Chest computed tomography in severe bronchopulmonary dysplasia: Comparing quantitative scoring methods.

PURPOSE: Bronchopulmonary dysplasia (BPD) is the most common complication of extreme preterm birth and structural lung abnormalities are frequently found in children with BPD. To quantify lung damage in BPD, three new Hounsfield units (HU) based chest-CT scoring methods were evaluated in terms of 1) intra- and inter-observer variability, 2) correlation with the validated Perth-Rotterdam-Annotated-Grid-Morphometric-Analysis (PRAGMA)-BPD score, and 3) correlation with clinical data. METHODS: Chest CT scans of children with severe BPD were performed at a median of 7 months corrected age. Hyper- and hypo-attenuated regions were quantified using PRAGMA-BPD and three new HU based scoring methods (automated, semi-automated, and manual). Intra- and inter-observer variability was measured using intraclass correlation coefficients (ICC) and Bland-Altman plots. The correlation between the 4 scoring methods and clinical data was assessed using Spearman rank correlation. RESULTS: Thirty-five patients (median gestational age 26.1 weeks) were included. Intra- and inter-observer variability was excellent for hyper- and hypo-attenuation regions for the manual HU method and PRAGMA-BPD (ICCs range 0.80-0.97). ICC values for the semi-automated HU method were poorer, in particular for the inter-observer variability of hypo- (0.22-0.71) and hyper-attenuation (-0.06-0.89). The manual HU method was highly correlated with PRAGMA-BPD score for both hyper- (ρs0.92, p < 0.001) and hypo-attenuation (ρs0.79, p < 0.001), while automated and semi-automated HU methods showed poor correlation for hypo- (ρs < 0.22) and good correlation for hyper-attenuation (ρs0.72-0.74, p < 0.001). Several scores of hyperattenuation correlated with the use of inhaled bronchodilators in the first year of life; two hypoattenuation scores correlated with birth weight. CONCLUSIONS: PRAGMA-BPD and the manual HU method have the best reproducibility for quantification of CT abnormalities in BPD.

The value of prognostic and predictive parameters in early-stage lung adenocarcinomas: A comparison between biopsies and resections.

INTRODUCTION: Since lung adenocarcinoma (LUAD) biopsies are usually small, it is questionable if their prognostic and predictive information is comparable to what is offered by large resection specimens. This study compares LUAD biopsies and resection specimens for their ability to provide prognostic and predictive parameters. METHODS: We selected 187 biopsy specimens with stage I and II LUAD. In 123 cases, subsequent resection specimens were also available. All specimens were evaluated for growth pattern, nuclear grade, fibrosis, inflammation, and genomic alterations. Findings were compared using non-parametric testing for categorical variables. Model performance was assessed using the area under the curve for both biopsies and resection specimens, and overall (OS) and disease-free survival (DFS) was calculated. RESULTS: The overall growth pattern concordance between biopsies and resections was 73.9%. The dominant growth pattern correlated with OS and DFS in resected adenocarcinomas and for high-grade growth pattern in biopsies. Multivariate analysis of biopsy specimens revealed that T2-tumors, N1-status, KRAS mutations and a lack of other driver mutations were associated with poorer survival. Model performance using clinical, histological and genetic data from biopsy specimens for predicting OS and DSF demonstrated an AUC of 0.72 and 0.69, respectively. CONCLUSIONS: Our data demonstrated the prognostic relevance of a high-grade growth pattern in biopsy specimens of LUAD. Combining clinical, histological and genetic information in one model demonstrated a suboptimal performance for DFS prediction and good performance for OS prediction. However, for daily practice, more robust (bio)markers are required to predict prognosis and stratify patients for therapy and follow-up.

Predicting complete finger extension in Dupuytren's disease.

Multiple studies have reported the effectiveness of treatment on contracture reduction in Dupuytren's disease. However, very few studies have attempted to quantify to which extent patient and disease characteristics influence the chance of achieving a straight finger after surgery. Therefore, the aim of this study is to explore to which extent pre-operative patient and disease characteristics can reliably predict a straight finger after surgery for Dupuytren's disease. In total, 812 and 281 patients, who underwent a limited fasciectomy or needle fasciotomy, respectively, were included in the final analyses. Analysis was performed using a logistic modeling framework. For both treatments, the combination of the extension deficit at baseline; which finger is most affected, which joint is most affected, and the number of affected fingers provided reliable predictions. Classical patient characteristics, such as age and sex, had no additional predictive value. The models presented in this study provide reliable predictions and could be helpful in informing patients and managing their expectations.

The prevalence of radiographic thumb base osteoarthritis: a meta-analysis.

INTRODUCTION: Osteoarthritis (OA) affects millions of people worldwide. In hand OA, the thumb base is the most affected single joint. The reported radiographic prevalence ranges from 0 to 100%, making the true radiographic prevalence unclear. Hence, we conducted a meta-analysis on the age and sex-specific prevalence of radiographic thumb base OA. METHODS: We performed a search in Embase, Medline Ovid, Web of Science Core Collection, Cochrane Central Register of Trials, and Google Scholar. We included studies of the general population that reported thumb base OA for males and females separately based on a hand radiograph and reported the age of these groups. Using meta-regression, we estimated the odds ratio (OR) of having radiographic thumb base OA for age and sex, while adjusting for within-study correlation. RESULTS: The initial search yielded 4,278 articles; we finally included 16 studies that reported the age- and sex-stratified prevalence. Taken together, there were 104 age and gender specific-prevalence rates that could be derived from the 16 studies. The prevalence of radiographic OA for the 50-year-old male and female participants was 5.8% and 7.3%, respectively, while the respective prevalence for 80-year-old male and female participants was 33.1% and 39.0%. We found an OR for having radiographic OA of 1.06 (95%CI [1.055-1.065], p < 0.001) per increasing year of age, and 1.30 (95%CI: 1.05-1.61], p = 0.014) for females. CONCLUSION: In the general population, radiographic thumb base OA is more prevalent in females and is strongly associated with age.

Dupilumab treatment in patients with atopic dermatitis: a comparative cohort study between the Netherlands and Japan shows a discrepancy in patient-reported outcome measures.

BACKGROUND: Dupilumab was equally effective among all racial subgroups in clinical trials, but a direct comparison in daily practice is lacking. OBJECTIVES: To investigate the effectiveness of dupilumab in patients with atopic dermatitis (AD) in the Netherlands and Japan over 80 weeks of treatment. METHODS: A longitudinal comparative cohort study was conducted in patients with AD who were treated with dupilumab in daily practice. We used linear mixed-effects models to determine changes over time. RESULTS: We found statistically significant differences in sex, disease onset, body mass index and therapeutic history between Dutch (n = 208) and Japanese (n = 153) patients. The baseline Eczema Area and Severity Index (EASI) score was higher in Japanese patients (23·8 vs. 14·8), while baseline Patient-Reported Outcome Measures (PROMs) were higher in Dutch patients. EASI scores decreased quickly to a level indicating 'mild disease' (EASI < 7), and remained low in both countries. However, PROMs showed different trajectories with better scores in Japan. CONCLUSIONS: Dupilumab showed significant, comparable and sustained improvement of EASI scores in Japanese and Dutch patients. However, we found striking differences in the effect on PROMs between the countries, with a better outcome in Japanese patients.

Fendrix® compared to Engerix® in HIV-infected patients nonresponding to initial- and re-vaccination schedule.

BACKGROUND: In HIV-infected patients, the immunogenicity of hepatitis B vaccines is impaired. In this randomised controlled study (RCT), we investigated the effect of Fendrix® versus double-dose Engerix® vaccination in previously non-responsive HIV-infected subjects. METHODS: Patients included those who were HIV-infected and non-responders to a primary (single-dose hepatitis B (HBV) vaccination) and a subsequent double-dose HBV revaccination schedule. Subjects were randomised 1:1 to receive Fendrix® (t = 0, 4, 8, 24 weeks) or double-dose Engerix® (t = 0, 4, 24 weeks) vaccinations. Primary efficacy, defined as anti-HBs response ≥ 10 IU/l, was evaluated at week 28 in both study arms. RESULTS: A subset of 48 patients non-responsive to HBV vaccination was selected, from a cohort of patients at our institution, who underwent HBV vaccination unsuccessfully either in a previous RCT or through standard care. The anti-HBs ≥ 10 IU/l response rate at week 28 in the Fendrix® arm and the Engerix® arm were 85.7% and 65.0%, respectively (p = 0.09). There was no significant difference between the two used vaccine types in the anti-HBs levels reached. In our institution, the overall response rate after initial standard-dose vaccination schedule and double-dose revaccination in our cohort was 75%. In this study, combining the effects of Fendrix and Engerix resulted in a 75% response rate in the 25% remaining non-responders on initial and double-dose revaccination series. This yielded an absolute 19% increase and an overall response to HBV vaccination in HIV-infected patients of around 94% in our cohort. CONCLUSION: These results together, suggest that continuing HBV vaccination in non-responders to a first course of single-dose vaccine and a double-dose revaccination scheme is worth the effort. No superiority of one of the investigated hepatitis B vaccines was shown in this cohort but an appropriate number of patients needed to achieve reliable answers was not achieved.

Multivariate joint modeling to identify markers of growth and lung function decline that predict cystic fibrosis pulmonary exacerbation onset.

BACKGROUND: Attenuated decreases in lung function can signal the onset of acute respiratory events known as pulmonary exacerbations (PEs) in children and adolescents with cystic fibrosis (CF). Univariate joint modeling facilitates dynamic risk prediction of PE onset and accounts for measurement error of the lung function marker. However, CF is a multi-system disease and the extent to which simultaneously modeling growth and nutrition markers improves PE predictive accuracy is unknown. Furthermore, it is unclear which routinely collected clinical indicators of growth and nutrition in early life predict PE onset in CF. METHODS: Using a longitudinal cohort of 17,100 patients aged 6-20 years (US Cystic Fibrosis Foundation Patient Registry; 2003-2015), we fit a univariate joint model of lung-function decline and PE onset and contrasted its predictive performance with a class of multivariate joint models that included combinations of growth markers as additional submodels. Outcomes were longitudinal lung function (forced expiratory volume in 1 s of % predicted), percentiles of body mass index, weight-for-age and height-for-age and PE onset. Relevant demographic/clinical covariates were included in submodels. We implemented a univariate joint model of lung function and time-to-PE and four multivariate joint models including growth outcomes. RESULTS: All five joint models showed that declining lung function corresponded to slightly increased risk of PE onset (hazard ratio from univariate joint model: 0.97, P < 0.0001), and all had reasonable predictive accuracy (cross-validated area under the receiver-operator characteristic curve > 0.70). None of the growth markers alongside lung function as outcomes in multivariate joint modeling appeared to have an association with hazard of PE. Jointly modeling only lung function and PE onset yielded the most accurate (area under the receiver-operator characteristic curve = 0.75) and precise (narrowest interquartile range) predictions. Dynamic predictions were accurate across forecast horizons (0.5, 1 and 2 years) and precision improved with age. CONCLUSIONS: Including growth markers via multivariate joint models did not yield gains in prediction performance, compared to a univariate joint model with lung function. Individualized dynamic predictions from joint modeling could enhance physician monitoring of CF disease progression by providing PE risk assessment over a patient's clinical course.