ERS International Congress 2023: highlights from the Thoracic Oncology Assembly.

Lung cancer is the leading cause of cancer mortality in the world. It greatly affects the patients' quality of life, and is thus a challenge for the daily practice in respiratory medicine. Advances in the genetic knowledge of thoracic tumours' mutational landscape, and the development of targeted therapies and immune checkpoint inhibitors, have led to a paradigm shift in the treatment of lung cancer and pleural mesothelioma. During the 2023 European Respiratory Society Congress in Milan, Italy, experts from all over the world presented their high-quality research and reviewed best clinical practices. Lung cancer screening, management of early stages of lung cancer, application of artificial intelligence and biomarkers were discussed and they will be summarised here.

Incidence, prevalence and long-term progression of Goh algorithm rated interstitial lung disease in systemic sclerosis in two independent cohorts in flanders: A retrospective cohort study.

OBJECTIVES: The epidemiology of interstitial lung disease (ILD) in systemic sclerosis (SSc) in Belgium is unknown. In literature, its prevalence varies between 19% and 52% in limited/diffuse cutaneous SSc (LcSSc/DcSSc). However, its prevalence in "early" SSc (pre-clinically overt SSc without [yet] skin involvement), nor its incidence rate in SSc (LcSSc/DcSSc/"early" SSc) has ever been described. Against this background, we aimed to determine the prevalence/incidence (rate) and progression of ILD in SSc. METHODS: 12-year follow-up data of consecutive SSc patients, included in two Flemish cohorts (University Hospitals Ghent and Leuven), were retrospectively analysed. ILD was classified according to the simplified Goh algorithm. Progression of ILD was defined as a relative decline of FVC ≥10%, a combined relative decline of FVC 5-10% and DLCO ≥15%, or as an increase in HRCT extent. RESULTS: 722 patients (60% LcSSc/ 20% DcSSc/ 20% "early" SSc, median (IQR) follow-up 39 [12-80] months) had baseline HRCT. 243 were rated to have ILD at baseline and 39 during follow-up (prevalence of 34%/ incidence rate of 20.3/1000PY, 95%CI:14.5-27.8). Amongst those with baseline ILD, 60% had lung functional progression at five years of follow-up. In the "early" SSc subgroup, eight patients were rated to have ILD at baseline and three during follow-up (prevalence of 6%/ incidence rate of 5.8/1000 PY, 95%CI:1.2-17.0). CONCLUSION: Both LcSSc and DcSSc patients should be monitored for ILD evolution. The low prevalence and incidence of ILD in the "early" SSc subgroup may instruct future decisions on the construction of uniform patient follow-up pathways in "early" SSc.

Dyspnea in homosexual male patients: throwback to an occasionally forgotten but severe clinical presentation of HIV/AIDS.

Pneumocystis jirovecii pneumonia (PJP) can be a severe indicator disease of acquired immunodeficiency syndrome (AIDS). We present two cases of homosexual male patients who came to the emergency unit of a Belgian hospital because of shortness of breath. Both men had been sent back home, initially diagnosed with a benign viral infection. Because of worsening symptoms and gradually evolving hypoxemia, both patients came back and were admitted to the hospital with a diagnosis of (microbiology proven) Pneumocystis jirovecii pneumonia. HIV serology in both men was tested and was clearly positive, indicating a new diagnosis of HIV infection. In this article, we provide an overview of this possibly severe AIDS defining condition. First, we give an introduction of the history of HIV/AIDS and its occurrence in homosexual males in Europe. Secondly, we provide an overview of the diagnosis and treatment of Pneumocystis jirovecii pneumonia. Finally, since the first case reports of Pneumocystis jirovecii pneumonia at the beginning of the AIDS epidemic also included homosexual men, we emphasize the potential importance of a sexual anamnesis in young male patients with an initial complaint of dyspnea.

Patient experiences of over-the-counter medicine purchases in Flemish community pharmacies.

OBJECTIVE: Patient use of over-the-counter (OTC) medicines contributes to improving public health and reducing public pharmaceutical expenditure. However, little is known of patient experiences of pharmacy distribution and services related to OTC medicines. The aim of this study is to explore patient experiences of purchasing OTC medicines in Flemish community pharmacies. METHOD: Data were gathered from an anonymous postal questionnaire survey of patients purchasing OTC medicines in a random sample of Flemish community pharmacies in April 2008. The self-administered questionnaire related to the most recent purchase of OTC medicines by a patient in a community pharmacy. The questionnaire included questions about: (a) sources of information about OTC medicines; (b) the patient relationship with pharmacist and physician; (c) organization and layout of the pharmacy; (d) distribution channels; and (e) patient satisfaction. Questions were generally measured using Likert scales. The questionnaire was piloted among patients. RESULTS: One hundred and fifty-five pharmacies consented to distribute questionnaires to five patients each, yielding a total of 358 useable questionnaires (response rate of 46%). The first point of contact about OTC medicines was the pharmacist (61% of patients), followed by the physician (29%). Newspapers and the internet were not viewed as primary sources of advice on OTC medicines. Patients tended to purchase OTC medicines for the acute treatment of pain, gastro-intestinal conditions, common cold, cough or musculo-skeletal pain. More than 75% of patients felt that pharmacists provided sufficient information about the health condition and OTC medicine use. About one-third of patients did not wish the physician to be informed of their OTC medicine use. Patients did not seem to agree with distribution channels for OTC medicines other than the community pharmacy. CONCLUSIONS: Flemish patients were satisfied with pharmacy distribution and services related to OTC medicines. They see an important role for pharmacists and physicians to accompany them in their OTC medicine use. Our results highlighted the need to strengthen communication between patients, pharmacists and physicians. It is also recommended that pharmacists keep an individual record detailing patient use of OTC and prescription medicines.

Study of recombinant antibody fragments and PAI-1 complexes combining protein-protein docking and results from site-directed mutagenesis.

Elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been correlated with cardiovascular diseases such as myocardial infarction and venous thrombosis. PAI-1 has also been shown to play an important role in tumor development, diabetes, and obesitas. Monoclonal antibodies MA-8H9D4 and MA-56A7C10, and their single-chain variable fragments (scFv), exhibit PAI-1-neutralizing properties. In this study, a rigid-body docking approach is used to predict the binding geometry of two distinct conformations of PAI-1 (active and latent) in complex with these antibody fragments. Resulting models were initially refined by using the dead-end elimination algorithm. Different filtering criteria based on the mutagenesis studies and structural considerations were applied to select the final models. These were refined by using the slow-cooling torsion-angle dynamic annealing protocol. The docked structures reveal the respective epitopes and paratopes and their potential interactions. This study provides crucial information that is necessary for the rational development of low-molecular weight PAI-1 inhibitors.

International trends in lifelong learning for pharmacists.

Lifelong learning for community pharmacists is shifting from continuing education (CE) towards continuing professional development (CPD) in some countries. The objectives of this report were to compare lifelong learning frameworks for community pharmacists in different countries, and determine to what extent the concept of CPD has been implemented. A literature search was conducted as well as an Internet search on the web sites of professional pharmacy associations and authorities in 8 countries. The results of this review show that the concept of CPD has been implemented primarily in countries that have a long tradition in lifelong learning, such as Great Britain. However, most countries have opted for the CE approach, eg, France, or for a combination of CE and CPD, eg, New Zealand. This approach combines the controllability by regulatory organizations that CE requires with the advantage of sustained behavior change seen in successful CPD programs.

Elucidation of the paratope of scFv-8H9D4, a PAI-1 neutralizing antibody derivative.

Interfering with increased levels of plasminogen activator inhibitor-1 (PAI-1) might offer new therapeutic strategies for a variety of cardiovascular diseases. Inactivation of PAI-1 can be accomplished by a number of monoclonal antibodies (MA), including MA-8H9D4. In a previous study, a single-chain variable fragment (scFv-8H9D4) was cloned and found to have the same properties as the parental MA-8H9D4. In the present study, we identified the residues of scFv-8H9D4 that contribute significantly to the paratope. The complementarity determining region 3 from the heavy (H3) and the light (L3) chain were analysed through site-directed mutagenesis. Out of twelve mutations, only four residues appeared to contribute to the paratope. The affinity of scFv-8H9D4-H3-L97D for PAI-1 was 38-fold decreased (K(A) = 4.8 +/- 0.2 x 10(7) M(-1) vs. 1.8 +/- 0.7 x 10(9) M(-1) for scFv-8H9D4) whereas scFv-8H9D4-H3-R98Y did not bind to PAI-1. The affinities of scFv-8H9D4-L3-Y91S and scFv-8H9D4-L3-F94D for PAI-1 were 9- and 5-fold reduced, respectively, whereas the combined mutation resulted in an 86-fold decreased affinity (K(A) = 2.1 +/- 0.2 x 10(7) M(-1)). In accordance with the affinity data, these mutants had no, or a reduced, PAI-1 inhibitory capacity, confirming that these four particular residues form the major interaction site of scFv-8H9D4 with PAI-1. In combination with the three-dimensional structure, these data contribute to the rational design of PAI-1 neutralizing compounds.