Citations

Introduction: Delirium is a common, severe neuropsychiatric syndrome in hospitalised older adults. We evaluated use of validated delirium assessment tools, adherence to national guidelines and prevalence and management of delirium across Scotland, identifying barriers to effective care. Methods: Secondary analysis of national survey data, collected by participating clinicians on World Delirium Awareness Day (15 March 2023). Results: Among 120 responses (3,257 patients), the 4AT was the most frequently used assessment tool (75%), while 14% of units reported using clinical judgement alone. The delirium assessment rate was 74%, with a prevalence of 22% at 8 am. Management protocols varied, with frequent routine non-pharmacological interventions including pain management (88%), hydration (87%) and open family visiting (80%). Barriers to delirium care included insufficient staffing and training. Conclusion: While many hospital settings follow national delirium guidelines, some still rely on clinical judgement for assessment, with variability in management protocols and practices. We have highlighted key barriers to effective delirium care in Scotland.

ABSTRACT Background Flat bone chondrosarcomas have worse outcomes than extremity tumors, but there is no data directly comparing the different flat bones. The aim of this study was to examine differences in recurrence and survival between pelvic and scapular chondrosarcoma. Methods One hundred and sixty‐nine (42 scapula, 127 pelvic) patients with chondrosarcoma who underwent surgical resection were reviewed. High‐grade tumors were defined as lesions that were Grade 3 or dedifferentiated on surgical pathology. Results Patients with low‐intermediate grade lesions of the scapula were more likely to have positive margins during definitive surgical management (14% vs. 3%, OR 5, 95% CI [1.15, 22.6], p = 0.02), however, this did not translate to differences in recurrence or survival ( p > 0.05). The presence of an associated soft tissue mass in low‐intermediate grade lesions was not associated with increased recurrence. Among high‐grade tumors, patients with scapular lesions had worse DSS (HR 2.99, 95% CI [1.05, 8.51], p = 0.04). One‐ and 2‐year DSS for high‐grade pelvic tumors was 75% and 57%, respectively, and 50% and 33% for scapular tumors. Conclusion Survival for high‐grade chondrosarcoma of the flat bones is poor, particularly for those of the scapula. Despite a higher rate of positive margins for low‐intermediate grade lesions of the scapula, there was no significant difference in survival compared to low‐intermediate grade lesions of the pelvis. Additional studies with larger sample sizes are needed to further elucidate differences between these locations.

Abstract Progression of disease within 24 months of initial immunochemotherapy (POD24) is a negative prognostic factor for patients with follicular lymphoma (FL). There is no standard treatment after POD24. Assembling an academic-based cohort from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence, we evaluated patterns of care and outcomes for 220 patients with FL with POD24 and retained FL histology. Therapy after POD24 was heterogeneous, with no treatment category accounting for >25% of the total. Among patients initially treated with bendamustine-rituximab, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was the predominant second-line choice (48%). Among patients initially treated with R-CHOP, aggressive salvage therapy was the predominant second-line choice (38%). Overall response rate to therapy after POD24 was 64% (95% confidence interval [CI], 56-70); complete response rate was 39% (95% CI, 32-46). The median event-free survival for therapy after POD24 was 9.8 months (95% CI, 7.3-12.1); 5-year overall survival (OS) was 71% (95% CI, 65-78). OS was inferior for patients aged >70 years (hazard ratio [HR], 2.31; 95% CI, 1.27-4.20) and those with high-risk FL International Prognostic Index scores at diagnosis (HR, 2.10; 95% CI, 1.23-3.60). No treatment category stood out with more favorable results. Cause of death was predominantly lymphoma related. Patients with follicular histology at their POD24 event had a low cumulative incidence of transformation (1.1% at 5 years). Our study is among the largest cohorts describing contemporary patterns of care for patients with POD24, providing a focused data set useful for interpreting and designing prospective clinical trials in this population.

Background: Osteochondritis dissecans (OCD) of the knee is a focal idiopathic alteration of subchondral bone and/or its precursor with risk for instability and disruption of adjacent cartilage. Treatment options focused on preventing premature osteoarthritis vary depending on multiple patient and lesion characteristics, including lesion mobility. Purpose: To differentiate lesion mobility before arthroscopy using a multivariable model that includes patient demographic characteristics and physical examination findings. Study Design: Cohort study (Diagnosis); Level of evidence, 2. Methods: Demographic, preoperative physical examination, and radiographic data were collected from a multicenter national prospective cohort of patients with OCD of the knee. Inclusion criteria included patients <19 years of age and patients with arthroscopically confirmed mobility status based on the Research on Osteochondritis Dissecans of the Knee arthroscopy classification. Multivariable logistic regression analysis using stepwise model selection was used to determine factors associated with the likelihood of a mobile versus an immobile lesion. A 75% partition of the data was used for model training, and 25% was used as a validation cohort. Quantitative model fit statistics were computed using the holdout data, including sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC), along with the corresponding 95% CI. Results: A total of 407 patients in the prospective cohort met inclusion criteria, and 62% were male. The mean ± SD age was 13.7 ± 2.2 years, height 161.8 ± 5.3 cm, and weight 59.2 ± 42.2 kg. Arthroscopic evaluation yielded 235 immobile and 172 mobile lesions. Multivariable analysis determined that the best model to predict lesion mobility included chronologic age ≥14 years ( P < .001), effusion on physical examination ( P < .001), and any loss of range of motion on physical examination ( P = .07), while controlling for male sex ( P = .38) and weight >54.4 kg ( P = .12). In the 25% holdout validation sample (n = 102), a sensitivity of 83%, a specificity of 82%, and an AUC of 0.89 (95% CI, 0.82-0.95) were achieved with these predictive factors. Conclusion: Age, effusion, and loss of motion can predict knee OCD lesion mobility at the time of arthroscopy. Education about lesion mobility can help with surgical planning and patient and family counseling.

Abstract BACKGROUND Recurrent anaplastic astrocytoma (AA), a grade 3 brain cancer, remains an unmet medical need. STELLAR was a phase III randomized, open-label trial of eflornithine (ornithine decarboxylase inhibitor) with lomustine versus lomustine alone, originally for patients with recurrent AA. However, as the WHO definition of AA evolved during trial conduct (e.g., excluding IDH wild-type disease), we determined results in both the original ITT population and by revised molecularly defined WHO 2021 diagnoses in pre-planned analyses. METHOD Key eligibility: age ≥ 18, AA (2016 WHO criteria), first recurrence ≥ 6 months after radiation and temozolomide, KPS ≥ 70, no imaging findings consistent with grade 4 glioblastoma. Stratification: IDH, age, resection extent, and geography. Patients were randomized to Arm A: eflornithine (2.8 g/m2 TID Q 2/3 weeks) with lomustine (90 mg/m2 Q 6 weeks) or Arm B: lomustine (110 mg/m2 Q 6 weeks). Primary endpoint was OS. The pre-specified hazard ratio (HR) goal was 0.667 based on projected median OS (mOS) increase to 18 months from 12 months. RESULTS 343 pts (172/171 Arms A/B) were randomized (105 sites, 8 countries). ITT analysis found no difference between arms (mOS 23.4 vs. 20.3 months, HR = 0.94). However, a pre-specified subset analysis in IDH mutant, 2021 WHO-defined grade 3 astrocytoma (n=194), showed significant improvement with eflornithine (mOS 34.9 vs. 23.5 months, HR = 0.64, log rank p = 0.016) and PFS (15.8 vs. 7.2 months, HR = 0.58, log rank p = 0.015). No difference was observed in the IDH wild-type subset. AEs were consistent with historic data. CONCLUSION There was no difference in OS between arms in the ITT analysis. However, medically meaningful and statistically significant OS and PFS benefits were observed with eflornithine in the pre-planned analysis of patients with molecularly defined 2021 WHO CNS grade 3 astrocytoma.

Knowledge of the adaptation of the soft tissue to mechanical factors and biomolecules would be essential to better understand the mechanism of tendon injury and to improve the outcome of tendon repair. The responses to these factors could be different for the distinct types of cells in the tendon: cells from the tendon sheath, fibroblasts from the epitenon surface, or fibroblasts from the internal endotenon. In this study, we examined the mechanical and histological characteristics of the rate of contraction of the collagen gel seeded with epitenon and endotenon fibroblasts. The rate of contraction and the mechanical property of the contracted construct depend on the gel concentration and also the treatment of TGF-β 1 .

Background: Pathologic reflux is a common debilitating digestive condition and anti-reflux surgery is an effective treatment option. Depending on the specifics of the procedure, anti-reflux surgery leads to distinct changes in the endoscopic appearance of the esophagogastric junction (EGJ). This American Foregut Society (AFS) white paper develops nomenclature for describing the endoscopic characteristics of the EGJ after commonly performed laparoscopic antireflux operations. Methods: The AFS Anti-Reflux Barrier Collaborative analyzed the anatomic manipulation and corresponding endoscopic appearance of the EGJ after commonly performed anti-reflux surgery including: (1) 360° anterior/posterior (AP) fundoplication (Nissen); (2) posterior partial fundoplication (Toupet); (3) anterior partial fundoplication (Watson, Dor); (4) magnetic sphincter augmentation; and (5) concomitant hiatal hernia repair with transoral fundoplication (cTIF). Results: Characteristics common to the anti-reflux surgery procedures include restoration of intra-abdominal esophageal length and crural diaphragm repair such that the hiatal aperture is no longer visible in the retroflexed endoscopic view. With regard to the geometry of anti-reflux procedures, the Collaborative established that when evaluated endoscopically in retroflection, the surgically constructed valve should be described in reference to the angle of His and the extent of anatomic change described in terms of (1) the depth of the anterior and posterior grooves, (2) the apposition of the valve collar to the endoscope, (3) the length of the valve, and (4) the position of the squamocolumnar junction relative to the lip of the valve. Conclusions: Current anti-reflux operations share much in common but employ varying degrees of valvular reconstruction leading to distinct endoscopic characteristics. Developing a consistent nomenclature for describing the appearance of the post-surgical valve is essential to develop a better understanding of how variables such as the tightness of the hiatal repair, tightness of the valve collar, and length of the valve can impact the outcome of anti-reflux surgery and predict reflux recurrence.

Background: Many medications, electrolyte perturbations, and several diseases can prolong the QTc beyond its 99 th percentile value resulting in acquired QT prolongation (AQTP). In contrast, approximately 1 in 2,000 people have congenital long QT syndrome (LQTS) hallmarked by pathological QT prolongation. Recently, we developed an AI-ECG model to distinguish these two groups, however this model does not elucidate which ECG segments distinguish LQTS from AQTP. Methods: Using the cohort from our previous study, all patients with LQTS evaluated in the Mayo Clinic Genetic Heart Rhythm Clinic and controls were included. Next, every patient/control with ≥1 ECG above age- and sex-specific 99 th percentile for QTc was selected and matched at 1:100 ratio. Subsequently, 5 ML algorithms (logistic regression, Naïve Bayes, random forest, Gradient boosting and XGBoost) were trained using 52 features representing segments of the 12-lead ECG (e.g. wave peak times, amplitudes, areas under wave, duration; 52x12 features). Training and testing sets were spilt at 80:20 ratio and 5-fold cross validation was performed to prevent overfitting. Following analysis, the top 100 features were re-analyzed to refine results. Results: Among >1,600 patients with LQTS, 690 had ≥ 1 ECG with a QTc above the established threshold compared to 28,186 controls. Following age- and sex-matching and splitting, 22,410 (training), and 5,776 (testing) ECGs were used. Of the 5 ML algorithms, XGBoost demonstrated best performance (AUC 0.913, accuracy 0.836, sensitivity 0.857, specificity 0.835) to distinguish LQTS from AQTP. Following filtering for the top 100 features, performance of the algorithm remained high with AUC of 0.912 (accuracy 0.84, sensitivity 0.841, specificity 0.84). The features with the greatest impact on classification output included time from T wave onset to T wave peak (leads V1, V4, V4), QRS interval duration (leads V1, V3, V4, aVR), and amplitude at end of ST segment (aVF). Conclusions: Distinguishing monogenetically driven LQTS from multi-factorial AQTP is critical in clinical practice for proper management, mitigation of offending QT-prolonging factors, and treatment. Building on our previously developed AI-ECG-LQTS ‘mutation detector’, this model identifies some of the elements within the ‘black box’ that distinguish an ECG and QTc stemming from a patient with LQTS compared to a similar prolonged QTc value that is arising due to non-genetic, acquired QT-prolonging factors.