Queen Elizabeth Hospital in King's Lynn, Norfolk, England. It is located on the outskirts of King's Lynn, to the eastern edge of the town. The catchment area of the Queen Elizabeth Hospital covers the West Norfolk area, South Lincolnshire and Northern part of Fenland District, Cambridgeshire, an area of approximately 1500 km² and 250,000 people. It is managed by the Queen Elizabeth Hospital King's Lynn NHS Foundation Trust. The Queen Elizabeth Hospital is named after Queen Elizabeth The Queen Mother, rather than Queen Elizabeth II.
Abstract Background Cancer survivors frequently develop cardiovascular events despite low rates of obstructive coronary disease. Coronary computed tomography angiography (CCTA) can identify high-risk plaque phenotype that may refine risk beyond stenosis severity. Purpose To assess whether high-risk plaque features on CCTA predict short-term cardiovascular events in cancer survivors. Methods We studied consecutive cancer survivors referred for clinically indicated CCTA between 2021–2025. High-risk plaque was defined by the presence of ≥1 high-risk feature (low attenuation plaque, positive remodelling, spotty calcification, or napkin-ring sign). Obstructive disease was defined as ≥50% stenosis. The primary outcome was a 12-month composite of acute coronary syndrome, revascularisation, or cardiovascular hospitalisation. Multivariable Cox regression adjusted for age, sex, diabetes, hypertension, dyslipidaemia, smoking, and coronary calcium category. Results Among 286 cancer survivors (mean age 54±11 years; 52% female), obstructive disease was present in 24 (8%). High-risk plaque features were identified in 47 (16%) and were more frequent in patients with prior chest radiotherapy (22% vs 13%). At 12 months, the composite outcome occurred in 20 patients (7.0%). Event rates were higher with high-risk plaque than without (14.9% vs 5.5%, p=0.01), while obstructive stenosis alone was not the dominant driver of events. High-risk plaque remained independently associated with outcomes after adjustment (adjusted hazard ratio 2.6, 95% CI 1.2–5.5). Notably, most events occurred in patients with non-obstructive but high-risk plaque phenotype. Conclusion In cancer survivors undergoing CCTA, high-risk plaque phenotype predicted short-term cardiovascular events despite low prevalence of obstructive disease. CCTA plaque characterisation may enable more targeted preventive strategies in cardio-oncology practice.
Human childbirth is hazardous compared with other primates, where both perinatal and maternal mortality remain a major global challenge despite advances in neonatal and obstetric care. The concept of the obstetric dilemma frames the evolutionary trade-off between the requirements of bipedal locomotion, which constrains pelvic dimensions, and the need to deliver a neonate with a relatively large cranium. The limits of the maternal pelvis increase the risk of obstructed labor for larger babies, while smaller babies are vulnerable to other causes of mortality such as growth restriction or failure to thrive postnatally. This means that birthweight is subject to stabilizing selection. Contributing to the regulation of birthweight and placental function are interactions between killer immunoglobulin-like receptors (KIRs) on maternal uterine natural killer cells and fetal human leukocyte antigen-C (HLA-C) molecules expressed on invading extravillous trophoblast cells. Distinct KIR -human leukocyte antigen genetic combinations are associated with specific reproductive outcomes. Maternal inhibitory KIR with fetal HLA-C2 group allotypes are associated with impaired trophoblast invasion, defective spiral artery remodeling, and increased risk of great obstetrical syndromes, such as preeclampsia. However, these same inhibitory interactions may enhance maternal resistance to certain pathogens. In contrast, activating KIR-human leukocyte antigen interactions seem to be protective against great obstetrical syndromes but appear to confer weaker pathogen resistance. The persistence of both activating and inhibitory KIR variants binding different HLA-C groups therefore reflects stabilizing selection. This immunogenetic interplay adds another dimension to the obstetric dilemma providing a framework for understanding the evolutionary origins of childbirth by linking the evolutionary pressures of a large fetal brain, constraints on pelvic dimensions, stabilizing selection on birthweight, and responses to infection. These ideas can help understand the complex evolutionary origins of obstetric risk seen today for many conditions including preeclampsia, obstructed labor, stillbirth, fetal growth restriction, and preterm labor. We speculate how modern medical care during childbirth will affect the frequency of these conditions in future.
Abstract Background Cancer survivors remain at increased risk of coronary events even when obstructive coronary disease is mild. A key gap in routine care is detecting ongoing vascular inflammation, particularly after chest radiotherapy. Pericoronary adipose tissue attenuation on coronary computed tomography angiography (CCTA) is a practical imaging marker of coronary inflammation. Purpose To determine whether chest radiotherapy is associated with higher pericoronary fat attenuation on CCTA, and whether this inflammatory signal relates to high-risk plaque phenotype. Methods We retrospectively analyzed consecutive adults undergoing clinically indicated CCTA between 2021–2025. Cancer survivors were stratified into prior chest radiotherapy versus no radiotherapy and compared with age- and sex-matched non-cancer controls. Pericoronary fat attenuation was measured as mean attenuation (Hounsfield units) around the proximal right coronary artery. Coronary stenosis severity (CAD-RADS) and high-risk plaque features (low attenuation plaque, positive remodeling, spotty calcification, napkin-ring sign) were recorded. A subset with complete blood count within ±30 days was used to examine associations with neutrophil-to-lymphocyte ratio (NLR). Results A total of 318 patients were included (198 cancer survivors, 120 controls; mean age 53±11 years; 54% female). Among survivors, 76 (38%) had prior chest radiotherapy. Obstructive coronary disease was uncommon and comparable across groups (≥50% stenosis: 9% radiotherapy vs 7% no radiotherapy vs 8% controls; p=0.81). Pericoronary fat attenuation was higher (less negative) in radiotherapy survivors compared with non-radiotherapy survivors and controls (−69±7 vs −73±6 vs −75±6 HU; p<0.001). High-risk plaque features were more frequent in the radiotherapy group (21% vs 13% vs 10%; p=0.03). After adjustment for traditional risk factors, chest radiotherapy remained independently associated with higher pericoronary fat attenuation (β=+3.1 HU, p=0.002). In the CBC subset (n=210), higher NLR showed a modest association with higher pericoronary fat attenuation (r=0.24, p=0.01). Conclusion Chest radiotherapy is associated with a measurable CCTA inflammatory signature using pericoronary fat attenuation, even when stenosis severity is similar. This pragmatic CT-based marker may help identify cancer survivors with persistent vascular inflammation and higher plaque vulnerability, supporting more targeted preventive strategies.
