Pulmonary Sequelae of COVID-19: Focus on Interstitial Lung Disease.

As the world transitions from the acute phase of the COVID-19 pandemic, a novel concern has arisen-interstitial lung disease (ILD) as a consequence of SARS-CoV-2 infection. This review discusses what we have learned about its epidemiology, radiological, and pulmonary function findings, risk factors, and possible management strategies. Notably, the prevailing radiological pattern observed is organising pneumonia, with ground-glass opacities and reticulation frequently reported. Longitudinal studies reveal a complex trajectory, with some demonstrating improvement in lung function and radiographic abnormalities over time, whereas others show more static fibrotic changes. Age, disease severity, and male sex are emerging as risk factors for residual lung abnormalities. The intricate relationship between post-COVID ILD and idiopathic pulmonary fibrosis (IPF) genetics underscores the need for further research and elucidation of shared pathways. As this new disease entity unfolds, continued research is vital to guide clinical decision making and improve outcomes for patients with post-COVID ILD.

Genetic and environmental factors in interstitial lung diseases: current and future perspectives on early diagnosis of high-risk cohorts.

Within the wide scope of interstitial lung diseases (ILDs), familial pulmonary fibrosis (FPF) is being increasingly recognized as a specific entity, with earlier onset, faster progression, and suboptimal responses to immunosuppression. FPF is linked to heritable pathogenic variants in telomere-related genes (TRGs), surfactant-related genes (SRGs), telomere shortening (TS), and early cellular senescence. Telomere abnormalities have also been identified in some sporadic cases of fibrotic ILD. Air pollution and other environmental exposures carry additive risk to genetic predisposition in pulmonary fibrosis. We provide a perspective on how these features impact on screening strategies for relatives of FPF patients, interstitial lung abnormalities, ILD multi-disciplinary team (MDT) discussion, and disparities and barriers to genomic testing. We also describe our experience with establishing a familial interstitial pneumonia (FIP) clinic and provide guidance on how to identify patients with telomere dysfunction who would benefit most from genomic testing.

Present and future perspectives in early diagnosis and monitoring for progressive fibrosing interstitial lung diseases.

Progressive fibrosing interstitial lung diseases (PF-ILDs) represent a group of conditions of both known and unknown origin which continue to worsen despite standard treatments, leading to respiratory failure and early mortality. Given the potential to slow down progression by initiating antifibrotic therapies where appropriate, there is ample opportunity to implement innovative strategies for early diagnosis and monitoring with the goal of improving clinical outcomes. Early diagnosis can be facilitated by standardizing ILD multidisciplinary team (MDT) discussions, implementing machine learning algorithms for chest computed-tomography quantitative analysis and novel magnetic-resonance imaging techniques, as well as measuring blood biomarker signatures and genetic testing for telomere length and identification of deleterious mutations in telomere-related genes and other single-nucleotide polymorphisms (SNPs) linked to pulmonary fibrosis such as rs35705950 in the MUC5B promoter region. Assessing disease progression in the post COVID-19 era also led to a number of advances in home monitoring using digitally-enabled home spirometers, pulse oximeters and other wearable devices. While validation for many of these innovations is still in progress, significant changes to current clinical practice for PF-ILDs can be expected in the near future.

European Medicines Agency approval summary: Zaltrap for the treatment of patients with oxaliplatin-resistant metastatic colorectal cancer.

On 1 February 2013, a marketing authorisation valid throughout the European Union was issued for aflibercept (Zaltrap) in combination with irinotecan/5-fluorouracil/folinic acid chemotherapy for the treatment of adults with metastatic colorectal cancer resistant to or progressive after an oxaliplatin-containing regimen. Aflibercept is a recombinant fusion protein which blocks the activation of vascular endothelial growth factor (VEGF) receptors and the proliferation of endothelial cells, acting as a soluble decoy receptor that binds to VEGF-A with higher affinity than its native receptors, as well as placental growth factor and VEGF-B. The use of aflibercept was studied in a randomised, double-blind, placebo-controlled phase III study, in patients with metastatic colorectal cancer (mCRC) who had previously been treated with an oxaliplatin-based treatment with or without prior bevacizumab. Aflibercept (n=612) was compared with placebo (n=614), both in combination with FOLFIRI (infusional fluorouracil, leucovorin and irinotecan). The primary endpoint of the study was overall survival (OS). The median OS in the intent-to-treat population was 13.5 months in subjects treated with aflibercept compared with 12.1 months for subjects in the control arm (stratified HR=0.817, 95% CI 0.714 to 0.935, stratified pvalue=0.0032). The frequency of adverse events was higher in the aflibercept arm compared with the placebo arm, reflecting the toxicity profile of anti-VEGF agents in combination with chemotherapy. This paper is based on the scientific review of the application leading to approval of aflibercept in the EU. The detailed scientific assessment report and product information for this product are available on the European Medicines Agency website (http://www.ema.europa.eu). Trial registration number NCT00561470, Results.