future improvement. Full article