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Over 10 million patients undergoing non-cardiac surgery annually experience major cardiovascular complications within 30 days, many due to destabilized atherosclerotic plaques. Reverse cholesterol transport (RCT), a key pathway for cholesterol removal by HDL and apoA-I, is critical in preventing plaque progression. While surgery-induced inflammation is known to impair HDL function, its effects on RCT and plaque stability remain unclear. To isolate the impact of surgical inflammation, independent of blood loss, we developed an abdominal laparotomy model in mice on a Western diet, minimizing blood loss and avoiding perioperative blood sampling. We assessed plasma cholesterol efflux capacity, performed proteomic analysis of HDL, and analyzed atherosclerotic plaques for lipid content, perilipin-2 (PLIN2), cleaved-caspase-3 (c-Casp-3), and necrotic core expansion. A novel dual-label, dual-cell-type RCT model was developed to compare RCT from macrophage-derived (BMDMs) and vascular smooth muscle cells (VSMCs)-derived foam cells. Recombinant apoA-I (rApoA-I) was tested for therapeutic rescue of impaired RCT. Surgery significantly reduced RCT for at least 48 hours, paralleled by a drop in cholesterol efflux capacity and inflammatory remodeling of HDL, marked by elevated serum amyloid A (SAA1/2) and reduced apoA-I. Plaques showed a 1.6-fold increase in intracellular lipids and PLIN2 expression at 24 hours post-surgery, with elevated c-Casp-3 indicating lipid-driven apoptosis. Foam cell analysis revealed increased PLIN2 in both CD45 (leukocyte) and CD45 (non-leukocyte) subtypes, with leukocyte foam cells expressing higher PLIN2. c-Casp-3 apoptotic cells were predominantly PLIN2 and of both leukocytic and non-leukocytic origin. By day 15, the necrotic core area increased by 1.5-fold with sustained loss of plaque cellularity. Using our dual-cell-type RCT model, we found that surgery significantly impaired BMDM RCT , while VSMC RCT remained largely unaffected, highlighting foam cell subtype-specific vulnerability to surgical inflammation. These findings were mirrored in general surgery patients, whose postoperative plasma exhibited markedly reduced cholesterol efflux capacity. In mice, rApoA-I treatment partially restored RCT and reduced plaque lipid accumulation. Surgical inflammation acutely impairs HDL function and RCT, triggering lipid accumulation, foam cell apoptosis, and accelerated plaque destabilization independent of blood loss. Immediate restoration of apoA-I at the time of surgery, aiming to counteract the acute phase response, may offer a targeted strategy to reduce postoperative cardiovascular risk.

Cytosolic lipid droplets (LDs) regulate lipid homeostasis, with abnormal LD dynamics linked to metabolic diseases like atherosclerosis. In macrophage foam cells, LDs undergo autophagic degradation via lipophagy, but the extent of this process in vascular smooth muscle cell (VSMC) foam cells remains unclear. To track lipophagy in real time, we developed a Rosella-PLIN2 biosensor by tagging perilipin 2 (PLIN2) with the fluorescent pH-biosensor Rosella. We show that proatherogenic lipoproteins and autophagy activators stimulate lipophagy in human macrophages. Targeting LDs with an LC3 fusion protein or LD-autophagy tethering compounds (LD-ATTECs) selectively enhanced lipophagy, promoting foam cell LD clearance. In an atherosclerosis model, Rosella-PLIN2 accurately tracked lipophagy in arterial foam cells, revealing distinct PLIN2 expression patterns in macrophage and non-leukocyte foam cells. We identified a lipophagy deficiency in VSMC foam cells and demonstrate that enhancing lipophagy promotes LD catabolism in primary VSMC foam cells. TREM2+ macrophages exhibited high lipid content and low lipophagy flux, whereas TREM2- macrophages had low lipid content and high lipophagy flux. Our findings highlight a cell-specific interplay between lipophagy and immunometabolism in arterial foam cells, unveiling novel therapeutic avenues for atherosclerosis. Additionally, the Rosella-PLIN2 model provides a powerful tool for studying LD metabolism, offering new insights into lipid homeostasis and disease mechanisms.

The Proprotein Convertase Subtilisin Kexin of type 9 (PCSK9) has been identified in 2003 as the third gene involved in familial hypercholesterolemia. PCSK9 binds to the membrane low-density lipoprotein receptor (LDLR) and promotes its cellular internalization and lysosomal degradation. Beyond this canonical role, PCSK9 was recently described to be involved in several immune responses. However, to date, the contribution of PCSK9 in food allergy remains unknown. Here, we showed that Pcsk9 deficiency or pharmacological inhibition of circulating PCSK9 with a specific monoclonal antibody (m-Ab) protected mice against symptoms of gliadin-induced-food allergy, such as increased intestinal transit time and ear oedema. Furthermore, specific PCSK9 inhibition during the elicitation steps of allergic process was sufficient to ensure anti-allergic effects in mice. Interestingly, the protective effect of PCSK9 inhibition against food allergy symptoms was independent of the LDLR as PCSK9 inhibitors remained effective in Ldlr deficient mice. In vitro, we showed that recombinant gain of function PCSK9 (PCSK9 D374Y) increased the percentage of mature bone marrow derived dendritic cells (BMDCs), promoted naïve T cell proliferation and potentiated the gliadin induced basophils degranulation. Altogether, our data demonstrate that PCSK9 inhibition is protective against gliadin induced food allergy in a LDLR-independent manner.

Background One young adult in two has entered university education in Western countries. Many of these young students will be exposed, during this transitional period, to substantial changes in living arrangements, socialisation groups, and social activities. This kind of transition is often associated with risky behaviour such as excessive alcohol consumption. So far, however, there is little evidence about the social determinants of alcohol consumption among college students. We set out to explore how college environmental factors shape college students' drinking behaviour. Methods In May 2010 a web questionnaire was sent to all bachelor and master students registered with an important Belgian university; 7,015 students participated (participation = 39%). The survey looked at drinking behaviour, social involvement, college environmental factors, drinking norms, and positive drinking consequences. Results On average each student had 1.7 drinks a day and 2.8 episodes of abusive drinking a month. We found that the more a student was exposed to college environmental factors, the greater the risk of heavy, frequent, and abusive drinking. Alcohol consumption increased for students living on campus, living in a dormitory with a higher number of room-mates, and having been in the University for a long spell. Most such environmental factors were explained by social involvement, such as participation to the student folklore, pre-partying, and normative expectations. Conclusions Educational and college authorities need to acknowledge universities’ responsibility in relation to their students’ drinking behaviour and to commit themselves to support an environment of responsible drinking.

Patient satisfaction is a key indicator of inpatient care quality and is associated with clinical outcomes following admission. Different patient characteristics have been inconsistently linked with satisfaction. This study aims to overcome previous limitations by assessing which patient characteristics are associated with satisfaction within a large study of psychiatric inpatients conducted across five European countries. All patients with a diagnosis of psychotic (F2), affective (F3) or anxiety/somataform (F4) disorder admitted to 57 psychiatric inpatient units in Belgium, Germany, Italy, Poland and the UK were included. Data were collected from medical records and face-to-face interviews, with patients approached within 2 days of admission. Satisfaction with inpatient care was measured on the Client Assessment of Treatment Scale. Higher satisfaction scores were associated with being older, employed, living with others, having a close friend, less severe illness and a first admission. In contrast, higher education levels, comorbid personality disorder and involuntary admission were associated with lower levels of satisfaction. Although the same patient characteristics predicted satisfaction within the five countries, there were significant differences in overall satisfaction scores across countries. Compared to other countries, patients in the UK were significantly less satisfied with their inpatient care. Having a better understanding of patient satisfaction may enable services to improve the quality of care provided as well as clinical outcomes for all patients. Across countries, the same patient characteristics predict satisfaction, suggesting that similar analytical frameworks can and should be used when assessing satisfaction both nationally and internationally.

Objectives The objective was to define a safe strategy to exclude pulmonary embolism (PE) in COVID-19 outpatients, without performing CT pulmonary angiogram (CTPA). Methods COVID-19 outpatients from 15 university hospitals who underwent a CTPA were retrospectively evaluated. D-Dimers, variables of the revised Geneva and Wells scores, as well as laboratory findings and clinical characteristics related to COVID-19 pneumonia, were collected. CTPA reports were reviewed for the presence of PE and the extent of COVID-19 disease. PE rule-out strategies were based solely on D-Dimer tests using different thresholds, the revised Geneva and Wells scores, and a COVID-19 PE prediction model built on our dataset were compared. The area under the receiver operating characteristics curve (AUC), failure rate, and efficiency were calculated. Results In total, 1369 patients were included of whom 124 were PE positive (9.1%). Failure rate and efficiency of D-Dimer > 500 µg/l were 0.9% (95%CI, 0.2–4.8%) and 10.1% (8.5–11.9%), respectively, increasing to 1.0% (0.2–5.3%) and 16.4% (14.4–18.7%), respectively, for an age-adjusted D-Dimer level. D-dimer > 1000 µg/l led to an unacceptable failure rate to 8.1% (4.4–14.5%). The best performances of the revised Geneva and Wells scores were obtained using the age-adjusted D-Dimer level. They had the same failure rate of 1.0% (0.2–5.3%) for efficiency of 16.8% (14.7–19.1%), and 16.9% (14.8–19.2%) respectively. The developed COVID-19 PE prediction model had an AUC of 0.609 (0.594–0.623) with an efficiency of 20.5% (18.4–22.8%) when its failure was set to 0.8%. Conclusions The strategy to safely exclude PE in COVID-19 outpatients should not differ from that used in non-COVID-19 patients. The added value of the COVID-19 PE prediction model is minor. Key Points • D-dimer level remains the most important predictor of pulmonary embolism in COVID-19 patients. • The AUCs of the revised Geneva and Wells scores using an age-adjusted D-dimer threshold were 0.587 (95%CI, 0.572 to 0.603) and 0.588 (95%CI, 0.572 to 0.603). • The AUC of COVID-19-specific strategy to rule out pulmonary embolism ranged from 0.513 (95%CI: 0.503 to 0.522) to 0.609 (95%CI: 0.594 to 0.623).

PurposeLong lengths of stay (LoS) in psychiatric hospitals or repeated admission may affect the social integration of patients with psychiatric disorders. So far, however, studies have been inconclusive. This study aimed to analyse whether long LoS or repeated admissions in psychiatric wards were associated in different ways with changes in the social integration of patients.MethodsWithin a prospective cohort study, data were collected on 2181 patients with a main ICD-10 diagnosis of psychotic, affective, or anxiety disorder, hospitalised in the UK, Italy, Germany, Poland, and Belgium in 2015. Social integration was measured at baseline and 1 year after admission using the SIX index, which includes four dimensions: employment, housing, family situation, and friendship. Regression models were performed to test the association between LoS, the number of admissions, and the change in social integration over the study period, controlling for patients’ characteristics (trial registration ISRCTN40256812).ResultsA longer LoS was significantly associated with a decrease in social integration (β = − 0.23, 95%CI − 0.32 to − 0.14, p = 0.03), particularly regarding employment (OR = 2.21, 95%CI 1.18–3.24, p = 0.02), housing (OR = 3.45, 95%CI 1.74–5.16, p < 0.001), and family situation (OR = 1.94, 95%CI 1.10–2.78, p = 0.04). In contrast, repeated admissions were only associated with a decrease in friendship contacts (OR = 1.15, 95CI% 1.08–1.22, p = 0.03).ConclusionsResults suggest that a longer hospital LoS is more strongly associated with a decrease in patients’ social integration than repeated admissions. Special attention should be paid to helping patients to find and retain housing and employment while hospitalised for long periods.

Several studies have observed socio-economic (SE) inequalities in smoking among adolescents, but its causes are not fully understood. This study investigates the association between parental and adolescent smoking, and whether this association is socially patterned. We used data from a survey administered in 2013 to students aged 14-17 years old of six European cities (n = 10 526). Using multilevel mixed-effects logistic regression, we modelled the probability of being a daily smoker as a function of parental smoking and SE status. We tested whether the smoking association differed across social strata. The prevalence of parental smoking was higher in low SE status adolescents. Boys and girls were more likely to smoke if they have a father [boys: adjusted odds ratio (AOR) = 1.90, 95% CI = 1.47-2.46; girls: AOR = 1.42, 95% CI = 1.09-1.86] and mother (boys: AOR = 1.77, 95% CI = 1.35-2.31; girls: AOR = 3.36, 95% CI = 2.56-4.40) who smoked. Among boys, the odds of smoking when having a smoking parent were higher in lower SE classes. However, this was not statistically significant, nor was it observed among girls. Adolescents are more likely to smoke when their father and mother smoke. Although the susceptibility to parental smoking was similar across social classes, SE differences in parental smoking contribute to the transmission of SE inequalities in smoking.

Peer networks at school and students’ position in these networks can influence their academic well-being. We study here individual students’ network position (isolation, popularity, social activity) and peer network structures at the school level (centralization, density, clustering, school connectedness) and their relations to students’ academic well-being (school burnout, SB; schoolwork engagement, SE). Classroom surveys for 14–16-year-olds (N = 11,015) were conducted in six European cities (SILNE survey). Students were asked to nominate up to five schoolmates with whom they preferred to do schoolwork. SB and SE correlated negatively (−0.32; p < 0.0001). Students had on average 3.4 incoming (popularity; range 0–5) and 3.4 outgoing (social activity; 0–5) social ties. Percentage of isolated students was 1.4. Students’ network position was associated weakly with academic well-being—popular students had less SB and higher SE, and socially active students had higher SE. School-level peer networks showed high clustering and school connectedness, but low density and low centralization. Clustering was associated with higher SB. Low centralization and high school connectedness protected from SB. Dense networks supported SE as did high average school connectedness. Correlations between these network indicators and academic well-being were, however, low. Our study showed that both students’ network position and network characteristics at the school level can influence adolescents’ academic well-being.

PurposeProviding effective treatment for immigrants is an increasing challenge for mental health services across Europe. Yet, little is known as to whether current practice is associated with different outcomes in migrant and non-migrant patients. We compared outcomes of inpatient psychiatric treatment for migrants and non-migrants in a sample from five European countries.MethodsPatients with psychotic disorders, affective disorders or anxiety/somatisation disorders admitted to routine psychiatric inpatient treatment were assessed in hospitals in Belgium, Germany, Italy, Poland and the United Kingdom. Treatment outcomes were satisfaction with care during hospitalisation, length of stay, readmission to hospital (any and, specifically, involuntary re-hospitalisation), as well as untoward incidents in a 1-year follow-up period. Outcomes were compared between patients born inside (non-migrants) and outside (migrants) the country of treatment, through mixed regression models.ResultsAcross all sites, 985 migrant patients and 6298 non-migrant patients were included. After accounting for the influence of confounding patient characteristics, migrants reported significantly lower treatment satisfaction, but there were no significant differences for length of stay and re-hospitalisations, in general and involuntary ones. Migrants had a lower rate of suicide attempts, but there was no significant difference in other types of untoward incidents in the year following the index admission.ConclusionThe study suggests that migrants are less satisfied with their hospital treatment, there is no evidence that routine inpatient care as currently provided results overall in poorer objective outcomes for migrants than in non-migrant populations.