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Background: The pancreas is a complex abdominal organ with many anatomical variations, and therefore automated pancreas segmentation from medical images is a challenging application. Purpose: In this paper, we present a framework for segmenting individual pancreatic subregions and the pancreatic duct from three‐dimensional (3D) computed tomography (CT) images. Methods: A multiagent reinforcement learning (RL) network was used to detect landmarks of the head, neck, body, and tail of the pancreas, and landmarks along the pancreatic duct in a selected target CT image. Using the landmark detection results, an atlas of pancreases was nonrigidly registered to the target image, resulting in anatomical probability maps for the pancreatic subregions and duct. The probability maps were augmented with multilabel 3D U‐Net architectures to obtain the final segmentation results. Results: To evaluate the performance of our proposed framework, we computed the Dice similarity coefficient (DSC) between the predicted and ground truth manual segmentations on a database of 82 CT images with manually segmented pancreatic subregions and 37 CT images with manually segmented pancreatic ducts. For the four pancreatic subregions, the mean DSC improved from 0.38, 0.44, and 0.39 with standard 3D U‐Net, Attention U‐Net, and shifted windowing (Swin) U‐Net architectures, to 0.51, 0.47, and 0.49, respectively, when utilizing the proposed RL‐based framework. For the pancreatic duct, the RL‐based framework achieved a mean DSC of 0.70, significantly outperforming the standard approaches and existing methods on different datasets. Conclusions: The resulting accuracy of the proposed RL‐based segmentation framework demonstrates an improvement against segmentation with standard U‐Net architectures. [ABSTRACT FROM AUTHOR]

In this work, the Schwarz primitive unit cell is used as the building block of different types of metastructures for steering and focusing elastic vibrations. The emergence of a Bragg-type bandgap when constructing a two-dimensional plate from such unit cells is experimentally validated. It is demonstrated that increasing both mass and porosity of the Schwarz primitive leads to a decrease in the frequency of the out-of-plane propagating wave targeted in this study. By arranging these modified Schwarz primitive unit cells in constant and graded layouts, two-dimensional plates with an embedded metabarrier and a metalens are numerically designed. The metabarrier protects an interior area of the plate from the propagating waves on a wide frequency band (approx. 1.4–3.4 kHz). Equally, the refractive index profile necessary for gradient index lenses is obtained via a progressive variation of the added mass or, alternatively, the porosity of the unit cell over a rectangular area. For the first time, bending of the out-of-plane mode towards the focusing point is practically validated in a challenging mesoscale experiment requiring the assembly of different three-dimensional printed sections of the plate. The increased porosity design is advantageous not only in terms of overall lightweight, but also towards additive manufacturing as it requires less material. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 1)'. [ABSTRACT FROM AUTHOR]

We investigate the familywise error rate (FWER) for time‐to‐event endpoints evaluated using a group sequential design with a hierarchical testing procedure for secondary endpoints. We show that, in this setup, the correlation between the log‐rank test statistics at interim and at end of study is not congruent with the canonical correlation derived for normal‐distributed endpoints. We show, both theoretically and by simulation, that the correlation also depends on the level of censoring, the hazard rates of the endpoints, and the hazard ratio. To optimize operating characteristics in this complex scenario, we propose a simulation‐based method to assess the FWER which, better than the alpha‐spending approach, can inform the choice of critical values for testing secondary endpoints. [ABSTRACT FROM AUTHOR]

Background. Beta‐hydroxybuturate (β‐OHB) supplements are commonly utilized in sports by both recreational and professional athletes. In a recent study, we observed a drop in testosterone levels following the oral ingestion of racemic sodium‐β‐OHB. In this investigation, we aim to determine whether a single oral dose of ketone ester (study I) and prolonged endogenous ketosis (study II) also reduces testosterone levels. Design. This investigation integrated samples from two distinct studies. Study I was a randomized, controlled, crossover trial with ten healthy, young male participants receiving either a weight‐adjusted ketone ester or control (water, CTR) and vice versa following an overnight fast. Repeated blood sampling was used to monitor plasma β‐OHB and testosterone levels. Study II, another randomized, controlled, crossover trial, included 11 middle‐aged participants (five males). They followed either a ketogenic diet (KD) characterized by low carbohydrates and high fat content or a standard diet (SDD) for three weeks. After each study period, participants underwent examination following an overnight fast, with repeated measures employed to analyze concentrations of plasma β‐OHB and sex hormone levels. Results. Study I: Testosterone decreased from 23.8 ± 2.4 nmol/l to 22.3 ± 2.5 nmol/l 300 minutes after the ketone ester and increased from 20.9 ± 2.1 nmol/l to 22.2 ± 1.9 300 minutes after CTR. This difference was not significant, p = 0.06. Study II. Total testosterone was unaffected after the KD compared to the SDD in men (20.2 ± 1.23 nmol/l vs. 18.2 ± 1.23 nmol/l (p = 0.1)) and was lower after KD in women (0.87 ± 0.06 vs. 1.1 ± 0.06 nmol/l (p < 0.0001)). Sex hormone‐binding globulin (SHBG) increased in men after KD compared with SDD (31.2 ± 2.6 nmol/l vs 25.0 ± 2.6 nmol/l, p < 0.0001) and women (26.5 ± 3.05 nmol/l vs 24.2 ± 3.05 nmol/l, p = 0.003). The free androgen index decreased after KD in men (ratio: 0.65 ± 0.05 vs. ratio: 0.74 ± 0.05, p = 0.04) and in women (ratio: 0.036 ± 0.006 vs. SDD 0.05 ± 0.006, p = 0.0001). Free estradiol index was also found lower after KD in men (ratio: 3.1 ± 0.8 vs. ratio: 4.8 ± 0.8, p = 0.0003) and in women (ratio: 1.2 ± 2.2 vs. 9.8 ± 2.2, p = 0.0001). Conclusion. Our findings indicate that the acute ingestion of ketone ester may not reduce testosterone levels in healthy young males. However, a three‐week exposure to KB from a KD results in an increase in SHBG in men and women with obesity as well as it lowers free testosterone and estradiol for men and women. We thus present evidence of crosstalk between alterations in a metabolite, β‐OHB, and the regulation of the hypothalamic‐pituitary‐gonadal axis from a KD. The clinical impact of this reduction remains to be investigated. This trial is registered with NCT04156477​ and NCT05012748. [ABSTRACT FROM AUTHOR]

Context Women with gestational diabetes mellitus (GDM) have an increased risk of long-term complications, including impaired glucose metabolism, type 2 diabetes (T2DM), cardiovascular disease, and obesity. In current clinical practice, a 1 size fits all approach to GDM is applied, although heterogeneity among women with GDM has been recognized. Objective To give the most adequate preventive care and postpartum (PP) guidance, we aimed to make a metabolic characterization and identify subgroups of women with previous GDM within the first year PP. Methods In this prospective cohort study, we collected data in gestational week 34-38, at 3 months, and 1 year PP on women with GDM who participated in a PP follow-up program in Central Region Denmark from April 2019 to December 2022. Results In total, 1270 women were included in the program in late pregnancy. Of the 768 women participating in either the oral glucose tolerance test 3 months PP (n = 545) or the 1-year follow-up (n = 493) or both (n = 261), 608 (79.2%) were normoglycemic, 137 (17.8%) had prediabetes, 20 (2.6%) had T2DM, and 3 (.4%) had developed T1DM. More than 40% of the women gained weight in the first year PP compared with their pregestational weight. Conclusion Our study shows that 20.8% of women with GDM who volunteered to participate in a clinical follow-up program developed prediabetes or diabetes (T1DM and T2DM) within the first year PP. The GDM diagnosis encompasses a heterogenetic group of women and a deeper characterization may provide an opportunity for a more personalized risk assessment to prevent the progression to T2DM. [ABSTRACT FROM AUTHOR]

Mitigating the energy requirements of artificial intelligence requires novel physical substrates for computation. Phononic metamaterials have vanishingly low power dissipation and hence are a prime candidate for green, always-on computers. However, their use in machine learning applications has not been explored due to the complexity of their design process. Current phononic metamaterials are restricted to simple geometries (e.g., periodic and tapered) and hence do not possess sufficient expressivity to encode machine learning tasks. A non-periodic phononic metamaterial, directly from data samples, that can distinguish between pairs of spoken words in the presence of a simple readout nonlinearity is designed and fabricated, hence demonstrating that phononic metamaterials are a viable avenue towards zero-power smart devices. [ABSTRACT FROM AUTHOR]

Purpose: Prostate MRI is established for the investigation of patients presenting with suspected early prostate cancer. Outcomes are dependent on both image quality and interpretation. This study assessed the impact of an educational intervention on participants’ theoretical knowledge of the technique. Methods: Eighty-one clinicians from two centers with varying experience in prostate MRI participated. Baseline knowledge was assessed with 10 written and image-based multiple-choice questions (MCQs) prior to a course including didactic lectures and hands-on interactive workshops on prostate MRI interpretation. Post-course, participants completed a second 10-question MCQ test, matched by format, themes, and difficulty, to assess for any improvement in knowledge and performance. Results were assessed using the Wilcoxon rank sum test, and the Wilcoxon signed-rank test for paired data. Results: Thirty-nine participants, including 25/49 (51.0%) and 14/32 (43.8%) at each center completed both assessments, with their results used for subsequent evaluation. Overall, there was a significant improvement from pre- (4.92 ± 2.41) to post-course scores (6.77 ± 1.46), p < 0.001 and at both Copenhagen (5.92 ± 2.25 to 7.36 ± 1.25) and Toronto (3.14 ± 1.51 to 5.71 ± 1.20); p = 0.005 and p = 0.002, respectively. Participants with no prostate MRI experience showed the greatest improvement (3.77 ± 1.97 to 6.18 ± 1.5, p < 0.001), followed by intermediate level (< 500 MRIs reported) experience (6.18 ± 1.99 to 7.46 ± 1.13, p = 0.058), then advanced (> 500 MRIs reported) experience (6.83 ± 2.48 to 7.67 ± 0.82, p = 0.339). Conclusions: A dedicated prostate MRI teaching course combining didactic lectures and hands-on workshops significantly improved short-term theoretical knowledge of the technique for clinicians with differing levels of experience. Critical relevance statement: A dedicated teaching course significantly improved theoretical knowledge of the technique particularly for clinicians with less reporting experience and a lower baseline knowledge. The multiple-choice questions format mapped improved performance and may be considered as part of future MRI certification initiatives. Key points: • Prostate MRI knowledge is important for image interpretation and optimizing acquisition sequences. • A dedicated teaching course significantly improved theoretical knowledge of the technique. • Improved performance was more apparent in clinicians with less reporting experience and a lower baseline knowledge. [ABSTRACT FROM AUTHOR]

Context Hyperglucagonemia may develop in type 2 diabetes due to obesity-prone hepatic steatosis (glucagon resistance). Markers of glucagon resistance (including the glucagon-alanine index) improve following diet-induced weight loss, but the partial contribution of lowering hepatic steatosis vs body weight is unknown. Objective This work aimed to investigate the dependency of body weight loss following a reduction in hepatic steatosis on markers of glucagon resistance in type 2 diabetes. Methods A post hoc analysis was conducted from 2 previously published randomized controlled trials. We investigated the effect of weight maintenance (study 1: isocaloric feeding) or weight loss (study 2: hypocaloric feeding), both of which induced reductions in hepatic steatosis, on markers of glucagon sensitivity, including the glucagon-alanine index measured using a validated enzyme-linked immunosorbent assay and metabolomics in 94 individuals (n = 28 in study 1; n = 66 in study 2). Individuals with overweight or obesity with type 2 diabetes were randomly assigned to a 6-week conventional diabetes (CD) or carbohydrate-reduced high-protein (CRHP) diet within both isocaloric and hypocaloric feeding-interventions. Results By design, weight loss was greater after hypocaloric compared to isocaloric feeding, but both diets caused similar reductions in hepatic steatosis, allowing us to investigate the effect of reducing hepatic steatosis with or without a clinically relevant weight loss on markers of glucagon resistance. The glucagon-alanine index improved following hypocaloric, but not isocaloric, feeding, independently of macronutrient composition. Conclusion Improvements in glucagon resistance may depend on body weight loss in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Here, we present a compilation of 95 ice temperature profiles from 85 boreholes from the Greenland ice sheet and peripheral ice caps, as well as local ice caps in the Canadian Arctic. Profiles from only 31 boreholes (36 %) were previously available in open-access data repositories. The remaining 54 borehole profiles (64 %) are being made digitally available here for the first time. These newly available profiles, which are associated with pre-2010 boreholes, have been submitted by community members or digitized from published graphics and/or data tables. All 95 profiles are now made available in both absolute (meters) and normalized (0 to 1 ice thickness) depth scales and are accompanied by extensive metadata. These metadata include a transparent description of data provenance. The ice temperature profiles span 70 years, with the earliest profile being from 1950 at Camp VI, West Greenland. To highlight the value of this database in evaluating ice flow simulations, we compare the ice temperature profiles from the Greenland ice sheet with an ice flow simulation by the Parallel Ice Sheet Model (PISM). We find a cold bias in modeled near-surface ice temperatures within the ablation area, a warm bias in modeled basal ice temperatures at inland cold-bedded sites, and an apparent underestimation of deformational heating in high-strain settings. These biases provide process level insight on simulated ice temperatures. [ABSTRACT FROM AUTHOR]

Nuclear Magnetic Resonance (NMR) spectra of human serum and plasma show, besides metabolites and lipoproteins, two characteristic signals termed GlycA and B arising from the acetyl groups of glycoprotein glycans from acute phase proteins, which constitute good markers for inflammatory processes. Here, we report a comprehensive assignment of glycoprotein glycan NMR signals observed in human serum, showing that GlycA and GlycB signals originate from Neu5Ac and GlcNAc moieties from N‐glycans, respectively. Diffusion‐edited NMR experiments demonstrate that signal components can be associated with specific acute phase proteins. Conventionally determined concentrations of acute phase glycoproteins correlate well with distinct features in NMR spectra (R2 up to 0.9422, p‐value <0.001), allowing the simultaneous quantification of several acute phase inflammation proteins. Overall, a proteo‐metabolomics NMR signature of significant diagnostic potential is obtained within 10–20 min acquisition time. This is exemplified in serum samples from COVID‐19 and cardiogenic shock patients showing significant changes in several acute phase proteins compared to healthy controls. [ABSTRACT FROM AUTHOR]

Nuclear Magnetic Resonance (NMR) spectra of human serum and plasma show, besides metabolites and lipoproteins, two characteristic signals termed GlycA and B arising from the acetyl groups of glycoprotein glycans from acute phase proteins, which constitute good markers for inflammatory processes. Here, we report a comprehensive assignment of glycoprotein glycan NMR signals observed in human serum, showing that GlycA and GlycB signals originate from Neu5Ac and GlcNAc moieties from N‐glycans, respectively. Diffusion‐edited NMR experiments demonstrate that signal components can be associated with specific acute phase proteins. Conventionally determined concentrations of acute phase glycoproteins correlate well with distinct features in NMR spectra (R2 up to 0.9422, p‐value <0.001), allowing the simultaneous quantification of several acute phase inflammation proteins. Overall, a proteo‐metabolomics NMR signature of significant diagnostic potential is obtained within 10–20 min acquisition time. This is exemplified in serum samples from COVID‐19 and cardiogenic shock patients showing significant changes in several acute phase proteins compared to healthy controls. [ABSTRACT FROM AUTHOR]

Background & Aims: Genome‐wide association studies have identified steatogenic variants that also showed pleiotropic effects on cardiometabolic traits in adults. We investigated the effect of eight previously reported genome‐wide significant steatogenic variants, individually and combined in a weighted genetic risk score (GRS), on liver and cardiometabolic traits, and the predictive ability of the GRS for hepatic steatosis in children and adolescents. Approach & Results: Children and adolescents with overweight (including obesity) from an obesity clinic group (n = 1768) and a population‐based group (n = 1890) were included. Cardiometabolic risk outcomes and genotypes were obtained. Liver fat was quantified using 1H‐MRS in a subset of 727 participants. Variants in PNPLA3, TM6SF2, GPAM and TRIB1 were associated with higher liver fat (p <.05) and with distinct patterns of plasma lipids. The GRS was associated with higher liver fat content, plasma concentrations of alanine transaminase (ALT), aspartate aminotransferase (AST) and favourable plasma lipid levels. The GRS was associated with higher prevalence of hepatic steatosis (defined as liver fat ≥5.0%) (odds ratio per 1‐SD unit: 2.17, p = 9.7E‐10). A prediction model for hepatic steatosis including GRS alone yielded an area under the curve (AUC) of 0.78 (95% CI 0.76–0.81). Combining the GRS with clinical measures (waist‐to‐height ratio [WHtR] SDS, ALT, and HOMA‐IR) increased the AUC up to 0.86 (95% CI 0.84–0.88). Conclusions: The genetic predisposition for liver fat accumulation conferred risk of hepatic steatosis in children and adolescents. The liver fat GRS has potential clinical utility for risk stratification. [ABSTRACT FROM AUTHOR]

Purpose: To compare two strategies: Prostate-specific antigen density (PSAd) and lesion volume measurement in ruling out significant prostate cancer (sPCa) in men with equivocal Prostate Imaging Reporting and Data System (PI-RADS) category 3 index lesions on biparametric magnetic resonance imaging. Methods: In total, 130 men from our database had index lesions with PI-RADS scores of 3. Prostate volume was measured using the ellipsoid method, in accordance with PI-RADS version 2.1 criteria. Index lesion volumes were also measured using the ellipsoidal formula on the diffusion-weighted imaging sequence with the highest b-value and sagittal T2 sequences. Results: Among 130 men with PI-RADS category 3 index lesions, 23 (18%) had sPCa. In total, 6 of the 89 men with PSAd < 0.15 ng/mL2 (7%) had sPCa, whereas 8 of the 49 men with index lesion volumes < 0.5 mL (16%) had sPCa. The difference was statistically significant (McNemar, p < 0.0001). Conclusion: The PSAd strategy performed better than the lesion volume strategy in ruling out sPCa in men with equivocal PI-RADS category 3 index lesions. [ABSTRACT FROM AUTHOR]

The editorial in Acta Radiologica announces the retirement of Professor Henrik S Thomsen after 7 years as Editor-in-Chief. The journal, one of the oldest in the world, was created in Sweden in 1917 and is supported by a Swedish foundation and five Nordic radiological societies. Despite challenges such as an increase in manuscripts for review, Acta Radiologica has maintained high quality and reduced the time from acceptance to print to 1-2 months. The journal will transition to being 100% electronic in 2025, a decision supported by the Nordic radiological societies. [Extracted from the article]

We experimentally demonstrate the capability of architected plates, with a frame-like cellular structure, to inhibit the propagation of elastic flexural waves. By leveraging the octet topology as a unit cell to design the tested prototypes, a broad and easy-to-tune bandgap is experimentally generated. The experimental outcomes are supported by extensive numerical analyses based on 3D solid elements. Drawing from the underlying dynamic properties of the octet cell, we numerically propose a tailorable design with enhanced filtering capabilities. We transform the geometry of the original unit cell by applying a uniaxial scaling factor that, by breaking the in-plane symmetry of the structure, yields independently tuned struts and consequently multiple tunable bandgaps within the same cell. Our findings expand the spectrum of available numerical analyses on the octet lattice, taking it a significant step closer to its physical implementation. The ability of the octet lattice to control the propagation of flexural vibrations is significant within various applications in the mechanical and civil engineering domains, and we note such frame-like designs could lead to advancements in energy harvesting and vibration protection devices (e.g., lightweight and resonance-tunable absorbers). [ABSTRACT FROM AUTHOR]

Summary: Background: Diagnosis of nonalcoholic fatty liver disease in children and adolescents currently requires advanced or invasive technologies. Objectives: We aimed to develop a method to improve diagnosis, using body composition indices and liver biochemical markers. Methods: To diagnose non‐alcoholic fatty liver disease, 767 Danish children and adolescents underwent clinical examination, blood sampling, whole‐body dual‐energy X‐ray absorptiometry scanning and proton magnetic resonance spectroscopy for liver fat quantification. Fourteen variables were selected as a starting point to construct models, narrowed by stepwise selection. Individuals were split into a training set for model construction and a validation test set. The final models were applied to 2120 Danish children and adolescents to estimate the prevalence. Results: The final models included five variables in different combinations: body mass index–standard deviation score, android‐to‐gynoid‐fat ratio, android‐regional fat percent, trunk‐regional fat percent and alanine transaminase. When validated, the sensitivity and specificity ranged from 38.6% to 51.7% and 87.6% to 91.9%, respectively. The estimated prevalence was 24.2%–35.3%. Models including alanine transaminase alongside body composition measurements displayed higher sensitivity. Conclusions: Body composition indices and alanine transaminase can be used to estimate non‐alcoholic fatty liver disease, with 38.6%–51.7% sensitivity and 87.6%–91.9%, specificity, in children and adolescents with overweight (including obesity). These estimated a 24.2%–35.3% prevalence in 2120 patients. [ABSTRACT FROM AUTHOR]

Here, we present a compilation of 85 ice temperature profiles from 79 boreholes from the Greenland Ice Sheet and peripheral ice caps, as well as local ice caps in the Canadian Arctic. Only 25 profiles (32 %) were previously available in open-access data repositories. The remaining 54 profiles (68 %) are being made digitally available here for the first time. These newly available profiles, which are associated with pre-2010 boreholes, have been submitted by community members or digitized from published graphics and/or data tables. All 85 profiles are now made available in both absolute (meters) and normalized (0 to 1 ice thickness) depth scales, and are accompanied by extensive metadata. This metadata includes a transparent description of data provenance. The ice temperature profiles span 70 years, with the earliest profile being from 1950 at Camp VI, West Greenland. To highlight the value of this database in evaluating ice flow simulations, we compare the ice temperature profiles from the Greenland Ice Sheet with an ice flow simulation by the Parallel Ice Sheet Model (PISM). We find a cold bias in modeled near-surface ice temperatures within the ablation area, a warm bias in modeled basal ice temperatures at inland cold-bedded sites, and an apparent underestimation of deformational heating in high-strain settings. These biases provide process-level insight on simulated ice temperatures. [ABSTRACT FROM AUTHOR]

Systemic administration of beta‐hydroxybutyrate (BHB) decreases whole‐body protein oxidation and muscle protein breakdown in humans. We aimed to determine any direct effect of BHB on skeletal muscle protein turnover when administered locally in the femoral artery. Paired design with each subject being investigated on one single occasion with one leg being infused with BHB and the opposing leg acting as a control. We studied 10 healthy male volunteers once with bilateral femoral vein and artery catheters. One artery was perfused with saline (Placebo) and one with sodium‐BHB. Labelled phenylalanine and palmitate were used to assess local leg fluxes. Femoral vein concentrations of BHB were significantly higher in the intervention leg (3.4 (3.2, 3.6) mM) compared with the placebo‐controlled leg (1.9 (1.8, 2.1) mM) with a peak difference of 1.4 (1.1, 1.7) mM, p < 0.0005. Net loss of phenylalanine for BHB vs Placebo −6.7(−10.8, −2.7) nmol/min vs −8.7(−13.8, −3.7) nmol/min, p = 0.52. Palmitate flux and arterio‐venous difference of glucose did not differ between legs. Under these experimental conditions, we failed to observe the direct effects of BHB on skeletal muscle protein turnover. This may relate to a combination of high concentrations of BHB (close to 2 mM) imposed systemically by spillover leading to high BHB concentrations in the saline‐infused leg and a lack of major differences in concentration gradients between the two sides—implying that observations were made on the upper part of the dose–response curve for BHB and the relatively small number of subjects studied. [ABSTRACT FROM AUTHOR]

Need for a review: Guidelines for management and prevention of contrast media extravasation have not been updated recently. In view of emerging research and changing working practices, this review aims to inform update on the current guidelines. Areas covered: In this paper, we review the literature pertaining to the pathophysiology, diagnosis, risk factors and treatments of contrast media extravasation. A suggested protocol and guidelines are recommended based upon the available literature. Key Points: • Risk of extravasation is dependent on scanning technique and patient risk factors. • Diagnosis is mostly clinical, and outcomes are mostly favourable. • Referral to surgery should be based on clinical severity rather than extravasated volume. [ABSTRACT FROM AUTHOR]

Measurement of β-hydroxybutyrate (BHB) in blood is used clinically as a measure of ketosis when diabetic ketoacidosis is expected. With the introduction of point-of-care testing (POCT) for blood-BHB, nonproductive time is reduced to a minimum in a potential critical situation; however, studies have observed inferior quality of POCT-BHB. Recently, the POCT device KetoSure (Roche) has been introduced to the clinic. In this study, we evaluated the imprecision and linearity of KetoSure and compared this to the established StatStrip Express (Nova Biomedical) based on spiked full blood samples. We found comparable imprecision for KetoSure and StatStrip Express. However, linearity was only observed in the lower part of the measuring range for both devices. In a method comparison, higher values of BHB were measured by KetoSure than by an enzymatic endpoint spectrophotometric reference method (mean bias: 21% (95% confidence interval (CI): 4%–37%)). Conversely, StatStrip Express returned lower values of BHB (mean bias: −16% (95% CI: −38%–7%), while the widely applied POCT device FreeStyle Precision Neo (Abbott) returned values equivalent with the reference method (mean bias: 5% (95% CI: −14%–24%). In samples with concentrations of BHB above the measuring range, the POCT devices could be provoked to return falsely low results. In conclusion, the quality of KetoSure is in line with other established POCT devices; however, the KetoSure measures higher concentrations than other POCT devices. As, linearity only was observed in the lower part of the measuring range and as falsely low measures could be provoked, we advise users to interpret results with precaution. [ABSTRACT FROM AUTHOR]

Background: Only limited data have been published on the diagnostic accuracy of combining biparametric (bp) magnetic resonance imaging (MRI) and prostate-specific antigen density (PSAd) to rule out biopsies. Purpose: The purpose is to assess the 2-year risk of being diagnosed with sPCa following the strategy of avoiding immediate biopsies in men with non-suspicious bp MRIs and a PSAd <0.15 ng/mL2. Material and Methods: Two hundred biopsy-naïve men with clinical suspicion of PCa underwent a pre-biopsy bp MRI from March to July 2019. Of these, 109 men had a Prostate Imaging Reporting and Data System (PI-RADS) score of 1–3 including 77 men with calculated PSAd <0.15 ng/mL2. As a result, no biopsies were performed in these 77 men, who were clinically followed up for at least 2 years and re-examined in case of rising suspicion of sPCa. The remaining 32 men with a calculated PSAd ≥0.15 ng/mL2 underwent systematic biopsies and targeted biopsies of any PI-RADS 3 lesion. Results: One of the 77 men (1.3%) had an sPCa diagnosed within 2 years of follow-up. All men were referred back to their general practitioner within 1 year and 9% (7/77) were re-referred to the urology department during follow-up. Among these men, 43% (3/7) continued to have PSA levels that were above their individual thresholds at confirmatory testing and underwent secondary MRI scans. Conclusions: No biopsies for men with bpMRI results exhibiting maximum PI-RADS 3 and with a PSAd <0.15 ng/mL2 resulted in a 2-year risk of being diagnosed with sPCa of 1.3%. [ABSTRACT FROM AUTHOR]

Background Prepregnancy overweight and excessive gestational weight gain (GWG) increase the risk of complications and offspring obesity. Objectives We aimed to investigate the effect of a high-protein low–glycemic index (HPLGI) diet on GWG, birth weight, and risk of gestational complications in pregnant women with obesity. Methods A total of 279 women with prepregnancy overweight or obesity (BMI: 28–45 kg/m2), between 18 and 45 y old, and in their late first trimester with singleton pregnancies, were randomly assigned to 1 of 2 ad libitum diets: a high-protein low–glycemic index diet (HPLGI: 25%–28% of energy from protein and glycemic index ≤ 55) and a moderate-protein moderate–glycemic index diet (MPMGI: 15%–18% of energy from protein and glycemic index ∼60). Diets were consumed from gestational week 15 and throughout pregnancy. Participants received dietary guidance by a clinical dietician 9 times to facilitate adherence. Results Out of 141 and 138 women randomly assigned to the HPLGI and MPMGI diets, 105 and 104 completed the intervention, respectively (75%). In the available case analyses, GWG was 6.8 ± 1.3 kg among women assigned the HPLGI diet and this was significantly lower, by −1.7 kg (95% CI: −2.8, −0.5 kg; P = 0.004), than the GWG of 8.5 ± 1.3 kg among women assigned the MPMGI diet. There were no significant differences between diets on major neonatal outcomes (birth weight and other anthropometric measures). The incidence of composite pregnancy complications was lower for the HPLGI than for the MPMGI diet (35.4% compared with 53.7%, respectively; P = 0.009), including cesarean delivery (15.4% compared with 28.8%, respectively; P = 0.03). There were no reported maternal, fetal, or neonatal deaths. Incidence of miscarriages (1%–2%) did not differ between groups. Conclusions A moderate increase in dietary protein in conjunction with a reduction in glycemic index during the last 2 trimesters of pregnancy reduced GWG and limited complications and cesarean deliveries among women with overweight or obesity. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Lifestyle modification and weight loss are cornerstones of type 2 diabetes management. However, carbohydrate restriction may have weight-independent beneficial effects on glycaemic control. This has been difficult to demonstrate because low-carbohydrate diets readily decrease body weight. We hypothesised that carbohydrate restriction enhances the beneficial metabolic effects of weight loss in type 2 diabetes. Methods: This open-label, parallel RCT included adults with type 2 diabetes, HbA1c 48–97 mmol/mol (6.5–11%), BMI >25 kg/m2, eGFR >30 ml min−1 [1.73 m]−2 and glucose-lowering therapy restricted to metformin or dipeptidyl peptidase-4 inhibitors. Participants were randomised by a third party and assigned to 6 weeks of energy restriction (all foods were provided) aiming at ~6% weight loss with either a carbohydrate-reduced high-protein diet (CRHP, percentage of total energy intake [E%]: CH30/P30/F40) or a conventional diabetes diet (CD, E%: CH50/P17/F33). Fasting blood samples, continuous glucose monitoring and magnetic resonance spectroscopy were used to assess glycaemic control, lipid metabolism and intrahepatic fat. Change in HbA1c was the primary outcome; changes in circulating and intrahepatic triacylglycerol were secondary outcomes. Data were collected at Copenhagen University Hospital (Bispebjerg and Herlev). Results: Seventy-two adults (CD 36, CRHP 36, all white, 38 male sex) with type 2 diabetes (mean duration 8 years, mean HbA1c 57 mmol/mol [7.4%]) and mean BMI of 33 kg/m2 were enrolled, of which 67 (CD 33, CRHP 34) completed the study. Body weight decreased by 5.8 kg (5.9%) in both groups after 6 weeks. Compared with the CD diet, the CRHP diet further reduced HbA1c (mean [95% CI] −1.9 [−3.5, −0.3] mmol/mol [−0.18 (−0.32, −0.03)%], p = 0.018) and diurnal mean glucose (mean [95% CI] −0.8 [−1.2, −0.4] mmol/l, p < 0.001), stabilised glucose excursions by reducing glucose CV (mean [95% CI] −4.1 [−5.9, −2.2]%, p < 0.001), and augmented the reductions in fasting triacylglycerol concentration (by mean [95% CI] −18 [−29, −6]%, p < 0.01) and liver fat content (by mean [95% CI] −26 [−45, 0]%, p = 0.051). However, pancreatic fat content was decreased to a lesser extent by the CRHP than the CD diet (mean [95% CI] 33 [7, 65]%, p = 0.010). Fasting glucose, insulin, HOMA2-IR and cholesterol concentrations (total, LDL and HDL) were reduced significantly and similarly by both diets. Conclusions/interpretation: Moderate carbohydrate restriction for 6 weeks modestly improved glycaemic control, and decreased circulating and intrahepatic triacylglycerol levels beyond the effects of weight loss itself compared with a CD diet in individuals with type 2 diabetes. Concurrent differences in protein and fat intakes, and the quality of dietary macronutrients, may have contributed to these results and should be explored in future studies. Trial registration: ClinicalTrials.gov NCT03814694. Funding: The study was funded by Arla Foods amba, The Danish Dairy Research Foundation, and Copenhagen University Hospital Bispebjerg Frederiksberg. [ABSTRACT FROM AUTHOR]

Time reversal (TR) is a method of focusing wave energy at a point in space. The optimization of a TR demonstration is described, which knocks over one selected LEGO minifigure among other minifigures by focusing the vibrations within an aluminum plate at the target minifigure. The aim is to achieve a high repeatability of the demonstration along with reduced costs to create a museum exhibit. By comparing the minifigure's motion to the plate's motion directly beneath its feet, it is determined that a major factor inhibiting the repeatability is that the smaller vibrations before the focal event cause the minifigure to bounce repeatedly and it ends up being in the air during the main vibrational focal event, which was intended to launch the minifigure. The deconvolution TR technique is determined to be optimal in providing the demonstration repeatability. The amplitude, frequency, and plate thickness are optimized in a laboratory setting. An eddy current sensor is then used to reduce the costs, and the impact on the repeatability is determined. A description is given of the implementation of the demonstration for a museum exhibit. This demonstration illustrates the power of the focusing acoustic waves, and the principles learned by optimizing this demonstration can be applied to other real-world applications. [ABSTRACT FROM AUTHOR]

An important step in the processing of seismic data that are recorded at the free surface is the isolation of the primary incident wavefield from the total recorded wavefield (which is contaminated with the immediate reflections off the free surface). We present a 3-D wavefield reconstruction technique, based on numerical wavefield injection along a closed boundary, that allows us to isolate this primary wavefield from measurements at the free surface. The technique consists of injecting only the three-component particle velocity recordings acquired at the free surface into a numerical wavefield simulation, and additionally requires information about the medium properties. The result of our proposed procedure is the separation of elastic waves into their first-order incident and reflected constituents, even when the recording or injection surface has sharp corners. With the use of synthetic data it is shown that the method achieves close to numerically exact wavefield separation, provided that the true elastic model in the interior is used. In practice, the parameters for a homogeneous elastic model can be determined efficiently from the surface data itself using an optimization scheme. Finally, the wavefield separation technique is successfully applied to experimental data, with particle velocity recordings acquired along five faces of a cubic granite rock volume. In addition to characterizing materials in laboratories, the presented technique has applications in numerical modelling and in so-called immersive experimentation, where the incident field is required to immerse an elastic object in an arbitrary larger, virtual elastic environment. [ABSTRACT FROM AUTHOR]

Purpose: We previously reported beneficial glucoregulatory effects of a fully provided carbohydrate-reduced, high-protein (CRHP) diet in patients with type 2 diabetes mellitus (T2DM) in a crossover 2 × 6-week trial, in which patients maintained their body weight. Here, we investigated physiological changes during an additional 6-month period on a self-selected and self-prepared CRHP diet. Methods: Twenty-eight patients with T2DM were instructed to consume a CRHP diet (30% of energy from carbohydrate and 30% from protein) for 24 weeks, after an initial 2 × 6-week trial when all food was prepared and provided to them. Patients received dietary advice every 2 weeks. At weeks 0, 6, 12 and 36, they underwent a 3-h intravenous glucose tolerance test, a 4-h mixed meal test, and a 48-h continuous glucose monitoring. Liver, muscle, pancreas, and visceral fat contents were measured by magnetic resonance imaging. Results: During the 24-week self-selected diet period (weeks 12–36), body weight, visceral fat, liver fat, and glycated haemoglobin were maintained at the same levels achieved at the end of the fully provided diet period, and were still lower than at baseline (P < 0.05). Postprandial insulinaemia and insulin secretion were significantly greater (P < 0.05). At week 36, fasting insulin and C-peptide levels increased (P < 0.01) and daily glycaemia decreased further (P < 0.05) when compared with the end of the fully provided diet period. Conclusion: Substituting dietary carbohydrate for protein and fat has metabolic benefits in patients with T2DM. These beneficial effects are maintained or augmented over the next 6 months when patients self-select and self-prepare this diet in a dietitian-supported setting. Trial registration: ClinicalTrials.gov NCT02764021. [ABSTRACT FROM AUTHOR]

Acta Radiologica celebrates its 100th anniversary in 2021. In this article, the foundation of the journal and its editors are described. During 100 years, the manuscript structure changed from single-author verbose monographs to multi-author collaborations on statistically analyzed research subjects. The authorship changed from purely Nordic authors to a truly international cadre of authors, and the size of the journal increased considerably, in issues per year, printed pages, and published articles per year. The Foundation of Acta Radiologica has been able to give out two prizes, the Xenia Forsselliana and the Acta Radiologica International Scientific Prize for the best manuscripts each year. The increasing submissions of manuscripts is an indication that Acta Radiologica will continue to publish important scientific results for many years to come. [ABSTRACT FROM AUTHOR]

This review focuses on the trends in contrast media (CM) research published in Acta Radiologica during the last 100 years, since the first edition in 1921. The main topics covered are the developments of iodine- and gadolinium-based CM. Other topics include manganese-based CM for magnetic resonance imaging (MRI) and barium for the investigation of the alimentary tract. From a historic point of view, special CM for use in cholegraphy and myelography are addressed in the review. Today, these imaging procedures are obsolete due to the development of computed tomography, MRI, and ultrasound. The historical use of radioactive thorium-based CM for angiography is also addressed. Furthermore, publications on adverse reactions to CM are reviewed. [ABSTRACT FROM AUTHOR]

Background: The apparent diffusion coefficient (ADC), as determined by whole-body diffusion-weighted MRI, may be useful as an outcome measure for monitoring response to treatment in chronic non-bacterial osteitis. Purpose: To test and demonstrate the feasibility of ADC-measurement methods for use as outcome measure in chronic non-bacterial osteitis. Materials and Methods: Using data from a randomized pilot study, feasibility of change-score ADC between baseline and second MRI (ΔADC12) and third MRI (ΔADC13) as outcome measure was assessed in three settings: "whole-lesion," "single-slice per lesion," and "index-lesion per patient". Bone marrow edema lesions were depicted on short tau inversion recovery sequence at baseline and copied to ADC maps at the three time-points. Correlations between the three settings were measured as were analysis of variances. Discriminant validity was assessed as inter- and intra-observer reproducibility and smallest detectable change. Results: 12 subjects were enrolled, and MRI was performed at baseline and weeks 12 and 36. Pearson correlation was high (r > 0.86; p ≤ 0.01) for ΔADC between single-slice—whole-lesion and whole-lesion—index-lesion and tended to be significant for single-slice—index-lesion settings (p = 0.06). For ΔADC12 and ΔADC13, Bland–Altman plots showed small differences (0.02, 0.03) and narrow 95% limits-of-agreement (−0.13–0.09, −0.07–0.05 μm2/s) between whole-lesion and single-slice ROI settings. Inter-observer reproducibility measured by intra-class correlation coefficient was poor-to-fair (range: 0.09–0.31), whereas intra-observer reproducibility was good-to-excellent (range: 0.67–0.90). Smallest detectable changes were between 0.21–0.28 μm2/s. Conclusion: ADC change-score as outcome measure was feasible, and the single-slice per lesion ROI setting performed almost equally to whole-lesion setting resulting in reduced assessment time. [ABSTRACT FROM AUTHOR]

Aim: To investigate the acute effect of ketone ester (KE) ingestion on appetite and plasma concentrations of acyl ghrelin (AG), unacylated ghrelin (UAG) and glucagon‐like peptide‐1 (GLP‐1) secretion, and to compare responses with those elicited by isocaloric glucose (GLU) administration. Methods: We examined 10 healthy young men on three separate occasions using a placebo (PBO)‐controlled crossover design. A KE versus taste‐matched isovolumetric and isocaloric 50% GLU and taste‐matched isovolumetric PBO vehicle was orally administered. Our main outcome measures were plasma concentrations of AG, UAG, glucose‐dependent insulinotropic polypeptide (GIP) and GLP‐1 along with appetite sensation scores assessed by visual analogue scale. Results: KE ingestion resulted in an average peak beta‐hydroxybutyrate concentration of 5.5 mM. AG and UAG were lowered by approximately 25% following both KE and GLU intake compared with PBO. In the case of AG, the differences were −52.1 (−79.4, –24.8) for KE and −48.4 (−75.4, −21.5) pg/mL for GLU intake (P <.01). Concentrations of AG remained lower with KE but returned to baseline and were comparable with PBO levels after GLU intake. GLP‐1, GIP, gastrin and cholecystokinin were not affected by KE ingestion. Conclusion: Our results suggest that the suppressive effects on appetite sensation scores associated with hyperketonaemia are more probable to be mediated through reduced ghrelin concentrations than by increased activity of cholecystokinin, gastrin, GIP or GLP‐1. [ABSTRACT FROM AUTHOR]

Background: New insights into post-contrast acute kidney injury (PC-AKI) have recently led to the guidelines on the prevention of PC-AKI being updated. However, little is known about the barriers and facilitators involved in guideline adherence by radiology practices. Purpose: To evaluate barriers and facilitators to the adherence of PC-AKI guidelines. Material and Methods: Radiologists visiting the European Society of Urogenital Radiology (ESUR) 2018 meeting, as well as ESUR members were contacted to fill in an electronic questionnaire on the implementation of PC-AKI guidelines applying to their local radiology practices. Results: Of the 145 responding radiologists representing radiology practices, 127 (88%) confirmed having a PC-AKI protocol in place in their radiology practice, of which 61 (48%) used a protocol as specified in a (inter)national guideline. The majority of radiology practices of the respondents used the ESUR guideline (40%). Barriers for not using PC-AKI prevention guidelines were related to a lack of outcome expectancy. Barriers for not using the protocol as specified were related to a lack of agreement with specific recommendations, lack of motivation, guideline-specific factors, and environmental factors. Self-reported facilitators consisted of guideline-specific factors. Conclusion: Guidelines for the prevention of PC-AKI seem to be widely implemented among radiology practices, and regularly locally modified because of barriers involved in agreement and behavior. Knowledge of the barriers and facilitators of guideline adherence will aid future efforts aimed at bridging the gap between awareness and implementation of evidence-based guidelines in radiology practices. [ABSTRACT FROM AUTHOR]

Background: The indication for treatment of type 1 diabetes(T1D) with the sodium–glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin has been withdrawn in Europe likely because of concern for diabetic ketoacidosis (DKA). We calculated the incidence of DKA in people with T1D treated with SGLT2i in Denmark. Methods: Clinical data from adults with T1D in Denmark were collected from nine outpatient clinics. Electronic health records made the search for DKA accurate. Results: From a population of 10.500 we observed 134 people treated with SGLT2i over a total period of 222 patient-years. Of those 72% were female, mean age (SD) was 51.4 (13.6) years and median duration of treatment (median, IQR) with an SGLT2i were 12.0 (6.0–29.0) months. The incidence of DKA was zero%. Conclusion: In 134 people with T1D treated with SGLT2i we found that none of the participants developed DKA during the treatment. [ABSTRACT FROM AUTHOR]

To assess the level of disease progression at confirmatory staging biopsies after 1 year of active surveillance (AS) and compare the detection rate of significant prostate cancers (PCas) in patients who underwent pre-biopsy biparametric magnetic resonance imaging (bpMRI) before the first set of diagnostic transrectal ultrasonography-guided biopsies (TRUS-bx) with the detection rate in patients who did not undergo pre-biopsy bpMRI. Comparison of two patient groups enrolled in AS. Patients in Group A (n = 127) underwent pre-biopsy bpMRI followed by TRUS-bx ± targeted biopsies. Patients in Group B (n = 127) were enrolled in AS based on biopsy results from TRUS-bx only. Overall, 6% of the patients in Group A and 20% of the patients in Group B had an upgrade in Gleason grade from insignificant to significant PCa at confirmatory staging biopsies (odds ratio [OR], 3.5; p =.002; 95% confidence interval [CI], 1.6–7.9). Patients who underwent pre-biopsy bpMRI before the first set of diagnostic biopsies had a reduced risk of reclassification and disease progression after 1 year of AS. Thus, pre-biopsy bpMRI improves the selection of men who should be enrolled in AS. [ABSTRACT FROM AUTHOR]

Breath-hold divers (BHD) enduring apnea for more than 4 min are characterized by resistance to release of reactive oxygen species, reduced sensitivity to hypoxia, and low mitochondrial oxygen consumption in their skeletal muscles similar to northern elephant seals. The muscles and myocardium of harbor seals also exhibit metabolic adaptations including increased cardiac lactate-dehydrogenase-activity, exceeding their hypoxic limit. We hypothesized that the myocardium of BHD possesses similar adaptive mechanisms. During maximum apnea 15O-H2O-PET/CT (n = 6) revealed no myocardial perfusion deficits but increased myocardial blood flow (MBF). Cardiac MRI determined blood oxygen level dependence oxygenation (n = 8) after 4 min of apnea was unaltered compared to rest, whereas cine-MRI demonstrated increased left ventricular wall thickness (LVWT). Arterial blood gases were collected after warm-up and maximum apnea in a pool. At the end of the maximum pool apnea (5 min), arterial saturation decreased to 52%, and lactate decreased 20%. Our findings contrast with previous MR studies of BHD, that reported elevated cardiac troponins and decreased myocardial perfusion after 4 min of apnea. In conclusion, we demonstrated for the first time with 15O-H2O-PET/CT and MRI in elite BHD during maximum apnea, that MBF and LVWT increases while lactate decreases, indicating anaerobic/fat-based cardiac-metabolism similar to diving mammals. [ABSTRACT FROM AUTHOR]

Acute intermittent porphyria is one of eight disorders arising from disturbances in heme biosynthesis where the precursors, 5‐aminolevulinate and porphobilinogen, are elevated in plasma and urine. Attacks are characterized by severe abdominal pain, vomiting and/or obstipation, neurological manifestations, and psychological disturbances. The mainstay of treatment is hemin infusion to induce the negative feedback of heme synthesis. Hemodialysis is casuistically suggested as an alternative treatment. We present a case report of a 78‐year‐old male with acute intermittent porphyria and renal failure treated with peritoneal dialysis resulting in complete discontinuance of longstanding painful and disabling porphyria attacks. [ABSTRACT FROM AUTHOR]

Background: D-3-hydroxybutyrate (D-3-OHB) is a ketone body that serves as an alternative nutritional fuel but also as an important signaling metabolite. Oral ketone supplements containing D/L-3-OHB are becoming a popular approach to achieve ketosis.Aim: To explore the gut-derived effects of ketone supplements.Methods: Eight healthy lean male volunteers were investigated on 2 separate occasions:An acetaminophen test was performed to evaluate gastric emptying and blood samples were obtained consecutively throughout the study period.Results: We show that oral consumption of D/L-3-OHB stimulates cholecystokinin release (P = 0.02), elevates insulin (P = 0.03) and C-peptide (P < 0.001) concentrations, and slows gastric emptying (P = 0.01) compared with matched intravenous D/L-3-OHB administration. Measures of appetite and plasma concentrations of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were unaffected by interventions.Conclusion: Our findings show that D/L-3-OHB exert incretin effects and indicate luminal sensing in the gut endothelium. This adds to our understanding of ketones as signaling metabolites and displays the important difference between physiological ketosis and oral ketone supplements. [ABSTRACT FROM AUTHOR]

The ability to extract information from scattered waves is usually limited to singly scattered energy even if multiple scattering might occur in the medium. As a result, the information in arrival times of higher-order scattered events is underexplored. This information is extracted using fingerprinting theory. This theory has never previously been applied successfully to real measurements, particularly when the medium is dispersive. The theory is used to estimate the arrival times and scattering paths of multiply scattered waves in a thin sheet using an automated scheme in a dispersive medium by applying an additional dispersion compensation method. Estimated times and paths are compared with predictions based on a sequence of straight ray paths for each scattering event given the known scatterer locations. Additionally, numerical modelling is performed to verify the interpretations of the compensated data. Since the source also acts as a scatterer in these experiments, initially, the predictions and the numerical results did not conform to the experimental observations. By reformulating the theory and the processing scheme and adding a source scatterer in the modelling, it is shown that predictions of all observed scattering events are possible with both prediction methods, verifying that the methods are both effective and practically achievable. [ABSTRACT FROM AUTHOR]

Background: The apparent diffusion coefficient (ADC) may be used as a biomarker to diagnose axial spondyloarthritis (axSpA) and monitor therapeutic response. Purpose: To measure the repeatability of the ADC in healthy individuals and in patients with axSpA with and without active sacroiliitis in a test–retest set-up, and to correlate ADC to conventional magnetic resonance imaging (MRI) bone marrow edema (BME) scores and clinical findings. Material and Methods: A total of 25 patients with axSpA and 24 sex- and age-matched healthy individuals were prospectively examined with MRI twice within 10 days. Short tau inversion recovery (STIR), T1-weighted and diffusion-weighted imaging sequences were performed. Mono-exponential ADC maps were based on four b-values: 0; 50; 500; and 800. Inter-study repeatability and intra-reader reproducibility were investigated in subgroups, as were associations with conventional MRI and clinical findings. Results: The inter-study repeatability for the median ADC was moderate for all individuals (intraclass correlation coefficient [ICC] 0.66); it was good in patients with axSpA (ICC 0.79) and poor in healthy individuals (ICC 0.27). Significant differences in ADC were found between women and men (P = 0.03), and between patients with versus without BME on STIR (P = 0.01). ADC was associated with an MRI BME score and with age in women. Conclusion: ADC seems to be a repeatable parameter in patients with axSpA but not in healthy individuals. ADC is correlated with MRI sacroiliac joint BME score and with age in women. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Dietary recommendations for treating type 2 diabetes are unclear but a trend towards recommending a diet reduced in carbohydrate content is acknowledged. We compared a carbohydrate-reduced high-protein (CRHP) diet with an iso-energetic conventional diabetes (CD) diet to elucidate the effects on glycaemic control and selected cardiovascular risk markers during 6 weeks of full food provision of each diet. Methods: The primary outcome of the study was change in HbA1c. Secondary outcomes reported in the present paper include glycaemic variables, ectopic fat content and 24 h blood pressure. Eligibility criteria were: men and women with type 2 diabetes, HbA1c 48–97 mmol/mol (6.5–11%), age >18 years, haemoglobin >6/>7 mmol/l (women/men) and eGFR >30 ml min−1 (1.73 m)−2. Participants were randomised by drawing blinded ballots to 6 + 6 weeks of an iso-energetic CRHP vs CD diet in an open label, crossover design aiming at body weight stability. The CRHP/CD diets contained carbohydrate 30/50 energy per cent (E%), protein 30/17E% and fat 40/33E%, respectively. Participants underwent a meal test at the end of each diet period and glycaemic variables, lipid profiles, 24 h blood pressure and ectopic fat including liver and pancreatic fat content were assessed at baseline and at the end of each diet period. Data were collected at Copenhagen University Hospital, Bispebjerg and Copenhagen University Hospital, Herlev. Results: Twenty-eight participants completed the study. Fourteen participants carried out 6 weeks of the CRHP intervention followed by 6 weeks of the CD intervention, and 14 participants received the dietary interventions in the reverse order. Compared with a CD diet, a CRHP diet reduced the primary outcome of HbA1c (mean ± SEM: −6.2 ± 0.8 mmol/mol (−0.6 ± 0.1%) vs −0.75 ± 1.0 mmol/mol (−0.1 ± 0.1%); p < 0.001). Nine (out of 37) pre-specified secondary outcomes are reported in the present paper, of which five were significantly different between the diets, (p < 0.05); compared with a CD diet, a CRHP diet reduced the secondary outcomes (mean ± SEM or medians [interquartile range]) of fasting plasma glucose (−0.71 ± 0.20 mmol/l vs 0.03 ± 0.23 mmol/l; p < 0.05), postprandial plasma glucose AUC (9.58 ± 0.29 mmol/l × 240 min vs 11.89 ± 0.43 mmol/l × 240 min; p < 0.001) and net AUC (1.25 ± 0.20 mmol/l × 240 min vs 3.10 ± 0.25 mmol/l × 240 min; p < 0.001), hepatic fat content (−2.4% [−7.8% to −1.0%] vs 0.2% [−2.3% to 0.9%]; p < 0.01) and pancreatic fat content (−1.7% [−3.5% to 0.6%] vs 0.5% [−1.0% to 2.0%]; p < 0.05). Changes in other secondary outcomes, i.e. 24 h blood pressure and muscle-, visceral- or subcutaneous adipose tissue, did not differ between diets. Conclusions/interpretation: A moderate macronutrient shift by substituting carbohydrates with protein and fat for 6 weeks reduced HbA1c and hepatic fat content in weight stable individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT02764021. Funding: The study was funded by grants from Arla Food for Health; the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen; the Department of Clinical Medicine, Aarhus University; the Department of Nutrition, Exercise and Sports, University of Copenhagen; and Copenhagen University Hospital, Bispebjerg. [ABSTRACT FROM AUTHOR]

Oncology-associated adverse drug/device reactions can be fatal. Some clinicians who treat single patients with severe oncology-associated toxicities have researched case series and published this information. We investigated motivations and experiences of select individuals leading such efforts. Clinicians treating individual patients who developed oncology-associated serious adverse drug events were asked to participate. Inclusion criteria included having index patient information, reporting case series, and being collaborative with investigators from two National Institutes of Health funded pharmacovigilance networks. Thirty-minute interviews addressed investigational motivation, feedback from pharmaceutical manufacturers, FDA personnel, and academic leadership, and recommendations for improving pharmacovigilance. Responses were analyzed using constant comparative methods of qualitative analysis. Overall, 18 clinicians met inclusion criteria and 14 interviewees are included. Primary motivations were scientific curiosity, expressed by six clinicians. A less common theme was public health related (three clinicians). Six clinicians received feedback characterized as supportive from academic leaders, while four clinicians received feedback characterized as negative. Three clinicians reported that following the case series publication they were invited to speak at academic institutions worldwide. Responses from pharmaceutical manufacturers were characterized as negative by 12 clinicians. One clinician’s wife called the post-reporting time the “Maalox month,” while another clinician reported that the manufacturer collaboratively offered to identify additional cases of the toxicity. Responses from FDA employees were characterized as collaborative for two clinicians, neutral for five clinicians, unresponsive for negative by six clinicians. Three clinicians endorsed developing improved reporting mechanisms for individual physicians, while 11 clinicians endorsed safety activities that should be undertaken by persons other than a motivated clinician who personally treats a patient with a severe adverse drug/device reaction. Our study provides some of the first reports of clinician motivations and experiences with reporting serious or potentially fatal oncology-associated adverse drug or device reactions. Overall, it appears that negative feedback from pharmaceutical manufacturers and mixed feedback from the academic community and/or the FDA were reported. Big data, registries, Data Safety Monitoring Boards, and pharmacogenetic studies may facilitate improved pharmacovigilance efforts for oncology-associated adverse drug reactions. These initiatives overcome concerns related to complacency, indifference, ignorance, and system-level problems as barriers to documenting and reporting adverse drug events- barriers that have been previously reported for clinician reporting of serious adverse drug reactions. [ABSTRACT FROM AUTHOR]

Objectives: To determine the diagnostic accuracy of 68gallium prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in comparison with 18F-fluoride-based PET/CT (NaF-PET/CT) and whole-body magnetic resonance imaging (WB-MRI) for the detection of bone metastases in patients with prostate cancer.Methods: Sixty patients with prostate cancer were included in the period May 2016 to June 2017. The participants underwent three scans (index tests) within 30 days: a NaF-PET/CT, a WB-MRI and a PSMA-PET/CT. Experienced specialists assessed the scans. In the absence of a histological reference standard, the final diagnosis was determined as a panel diagnosis. Measures of the diagnostic performances of the index tests were calculated from patient-based dichotomous outcomes (0 or ≥ 1 bone metastasis) and pairwise compared (McNemar test). For each index test, the agreement with the final diagnosis with regard to the number of bone metastases detected (0, 1-5, > 5) and the inter-reader agreement was calculated (kappa coefficients).Results: Fifty-five patients constituted the final study population; 20 patients (36%) were classified as having bone metastatic disease as their final diagnosis. The patient-based diagnostic performances were (sensitivity, specificity, overall accuracy) PSMA-PET/CT (100%, 100%, 100%), NaF-PET/CT (95%, 97%, 96%) and WB-MRI (80%, 83%, 82%). The overall accuracy of PSMA-PET/CT was significantly more favourable compared to WB-MRI (p = 0.004), but not to NaF-PET/CT (p = 0.48). PSMA-PET/CT classified the number of bone metastases reliably compared to the final diagnosis (kappa coefficient 0.97) and with an "almost perfect" inter-reader agreement (kappa coefficient 0.93).Conclusions: The overall accuracy of PSMA-PET/CT was significantly more advantageous compared to WB-MRI, but not to NaF-PET/CT.Key Points: • PSMA-PET/CT assessed the presence of bone metastases correctly in all 55 patients • PSMA-PET/CT was more advantageous compared to WB-MRI • No difference was found between PSMA-PET/CT and NaF-PET/CT. [ABSTRACT FROM AUTHOR]

Graph I am pleased to announce Dr Fleur Kilburn-Toppin, Consultant Radiologist, Cambridge University Hospital, has accepted our invitation to become section editor within the field of breast imaging. Dr Fleur Kilburn-Toppin has been a Consultant Radiologist in Cambridge University Hospital since 2015, having graduated from Cambridge University in 2006 and subsequently undertaken her radiology training and Breast Fellowship. We are very happy that Dr Fleur Kilburn-Toppin has accepted the invitation to become section editor for the field of Breast Radiology, and we look forward to working with her. [Extracted from the article]

Background: Acute inflammation, and subsequent release of bacterial products (e.g. LPS), inflammatory cytokines, and stress hormones, is catabolic, and the loss of lean body mass predicts morbidity and mortality. Lipid intermediates may reduce protein loss, but the roles of free fatty acids (FFAs) and ketone bodies during acute inflammation are unclear. Objective: We aimed to test whether infusions of 3-hydroxybutyrate (3OHB), FFAs, and saline reduce protein catabolism during exposure to LPS and Acipimox (to restrict and control endogenous lipolysis). Design: A total of 10 healthy male subjects were randomly tested 3 times, with: 1) LPS, Acipimox (Olbetam) and saline, 2) LPS, Acipimox, and nonesterified fatty acids (Intralipid), and 3) LPS, Acipimox, and 3OHB, during a 5-h basal period and a 2-h hyperinsulinemic, euglycemic clamp. Labeled phenylalanine, tyrosine, and urea tracers were used to estimate protein kinetics, and muscle biopsies were taken for Western blot analysis of protein metabolic signaling. Results: 3OHB infusion increased 3OHB concentrations (P < 0.0005) to 3.5 mM and decreased whole-body phenylalanine-to-tyrosine degradation. Basal and insulin-stimulated net forearm phenylalanine release decreased by >70% (P < 0.005), with both appearance and phenylalanine disappearance being profoundly decreased. Phosphorylation of eukaryotic initiation factor 2α at Ser51 was increased in skeletal muscle, and S6 kinase phosphorylation at Ser235/236 tended (P = 0.074) to be decreased with 3OHB infusion (suggesting inhibition of protein synthesis), whereas no detectable effects were seen on markers of protein breakdown. Lipid infusion did not affect phenylalanine kinetics, and insulin sensitivity was unaffected by interventions. Conclusion: During acute inflammation, 3OHB has potent anticatabolic actions in muscle and at the whole-body level; in muscle, reduction of protein breakdown overrides inhibition of synthesis. [ABSTRACT FROM AUTHOR]

Background Patient acceptance is an important factor when implementing imaging methods in clinical practice in line with availability, diagnostic accuracy, and cost-effectiveness. Purpose To investigate patient experience and acceptance regarding18F-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT), 11 C-choline-PET/CT, whole-body magnetic resonance imaging (WB-MRI), and 99mTc-hydroxymethane diphosphonate (HDP) single photon emission/computed tomography (SPECT/CT). Material and Methods One hundred and forty-nine patients with prostate cancer filled in a questionnaire regarding their experience of the imaging procedures they had been undergoing as part of a diagnostic accuracy study. Each patient had been undergoing a NaF-PET/CT, a WB-MRI, and either a SPECT/CT (group A) or a choline-PET/CT (group B). Results All four imaging methods received overall experience ratings at the favorable end of a 5-point Likert scale with the two PET/CT scans receiving marginally better average ratings (2.0) compared to SPECT/CT (2.2) and WB-MRI (2.3). The arm positioning above the head was the most uncomfortable part of the three nuclear medicine scans, whereas the acoustic noise was the most unpleasant part of the WB-MRI. The experience of staff instruction was relatively strongly correlated to the overall scanning experience of all four imaging modalities. Overall, the patients were willing to repeat the four imaging methods and NaF-PET/CT was the method most preferred in both groups. Conclusion Four imaging procedures were evaluated from the perspective of a selected group of prostate cancer patients. NaF-PET/CT, choline-PET/CT, WB-MRI, and bone SPECT/CT are well accepted imaging methods, and most patients prefer NaF-PET/CT. [ABSTRACT FROM AUTHOR]

Objectives: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI). The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers. AREAS COVERED IN PART 2: Topics reviewed include stratification of PC-AKI risk, the need to withdraw nephrotoxic medication, PC-AKI prophylaxis with hydration or drugs, the use of metformin in diabetic patients receiving contrast medium and the need to alter dialysis schedules in patients receiving contrast medium.Key Points: • In CKD, hydration reduces the PC-AKI risk • Intravenous normal saline and intravenous sodium bicarbonate provide equally effective prophylaxis • No drugs have been consistently shown to reduce the risk of PC-AKI • Stop metformin from the time of contrast medium administration if eGFR < 30 ml/min/1.73 m 2 • Dialysis schedules need not change when intravascular contrast medium is given. [ABSTRACT FROM AUTHOR]

Purpose: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI). The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers. AREAS COVERED IN PART 1: Topics reviewed include the terminology used, the best way to measure eGFR, the definition of PC-AKI, and the risk factors for PC-AKI, including whether the risk with intravenous and intra-arterial contrast medium differs.Key Points: • PC-AKI is the preferred term for renal function deterioration after contrast medium. • PC-AKI has many possible causes. • The risk of AKI caused by intravascular contrast medium has been overstated. • Important patient risk factors for PC-AKI are CKD and dehydration. [ABSTRACT FROM AUTHOR]

Background Multiparametric magnetic resonance imaging (mpMRI) can improve detection of clinically significant prostate cancer (csPCa). Purpose To compare mpMRI score subgroups to systematic transrectal ultrasound-guided biopsies (TRUSbx) and prostate-specific antigen (PSA)-based findings for detection of csPCa in men undergoing repeat biopsies. Material and Methods MpMRI was performed prior to re-biopsy in 289 prospectively enrolled patients. All underwent repeat TRUSbx followed by targeted biopsies (MRITB) of any mpMRI-identified lesion. MpMRI suspicion grade, PSA level, and density (PSAd) were compared with biopsy results and further matched to the radical prostatectomy (RP) specimen if available. Results PCa was detected in 128/289 (44%) patients with median age, PSA, and prior negative TRUSbx of 64 (interquartile range [IQR] = 59-67), 12.0 ng/mL (IQR = 8.3-19.1), and 2 (IQR = 1-3), respectively. TRUSbx detected PCa in 108/289 (37%) patients, of which 49 (45%) had insignificant cancer. MRITB was performed in 271/289 (94%) patients and detected PCa in 96 (35%) with 78 (81%) having csPCa. MpMRI scores showed a high association between suspicion level and biopsy results on both lesion and patient level ( P < 0.001). MpMRI was better than PSA and PSAd ( P < 0.001) to identify patients with missed csPCa. In total, 64/128 (50%) patients underwent RP; 60/64 had csPCa. MpMRI was significantly better in predicting csPCa on RP compared with TRUSbx ( P = 0.019) as MRITB and TRUSbx correctly identified 47/60 (78%) and 35/60 (58%) patients, respectively. Conclusion MpMRI improves detection of missed csPCa and suspicion scores correlate well with biopsy and RP results on both patient and lesion level. [ABSTRACT FROM AUTHOR]