Differences Between MR Brain Region Segmentation Methods: Impact on Single-Subject Analysis.

For the segmentation of magnetic resonance brain images into anatomical regions, numerous fully automated methods have been proposed and compared to reference segmentations obtained manually. However, systematic differences might exist between the resulting segmentations, depending on the segmentation method and underlying brain atlas. This potentially results in sensitivity differences to disease and can further complicate the comparison of individual patients to normative data. In this study, we aim to answer two research questions: 1) to what extent are methods interchangeable, as long as the same method is being used for computing normative volume distributions and patient-specific volumes? and 2) can different methods be used for computing normative volume distributions and assessing patient-specific volumes? To answer these questions, we compared volumes of six brain regions calculated by five state-of-the-art segmentation methods: Erasmus MC (EMC), FreeSurfer (FS), geodesic information flows (GIF), multi-atlas label propagation with expectation-maximization (MALP-EM), and model-based brain segmentation (MBS). We applied the methods on 988 non-demented (ND) subjects and computed the correlation (PCC-v) and absolute agreement (ICC-v) on the volumes. For most regions, the PCC-v was good ( > 0.75 ), indicating that volume differences between methods in ND subjects are mainly due to systematic differences. The ICC-v was generally lower, especially for the smaller regions, indicating that it is essential that the same method is used to generate normative and patient data. To evaluate the impact on single-subject analysis, we also applied the methods to 42 patients with Alzheimer's disease (AD). In the case where the normative distributions and the patient-specific volumes were calculated by the same method, the patient's distance to the normative distribution was assessed with the z-score. We determined the diagnostic value of this z-score, which showed to be consistent across methods. The absolute agreement on the AD patients' z-scores was high for regions of thalamus and putamen. This is encouraging as it indicates that the studied methods are interchangeable for these regions. For regions such as the hippocampus, amygdala, caudate nucleus and accumbens, and globus pallidus, not all method combinations showed a high ICC-z. Whether two methods are indeed interchangeable should be confirmed for the specific application and dataset of interest.

Towards automated extraction of 2D standard fetal head planes from 3D ultrasound acquisitions: A clinical evaluation and quality assessment comparison.

INTRODUCTION: Clinical evaluation of deep learning (DL) tools is essential to compliment technical accuracy metrics. This study assessed the image quality of standard fetal head planes automatically-extracted from three-dimensional (3D) ultrasound fetal head volumes using a customised DL-algorithm. METHODS: Two observers retrospectively reviewed standard fetal head planes against pre-defined image quality criteria. Forty-eight images (29 transventricular, 19 transcerebellar) were selected from 91 transabdominal fetal scans (mean gestational age = 26 completed weeks, range = 20+5-32+3 weeks). Each had two-dimensional (2D) manually-acquired (2D-MA), 3D operator-selected (3D-OS) and 3D-DL automatically-acquired (3D-DL) images. The proportion of adequate images from each plane and modality, and the number of inadequate images per plane was compared for each method. Inter and intra-observer agreement of overall image quality was calculated. RESULTS: Sixty-seven percent of 3D-OS and 3D-DL transventricular planes were adequate quality. Forty-five percent of 3D-OS and 55% of 3D-DL transcerebellar planes were adequate. Seventy-one percent of 3D-OS and 86% of 3D-DL transventricular planes failed with poor visualisation of intra-cranial structures. Eighty-six percent of 3D-OS and 80% of 3D-DL transcerebellar planes failed due to inadequate visualisation of cerebellar hemispheres. Image quality was significantly different between 2D and 3D, however, no significant difference between 3D-modalities was demonstrated (p < 0.005). Inter-observer agreement of transventricular plane adequacy was moderate for both 3D-modalities, and weak for transcerebellar planes. CONCLUSION: The 3D-DL algorithm can automatically extract standard fetal head planes from 3D-head volumes of comparable quality to operator-selected planes. Image quality in 3D is inferior to corresponding 2D planes, likely due to limitations with 3D-technology and acquisition technique. IMPLICATIONS FOR PRACTICE: Automated image extraction of standard planes from US-volumes could facilitate use of 3DUS in clinical practice, however image quality is dependent on the volume acquisition technique.

Design and methods of the REMOVAL-HD study: a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients.

BACKGROUND: Removal of uraemic toxins is inadequate using current dialysis strategies. A new class of dialysis membranes have been developed that allow clearance of larger middle molecules. The REMOVAL-HD study (a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients) will address safety, efficacy and the impact on patient-centred outcomes with the use of a mid cut-off (MCO) dialyser in a chronic haemodialysis (HD) population. METHODS: REMOVAL-HD is an open label, prospective, non-randomised, single-arm, multi-centre device study in 85 chronic HD participants. All visits will be conducted during regular HD sessions and participants will undergo a 1 month wash-in period using a standardised high flux dialyser, 6 months of intervention with a MCO dialyser and 1 month of wash-out using a high flux dialyser. The primary endpoint is change in pre-dialysis concentrations of serum albumin, with secondary endpoints including the efficacy of clearance of free light chains and ß-2 microglobulin, and patient-centred outcomes including quality of life, symptom burden, functional status, nutritional status, hospitalisation and death. DISCUSSION: MCO dialysers are a novel form of HD membrane. The REMOVAL-HD study is a pivotal study designed to monitor the immediate and medium-term effects following exposure to this dialyser. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482 . Date of registration - 21/06/2016.

Urinary Tract Infections in the First Year Post-Kidney Transplantation: Potential Benefits of Treating Asymptomatic Bacteriuria.

BACKGROUND: Urinary tract infections (UTIs) are the commonest infectious complication in kidney transplant recipients (KTRs). No recommendations exist regarding treatment of asymptomatic bacteriuria. We aimed to identify potential risk factors and microbiological profile for UTIs, the role of treatment of asymptomatic bacteriuria, and effects on graft outcomes of bacteriuria within the first year post-transplantation. METHODS: We performed a retrospective analysis of UTIs in KTRs transplanted between January 2012 and December 2013 in 2 transplantation centers. Patients were routinely commenced on prophylactic sulfamethoxazole-trimethoprim. Clinical and microbiological data were analyzed for the first year following transplantation. RESULTS: In all, 276 KTRs were evaluated; 67% were men, with a mean age of 51 years. At 12 months post-transplantation 158 (57%) KTRs had no bacteriuria, 75 (27%) had asymptomatic bacteriuria, 21 (8%) had symptomatic UTIs without further complication, and 22 (8%) with UTIs developed either pyelonephritis or urosepsis. Most frequent pathogens identified were Enterococcus faecalis and Escherichia coli, and 36% of organisms were multidrug resistant. Female sex was a risk factor for infection (P = .002), and presence of a double-J ureteral stent significantly increased the risk of asymptomatic bacteriuria and symptomatic UTIs (P = .003). Diabetes, age, and prior transplantation did not increase risk. Presence of infection was not associated with increased rejection, with similar renal function at 12 months. For episodes of bacteriuria (n = 420, asymptomatic n = 324), untreated asymptomatic bacteriuria (n = 185) followed by symptomatic UTI with the same organism was significantly higher (P = .002) compared with cases of treated asymptomatic bacteriuria (n = 139). CONCLUSION: Bacteriuria post-kidney transplantation is common, affecting nearly half of KTRs in the first year after transplantation. Treatment of asymptomatic bacteriuria may be beneficial to prevent subsequent episodes of symptomatic UTIs.

Parenteral iron polymaltose changes i:c-terminal FGF23 ratios in iron deficiency, but not in dialysis patients.

BACKGROUND/OBJECTIVES: Iron and phosphate are both vital to many biological cellular processes with central roles in energy metabolism, cellular proliferation and nucleic acid synthesis. Regulatory pathways in some of these metabolic pathways may intersect at fibroblast growth factor 23 (FGF23), a major phosphate regulatory hormone. Iron is reported to induce hypophosphataemia in rare cases, and recent reports suggest that iron deficiency may upregulate FGF23 synthesis by mechanisms involving hypoxia-inducible factor 1α (HIF1α). Our objective was to evaluate the effect of administration of intravenous iron polymaltose on intact and c-terminal FGF23 (i:cFGF23) ratios in two independent cohorts of patients, iron-deficient but non-inflamed patients and haemodialysis (HD)-dependent patients, and to examine the balance of synthesis and degradation. SUBJECTS/METHODS: We studied biochemical effects of intravenous iron polymaltose on both iFGF23 and cFGF23 fragments and their ratios in two patient groups: iron-deficient patients with normal renal function (ID-norm) and HD patients receiving iron supplementation (HD-ESKD) at a single institution. Patients were tested at baseline, day 4 and day 12 post iron administration. RESULTS: Parenteral iron polymaltose resulted in increased i:cFGF23 ratios in ID-norm patients where circulating cFGF23 levels decreased with no appreciable effect on iFGF23, whereas no significant changes in i:cFGF23 ratios were observed in HD-ESKD patients following intravenous administration of 100mg iron polymaltose. CONCLUSIONS: Dysregulation of intracellular FGF23-processing mechanisms may be related to iron deficiency per se rather than iron repletion with iron polymaltose. In ID-norm, i:cFGF23 ratios altered with iron administration without significant clinical alterations in mineral parameters, implying that other regulatory mechanisms may be important. Finally, iron supplementation in HD-ESKD patients does not appear to significantly affect i:cFGF23 ratios already disturbed by a chronic inflammatory or functionally iron-deficient state.

Increase in nephrology advanced trainee numbers in Australia and associated reduction in clinical exposure over the past decade.

BACKGROUND: Advanced training in nephrology should provide broad experience in all aspects of nephrology. In Australia, the Specialist Advisory Committee in Nephrology oversees nephrology training, and recent increases in advanced trainee numbers have led to concern about dilution of training experience. No study has examined variations in clinical exposure for nephrology trainees in Australia. AIM: To assess the changes in nephrology advanced training in Australia with respect to trainee numbers and exposure to patients and procedures over the past 10 years. METHODS: A retrospective study was performed by obtaining all available Royal Australasian College of Physician supervisor reports from 2000 to 2010 to determine differences in clinical exposure and procedures performed by nephrology trainees. RESULTS: Five hundred and forty-two reports were reviewed involving 208 nephrology trainees in Australia across 53 different training sites. In 2000, 22 trainees were undertaking a core clinical year of training. Trainee numbers have steadily risen from 33 in 2004 to 84 in 2010. The greatest increases have occurred in New South Wales, Victoria and Queensland (sixfold, threefold and fivefold increases respectively). Trainee exposure to dialysis patients has gradually decreased in the past decade. The average number per trainee per year in 2000 compared with 2010 were 66 versus 43 (P = 0.02) and 28 versus 16 (P = 0.01) for haemodialysis and peritoneal dialysis respectively. Acute kidney injury cases per trainee showed a gradual nonsignificant reduction over time and average procedural numbers per trainee decreased significantly from 2000 to 2010 with fewer temporary dialysis catheters inserted per year (39 vs 10, P < 0.01) and fewer renal biopsies performed per year (65 vs 41, P < 0.01). The proportion of trainees working in a hospital that does not provide exposure to acute transplantation has steadily increased from 15% in 2003 to 44% in 2010. CONCLUSIONS: There has been a dramatic and significant increase in nephrology advanced trainee numbers over the past decade at a more rapid rate than the growth in dialysis and transplant patient numbers. This study suggests that training experience has diminished over the past decade and supports a 3-year core clinical nephrology training programme in Australia.