Joachim Aerts’s research while affiliated with Erasmus MC and other places

PURPOSE CD276 (B7-H3) is an immunoregulatory protein that plays an important role in the inhibition of T-cell function. CD276 is overexpressed on a variety of human solid cancer cells with limited expression in normal tissues, making it an appealing target for innovative cancer immunotherapy approaches. Pleural mesothelioma (PM) is a highly aggressive disease with a need for new treatment options. Our objective was to investigate the expression of CD276 in the multicenter PM cohort of the European Thoracic Oncology Platform Mesoscape project and correlate the results with annotated clinical data. MATERIALS AND METHODS Using tissue microarrays (TMAs), the expression of CD276, assessed using a semiquantitative aggregate H -score method on the membrane (and secondarily in the cytoplasm), was correlated with clinicopathologic characteristics and survival outcome. RESULTS CD276 immunohistochemistry results were available for 353 patients, with mostly epithelioid histology (71%). Membranous CD276 expression was present in 86%. High membranous CD276 expression ( H -score ≥the median H -score of 120) was significantly more common in females ( P = .0029; 71% v 47%) and in epithelioid histology ( P < .001; 59% v 29%), whereas no significant association in clinical outcome (overall survival [OS]/progression-free survival) was found. Cross-validation of the TMA method using whole sections revealed a moderate agreement for membranous assessment (Cohen's kappa = 0.47) and a lower agreement for cytoplasm assessment (Cohen's kappa = 0.37). In an exploratory analysis, high cytoplasmic CD276 expression was associated with worse prognosis (OS, log-rank P = .043), but was not significant when adjusting for other clinical variables. CONCLUSION Although no prognostic value of CD276 expression was found, its high membranous expression (86%) in the PM samples of the study supports further research of its potential as a therapeutic target for this disease.

Background Many patients hospitalized for COVID-19 experience long-term health problems, but comprehensive longitudinal data up to 2 years remain limited. We aimed to (1) assess 2-year trajectories of health outcomes, including comparison between intensive care unit (ICU) treated and non-ICU-treated patients, and (2) identify risk factors for prominent health problems post-hospitalization for COVID-19. Methods The CO-FLOW multicenter prospective cohort study followed adults hospitalized for COVID-19 at 3, 6, 12, and 24 months post-discharge. Measurements included patient-reported outcomes (a.o., recovery, symptoms, fatigue, mental health, sleep quality, return to work, health-related quality of life [HRQoL]), and objective cognitive and physical tests. Additionally, routine follow-up data were collected. Results 650 patients (median age 60.0 [IQR 53.0–67.0] years; 449/650 [69%] male) surviving hospitalization for COVID-19 were included, of whom 273/650 (42%) received ICU treatment. Overall, outcomes improved over time. Nonetheless, 73% (322/443) of patients had not completely recovered from COVID-19, with memory problems (274/443; 55%), concentration problems (259/443; 52%), and dyspnea (251/493; 51%) among most frequently reported symptoms at 2 years. Moreover, 61% (259/427) had poor sleep quality, 51% (222/433) fatigue, 23% (102/438) cognitive failures, and 30% (65/216) did not fully return to work. Objective outcome measures showed generally good physical recovery. Most outcomes were comparable between ICU- and non-ICU-treated patients at 2 years. However, ICU-treated patients tended to show slower recovery in neurocognitive symptoms, mental health outcomes, and resuming work than non-ICU-treated patients, while showing more improvements in physical outcomes. Particularly, female sex and/or pre-existing pulmonary disease were major risk factors for poorer outcomes. Conclusions 73% (322/443) of patients had not completely recovered from COVID-19 by 2 years. Despite good physical recovery, long-term neurocognitive complaints, dyspnea, fatigue, and impaired sleep quality persisted. ICU-treated patients showed slower recovery in neurocognitive and mental health outcomes and resumption of work. Tailoring long-term COVID-19 aftercare to individual residual needs is essential. Follow-up is required to monitor further recovery. Trial registration : NL8710, registration date 12-06-2020.

Background MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression. Differential miRNA expression, which is widely shown to be associated with the pathogenesis of various diseases, can be influenced by lifestyle factors, including smoking. This study aimed to investigate the plasma miRNA signature of smoking habits, the potential effect of smoking cessation on miRNA levels, and relate the findings with lung cancer incidence. Results A targeted RNA-sequencing approach measured plasma miRNA levels in 2686 participants from the population-based Rotterdam study cohort. The association between cigarette smoking (current versus never) and 591 well-expressed miRNAs was assessed via adjusted linear regression models, identifying 41 smoking-associated miRNAs that passed the Bonferroni-corrected threshold ( P < 0.05/591 = 8.46 × 10 –5 ). Moreover, we found 42 miRNAs with a significant association ( P < 8.46 × 10 –5 ) between current (reference group) and former smokers. Then, we used adjusted linear regression models to explore the effect of smoking cessation time on miRNA expression levels. The expression levels of two miRNAs were significantly different within 5 years of cessation ( P < 0.05/41 = 1.22 × 10 –3 ) from current smokers, while for cessation time between 5 and 15 years we found 19 miRNAs to be significantly different from current smokers, and finally, 38 miRNAs were significantly different after more than 15 years of cessation time ( P < 1.22 × 10 –3 ). These results imply the reversibility of the smoking effect on plasma levels of at least 38 out of the 41 smoking-miRNAs following smoking cessation. Next, we found 8 out of the 41 smoking-related miRNAs to be nominally associated ( P < 0.05) with the incidence of lung cancer. Conclusions This study demonstrates smoking-related dysregulation of plasma miRNAs, which might have a potential for reversibility when comparing different smoking cessation groups. The identified miRNAs are involved in several cancer-related pathways and include 8 miRNAs associated with lung cancer incidence. Our results may lay the groundwork for further investigation of miRNAs as potential mechanism linking smoking, gene expression and cancer.