Search Results (5,575)

Background: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) were historically considered contraindicated in severe aortic stenosis (AS) due to theoretical haemodynamic risks. Contemporary evidence increasingly challenges this paradigm, yet data on preoperative use and postoperative outcomes remain limited. We examined the association between preoperative ACEi/ARB use and mortality following aortic valve replacement. Methods: We conducted a retrospective cohort study of 198 consecutive patients undergoing transcatheter (TAVI) or surgical aortic valve replacement (SAVR) at a single tertiary centre between May 2020 and March 2025. Complete one-year follow up was available for 185 patients (93%). The primary outcome was one-year all-cause mortality. Multivariable logistic regression adjusted for age, sex, hypertension, diabetes, LVEF, and procedure type. Results: Of 198 patients, 80 (40%) were receiving ACEi/ARB therapy preoperatively. ACEi/ARB users had a higher prevalence of hypertension (82% vs. 53%, p < 0.001) and diabetes (48% vs. 27%, p = 0.005) but similar age, valve area, and ejection fraction. Unadjusted one-year mortality was lower in the ACEi/ARB group (7% vs. 19%; odds ratio [OR] 0.33, 95% CI 0.12–0.91, p = 0.030). After multivariable adjustment for confounders including age, diabetes, and hypertension, the association did not reach statistical significance (adjusted OR 0.33, 95% CI 0.10–1.12, p = 0.075). Among diabetic patients, unadjusted one-year mortality was numerically lower in the ACEi/ARB group (12% vs. 35%, p = 0.038); however, six subgroup comparisons were performed and this result would not survive Bonferroni correction (threshold p < 0.008). This exploratory finding should be interpreted with caution given the small sample size and absence of adjustment for confounders. Conclusions: Preoperative ACEi/ARB use was associated with lower unadjusted one-year mortality, but this association did not reach statistical significance after multivariable adjustment and residual confounding cannot be excluded. ACEi/ARB use was not associated with increased mortality in this cohort. These hypothesis-generating findings from a single-centre observational study require confirmation in adequately powered prospective trials. Full article

The presence of microplastics (<5 mm) has become a major threat to marine ecosystems and the organisms inhabiting them. This issue affects a wide range of animals, including commercially important marine fish, whose ingestion of microplastics can cause mechanical and metabolic damage. This study aimed to characterize the main types of microplastic-like particles ingested by Centropomus viridis, Cynoscion othonopterus, Pomadasys macracanthus, Diapterus peruvianus, Lutjanus colorado, and Scomberomorus sierra, important commercial fish species in northwestern Mexico. Four sampling events were conducted over an annual cycle (November to August) in the lagoon and insular systems of Navachiste and Ohuira, Sinaloa, Mexico (RAMSAR sites 1826 and 2025). A total of 556 individuals were captured, and their stomach contents were analyzed using stereoscopic microscopy. Systematic sediment sampling was also performed at each capture site (El Coloradito, El Caracol, El Huitussi, El Aparecido, El Cerro Cabezón, Topolobampo, El Cerro Partido, and El Tortugo) by examining the upper 30 cm of sediment to ensure representativeness of the particle inventory. Four of the six analyzed species (C. viridis, C. othonopterus, P. macracanthus, and D. peruvianus) contained microplastic-like particles (MP-p), totaling 163 items, with an average ingestion rate of 0.29 items individual⁻¹. The omnivorous species D. peruvianus showed the highest ingestion (0.52 items individual⁻¹; 0.0029 items g⁻¹ wet weight). Five categories of MP-p were distinguished based on morphology and fluorescence; however, their polymeric identity cannot be confirmed without spectroscopic analyses. Sediment results showed that most microplastic-like fragments occurred at site 2025 during autumn, spring, and summer, while levels at site 1826 did not differ significantly. This study provides the first evidence of microplastic contamination in these fish species and in this region of northwestern Mexico. Full article

Background/Objectives: The medial meniscus is crucial for load transmission and knee stability. Meniscal tears disrupt joint biomechanics, increasing the risk of cartilage degeneration. However, few studies have quantitatively compared how different tear types affect stress and contact mechanics using finite element analysis (FEA). This study aims to analyze stress distributions for various meniscal tear types and develop a predictive model for meniscal stress behavior. This study investigates how stress distributions differ between healthy and torn medial menisci under identical loading conditions. The study examines which meniscal tear type produces the highest stress concentrations. The effects of different tear types on penetration, gap formation, pressure distribution, and sliding distance at the meniscus interface are also analysed. Materials and Methods: The FEA model of the knee joint, including femoral and tibial cartilage and the medial meniscus, was developed. Simulations were conducted for a healthy meniscus and for menisci with radial, horizontal and complex tears. Stress, penetration, gap, pressure, and sliding distance were calculated, and a mathematical model describing their relationships was established. Results: All torn menisci exhibited significantly higher stresses than the healthy meniscus (p < 0.001). Radial tears generated the highest stress concentrations (p < 0.001). Pressure was mainly influenced by meniscal geometry, while the gap remained nearly constant. Penetration increased slightly (p < 0.05). The predictive model demonstrated a strong correlation between meniscal stress and interface parameters (R² > 0.9). In a healthy meniscus, stress distribution is homogeneous (≈26 MPa). Stress concentration increases depending on the tear type: limited in a horizontal tear (≈26.5 MPa), significant in a vertical tear (≈30.8 MPa), and highest in a radial tear (≈40.6 MPa). These results indicate that as the tear progresses, the load-bearing capacity of the meniscus decreases, and stresses concentrate at the tear edges. Conclusions: Meniscal tears, especially radial ones, substantially alter knee biomechanics and elevate tissue stress. These biomechanical insights highlight the importance of early diagnosis and targeted rehabilitation strategies to prevent further cartilage damage and osteoarthritis progression. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is increasingly observed in patients undergoing supracricoid laryngeal surgery; however, the impact of postoperative anatomical changes on sleep-disordered breathing remains insufficiently characterized. This pilot study aimed to assess the incidence and severity of OSA after Open Partial Horizontal Laryngectomy type II (OPHL II) and to evaluate correlations between polysomnographic parameters and radiologic measurements of the neolarynx. Methods: A prospective observational cohort study was conducted on ten patients who underwent OPHL II between 2019 and 2024 and were evaluated at least one year postoperatively. The sample size was determined using a conservative estimate appropriate for a pilot prospective study, which required a long postoperative follow-up period of at least one year. All patients completed Stop-Bang, Berlin, and Epworth questionnaires and underwent overnight polysomnography. Cervical CT scans were used to measure airway length to the vocal cords (ALVC), supralaryngeal tract horizontal (SVTH) and vertical (SVTV) segments, and the base-of-tongue–to–cervical-body distance (BTCB). Results: OSA was detected in all patients: 40% mild, 30% moderate, and 30% severe. Mean AHI was 25.5 ± 18.9 events/h, and OSA severity strongly correlated with AHI (rho = 0.94; p < 0.0001). Among radiologic parameters, SVTV showed a positive correlation with OSA severity (rho = 0.82; p = 0.0035), while BTCB demonstrated a significant negative correlation (rho = −0.71; p = 0.0207). No significant associations were found for ALVC or SVTH. Conclusions: Supracricoid laryngectomy produces anatomical changes that predispose patients to OSA. Radiologic metrics—particularly SVTV and BTCB—appear to be meaningful predictors of OSA severity. A multidisciplinary approach is essential for early diagnosis and management. Due to the small number of patients enrolled larger multicenter studies are needed to confirm these findings and define radiologic criteria associated with postoperative OSA. Full article

Background: Outdoor time in early childhood education and care (ECEC) settings provides important opportunities for children’s physical activity. Evidence is limited on whether different organizational outdoor conditions influence not only activity intensity but also the contextual characteristics of children’s movement. Methods: An observational study was conducted using the Observational System for Recording Physical Activity in Children—Preschool Version (OSRAC-P). The study was conducted in two public ECEC centers. Not all children were observed across all three conditions due to the field-based design. A total of 7440 observation intervals were analyzed from preschool children across three outdoor conditions (structured educator-led physical activity, outdoor free play, and outdoor free play with additional portable equipment) using a momentary time-sampling protocol (10 s observation + 50 s recording), resulting in one interval per minute. Physical activity intensity, activity type, equipment use, and social context were coded. Contextual differences were analyzed using chi-square tests with standardized residuals, and activity intensity using linear mixed-effects models. Results: No significant differences were found between outdoor conditions in physical activity intensity, sedentary behavior, and moderate-to-vigorous physical activity (all p > 0.05). About one-third of the variance in activity intensity was attributable to individual differences between children (ICC ≈ 33%). Differences were observed in contextual characteristics. Structured activity involved more locomotor activities and greater adult involvement, with 49.4% of intervals occurring in groups with an educator present. Free play with portable equipment showed more manipulative activities, greater equipment use, and mostly peer interactions without adult presence (55.5%), while free play without additional equipment involved more stationary behavior and activities without equipment (46.9%). Conclusions: Although physical activity intensity did not differ across conditions, the structure, material context, and social organization of children’s activity varied, highlighting the practical importance of intentionally combining different outdoor activity formats to support diverse movement patterns in ECEC settings. Full article

Background: Cutaneous adverse events (cAEs) are among the most frequent immune-related toxicities associated with immune checkpoint inhibitors (ICIs). Previous clinical trials have reported higher rates of dermatologic toxicity with anti-CTLA-4 agents compared to Programmed Cell Death (PD-1)/ Programmed Cell Death-1 Ligand (PD-L1) inhibitors. However, real-world data may differ due to evolving clinical experience and improved AE management strategies. Methods: We conducted a retrospective analysis of patients treated with ICIs to assess the incidence and severity of cAEs —specifically rash and pruritus—across different treatment regimens and PD-L1 expression subgroups, 285 patients treated with ICIs at Soroka Medical center during the years August 2018–November 2025. Results: Regarding dermatologic toxicity, 57 out of 285 patients (20%) experienced a rash. Among them, 46 patients (16% of total; 81% of those with rash) had grade 1, 7 patients (2% of total; 12% of those with rash) had grade 2, and 4 patients (1% of total; 7% of those with rash) had grade 3 reactions. No grade 4 or life-threatening cases were observed. Additionally, 47 patients (16.5%) developed pruritus, all grade 1–2. When stratified by treatment type, PD-L1 expression and the occurrence of immune-related adverse events, specifically rash and pruritus, were significantly associated with survival outcomes (p < 0.001). Patients with expressions of PD-L1 ≥1% had longer median overall survival (34.0 months) compared to those with expressions of PD-L1 < 1% (20.0 months), and longer progression-free survival (22.0 vs. 13.0 months). When considering rash, overall survival ranged from 19.0 months (PD-L1 < 1% with rash) to 36.0 months (PD-L1 ≥1% without rash), and progression-free survival ranged from 12.0 to 27.0 months. The presence of pruritus was associated with the most favorable outcomes, with median overall survival reaching 48.0 months and progression-free survival 31.0 months in patients with PD-L1 ≥1% and pruritus. All comparisons showed statistically significant differences (p < 0.001). Conclusion: These findings highlight that higher PD-L1 expression and the presence of immune-related adverse events—particularly pruritus—may serve as important prognostic indicators and could help inform personalized treatment strategies. The incidence and severity of cAEs in our study were consistent with prior clinical trials. The low frequency of grade ≥ 3 events may reflect increased familiarity with ICIs, leading to earlier recognition of adverse events, better patient education, and more effective management of skin toxicities. Full article

Background/Objectives: Perioperative blood transfusion (BTF) remains controversial regarding its impact on oncological outcomes in colorectal cancer (CRC). This study aimed to evaluate the association between BTF, transfusion volume, and long-term prognosis in CRC patients undergoing radical resection. Methods: We conducted a retrospective cohort study of 1777 CRC patients who underwent radical surgery at the Fourth Hospital of Hebei Medical University between December 2007 and April 2015. Propensity score matching (PSM) was applied to minimize selection bias between BTF and non-BTF groups. Logistic regression identified factors associated with BTF receipt. Cox proportional hazards models assessed the association between BTF and 5-year overall survival (OS). X-tile analysis determined optimal cut-off values for transfusion volume stratification. Results: Among 1777 patients, 729 (41.02%) received BTF. After PSM, 524 well-matched pairs showed balanced baseline characteristics. Intestinal obstruction was independently associated with BTF requirement (p < 0.001). The BTF group demonstrated significantly inferior 1-, 3-, and 5-year OS compared with non-BTF groups in both overall and PSM cohorts (all p < 0.01). Multivariate Cox analysis identified BTF as an independent adverse prognostic factor (HR = 1.44, 95% CI 1.09–1.89, p = 0.01). X-tile analysis stratified patients into non-BTF, small-volume (≤4 units), and massive-volume (>4 units) groups. Massive-volume transfusion showed the poorest survival outcomes (p < 0.0001) and was independently associated with worse OS (HR = 1.61, 95% CI 1.18–2.20, p = 0.003). Supplementary analyses indicated that no independent association was observed between survival outcomes and either preoperative inflammatory markers or the specific timing and type of transfusion. Conclusions: BTF, particularly when exceeding 4 units, independently predicts inferior long-term survival in CRC patients following radical resection. These findings support the implementation of restrictive transfusion strategies in perioperative CRC management. Given its retrospective observational design, this study shows an association but does not establish causality, and our findings should be interpreted in light of the aforementioned limitations. Full article

Background/Objectives: Autoimmune thyroiditis affects physical and cognitive development in children. Therefore, early detection can prevent symptoms that could lead to lifelong changes. Autoimmune thyroiditis can frequently accompany type 1 diabetes (T1DM) and celiac disease (CD). The goal in this study is to evaluate its usability as a screening method by assessing thyroid elasticity in children with negative thyroid autoantibodies and T1DM or CD. Methods: This cross-sectional, case–control, single-center study was conducted with children who had applied to the Pediatrics outpatient clinic of Kayseri City Education and Research Hospital (Turkey). The study included three groups of cases (T1DM, CD and control). The value of the shear wave elastography (SWE) color map was recorded in kPa. Comparisons between two independent groups were conducted using either Student’s t-test or the Mann–Whitney U-test, while categorical variables were analyzed with the Chi-square test. A correlation analysis was conducted to evaluate the relationship between the variables. Results: The study cohort comprised 185 children, of whom 71 had T1DM, 54 had CD, and 60 constituted the healthy control group. The participants ranged in age from 4 to 17.9 years, with a mean age of 11.4 ± 3.8 years. The gender distribution did not differ significantly between the groups. Anti-thyroid peroxidase (TPOAb) levels did not differ significantly between the groups (p = 0.894). Thyroid volume or standard deviation score did not differ significantly between the groups. Corresponding SWE values in the T1DM, CD and control groups were 7.7 (6.0–9.3), 5.9 (5.2–7.9) versus 7.1 (6.0–9.6), respectively (p = 0.002). Correlations were significantly associated between SWE scores and anti-thyroglobulin (TgAb), thyroid volume, mean hemoglobin A1c (HbA1c), and time elapsed from a diagnosis of CD. Conclusions: The SWE scores were observed to be higher in children with T1DM compared to those with CD. Full article

Background: Malignant salivary gland tumors represent a highly diverse group of neoplasms, their heterogeneity likely arising due to variable origin in different tissue components. Emerging evidence suggests that SOX-2 and EZH-2 play critical roles in salivary gland carcinogenesis, being related to tumor cell stemness potential, along with accelerated tumor progression and unfavorable clinical outcomes. The aim of this study was to assess the association between SOX-2 and EZH-2 expression, survival parameters, and tumors’ pathological characteristics in a group of patients with primary epithelial malignant salivary gland tumors (MSGTs) and to evaluate their value as diagnostic and prognostic markers. Methods: Our study group comprised 104 patients with primary epithelial MSGTs diagnosed in “Sf. Spiridon” County Hospital, Iasi, over a period of fifteen years. Pathological parameters and survival evaluation, along with SOX-2 and EZH-2 immunohistochemistry assessment and scoring, were conducted, and the associations between different parameters were analyzed. Results: High SOX-2 immunoexpression was significantly associated with lymphatic invasion (LY) (p = 0.003), pT stage (p = 0.010), histological tumor type (p = 0.003), and tumor grading (p = 0.037), while high EZH-2 immunoexpression was significantly associated with perineural invasion (PnI) (p < 0.001), vascular invasion (p = 0.038), LY (p = 0.001), tumor grading (p = 0.002), and pathological extranodal extension (pENE) (p = 0.018). The tumors with high SOX-2 and EZH-2 expressions were associated with a reduced overall survival (OS) (p = 0.013 and p = 0.011). Cox regression analysis revealed that pT (HR = 1.826, p = 0.019), LY (HR = 0.318, p = 0.007), and tumor grade (HR = 0.505, p = 0.021) added to high SOX-2 and EZH-2 immunoexpression independently predicted a poor survival outcome (HR = 2.373, p = 0.016 and HR = 2.746, p = 0.015). Conclusions: Our findings suggest that SOX-2 and EZH-2 may serve as biomarkers of aggressive behavior and a poor prognosis in primary epithelial MSGTs, providing potential opportunities for precision-targeted therapies. Full article

Background/Objectives: Substance use disorder (SUD) in pregnancy is an increasingly complex public health challenge that is known to worsen maternal and neonatal outcomes. Rates of polysubstance use are steadily rising. The objective of this study was to assess the impact of co-occurring opioid and stimulant use disorder on adverse pregnancy outcomes (APOs) among inpatient pregnancy hospitalizations. Methods: We conducted a cross-sectional analysis of inpatient pregnancy hospitalizations for delivery admissions from the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) from 2016 to 2020. ICD-10 codes were used to identify patients with opioid and stimulant use disorder and with APOs. APO was defined as a composite to include hypertensive disorders of pregnancy, antepartum hemorrhage, postpartum hemorrhage, preterm birth, and fetal growth restriction. Multivariable logistic regression analyses were undertaken to predict the likelihood of APOs among pregnancy hospitalizations with opioid use, stimulant use, or co-occurring (opioid and stimulant) use disorders. Sociodemographic covariates, including age, race and/or ethnicity, insurance payor type, and income level, were accounted for. Results: From 2016 to 2020, 32,602 delivery hospitalizations complicated by stimulant or opioid use disorder were identified. Of these admissions, 21,049 (64.6%) had opioid use disorder, 9472 (29.1%) had stimulant use disorder, and 2081 (6.4%) had co-occurring opioid and stimulant use disorder. In the entire cohort, the prevalence of APOs was significantly highest among pregnancy delivery hospitalizations with co-occurring opioid use and stimulant use disorder (1136/2081—54.6%, p < 0.001), as compared with opioid use disorder (8923/21,049—42.4%) or stimulant use disorder alone (4654/9472—49.1%). Rates of APOs increased in subsequent years for all cohort groups. Adjusting for relevant sociodemographic covariates, co-occurring opioid and stimulant use disorder was an independent predictor of APO (aOR 3.65; CI 95%, 3.34–3.99). In comparison, opioid use disorder and stimulant use disorder were independent predictors of APOs with a less strong correlation, aOR 2.22 (CI 95%, 2.16–2.29) and aOR 2.89 (CI 95%, 2.77–3.02), respectively. Conclusions: Patients with co-occurring opioid and stimulant use disorder have the highest exposure risk for APOs, acting as an independent predictor for APOs when adjusting for sociodemographic covariates. Full article

Background: Diabetic foot ulcer (DFU) is a major complication of type 2 diabetes (T2D), frequently resulting in disability, lower-limb amputation, and substantial healthcare burden. Early identification of patients at high risk of progressing to severe DFU is essential for timely intervention, yet evidence on associated risk factors remains limited in Bangladesh. This study aims to identify demographic, clinical, and behavioral predictors of severe DFU to support early management strategies. Methods: A cross-sectional study was conducted among 159 DFU patients attending the Rajshahi Diabetic Association General Hospital, Bangladesh. Data on demographic characteristics, clinical variables, and behavioral factors were obtained through structured questionnaires and standardized examinations. Severe DFU was defined as Wagner grades 3–5, while grades 0–2 were considered non-severe. Firth’s penalized logistic regression was used to identify determinants of severe DFU. Model performance was assessed using ROC analysis, calibration belt analysis, and decision curve analysis (DCA). Results: Among the 159 participants, 101 (63.5%) presented with severe DFU. Patients with severe DFU had significantly higher BMI (26.1 vs. 23.7 kg/m²), treatment costs (50,000 vs. 20,000 BDT), and were older (57 vs. 54 years). Severe DFU was also associated with higher prevalence of peripheral arterial disease (PAD) (29.7% vs. 3.4%), prior amputation (31.7% vs. 3.4%), peripheral neuropathy (PN) (86.1% vs. 58.6%), and poor glycemic control (71.3% vs. 30.7%) (all p < 0.05). Firth’s regression identified older age (aOR 1.08), poor glycemic control (aOR 3.90), PN (aOR 3.41), PAD (aOR 7.54), and previous amputation (aOR 13.67) as independent predictors of severe DFU. Conclusions: Older age, uncontrolled glycemia, PN, PAD, and prior amputation were significantly associated with severe stages of DFU. Early detection and targeted management of these factors are critical to reducing complications and lowering the healthcare burden. Full article

Background/Objectives: Instrument fracture remains a significant complication in endodontics. This study compared the resistance to cyclic fatigue failure between rotary and reciprocating nickel–titanium file systems, as well as differences related to file size and taper. Methods: Nineteen rotary and reciprocating file types (n = 10 per group) were evaluated in three independent test series, harmonized according to file size and system. Cyclic fatigue testing was conducted using a static model with a stainless-steel artificial canal, with an internal diameter of 0.9 mm, a 75° curvature angle, and a fixed radius for each series. Files were operated using preset programs on the X-Smart Plus, Rooter X3000, and Sendoline Endo torque-controlled motors. Time to fracture was recorded digitally, and the total number of full rotations to failure was calculated. The fractured fragments were examined with scanning electron microscopy and fractographic analysis. The data were analyzed using linear models in Stata version 19, with significance set at p ≤ 0.05. Results: Reciprocating file systems demonstrated greater time-to-fracture fatigue resistance than rotary systems. However, these differences were diminished or, in some cases, eliminated when normalized to the number of complete rotations. Fractographic analysis indicated that fractures predominantly resulted from tensile stress rather than shear forces. Conclusions: Reciprocating kinematics generally enhanced fatigue resistance compared with continuous rotation. The results suggest that fatigue resistance in machine-driven nickel–titanium instruments cannot be predicted by motion type or file design alone but reflects a complex interaction between alloy composition, heat treatment, and cross-sectional geometry. Full article

Background/Objectives: Gastro-resistant multiparticulate systems are designed to protect drugs in acidic environments and to ensure intestinal release. In practice, the method of administration may need to be modified: pellet-containing capsules opened or tablets halved for patients with swallowing difficulties, yet the type of liquid used for administration is often not specified. This study examined the stability of gastro-resistant coated pellets after exposure to various aqueous media prior to ingestion. Methods: To evaluate administration instructions, 103 Summaries of Product Characteristics of gastro-resistant products were reviewed. Pellets were produced using a bottom-spray fluidized bed process and coated with Eudragit L 30 D-55. Dissolution testing in pH 1.2 medium was performed after pre-soaking the pellets for 5, 15, and 30 min in beverages with various pH and conductivity. Drug release was measured by UV-VIS method, and morphological changes were assessed by image analysis. Marketed gastro-resistant products were also examined visually. Results: SmPC review revealed that the beverage for intake was frequently unspecified. Among the tested beverages differences in pH and conductivity were observed. Alkaline medicinal mineral waters induced increased and time-dependent premature drug release compared to tap and filtered water. Image analysis indicated a reduction in surface area after exposure to alkaline media. Conclusions: Contact with non-specified aqueous media before swallowing may weaken the protective function of gastro-resistant films. More explicit recommendations on suitable administration manipulation and media may improve therapeutic consistency. Full article