The impact of survivorship care plans on adolescent and young adult head and neck cancer survivors and their primary care providers.

PURPOSE: A cross sectional study of adolescent and young adult (AYA) head and neck (H&N) cancer survivors was performed to assess late effects. Survivorship care plans (SCPs) were generated and evaluated by participants and their primary care providers (PCPs). METHODS: AYA H&N survivors who had been discharged over 5 years prior from our institution were assessed in recall consultation by a radiation oncologist. Late effects were assessed and individualized SCPS were created for each participant. Participants completed a survey evaluating the SCP. PCPs were surveyed before the consultation and after evaluating the SCP. RESULTS: 31/36 participants (86%) completed the SCP evaluation. The SCP was considered to be a positive experience for 93% of participants. Most of the AYA participants indicated that the information provided in the SCP helped them understand the need for follow-up to assess late effects (90%). The pre-consultation PCP survey response rate was 13/27 (48%) and only 34% were comfortable in providing survivorship care for AYA H&N cancer patients. The PCP response rate to the survey that accompanied the SCP was 15/27 (55%) and the majority (93%) reported that the SCP would be helpful to care for other AYA and non-AYA cancer survivors in their practice. CONCLUSIONS: Our research suggested that AYA head and neck cancer survivors valued the SCPs as did their PCPs. IMPLICATIONS FOR CANCER SURVIVORS: The introduction of SCPs is likely to help improve survivorship and transitioning of care from the oncology clinic to PCP in this population.

Genetic Variation in 9p21 and the Plasma Proteome.

Single nucleotide polymorphisms (SNPs) in the noncoding region of 9p21 have been associated with cardiovascular disease (CVD), but the mechanisms by which these genetic variants contribute to the pathogenesis of CVD remain unknown since no annotated proteins are present in this region of DNA. The objective of the current study was to determine if 9p21 genotypes are associated with distinct plasma proteins in young adults. Subjects were 1611 young adults aged 20-29 years from the Toronto Nutrigenomics and Health Study (1098 females and 513 males). DNA was isolated from fasting blood to analyze four SNPs in 9p21 (rs2383206, rs10757274, rs10757278, and rs1333049). Abundant plasma proteins ( n = 54) were measured using liquid chromatography multiple reaction monitoring mass spectrometry. Analysis of covariance was used to determine differences in plasma proteins between genotypes. In Caucasians ( n = 524), four SNPs were associated with apolipoprotein E and two with haptoglobin-ß-chain concentration. In East Asians ( n = 388), three SNPs were associated with α-1b-Glycoprotein, two with apolipoprotein B-100, one with apolipoprotein E and one with haptoglobin-ß-chain concentration. In South Asians ( n = 117), one SNP was associated with apolipoprotein B-100 concentration. Our findings suggest that 9p21 genotypes may play a role in various pathophysiological pathways that contribute to risk of CVD in early adulthood that might be distinct among different ethnocultural groups.

Canadian Society of Nephrology commentary on the KDIGO clinical practice guideline for CKD evaluation and management.

We congratulate the KDIGO (Kidney Disease: Improving Global Outcomes) work group on their comprehensive work in a broad subject area and agreed with many of the recommendations in their clinical practice guideline on the evaluation and management of chronic kidney disease. We concur with the KDIGO definitions and classification of kidney disease and welcome the addition of albuminuria categories at all levels of glomerular filtration rate (GFR), the terminology of G categories rather than stages to describe level of GFR, the division of former stage 3 into new G categories 3a and 3b, and the addition of the underlying diagnosis. We agree with the use of the heat map to illustrate the relative contributions of low GFR and albuminuria to cardiovascular and renal risk, though we thought that the highest risk category was too broad, including as it does people at disparate levels of risk. We add an albuminuria category A4 for nephrotic-range proteinuria and D and T categories for patients on dialysis or with a functioning renal transplant. We recommend target blood pressure of 140/90mm Hg regardless of diabetes or proteinuria, and against the combination of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors. We recommend against routine protein restriction. We concur on individualization of hemoglobin A1c targets. We do not agree with routine restriction of sodium intake to <2g/d, instead suggesting reduction of sodium intake in those with high intake (>3.3g/d). We suggest screening for anemia only when GFR is <30mL/min/1.73m(2). We recognize the absence of evidence on appropriate phosphate targets and methods of achieving them and do not agree with suggestions in this area. In drug dosing, we agree with the recommendation of using absolute clearance (ie, milliliters per minute), calculated from the patient's estimated GFR (which is normalized to 1.73m(2)) and the patient's actual anthropomorphic body surface area. We agree with referral to a nephrologist when GFR is <30mL/min/1.73m(2) (and for many other scenarios), but suggest urine albumin-creatinine ratio > 60mg/mmol or proteinuria with protein excretion > 1g/d as the referral threshold for proteinuria.

Abnormal multisensory temporal discrimination in Parkinson's disease.

Cognitive deficits are prevalent in Parkinson's disease (PD), ranging from mild deficits in perception and executive function to severe dementia. Multisensory integration (MSI), the ability to pool information from different sensory modalities to form a combined, coherent perception of the environment, is known to be impaired in PD. This study investigated the disruption of audiovisual MSI in PD patients by evaluating temporal discrimination ability between auditory and visual stimuli with different stimulus onset asynchronies (SOAs). The experiment was conducted with Fifteen PD patients and fifteen age-matched healthy controls where participants were requested to report whether the audiovisual stimuli pairs were temporal simultaneous. The temporal binding window (TBW), the time during which sensory modalities are perceived as synchronous, was adapted as the comparison index between PD patients and healthy individuals. Our results showed that PD patients had a significantly wider TBW than healthy controls, indicating abnormal audiovisual temporal discrimination. Furthermore, PD patients had more difficulty in discriminating temporal asynchrony in visual-first, but not in auditory-first stimuli, compared to healthy controls. In contrast, no significant difference was observed for auditory-first stimuli. PD patients also had shorter reaction times than healthy controls regardless of stimulus priority. Together, our findings point to abnormal audiovisual temporal discrimination, a major component of MSI irregularity, in PD patients. These results have important implications for future models of MSI experiments and models that aim to uncover the underlying mechanism of MSI in patients afflicted with PD.

Unveiling the lead exposure attributed burden in Iran from 1990 to 2019 through the lens of the Global Burden of Disease study 2019.

This study aimed to investigate the estimated burden attributed to lead exposure (LE), at the national and subnational levels from 1990 to 2019 in Iran. The burden attributed to LE was determined through the estimation of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs) and years lived with disability (YLDs) using the comparative risk assessment method of Global Burden of Disease (GBD) study presenting as age-standardized per 100,000 person year (PY) with 95% uncertainty intervals (95% UI). Furthermore, the burden of each disease were recorded independently. Eventually, the age-standardized YLLs, DALYs, deaths and YLDs rates attributed to LE demonstrated a decrease of 50.7%, 48.9%, 38.0%, and 36.4%, respectively, from 1990 to 2019. The most important causes of LE burden are divided into two acute and chronic categories: acute, mainly causes mental disorders (DALYs rate of 36.0 in 2019), and chronic, results in cardiovascular diseases (CVDs) (DALYs rate of 391.8) and chronic kidney diseases (CKDs) (DALYs rate of 26.6), with CVDs bearing the most significant burden. At the sub-national level, a decrease in burden was evident in most provinces; moreover, low and low-middle SDI provinces born the highest burden. The burden increased mainly by ageing and was higher in males than females. It was concluded that although the overall decrease in the burden; still it is high, especially in low and low-middle SDI provinces, in advanced ages and in males. Among IDID, CKDs and CVDs that are the most important causes of LE-attributed burden in Iran; CVDs bear the highest burden.

CYP1A2 Genetic Variation, Coffee Intake, and Kidney Dysfunction.

Importance: Caffeine is detoxified by cytochrome P450 1A2 (CYP1A2), and genetic variation in CYP1A2 impacts the rate of caffeine clearance. Factors that may modify the association between coffee intake and kidney disease remain unclear. Objective: To assess whether CYP1A2 genotype modifies the association between coffee intake and kidney dysfunction. Design, Setting, and Participants: The Hypertension and Ambulatory Recording Venetia Study (HARVEST) was a prospective cohort study of individuals with stage 1 hypertension in Italy; HARVEST began on April 1, 1990, and follow-up is ongoing. The current study used data from April 1, 1990, to June 30, 2006, with follow-up of approximately 10 years. Blood pressure and biochemical data were collected monthly during the first 3 months, then every 6 months thereafter. Data were analyzed from January 2019 to March 2019. Participants were screened and recruited from general practice clinics. The present study included 1180 untreated participants aged 18 to 45 years with stage 1 hypertension; those with nephropathy, diabetes, urinary tract infection, and cardiovascular disease were excluded. Exposures: Coffee intake and CYP1A2 genotype rs762551 were exposures analyzed over a median follow-up of 7.5 (IQR, 3.1-10.9) years. Main Outcomes and Measures: Albuminuria (defined as an albumin level of ≥30 mg/24 h) and hyperfiltration (defined as an estimated glomerular filtration rate of ≥150 mL/min/1.73 m2) were the primary outcomes as indicators of kidney dysfunction. Results: Among 1180 participants, genotyping, lifestyle questionnaires, and urine analysis data were obtained from 604 individuals (438 [72.5%] male) with a mean (SD) age of 33.3 (8.5) years and a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 25.4 (3.4). A total of 158 participants (26.2%) consumed less than 1 cup of coffee per day, 379 (62.7%) consumed 1 to 3 cups per day, and 67 (11.1%) consumed more than 3 cups per day. Genotype frequencies for rs762551 (260 participants [43.1%] with genotype AA, 247 participants [40.8%] with genotype AC, and 97 participants [16.1%] with genotype CC) did not differ between coffee intake categories. The level of risk of developing albuminuria, hyperfiltration, and hypertension, assessed by Cox regression and survival analyses, was not associated with coffee intake in the entire group or among fast metabolizers. The risks of albuminuria (adjusted hazard ratio [aHR], 2.74; 95% CI, 1.63-4.62; P < .001), hyperfiltration (aHR, 2.11; 95% CI, 1.17-3.80; P = .01), and hypertension (aHR, 2.81; 95% CI, 1.51-5.23; P = .001) increased significantly among slow metabolizers who consumed more than 3 cups per day. Conclusions and Relevance: In this study, the risks of albuminuria, hyperfiltration, and hypertension increased with heavy coffee intake only among those with the AC and CC genotypes of CYP1A2 at rs762551 associated with slow caffeine metabolism, suggesting that caffeine may play a role in the development of kidney disease in susceptible individuals.

Flexibility and sensitivity in gene regulation out of equilibrium.

Cells adapt to environments and tune gene expression by controlling the concentrations of proteins and their kinetics in regulatory networks. In both eukaryotes and prokaryotes, experiments and theory increasingly attest that these networks can and do consume bio-chemical energy. How does this dissipation enable cellular behaviors unobtainable in equilibrium? This open question demands quantitative models that transcend thermodynamic equilibrium. Here we study the control of a simple, ubiquitous gene regulatory motif to explore the consequences of departing equilibrium in kinetic cycles. Employing graph theory, we find that dissipation unlocks nonmonotonicity and enhanced sensitivity of gene expression with respect to a transcription factor's concentration. These features allow a single transcription factor to act as both a repressor and activator at different levels or achieve outputs with multiple concentration regions of locally-enhanced sensitivity. We systematically dissect how energetically-driving individual transitions within regulatory networks, or pairs of transitions, generates more adjustable and sensitive phenotypic responses. Our findings quantify necessary conditions and detectable consequences of energy expenditure. These richer mathematical behaviors-feasibly accessed using biological energy budgets and rates-may empower cells to accomplish sophisticated regulation with simpler architectures than those required at equilibrium. Significance Statement: Growing theoretical and experimental evidence demonstrates that cells can (and do) spend biochemical energy while regulating their genes. Here we explore the impact of departing from equilibrium in simple regulatory cycles, and learn that beyond increasing sensitivity, dissipation can unlock more flexible input-output behaviors that are otherwise forbidden without spending energy. These more complex behaviors could enable cells to perform more sophisticated functions using simpler systems than those needed at equilibrium.

Patient-Reported Outcomes in Adolescent and Young Adult Head and Neck Cancer Survivors Treated with Radiotherapy.

Purpose: There are few studies of adolescent and young adult (AYA) head and neck (H&N) cancer survivors treated with radiotherapy. A recall of AYA H&N survivors was performed and this article evaluates their cross-sectional patient-reported outcomes. Methods: AYA H&N cancer survivors who had received radiotherapy in British Columbia between 1970 and 2010 participated in this study. Participants completed the Psychosocial Screen for Cancer-Revised (PSSCAN-R), Research and Development (RAND)-36 health-related quality of life, and the Vanderbilt Head and Neck Symptom Survey, version 2.0 (VHNSS 2.0), to evaluate late effects from treatment. Results: There were 36 participants in the study. Severe symptoms (greater than or equal to 4/10) were reported on the VHNSS 2.0 by 51% of participants for xerostomia, 35% for dysphagia, and 37% for dental/mucosal sensitivity. On the PSSCAN-R, 35% had moderate/high anxiety scores and 48% had moderate/high depression scores. The mean RAND-36 participant scores were as follows: physical functioning, 86.1; physical role functioning, 71.4; emotional role functioning, 75.1; energy/fatigue, 56.6; emotional well-being, 74.6; social functioning, 76.3; bodily pain, 71.7; and general health, 65.6. Conclusions: AYA survivors in our study reported significant late effects from H&N radiotherapy and high depression and anxiety scores, but generally high health-related quality of life. Prospective evaluation of psychosocial needs and H&N-related complications is warranted in this subgroup at high risk of late effects from treatment.

Genetic variation in 9p21, dietary patterns, and insulin sensitivity.

Background: Single nucleotide polymorphisms in the 9p21 region have been associated with cardiovascular disease and to a lesser extent insulin sensitivity. Previous studies have focused on older populations, and few have examined the impact of gene-diet interactions. The objective of this study was to determine the interaction between dietary patterns and 9p21 genotypes on insulin sensitivity in young adults from different ethnic groups. Methods: Subjects were 1,333 participants aged 20-29 years from the Toronto Nutrigenomics and Health Study (405 men and 928 women; 776 Caucasians and 557 East Asians). Fasting blood was collected to measure glucose, insulin, c-reactive protein and serum lipids, as well as to isolate DNA for genotyping subjects for five SNPs in 9p21 (rs10757274, rs10757278, rs1333049, rs2383206, and rs4977574). Insulin resistance (HOMA-IR) and beta-cell dysfunction (HOMA-Beta) were calculated from fasting insulin and glucose concentrations. The Toronto-modified Harvard 196-item semi-quantitative food frequency questionnaire was used to measure dietary intake over 1 month and principal components analysis was used to identify three dietary patterns (Prudent, Western and Eastern). ANOVA and ANCOVA were used to examine gene-diet interactions on markers of insulin sensitivity. Results: Significant gene-diet interactions on insulin sensitivity using HOMA-IR were observed with all five SNPs, which remained significant after adjusting for covariates (p < 0.05). Among those who were homozygous for the 9p21 risk allele (rs1333049), fasting insulin was 40% higher in those who were consuming a low-prudent diet compared to those consuming a high-prudent diet (p < 0.05). No differences were observed between those following a low versus high-prudent diet among those who did not carry a 9p21 risk allele. Similar findings were observed with HOMA-Beta, however, the association was only significant for rs10757274 (p = 0.04). Conclusion: Our findings suggest that a prudent dietary pattern may protect against the effects of 9p21 risk genotypes on insulin sensitivity.

A cross-sectional assessment of long-term effects in adolescent and young adult head and neck cancer survivors treated with radiotherapy.

PURPOSE: Adolescent and young adult (AYA) head and neck (H&N) cancer survivors are at risk of long-term complications. A cross-sectional study of survivors recalled for clinical evaluation was performed to evaluate late effects in this population. METHODS: Surviving patients who had been diagnosed with H&N cancer between the ages of 15 and 39 years and treated with radiation therapy (RT) in British Columbia between 1970 and 2010 were invited to participate in this study. Survivors were assessed in consultation by a radiation oncologist for a complete history and physical exam. Comprehensive data collection of subjective and objective late effects of RT and screening investigations were completed. RESULTS: Of 36 AYA H&N participants, the majority were female (61%), and the most common tumour sites were thyroid (28%), oropharynx (17%), salivary gland (14%) and larynx (14%). Dental extractions post treatment was performed for 33% and dental implants for 17%. The majority (72%) reported xerostomia, 50% had dysphagia to solids and 25% hearing loss. Of the non-thyroid cancer patients who underwent RT to their neck, 45% developed hypothyroidism. There were 28% of participants with asymptomatic carotid stenosis and 27% with thyroid nodules; all were diagnosed after recall screening. CONCLUSIONS: Survivors of AYA H&N cancer treated with RT reported numerous long-term complications. Comprehensive follow-up and screening guidelines should be established for this at-risk population. IMPLICATIONS FOR CANCER SURVIVORS: AYA H&N cancer survivors and their primary care practitioners should be educated on screening recommendations and the risk of late effects.

Automatic detection of brachytherapy seeds in 3D ultrasound images using a convolutional neural network.

A novel approach for automatic localization of brachytherapy seeds in 3D transrectal ultrasound (TRUS) images, using machine learning based algorithm, is presented. 3D radiofrequency ultrasound signals were collected from 13 patients using the linear array of the TRUS probe during the brachytherapy procedure in which needles are used for insertion of stranded seeds. Gold standard for the location of seeds on TRUS data were obtained with the guidance of the complete reconstruction of the seed locations from multiple C-arm fluoroscopy views and used in the creation of the training set. We designed and trained a convolutional neural network (CNN) model that worked on 3D cubical sub-regions of the TRUS images, that will be referred to as patches, representing seed, non-seed within a needle track and non-seed elsewhere in the images. The models were trained with these patches to detect the needle track first and then the individual seeds within the needle track. A leave-one-out cross validation approach was used to test the model on the data from eight of the patients, for whom accurate seed locations were available from fluoroscopic imaging. The total inference time was about 7 min for needle track detection in each patient's image and approximately 1 min for seed detection in each needle, leading to a total seed detection time of less than 15 min. Our seed detection algorithm achieved [Formula: see text] precision, [Formula: see text] recall and [Formula: see text] F1_score. The results from our CNN-based method were compared to manual seed localization performed by an expert. The CNN model yielded higher precision (lower false discovery rate) compared to the manual method. The automated approach requires little modification to the current clinical setups and offers the prospect of application in real time intraoperative dosimetric analysis of the implant.

Canadian Society of Nephrology Commentary on the Kidney Disease Improving Global Outcomes 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder.

PURPOSE OF REVIEW: (1) To provide commentary on the 2017 update to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD); (2) to apply the evidence-based guideline update for implementation within the Canadian health care system; (3) to provide comment on the care of children with chronic kidney disease (CKD); and (4) to identify research priorities for Canadian patients. SOURCES OF INFORMATION: The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD. METHODS: The commentary committee co-chairs selected potential members based on their knowledge of the Canadian kidney community, aiming for wide representation from relevant disciplines, academic and community centers, and different geographical regions. KEY FINDINGS: We agreed with many of the recommendations in the clinical practice guideline on the diagnosis, evaluation, prevention, and treatment of CKD-MBD. However, based on the uncommon occurrence of abnormalities in calcium and phosphate and the low likelihood of severe abnormalities in parathyroid hormone (PTH), we recommend against screening and monitoring levels of calcium, phosphate, PTH, and alkaline phosphatase in adults with CKD G3. We suggest and recommend monitoring these parameters in adults with CKD G4 and G5, respectively. In children, we agree that monitoring for CKD-MBD should begin in CKD G2, but we suggest measuring ionized calcium, rather than total calcium or calcium adjusted for albumin. With regard to vitamin D, we suggest against routine screening for vitamin D deficiency in adults with CKD G3-G5 and G1T-G5T and suggest following population health recommendations for adequate vitamin D intake. We recommend that the measurement and management of bone mineral density (BMD) be according to general population guidelines in CKD G3 and G3T, but we suggest against routine BMD testing in CKD G4-G5, CKD G4T-5T, and in children with CKD. Based on insufficient data, we also recommend against routine bone biopsy in clinical practice for adults with CKD or CKD-T, or in children with CKD, although we consider it an important research tool. LIMITATIONS: The committee relied on the evidence summaries produced by KDIGO. The CSN committee did not replicate or update the systematic reviews.

JUSTIFICATION: (1) Commenter les recommandations du KDIGO 2017 (Kidney Disease Improving Global Outcomes) sur les bonnes pratiques cliniques pour le diagnostic, l'évaluation et le traitement des troubles du métabolisme minéral osseux associés aux maladies rénales chroniques (TMO-MRC); (2) appliquer les lignes directrices actualisées et fondées sur les données probantes en vue de leur mise en œuvre dans le système de soins de santé canadien; (3) commenter les soins prodigués aux enfants atteints d'insuffisance rénale chronique (IRC) et (4) définir les priorités de recherche des patients Canadiens. SOURCES: Les recommandations du KDIGO 2017 (Kidney Disease Improving Global Outcomes) sur les bonnes pratiques cliniques pour le diagnostic, l'évaluation et le traitement des troubles du métabolisme minéral osseux associés aux maladies rénales chroniques (TMO-MRC). MÉTHODOLOGIE: Les coprésidents du comité ont sélectionné les membres potentiels sur la base de leur connaissance du secteur de la santé rénale au Canada, tout en visant une bonne représentation de toutes les disciplines concernées, des centres universitaires et communautaires et des différentes régions géographiques. PRINCIPAUX COMMENTAIRES: Nous approuvons un grand nombre des recommandations du KDIGO. Cependant, compte tenu de la rareté des anomalies du calcium et du phosphate et de la faible probabilité d'anomalies graves de la PTH (hormone parathyroïde), nous déconseillons le dépistage et la surveillance des taux de calcium, de phosphate, de PTH et de phosphatase alcaline chez les adultes atteints d'IRC de stade G3. Nous suggérons de mesurer ces paramètres chez les adultes de stade G4 et nous le recommandons pour les patients de stade G5. Chez les enfants, nous appuyons la recommandation de commencer la surveillance des TMO-MRC dès le stade G2, mais nous suggérons de mesurer le calcium ionisé plutôt que les taux de calcium total ou de calcium corrigé en fonction de l'albumine. En ce qui concerne la vitamine D, nous déconseillons le dépistage de routine des carences chez les adultes atteints d'IRC de stade G3 à G5 et G1T à G5T; nous suggérons plutôt de suivre les recommandations visant la population générale pour un apport adéquat en vitamine D. Nous recommandons que la mesure et la prise en charge de la densité minérale osseuse (DMO) se fassent en suivant les recommandations pour la population générale chez les adultes atteints d'IRC de stade G3 et G3T, mais nous déconseillons les tests de DMO de routine chez les adultes de stades G4-G5 et G4T-G5T, de même que chez les enfants atteints d'IRC. En raison de données insuffisantes, nous déconseillons également la pratique systématique d'une biopsie osseuse chez les adultes atteints d'IRC ou d'IRC-TMO, ainsi que chez les enfants atteints d'IRC, bien que nous la considérions comme un important outil de recherche. LIMITES: Le comité s'est appuyé sur le résumé des preuves rédigé par le KDIGO. Le comité de la SCN n'a pas reproduit ou mis à jour les revues systématiques.

Accurate and robust deep learning-based segmentation of the prostate clinical target volume in ultrasound images.

The goal of this work was to develop a method for accurate and robust automatic segmentation of the prostate clinical target volume in transrectal ultrasound (TRUS) images for brachytherapy. These images can be difficult to segment because of weak or insufficient landmarks or strong artifacts. We devise a method, based on convolutional neural networks (CNNs), that produces accurate segmentations on easy and difficult images alike. We propose two strategies to achieve improved segmentation accuracy on difficult images. First, for CNN training we adopt an adaptive sampling strategy, whereby the training process is encouraged to pay more attention to images that are difficult to segment. Secondly, we train a CNN ensemble and use the disagreement among this ensemble to identify uncertain segmentations and to estimate a segmentation uncertainty map. We improve uncertain segmentations by utilizing the prior shape information in the form of a statistical shape model. Our method achieves Hausdorff distance of 2.7 ±â€¯2.3 mm and Dice score of 93.9 ±â€¯3.5%. Comparisons with several competing methods show that our method achieves significantly better results and reduces the likelihood of committing large segmentation errors. Furthermore, our experiments show that our approach to estimating segmentation uncertainty is better than or on par with recent methods for estimation of prediction uncertainty in deep learning models. Our study demonstrates that estimation of model uncertainty and use of prior shape information can significantly improve the performance of CNN-based medical image segmentation methods, especially on difficult images.

Associations of Calcium from Food Sources Versus Phosphate Binders with Serum Calcium and FGF23 in Hemodialysis Patients.

BACKGROUND: Dysregulated serum calcium and FGF23 are associated with increased mortality and morbidity rates in patients receiving hemodialysis. Preliminary data suggest serum calcium regulates FGF23 secretion independently of serum phosphate, parathyroid hormone, and 25-OH vitamin D. It is unclear to what extent dietary and prescription sources of calcium influence calcium and FGF23 levels, and whether they confound this relationship. In this cross-sectional analysis of a multi-ethnic cohort of prevalent hemodialysis patients, association of dietary calcium and prescribed calcium were examined against serum calcium and FGF23. Bi- and multivariable linear regression was used for all analyses. RESULTS: 81 patients (mean age 58 years, dialysis vintage 2 years, 51 men) participated. Dietary calcium was inversely associated with FGF23 (p = 0.04) however association of FGF23 with prescribed calcium did not reach statistical significance (0.08). In multivariable models, dietary calcium and prescribed calcium were associated in opposing directions with serum calcium (prescribed calcium; ß-coefficient = -0.35, p = 0.005 versus dietary calcium; ß-coefficient = 0.35, p = 0.03). FGF23 was independently associated with serum calcium (p = 0.007). CONCLUSIONS: We found differing, sometimes opposing, associations between serum calcium and FGF23 levels when considering prescribed versus dietary sources of calcium. Serum calcium and FGF23 were strongly correlated regardless of possible confounders examined in this hemodialysis cohort. Dietary calcium was associated with higher serum calcium and lower FGF23 concentrations, while prescribed calcium was only inversely associated with serum calcium. Further studies are required to confirm these associations and determine causality.

Associations between echocardiographic findings and prospective changes in residual renal function in patients new to peritoneal dialysis.

Although echocardiograms are often performed when peritoneal dialysis is started, associations between commonly reported findings and prospective changes in renal function remain understudied. Ninety-nine of 101 patients in the Trio Trial had transthoracic echocardiograms within 6 months of dialysis initiation, and measurements of residual renal function every six weeks for up to two years. Generalized mixed modelling linear regression in STATA was used to examine associations between left atrial size, left ventricular hypertrophy, left ventricular ejection fraction, right ventricular systolic pressure, and left valvular calcification with subsequent slopes in renal function. After echocardiography (performed a median of 16 days following peritoneal dialysis initiation) right ventricular systolic pressure was associated with faster, while declining left ventricular ejection fraction and valvular calcification were associated with slower declines in residual renal function. Future studies could be conducted to confirm these findings, and identify pathophysiological mechanisms.

Genetic variation in 9p21 is associated with fasting insulin in women but not men.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the 9p21 region have been associated with cardiovascular disease (CVD), but previous studies have focussed on older populations. The objective of this study was to determine the association between 9p21 genotypes and biomarkers of CVD risk in young adults from different ethnocultural groups. METHODS: Subjects were 1,626 participants aged 20-29 years from the Toronto Nutrigenomics and Health Study. Fasting blood was collected to measure glucose, insulin, c-reactive protein and serum lipids, as well as to isolate DNA for genotyping subjects for five SNPs in 9p21. Analyses were conducted for the entire population and separately for women (n = 1,109), men (n = 517), Caucasians (n = 771), East Asians (n = 561) South Asians (n = 175) and Others (n = 119). ANOVA and ANCOVA were used to examine if 9p21 genotypes were associated with biomarkers of CVD risk. RESULTS: In the entire group, the risk alleles of rs10757278 and rs2383206 were associated with higher mean insulin (p = 0.01). Risk alleles for rs4977574, rs10757278, rs2383206, rs1333049 and rs10757274 were associated with higher serum insulin in women (p = 0.008, p = 0.008, p = 0.0003, p = 0.002, and p = 0.001, respectively), but not in men (p = 0.41, p = 0.13, p = 0.31, p = 0.34, and 0.35, respectively). The association between 9p21 and insulin remained significant among women not taking hormonal contraceptives (HC), but was not significant among women taking HCs. CONCLUSION: Our findings suggest that 9p21 genotypes may play a role in the development of insulin resistance in early adulthood among women, but not men, and the effects appear to be attenuated by HC use.

Prostate segmentation in transrectal ultrasound using magnetic resonance imaging priors.

PURPOSE: In the current standard of care, real-time transrectal ultrasound (TRUS) is commonly used for prostate brachytherapy guidance. As TRUS provides limited soft tissue contrast, segmenting the prostate gland in TRUS images is often challenging and subject to inter-observer and intra-observer variability, especially at the base and apex where the gland boundary is hard to define. Magnetic resonance imaging (MRI) has higher soft tissue contrast allowing the prostate to be contoured easily. In this paper, we aim to show that prostate segmentation in TRUS images informed by MRI priors can improve on prostate segmentation that relies only on TRUS images. METHODS: First, we compare the TRUS-based prostate segmentation used in the treatment of 598 patients with a high-quality MRI prostate atlas and observe inconsistencies at the apex and base. Second, motivated by this finding, we propose an alternative TRUS segmentation technique that is fully automatic and uses MRI priors. The algorithm uses a convolutional neural network to segment the prostate in TRUS images at mid-gland, where the gland boundary can be clearly seen. It then reconstructs the gland boundary at the apex and base with the aid of a statistical shape model built from an MRI atlas of 78 patients. RESULTS: Compared to the clinical TRUS segmentation, our method achieves similar mid-gland segmentation results in the 598-patient database. For the seven patients who had both TRUS and MRI, our method achieved more accurate segmentation of the base and apex with the MRI segmentation used as ground truth. CONCLUSION: Our results suggest that utilizing MRI priors in TRUS prostate segmentation could potentially improve the performance at base and apex.

The Trio Trial - A Randomized Controlled Clinical Trial Evaluating the Effect of a Biocompatible Peritoneal Dialysis Solution on Residual Renal Function.

UNLABELLED: ♦ BACKGROUND AND OBJECTIVE: Residual renal function (RRF) correlates with mortality and morbidity rates in patients receiving peritoneal dialysis (PD). We examined the effect of a biocompatible PD solution (Gambrosol Trio; Gambro Lundia AB, Lund, Sweden) with lower concentrations of glucose degradation products on rates of decline in RRF. ♦ DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Incident patients at 2 centers in Canada and 1 in Hong Kong were randomized (by minimization) in an open-label parallel group trial to receive Gambrosol Trio or standard PD solution (Dianeal; Baxter Healthcare, Mississauga, Canada) for 2 years. Primary outcome was slope of RRF. Secondary outcomes were urine volumes, fluid and nutrition indices, PD and membrane characteristics, peritonitis rates, adverse events, and PD technique survival. ♦ RESULTS: Residual renal function declined by 0.132 mL/minute/1.73 m(2)/month in 51 patients allocated to biocompatible, and 0.174 mL/minute/1.73 m(2)/month in 50 patients allocated to standard PD solution (difference 0.042 mL/minute/1.73 m(2)/month, p = 0.001). Urine volume, body mass index, normalized protein catabolic rates, and fat mass were higher; total body water, peritoneal ultrafiltration, and D/P creatinine did not differ; and serum phosphate, rates of icodextrin, and automated cycler use were lower with Gambrosol Trio use. There were more peritonitis events with Gambrosol Trio use, while PD technique survival did not differ between groups. ♦ CONCLUSIONS: The use of the biocompatible PD solution Gambrosol Trio was associated with slower rates of decline in RRF, fluid and nutrition benefits, and increased peritonitis rates. TRIAL NUMBER: ISRCTN26252543.

MgCaCO3 versus CaCO3 in peritoneal dialysis patients--a cross-over pilot trial.

BACKGROUND: Despite adverse effects such as constipation, vascular calcification, and hypercalcemia, calcium-based salts are relatively affordable and effective phosphate binders that remain in widespread use in the dialysis population. We conducted a pilot study examining whether the use of a combined magnesium/calcium-based binder was as effective as calcium carbonate at lowering serum phosphate levels in peritoneal dialysis (PD) patients. METHODS: This was a cross-over, investigator-masked pilot study in which prevalent PD patients received calcium carbonate alone (200 mg calcium per tablet) or calcium magnesium carbonate (100 mg calcium, 85 mg magnesium per tablet). Primary outcome was serum phosphate level at 3 months. Analysis was as per protocol. RESULTS: Twenty patients were recruited, 17 completed the study. Mean starting dose was 11.35 ± 7.04 pills per day of MgCaCO3 and 9.00 ± 4.97 pills per day of CaCO3. Mean phosphate levels fell from 2.13 mmol/L to 2.01 mmol/L (95% confidence interval (CI): 1.76 - 2.30, p = 0.361) in the MgCaCO3 group, and 1.81 mmol/L (95% CI: 1.56 - 2.0, p = 0.026) in the CaCO3 alone group. Six (35%) patients taking MgCaCO3 and 9 (54%) taking CaCO3 alone achieved Kidney Disease Outcomes Quality Initiative (KDOQI) serum phosphate targets at 3 months. Diarrhea developed in 9 patients taking MgCaCO3 and 3 taking CaCO3. Serum magnesium exceeded 1.4 mmol/L in 5 patients taking MgCaCO3 while serum calcium exceeded 2.65 mmol/L in 3 patients receiving CaCO3. When compared to the initial dose, the prescribed dose at 3 months was reduced by 44% (to 6.41 tablets/day) in the MgCaCO3 group and by 8% (to 8.24 pills per day) in the CaCO3 alone group. CONCLUSION: Compared with CaCO3 alone, the preparation and dose of MgCaCO3 used in this pilot study was no better at lowering serum phosphate levels in PD patients, and was associated with more dose-limiting side effects.

Intra-operative prostate brachytherapy dosimetry based on partial seed localization in ultrasound and registration to C-arm fluoroscopy.

Intraoperative dosimetry during prostate brachytherapy is a long standing clinical problem. We propose a novel framework to address this problem by reliable detection of a subset of seeds from 3D transrectal ultrasound and registration to fluoroscopy. Seed detection in ultrasound is achieved through template matching in the RF ultrasound domain followed by thresholding and spatial filtering based on the fixed distance between stranded seeds. This subset of seeds is registered to the complete reconstruction of the implant in C-arm fluoroscopy. We report results, validated with a leave-one-needle-out approach, both in a phantom (average post-registration seed distance of 2.5 mm) and in three clinical patient datasets (average error: 3.9 mm over 113 seeds).