Regional contrast agent quantification in a mouse model of myocardial infarction using 3D cardiac T1 mapping

<p>Abstract</p> <p>Background</p> <p>Quantitative relaxation time measurements by cardiovascular magnetic resonance (CMR) are of paramount importance in contrast-enhanced studies of experimental myocardial infarction. First, compared to qualitative measurements based on signal intensity changes, they are less sensitive to specific parameter choices, thereby allowing for better comparison between different studies or during longitudinal studies. Secondly, T₁measurements may allow for quantification of local contrast agent concentrations. In this study, a recently developed 3D T₁mapping technique was applied in a mouse model of myocardial infarction to measure differences in myocardial T₁before and after injection of a liposomal contrast agent. This was then used to assess the concentration of accumulated contrast agent.</p> <p>Materials and methods</p> <p>Myocardial ischemia/reperfusion injury was induced in 8 mice by transient ligation of the LAD coronary artery. Baseline quantitative T₁maps were made at day 1 after surgery, followed by injection of a Gd-based liposomal contrast agent. Five mice served as control group, which followed the same protocol without initial surgery. Twenty-four hours post-injection, a second T₁measurement was performed. Local ΔR₁values were compared with regional wall thickening determined by functional cine CMR and correlated to <it>ex vivo </it>Gd concentrations determined by ICP-MS.</p> <p>Results</p> <p>Compared to control values, pre-contrast T₁of infarcted myocardium was slightly elevated, whereas T₁of remote myocardium did not significantly differ. Twenty-four hours post-contrast injection, high ΔR₁values were found in regions with low wall thickening values. However, compared to remote tissue (wall thickening > 45%), ΔR₁was only significantly higher in severe infarcted tissue (wall thickening < 15%). A substantial correlation (<it>r </it>= 0.81) was found between CMR-based ΔR₁values and Gd concentrations from <it>ex vivo </it>ICP-MS measurements. Furthermore, regression analysis revealed that the effective relaxivity of the liposomal contrast agent was only about half the value determined <it>in vitro</it>.</p> <p>Conclusions</p> <p>3D cardiac T₁mapping by CMR can be used to monitor the accumulation of contrast agents in contrast-enhanced studies of murine myocardial infarction. The contrast agent relaxivity was decreased under <it>in vivo </it>conditions compared to <it>in vitro </it>measurements, which needs consideration when quantifying local contrast agent concentrations.</p

Preconception Lifestyle and Cardiovascular Health in the Offspring of Overweight and Obese Women

Funding: The LIFEstyle study was funded by ZonMw, the Dutch Organization for Health Research and Development, grant number: 50-50110-96-518. The follow-up of the LIFEstyle trial was funded by grants from the Dutch Heart Foundation (2013T085) and the European Commission (Horizon2020 project 633595 DynaHealth). None of these organizations had a role in data collection, analysis, interpretation of data, or writing the report. Acknowledgments: We thank all participants of the WOMB project, all participating hospitals and their staff and the members of the Dutch Consortium (www.studies-obsgyn.nl) for their hard work and dedication. Furthermore,we thank all members of the WOMB project who contributed to the follow-up study.Peer reviewedPublisher PD

Women, their Offspring and iMproving lifestyle for Better cardiovascular health of both (WOMB project) : A protocol of the follow-up of a multicentre randomised controlled trial

The LIFEstyle study was supported by a grant from The Netherlands Organization for Health Research and Development (50-50110-96-518). The WOMB project is funded by the Dutch Heart Foundation (2013T085) and the European Commission (Horizon2020 project ‘DynaHealth’, 633595).Peer reviewedPublisher PD

Effects of a preconception lifestyle intervention in obese infertile women on diet and physical activity; : A secondary analysis of a randomized controlled trial

Funding: The LIFEstyle study was funded by ZonMw, the Dutch Organization for Health Research and Development, grant number: 50- 50110-96-518. TvE is supported by grants from the Dutch Heart Foundation (2013T085) and the European Commission (Horizon2020 project 633595 DynaHealth). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PD

Real-world evidence of adjuvant gemcitabine plus capecitabine vs gemcitabine monotherapy for pancreatic ductal adenocarcinoma

The added value of capecitabine to adjuvant gemcitabine monotherapy (GEM) in pancreatic ductal adenocarcinoma (PDAC) was shown by the ESPAC-4 trial. Real-world data on the effectiveness of gemcitabine plus capecitabine (GEMCAP), in patients ineligible for mFOLFIRINOX, are lacking. Our study assessed whether adjuvant GEMCAP is superior to GEM in a nationwide cohort. Patients treated with adjuvant GEMCAP or GEM after resection of PDAC without preoperative treatment were identified from The Netherlands Cancer Registry (2015-2019). The primary outcome was overall survival (OS), measured from start of chemotherapy. The treatment effect of GEMCAP vs GEM was adjusted for sex, age, performance status, tumor size, lymph node involvement, resection margin and tumor differentiation in a multivariable Cox regression analysis. Secondary outcome was the percentage of patients who completed the planned six adjuvant treatment cycles. Overall, 778 patients were included, of whom 21.1% received GEMCAP and 78.9% received GEM. The median OS was 31.4 months (95% CI 26.8-40.7) for GEMCAP and 22.1 months (95% CI 20.6-25.0) for GEM (HR: 0.71, 95% CI 0.56-0.90; logrank P =.004). After adjustment for prognostic factors, survival remained superior for patients treated with GEMCAP (HR: 0.73, 95% CI 0.57-0.92, logrank P =.009). Survival with GEMCAP was superior to GEM in most subgroups of prognostic factors. Adjuvant chemotherapy was completed in 69.5% of the patients treated with GEMCAP and 62.7% with GEM (P =.11). In this nationwide cohort of patients with PDAC, adjuvant GEMCAP was associated with superior survival as compared to GEM monotherapy and number of cycles was similar

How baseline, new-onset, and persistent depressive symptoms are associated with cardiovascular and non-cardiovascular mortality in incident patients on chronic dialysis

AbstractObjectiveDepressive symptoms are associated with mortality among patients on chronic dialysis therapy. It is currently unknown how different courses of depressive symptoms are associated with both cardiovascular and non-cardiovascular mortality.MethodsIn a Dutch prospective nation-wide cohort study among incident patients on chronic dialysis, 1077 patients completed the Mental Health Inventory, both at 3 and 12months after starting dialysis. Cox regression models were used to calculate crude and adjusted hazard ratios (HRs) for mortality for patients with depressive symptoms at 3months only (baseline only), at 12months only (new-onset), and both at 3 and 12months (persistent), using patients without depressive symptoms at 3 and 12months as reference group.ResultsDepressive symptoms at baseline only seemed to be a strong marker for non-cardiovascular mortality (HRadj 1.91, 95% CI 1.26–2.90), whereas cardiovascular mortality was only moderately increased (HRadj 1.41, 95% CI 0.85–2.33). In contrast, new-onset depressive symptoms were moderately associated with both cardiovascular (HRadj 1.66, 95% CI 1.06–2.58) and non-cardiovascular mortality (HRadj 1.46, 95% CI 0.97–2.20). Among patients with persistent depressive symptoms, a poor survival was observed due to both cardiovascular (HRadj 2.14, 95% CI 1.42–3.24) and non-cardiovascular related mortality (HRadj 1.76, 95% CI 1.20–2.59).ConclusionThis study showed that different courses of depressive symptoms were associated with a poor survival after the start of dialysis. In particular, temporary depressive symptoms at the start of dialysis may be a strong marker for non-cardiovascular mortality, whereas persistent depressive symptoms were associated with both cardiovascular and non-cardiovascular mortality

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch