Conflicting data have been reported on the risk for venous thrombosis in subjects with low free protein S levels. We performed a post-hoc analysis in a single-center retrospective thrombophilic ...family cohort, to define the optimal free protein S level that can identify subjects at risk for venous thrombosis. Relatives (1143) were analyzed. Relatives with venous thrombosis (mean age 39 years) had lower free protein S levels than relatives without venous thrombosis (P < .001), which was most pronounced in the lowest quartile. Only relatives with free protein S levels less than the 5th percentile (< 41 IU/dL) or less than the 2.5th percentile (< 33 IU/dL) were at higher risk of first venous thrombosis compared with the upper quartile (> 91 IU/dL); annual incidence 1.20% (95% confidence interval CI, 0.72–1.87) and 1.81% (95% CI, 1.01–2.99), respectively; adjusted hazard ratios 5.6, (95% CI, 2.7–11.5) and 11.3 (95% CI, 5.4–23.6). Recurrence rates were 12.12% (95 CI, 5.23–23.88) and 12.73% (95% CI, 5.12–26.22) per year; adjusted hazard ratios were 3.0 (95% CI, 1.03–8.5) and 3.4 (95% CI, 1.1–10.3). In conclusion, free protein S level can identify young subjects at risk for venous thrombosis in thrombophilic families, although the cutoff level lies far below the normal range in healthy volunteers.
To evaluate the additional value of dobutamine stress testing in patients with repaired tetralogy of Fallot (TOF) by relating stress imaging parameters at baseline to relevant parameters of clinical ...condition and right ventricular (RV) size during a serial follow-up.
We prospectively included 27 patients (14 ± 4 years at baseline), who were studied twice with a 5-year interval. Patients underwent cardiovascular magnetic resonance imaging to assess RV systolic and diastolic function at rest and during dobutamine stress. Normal response to dobutamine was defined as a decrease in RV end-systolic volume, and a increase in RV ejection fraction (EF) during stress. Exercise testing and electrocardiography were performed to determine peak oxygen uptake (peak VO₂), QRS duration, and QT interval corrected for heart rate (QTc) interval. RV volumes, QRS duration, and QTc interval increased significantly from baseline to follow-up; peak VO₂ tended to decrease (95 ± 20-89 ± 14%, P = 0.086). Response to dobutamine was normal in 26 of 27 patients and remained stable during the follow-up relative increase in RVEF during stress: +25 ± 9% (baseline) vs. +27 ± 10% (follow-up). A smaller relative increase in RVEF during stress at baseline related to a larger relative decrease in peak VO₂ during the follow-up (r = 0.59, P = 0.004). No significant associations were found with the relative increase in QRS duration, QTc interval, or RV end-diastolic volume during a 5-year follow-up.
In a young TOF population, response to dobutamine stress was normal and remained stable during the 5-year follow-up. A smaller increase in RVEF during stress at baseline was predictive for a larger decrease in peak VO₂ during the 5-year follow-up.
Abstract Aims To describe smoking habits in adults with congenital heart disease (ACHD) and to assess the relationship between smoking exposure and cardiovascular mortality. Methods Data on smoking ...history and cardiovascular mortality were extracted from the Euro Heart Survey on adult congenital heart disease — a retrospective cohort study, that included patients diagnosed with 1 of 8 subgroups of ACHD (Atrial Septal Defects, Ventricular Septal Defects, Marfan Syndrome, Aortic Coarctation, Tetralogy of Fallot (ToF), Transposition of the Great Arteries (TGA), Fontan circulation, and Cyanotic disease). Results Complete data of 3375 ACHD patients (median age 28 years) were available for analysis. At inclusion, 9.3% ( n = 314) were current smokers and 4.2% ( n = 142) of the patients had smoked in the past. During a median follow-up of 5.1 years, 101 patients (3%) died. In the majority of cases the cause of death was cardiovascular ( n = 81; 80%). Kaplan–Meier and Cox survival analysis for each of the defects separately showed a significantly increased age and sex-adjusted cardiovascular mortality associated with smoking exposure in TGA patients (Hazard ratio 4.2 (95% CI 1.0–16.8); P = 0.044). Also in ToF mortality was higher amongst smokers, though not significantly (HR 3.4 (95% CI 0.6–18.5); P = 0.15). In the remaining defects no relationship between smoking and cardiovascular mortality was observed. Conclusion The prevalence of smoking amongst ACHD patients is relatively low. Smoking exposure is associated with increased cardiovascular mortality in patients with TGA. Prospective long-term follow-up studies are necessary.
Calcium (Ca), phosphate (P), and parathyroid hormone (PTH) are important variables influencing the risk for cardiovascular disease in dialysis patients. We studied the influence of long-standing Ca-P ...disregulation on renal transplant survival.
Pretransplant PTH, Ca, P, total protein (TP), albumin, and alkaline phosphatase (AP) values were gathered in all 407 patients that received a renal transplant in our center between January 1, 2000 and July 1, 2004. Other variables expected to influence the risks were included. RESULTS. In the Cox proportional hazards analysis the risk for graft failure censored for death was significantly influenced by pretransplant PTH concentration (P = 0.008) and donor type (P < 0.001). The influence of PTH on the risk for patient death was not significant. The risk for acute rejection was studied but PTH level did not have a significant influence on this risk (P = 0.055). The risk for delayed graft function was not influenced by PTH level.
Serum PTH levels have an independent influence on the risk for graft failure censored for death. Efforts to improve calcium-phosphate-PTH homeostasis in patients on the waiting list for renal transplantation should be encouraged also to improve graft survival.
Optoacoustic imaging offers the promise of high spatial resolution and, at the same time, penetration depths well beyond the conventional optical imaging technologies, advantages that would be ...favorable for a variety of clinical applications. However, similar to optical fluorescence imaging, exogenous contrast agents, known as sonophores, need to be developed for molecularly targeted optoacoustic imaging. Despite numerous optoacoustic contrast agents that have been reported, there is a need for more rational design of sonophores. Here, using a library screening approach, we systematically identified and evaluated twelve commercially available near-infrared (690-900 nm) and highly absorbing dyes for multi-spectral optoacoustic tomography (MSOT). In order to achieve more accurate spectral deconvolution and precise data quantification, we sought five practical mathematical methods, namely direct classical least squares based on UV-Vis (UV/Vis-DCLS) or optoacoustic (OA-DCLS) spectra, non-negative LS (NN-LS), independent component analysis (ICA) and principal component analysis (PCA). We found that OA-DCLS is the most suitable method, allowing easy implementation and sufficient accuracy for routine analysis. Here, we demonstrate for the first time that our biocompatible nanoemulsions (NEs), in combination with near-infrared and highly absorbing dyes, enable non-invasive
in vivo
MSOT detection of tumors. Specifically, we found that NE-IRDye QC1 offers excellent optoacoustic performance and detection compared to related near-infrared NEs. We demonstrate that when loaded with low fluorescent or dark quencher dyes, NEs represent a flexible and new class of exogenous sonophores suitable for non-invasive pre-clinical optoacoustic imaging.
Dark Quencher, IRDye QC1 in nanoemulsion form offers excellent optoacoustic performance, suitable for non-invasive pre-clinical optoacoustic imaging.
Dark Quencher, IRDye QC1 in nanoemulsion form offers excellent optoacoustic performance, suitable for non-invasive pre-clinical optoacoustic imaging.
Optoacoustic imaging offers the promise of high ...spatial resolution and, at the same time, penetration depths well beyond the conventional optical imaging technologies, advantages that would be favorable for a variety of clinical applications. However, similar to optical fluorescence imaging, exogenous contrast agents, known as sonophores, need to be developed for molecularly targeted optoacoustic imaging. Despite numerous optoacoustic contrast agents that have been reported, there is a need for more rational design of sonophores. Here, using a library screening approach, we systematically identified and evaluated twelve commercially available near-infrared (690–900 nm) and highly absorbing dyes for multi-spectral optoacoustic tomography (MSOT). In order to achieve more accurate spectral deconvolution and precise data quantification, we sought five practical mathematical methods, namely direct classical least squares based on UV-Vis (UV/Vis-DCLS) or optoacoustic (OA-DCLS) spectra, non-negative LS (NN-LS), independent component analysis (ICA) and principal component analysis (PCA). We found that OA-DCLS is the most suitable method, allowing easy implementation and sufficient accuracy for routine analysis. Here, we demonstrate for the first time that our biocompatible nanoemulsions (NEs), in combination with near-infrared and highly absorbing dyes, enable non-invasive
in vivo
MSOT detection of tumors. Specifically, we found that NE-IRDye QC1 offers excellent optoacoustic performance and detection compared to related near-infrared NEs. We demonstrate that when loaded with low fluorescent or dark quencher dyes, NEs represent a flexible and new class of exogenous sonophores suitable for non-invasive pre-clinical optoacoustic imaging.
When first published, this article inadvertently listed the Dutch NODO group individually within the author list without specifying the names of the collaborators. The collaborators have been listed ...within the Acknowledgements section only. The corrected author list is presented in this Correction.
While acute myocardial infarction mortality declines, patients continue to face reinfarction and/or heart failure. The immune system, which intimately interacts with healthy and diseased tissues ...through resident and recruited leukocytes, is a central interface for a global host response to ischemia. Pathways that enhance the systemic leukocyte supply may be potential therapeutic targets. Pre-clinically, imaging helps to identify immunity's decision nodes, which may serve as such targets. In translating the rapidly-expanding pre-clinical data on immune activity, the difficulty of obtaining multiple clinical tissue samples from involved organs is an obstacle that whole-body imaging can help overcome. In patients, molecular and cellular imaging can be integrated with blood-based diagnostics to assess the translatability of discoveries, including the activation of hematopoietic tissues after myocardial infarction, and serve as an endpoint in clinical trials. In this review, we discuss these concepts while focusing on imaging immune activity in organs involved in ischemic heart disease.
Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP and may run a severe course. Evidence suggests that vigorous periprocedural ...hydration can prevent PEP, but studies to date have significant methodological drawbacks. Importantly, evidence for its added value in patients already receiving prophylactic rectal non-steroidal anti-inflammatory drugs (NSAIDs) is lacking and the cost-effectiveness of the approach has not been investigated. We hypothesize that combination therapy of rectal NSAIDs and periprocedural hydration would significantly lower the incidence of post-ERCP pancreatitis compared to rectal NSAIDs alone in moderate- to high-risk patients undergoing ERCP.
The FLUYT trial is a multicenter, parallel group, open label, superiority randomized controlled trial. A total of 826 moderate- to high-risk patients undergoing ERCP that receive prophylactic rectal NSAIDs will be randomized to a control group (no fluids or normal saline with a maximum of 1.5 mL/kg/h and 3 L/24 h) or intervention group (lactated Ringer's solution with 20 mL/kg over 60 min at start of ERCP, followed by 3 mL/kg/h for 8 h thereafter). The primary endpoint is the incidence of post-ERCP pancreatitis. Secondary endpoints include PEP severity, hydration-related complications, and cost-effectiveness.
The FLUYT trial design, including hydration schedule, fluid type, and sample size, maximize its power of identifying a potential difference in post-ERCP pancreatitis incidence in patients receiving prophylactic rectal NSAIDs.
EudraCT: 2015-000829-37 . Registered on 18 February 2015.
13659155 . Registered on 18 May 2015.
Conflicting data have been reported on the risk for venous thrombosis in subjects with protein S type III deficiency. As some studies included subjects with protein S type I deficiency, combined with ...an inadequate cut-off level for defining protein S type III deficiency (i.e. lower limit in healthy volunteers, generally < 65 IU/dL) might explain this discrepancy. We performed a single center retrospective study in a large cohort of families wherein probands had thrombosis and a thrombophilic defect, to define an optimal free protein S level that can identify subjects at risk for venous thrombosis. Probands were excluded as were relatives with protein S type I deficiency. Free protein S antigen levels were measured after precipitation of protein S complexed with C4b-binding protein with polyethylene glycol. 1143 relatives were analyzed. Mean age at onset of the first episode of venous thrombosis was 39 years. Relatives with venous thrombosis had lower free protein S levels than relatives without venous thrombosis (P< 0.001), which was most pronounced in the lowest quartile (Figure). Only relatives with free protein S levels below the 5th percentile (< 41 IU/dL) or below the 2.5th percentile (< 33 IU/dL) were at higher risk of first venous thrombosis compared to relatives with free protein S levels in the upper quartile (³ 91 IU/dL); annual incidence 1.20% (95% CI, 0.72–1.87), and 1.81% (95% CI, 1.01–2.99), respectively; hazard ratio, adjusted for age, sex and thrombophilic defects 6.7, (95% CI, 3.3–13.5) and 11.3 (95% CI, 5.2–22.1). Recurrence rates in these subgroups were 12.12% (95 CI, 5.23–23.88) and 12.73% (95% CI, 5.12–26.22) per year. Relatives with free protein S levels lower than the 5th or 2.5th percentile had an adjusted 2.8 (95% CI, 0.8–8.6) and 3.1 (95% CI, 0.9–10.5) fold higher risk of recurrence compared to relatives with free protein S levels in the upper quartile. We conclude that decreased free protein S levels are a risk factor for venous thrombosis. However, the free protein S level to identify subjects at risk for venous thrombosis due to protein S type III deficiency lies far below the lower limit of the laboratory reference range obtained from healthy volunteers.
Display omitted
Gray dashed, dashed dotted and dotted lines display free protein S level for relatives with and without venous thrombosis at cumulative frequency of 25%, 50% and 75%, respectively.
PDF
