Natural history, dynamics, and ecology of human papillomaviruses in genital infections of young women: protocol of the PAPCLEAR cohort study.

INTRODUCTION: Human papillomaviruses (HPVs) are responsible for one-third of all cancers caused by infections. Most HPV studies focus on chronic infections and cancers, and we know little about the early stages of the infection. Our main objective is to better understand the course and natural history of cervical HPV infections in healthy, unvaccinated and vaccinated, young women, by characterising the dynamics of various infection-related populations (virus, epithelial cells, vaginal microbiota and immune effectors). Another objective is to analyse HPV diversity within hosts, and in the study population, in relation to co-factors (lifestyle characteristics, vaccination status, vaginal microbiota, human genetics). METHODS AND ANALYSIS: The PAPCLEAR study is a single center longitudinal study following 150 women, aged 18-25 years, for up to 2 years. Visits occur every 2 or 4 months (depending on HPV status) during which several variables are measured, such as behaviours (via questionnaires), vaginal pH, HPV presence and viral load (via qPCR), local concentrations of cytokines (via MesoScale Discovery technology) and immune cells (via flow cytometry). Additional analyses are outsourced, such as titration of circulating anti-HPV antibodies, vaginal microbiota sequencing (16S and ITS1 loci) and human genotyping. To increase the statistical power of the epidemiological arm of the study, an additional 150 women are screened cross-sectionally. Finally, to maximise the resolution of the time series, participants are asked to perform weekly self-samples at home. Statistical analyses will involve classical tools in epidemiology, genomics and virus kinetics, and will be performed or coordinated by the Centre National de la Recherche Scientifique (CNRS) in Montpellier. ETHICS AND DISSEMINATION: This study has been approved by the Comité de Protection des Personnes Sud Méditerranée I (reference number 2016-A00712-49); by the Comité Consultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Santé (reference number 16.504); by the Commission Nationale Informatique et Libertés (reference number MMS/ABD/AR1612278, decision number DR-2016-488) and by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (reference 20160072000007). Results will be published in preprint servers, peer-reviewed journals and disseminated through conferences. TRIAL REGISTRATION NUMBER: NCT02946346; Pre-results.

COLIN trial: Value of colchicine in the treatment of patients with acute myocardial infarction and inflammatory response.

BACKGROUND: Inflammation is involved during acute myocardial infarction, and could be an interesting target to prevent ischaemia-reperfusion injuries. Colchicine, known for its pleiotropic anti-inflammatory effects, could decrease systemic inflammation in this context. AIMS: To evaluate the impact of colchicine on inflammation in patients admitted for ST-segment elevation myocardial infarction (STEMI). METHODS: All patients admitted for STEMI with one of the main coronary arteries occluded, and successfully treated with percutaneous coronary intervention, were included consecutively. Patients were randomized to receive either 1mg colchicine once daily for 1 month plus optimal medical treatment or optimal medical treatment only. C-reactive protein (CRP) was assessed at admission and daily until hospital discharge. The primary endpoint was CRP peak value during the index hospitalization. RESULTS: Forty-four patients were included: 23 were treated with colchicine; 21 received conventional treatment only. At baseline, both groups were well balanced regarding age, sex, risk factors, thrombolysis in myocardial infarction flow and reperfusion delay. The culprit artery was more often the left anterior descending artery in the colchicine group (P=0.07), reflecting a more severe group. There was no significant difference in mean CRP peak value between the colchicine and control groups (29.03mg/L vs 21.86mg/L, respectively; P=0.36), even after adjustment for type of culprit artery (26.99 vs 24.99mg/L, respectively; P=0.79). CONCLUSION: In our study, the effect of colchicine on inflammation in the context of STEMI could not be demonstrated. Further larger studies may clarify the impact of colchicine in acute myocardial infarction.