Search Results (3,528)

Background: Lattice Radiotherapy (LRT), a spatially fractionated stereotactic radiotherapy (SBRT) technique, has shown promising results in the palliative treatment of large tumors. The focus of our first analysis of 56 lesions >/=7cm was on the extent of shrinkage following palliative LRT (mean 50%) and assessment of its effect duration (: mean 6 months). Herewith we present an updated analysis of our single-center LRT cohort, with a focus on LRT outcome across diagnoses and applied LRT regimens. Methods: We assessed the clinical outcome following LRT in 66 patients treated for 81 lesions between 01.2022 and 05.2025. LRT protocols included simultaneous integrated boost (sib-) LRT in 49 lesions (5 × 4–5 Gy to the entire mass with sib of 9–13 Gy to lattice vertices). Alternatively mainly in pre-irradiated and/or very large lesions—a single-fraction stereotactic LRT (SBRT-LRT) of 1 × 20 Gy to vertices only was delivered to 26 lesions. In six cases with modest response to single fraction SBRT-LRT, the sib-LRT schedule was added 4–8 weeks later. Results: The median age was 68 years (18–93). Main tumor locations were abdomino-pelvic (n = 34) and thoracic (n = 17). Histopathological diagnoses included carcinoma (n = 34), sarcoma (n = 31), and melanoma (n = 16). 31% of all lesions have been previously irradiated. 73% of cases underwent concurrent or peri-LRT systemic therapy. The mean/median overall survival (OS) time of the cohort was 7.6/4.6 months (0.4–40.2), 11.9/5.8 months in 16/66 alive, and 6.4/4.3 months in deceased patients, respectively. 82% of symptomatic patients reported immediate subjective improvement (PROM), with a lifelong response duration in most cases. Progressive disease (PD: >10% increase in initial volume) was found in 9%, stable disease (SD +/−10% of initial volume) in 19% of scanned lesions, and shrinkage (>10% reduction in initial volume) in 75%, with a mean/median tumor volume reduction of 51/60%. The extent of shrinkage was found to be 11–30%/31–60%/61–100% in 38/24/38% of lesions. Response rates (PD, SD, shrinkage) following the two applied LRT regimens, as well as those related to sarcoma and carcinoma diagnoses, were found to be comparable. Treatment tolerance was excellent (G0-1). Conclusions: Palliative LRT provides rapid subjective relief in ~80% of symptomatic patients. Radiologic shrinkage was stated in 75% of FU-scanned lesions, with a lifelong effect duration in most patients. LRT was found effective across histologies, with a similar extent of shrinkage in carcinoma and sarcoma following 1F SBRT- and 5F sib-LRT regimens, respectively. Full article

Introduction: Osteoarthritis (OA) is a chronic degenerative joint disease with limited treatment options focused primarily on symptom management. Emerging evidence suggests that dietary interventions may influence inflammation and pain through modulation of the gut microbiome and metabolome. Methods: We conducted a 4-week open-label pilot trial evaluating the effects of an anti-inflammatory dietary intervention (ITIS diet) in 20 patients with knee OA (ClinicalTrials.gov ID: NCT05559463, registered prior to enrollment; sponsor: University of California, San Diego; responsible party: Monica Guma; study start date: 1 October 2021). The following were assessed before and after the intervention: (1) clinical outcomes; (2) gut and salivary microbiomes; and (3) salivary, stool, and plasma metabolomes. Responders were defined as patients achieving ≥30% reduction in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores. Results: The ITIS diet was well-tolerated, with good adherence (66.2%) and a significant improvement in clinical outcomes, including reduced pain and improved overall health measured with the visual analog scale (VAS). Responders (n = 8) showed distinct gut microbiome and metabolome profiles compared to non-responders (n = 12). Notably, taxa within the Lachnospiraceae family exhibited dynamic, bidirectional shifts post-intervention: Anaerostipes and Limivivens were enriched among responders and negatively correlated with pain scores, while Oliverpabstia and Fusicatenibacter were depleted following dietary intervention. These taxa also showed strong correlations with anti-inflammatory metabolites, including hydroxydecanoic acid derivatives and pyridoxine. Furthermore, subsequent network analysis revealed more structured and selective microbiome–metabolome interactions in responders, specifically post-intervention. Conclusions: This pilot study shows that a short-term anti-inflammatory dietary intervention was associated with meaningful changes in the gut microbiome and metabolome. Members of the Lachnospiraceae family emerged as key taxa associated with pain reduction and anti-inflammatory metabolite production. Our findings suggest that specific microbial responses—rather than global diversity changes—may underlie dietary responsiveness in OA. Although exploratory and limited by sample size, our results support further investigation into personalized, microbiome-informed nutritional strategies for OA management. Full article

(1) Background: Idiopathic or familial nasal hyperkeratosis (NHK) may be considered a cosmetic issue in its uncomplicated form. Nevertheless, the prevention of secondary lesions could be advised by proper management. (2) Methods: In this multicentre, prospective, open-label pilot study, dogs with familial or idiopathic NHK received a topical emollient balm twice daily for 60 days. Evaluation of the global dermatological score (GDS; 0–12) on D0, D30, and D60 by owners and investigators was the main outcome. The score’s percentage decrease versus D0; the evolution of “dryness”, “lichenification”, “crusts”, and “affected area” (0–3); the correlation between observers and the evaluation of clinical improvement; and animal discomfort rated using a VAS (0–10) during follow-up were analysed. (3) Results: Twenty dogs completed the study. The mean GDS decreased significantly from Day 0 to Day 30 and Day 60 (p < 0.0001), with percentage reductions of 44.9% and 54.5% (investigators) and 54.3% and 62.3% (owners) on Day 30 and Day 60, respectively. Correlations between investigators and owners were significant for dryness, crusts (at Day 60), and the affected area, but not for lichenification. Animal discomfort scores decreased by more than 50% from Day 0. Owners reported high satisfaction with the product (mean score 8.1/10) and no adverse events occurred. (4) Conclusions: This open-label pilot study suggests that the tested balm is well tolerated and may improve clinical signs of NHK in dogs. Given the lack of a control group, small sample size, and absence of blinding, these results should be considered preliminary. Further randomized controlled trials and formal validation of the scoring system are warranted. Full article

Background: With increasing involvement of pharmacists in clinical situations and expanding scope of practice, the expectation and management of uncertainty is a desirable component of pharmacy education, leading to improved uncertainty tolerance (UT) as pharmacists. Methods: The purpose of this pilot study was to determine whether an inpatient rounding simulation (IRS) that exposes student pharmacists to a level of uncertainty leads to changes in tolerance of ambiguity scale (TAS) scores and self-reflection comments. A pre-/post-observational, pilot survey study was conducted, including student pharmacists in their second professional year at the United States School of Pharmacy who were enrolled in an associated lab-based course in Spring 2024. Student teams completed a mock IRS and responded to clinical questions in a timed environment. Students completed pre-/post-simulation TAS and self-reflection on uncertainty/UT within the simulation. Pre-/post-simulation TAS scores were analyzed with a paired t-test. Qualitative analysis was used to identify themes in self-reflection. Results: 59 students responded (48% response rate). TAS was not different pre-/post-IRS (63.2 vs. 62.6, p = 0.63). When individual subscales were compared, a statistically significant difference was found in the insolubility subscale (10.5 vs. 9.5; p = 0.02). Themes of uncertainty that emerged during qualitative analysis of pre-simulation included the clinical question posed to the team. Student pharmacists overcame uncertainty pre-simulation by working with their team and relying on the availability of resources. Themes of uncertainty emerging during qualitative analysis of post-simulation included discerning the best answer. Student pharmacists overcame uncertainty post-simulation by working with their team and cited working with their team as a positive aspect of the IRS experience. Conclusions: In this pilot study, student pharmacists had high TAS scores both pre- and post-simulation. Students utilized their teams and cited this as a positive in an uncertain environment. Full article

Diabetes is increasingly recognized as a chronic inflammatory disease marked by systemic metabolic disturbances, with endothelial dysfunction playing a central role in its complications. Hyperglycemia, a hallmark of diabetes, drives endothelial damage by inducing excessive reactive oxygen species (ROS) production, particularly hydrogen peroxide (H₂O₂). This oxidative stress impairs endothelial cells, which are vital for vascular health, leading to severe complications such as diabetic nephropathy, retinopathy, and coronary artery disease—major causes of morbidity and mortality in diabetic patients. Recent studies have highlighted the therapeutic potential of placenta-derived mesenchymal stem cells (pMSCs), in mitigating these complications. pMSCs exhibit anti-inflammatory, antioxidant, and tissue-repair properties, showing promise in reversing endothelial damage in laboratory settings. To explore their efficacy in a more physiologically relevant context, we used a streptozotocin (STZ)-induced diabetic mouse model, which mimics type 1 diabetes by destroying pancreatic beta cells and causing hyperglycemia. pMSCs were administered via intra-peritoneal injections, and their effects on endothelial injury and tissue damage were assessed. Metabolic tests, including glucose tolerance tests (GTTs) and insulin tolerance tests (ITTs) revealed that pMSCs did not restore metabolic homeostasis or improve glucose regulation. However, histopathological kidney, heart, and eye tissue analyses demonstrated significant protective effects. pMSCs preserved glomerular structure in the kidneys, protected cardiac blood vessels, and maintained retinal integrity, suggesting their potential to address diabetes-related tissue injuries. Although these findings underscore the therapeutic potential of pMSCs for diabetic complications, further research is needed to optimize dosing, elucidate molecular mechanisms, and evaluate long-term safety and efficacy. Combining pMSCs with other therapies may enhance their benefits, paving the way for future clinical applications. Full article

Recurrent urinary tract infections (UTIs) pose a significant clinical challenge in both human and veterinary medicine, due to antibiotic-resistant and biofilm-forming bacteria. We hypothesized that high glucose levels in diabetic animals enhance biofilm formation and reduce antibiotic efficacy, promoting infection persistence. This study analyzed Escherichia coli from a diabetic female Labrador Retriever with recurrent UTIs over 18 months, focusing on antimicrobial resistance, biofilm-forming capacity, and genomic characterization. Most isolates (9/11) were resistant to ampicillin and fluoroquinolones. Whole genome sequencing of six selected isolates revealed that they belonged to the multidrug-resistant ST1193 lineage, a globally emerging clone associated with persistent infections. Phylogenetic analysis revealed clonal continuity across six UTI episodes, with two distinct clones identified: one during a coinfection in the second episode and another in the last episode. High-glucose conditions significantly enhanced biofilm production and dramatically reduced antibiotic susceptibility, as evidenced by a marked increase in minimum biofilm inhibitory concentrations (MBICs), which were at least 256-fold higher than the corresponding minimum inhibitory concentration (MIC). Sulfamethoxazole–trimethoprim demonstrated the strongest antibiofilm activity, though this was attenuated in glucose-supplemented environments. This research highlights the clinical relevance of glucosuria in diabetic patients and emphasizes the need for therapeutic strategies targeting biofilm-mediated antibiotic tolerance to improve the management of recurrent UTIs. Full article

Background/Objectives: Patients with inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS) exhibit complex clinical profiles due to autonomic dysfunction. While sinus node sparing (SNS) hybrid ablation is emerging as a promising therapy, there are no established guidelines worldwide for post-procedure patient management and care is mainly based on telemonitoring. In contrast, our hybrid cardiac rehabilitation (HCR) program integrates inpatient care and home-based telerehabilitation. We aim to evaluate the implementation of the HCR program, patient acceptance and adherence, and the effectiveness of the Malmö POTS scoring system in monitoring disease progression and rehabilitation outcomes. Methods: Patients underwent a personalized HCR program after SNS. The program included early mobilization, psychological support, respiratory therapy, and structured exercise. Clinical outcomes were assessed using symptom burden (Malmö POTS score), ECG parameters, exercise duration, perceived exertion, and rehabilitation adherence. Results: All patients completed the inpatient phase, and 87% completed the home-based phase. In the early postoperative period, pericarditis, anemia, and benign rhythm disturbances were mild and self-limiting. The Malmö POTS score decreased from 65.3 to 25.7. Lower perceived exertion early in the program correlated with clinical improvement. At the 2-month follow-up, 81% of patients no longer met the clinical criteria for IST/POTS without the use of medications. The program was evaluated as safe, feasible, and well-tolerated, with high patient satisfaction. Conclusions: A well-organized hybrid cardiac rehabilitation program after SNS is feasible, safe, and well-tolerated in IST/POTS patients. The Malmö POTS score may support outcome monitoring. The integration of individualized training and telemedicine represents a promising development for patients post-SNS ablation. While this study demonstrates feasibility and potential benefits, further controlled studies are needed to evaluate its impact on long-term recovery and symptom control. Full article

Background and Clinical Significance: Inflammatory myofibroblastic tumors (IMTs) are rare neoplasms with low metastatic potential but a high recurrence rate. Approximately 60–80% of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, making ALK inhibitors (ALKis) a key therapeutic option. However, resistance to ALKis remains a significant clinical challenge, necessitating alternative treatment strategies. Case Presentation: We report the case of a 23-year-old woman diagnosed with a metastatic TPM3::ALK fusion-positive IMT, initially managed with crizotinib and ceritinib. Disease progression prompted a switch to alectinib, followed by lorlatinib in combination with immune checkpoint inhibitors (nivolumab + ipilimumab). The patient tolerated this regimen well, with manageable side effects, and has remained progression-free for over three years, demonstrating the potential efficacy of ALK-ICI combination therapy. Conclusions: This case highlights the rapid development of resistance to first- and second-generation ALKis and the emerging role of immune checkpoint inhibitors (ICIs) in IMT treatment. PD-L1 expression in ALK-positive IMTs suggests an immune escape mechanism, supporting combination ALK-ICI therapy as a viable approach. The successful long-term disease control achieved in this case underscores the importance of molecular profiling in guiding personalized treatment strategies for IMT. This report contributes to the growing body of evidence supporting precision medicine and immunotherapy in rare sarcomas. Full article

Aims: Individual weight loss results achieved with Glucagon-like Peptide-1 receptor agonists (GLP-1RA) vary significantly. Our aim was to describe the characteristics of patients with obesity who achieved ≥ 20% total weight loss (TWL) on liraglutide and appraise those findings through the prism of an evolving spectrum of GLP-1RA. Methods: This longitudinal prospective cohort study included 21 patients (90.5% females, age 50 (IQR 17) years, class II/III obesity (Body Mass Index ≥ 35 kg/m²) followed at the Edmonton Adult Bariatric Clinic for 65.1 (IQR 15.5) weeks. All patients received treatment with liraglutide 3.0 mg subcutaneously daily along with involvement in an integrated lifestyle modification program. Results: Liraglutide was well-tolerated, with its benefits experienced by >90% of patients. The vast majority were consistently tracking calories (95.2%, n = 20) and protein intake (90.5%, n = 19), achieving a calorie deficit of 651 (IQR 323) kcal/day, and had their mental health conditions and psychological issues successfully managed. At 16, 26, and 52 weeks, TWL was 14.3% (IQR 3.7), 18.7% (IQR 8.8), and 25.9% (IQR 9.6), respectively (p < 0.001). Over 20% TWL was achieved by 72.2% of patients by week 52. Conclusions: A select number of patients with obesity will attain weight loss that rivals bariatric surgery using liraglutide monotherapy. Despite liraglutide being less effective compared to newer agents on the market, some individuals will respond strongly and should be considered when other therapies are inaccessible. Given the societal burden and numerous challenges faced by people with obesity, GLP-1RA should be pursued in clinical practice to assist in achieving weight loss goals while being convenient and safe. Full article

Periodontitis is one of the most common inflammatory diseases and it is linked to the presence of a dysbiotic subgingival microbiome. The purpose of this review is to evaluate the impact of antimicrobial photodynamic therapy (aPDT) on the subgingival microbiome. Herein, based on an extensive evaluation of randomized controlled trials (RCTs), the effects of aPDT as a supplement to non-surgical periodontal therapy (NSPT) were found to be the main focus of these works. Studies that focused on analyzing microbiological results were selected, yielding contradictory results. The observed microbiological changes were variable, even though some studies showed notable improvements in clinical indicators such as bleeding on probing (BOP), clinical attachment level (CAL), and probing depth (PD). Several studies found that aPDT did not significantly reduce important periodontal pathogens such Tannerella forsythia, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. Nevertheless, after multiple aPDT sessions, other studies reported positive changes in the subgingival microbiome, with a rise in beneficial bacteria and a decrease in periodontopathogens. While aPDT seems to be a safe and well-tolerated adjuvant to non-surgical periodontal therapy, there is still conflicting evidence regarding how well it modulates the subgingival microbiota. Additional long-term research with larger sample sizes is required to evaluate the microbiological and clinical advantages of aPDT. Full article

Glucosinolates (GSLs) and their breakdown products, isothiocyanates (ITCs), are bioactive compounds with anti-inflammatory, antioxidant, and anticancer properties, mediated through key pathways such as Nrf2, NF-κB, and epigenetic regulation. However, their limited and variable bioavailability remains a key challenge. This review summarises the current clinical evidence on GSLs and ITCs, with a focus on their health effects and metabolic fate in humans. Recent findings on enzymatic and microbial metabolism are discussed, along with results from interventions involving whole vegetables, sprouts, and extracts. Although promising effects on blood pressure, lipid profiles, and glycaemic control have been observed, clinical studies are often limited by small sample sizes, study heterogeneity, and high inter-individual variability, particularly related to gut microbiota and host metabolic phenotype. Challenges like inconsistent biomarkers, formulation variability, and tolerability issues complicate data interpretation. To realise their full potential, larger, standardised, microbiome-informed trials with validated biomarkers and optimised delivery are needed to clarify host–compound–microbiome interactions and support evidence-based disease prevention strategies. Full article

Background: Periprosthetic joint infections (PJIs) remain among the most challenging complications in orthopedic surgery, often requiring prolonged antibiotic therapy and complex surgical interventions. Oritavancin, a long-acting semisynthetic lipoglycopeptide approved for acute bacterial skin and skin structure infections, has emerged as a potential off-label agent in PJI treatment due to its favorable pharmacokinetic properties, potent Gram-positive coverage, and documented antibiofilm activity. Objectives: This comprehensive review aims to assess the current clinical and preclinical data regarding the potential use of oritavancin in the management of PJIs. Methods: A comprehensive literature search was conducted in three major databases. Results: Six studies were included. In vitro data demonstrated strong activity of oritavancin against methicillin-resistant Staphylococcus aureus and S. epidermidis biofilms, particularly in synergy with rifampin. Clinical reports described successful outcomes in both acute and chronic PJI cases, including those with limited surgical options. Weekly or monthly dosing regimens were well-tolerated and effective in suppressive and curative contexts. Adverse events were infrequent but included infusion-related reactions. Conclusions: Oritavancin represents a promising adjunct or alternative to conventional antimicrobial regimens in PJIs, particularly for outpatient management or in patients with multidrug-resistant Gram-positive infections. Further prospective studies are needed to define its role, optimal dosing, and long-term efficacy in this complex clinical setting. Full article

Background and Clinical Significance: Zoledronic acid (ZA) is a widely used bisphosphonate for the prevention of skeletal-related events in patients with metastatic bone disease. While it is generally well tolerated, rare immune-mediated complications may be underrecognized. To date, myocarditis has not been reported in association with ZA. Case Presentation: A 35-year-old woman with metastatic pheochromocytoma developed acute, non-exertional chest pain approximately 36 h after receiving her first intravenous ZA infusion. Laboratory testing revealed elevated high-sensitivity troponin T, peaking at 1182 ng/L. Cardiac magnetic resonance imaging (CMR) demonstrated myocardial edema and subepicardial late gadolinium enhancement, consistent with acute myocarditis per the 2018 revised Lake Louise criteria. An extensive diagnostic workup excluded infectious, autoimmune, and ischemic causes. Symptoms and troponin levels improved following ZA discontinuation and supportive care. In the absence of alternative etiologies, and given the close temporal association with ZA administration, the diagnosis of presumed ZA-associated myocarditis was supported by clinical presentation, biochemical markers, and CMR findings, recognizing that histopathological confirmation is rarely pursued in clinically stable patients. Conclusions: To our knowledge, this is the first reported case of presumed zoledronic acid–associated myocarditis confirmed by cardiac MRI. This report highlights the diagnostic utility of CMR in suspected drug-related cardiac inflammation and the importance of considering myocarditis in patients presenting with unexplained chest pain following ZA infusion, particularly when other causes have been excluded. Full article

Background/Objectives: After first-line treatment, elderly patients with acute myeloid leukemia (AML) often become unfit to continue intensive chemotherapy despite having achieved a response. This trial aimed to determine the efficacy of maintenance treatment with azacitidine in AML patients who are ineligible to continue intensive treatment after remission. Methods: A single-arm, multicenter, phase II clinical trial (EudraCT: 2010-020432-18) including patients with AML with complete (CR) or partial remission (PR) after one or two cycles of intensive induction chemotherapy and ineligible to continue intensive treatment was conducted. Efficacy was measured as the response rate, progression-free survival (PFS), and overall survival (OS), and was assessed in the intention-to-treat (ITT) population (all patients). Quality of life was also assessed. Results: Thirty-two patients were included, with a mean age of 73.3 years (SD 3.8) (53.1% male); sixteen patients (50.0%) reached the sixth treatment cycle. The best response was CR in 11 patients (68.8%) and PR in 2 patients (12.5%) at cycle six, and CR in 15 patients (46.9%) and PR in 5 patients (15.6%) overall. The median PFS was 6.7 months (95% CI 3.1–8.7), and OS was 11.5 months (95% CI 6.6–15.9). The daily function (p = 0.0296), cognitive function (p = 0.0412), and social function (p = 0.0275) scales of the EORTC QLQ-C30 questionnaire significantly improved. Thirty-one patients (96.9%) experienced adverse events; six (1.9%) were serious. Conclusions: Azacitidine is a safe and well-tolerated maintenance treatment option for AML patients unfit for intensive therapy following a response to induction, although the single-arm phase II design precludes direct causal inference. Patients achieved promising results regarding PFS and remission rates, with improved quality of life. Full article

Background: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery with cardiopulmonary bypass (CPB) affecting between 5% and 40% of patients, which leads to hemodynamic instability, an increased risk of thromboembolism, decompensated heart failure, prolonged hospitalization, and higher treatment costs. Currently, there are no universally accepted guidelines for preventing POAF. Methods: A single-center, prospective, randomized controlled trial, “The Effect of Colchicine on the Occurrence of Atrial Fibrillation after Cardiac Surgery” (CAFE), ClinicalTrials.gov ID: NCT06798714, was conducted. The study included 140 patients with coronary artery disease randomized into two groups of 70 patients each. Group 1 (control group) received standard postoperative care. Group 2 (intervention group) received colchicine (Colchicum-Dispert at a dose of 500 mcg 4 h before coronary artery bypass grafting (CABG) with CPB and at a dose of 500 mcg twice daily for 10 days postoperatively) and underwent intraoperative pericardial fenestration using an original technique. Results: Perioperative colchicine administration combined with intraoperative pericardial fenestration reduced POAF incidence to 2.9% compared to the control group with POAF incidence of 12.9% (p < 0.05). This management strategy was not associated with an increased incidence of infectious complications, gastrointestinal disorders, or elevated levels of alanine aminotransferase, aspartate aminotransferase, or creatinine. Conclusions: Perioperative colchicine administration combined with pericardial fenestration during CABG with CPB is associated with a reduced POAF incidence, good tolerability, and does not contribute to an increased incidence of infectious complications or impaired liver and renal function. Full article