Search

Background: The capacity of high-density lipoprotein cholesterol (HDL) to acquire free cholesterol (FC) from triglyceride-rich lipoproteins during lipoprotein lipase-dependent lipolysis in a process of reverse remnant cholesterol transport, has been proposed as a key biological function of HDL particles that underlies the U-shaped relationship between HDLcholesterol and cardiovascular diseases. Although reverse remnant cholesterol transport has been evaluated in a fasting state, it has never been explored under nonfasting conditions., Methods and Results: FC transfer was evaluated in healthy men (n=78) before and throughout the postprandial phase up to 8 hours after consumption of a test meal. Postprandially, the capacity of HDL to acquire FC increased progressively, reaching a maximal mean value of 98.5%±22.5% 6 hours after meal intake ( P <0.05). Analysis of the study population according to tertiles of postprandial variation of FC transfer identified subjects exhibiting reduced capacity of HDL to acquire FC (tertile 1), those for whom the capacity of HDL to acquire FC remained unchanged (tertile 2), and subjects characterized by an enhanced FC transfer during the postprandial phase (tertile 3). Across the tertiles, we found an inverse relationship between the maximal postprandial change in FC transfer to HDL and the degree of postprandial triglyceride response., Conclusions: Healthy individuals exhibiting exacerbated postprandial triglyceride response and reduced HDL cholesterol levels feature reduced FC transfer to HDL during the postprandial state. These data suggest that to normalize postprandial triglyceride response, 2 conditions need to be fulfilled: notably elevated FC transfer to HDL in the postprandial phase and increased levels of acceptor HDL particles.

Prematurity remains a leading cause of mortality and morbidity in neonates and children. Prevention of preterm birth and of its complications is a major public health issue. From before conception to long term follow up, many health actors are engaged in this preventive strategy with the same goal : to give the best quality of life for these vulnerable young patients. We will review different preventive aspects during antenatal and perinatal period, during NICU (Neonatal Intensive Care Unit) stay and after discharge. Prevention of prematurity's complications requires a global approach including respiratory, nutritional and infectious aspects among others. Neuroprotective strategies are a key point of this global approach.

Background: Patients with systemic lupus erythematosus (SLE) exhibit a high risk for cardiovascular diseases (CVD) which is not fully explained by the classical Framingham risk factors. SLE is characterized by major metabolic alterations which can contribute to the elevated prevalence of CVD., Methods: A comprehensive analysis of the circulating metabolome and lipidome was conducted in a large cohort of 211 women with SLE who underwent a multi-detector computed tomography scan for quantification of coronary artery calcium (CAC), a robust predictor of coronary heart disease (CHD)., Findings: Beyond traditional risk factors, including age and hypertension, disease activity and duration were independent risk factors for developing CAC in women with SLE. The presence of coronary calcium was associated with major alterations of circulating lipidome dominated by an elevated abundance of ceramides with very long chain fatty acids. Alterations in multiple metabolic pathways, including purine, arginine and proline metabolism, and microbiota-derived metabolites, were also associated with CAC in women with SLE. Logistic regression with bootstrapping of lipidomic and metabolomic variables were used to develop prognostic scores. Strikingly, combining metabolic and lipidomic variables with clinical and biological parameters markedly improved the prediction (area under the curve: 0.887, p < 0.001) of the presence of coronary calcium in women with SLE., Interpretation: The present study uncovers the contribution of disturbed metabolism to the presence of coronary artery calcium and the associated risk of CHD in SLE. Identification of novel lipid and metabolite biomarkers may help stratifying patients for reducing CVD morbidity and mortality in SLE., Funding: INSERM and Sorbonne Université., Competing Interests: Declaration of interests The authors declare no competing financial interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Case Report: A 56-year-old male patient with terminal renal insufficiency received a living donor kidney transplant from his wife in June 2007. Initial immunosuppression consisted of prednisolone, tacrolimus, and mycophenolate mofetil (MMF). 4 months after transplantation, the serum creatinine increased to 192 micromol/l and urinary analysis revealed the presence of decoy cells. A biopsy showed a focal interstitial nephritis and SV40 antigen was detected in tubular nuclei. Polymerase chain reaction (PCR) in serum and urine showed high titers of BK virus. Tacrolimus was stopped, MMF was reduced, and leflunomide (20 mg/day) was started. The patient was readmitted because the serum creatinine further increased to 262 micromol/l. Leflunomide concentrations were in the target range, but renal biopsy still revealed the presence of BK virus nephropathy. MMF was stopped. Serum creatinine stabilized at 233 micromol/l and PCR for BK virus in serum was negative. In April 2008, a deterioration of renal function occurred (serum creatinine 308 micromol/l) and renal biopsy revealed signs of acute interstitial rejection without the presence of SV40 antigen. A methylprednisolone pulse therapy for 5 days was performed and cyclosporine was added. After a few weeks serum creatinine increased to 444 micromol/l and a new biopsy revealed the reoccurrence of BK virus nephropathy. Since the tubulointerstitial injury was > 80%, no further therapy was performed and soon after dialysis therapy was initiated., Conclusion: BK virus nephropathy is a still rare, but increasing complication of renal transplantation, presumably mediated by intensive immunosuppression. The disease can induce graft dysfunction and may ultimately lead to graft failure. BK virus nephropathy can trigger acute rejection. Unfortunately, therapy of BK virus nephropathy and acute rejection is just the opposite: BK virus nephropathy requires a reduction of immunosuppression whereas acute rejection calls for intensification. A potential therapeutic approach may be leflunomide, an immunosuppressive substance with antiviral properties, but potential severe side effects. The described case demonstrates the frustrating course of a graft from a living donor despite initial successful therapy with leflunomide and illustrates the problems choosing between intensive and moderate immunosuppression.