Comparison of pregnancy outcomes in Dutch kidney recipients with and without calcineurin inhibitor exposure:a retrospective study

Within pregnancies occurring between 1986 and 2017 in Dutch kidney transplant recipients (KTR), we retrospectively compared short-term maternal and foetal outcomes between patients on calcineurin inhibitor (CNI) based (CNI+) and CNI-free immunosuppression (CNI-). We identified 129 CNI+ and 125 CNI- pregnancies in 177 KTR. Demographics differed with CNI+ having higher body mass index (P = 0.045), shorter transplant-pregnancy interval (P < 0.01), later year of transplantation and -pregnancy (P < 0.01). Serum creatinine levels were numerically higher in CNI+ in all study phases, but only reached statistical significance in third trimester (127 vs. 105 mu m; P < 0.01), where the percentual changes from preconceptional level also differed (+3.1% vs. -2.2% in CNI-; P = 0.05). Postpartum both groups showed 11-12% serum creatinine rise from preconceptional level. Incidence of low birth weight (LBW) tended to be higher in CNI+ (52% vs. 46%; P = 0.07). Both groups showed equal high rates of preterm delivery. Using CNIs during pregnancy lead to a rise in creatinine in the third trimester but does not negatively influence the course of graft function in the first year postpartum or direct foetal outcomes. High rates of preterm delivery and LBW in KTR, irrespective of CNI use, classify all pregnancies as high risk

Autonomic neuropathy predisposes to rosiglitazone-induced vascular leakage in insulin-treated patients with type 2 diabetes: a randomised, controlled trial on thiazolidinedione-induced vascular leakage

Contains fulltext : 88447.pdf (publisher's version ) (Closed access)AIMS/HYPOTHESIS: The mechanism of fluid-related complications caused by thiazolidinedione derivatives is unclear. One potential mechanism is thiazolidinedione-induced arterial vasodilatation, which results in vascular leakage and a fall in blood pressure, normally counterbalanced by sympathetic activation and subsequent renal fluid retention. We hypothesised that thiazolidinedione-induced vascular leakage will be particularly prominent in patients with autonomic neuropathy. METHODS: We conducted a randomised, double-blind, placebo-controlled, parallel study in 40 patients with type 2 diabetes on insulin treatment recruited from a university medical centre. The randomisation was performed by a central office using a randomisation schedule. Both treatment groups, placebo (n = 21) and rosiglitazone (n = 19), were stratified for sex and level of autonomic neuropathy as assessed by Ewing score (or=2.5). We investigated the effects of 16 weeks of treatment with rosiglitazone 4 mg twice daily on vascular leakage (transcapillary escape rate of albumin, TERalb), body weight, extracellular volume and plasma volume. RESULTS: Thirty-nine patients were included in the analysis. In patients with high Ewing scores (n = 16), rosiglitazone increased TERalb significantly (DeltaTERalb: rosiglitazone +2.43 +/- 0.45%/h, placebo -0.11 +/- 0.15%/h, p = 0.002), while rosiglitazone had no effect in the patients with low Ewing scores (n = 23). Rosiglitazone-induced increases in TERalb and Ewing score at baseline were correlated (r = 0.65, p = 0.02). There was no correlation between Ewing score and rosiglitazone-induced changes in fluid variables. One subject was withdrawn from the study because of atrial fibrillation. CONCLUSIONS/INTERPRETATION: Rosiglitazone may increase vascular leakage in insulin-treated patients with type 2 diabetes with autonomic neuropathy. Autonomic neuropathy did not exaggerate rosiglitazone-induced fluid retention. Therefore, autonomic neuropathy should be considered as a risk factor for thiazolidinedione-induced oedema, not for thiazolidinedione-induced fluid retention. TRIAL REGISTRATION: ClinicalTrials.gov NCT00422955. FUNDING: GlaxoSmithKline.1 september 201

A nationwide Dutch cohort study shows relatively good pregnancy outcomes after kidney transplantation and finds risk factors for adverse outcomes

Although numbers of pregnancy after kidney transplantation (KT) are rising, high risks of adverse pregnancy outcomes (APO) remain. Though important for pre-conception counselling and pregnancy monitoring, analyses of pregnancy outcomes after KT per pre-pregnancy estimated glomerular filtration rate-chronic kidney disease (eGFR-CKD)-categories have not been performed on a large scale before. To do this, we conducted a Dutch nationwide cohort study of consecutive singleton pregnancies over 20 weeks of gestation after KT. Outcomes were analyzed per pre-pregnancy eGFR-CKD category and a composite APO (cAPO) was established including birth weight under 2500 gram, preterm birth under 37 weeks, third trimester severe hypertension (systolic blood pressure over 160 and/or diastolic blood pressure over 110 mm Hg) and/or over 15% increase in serum creatinine during pregnancy. Risk factors for cAPO were analyzed in a multilevel model after multiple imputation of missing predictor values. In total, 288 pregnancies in 192 women were included. Total live birth was 93%, mean gestational age 35.6 weeks and mean birth weight 2383 gram. Independent risk factors for cAPO were pre-pregnancy eGFR, midterm percentage serum creatinine dip and midterm mean arterial pressure dip; odds ratio 0.98 (95% confidence interval 0.96-0.99), 0.95 (0.93-0.98) and 0.94 (0.90-0.98), respectively. The cAPO was a risk indicator for graft loss (hazard ratio 2.55, 1.09-5.96) but no significant risk factor on its own when considering pre-pregnancy eGFR (2.18, 0.92-5.13). This was the largest and most comprehensive study of pregnancy outcomes after KT, including pregnancies in women with poor kidney function, to facilitate individualized pre-pregnancy counselling based on pre-pregnancy graft function. Overall obstetric outcomes are good. The risk of adverse outcomes is mainly dependent on pre-pregnancy graft function and hemodynamic adaptation to pregnancy

Quantitative analysis of metal artifact reduction in total hip arthroplasty using virtual monochromatic imaging and orthopedic metal artifact reduction, a phantom study

Objective: To quantify metal artifact reduction using 130 keV virtual monochromatic imaging (VMI) with and without orthopedic metal artifact reduction (O-MAR) in total hip arthroplasty. Methods: Conventional polychromatic images and 130 keV VMI of a phantom with pellets representing bone with unilateral or bilateral prostheses were reconstructed with and without O-MAR on a dual-layer CT. Pellets were categorized as unaffected, mildly affected and severely affected. Results: When 130 keV VMI with O-MAR was compared to conventional imaging with O-MAR, a relative metal artifact reduction in CT values, contrast-to-noise (CNR), signal-to-noise (SNR) and noise in mildly affected pellets (67%, 74%, 48%, 68%, respectively; p < 0.05) was observed but no significant relative metal artifact reduction in severely affected pellets. Comparison between 130 keV VMI without O-MAR and conventional imaging with O-MAR showed relative metal artifact reduction in CT values, CNR, SNR and noise in mildly affected pellets (92%, 72%, 38%, 51%, respectively; p < 0.05) but negative relative metal artifact reduction in CT values and noise in severely affected pellets (− 331% and -223%, respectively; p < 0.05), indicating aggravation of metal artifacts. Conclusion: Overall, VMI of 130 keV with O-MAR provided the strongest metal artifact reduction

Maternal, Decidual, and Neonatal Lymphocyte Composition Is Affected in Pregnant Kidney Transplant Recipients

Pregnancy after renal transplantation is associated with an increased risk of complications. While a delicately balanced uterine immune system is essential for a successful pregnancy, little is known about the uterine immune environment of pregnant kidney transplant recipients. Moreover, children born to kidney transplant recipients are exposed in utero to immunosuppressive drugs, with possible consequences for neonatal outcomes. Here, we defined the effects of kidney transplantation on the immune cell composition during pregnancy with a cohort of kidney transplant recipients as well as healthy controls with uncomplicated pregnancies. Maternal immune cells from peripheral blood were collected during pregnancy as well as from decidua and cord blood obtained after delivery. Multiparameter flow cytometry was used to identify and characterize populations of cells. While systemic immune cell frequencies were altered in kidney transplant patients, immune cell dynamics over the course of pregnancy were largely similar to healthy women. In the decidua of women with a kidney transplant, we observed a decreased frequency of HLA-DR(+) Treg, particularly in those treated with tacrolimus versus those that were treated with azathioprine next to tacrolimus, or with azathioprine alone. In addition, both the innate and adaptive neonatal immune system of children born to kidney transplant recipients was significantly altered compared to neonates born from uncomplicated pregnancies. Overall, our findings indicate a significant and distinct impact on the maternal systemic, uterine, and neonatal immune cell composition in pregnant kidney transplant recipients, which could have important consequences for the incidence of pregnancy complications, treatment decisions, and the offspring’s health

Coronary Artery Calcium Scoring:Toward a New Standard

OBJECTIVES: Although the Agatston score is a commonly used quantification method, rescan reproducibility is suboptimal, and different CT scanners result in different scores. In 2007, McCollough et al (Radiology 2007;243:527-538) proposed a standard for coronary artery calcium quantification. Advancements in CT technology over the last decade, however, allow for improved acquisition and reconstruction methods. This study aims to investigate the feasibility of a reproducible reduced dose alternative of the standardized approach for coronary artery calcium quantification on state-of-the-art CT systems from 4 major vendors. MATERIALS AND METHODS: An anthropomorphic phantom containing 9 calcifications and 2 extension rings were used. Images were acquired with 4 state-of-the-art CT systems using routine protocols and a variety of tube voltages (80-120 kV), tube currents (100% to 25% dose levels), slice thicknesses (3/2.5 and 1/1.25 mm), and reconstruction techniques (filtered back projection and iterative reconstruction). Every protocol was scanned 5 times after repositioning the phantom to assess reproducibility. Calcifications were quantified as Agatston scores. RESULTS: Reducing tube voltage to 100 kV, dose to 75%, and slice thickness to 1 or 1.25 mm combined with higher iterative reconstruction levels resulted in an on average 36% lower intrascanner variability (interquartile range) compared with the standard 120 kV protocol. Interscanner variability per phantom size decreased by 34% on average. With the standard protocol, on average, 6.2 ± 0.4 calcifications were detected, whereas 7.0 ± 0.4 were detected with the proposed protocol. Pairwise comparisons of Agatston scores between scanners within the same phantom size demonstrated 3 significantly different comparisons at the standard protocol (P 0.05). CONCLUSIONS: On state-of-the-art CT systems of 4 different vendors, a 25% reduced dose, thin-slice calcium scoring protocol led to improved intrascanner and interscanner reproducibility and increased detectability of small and low-density calcifications in this phantom. The protocol should be extensively validated before clinical use, but it could potentially improve clinical interscanner/interinstitutional reproducibility and enable more consistent risk assessment and treatment strategies

The anterior longitudinal ligament in diffuse idiopathic skeletal hyperostosis: ossified or displaced?

Diffuse idiopathic skeletal hyperostosis (DISH) is often theorized to be an ossification of the anterior longitudinal ligament (ALL). Using computed tomography (CT) imaging and cryomacrotome sectioning we investigated the spatial relationship between the ALL and newly formed bone in DISH to test this hypothesis. In the current study, four human cadaveric spines diagnosed with DISH using CT imaging were frozen and sectioned using a cryomacrotome. Photographs were obtained of the specimen at 125µm intervals. Manual segmentations of the ALL on cryomacrotome photographs were projected onto the three-dimensional reconstructed CT scans. The presence and location of newly formed bone were assessed in relationship to the location of the ALL. The ALL could be identified and segmented on the photographs at all levels. The ALL was located at the midline at levels where no new bone had formed. At the locations where new bone had abundantly formed, the ALL was displaced towards to the contralateral side and not replaced by bony tissue. The displacement of the - morphologically normal appearing - ALL away from the newly formed bone implies that newly formed bone in DISH may not originate from the ALL. This article is protected by copyright. All rights reserved