Search Results (244)

Background: The education process for newly diagnosed Type 1 diabetes mellitus (T1D) patients and their families, primarily led by diabetes specialist nurses, is essential for gaining knowledge about the disease and its management. However, few assessment tools have been employed to evaluate long-term knowledge retention among T1D patients years after diagnosis. Methods: We developed a 20-question test to assess the knowledge of patients and their families at the conclusion of the initial education process and again 6–12 months later. Demographic and clinical data were also collected. Statistical analyses included comparisons between the first and second test results, as well as evaluation of potential contributing factors. The internal consistency and construct validity of the questionnaire were evaluated. Results: Forty-four patients completed both assessments, with a median interval of 11.5 months between them. The average score on the first test was 88.6, which declined to 82.7 on the second assessment (p < 0.001). In univariate analysis, factors positively associated with higher scores included Jewish ethnicity, lower HbA1c levels, and shorter hospitalization duration. Multivariate analysis revealed that parents had lower odds of experiencing a significant score decline compared to patients. Cronbach’s alpha was 0.69, and Principal Component Analysis (PCA) identified eight components accounting for 67.1% of the total variance. Conclusions: Healthcare providers should consider offering re-education to patients and their families approximately one year after diagnosis, with particular attention to high-risk populations during the initial education phase. Further studies are needed to examine this tool’s performance in larger cohorts. Full article

Background: Obese women have a significantly higher risk of bearing breast tumors that are resistant to therapies and are associated with poorer prognoses/treatment outcomes. Breast cancer-promoting action of obesity is often attributed to elevated levels of insulin, glucose, inflammatory mediators, and misbalanced estrogen production in adipose tissue under obese conditions. Metabolic endotoxemia, characterized by chronic presence of extremely low levels of bacterial endotoxin (lipopolysaccharide [LPS]) in the circulation, is a less explored obesity-associated factor. Results: Here, utilizing in vitro and in vivo models of breast carcinoma (BC), we report that subclinical levels of LPS typical for metabolic endotoxemia enhance the malignant phenotype of breast cancer cells and accelerate breast tumor progression. Conclusions: Our study, while focusing primarily on the direct effects of metabolic endotoxemia on breast tumor progression, also suggests that metabolic endotoxemia can contribute to obesity–breast cancer link. Thus, our findings add novel mechanistic insights into how obesity-associated metabolic changes, particularly metabolic endotoxemia, modulate the biological and clinical behavior of breast carcinoma. In turn, understanding of the mechanistic aspects underlying the association between obesity and breast cancer could help inform better strategies to reduce BC risk in an increasingly obese population and to suppress the breast cancer-promoting consequences of excess adiposity. Full article

Diffuse axonal brain injury (DAI) is a common, debilitating consequence of traumatic brain injury, yet its detection and severity grading remain challenging in clinical and experimental settings. This study evaluated the sensitivity of diffusion tensor imaging (DTI), histology, and neurological severity scoring (NSS) in assessing injury severity in a rat model of isolated DAI. A rotational injury model induced mild, moderate, or severe DAI in male and female rats. Neurological deficits were assessed 48 h after injury via NSS. Magnetic resonance imaging, including DTI metrics, such as fractional anisotropy (FA), relative anisotropy (RA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD), was performed prior to tissue collection. Histological analysis used beta amyloid precursor protein immunohistochemistry. Sensitivity and variability of each method were compared across brain regions and the whole brain. Histology was the most sensitive method, requiring very small groups to detect differences. Anisotropy-based MRI metrics, especially whole-brain FA and RA, showed strong correlations with histology and NSS and demonstrated high sensitivity with low variability. NSS identified injury but required larger group sizes. Diffusivity-based MRI metrics, particularly RD, were less sensitive and more variable. Whole-brain FA and RA were the most sensitive MRI measures of DAI severity and were comparable to histology in moderate and severe groups. These findings support combining NSS and anisotropy-based DTI for non-terminal DAI assessment in preclinical studies. Full article

Background/Objectives: Overt hypothyroidism during pregnancy has been linked to adverse outcomes, including preterm birth, low birth weight, and impaired fetal neurocognitive development. This study aimed to evaluate pregnancy complications in women with overt hypothyroidism (TSH ≥ 10) through a cross-sectional study. Methods: Data from 259,897 live-birth pregnancies (2013–2022) from Clalit Health Services (CHS) were analyzed. The study included all CHS-insured women aged ≥ 18 years with available TSH results during pregnancy. Overt hypothyroidism was defined as a mean TSH ≥ 10 mIU/L, while the euthyroid reference group had TSH levels < 4 mIU/L and no history of hypothyroidism or levothyroxine use. Cases of overt hypothyroidism were matched with 15 controls using propensity score-based matching. Covariates included maternal age, ethnicity, socioeconomic status, IVF use, recurrent pregnancy loss, and smoking. Pregnancy complications were compared between groups using descriptive statistics and univariate analysis. A quasi-Poisson regression model was used to assess complication risk in overt hypothyroidism versus matched controls. Results: The final analysis included 9125 euthyroid and 611 overt hypothyroid pregnancies, with comparable baseline characteristics between groups. No significant differences were found in maternal age, ethnicity, socioeconomic scores, IVF rates, recurrent pregnancy loss, diabetes, smoking, gestational age at delivery, or rates of preterm birth, pre-eclampsia, gestational diabetes, cesarean section, and intrauterine growth restriction. Overall, overt hypothyroidism was not associated with increased complications. Sensitivity analyses using maximum TSH levels during pregnancy showed a slightly elevated risk for pregnancy complications (IRR 1.1, CI 1.04–1.18; p = 0.002). Conclusions: Overt hypothyroidism was not associated with an increased risk of adverse pregnancy outcomes when adjusted for confounding factors, suggesting that treatment decisions should be made on an individual basis. Full article

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare genetic disorder, often leading to injuries and serious infections. In 2018, we established a multidisciplinary clinic (MDC) to provide structured, proactive care. We assessed the MDC’s impact on hospitalizations, surgeries, and infection rates. Methods: A retrospective study of genetically confirmed CIPA patients, treated from 2014 to 2024. Data from electronic medical records were compared between the pre-MDC (2014–2017) and post-MDC (2018–2024) periods. The core MDC team includes an infectious disease specialist, orthopedic surgeon, and nurses. The patients are stratified according to their carriage of resistant organisms and are managed using strict infection control measures. Follow-ups are scheduled routinely or as needed. Treatment is guided by clinical findings and culture results. Results: A total of 59 patients were included in the study. The baseline age did not differ significantly between the two periods. Hospitalization rates declined by 30.7% (from 57.7 to 40.0 per 1000 days), and clinic visits decreased by 42.9% (25.5 to 14.6). Overall surgical rates remained stable (2.8 to 2.7), with a 61.9% decrease in eye surgeries and a 130.5% increase in elective tooth extractions. Infection rates increased by 52% (from 6.6 to 10.1 per 1000 days). Conclusions: The implementation of the MDC bundle led to reduced hospitalizations, clinic visits, and eye surgeries, alongside the increased use of elective tooth extractions and culture testing. Closer monitoring and early infection management contributed to fewer severe complications. These findings support the value of structured, proactive multidisciplinary care in improving outcomes for children with CIPA. Full article

Objectives: The objective of this study was to evaluate the agreement and clinical interchangeability of intraocular pressure (IOP) measurements obtained with the mechanical Haag-Streit AT900 Goldmann applanation tonometer (mGAT) and the digital Huvitz HT5000 applanation tonometer (dGAT). Methods: This retrospective comparative study included 53 eyes of 28 patients undergoing routine ophthalmologic evaluation. Each eye underwent IOP measurement using both mGAT and dGAT in a randomized sequence. Central corneal thickness (CCT) was also recorded. Pearson’s correlation coefficient was used to determine correlation between paired IOP measurements. Bland–Altman plots were graphed for the analysis of differences for IOP between the instruments. Results: A total of 53 eyes of 28 patients (15 males) were included in the study. The mean age of the patients was 62.6 years. The mean mGAT and dGAT measurements were 16.3 ± 6.6 mmHg (range 9–50) and 16.4 ± 6.2 mmHg (range 8.8–45.9), respectively (p = 0.53). A strong, significant positive correlation was found for paired IOP measurements by the two instruments (r = 0.98; p < 0.0001). Bland–Altman analysis revealed 95% limits of agreement from −2.5 to +2.3 mmHg, with a small but statistically significant proportional bias favoring mGAT at higher IOP levels. Additionally, 91% of paired measurements were within ±2 mmHg. CCT-related differences were statistically and clinically insignificant. Conclusions: IOP measurements obtained with mGAT and dGAT were highly correlated and clinically interchangeable for the range tested. The Huvitz HT5000 may serve as a reliable alternative to the classic Goldmann tonometer in routine clinical settings. Full article

Aims: The global prevalence of pulmonary hypertension (PHT) among the elderly population aged 65 years and above is estimated to be 10%. While it is known to be associated with poor prognoses in patients with cardiovascular or pulmonary diseases, the significance of PHT as an incidental finding among individuals without these conditions remains unclear. The aim of this study was to investigate the relationship between incidental PHT detected by echocardiography and long-term all-cause mortality in patients without known cardiovascular or pulmonary diseases. Methods and Results: This retrospective, single-center cohort study included 8283 patients who underwent two consecutive echocardiographic examinations evaluating pulmonary pressure by assessing the maximal velocity of the tricuspid regurgitation jet. In total, 1705 (20.6%) patients were found to have PHT during the first echocardiography. Using a Cox proportional hazard model for all-cause mortality, PHT was found to be a significant and independent risk factor for all-cause mortality, increasing the risk by 34% (Adj. HR—1.34, 95% CI 1.21–1.47, p < 0.001). There was a direct relationship between PHT severity and long-term all-cause mortality, with patients with severe PHT having a two-fold higher risk compared to those with normal pulmonary blood pressure (Adj. HR—2, 95% CI: 1.58–2.54, p < 0.001). A “cutoff point” of sPAP > 40 mmHg was established, where pulmonary pressure values remained high and even worsened over time (p < 0.001). Conclusions: The incidental diagnosis of PHT by echocardiography in patients without known cardiovascular or pulmonary diseases is an independent risk factor for long-term all-cause mortality. Patients with sPAP ≥ 40 mmHg warrant a comprehensive clinical assessment. Full article

Bariatric surgery involves major changes in the anatomy and physiology of the gastrointestinal tract, which may alter oral drug bioavailability and efficacy. Phosphodiesterase-5 inhibitor (PDE5i) drugs are the first-line treatment of erectile dysfunction, a condition associated with a higher BMI. In this paper, we examine the PDE5i vardenafil for possible post-bariatric changes in solubility/dissolution and absorption. Vardenafil solubility was determined in vitro, as well as ex vivo using aspirated gastric contents from patients prior to vs. following bariatric procedures. Dissolution was tested in vitro under unoperated stomach vs. post-gastric sleeve/bypass conditions. Lastly, the gathered solubility/dissolution data were used to produce an in silico physiologically based pharmacokinetic (PBPK) model (GastroPlus^®), where gastric volume, pH, and transit time, as well as proximal GI bypass (when relevant) were all adjusted for, evaluating vardenafil dissolution, gastrointestinal compartmental absorption, and pharmacokinetics before vs. after different bariatric procedures. pH-dependent solubility was demonstrated for vardenafil with low (pH 7) vs. high solubility (pH 1–5), which was confirmed ex vivo. The impaired dissolution of all vardenafil doses under post-gastric bypass conditions was demonstrated, contrary to complete (100%) dissolution under pre-surgery and post-sleeve gastrectomy conditions. Compared to unoperated individuals, PBPK simulations revealed altered pharmacokinetics post-gastric bypass (but not after sleeve gastrectomy), with 30% lower peak plasma concentration (C_max) and 40% longer time to C_max (T_max). Complete absorption after gastric bypass is predicted for vardenafil, which is attributable to significant absorption from the large intestine. The biopharmaceutics and PBPK analysis indicate that vardenafil may be similarly effective after sleeve gastrectomy as before the procedure. However, results after gastric bypass question the effectiveness of this PDE5i. Specifically, vardenafil’s onset of action might be delayed and unpredictable, negatively affecting the practicality of the intended use. Full article

Background: Venous sinus stenting is a promising treatment for intracranial venous disorders, such as idiopathic intracranial hypertension and pulsatile tinnitus, associated with transverse sinus stenosis. The VIVA Stent System (VSS) is a novel self-expanding braided venous stent designed to navigate tortuous cerebral venous anatomy. This preclinical study assessed the safety, thrombogenicity, and performance of the VSS in a swine model. Methods: Fifteen swine underwent bilateral internal mammary vein stenting with either the VSS (n = 9) or the PRECISE^® PRO RX stent (n = 6, reference). Fluoroscopy and thrombogenicity assessments were conducted on the day of stenting, clinical pathology analysis was carried out throughout the in-life phase, and CT Venography was performed before sacrifice. Animals were sacrificed at 30 ± 3 or 180 ± 11 days post-stenting for necropsy and histological evaluation. Results: Fluoroscopic angiography confirmed the successful VSS deployment with complete venous wall apposition and no vessel damage. The VSS achieved the highest scores on a four-point Likert scale for most performance parameters. No thrombus formation was observed on either delivery system. CT Venography confirmed vessel patency, no stent migration, and complete stent integrity. Histopathology showed a mild, expected foreign body reaction at 30 days, which resolved by 180 days, indicating normal healing progression. Both stents showed increased luminal diameter and decreased wall thickness at 180 days, suggesting vessel recovery. No adverse reactions were observed in non-target organs. Conclusions: The VSS exhibited favorable safety, procedural performance, and thromboresistance in a swine model, supporting its potential clinical use for treating transverse sinus stenosis and related conditions. Full article

Background/Objectives: Weaning failure remains a major challenge in patients requiring prolonged mechanical ventilation. This study aimed to describe outcomes in patients ventilated for >14 days and identify specific predictors of weaning success. Methods: A retrospective analysis of 88 patients from the Soroka University Medical Center database was conducted. Outcomes in the successful weaning (SW) group were compared to those in the failed weaning (FW) group. Predictors of weaning success were analyzed using multivariate logistic regression. Results: Forty patients (45%) were successfully weaned and discharged to rehabilitation or home. In-hospital mortality was 28%, with deaths occurring exclusively in the FW group (p < 0.001). One-month and one-year post-discharge all-cause mortality rates were 11% and 28%, respectively, with no group differences. Hypoalbuminemia and the Sequential Organ Failure Assessment (SOFA) score at admission significantly predicted weaning failure (odds ratio: 5.71 and 0.54, respectively). Demographics, comorbidities, ventilation indications, admission data, and diuretic use were not predictive. Conclusions: Hypoalbuminemia and the SOFA score at admission were key predictors of weaning success in patients ventilated for more than 2 weeks. Age and comorbidities were not significant. Prospective studies on albumin supplementation and high-protein diets are warranted to assess their impact on weaning outcomes. Full article

Background: Colonoscopy is an important and essential diagnostic and screening tool for colorectal cancer and other pathologies in the colon. High-quality bowel preparation (BP) is a key quality measure of colonoscopy and is critical for maximizing its effectiveness, including enhancing adenoma detection rates. However, inadequate bowel preparation (IBP) remains a frequent challenge and is influenced by multiple factors. This review aims to summarize and evaluate educational and technological interventions implemented before colonoscopy to improve BP quality. Methods: The methodology comprised a structured narrative review of studies published in English, including randomized controlled trials, prospective studies, observational cohorts, and meta-analyses. Interventions were categorized by their delivery mode and impact on BP adequacy. Interventions included written materials, internet-based education modules, short message service (SMS) reminders, visual aids, instructional videos, verbal communication, telephone support, smartphone applications, and virtual reality (VR) platforms. Results: Most studies reported significant improvements in BP quality with enhanced patient education, particularly with the use of instructional videos and smartphone applications. Verbal communication and telephone support also demonstrated positive outcomes but were limited by resource availability. VR represents a promising emerging technology, though its implementation remains costly and complex. Conclusions: Enhanced educational interventions are proven methods to optimize BP quality. The selection of an appropriate modality should consider patient characteristics, technological accessibility, and institutional resources. Personalized strategies targeting high-risk populations can further reduce IBP rates and improve overall colonoscopy outcomes. Full article

Background/Objectives: Uncontrolled or long-standing diabetes can lead to proliferative diabetic retinopathy (PDR), a condition that significantly impairs vision. A subset of patients does not respond adequately to conventional therapies, such as intravitreal injections of anti-vascular endothelial growth factor (VEGF) or laser treatment. This study aims to identify potential biomarkers for alternative treatment pathways in the vitreous and blood of patients with severe PDR. Methods: Vitreous samples were collected from PDR patients (n = 3) undergoing vitrectomy for vitreous hemorrhage and from control patients (n = 9) undergoing ocular surgery for epiretinal membrane or macular holes. Blood samples were collected from a separate group of PDR patients (n = 13) and non-diabetic control patients without retinopathy (n = 13). Medical histories were obtained. Two-stage real-time quantitative polymerase chain reaction (qPCR) was used to evaluate mRNA expression levels of genes potentially implicated in PDR, including HIF2A, PAI-1, TIE1, TIE2, ANGPT2, and VEGFA. Molecular and statistical analyses were performed to compare PDR and control vitreous and blood samples. Results: The PDR vitrectomy group included two females and one male, aged 71–77 years (mean 74 years). All participants had undergone pan-retinal photocoagulation and two had received anti-VEGF injections before vitrectomy. These participants had elevated HbA1c levels. Targeted vitreous gene analysis revealed varying levels of increased expression of all genes examined as compared to the control group. A trend for increased median expression was demonstrated for all examined genes: HIF2A by 1.44-fold (PDR = 2.50, control = 1.74, p = 0.21), PAI-1 by 1.56-fold (PDR = 3.00, control = 1.93, p = 0.37), TIE1 by 1.36-fold (PDR = 2.33, control = 1.72, p = 0.66), TIE2 by 2.06-fold (PDR = 2.81, control = 1.36, p = 0.51), ANGPT2 by 2.93-fold (PDR = 6.32, control = 2.16, p = 0.1), and VEGFA by 3.53-fold (PDR = 3.51, control = 0.99, p = 0.08). PDR blood sample analysis as compared to controls showed a trend for increased expression of VEGFA by 1.2-fold (PDR = 0.88, control = 0.74, p = 0.57), whereas the other examined genes showed a trend of reduced expression; HIF2A decreased by 0.50-fold (PDR = 0.38, control = 0.75, p = 0.07), PAI by 0.51-fold (PDR = 0.35, control = 0.69, p = 0.09), TIE-1 by 0.79-fold (PDR = 0.79, control = 1.00, p = 0.54), TIE-2 by 0.70-fold (PDR = 0.58, control = 0.82, p = 0.34), and ANGPT2 by 0.45-fold (PDR = 0.51, control = 1.15, p = 0.11). Conclusions: Vitreous sample analysis revealed a trend of increased mRNA expression of ANGPT2 and VEGFA in patients with PDR. Blood sample analysis did not show a significant increase of VEGFA mRNA expression but a decreased trend of HIF2A, PAI-1, and ANGPT2 mRNA expression. These trends warrant validation in a larger cohort to explore alternative pathways for targeted treatment. Full article

Background: Cardiopulmonary exercise testing (CPET) is a valuable diagnostic and prognostic tool for assessing the integrated function of the cardiopulmonary and muscular systems during exercise. The initiation of a CPET program is complex, and data on early implementation in academic centers remain relatively limited. Objective: to evaluate the initial integration of CPET within a pulmonary department, focusing on patient demographics, referral indications, test performance, and factors associated with anaerobic threshold achievement. Methods: A retrospective cohort study was conducted at a single tertiary care center, including all patients who underwent their first CPET between February 2016 and December 2022. Demographic, clinical, and functional parameters were extracted. Multivariable logistic regression was used to identify variables associated with anaerobic threshold achievement, defined as a respiratory exchange ratio (RER) ≥ 1.1. Results: The cohort included 434 patients (mean age 60.3 ± 14.1 years; 54% male; mean BMI 29.2 ± 5.6 kg/m²). The most common indication for testing was dyspnea (50%). Tests were most frequently terminated due to leg discomfort (39%) and dyspnea (38.8%). Achievement of RER ≥ 1.1 was independently associated with lower BMI (aOR = 0.91; 95% CI: 0.88–0.95; p < 0.001), higher FVC % predicted (aOR = 1.02; 95% CI: 1.00–1.03; p = 0.028), and greater minute ventilation volume (aOR = 1.02; 95% CI: 1.01–1.03; p < 0.001), and it was less likely in patients referred for cardiovascular disease (aOR = 0.37; 95% CI: 0.21–0.64; p < 0.001). No consistent temporal trend in RER achievement was observed across the study period. Conclusions: CPET was most commonly utilized in response to patient-reported dyspnea, with test termination frequently driven by subjective symptoms rather than objective clinical criteria. Anaerobic threshold achievement was more strongly associated with individual physiological characteristics than with institutional experience. These findings underscore the importance of patient preparation and pulmonary functional capacity in optimizing CPET performance. Full article

This study investigates social support type and long-term mortality following AMI. Demographic and clinical data were collected retrospectively from a tertiary hospital for all patients with AMI (2011–2017). Study groups based on support type were defined: (1) employed partner (served as the reference group); (2) unemployed partner; (3) no partner, family support; (4) institutional or benefit-dependent; and (5) non-kin support (caregiver). Ten-year all-cause mortality risk was assessed and compared between the groups. We identified 2652 AMI patients with recorded support type: mean age 67.6 (SD = 14) years, 66% male; 40% had no partner, followed by those with an unemployed partner (31%). Over the follow-up of (median) 7.6 years, 1471 patients died; significantly higher mortality rates were observed in patients without family support (67.9%) or receiving non-kin support (94.9%). Those with non-kin support were at the highest mortality risk, AdjHR = 2.20, 95% CI: 1.67–2.91, p < 0.001, as compared with the reference group. Subgroup analyses found women below age 75 years, Arab women, and those with higher functional status to be most vulnerable to mortality in the absence of family support. Lack of family support was associated with increased long-term mortality among AMI patients. Assessment of support status among AMI patients is integral for secondary prevention. Full article

Objectives: We aimed to investigate the association between acute kidney injury (AKI) and the risk for long-term (up to 10 years) all-cause mortality among elderly compared with younger patients following an acute myocardial infarction (AMI). Methods: This study was a retrospective analysis of the Soroka Acute Myocardial Infarction registry and covered the years 2002 to 2017. It included patients diagnosed with an AMI who had a baseline estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m² and serum creatinine measurements available during hospitalization. The patients were stratified by age: elderly (aged 65 years or older at admission) and younger. In each stratum, two groups were defined based on the presence of an AKI. The survival approach (Kaplan–Meier survival curves, log-rank test and Cox regressions) was utilized to estimate and compare the probability of long-term (up to 10 years) all-cause mortality in each group. Results: Among the 10,511 eligible patients, which consisted of 6132 younger patients (58.3%) and 4379 elderly (41.7%), an AKI occurred in 15.2% of cases, where the elderly patients experienced a higher incidence than the younger patients (20.9% vs. 11.2%, p < 0.001). The presence of an AKI significantly increased the risk of death in both age groups, with the association being stronger among the younger patients (AdjHR = 1.634, 95% CI: 1.363–1.959, p < 0.001) than among the elderly (AdjHR = 1.278, 95% CI: 1.154–1.415, p < 0.001, p-for-interaction = 0.020). Conclusions: An AKI following an AMI was associated with a high risk for long-term all-cause mortality in both age groups, with a stronger association among younger patients. Full article