Sickle cell disease (SCD) is due to the mutation of haemoglobin (Hb), from HbA to HbS and characterised by recurrent vaso-occlusive crises (VOC), which can progress to acute chest syndrome (ACS), a leading cause of death in adults with SCD. Hypoxia is a key modifiable factor in the polymerisation of HbS and the pathogenesis of VOC. High-flow nasal oxygen (HFNO) delivers humidified gas at high oxygen concentrations and flow rates: the former may reverse sickling (metabolic effect) to accelerate VOC resolution and prevent ACS, while the latter may reduce the risk of ACS by mitigating hypercapnia and generating positive airway pressure that limits hypoventilation and atelectasis (pulmonary effect). The study hypothesises that HFNO is a safe and effective strategy for treating VOC and preventing secondary ACS, and will assess this using a multi-arm multi-stage (MAMS) trial design.

This is a prospective, multicentre, randomised, open-label controlled trial following an MAMS design with three phases and four arms: one control (low-flow oxygen) and three HFNO intervention arms with varying fraction of inspired oxygen levels (low, intermediate, high). The pilot stage will assess safety and feasibility, using the rate of cardiac and neurological events as the primary endpoint. In the activity stage, arms demonstrating acceptable safety will be compared for efficacy based on the rate of VOC resolution without complications by day 5, allowing selection of the most promising arm. The final efficacy stage will compare the selected HFNO strategy to control, with prevention of secondary ACS by day 14 as the primary endpoint. The study aims to enrol up to 350 VOC episodes in total.

The study has been granted ethical approval (CPP SUD MEDITERRANEE IV). Following the provision of informed consent, patients will be included in the study. The results will be submitted for publication in peer-reviewed journals.

NCT03976180.

Endovascular aortic aneurysm repair (EVAR) requires long-term surveillance to detect and treat postoperative complications. However, prediction models to optimise follow-up strategies are still lacking. The primary objective of this study is to develop predictive models of post-operative outcomes following elective EVAR using Artificial Intelligence (AI)-driven analysis. The secondary objective is to investigate morphological aortic changes following EVAR.

This international, multicentre, observational study will retrospectively include 500 patients who underwent elective EVAR. Primary outcomes are EVAR postoperative complications including deaths, re-interventions, endoleaks, limb occlusion and stent-graft migration occurring within 1 year and at mid-term follow-up (1 to 3 years). Secondary outcomes are aortic anatomical changes. Morphological changes following EVAR will be analysed and compared based on preoperative and postoperative CT angiography (CTA) images (within 1 to 12 months, and at the last follow-up) using the AI-based software PRAEVAorta 2 (Nurea). Deep learning algorithms will be applied to stratify the risk of postoperative outcomes into low or high-risk categories. The training and testing dataset will be respectively composed of 70% and 30% of the cohort.

The study protocol is designed to ensure that the sponsor and the investigators comply with the principles of the Declaration of Helsinki and the ICH E6 good clinical practice guideline. The study has been approved by the ethics committee of the University Hospital of Patras (Patras, Greece) under the number 492/05.12.2024. The results of the study will be presented at relevant national and international conferences and submitted for publication to peer-review journals.

This systematic review investigated available evidence on the stand-alone and incremental predictive performance of ophthalmic artery Doppler (OAD) for pre-eclampsia.

Systematic review.

We conducted a literature search from PubMed (Medline), the Cochrane CENTRAL, EMBASE and Scopus from inception to 8 April 2025.

Studies eligible for inclusion were prospective or retrospective cohort studies, case-control studies or randomised controlled trials that reported on the predictive performance of OAD for pre-eclampsia in singleton pregnancies; and conducted in either high-income country (HIC) or low- and middle-income country (LMIC).

Two reviewers independently screened and assessed articles for inclusion. One reviewer then extracted data using a standardised data extraction sheet, and any uncertainties were discussed with a second reviewer. The Prediction model Risk of Bias Assessment Tool was used for quality and risk of bias assessment. Findings were summarised and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement and synthesised qualitatively.

We identified and included 11 observational studies (3 from HIC and 8 from LMICs) with a total of 12 150 singleton pregnancies, of which 517 (4.3%) were complicated by pre-eclampsia at end of follow-up. The included studies were of varied quality, with three at low risk of bias, four at unclear risk and four at high risk. No interventional study was identified. Three studies (27.3%) recruited high-risk pregnancies (defined according to the American College of Obstetricians and Gynecologists (ACOG) criteria as one or more of the following: chronic hypertension, personal or family history of pre-eclampsia, early (≤18 years) or late (≥40 years) first pregnancy, primipaternity, chronic kidney disease, increased body mass index >30 kg/m², presence of diabetes mellitus prior to pregnancy, autoimmune disease and thrombophilia), while eight studies (72.7%) recruited undetermined risk pregnancies. Stand-alone performance of OAD (interpreted by area under the receiver operating curve at 95% CI) showed that in the first trimester, the peak systolic velocity (PSV) ratio demonstrated very good predictive ability (0.97, 95% CI 0.92 to 1.0) (n=1 study), and the second PSV (PSV₂) demonstrated very good predictive ability (0.91, 95% CI 0.82 to 0.99) (n=1 study). Also, PSV₂ demonstrated fair predictive ability (0.61, 95% CI 0.42 to 0.79; and 0.53, 95% CI 0.40 to 0.66) for early and late pre-eclampsia, respectively (n=1 study). In the second trimester, the PSV ratio demonstrated very good predictive ability (0.88, 95% CI 0.84 to 0.91) (n=1 study), and PSV₂ demonstrated good predictive ability (0.73, 95% CI 0.66 to 0.81; and 0.76, 95% CI 0.71 to 0.81) for pre-eclampsia (n=2 studies). In the third trimester, the PSV ratio demonstrated good predictive ability (0.82, 95% CI 0.73 to 0.89; and 0.77, 95% CI 0.71 to 0.82) for preterm and term pre-eclampsia, respectively (n=1 study). Also, PSV₂ demonstrated good predictive ability 0.70 (0.57 to 0.84) (n=1 study).

Subsequently, in the second trimester, PSV ratio demonstrated better incremental predictive performance than uterine artery pulsatility index for preterm pre-eclampsia, when added to maternal factors and mean arterial pressure (MAP) (56.1%–80.2% vs 56.1%–74.8% detection rate (DR) at 10% FPR) (n=1 study). Also in the third trimester, adding PSV ratio to maternal factors and MAP was superior to soluble fms-like tyrosine kinase-1/placental growth factor ratio in predicting pre-eclampsia at

The ophthalmic artery PSV ratio and PSV₂ are potentially useful ultrasound markers for pre-eclampsia prediction. Particularly in the second trimester, adding PSV ratio to maternal factors and MAP significantly improved the prediction of preterm pre-eclampsia. Given the burden of early and preterm pre-eclampsia in low-resource settings, OAD appears promising for pre-eclampsia screening in these settings where serum biomarkers may be expensive and inaccessible, and where uterine artery Doppler may not be technically feasible. However, the extent to which this novel marker is implemented in routine antenatal care should be guided by larger and sufficiently powered validation studies.

CRD42022324569.