Search Results (2,964)

Background/Objectives: Spinal Muscular Atrophy (SMA) is a genetic neurodegenerative disease characterized by severe muscle weakness and atrophy. Advances in disease-modifying therapies have dramatically changed the natural history of SMA and the outcome measures that are used to assess the clinical response to therapy. Standard assessment methods for SMA are limited in their ability to detect minor changes in fine motor abilities and in patients’ daily functions. The aim of this pilot study was to evaluate the feasibility and preliminary use of the Touchscreen-Assessment Tool (TATOO) alongside standardized tools to detect changes in upper extremity motor function among individuals with SMA receiving nusinersen therapy. Methods: Thirteen individuals with genetically-confirmed SMA, aged 6–23 years, eight with SMA type 2, and five with SMA type 3, participated. The patients continued the maintenance dosing of nusinersen during the study period. They were evaluated at the onset of the study, then twice more at intervals at least six months apart. Upper extremity functional assessments were performed via the TATOO and standardized tools: the Hand Grip Dynamometer (HGD), Pinch Dynamometer (PD), Revised Upper Limb Module (RULM), and Nine-Hole Peg Test (NHPT). Results: Significant changes in fine motor function were detected using the TATOO together with other standardized tools. Participants demonstrated notable improvements in hand grip strength and fine motor performance, as measured by the NHPT. The RULM results were not statistically significant for the total study group, particularly in ambulatory patients with SMA type 3. TATOO provided detailed metrics, and revealed enhancements in accuracy and speed across various tasks. However, given the small sample size, the lack of a control group, and the lack of baseline assessment before receiving therapy, these findings should be considered preliminary and exploratory. Conclusions: The findings suggest that the TATOO, alongside traditional assessment tools, offers a sensitive measure of fine motor function changes in patients with SMA. This study highlights the potential of touchscreen-based assessments to address gaps in current outcome measures and emphasizes the need for larger, multicenter studies that will include pre-treatment, baseline, and control data. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a major global health threat, with children at higher risk due to developmental differences in drug metabolism, limited treatment options and inappropriate antibiotic use. Pediatric antimicrobial stewardship programs (ASPs) face implementation challenges, often relying on adult-based guidelines and limited pediatric-specific evidence. This study aimed to identify and prioritize the most critical areas for pediatric ASP intervention development through a structured, multi-round Delphi consensus process with experts in antimicrobial stewardship and infectious diseases. Method: A four-round modified Delphi process was conducted to identify and prioritize key pediatric ASP interventions. Experts in antimicrobial stewardship and infectious diseases were recruited through an existing clinical trial. Using an iterative survey and in-person discussions, experts provided input on priority areas, which were thematically grouped and refined across rounds. Structured feedback supported real-time refinement and consensus-building. Results: Twenty experts participated in the process, generating 25 priority items in Round 1 through open-ended responses. These were narrowed to seven key priorities through structured voting and discussion. The final items were clustered into three intersecting themes: Care Settings, Prescriptions, and Strategies. Care Settings focused on high-impact areas such as outpatient clinics and intensive care units, where misuse is common and/or care is complex. The prescriptions theme prioritized shorter durations and narrow-spectrum agents. The strategy theme highlighted the need for outcome-based metrics, improved diagnostic stewardship, and routine tracking of patient outcomes to guide and assess stewardship efforts. Conclusions: This expert consensus identified key priorities for pediatric ASPs, providing a foundation for future interventions. Findings can be used to inform policy and practice, improving the appropriate use of antimicrobials in pediatrics and combating AMR. Full article

Background: Antimicrobial drugs are used to treat bacterial diseases in livestock production systems, including bovine respiratory disease (BRD) in feedlot cattle. It is recommended that therapeutic antimicrobial use (AMU) in food animals be informed by diagnostic tests to limit the emergence of antimicrobial resistance (AMR) and preserve the effectiveness of available drugs. Recent evidence demonstrates preliminary support for the pen as a prospective target for AMR testing-based interventions in higher-risk cattle. Methods: A previously reported agent-based model (ABM) was modified and then used in this study to investigate the potential for different pen-level sampling and laboratory testing-informed BRD treatment strategies to favorably impact selected antimicrobial stewardship and management outcomes in the western Canadian context. The incorporation of sample testing to guide treatment choice was hypothesized to reduce BRD relapses, subsequent AMU treatments and resultant AMR in sentinel pathogen Mannheimia haemolytica. The ABM was extended to include a discrete event simulation (DES) workflow that models the testing process, including the time at sample collection (0 or 13 days on feed) and the type of AMR diagnostic test (antimicrobial susceptibility testing or long-read metagenomic sequencing). Candidate testing scenarios were simulated for both a test-only control and testing-informed treatment (TI) setting (n = 52 total experiments). Key model outputs were generated for both the pen and feedlot levels and extracted to data repositories. Results: There was no effect of the TI strategy on the stewardship or economic outcomes of interest under baseline ecological and treatment conditions. Changes in the type and number of uses by antimicrobial class were observed when baseline AMR in M. haemolytica was assumed to be higher at feedlot arrival, but there was no corresponding impact on subsequent resistance or morbidity measures. The impacts of sample timing and diagnostic test accuracy on AMR test positivity and other outputs were subsequently explored with a theoretical “extreme” BRD treatment protocol that maximized selection pressure for AMR. Conclusions: The successful implementation of a pen-level sampling and diagnostic strategy would be critically dependent on many interrelated factors, including the BRD treatment protocol, the prevalences of resistance to the treatment classes, the accuracy of available AMR diagnostic tests, and the selected “treatment change” thresholds. This study demonstrates how the hybrid ABM-DES model can be used for future experimentation with interventions proposed to limit AMR risk in the context of BRD management. Full article

Background: Conventional HF treatment in transthyretin cardiac amyloidosis (ATTR-CA) resulting in restrictive cardiomyopathy is debated due to absent trial evidence in this specific sub-population of heart failure (HF) patients. Current European Society of Cardiology guidelines recommend the use of diuretics and mineralocorticoid receptor antagonists (MRAs). However, beta-blockers (BBs) and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs) are often discontinued due to hypotension or bradycardia. This study assesses real-world HF treatment patterns and their impact on survival in a multinational ATTR-CA cohort. Methods: A retrospective analysis of 794 ATTR-CA patients examined baseline BB, ACEi/ARB, and MRA prescriptions. The cohort was divided based on guideline publication dates. Results: Patients were predominantly male (73.2%) with a median age of 78 years. Prescription of diuretics (52.8%) and disease-modifying therapy (44.9%), mostly tafamidis, was common. BBs (43.7%) and ACEi/ARBs (41.2%) were prescribed more often in patients with higher NYHA class, elevated NT-proBNP, and more comorbidities. Blood pressure and heart rate were similar regardless of BB or ACEi/ARB use. BB prescription and combination therapy with BB and ACEi/ARB increased over time. Neither BB nor ACEi/ARB use significantly impacted mortality when analyzed in a multivariate Cox proportional hazard regression. Conclusions: Use of BBs and ACEi/ARBs has increased over time, particularly in advanced-stage ATTR-CA patients, and although these therapies appear to be reasonably tolerated, survival was not significantly altered. Full article

The term heart disease refers to a wide range of conditions that impact the heart and blood vessels. It continues to be a major global cause of morbidity and mortality. The narrowing or blockage of blood vessels, which can result in major medical events like heart attacks, angina (chest pain) or strokes, is a common issue linked to heart disease. In order to lower the risk of serious complications and facilitate prompt medical intervention, early diagnosis and prediction are essential. This study developed predictive models that can precisely identify people at risk by applying a variety of machine learning algorithms to a structured dataset on heart disease. Blood pressure, cholesterol, age, gender, and other health-related indicators are among the 13 essential characteristics that make up the dataset. Numerous machine learning models such as Naïve Bayes, K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Decision Tree, Random Forest, and others were trained using these features. Using the RapidMiner platform, which offered a visual environment for data preprocessing, model training, and performance analysis, all models were created and assessed. The best-performing model was the Naïve Bayes classifier which achieved an impressive accuracy rate of 90% after extensive testing and comparison of performance metrics like accuracy precision and recall. This outcome shows how well the model can predict heart disease in actual clinical settings. By supporting individualized health recommendations, enabling early diagnosis, and facilitating timely treatment, the effective application of such models can significantly benefit patients and healthcare professionals. Furthermore, heart disease incidence can be considerably decreased by identifying and addressing modifiable risk factors such as high blood pressure, elevated cholesterol, smoking, diabetes, and physical inactivity. In summary, machine learning has the potential to improve the identification and treatment of heart-related disorders. This study highlights the value of data-driven methods in healthcare and indicates that incorporating predictive models into standard medical procedures may enhance patient outcomes, lower healthcare expenses, and improve public health administration. Full article

Extracellular vesicles (EVs) from mesenchymal stem cells hold therapeutic promise for inflammatory and degenerative diseases; however, limited delivery and targeting capabilities hinder their clinical use. In this study, we sought to enhance the anti-inflammatory and chondroprotective effects of EVs through CAP-LAMP2b (chondrocyte affinity peptide fused to an EV membrane protein) engineering and ADAMTS4 gene editing hybrid vesicle formation. Human umbilical cord MSCs (hUCMSCs) were characterized via morphology, immunophenotyping, and trilineage differentiation. EVs from control and CAP-LAMP2b-transfected hUCMSCs were fused with liposomes carrying CRISPR-Cas9 ADAMTS4 gRNA. DiI-labeled EV uptake was assessed via fluorescence imaging. CAP-LAMP2b was expressed in hUCMSCs and their EVs. EVs exhibited the expected size (~120 nm), morphology, and exosomal markers (CD9, CD63, CD81, HSP70). CAP-modified hybrid EVs significantly enhanced chondrocyte uptake compared to control EVs and liposomes. IL-1β increased ADAMTS4 expression, whereas CAP-LAMP2b-ADAMTS4 EVs, particularly clone SG3, reversed these effects by reducing ADAMTS4 and restoring aggrecan. Western blotting confirmed suppressed ADAMTS4 and elevated aggrecan protein. CAP-LAMP2b-ADAMTS4 EVs, therefore, showed superior uptake and therapeutic efficacy in inflamed chondrocytes, attenuating inflammatory gene expression and preserving matrix integrity. These results support engineered EVs as a promising cell-free approach for cartilage repair and osteoarthritis treatment. Full article

Background and Objectives: a “vicious vortex” model was proposed to explain the pathophysiology of bronchiectasis, incorporating abnormal mucus, altered mucociliary clearance and chronic inflammation. Evidently, airway clearance needs to be implemented in the patient’s daily routine for a protracted period in order to ameliorate the clinical outcomes. High Flow therapy (HFT) has several physiologic effects and represents a valid therapy for various respiratory diseases. The aim of this study is to assess clinical and radiologic effects of long-term HFT in adult non-CF bronchiectasis. Materials and Methods: This is a retrospective observational cohort study including adult patients affected by bronchiectasis and frequent exacerbations and hospitalizations. A chest HRCT was performed, and a quantitative evaluation of the scans was conducted applying a modified Bhalla score of five items. A total of 44 patients completed the follow up, 23 in the HF-group and 21 in the controls (No-HF group). Results: The median follow up was 41 months (range 36–48 months). The mean age was 65 years, 45% were females. After treatment the annual rate of exacerbations was significantly lower in the HF group (1.2 ± 0.95 versus 3.5 ± 1.0 per year, p < 0.0001). The annual rate of hospitalizations was significantly lower in the HF group (0.4 ± 0.52 versus 1 ± 0.93 per year, p = 0.01). The total score of the modified Bhalla improved after treatment in the HF group with a mean score of 5.32 versus 8.38, p = 0.034. The difference was substantially due to the lower score of mucoid impactions in the HF group. Conclusions: Bronchiectasis is an evolutive disease. Long-term HFT reduces the annual rate of exacerbation and hospitalization. In addition, HFT prevents mucoid impaction and potentially influences the radiological evolution of the disease. Full article

Background and Objectives: This study aimed to evaluate the treatment outcomes of adults with pulmonary drug-susceptible tuberculosis (DS-TB) in Lithuania over 22 years, and to examine associations between treatment outcomes, various risk factors, and temporal trends. Materials and Methods: A retrospective cohort analysis was conducted using data from the National Tuberculosis Information System from 2000 to 2021. A total of 18,697 adult patients with DS-TB were included. Patients were grouped into three time periods: Period I (2000–2007), Period II (2008–2015), and Period III (2016–2021). Treatment outcomes were categorized as successful (treatment completed with recovery) or unsuccessful (patients who encountered treatment failure, died during treatment, or converted to drug-resistant tuberculosis). Associations with individual risk factors, including smoking, alcohol use, comorbidities, and sociodemographic variables, were analyzed. Results: Treatment success rates improved steadily across the study periods: 82.3% in Period I, 84.4% in Period II, and 87.6% in Period III. Mortality rates declined over time but remained substantial: 17.1%, 15.2%, and 12.0% in Periods I, II, and III, respectively. Non-lethal treatment failures decreased slightly (0.6%, 0.4%, and 0.4%). Multivariate analysis identified significant associations between treatment failure and multiple risk factors, including low BMI, male gender, unemployment, homelessness, smoking, alcohol and substance use, and comorbid conditions such as cancer, cardiovascular disease, chronic lung disease, diabetes mellitus, HIV, and renal failure. Conclusions: Treatment outcomes for DS-TB in Lithuania have improved over the past two decades; however, certain modifiable risk factors—such as low BMI, homelessness, substance use, and comorbidities—remain strongly linked to treatment failure. To further improve outcomes, targeted interventions such as nutritional support, housing programs, and integrated addiction services should be prioritized for high-risk groups within national TB control efforts. Full article

Spastic paraplegia 80 (SPG80), caused by mutations in ubiquitin-associated protein 1 (UBAP1), is a pure form of juvenile-onset hereditary spastic paraplegia (HSP) and leads to progressive motor dysfunction. Despite recent advances in the molecular analyses of HSP, disease-modifying therapy has not been established for HSP including SPG80. In the present study, we evaluated the therapeutic potential of 4-phenylbutyric acid (4-PBA), a chemical chaperone and histone deacetylase inhibitor, in Ubap1 knock-in (KI) mice expressing a disease-associated truncated UBAP1 variant. We found that 4-PBA administration significantly improved the motor performance of KI mice in the rotarod and beam walk tests, with maximal benefits achieved when given during pre- or early-symptomatic stages. Partial efficacy was also observed when treatment began after symptom onset in KI mice. Furthermore, 4-PBA attenuated spinal microglial activation and partially restored microglial morphology, although astrocytic reactivity remained unchanged. These findings support 4-PBA as a candidate therapeutic compound for SPG80 and highlight the potential of proteostasis-targeted interventions in HSPs. Full article

Objectives: The aim was to measure wait times for rheumatologist consultation and disease-modifying antirheumatic drug (DMARD) treatment and examine their association with travel time to primary care practitioners (PCP) and rheumatologists within a centralized intake system, respectively. Methods: Within a centralized intake system serving 4.2 million people, we measured wait time for rheumatologist consultations and DMARD treatment for an RA incidence cohort between 1 April 2015 and 31 March 2020. Wait times were reported as the median with the interquartile range (IQR). Using multivariate logistics regression models, we examined the impact of travel times to primary/rheumatology care on wait times for rheumatologist consultation (28-day benchmark) and DMARD treatment (14-day benchmark). Travel times were defined according to quantiles and pre-defined categories. Results: The median wait time was 47 days (IQR: 18–114) for rheumatologist consultations (36% meeting the benchmark) and 35 days (IQR: 1–132) for DMARD treatment (43% meeting the benchmark). Patients living >120 min away had lower odds of meeting the 28-day consultation benchmark compared with those within 30 min (OR 0.64; 95% CI: 0.42–0.97). Compared with patients driving ≤30 min, lower odds of meeting the 14-day benchmark for DMARD treatment were observed for those driving over 60 min to PCPs (OR 0.62; 95% CI: 0.39–0.99) and patients driving 30–60 min to rheumatologists (OR 0.68; 95% CI: 0.55–0.85). Conclusion: RA management was suboptimal due to low rates of meeting RA consultation and treatment benchmarks, which was significantly associated with long travel times to both primary and RA care within a centralized triage system. This highlights the need for complementary strategies (e.g., tele-rheumatology, travel support, or alternate care providers) to ensure timely RA care in rural and remote communities. Full article

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting the joints, with neurogenic inflammation involving the nervous system being a hallmark of the condition. Treatments include medications such as disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and biologics targeting inflammatory pathways. Yet, these treatments are not curative for RA. Heat Shock Proteins (HSPs) are molecular chaperones with immunoregulatory properties; however, their role is not yet fully understood, as these molecules may play a dual, pro- and anti-inflammatory role. In this study, we evaluated the protein expression levels of HSPs 27, 60, 70, and 90 in the synovial membrane and spinal cord of the RA rats’ model to determine their roles during the disease course, both on the neurological and immunological levels. Furthermore, HSP levels have been evaluated in the spinal cord of control and RA rats’ model after high and low doses of ketamine injection. Significant changes in Hsp60, 70, and 90 expression levels were observed only in the spinal cord of RA rats. We demonstrated that blocking N-methyl-D-aspartate receptors with ketamine can modulate spinal cord HSPs expression in RA rats and subsequently impact neurogenic inflammation and adult neurogenesis. This suggests that HSPs may be a promising target for RA treatment due to their complex immunomodulatory effects and potential interactions with the nervous system. Further research is needed to explore their therapeutic potential and develop effective interventions for RA. Full article

Background: Amino acid tracer positron emission tomography–magnetic resonance imaging (PET-MRI) was shown to be superior to MRI alone for evaluating central nervous system (CNS) tumours in adults. This study aimed to investigate the utility of amino acid PET-MRI in children with CNS tumours. Methods: We reviewed the amino acid PET-MRI findings of children with suspected or confirmed CNS neoplasms managed in a territory-wide referral centre in Hong Kong from 2022 to 2025. Maximal standardized uptake values (SUVmax) were captured, and tumour-to-background SUVmax ratios (TBRmax) were measured with reference to adjacent or contralateral normal brain structures. Comparisons were made among patients with clinical high-grade and low-grade/non-neoplastic lesions. Results: Thirty-seven patients were included, with 63 PET-MRIs performed. PET-MRI was performed as part of initial diagnostics in 41% of the cases, for response assessment in 48%, and evaluation of residual/relapsed disease in 11%. High-grade lesions had a significantly higher SUVmax and TBRmax compared to low-grade/non-malignant lesions (median SUVmax 3.7 vs. 1.6, p = 0.00006; median TBRmax 2.06 vs. 0.91, p = 0.00002). Optimal SUVmax and TBRmax cut-offs by ROC analysis were 2.38 and 1.62, respectively. Similar performance was reproduced by focusing on the subset of patients with suspected CNS germ cell tumours (CNS-GCT). The impact of amino acid PET availability is considerable, as clinical management was modified in 65% of patients. Conclusions: Our study demonstrates the performance and clinical utility of amino acid PET-MRI in the management of children with CNS pathologies. Amino acid PET-MRI contributes to the diagnosis, monitoring, and treatment guidance of these patients, providing crucial information for decision-making. Full article

Background: Nurses play a central role in the management of inflammatory joint diseases (IJD), of which the success depends on patient adherence to treatment, self-monitoring, timely detection of adverse drug reactions (ADRs), and adopting a healthy lifestyle. This study sought to examine the opinions of patients with IJD regarding the educational and supportive contributions of nurses. Methods: The research is based on a cross-sectional survey of patients with IJD treated with biologic disease-modifying antirheumatic drugs (bDMARDs) in two rheumatology clinics in Plovdiv, Bulgaria, from the beginning of August 2024 to the end of January 2025. The group included patients of three diagnoses: (1) rheumatoid arthritis (RA), (2) psoriatic arthritis (PsA), and (3) axial spondyloarthritis (axSpA). Results: Regardless of the diagnosis, and after adjusting for covariates, patients rated the roles of nurses in disease treatment and management, the acquisition of self-injection skills for bDMARDs, the implementation of a healthy lifestyle, and the maintenance of psychological well-being at the higher end of the 0 to 4 scale. However, the axSpA patients were less affirmative in their responses compared to the RA and PsA patients. In the RA and PsA groups, the working patients were associated with the lowest ratings, followed by retirees with disability. Conclusions: Our findings indicate that nurse-led education in patient self-management skills is greatly appreciated by patients with IJD. Further developments in specialized training programs tailored to the specific needs of different diagnoses and in consideration of patients’ social status will lead to increased patient satisfaction and a better overall quality of life. Full article

This review article aims to provide an overview of the pathophysiology, diagnosis, and contemporary management of cardiac amyloidosis (CA) as well as identify the knowledge gaps and areas of potential research. CA can be divided into two main groups: transthyretin cardiac amyloidosis (ATTR-CA) and light chain cardiac amyloidosis (AL-CA). The former further separates into wild-type transthyretin (ATTRwt) and hereditary transthyretin (ATTRv). African Americans, males, and people older than 75 are the most common demographics affected by this disease. Thanks to an increased understanding of this disease combined with better diagnostic techniques, there is growing awareness and a surge of clinical trials aimed at improving outcomes of CA. The diagnosis and treatment of CA is multifaceted and complex, relying on multiple imaging modalities and the cooperation of specialists to deliver effective treatments. While some disease-modifying agents have been introduced recently, their extraordinary cost limits their benefit or they are supported by limited evidence. Other agents are currently undergoing phase 3 trials. To date, there is scarce data surrounding optimal diagnostic and treatment strategies, including a potential role for combination therapies. Critically, it is imperative that physicians develop close relationships with the patient that addresses not only their individual health needs but also their unique psychosocial situation. Therefore, more clinical trials, protocols and patient resources are needed to better inform and guide providers managing these complex patient needs. Full article

Background: Osteoarthritis (OA) is a major global health issue, increasing with aging and obesity. Current therapies mainly address symptoms without modifying disease progression. Platelet-rich growth factor (PRGF) therapy has potential regenerative effects through high cytokines and growth factors, but the outcomes of these therapies remain heterogeneous. This study explores the relationship between patient nutritional status, PRGF characteristics, and clinical outcomes in knee OA treatment. Methods: Baseline anthropometric, metabolic, and nutritional assessments of 41 patients with knee OA who underwent PRGF treatment were conducted. Blood samples were analyzed for metabolic and inflammatory markers. PRGF composition was assessed by protein content and extracellular vesicle (EV) markers. KOOS and VAS pain scores were collected at 2, 6, and 12 months. Responders improved KOOS by ≥10 points. An elastic-net regularized logistic model allowed the identification of the predictors of treatment response. Results: KOOS and VAS scores improved significantly at all follow-ups. At 2 months, the PRGF of responder patients showed higher PRGF G-CSF levels; at 12 months, increased CD49e and HLA-ABC expression. Higher BMI correlated with increased IL-6, IL-1ra, and resistin in PRGF samples. Hypercholesterolemic patients displayed altered EV profiles, with elevated levels of CD8 but reduced CD49e, HLA-ABC, CD42a, and CD31. Multivariate analysis identified BMI, biceps fold, fat percentage, red blood cell, platelet, and neutrophil counts as predictors of early response. Conclusions: Metabolic and immunological factors influence PRGF composition and clinical efficacy in knee OA. Baseline body composition and hematological parameters as key predictors of response, highlighting the potential of personalized PRGF therapy. Full article