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Distal radius fractures are common and are managed with or without surgery. Current evidence indicates surgical treatment is not superior to nonsurgical treatment at 12 months.Does surgical treatment for displaced distal radius fractures in patients 60 years or older provide better patient-reported wrist pain and function outcomes than nonsurgical treatment at 24 months?In this secondary analysis of a combined multicenter randomized clinical trial (RCT) and a parallel observational study, 300 patients were screened from 19 centers in Australia and New Zealand. Of these, 166 participants were randomized to surgical or nonsurgical treatment. Participants who declined randomization (n = 134) were included in the parallel observational group with the same treatment options and follow-up. Participants were followed up at 3, 12, and 24 months by a blinded assessor. The 24-month outcomes are reported herein. Data were collected from December 1, 2016, to December 31, 2020, and analyzed from February 4 to October 21, 2021.Surgical treatment consisting of open reduction and internal fixation using a volar-locking plate (VLP group) and nonsurgical treatment consisting of closed reduction and cast immobilization (CR group).The primary outcome was patient-reported function using the Patient-Rated Wrist Evaluation (PRWE) questionnaire. Secondary outcomes included health-related quality of life, wrist pain, patient-reported treatment success, patient-rated bother with appearance, and posttreatment complications.Among the 166 randomized and 134 observational participants (300 participants; mean [SD] age, 71.2 [7.5] years; 269 women [89.7%]), 151 (91.0%) randomized and 118 (88.1%) observational participants were followed up at 24 months. In the RCT, no clinically important difference occurred in mean PRWE scores at 24 months (13.6 [95% CI, 9.1-18.1] points for VLP fixation vs 15.8 [95% CI, 11.3-20.2] points for CR; mean difference, 2.1 [95% CI, -4.2 to 8.5]; P = .50). There were no between-group differences in all other outcomes except for patient-reported treatment success, which favored VLP fixation (33 of 74 [44.6%] in the CR group vs 54 of 72 [75.0%] in the VLP fixation group reported very successful treatment; P = .002). Rates of posttreatment complications were generally low and similar between treatment groups, including deep infection (1 of 76 [1.3%] in the CR group vs 0 of 75 in the VLP fixation group) and complex regional pain syndrome (2 of 76 [2.6%] in the CR group vs 1 of 75 [1.3%] in the VLP fixation group). The 24-month trial outcomes were consistent with 12-month outcomes and with outcomes from the observational group.Consistent with previous reports, these findings suggest that VLP fixation may not be superior to CR for displaced distal radius fractures for patient-rated wrist function in persons 60 years or older during a 2-year period. Significantly higher patient-reported treatment success at 2 years in the VLP group may be attributable to other treatment outcomes not captured in this study.ANZCTR.org Identifier: ACTRN12616000969460.

To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.F Hoffmann-La Roche.

Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.F Hoffmann-La Roche.

List of the Tumor types having mutations in both MYH9 and RHOA genes in the cBioPortal for Cancer Genomics database

List of the tumor specific mutations identified by whole-genome sequencing and validated in the 10 pairs of MPM tumor and germline DNA samples

Expression levels of candidate genes in 151 patients by gender and histology

List of SNVs identified in the analyzed genes

Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (P < 0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that nonepitheliod histology (P = 0.037), whereas CDKN2A deletions occurred more frequently in nonepithelioid subtypes among men (P = 0.021) and were correlated with shorter overall survival for the entire cohort (P = 0.002) and for men (P = 0.012). Furthermore, women were more likely to harbor TP53 mutations (P = 0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in nonepithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM. Cancer Res; 76(2); 319–28. ©2015 AACR.

List of the 51 canonical pathways significantly enriched (p

Schematic representation of the SNVs and/or chromosomal aberrations identified in BAP1, NF2, TP53, MYH9, RHOA, MYH6, MYH10, PIK3C2A, TNFRSF1A, and 22q and 9p in a panel of 147 MPM tumors.

Expression levels for BAP1, NF2, TP53, MYH9, MYH6, MYH10, PIK3C2A, RHOA, and TNFRSF1A detected by Affymetrix® Human Gene 1.1 ST Array in 151 MPM

Whole genome sequencing data analysis of 10 MPM tumor and matched DNA generated by Complete Genomics platform

Purpose To report the 10-year outcomes of eyes with neovascular age-related macular degeneration (nAMD) treated with vascular endothelial growth factor (VEGF) inhibitors. Design Ten-year, retrospective cohort study. Participants A total of 1046 patients who commenced treatment with anti-VEGF for nAMD. Methods Anti-VEGF–naive eyes diagnosed with nAMD that commenced treatment between November 2006 and December 2009 were identified. Data collected included the baseline demographics, visual acuity (VA), and number of intravitreal injections. Baseline fundus fluorescein angiograms and OCT images were graded for choroidal neovascularization type. OCT images were graded for central macular thickness (CMT) and the presence of fluid over the 10 years. Main Outcome Measures Change in vision at 10 years. Secondary outcomes included the proportion of eyes with 20/40 vision or better and 20/200 or worse, the proportion of eyes that were dry on OCT imaging, and the number of injections. Results Of 1046 eligible eyes, 10-year data were available for 293 (28%), which were included in the analyses. Eyes received 58.1 (standard deviation [SD], 33.6) injections during the 10 years. The mean CMT decreased from 355.5 μm (SD, 107.8 μm) to 264.2 (SD, 79.5) μm (P Conclusions On average, eyes with nAMD maintained starting VA when treated with VEGF inhibitors for 10 years. With ongoing regular treatment, a greater proportion of eyes achieved VA of 20/40 or better at 10 years than at presentation.

This case series examines the spectrum of imaging findings at chest radiography, US, CT, and MRI in 35 children admitted to a tertiary pediatric hospital in April and May 2020 with a post–coronavirus disease 2019 inflammatory condition known as multisystem inflammatory syndrome in children. The constellation of findings includes airway inflammation and rapid development of pulmonary edema on thoracic images, coronary artery aneurysms, and extensive right iliac fossa inflammatory changes on abdominal images. Awareness of this emerging condition and the expected multi-organ imaging findings will aid radiologists in the assessment of these complex cases. © RSNA, 2020

OBJECTIVES There is increasing evidence that performing superior cavopulmonary connection (SCPC) at 3 months reduces mortality: reducing the risky ‘interstage’ period, volume off-loading the ventricle and reducing coronary steal, hopefully preserving ventricular function. Our objective was to describe our experience of early SCPC with preoperative computer tomography (CT) assessment compared to later connection at 6 months. METHODS Patients undergoing Norwood procedure from 2005 to 2020 were divided into 2 eras were described and compared. Era 1 from 2005 to 2016 when SCPC was undertaken at 6 months: and era 2 (2017–2020) when an earlier operation was performed. Demographics, mortality (interstage, early and late following SCPC) and data on postoperative course and complications were recorded. RESULTS In era 1, 191 patients underwent Norwood (120 survivors to SCPC) and 28 patients (23 survivors) in era 2. There were no significant differences in the demographics. Interstage mortality was 17.8% in era 1 and 8.0% in era 2 but not significantly significant (P = 0.22). The median (interquartile range) age at pre-imaging and SCPC was significantly lower: 99 (81–120) vs 77 (47–102) days and 175 (117–208) vs 106 (102–122) days in era 1 vs era 2 (P CONCLUSIONS Early SCPC with CT assessment is feasible and although intensive care unit length of stay was slightly longer there was no change in the overall length of stay and no change in postoperative mortality or complications.

Background Multiple co-morbidities complicate initiation of medical therapy in patients with heart failure with reduced ejection fraction (HFrEF). Adherence to guidelines based on individual patient profiles is not well described. This paper examines the effect of individual patient profiles on guideline recommended therapies for HFrEF. Methods This was a prospective, observational, non-randomised study of hospitalised HFrEF patients over 30 days, from 2014 to 2017 in 16 hospitals. A previously developed algorithm-based guideline adherence score was used to determine adherence to key performance indicators: prescribing of beta blockers, angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), mineralocorticoid-receptor antagonist (MRAs) for HFrEF patients and early outpatient and heart failure (HF) disease management program review. Patients were classified as low, moderate and excellent adherence to medical therapy. Results Of the 696 HFrEF patients, 69.1% (n=481) were male with an average age of 73.15 years (SD±14.5 years). At discharge, 64.6% (n=427) were prescribed an ACEI/ARB, 78.7% (n=525) a beta blocker and 45.3% (n=302) prescribed MRA. Based on individual patient profiles, 18.2% (n=107) of eligible patients received an outpatient clinic and HF disease management program review within 30 days and 41.5% (n=71) were prescribed triple therapy. Based on individual profiles, 13% (n=21) of patients received an excellent guideline adherence score. Conclusion Individual patient profiles impact on adherence to guideline recommendations. Review in transitional care and prescribing of triple pharmacotherapy is suboptimal. Translational strategies to facilitate the implementation of guideline recommended therapies is warranted.

Background We are performing a combined randomised and observational study comparing internal fixation to non-surgical management for common wrist fractures in older patients. This paper describes the statistical analysis plan. Methods/design A Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly (CROSSFIRE) is a randomised controlled trial comparing two types of usual care for treating wrist fractures in older patients, surgical fixation using volar locking plates and non-surgical treatment using closed reduction and plaster immobilisation. The primary aim of this comparative-effectiveness study is to determine whether surgery is superior to non-surgical treatment with respect to patient-reported wrist function at 12 months post treatment. The secondary outcomes include radiographic outcomes, complication rates and patient-reported outcomes including quality of life, pain, treatment success and cosmesis. Primary analysis will use a two-sample t test and an intention-to-treat analysis using the randomised arm of the study. Statistical analyses will be two-tailed and significance will be determined by p Discussion This statistical analysis plan describes the analysis of the CROSSFIRE study which aims to provide evidence to aid clinical decision-making in the treatment of distal radius fractures in older patients. Trial registration CROSSFIRE was approved by The Hunter New England Human Research Ethics Committee (HNEHREC Reference No: 16/02/17/3.04). Registered on 22 July 2016 with The Australian and New Zealand Clinical Trials Registry (ANZCTR Number; ACTRN12616000969460). This manuscript is based on v.11 of the statistical analysis plan. A copy of v.11, signed by the chief investigator and the senior statistician is kept at the administering institution.