Androgen deprivation and radiotherapy with or without docetaxel for localized high-risk prostate cancer: Long-term follow-up from the randomized NRG Oncology RTOG 0521 trial

BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer. OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT. DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (\u3e50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was overall survival (OS). Analyses with Cox proportional hazards were performed as prespecified in the protocol; however, there was evidence of nonproportional hazards. Thus, a post hoc analysis was performed using the restricted mean survival time (RMST). The secondary endpoints included biochemical failure, distant metastasis (DM) as detected by conventional imaging, and disease-free survival (DFS). RESULTS AND LIMITATIONS: After 10.4 yr of median follow-up among survivors, the hazard ratio (HR) for OS was 0.89 (90% confidence interval [CI] 0.70-1.14; one-sided log-rank p = 0.22). Survival at 10 yr was 64% for ADT + EBRT and 69% for ADT + EBRT + docetaxel. The RMST at 12 yr was 0.45 yr and not statistically significant (one-sided p = 0.053). No differences were detected in the incidence of DFS (HR = 0.92, 95% CI 0.73-1.14), DM (HR = 0.84, 95% CI 0.73-1.14), or prostate-specific antigen recurrence risk (HR = 0.97, 95% CI 0.74-1.29). Two patients had grade 5 toxicity in the chemotherapy arm and zero patients in the control arm. CONCLUSIONS: After a median follow-up of 10.4 yr among surviving patients, no significant differences are observed in clinical outcomes between the experimental and control arms. These data suggest that docetaxel should not be used for high-risk localized prostate cancer. Additional research may be warranted using novel predictive biomarkers. PATIENT SUMMARY: No significant differences in survival were noted after long-term follow-up for high-risk localized prostate cancer patients in a large prospective trial where patients were treated with androgen deprivation therapy + radiation to the prostate ± docetaxel

COVID-19 vaccination in autoimmune diseases (COVAD) Study: vaccine safety and tolerance in rheumatoid arthritis

OBJECTIVES: The COVID-19 vaccination in autoimmune diseases (COVAD) study aimed to assess short-term COVID-19 vaccination-related adverse events (AEs) in rheumatoid arthritis (RA) patients. METHODS: An online self-reported questionnaire (March-December 2021) was used to capture data related to COVID-19 vaccination-related AEs in RA, other autoimmune rheumatic diseases (AIRDs) (excluding RA and inflammatory myositis), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). Descriptive and multivariable regression analyses were performed. RESULTS: Of the 9462 complete respondents, 14.2% (n = 1347) had been diagnosed with RA who had a mean (standard deviation) age of 50.7 (13.7) years, and 74.2% were women, and 49.3% were Caucasian. In total, 76.9% and 4.2% of patients with RA reported minor and major AEs, respectively. Patients with active and inactive RA had similar AE and hospitalization frequencies. Overall, AEs were reported more frequently by BNT162b2 and mRNA-1273 recipients and less frequently by BBV152 recipients compared with the rest. Major AE and hospitalization frequencies were similar across recipients of different vaccines. Patients receiving methotrexate and hydroxychloroquine reported fewer minor AEs than those patients not on them. Compared with HCs and patients with other AIRDs, patients with RA reported similar total AEs, overall minor AEs, and hospitalizations. Compared with nrAIDs, patients with RA reported lower frequencies of overall AEs, minor AEs (both OR = 0.7; 95%CI = 0.5-0.9), and injection site pain (OR = 0.6; 95%CI = 0.5-0.8) with similar major AE and hospitalization frequencies. CONCLUSION: Despite the differences in AE frequency across different COVID-19 vaccines, all were well tolerated in patients with RA and were comparable to HCs providing reassurance to the safety of COVID-19 vaccination in them

World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF) Core Set Development for Interstitial Lung Disease

Background: The World Health Organization (WHO) introduced the International Classification of Functioning, Disability, and Health (ICF) as a scientific method of disability data collection comprised of >1,200 categories describing the spectrum of impairment types (functional, symptoms-based and anatomical) under the bio-psycho-social model with consideration of environmental and personal factors (pf). ICF Core Sets and ICF Checklists are streamlined disease-specific resources for clinical use, service provision, and for use in health economics and health policy. ICF can disclose strengths and weaknesses across multiple patient-reported outcome measures (PROMs) and help consolidate best-fitting question-items from multiple PROMs. Interstitial lung diseases (ILDs), are generally progressive, with restrictive physiology sometimes occurring in the context of multi-organ autoimmunity/inflammatory conditions such as connective tissue diseases (CTDs). In spite of significant associated morbidity and potential disability, ILD has yet to be linked to the ICF. Methods: Each instrument and their question-items within the consensus-recommended core sets for clinical trials in ILD were deconstructed to single concept units, and then linked per updated ICF linkage rules. Inter-linker agreement was established. Three additional subsequently validated measures were also included. Results: One-hundred-eleven ICF categories were identified for ten PROMs and three traditional objective measures that were amenable to ICF linkage. The proportion of agreement ranged from 0.79 (95% CI: 0.62, 0.91) to 0.93 (0.76, 0.99) with the overall proportion of inter-linker agreement being very high 0.86 (0.82, 0.89) for the initial instruments, with 94-100% for the three additional PROMs. Thirty-four new 'Personal Factors' emerged to capture disease-specific qualities not elsewhere described in ICF, e.g. 'pf_embarrassed by cough' or 'pf_panic/afraid when can't get a breath'. Conclusion: This first known effort in ICF linkage of ILD has provided important revelations on the current utility of the ICF in lung disease. Results have indicated areas for meaningful assessment of ICF descriptors for lung impairment. The mapping across PROMs provides insight into possibilities of developing more streamline and precise instrumentation. Finally, familiarity with the ICF in ILD may enable clinicians to experience a smoother transition with the imminent harmonization of ICD and ICF, ICD-11

Diatom Hotspots Driven by Western Boundary Current Instability

Climatic changes have decreased the stability of the Gulf Stream (GS), increasing the frequency at which its meanders interact with the Mid-Atlantic Bight (MAB) continental shelf and slope region. These intrusions are thought to suppress biological productivity by transporting low-nutrient water to the otherwise productive shelf edge region. Here we present evidence of widespread, anomalously intense subsurface diatom hotspots in the MAB slope sea that likely resulted from a GS intrusion in July 2019. The hotspots (at ∼50 m) were associated with water mass properties characteristic of GS water (∼100 m); it is probable that the hotspots resulted from the upwelling of GS water during its transport into the slope sea, likely by a GS meander directly intruding onto the continental slope east of where the hotspots were observed. Further work is required to unravel how increasingly frequent direct GS intrusions could influence MAB marine ecosystems

Generation of a core set of items to develop classification criteria for Scleroderma renal crisis using consensus methodology

BACKGROUND This project was undertaken to generate a core set of items to develop classification criteria for scleroderma renal crisis (SRC) using consensus methodology. METHODS An international, multidisciplinary panel of experts was invited to participate in a 3-round Delphi exercise developed using a survey based on items identified by a scoping review. In Round 1, participants were asked to identify omissions and clarify ambiguities regarding the items in the survey. In Round 2, participants were asked to rate the validity and feasibility of the items using Likert-type scales ranging from 1-9 (1= very invalid/unfeasible, 5 = uncertain, 9 = very valid/feasible). In Round 3, participants reviewed the results and comments of Round 2, and were asked to provide final ratings. Items rated as highly valid and feasible (both median scores ≥7) in Round 3 were selected as the provisional core set of items. A consensus meeting using nominal group technique (NGT) followed to further reduce the core set of items. RESULTS Ninety-nine experts from 16 countries participated in the Delphi exercise. Of the 31 items in the survey, consensus was achieved on 13, including hypertension, renal insufficiency, proteinuria and hemolysis. Eleven experts took part in the NGT discussion, where consensus was achieved in 5 domains: blood pressure, acute kidney injury, microangiopathic hemolytic anemia, target organ dysfunction, and renal histopathology. CONCLUSIONS A core set of items that characterize SRC was identified using consensus methodology. This core set will be used in future data-driven phases of this project to develop classification criteria for SRC. This article is protected by copyright. All rights reserved

COVID-19 severity and vaccine breakthrough infections in idiopathic inflammatory myopathies, other systemic autoimmune and inflammatory diseases, and healthy controls: a multicenter cross-sectional study from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) survey

OBJECTIVES: We aimed to compare the spectrum and severity of COVID-19 and vaccine breakthrough infections (BIs) among patients with IIMs, other systemic autoimmune and inflammatory diseases (SAIDs), and healthy controls (HCs). METHODS: This is a cross-sectional study with data from the COVAD study, a self-reported online global survey that collected demographics, COVID-19 history, and vaccination details from April to September 2021. Adult patients with at least one COVID-19 vaccine dose were included. BIs were defined as infections occurring > 2 weeks after any dose of vaccine. Characteristics associated with BI were analyzed with a multivariate regression analysis. RESULTS: Among 10,900 respondents [42 (30-55) years, 74%-females, 45%-Caucasians] HCs were (47%), SAIDs (42%) and IIMs (11%). Patients with IIMs reported fewer COVID-19 cases before vaccination (6.2%-IIM vs 10.5%-SAIDs vs 14.6%-HC; OR = 0.6, 95% CI 0.4-0.8, and OR = 0.3, 95% CI 0.2-0.5, respectively). BIs were uncommon (1.4%-IIM; 1.9%-SAIDs; 3.2%-HC) and occurred in 17 IIM patients, 13 of whom were on immunosuppressants, and 3(18%) required hospitalization. All-cause hospitalization was higher in patients with IIM compared to HCs [23 (30%) vs 59 (8%), OR = 2.5, 95% CI 1.2-5.1 before vaccination, and 3 (18%) vs 9 (5%), OR = 2.6, 95% CI 1.3-5.3 in BI]. In a multivariate regression analysis, age 30-60 years was associated with a lower odds of BI (OR = 0.7, 95% CI 0.5-1.0), while the use of immunosuppressants had a higher odds of BI (OR = 1.6, 95% CI 1.1-2.7). CONCLUSIONS: Patients with IIMs reported fewer COVID-19 cases than HCs and other SAIDs, but had higher odds of all-cause hospitalization from COVID-19 than HCs. BIs were associated with the use of immunosuppressants and were uncommon in IIMs

Risk stratification and response to therapy in patients with pulmonary arterial hypertension and comorbidities: A COMPERA analysis

Background: A diagnosis of idiopathic pulmonary arterial hypertension (IPAH) is frequently made in elderly patients who present with comorbidities, especially hypertension, coronary heart disease, diabetes mellitus, and obesity. It is unknown to what extent the presence of these comorbidities affects the response to PAH therapies and whether risk stratification predicts outcome in patients with comorbidities. Methods: We assessed the database of COMPERA, a European pulmonary hypertension registry, to determine changes after initiation of PAH therapy in WHO functional class (FC), 6-minute walking distance (6MWD), brain natriuretic peptide (BNP) or N-terminal fragment of probrain natriuretic peptide (NT-pro-BNP), and mortality risk assessed by a 4-strata model in patients with IPAH and no comorbidities, 1-2 comorbidities and 3-4 comorbidities. Results: The analysis was based on 1,120 IPAH patients (n = 208 [19%] without comorbidities, n = 641 [57%] with 1-2 comorbidities, and n = 271 [24%] with 3-4 comorbidities). Improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk from baseline to first follow-up were significantly larger in patients with no comorbidities than in patients with comorbidities, while they were not significantly different in patients with 1-2 and 3-4 comorbidities. The 4-strata risk tool predicted survival in patients without comorbidities as well as in patients with 1-2 or 3-4 comorbidities. Conclusions: Our data suggest that patients with IPAH and comorbidities benefit from PAH medication with improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk, albeit to a lesser extent than patients without comorbidities. The 4-strata risk tool predicted outcome in patients with IPAH irrespective of the presence of comorbidities