OBJECTIVE: The study objectives were (i) to explore the agreement between the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and physical examination in assessing enthesitis in patients with spondyloarthritis (SpA) and (ii) to investigate the prevalence and clinical relevance of subclinical enthesitis in this population. METHODS: Twenty rheumatology centers participated in this cross-sectional study. Patients with SpA, including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for "active enthesitis" by our group. Subclinical enthesitis was defined as the presence of "active enthesitis" in ≥1 enthesis in patients with SpA without clinical enthesitis (ie, number of positive entheses on physical examination and Leeds Enthesitis Index score = 0). RESULTS: A total of 4,130 entheses in 413 patients with SpA (224 with axSpA and 189 with PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (ie, enthesophytes) to almost perfect (ie, power Doppler and "active enthesitis"). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158 (38.3%) of 413 patients with SpA with clinical enthesitis, 108 (68.4%) exhibited no "active enthesitis" on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of patients with SpA with and without subclinical enthesitis. CONCLUSION: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in patients with SpA.
- MeSH
- Achilles Tendon diagnostic imaging MeSH
- Axial Spondyloarthritis diagnostic imaging MeSH
- Adult MeSH
- Enthesopathy * diagnostic imaging MeSH
- Physical Examination * MeSH
- Middle Aged MeSH
- Humans MeSH
- Cross-Sectional Studies MeSH
- Arthritis, Psoriatic diagnostic imaging complications MeSH
- Spondylarthritis * diagnostic imaging complications MeSH
- Ultrasonography * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Patients with testicular lymphoma are at an increased risk of central nervous system (CNS) disease. Optimal strategy for CNS relapse prevention is unknown. We analyzed treatment strategies, cumulative incidence of CNS relapse and prognosis in 229 patients with diffuse large B-cell lymphoma (DLBCL) and testicular involvement: 157 primary testicular lymphomas (PTL) in clinical stages IE/IIE and 72 patients in advanced stages (T-DLBCL) IIIE/IV. Treatments for PTL vs. T-DLBCL included: rituximab-based chemotherapy (80.9% vs. 90.3%), orchiectomy (94.3% vs. 65.3%) and contralateral testicular irradiation (59.8% vs. 44.4%). Majority (84.3%) received CNS prophylaxis with similar rates of prophylactic methotrexate (intravenous 19.1% vs. 16.6%, intrathecal 40.8% vs. 40.4%, or both 24.2% vs. 27.8%) between PTL and T-DLBCL (p = 0.89). Median follow-up was 51.8 months. CNS relapses occurred in 14 (6.1%) of 63 relapsing patients. The 5-year cumulative incidence of CNS relapse in PTL was 4.5% and in T-DLBCL 12.1%. Median time to CNS relapse was 21.9 months. In univariate analyses, orchiectomy was the single significant factor associated with lower risk of CNS relapse in PTL (HR = 0.11 [95% CI, 0-0.124], p = 0.001). Rituximab significantly reduced CNS relapse risk in T-DLBCL (HR = 0.1002, p = 0.0005). Median progression-free survival (PFS) and overall survival (OS) following CNS relapse was dismal in T-DLBCL compared to PTL (PFS 1.6 vs. 37.8 months, p = 0.04 and OS 2.3 vs. 37.8 months, p = 0.05). This study confirmed a favorable impact of rituximab in prevention of CNS relapse in T-DLBCL. Methotrexate prophylaxis did not alter CNS relapse risk. Prognosis of CNS relapse is particularly poor in T-DLBCL.
- MeSH
- Lymphoma, Large B-Cell, Diffuse * therapy epidemiology MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Methotrexate therapeutic use MeSH
- Young Adult MeSH
- Central Nervous System Neoplasms * therapy epidemiology prevention & control mortality MeSH
- Follow-Up Studies MeSH
- Orchiectomy MeSH
- Prognosis MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Retrospective Studies MeSH
- Rituximab * therapeutic use MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Testicular Neoplasms * therapy pathology epidemiology MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. METHODS: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk. RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking (RERI = 0.24, 95% confidence interval [CI] = 0.13, 0.36), ever smoking (0.11 [0.05, 0.16]), high body mass index (female 0.09 [0.05, 0.13], male 0.10 [0.05, 0.14]), or high red meat intake (highest versus lowest quartile 0.18 [0.09, 0.27]) was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/nonsteroidal anti-inflammatory drugs use (-0.16 [-0.20, -0.11]) or higher intake of fruit, fiber, or calcium (highest quartile versus lowest quartile -0.12 [-0.18, -0.050]; -0.16 [-0.23, -0.09]; -0.11 [-0.18, -0.05], respectively) than those with average genetic susceptibility. CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.
- MeSH
- Diet MeSH
- Adult MeSH
- Genetic Predisposition to Disease * MeSH
- Body Mass Index MeSH
- Gene-Environment Interaction * MeSH
- Polymorphism, Single Nucleotide MeSH
- Colorectal Neoplasms * genetics epidemiology MeSH
- Smoking adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Logistic Models MeSH
- Alcohol Drinking MeSH
- Risk Factors MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
PURPOSE: STereotactic Arrhythmia Radioablation (STAR) showed promising results in patients with refractory ventricular tachycardia. However, clinical data are scarce and heterogeneous. The STOPSTORM.eu consortium was established to investigate and harmonize STAR in Europe. The primary goal of this benchmark study was to investigate current treatment planning practice within the STOPSTORM project as a baseline for future harmonization. METHODS AND MATERIALS: Planning target volumes (PTVs) overlapping extracardiac organs-at-risk and/or cardiac substructures were generated for 3 STAR cases. Participating centers were asked to create single-fraction treatment plans with 25 Gy dose prescriptions based on in-house clinical practice. All treatment plans were reviewed by an expert panel and quantitative crowd knowledge-based analysis was performed with independent software using descriptive statistics for International Commission on Radiation Units and Measurements report 91 relevant parameters and crowd dose-volume histograms. Thereafter, treatment planning consensus statements were established using a dual-stage voting process. RESULTS: Twenty centers submitted 67 treatment plans for this study. In most plans (75%) intensity modulated arc therapy with 6 MV flattening filter free beams was used. Dose prescription was mainly based on PTV D95% (49%) or D96%-100% (19%). Many participants preferred to spare close extracardiac organs-at-risk (75%) and cardiac substructures (50%) by PTV coverage reduction. PTV D0.035cm3 ranged from 25.5 to 34.6 Gy, demonstrating a large variety of dose inhomogeneity. Estimated treatment times without motion compensation or setup ranged from 2 to 80 minutes. For the consensus statements, a strong agreement was reached for beam technique planning, dose calculation, prescription methods, and trade-offs between target and extracardiac critical structures. No agreement was reached on cardiac substructure dose limitations and on desired dose inhomogeneity in the target. CONCLUSIONS: This STOPSTORM multicenter treatment planning benchmark study not only showed strong agreement on several aspects of STAR treatment planning, but also revealed disagreement on others. To standardize and harmonize STAR in the future, consensus statements were established; however, clinical data are urgently needed for actionable guidelines for treatment planning.
- MeSH
- Benchmarking * MeSH
- Radiotherapy Dosage MeSH
- Tachycardia, Ventricular surgery radiotherapy MeSH
- Consensus * MeSH
- Organs at Risk * radiation effects MeSH
- Humans MeSH
- Radiotherapy Planning, Computer-Assisted * standards methods MeSH
- Radiosurgery * standards methods MeSH
- Radiotherapy, Intensity-Modulated methods standards MeSH
- Heart radiation effects MeSH
- Arrhythmias, Cardiac MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Europe MeSH
INTRODUCTION: Diagnostic cortical stimulation (CS) in intracranial electroencephalography (iEEG) is an established epilepsy presurgical assessment tool to delineate relevant brain functions and elicit habitual epileptic seizures. Currently, no consensus exists as to whether CS should be routinely performed in pediatric patients. A significant challenge is their limited ability to cooperate during the procedure or to describe non-observable seizure semiology features. Our goal was to identify the spectrum of CS practices in Canada, for both eloquent cortex mapping and seizure stimulation. METHODS: An online survey, answered by all 8 Canadian pediatric epilepsy centers, enquired about implantation, stimulation methods, and use of standardized protocols. A systematic literature review extracted detailed stimulation parameters. RESULTS: Most of the institutions (n = 7/8) reported performing CS during presurgical evaluation. Four institutions indicated they perform stimulation in all implanted patients for the purpose of eloquent cortex mapping and seizure stimulation. The majority of physicians had their individual approach to CS. A largely variable approach to CS, mainly in the choice of stimulation parameters (i.e., train and pulse duration), was observed, with the highest variance concerning the purpose of seizure stimulation. The literature review highlighted an overall small sample size and minimal number of publications. Even though there is a rising trend towards stereotactic iEEG implantation, more data were available on subdural EEGs. CONCLUSION: This study shows individual and sparsely validated approach to CS in pediatric epilepsy. The literature review underscores the urgent need to harmonize pediatric intracranial EEG practices. More multicenter studies are needed to identify safe stimulation thresholds and allow implementation of evidence-based guidelines.
- MeSH
- Child MeSH
- Electroencephalography methods MeSH
- Electrocorticography methods MeSH
- Epilepsy surgery physiopathology diagnosis MeSH
- Humans MeSH
- Brain Mapping * methods MeSH
- Cerebral Cortex physiopathology MeSH
- Pediatrics methods MeSH
- Surveys and Questionnaires MeSH
- Seizures * physiopathology diagnosis MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Systematic Review MeSH
- Geographicals
- Canada MeSH
PURPOSE: Tropomyosin receptor kinase (TRK) fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients. EXPERIMENTAL DESIGN: We conducted an international retrospective cohort study of patients with TRK fusion-driven central nervous system tumors. RESULTS: A total of 119 patients were identified. The median age at the time of diagnosis was 4.5 years. The majority were reported to have a histology consistent with a diagnosis of high-grade glioma (HGG; 57.1%) followed by low-grade glioma (LGG; 27.7%). Pediatric patients had a better prognosis, with a median overall survival of 185.5 months compared with 24.8 months in adults (P < 0.0001). Patients with LGG also had a better outcome when compared with HGG (P = 0.0012). The objective response was 68.8% with larotrectinib compared with 38.1% for nontargeted treatment. CONCLUSIONS: Children with LGG had a favorable outcome compared with adult glioma and HGG. TRK inhibitors seem to improve tumor control.
- MeSH
- Child MeSH
- Adult MeSH
- Gene Fusion MeSH
- Oncogene Proteins, Fusion * genetics MeSH
- Glioma * genetics pathology mortality therapy MeSH
- Protein Kinase Inhibitors therapeutic use MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Membrane Glycoproteins MeSH
- Adolescent MeSH
- Young Adult MeSH
- Central Nervous System Neoplasms * genetics therapy mortality pathology MeSH
- Child, Preschool MeSH
- Prognosis MeSH
- Pyrazoles therapeutic use MeSH
- Pyrimidines therapeutic use MeSH
- Receptor, trkA * genetics antagonists & inhibitors MeSH
- Receptor, trkB genetics antagonists & inhibitors MeSH
- Receptor, trkC genetics antagonists & inhibitors MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Neoplasm Grading MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The Satisfaction With Life Scale (SWLS) is a widely used self-report measure of subjective well-being, but studies of its measurement invariance across a large number of nations remain limited. Here, we utilised the Body Image in Nature (BINS) dataset-with data collected between 2020 and 2022 -to assess measurement invariance of the SWLS across 65 nations, 40 languages, gender identities, and age groups (N = 56,968). All participants completed the SWLS under largely uniform conditions. Multi-group confirmatory factor analysis indicated that configural and metric invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional SWLS model has universal applicability. Full scalar invariance was achieved across gender identities and age groups. Based on alignment optimisation methods, partial scalar invariance was achieved across all but three national groups and across all languages represented in the BINS. There were large differences in latent SWLS means across nations and languages, but negligible-to-small differences across gender identities and age groups. Across nations, greater life satisfaction was significantly associated with greater financial security and being in a committed relationship or married. The results of this study suggest that the SWLS largely assesses a common unidimensional construct of life satisfaction irrespective of respondent characteristics (i.e., national group, gender identities, and age group) or survey presentation (i.e., survey language). This has important implications for the assessment of life satisfaction across nations and provides information that will be useful for practitioners aiming to promote subjective well-being internationally.
- MeSH
- Adult MeSH
- Factor Analysis, Statistical MeSH
- Gender Identity * MeSH
- Language MeSH
- Quality of Life MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Personal Satisfaction * MeSH
- Surveys and Questionnaires MeSH
- Psychometrics methods MeSH
- Aged MeSH
- Age Factors MeSH
- Self Report MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015. Since its conception, MIBiG has been regularly updated to expand data coverage and remain up to date with innovations in natural product research. Here, we describe MIBiG version 4.0, an extensive update to the data repository and the underlying data standard. In a massive community annotation effort, 267 contributors performed 8304 edits, creating 557 new entries and modifying 590 existing entries, resulting in a new total of 3059 curated entries in MIBiG. Particular attention was paid to ensuring high data quality, with automated data validation using a newly developed custom submission portal prototype, paired with a novel peer-reviewing model. MIBiG 4.0 also takes steps towards a rolling release model and a broader involvement of the scientific community. MIBiG 4.0 is accessible online at https://mibig.secondarymetabolites.org/.
Liver-enriched antimicrobial peptide 2 (LEAP2) is a natural antagonist/inverse agonist of ghrelin receptor GHSR. Its truncated palmitoylated analog palm-LEAP2(1-14) promised anti-obesity properties because it exhibited favourable stability and an acute anorexigenic effect in our previous studies. Here we demonstrate desirable palm-LEAP2(1-14) pharmacokinetics, with significant levels of the peptide persisting in mouse blood 3 h after its subcutaneous administration. Palm-LEAP2 (1-14) reduced ghrelin-induced c-Fos immunoreactivity in arcuate nucleus and area postrema, in line with previously described silencing of ghrelin orexigenic effect. In spite of this, anti-obesity effect was not reached by two-week palm-LEAP2(1-14) treatment in mice with diet-induced obesity. Similarly, palm-LEAP2(1-14) administered simultaneously with high-fat diet feeding for 8 weeks did not protect mice from development of obesity and related biochemical changes. However, palm-LEAP2(1-14) kept its ability to attenuate liver de novo lipogenesis, and prominently lowered liver gene expression of nuclear receptors PPARG, SREBF1 and PPARA, and also expression of lipogenic and lipolytic enzymes. In our recent study, we described a high-fat diet-induced ghrelin resistance, reversible by switch to standard diet, followed by resistance to the acute anorexigenic effects of palm-LEAP2(1-14). Here we conclude that this resistance to palm-LEAP2(1-14) in obesity is probably selective and does not concern its ability to inhibit liver lipid metabolism.
- MeSH
- Diet, High-Fat * adverse effects MeSH
- Ghrelin * metabolism MeSH
- Liver * metabolism drug effects MeSH
- Antimicrobial Cationic Peptides metabolism MeSH
- Lipogenesis drug effects genetics MeSH
- Lipid Metabolism * drug effects MeSH
- Mice, Inbred C57BL * MeSH
- Mice MeSH
- Obesity * metabolism MeSH
- Peptide Fragments MeSH
- Proto-Oncogene Proteins c-fos metabolism genetics MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 μ mol/L=0, K1: 250-450 μ mol/L=4, K2: >450 μ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.
- MeSH
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis * diagnosis MeSH
- Atrophy MeSH
- Fibrosis MeSH
- Creatinine MeSH
- Kidney MeSH
- Middle Aged MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Antibodies, Antineutrophil Cytoplasmic * MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
