Pancreas-related persisting sequelae in ALL survivors with a history of asparaginase-associated pancreatitis: A part of the ALL-STAR study.

OBJECTIVES: Asparaginase-associated pancreatitis (AAP) occurs in up to 18% of patients treated for acute lymphoblastic leukemia (ALL); however, long-term sequelae are largely unexplored. We aimed to explore pancreatic sequelae among ALL survivors with and without AAP. METHODS: We investigated pancreatic sequelae in a national cohort of ALL survivors, aged 1-45 years at ALL diagnosis treated according to the NOPHO-ALL2008 protocol and included sex- and age-matched community controls. RESULTS: We included 368 survivors (median follow-up 6.9 years), including 47 survivors with AAP and 369 controls. The p-lipase and p-pancreas-type amylase levels were lower in AAP survivors compared with both non-AAP survivors (Medians: 23 U/L [IQR 14-32] and 18 U/L [IQR 10-25] versus 29 [IQR 24-35] and 22 [17-28], p < .001 and p = .002) and community controls (28 U/L [IQR 22-33] and 21 U/L [IQR 17-26], both p < .006). Fecal-elastase was more frequently reduced in AAP survivors compared with non-AAP survivors (7/31 vs. 4/144, p = .001). Persisting pancreatic sequelae were found in 15/47 of AAP survivors and 20/323 of non-AAP survivors (p < .001), including diabetes mellitus in 2/39 of AAP survivors and 2/273 of non-AAP survivors. CONCLUSIONS: ALL survivors with AAP are at increased risk of persisting pancreatic dysfunction and require special attention during follow-up.

Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease.

Obesity is a strong predictor for metabolic associated fatty liver disease (MAFLD), which has been associated with decreased insulin like growth factor 1 (IGF-1). In obesity, weight loss increases growth hormone secretion, but this is not unequivocally associated with increases in serum IGF-1 and IGF binding protein-3 (IGFBP-3). We studied the changes in the IGF axis in relation to weight loss and improvement in insulin resistance in children with or without MALFD after 10 weeks of lifestyle intervention at a weight loss camp (WLC). We investigated 113 (66 females) Caucasian children with obesity, median age 12.4 (range 7.3-14.6) years, before and after 10 weeks of lifestyle intervention at a WLC. We investigated children who was either MAFLD positive (n = 54) or negative (n = 59) before and after WLC. Children with MAFLD had lower baseline IGF-1 (249 ± 112 vs 278 ± 107 µg/l, P = 0.048), whereas the IGF-1/IGFBP-3 molar ratio was similar to children without MAFLD (19.4 ± 6.6 vs. 21.8 ± 6.6%, P = 0.108). When all children were considered as one group, WLC decreased SDS-BMI and HOMA-IR (P < 0.001, both) and increased IGF-1 (264 ± 110 vs 285 ± 108 µg/l, P < 0.001) and the IGF/IGFBP-3 molar ratio (20.7 ± 6.7 vs 22.4 ± 6.1%, P < 0.001). When categorized according to liver status, IGF-1 increased significantly in children with MAFLD (P = 0.008) and tended to increase in children without MAFLD (P = 0.052).   Conclusions: Ten weeks of lifestyle intervention decreased insulin resistance and improved the IGF axis. We observed slight differences in the IGF axis in relation to MAFLD status. This suggests that the IGF axis is primarily influenced by insulin resistance rather than MAFLD status. What is New: • Weight loss decreases insulin resistance and subsequently increases the IGF axis in children with obesity. • Children with MAFLD had an aberration in the IGF axis compared to their MAFLD negative counter parts and the IGF axis was primarily influenced by the decreased BMI-SDS and insulin resistance, rather than MAFLD status. What is Known: • NAFLD has previously been associated with reduced serum IGF-1 concentrations. • Data on the impact of MAFLD and aberrations in the growth hormone and IGF axis and the effects of lifestyle interventions in children are limited.

Difficulty and importance of diagnosing stenosis of renal branch artery in fibromuscular dysplasia: a case report.

A 16-year-old patient presented with abdominal pain and sustained hypertension. Thorough evaluation including renography with and without captopril and renal vein renin sampling were normal. Duplex ultrasound, however, raised suspicion of a renal artery stenosis. This was confirmed by computed tomography angiography which showed a severe branch artery stenosis with post-stenotic dilatation consistent with focal fibromuscular dysplasia (FMD). As the hypertension was resistant to 3 classes of antihypertensive treatment, percutaneous transluminal renal angioplasty (PTRA) was offered. The procedure had immediate effect on the blood pressure. Without medication the patient remains normotensive 4 years after and the abdominal pain has only sporadically returned. The presented case illustrates the challenging process of diagnosing FMD-related renal branch artery stenosis as well as the potential benefits of PTRA in this patient group.

Web-Based GPU-Accelerated Application for Multiplanar Reconstructions from Conventional 2D Ultrasound.

PURPOSE: In ultrasound education there is a need for interactive web-based learning resources. The purpose of this project was to develop a web-based application that enables the generation and exploration of volumetric datasets from cine loops obtained with conventional 2D ultrasound. MATERIALS AND METHODS: JavaScript code for ultrasound video loading and the generation of volumetric datasets was created and merged with an existing web-based imaging viewer based on JavaScript and HTML5. The Web Graphics Library was utilized to enable hardware-accelerated image rendering. RESULTS: The result is a web application that works in most major browsers without any plug-ins. It allows users to load a conventional 2D ultrasound cine loop which can subsequently be manipulated with on-the-fly multiplanar reconstructions as in a Digital Imaging and Communications in Medicine (DICOM) viewer. The application is freely accessible at (http://www.castlemountain.dk/atlas/index.php?page=mulrecon&mulreconPage=sonoviewer) where a demonstration of web-based sharing of generated cases can also be found. CONCLUSION: The developed web-based application is unique in its ability to easily perform loading of one's own ultrasound clips and conduct multiplanar reconstructions where interactive cases can be shared on the Internet.

Superior Reproducibility of the Leading to Leading Edge and Inner to Inner Edge Methods in the Ultrasound Assessment of Maximum Abdominal Aortic Diameter.

OBJECTIVES: Controversy exists regarding optimal caliper placement in ultrasound assessment of maximum abdominal aortic diameter. This study aimed primarily to determine reproducibility of caliper placement in relation to the aortic wall with the three principal methods: leading to leading edge (LTL), inner to inner edge (ITI), and outer to outer edge (OTO). The secondary aim was to assess the mean difference between the OTO, ITI, and LTL diameters and estimate the impact of using either of these methods on abdominal aortic aneurysm (AAA) prevalence in a screening program. METHODS: Radiologists (n=18) assessed the maximum antero-posterior abdominal aortic diameter by completing repeated caliper placements with the OTO, LTL, and ITI methods on 50 still abdominal aortic images obtained from an AAA screening program. Inter-observer reproducibility was calculated as the limit of agreement with the mean (LoA), which represents expected deviation of a single observer from the mean of all observers. Intra-observer reproducibility was assessed averaging the LoA for each observer with their repeated measurements. Based on data from an AAA screening trial and the estimated mean differences between the three principal methods, AAA prevalence was estimated using each of the methods. RESULTS: The inter-observer LoA of the OTO, ITI, and LTL was 2.6, 1.9, and 1.9 mm, whereas the intra-observer LoA was 2.0, 1.6, and 1.5 mm, respectively. Mean differences of 5.0 mm were found between OTO and ITI measurements, 2.6 mm between OTO and LTL measurements, and 2.4 mm between LTL and ITI measurements. The prevalence of AAA almost doubled using OTO instead of ITI, while the difference between ITI and LTL was minor (3.3% vs. 4.0% AAA). CONCLUSIONS: The study shows superior reproducibility of LTL and ITI compared with the OTO method of caliper placement in ultrasound determination of maximum abdominal aortic diameter, and the choice of caliper placement method significantly affects the prevalence of AAAs in screening programs.

Short-term complications for percutaneous ultrasound-guided biopsy of renal masses in adult outpatients.

Background Ultrasound-guided percutaneous kidney tumor biopsy (UGPKB) plays an important role in the diagnosis of renal tumor but there are no consensuses with respect to the length and the extend of the post-biopsy observation period. Purpose To assess the short-term complication rate after UGPKB and to evaluate whether the onset of complications allows for the procedure to be performed in an outpatient setting with same-day discharge. Material and Methods Between March 2012 and March 2014, a total of 287 UGPKB were performed in an outpatient setting at a Danish university referral center. All patient records were retrospectively reviewed and post-biopsy complications as well as biochemical parameters were registered. Results The overall complication rate was 3.8% (11 patients). Major complications occurred in 1.0% of all cases (three patients); one patient with ongoing bleeding that required intervention and two patients with septicemia. Minor complications occurred in 2.8% of cases (eight patients); six patients with self-limiting gross hematuria, one patient with small asymptomatic subcapsular hematoma, and one patient with vasovagal syncope. The timing of both minor and major complication onset ranged from the time of biopsy and up to four days after discharge. Conclusion UGPKB of indeterminate renal masses in adult patients in an outpatient setting appears to be a safe procedure with a very low rate of major complications. Same-day discharge after renal mass biopsy seems feasible.

KETAMINE-MEDETOMIDINE AND KETAMINE-MEDETOMIDINE-MIDAZOLAM ANESTHESIA IN CAPTIVE CHEETAHS (ACINONYX JUBATUS)-COMPARISON OF BLOOD PRESSURE AND KIDNEY BLOOD FLOW.

Six clinically healthy captive cheetahs ( Acinonyx jubatus ) were anesthetized twice using two different drug combinations to investigate if blood pressure and kidney blood flow are affected by medetomidine dosage. Protocol KM (2.0 mg/kg ketamine and 0.05 mg/kg medetomidine) was compared with protocol KMM (2.0 mg/kg ketamine, 0.02 mg/kg medetomidine, and 0.1 mg/kg midazolam). Heart rate (HR), respiratory rate (RR), body temperature, end-tidal carbon dioxide pressure (ETCO2), and anesthetic depth were monitored every 10 min. Noninvasive mean (MAP), systolic (SAP), and diastolic (DAP) arterial blood pressure were measured, and Duplex Doppler ultrasonography was performed on the kidneys. The mean arterial resistive index (RI) was determined and the pulse pressure index (PPI) was calculated, as indicators for kidney blood flow. There were no significant differences in induction and recovery times. MAP was significantly higher with KM than KMM at 35 min, and in both protocols decreased significantly after atipamezole administration. DAP was significantly higher at 25 and 35 min in animals anesthetized with KM; it also decreased significantly with both protocols after atipamezole administration. The PPI was significantly lower throughout the procedure with KM, and with both protocols increased significantly after atipamezole administration. Both the higher blood pressure and the reduced PPI with KM were likely a direct effect of the higher medetomidine dosage, and these findings indicate that lower medetomidine dosages might reduce hypertension and lead to a better PPI in cheetah immobilization.

Bosniak classification system: a prospective comparison of CT, contrast-enhanced US, and MR for categorizing complex renal cystic masses.

Background The Bosniak classification was originally based on computed tomographic (CT) findings. Magnetic resonance (MR) and contrast-enhanced ultrasonography (CEUS) imaging may demonstrate findings that are not depicted at CT, and there may not always be a clear correlation between the findings at MR and CEUS imaging and those at CT. Purpose To compare diagnostic accuracy of MR, CEUS, and CT when categorizing complex renal cystic masses according to the Bosniak classification. Material and Methods From February 2011 to June 2012, 46 complex renal cysts were prospectively evaluated by three readers. Each mass was categorized according to the Bosniak classification and CT was chosen as gold standard. Kappa was calculated for diagnostic accuracy and data was compared with pathological results. Results CT images found 27 BII, six BIIF, seven BIII, and six BIV. Forty-three cysts could be characterized by CEUS, 79% were in agreement with CT (κ = 0.86). Five BII lesions were upgraded to BIIF and four lesions were categorized lower with CEUS. Forty-one lesions were examined with MR; 78% were in agreement with CT (κ = 0.91). Three BII lesions were upgraded to BIIF and six lesions were categorized one category lower. Pathologic correlation in six lesions revealed four malignant and two benign lesions. Conclusion CEUS and MR both up- and downgraded renal cysts compared to CT, and until these non-radiation modalities have been refined and adjusted, CT should remain the gold standard of the Bosniak classification.

Inter- and intraobserver agreement in detection of testicular microlithiasis with ultrasonography.

BACKGROUND: Ultrasonography of the testis is a well-established diagnostic tool in detection of testicular microlithiasis (TML). Operator-dependent diagnostic variation related to skill, knowledge, and operator consistency are factors that influence detection of TML. PURPOSE: To determine inter- and intraobserver agreement for detection of TML using ultrasonography for a group of physicians with no or limited experience compared to a group of experience senior radiologists. MATERIAL AND METHODS: Between May and September 2014 a total of six observers evaluated 34 patients scrotal ultrasonography recorded from September to December 2013. The observers were blinded to patient history and previous ultrasonography. Three of the observers had no or limited experience with detection of TML, and three of the observers had more than 15 years of experience. Each observer reviewed all the scrotal ultrasonography recordings twice with a time interval of 3 months. RESULTS: The inter-observer agreement showed substantial agreement and up to almost perfect agreement (κ = 0.86). Both the experienced and less experienced observers had a higher agreement in detecting and grading TML in their second reading. CONCLUSION: The ultrasonography grading system of TML in this study showed to be reproducible, with an inter- and intraobserver agreement ranging between substantial agreement and up to almost perfect agreement with many years of experience not necessarily being essential.

Bosniak classification system: inter-observer and intra-observer agreement among experienced uroradiologists.

BACKGROUND: The Bosniak classification is a diagnostic tool for the differentiation of cystic changes in the kidney. The process of categorizing renal cysts may be challenging, involving a series of decisions that may affect the final diagnosis and clinical outcome such as surgical management. PURPOSE: To investigate the inter- and intra-observer agreement among experienced uroradiologists when categorizing complex renal cysts according to the Bosniak classification. MATERIAL AND METHODS: The original categories of 100 cystic renal masses were chosen as "Gold Standard" (GS), established in consensus by two experienced uroradiologists. Three experienced uroradiological readers were blinded from the previous CT reports. Weighted κ was calculated to assess agreement, defined as: fair, 0.21-0.40; moderate, 0.41-0.60; good, 0.61-0.80; and very good, 0.81-1.00. RESULTS: For readers the distribution of correctly classified lesions were as follows: BI, 95-100%; BII, 59-93%; BIIF, 54-92%; BIII, 58-95%; and B IV, 77-100% for the first review. Weighted κ for inter-observer/intra-observer variation was for Reader A: 0.85/0.99, Reader B: 0.97/0.99, and Reader C: 0.98/0.99, (P ≤ 0.001). CONCLUSION: According to the calculated weighted κ all readers performed "very good" for both inter-observer and intra-observer variation. Most variation was seen in cysts catagorized as Bosniak II, IIF, and III. These results show that radiologists who evaluate complex renal cysts routinely may apply the Bosniak classification reproducibly.

Preoperative planning of renal transplantation: a comparison of non-contrast-enhanced ultrasonography, computed tomography, and magnetic resonance angiography with observations from surgery.

BACKGROUND: Many candidates for kidney transplantation need to undergo vessel examination before the transplantation procedure. PURPOSE: To identify the optimal preoperative modality for the examination of vessel status without the use of contrast agents in kidney transplant candidates. MATERIAL AND METHODS: Fifty-three consecutive patients were examined and 31 patients were transplanted. Ultrasonography (US), non-contrast-enhanced computed tomography (NCCT), and non-contrast-enhanced magnetic resonance angiography (NCMRA) were compared using inspection during kidney transplantation (TX) as a reference standard. The sensitivity and specificity to severe arteriosclerotic changes and the accuracy were calculated. Kappa statistics were used to assess the agreement between TX and the different examination modalities, and McNemar's test was used to test for significant differences. RESULTS: US had higher sensitivity (1.0) and better agreement with observations from surgery (k = 0.89) than both NCCT (sensitivity = 0.60; k = 0.72) and NCMRA (sensitivity = 0.20; k = 0.30). No significant difference was found between TX and US (P = 0.3173) or TX and NCCT (P = 0.1573), but there was a significant difference between TX and NCMRA (P = 0.0455). US was inconclusive in 20% of cases, and the internal iliac artery could not be visualized in 69% of cases. CONCLUSION: Either US or NCCT can be used as the preferred preoperative imaging modality to examine vessel status before kidney transplantation, but a combination of the two is preferable. NCMRA should not be used as the sole imaging modality for preoperative imaging before kidney transplantation because of its low sensitivity in detecting severe arteriosclerotic disease without the presence of stenosis.

Drainage of large pleural effusions increases left ventricular preload.

OBJECTIVES: The aim of the study was to investigate if pleurocentesis in patients with pleural effusion would lead to changes in systolic and diastolic function of the left ventricle. DESIGN: The study was descriptive, and patients were their own controls. SETTING: The setting was a single-center university hospital. PARTICIPANTS: Patients with pleural effusion requiring pleurocentesis were eligible for inclusion. INTERVENTIONS: The participants who had pleurocentesis performed were available for analysis. MEASUREMENTS AND MAIN RESULTS: Prior to pleurocentesis and approximately 1 hour after, patients were examined primarily with transthoracic echocardiography. The examination included measurements of left ventricular volumes and measures of diastolic function assessed by Doppler echocardiography. Thirty-five patients were included, and 11 later were excluded, yielding a study population of 24. Preload, expressed as left ventricular end-diastolic volume, increased significantly from before to after pleurocentesis (p=0.014). None of the diastolic parameters showed significant results. Significant changes were observed for heart rate, supplementary O2, respiratory frequency, and saturation. CONCLUSIONS: Pleurocentesis increased left ventricular preload and improved respiratory function.

Migration of a contraceptive implant to the lung.

This case report details a rare case of contraceptive implant migration in a young woman. The migration was discovered three years post-insertion during a routine replacement visit. Despite the absence of pulmonary symptoms, a CT scan revealed the implant in the inferior lobe of the right lung. The patient was referred for further evaluation, but immediate surgical removal was deferred. This case report highlights the importance of healthcare providers recognising migration as a rare complication during implantation and suggests self-examination as a potential preventive strategy.

Integration of long-read sequencing, DNA methylation and gene expression reveals heterogeneity in Y chromosome segment lengths in phenotypic males with 46,XX testicular disorder/difference of sex development.

BACKGROUND: 46,XX testicular disorder/difference of sex development (46,XX DSD) is a rare congenital condition, characterized by a combination of the typical female sex chromosome constitution, 46,XX, and a variable male phenotype. In the majority of individuals with 46,XX DSD, a Y chromosome segment containing the sex-determining region gene (SRY) has been translocated to the paternal X chromosome. However, the precise genomic content of the translocated segment and the genome-wide effects remain elusive. METHODS: We performed long-read DNA sequencing, RNA sequencing and DNA methylation analyses on blood samples from 46,XX DSD (n = 11), male controls (46,XY; variable cohort sizes) and female controls (46,XX; variable cohort sizes), in addition to RNA sequencing and DNA methylation analysis on blood samples from males with Klinefelter syndrome (47,XXY, n = 22). We also performed clinical measurements on all 46,XX DSD and a subset of 46,XY (n = 10). RESULTS: We identified variation in the translocated Y chromosome segments, enabling subcategorization into 46,XX DSD (1) lacking Y chromosome material (n = 1), (2) with short Yp arms (breakpoint at 2.7-2.8 Mb, n = 2), (3) with medium Yp arms (breakpoint at 7.3 Mb, n = 1), and (4) with long Yp arms (n = 7), including deletions of AMELY, TBLY1 and in some cases PRKY. We also identified variable expression of the X-Y homologues PRKY and PRKX. The Y-chromosomal transcriptome and methylome reflected the Y chromosome segment lengths, while changes to autosomal and X-chromosomal regions indicated global effects. Furthermore, transcriptional changes tentatively correlated with phenotypic traits of 46,XX DSD, including reduced height, lean mass and testicular size. CONCLUSION: This study refines our understanding of the genetic composition in 46,XX DSD, describing the translocated Y chromosome segment in more detail than previously and linking variability herein to genome-wide changes in the transcriptome and methylome.

Our sex chromosome constitution determines our sex, with the presence of a Y chromosome causing male sex determination (typically 46,XY) and the lack hereof resulting in female sex development (typically 46,XX). However, individuals can become male despite of them presenting with the classical female chromosome constitution. We term this "46,XX testicular disorder/difference of sex development" or "46,XX DSD" for short. Individuals with this condition are affected by a number of traits, such as infertility, short stature and altered hormone levels. We know that most cases of 46,XX DSD are caused by the sex-determining region of the Y chromosome being moved to one of the X chromosomes. However, we do not know the more precise size of the Y-chromosomal section or its effects on the genome. In this study we investigated 11 individuals with 46,XX DSD using novel and precise techniques than previously applied. Analyzing DNA, we found that their Y-chromosomal sections varied. This was reflected in multiple types of additional genetic analyses, investigating modifications to DNA and expression of genes. Our findings are the most accurate description of the Y-chromosomal section in 46,XX DSD to date, and indicate that the genomes of individuals with 46,XX DSD differ, with many potential mechanisms of action.

Protection against high intravascular pressure in giraffe legs.

The high blood pressure in giraffe leg arteries renders giraffes vulnerable to edema. We investigated in 11 giraffes whether large and small arteries in the legs and the tight fascia protect leg capillaries. Ultrasound imaging of foreleg arteries in anesthetized giraffes and ex vivo examination revealed abrupt thickening of the arterial wall and a reduction of its internal diameter just below the elbow. At and distal to this narrowing, the artery constricted spontaneously and in response to norepinephrine and intravascular pressure recordings revealed a dynamic, viscous pressure drop along the artery. Histology of the isolated median artery confirmed dense sympathetic innervation at the narrowing. Structure and contractility of small arteries from muscular beds in the leg and neck were compared. The arteries from the legs demonstrated an increased media thickness-to-lumen diameter ratio, increased media volume, and increased numbers of smooth muscle cells per segment length and furthermore, they contracted more strongly than arteries from the neck (500 ± 49 vs. 318 ± 43 mmHg; n = 6 legs and neck, respectively). Finally, the transient increase in interstitial fluid pressure following injection of saline was 5.5 ± 1.7 times larger (n = 8) in the leg than in the neck. We conclude that 1) tissue compliance in the legs is low; 2) large arteries of the legs function as resistance arteries; and 3) structural adaptation of small muscle arteries allows them to develop an extraordinary tension. All three findings can contribute to protection of the capillaries in giraffe legs from a high arterial pressure.

Sensorimotor responsiveness and resolution in the giraffe.

The ability of an animal to detect and respond to changes in the environment is crucial to its survival. However, two elements of sensorimotor control - the time required to respond to a stimulus (responsiveness) and the precision of stimulus detection and response production (resolution) - are inherently limited by a competition for space in peripheral nerves and muscles. These limitations only become more acute as animal size increases. In this paper, we investigated whether the physiology of giraffes has found unique solutions for maintaining sensorimotor performance in order to compensate for their extreme size. To examine responsiveness, we quantified three major sources of delay: nerve conduction delay, muscle electromechanical delay and force generation delay. To examine resolution, we quantified the number and size distribution of nerve fibers in the sciatic nerve. Rather than possessing a particularly unique sensorimotor system, we found that our measurements in giraffes were broadly comparable to size-dependent trends seen across other terrestrial mammals. Consequently, both giraffes and other large animals must contend with greater sensorimotor delays and lower innervation density in comparison to smaller animals. Because of their unconventional leg length, giraffes may experience even longer delays compared with other animals of the same mass when sensing distal stimuli. While there are certainly advantages to being tall, there appear to be challenges as well - our results suggest that giraffes are less able to precisely and accurately sense and respond to stimuli using feedback alone, particularly when moving quickly.

Carotid intima-media thickness is increased in Turner syndrome: multifactorial pathogenesis depending on age, blood pressure, cholesterol and oestrogen treatment.

OBJECTIVE: Carotid intima-media thickness (IMT) may potentially supplement cardiovascular risk assessment in Turner syndrome (TS), where cardiovascular risk is high and appropriate risk stratification difficult. Knowledge of IMT in TS is scarce, and this study aimed to enhance insight into the cardiovascular risk marker. DESIGN, PATIENTS AND MEASUREMENTS: IMT was cross-sectionally assessed by ultrasonography of the common carotid artery (cIMT) and carotid bulb (bIMT) in TS (n = 69, age 40 ± 10 years) and age-matched, healthy female controls (n = 67). Additional prospective IMT assessment was performed in TS over 2·4 ± 0·3 years. Metabolic biomarkers and 24-h ambulatory blood pressure were also assessed. RESULTS: cIMT and bIMT (body surface area indexed) were increased in TS (P < 0·05) with 17-18% having IMTs that exceeded the 95th percentile of the controls (P < 0·05). Blood pressure, heart rate, glycosylated haemoglobin A1c and high-density lipoprotein cholesterol were increased in TS, where 43% received antihypertensive treatment. cIMT decreased during follow-up, coinciding with intensified cardiovascular risk prophylaxis, whereas bIMT was unchanged. In multiple regression analyses (R = 0·52-0·69, P < 0·05), baseline IMT in TS increased with age, blood pressure and cholesterol as well as in the presence of diabetes whilst IMT was inversely associated with duration of oestrogen replacement. In an analogue analysis, the prospective changes in cIMT (R = 0·37, P < 0·05) were beneficially influenced by antihypertensive treatment and oestrogen therapy and adversely by the presence of diabetes. CONCLUSION: Carotid IMT was abnormal in TS and negatively influenced by age, metabolic biomarkers, blood pressure and short duration of oestrogen treatment. Attention to common cardiovascular and endocrine risk markers over more than 2 years appeared to influence IMT beneficially.

Effect of a 10-week weight loss camp on fatty liver disease and insulin sensitivity in obese Danish children.

BACKGROUND AND OBJECTIVE: Childhood nonalcoholic fatty liver disease (NAFLD) associated with insulin resistance and obesity is a growing problem and increases the risk of cirrhosis, type 2 diabetes mellitus, and cardiovascular complications. We examined the effects of a 10-week "weight loss camp" residency in obese children on the prevalence and degree of NAFLD and insulin sensitivity with 12-month follow-up. METHODS: At the camp, 117 obese white children (body mass index 28.0 ±â€Š3.6  kg/m, age 12.1 ±â€Š1.3 years) exercised moderately for 1 hour/day and restricted their energy intake to induce weight loss. NAFLD was diagnosed and graded using ultrasound and transaminasemia. Insulin sensitivity and glucose tolerance were assessed using homeostasis model assessment and oral glucose tolerance test. We performed anthropometric measurements and determined body composition using bioimpedance. Data were collected from 71 of 117 children at entry, after the 10 weeks at the camp, and 12 months after the camp ended. RESULTS: The children showed an average weight loss of 7.1 ±â€Š2.7  kg during the camp. At baseline, 43% had ultrasonographic liver steatosis, 50% elevated transaminases (>25  IU/L), and reduced insulin sensitivity. These abnormalities were mutually related and improved significantly during the camp (P ≤ 0.05). Liver fat improvement was sustained at 12 months. At the 12-month follow-up, 17 of 71 (24%) children maintained the body weight. CONCLUSIONS: This short-term diet and exercise program induced weight loss, markedly improved all aspects of the threatening condition of NAFLD, and reduced insulin sensitivity in childhood obesity; 24% of the children maintained weight loss at least until the 12-month follow-up.

Oversized vein grafts develop advanced atherosclerosis in hypercholesterolemic minipigs.

BACKGROUND: Accelerated atherosclerosis is the main cause of late aortocoronary vein graft failure. We aimed to develop a large animal model for the study of pathogenesis and treatment of vein graft atherosclerosis. METHODS: An autologous reversed jugular vein graft was inserted end-to-end into the transected common carotid artery of ten hypercholesteroemic minipigs. The vein grafts were investigated 12-14 weeks later with ultrasound and angiograpy in vivo and microscopy post mortem. RESULTS: One minipig died during follow up (patent vein graft at autopsy), and one vein graft thrombosed early. In the remaining eight patent vein grafts, the mean (standard deviation) intima-media thickness was 712 µm (276 µm) versus 204 µm (74 µm) in the contralateral control internal jugular veins (P < .01). Advanced atherosclerotic plaques were found in three of four oversized vein grafts (diameter of graft > diameter of artery). No plaques were found in four non-oversized vein grafts (P < .05). CONCLUSIONS: Our model of jugular vein graft in the common carotid artery of hypercholesterolemic minipigs displayed the components of human vein graft disease, i.e. thrombosis, intimal hyperplasia, and atherosclerosis. Advanced atherosclerosis, the main cause of late failure of human aortocoronary vein grafts was only seen in oversized grafts. This finding suggests that oversized vein grafts may have detrimental effects on patient outcome.

Renal Artery Stenting in Consecutive High-Risk Patients With Atherosclerotic Renovascular Disease: A Prospective 2-Center Cohort Study.

Background The aim of this study was to prospectively evaluate the effects of renal artery stenting in consecutive patients with severe atherosclerotic renal artery stenosis and high-risk clinical presentations as defined in a national protocol developed in 2015. Methods and Results Since the protocol was initiated, 102 patients have been referred for revascularization according to the following high-risk criteria: severe renal artery stenosis (≥70%) with true resistant hypertension, rapidly declining kidney function, or recurrent heart failure/sudden pulmonary edema. At baseline, the mean 24-hour ambulatory systolic blood pressure was 166.2 mm Hg (95% CI, 162.0-170.4), the defined daily dose of antihypertensive medication was 6.5 (95% CI, 5.8-7.3), and the estimated glomerular filtration rate was 41.1 mL/min per 1.73m2 (95% CI, 36.6-45.6). In 96 patients with available 3-month follow-up data, mean 24-hour ambulatory systolic blood pressure decreased by 19.6 mm Hg (95% CI, 15.4-23.8; P<0.001), the defined daily dose of antihypertensive medication was reduced by 52% (95% CI, 41%-62%; P<0.001), and estimated glomerular filtration rate increased by 7.8 mL/min per 1.73m2 (95% CI, 4.5-11.1; P<0.001). All changes persisted after 24 month follow-up. Among 17 patients with a history of hospitalization for acute decompensated heart failure, 14 patients had no new episodes after successful revascularization. Conclusions In this prospective cohort study, we observed a reduction in blood pressure and antihypertensive medication, an increase in estimated glomerular filtration rate, and a decrease in new hospital admissions attributable to heart failure/sudden pulmonary edema after renal artery stenting. Registration URL: https://clinicaltrials.gov. Identifier: NCT02770066.