bluuebunny/crossref_metadata_2025_split huggingface dataset:
1309-P: Utilizing a Clinical Decision Support System for Hypoglycemia Management
Authors: GIBBS JACQUELYN R. , BERGER KIMBERLY , FALCIGLIA MERCEDES 
Published: June 2019

Per American Diabetes Association guidelines, every hospital should adopt a hypoglycemia management protocol and all episodes of hypoglycemia should be documented in the medical record and tracked. Chart audit findings at a large urban acute care hospital revealed that nurses were not always compliant with documentation and/or adherence to the hypoglycemia treatment protocol. Thus, a quality improvement (QI) project was implemented to improve documentation compliance and adherence to the treatment protocol.
A clinical decision support system (CDSS) was embedded into the electronic health record (EHR) to enable the treatment protocol to be visible to nurses at the point of care and a hypoglycemia flow sheet was implemented for documentation. Retrospective chart reviews (n=150) were conducted prior to and after implementation of the QI project to determine if the CDSS and flow sheet were associated with changes in compliance. Chart review evaluated the number of episodes were interventions were documented utilizing the required method and if the hypoglycemia treatment protocol was followed, not followed, or unclear.
The CDSS was associated with improvements in both documentation compliance, (72 to 87%) and adherence to the treatment protocol for hypoglycemia, (54 to 69%). There was a statistically significant relationship between the type of documentation utilized (pre-implementation vs. post implementation) and whether or not the treatment protocol was followed, not followed, or unclear (p=0.0003).
Incorporating a CDSS into the EHR may help nurses comply with management of hypoglycemia and its documentation. Hypoglycemia during hospitalization poses a risk to patient safety, therefore additional strategies should be explored to further improve adherence to hypoglycemia treatment protocols.

Disclosure
J.R. Gibbs: None. K. Berger: None. M. Falciglia: None.
1310-P: Outcomes Before and After Implementation of a Comprehensive Multidisciplinary Cardiovascular Diabetes Program among Patients with Diabetes Undergoing Coronary Artery Bypass Grafting (CABG)
Authors: SIRAJ ELIAS S. , NELSON AARON , BRUSH JOHN E. , ULLAL JAGDEESH , LAMICHHANE RAJAN , SHEEHAN BRYNN E. 
Published: June 2019

Background: Most studies demonstrating the benefit of perioperative glycemic control in patients undergoing CABG have primarily focused on inpatient glucose management protocols only. Our study evaluated outcomes before and after implementation of an innovative, comprehensive cardiovascular diabetes program in patients with diabetes undergoing CABG.
Methods: In March 2015, Sentara Heart Hospital and Eastern Virginia Medical School implemented a Multidisciplinary Cardiovascular Diabetes Program. The inpatient aspect focuses on patient education and optimizing glycemic control with the use of Glucommander, an electronic glucose management system. Representatives from endocrinology, cardiology and cardiothoracic surgery meet monthly to review outcomes and develop policy. Patients return for a visit with the surgical and endocrine teams 1-2 weeks after discharge, followed by cardiac rehabilitation. Our retrospective study was designed to compare clinical outcomes for the period of 2 years pre- and 2 years post-implementation of the program. Data from 1013 patients (444 pre; 569 post) were extracted from the Society of Thoracic Surgeons CABG database and the EPIC electronic health record.
Results: After implementation of the program, the frequency of blood glucose values &lt;70 mg/dl was reduced by 42% (from 1.52% to 0.89%; p &lt; 0.001) and the length of stay (LOS) decreased from 12.4 days to 11.2 days (p = 0.026). Multiple regression analyses showed the post-implementation period was associated with shorter LOS and reduced hospital charges. Poor glycemic control, infections and cardiovascular complications had a negative effect on LOS, readmissions and hospital charges.
Conclusion: The implementation of a comprehensive, multidisciplinary program for patients with diabetes undergoing CABG resulted in significantly less hypoglycemia, shorter LOS and reduced hospital charges.

Disclosure
E.S. Siraj: Advisory Panel; Self; Sanofi. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. A. Nelson: None. J.E. Brush: None. J. Ullal: None. R. Lamichhane: None. B.E. Sheehan: None.

Funding
EVMS-Sentara Healthcare Analytics and Delivery Science Institute
132-OR: Effects of Dapagliflozin, an SGLT2 Inhibitor, on Hepatic Steatosis and Fibrosis Evaluated by Transient Elastography in Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease
Authors: ASO YOSHIMASA , JOJIMA TERUO , IIJIMA TOSHIE , USUI ISAO 
Published: June 2019

Objective: To investigate the effects of dapagliflozin on liver steatosis and fibrosis evaluated in patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD).
Research Design and Methods: In a randomized, active-controlled, open-label trial, 57 patients with type 2 diabetes and NAFLD were randomized to a dapagliflozin (5 mg/day) group (n=33) or to the control group (n=24) and were treated for 24 weeks. Hepatic steatosis and fibrosis were assessed by using a transient elastography (FibroScan) to measure the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively.
Results: At baseline, LSM was positively correlated with several markers and scoring systems for liver fibrosis in a total of 57 patients with T2D and NAFLD. In week 24, CAP showed a significant decrease from 314±61 to 290±73 dB/m (P=0.0424) in the dapagliflozin group, while there was no significant change in the control group. In addition, LSM tended to decrease from 9.49±6.05 kPa to 8.01±5.78 kPa in the dapagliflozin group. In 14 patients from this group with LS values ≥8.0 kPa, indicating significant liver fibrosis, LSM decreased significantly from 14.7±5.7 to 11.0±7.3 kPa (P=0.0158). Furthermore, serum alanine aminotransferase and γ-glutamyltranspeptidase levels decreased in the dapagliflozin group, but not in the control group, and visceral fat mass was significantly reduced in the dapagliflozin group.
Conclusions: Based on these findings, the SGLT2 inhibitor dapagliflozin improves liver steatosis in parallel with a decrease of liver enzymes in patients with type 2 diabetes and NAFLD, and attenuates liver fibrosis in only patients with significant liver fibrosis. (UMIN000022155)

Disclosure
Y. Aso: Research Support; Self; Ono Pharmaceutical Co., Ltd. T. Jojima: None. T. Iijima: None. I. Usui: None.
1326-P: Metformin Increases GLP-1 Concentrations and Improves Glycemia in Youth with Type 2 Diabetes
Authors: CRAVALHO CELESTE K. , MEYERS ABBY G. , MABUNDO LILIAN , COURVILLE AMBER B. , BERNSTEIN SHANNA , DAI YUHAI , WALTER MARY , CHACKO SHAJI , HAYMOND MOREY W. , CHUNG STEPHANIE T. 
Published: June 2019

Metformin is the only approved oral agent for youth with type 2 diabetes (T2D), but its mechanism of action remains controversial. Recent data suggests a primary role for the entero-insular instead of the gluconeogenic pathway, but there is no data in youth, in whom metformin efficacy is ∼50%. Our objectives were to: (1) compare incretin concentrations, glucagon-like 1 peptide (GLP-1) and gastric inhibitory polypeptide (GIP) in 12 youth with T2D not on metformin to 10 healthy age and BMI-matched controls, and (2) determine the change in incretins and gluconeogenesis (GNG) after 3 months of metformin in 8 youth with T2D. Intact GLP-1 and total GIP were measured at 0 and 2-hour during a 75g OGTT and basal GNG (2H20) and glucose production (6,62H2glucose) measured after an overnight fast. Compared to controls, youth with T2D before metformin had higher HbA1c and glucose levels and lower fasting and 2-hour GLP-1 (P&lt;0.05 Table). After metformin, HbA1c decreased and fasting GLP-1 increased but there was no change in BMI, GNG or glucose production (P&gt;0.1 Table). Post-metformin GLP-1 was comparable to levels in controls (P&gt;0.1). There was no difference in GIP between youth with and without T2D and no change with metformin. Overall, improved glycemic control with short-term metformin in youth was associated with increased GLP-1 concentrations independent of changes in BMI and GNG supporting an entero-insular mechanistic pathway.

Disclosure
C.K. Cravalho: None. A.G. Meyers: None. L. Mabundo: None. A.B. Courville: None. S. Bernstein: None. Y. Dai: None. M. Walter: None. S. Chacko: None. M.W. Haymond: Advisory Panel; Self; Daiichi Sankyo Company, Limited, Zealand Pharma A/S. Stock/Shareholder; Self; Xeris Pharmaceuticals, Inc. Other Relationship; Self; AstraZeneca. S.T. Chung: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases
1327-P: Baseline Characteristics of Latino Youth with Prediabetes: The Preventing Diabetes in Latino Youth Cohort
Authors: OLSON MICAH , KONOPKEN YOLANDA P. , CASTRO FELIPE G. , HU HOUCHUN H. , KELLER COLLEEN , PATRICK DONALD L. , WILLIAMS ALLISON , AYERS STEPHANIE , KNOWLER WILLIAM C. , PIMENTEL JANIEL , PENA ARMANDO , SOLTERO ERICA G. , SHAIBI GABRIEL Q. 
Published: June 2019

Background: Latino youth are disproportionately impacted by type 2 diabetes (T2D). Prediabetes is an intermediate stage in the pathogenesis of T2D and represents a critical opportunity for prevention in adults. In youth and adults, prediabetes is identified by HbA1c, fasting glucose, and/or 2-hour glucose (2HrGluc). In youth, it is not well-characterized whether prediabetes by each criterion confers a similar metabolic profile. The objective of this study is to compare baseline characteristics of prediabetic Latino youth enrolled in a randomized, controlled diabetes prevention trial based on hyperglycemic status.
Methods: Participants were selected for the following inclusion criteria: 1) Latino ancestry, 2) Age 12-16 years, 3) BMI ≥ 95th percentile for age and sex, and 4) Prediabetes defined as HbA1c ≥ 5.7% and &lt; 6.5%, fasting glucose ≥ 100 and &lt; 126 mg/dL, or 2HrGluc ≥ 120 and &lt; 200 mg/dL after an OGTT.
Results: Ninety-four youth (age 13.5±1.4 years, 59 male/35 female) met inclusion criteria with 25% eligible by HbA1c, 45% by 2HrGluc, and 30% based on more than one criterion. No participant met eligibility by fasting glucose alone. Those who met eligibility by more than one criterion were more likely to be exposed to gestational diabetes in utero (19.2%) compared to 2HrGluc (7.9%) or HbA1c (0%) groups, P=0.04. The multiple eligibility group also exhibited higher hepatic fat fraction by MRI (11.9%) compared to 2HrGluc (7.6%) and HbA1c (6.6%) groups, P=0.055. There were no statistically significant differences between eligibility groups in body fat percentage, BMI percentile, diabetes family history, liver enzymes, or lipid profiles.
Conclusion: These data suggest that obese Latino adolescents with prediabetes according to more than one criteria were more likely to be exposed to hyperglycemia in utero and exhibit higher liver fat content. Whether prediabetes criteria are associated with a differential response to lifestyle intervention will be tested in this clinical trial.

Disclosure
M. Olson: None. Y.P. Konopken: None. F.G. Castro: None. H.H. Hu: None. C. Keller: None. D.L. Patrick: None. A. Williams: None. S. Ayers: None. W.C. Knowler: None. J. Pimentel: None. A. Pena: None. E.G. Soltero: None. G.Q. Shaibi: None.

Funding
National Institutes of Health (R01DK107579P)
1335-P: Weight Status and Cardiometabolic Risk Factors among Adolescents in Japan
Authors: MORIKAWA SAKIKO Y. , FUJIHARA KAZUYA , ISHII DAI , NEDACHI RINA , ISHIZAWA MASAHIRO , ISHIGURO HAJIME , MATSUBAYASHI YASUHIRO , YAMADA TAKAHO , KODAMA SATORU , SONE HIROHITO 
Published: June 2019

Pediatric obesity is associated with clustered cardiometabolic risk and the future incidence of diabetes. However, few studies have determined the effect of pediatric obesity in Asia, where obesity is less common than in Western countries. Thus, we clarified whether metabolic risk factors are associated with weight status including slight overweight and underweight among Japanese adolescents. We performed a cross-sectional analysis of 2241 Japanese adolescents (1180 boys) aged 13-14 years whose height, weight, HbA1c, blood pressure (BP), and serum lipids were measured. Participants were classified as underweight, normal weight, slightly overweight, overweight, or obese according to both the universal and Asian cutoffs of the International Obesity Task Force, which correspond to adult BMI cutoffs. The clustered cardiometabolic risk (Z-CMR) was estimated by summing standardized sex-specific Z scores of HbA1c, mean arterial pressure (MAP), and non-high-density lipoprotein cholesterol (non-HDL-C). Linear regression analysis showed that MAP (sex-specific Z score), non-HDL-C (sex-specific Z score), and Z-CMR were higher in the slightly overweight, overweight, and obese groups than in the normal weight group after adjusting for confounders. Compared with the normal weight group, the slightly overweight, overweight, and obese groups had significantly higher odds ratios (ORs) for high BP [OR = 1.38 (95% CI, 1.03-1.85); OR = 2.63 (1.77-3.91); and OR = 2.39 (1.57-3.64), respectively]. Compared with the normal weight group, underweight boys, but not girls, had a significantly lower OR for high Z-CMR [OR = 0.20 (0.05-0.84)]. Our results indicated that adolescents classified as slightly overweight had higher levels of BP, serum lipids (but not HbA1c), and clustered cardiometabolic risk than those classified as normal weight. This observation demonstrated that significant associations between weight status and cardiometabolic risk factors could be seen during adolescence even in East Asia.

Disclosure
S.Y. Morikawa: None. K. Fujihara: None. D. Ishii: None. R. Nedachi: None. M. Ishizawa: None. H. Ishiguro: None. Y. Matsubayashi: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.
134-LB: Treatment Patterns and Outcomes Before and After Human Regular U-500 Insulin Initiation via Kwikpen in U.S. Veterans with Type 2 Diabetes
Authors: CHEN JIELING , FAN LUDI , JUNEJA RATTAN , BORRA SUJANA , HUANG AHONG , WANG LI 
Published: June 2019

Introduction: Human regular U-500 insulin (U-500R) improves glycemic control in people with type 2 diabetes (PwT2D) inadequately controlled with high doses of other insulins. Limited evidence exists on treatment patterns and outcomes in PwT2D who initiate U-500R using a U-500R KwikPen (U500KP) in the real-world setting.
Methods: Adults with ≥2 claims for T2D and initiating U500KP (index date: 1st claim) in Veterans Health Administration data (01MAR2016-01JUN2017) were identified. Inclusion criteria included continuous enrollment and ≥1 A1C measure in 9 months of both pre- and post-index date and no U-500R use in 9 months pre-index. Treatment patterns and outcomes including observed total daily dose (TDD), A1C level, and hypoglycemia events (ICD-9 diagnosis codes, glucagon administration, blood glucose ≤70 mg/dl) per patient per year (PPPY) in 9 months pre- and post-index were compared using paired t-test and McNemar’s test. Linear Mixed Model (LMM) was used to confirm the effect of U500KP initiation on A1C, adjusting for demographics, Quan-Charlson Comorbidity Index (Q-CCI) and TDD.
Results: PwT2D who initiated U500KP were identified (n=647). Mean age was 64 years, most were white (80%) and men (97%). Mean Q-CCI score was 3.8. After initiating U500KP, mean TDD increased from 188 to 270 units. 62% of the PwT2D had a TDD ≤200 units in the pre-index period, with 27% remaining on ≤200 units post-index. After U-500R initiation, mean A1C decreased from 9.5% to 8.7% (p&lt;0.0001). LMM confirmed this A1C decrease was significant. Hypoglycemic events PPPY increased from 4.3 to 5.3 (p&lt;0.05).
Conclusions: Post-U500KP initiation, there is a clinically significant drop in A1C accompanied by an average increase of 1 hypoglycemic event/year. Analysis showed that most PwT2D requiring high dose insulin starting U500KP were on TDD ≤200 units pre-index. After initiation of U500KP, TDD increased by ∼80 units with 1 in 4 PwT2D continuing on TDD ≤200 units.

Disclosure
J. Chen: Employee; Self; Eli Lilly and Company. L. Fan: Employee; Self; Lilly Diabetes. Stock/Shareholder; Self; Lilly Diabetes. R. Juneja: Employee; Self; Eli Lilly and Company. S. Borra: Other Relationship; Self; STATinMED. A. Huang: Other Relationship; Self; STATinMED. L. Wang: Other Relationship; Self; STATinMED.
1347-P: Improvement in Peripheral Insulin Sensitivity (IS) with Metformin (MET) in Adolescents with Type 1 Diabetes (T1D) Is Not Mediated by Muscle Mitochondrial Change
Authors: TOMMERDAHL KALIE L. , CREE-GREEN MELANIE , BJORNSTAD PETTER , CARREAU ANNE-MARIE , REYES YESENIA GARCIA , BAUMGARTNER AMY D. , BROWN MARK S. , NEWCOMER BRADLEY , REUSCH JANE E.B. , NADEAU KRISTEN J. 
Published: June 2019

T1D youth are insulin resistant and we recently demonstrated that whole-body IS improved after 3 months of MET therapy. We also found that youth with T1D and type 2 diabetes both have skeletal muscle mitochondrial dysfunction that correlated with IS, but with a unique pattern in T1D. We aimed to determine if improvement in IS in T1D youth following MET was related to improvement in mitochondrial function. Forty-nine youth aged 12-21 years with T1D participated in Effects of MEtformin on CardiovasculaR Function in AdoLescents with T1D (EMERALD), a randomized, double-blind, placebo-controlled study. Youth were randomized to 3 months of MET titrated to 1000mg BID over 4 weeks or placebo (PLA). Assessments prior to and after MET or PLA included a hyperinsulinemic euglycemic clamp (80 mU/m2/minute insulin) to evaluate IS (glucose infusion rate [GIR]) and, in a subset of youth, calf 31Phosphorus magnetic resonance spectroscopy (MRS) before, during, and after 90 sec of near-maximal isometric exercise to evaluate post-exercise muscle mitochondrial function. Change with treatment for each group was compared via t-test or Mann Whitney U, as appropriate. Twenty-two youth with pre/post MRS (n=12 MET, n=10 PLA, 16.3±2.1 years, 45% female, 91% Caucasian, BMI 25.6±3.9 kg/m2, 7.4±3.7 years T1D duration, HbA1c 8.2±1.1%) were included. GIR increased more in the MET group (MET 1.5 [1.1-2.1] vs. PLA 0.4 [-0.1-0.9] mg/kg/minute, p=0.024). There were no differences between groups in any mitochondrial measure (initial phosphocreatine [PCr] synthesis, ADP and PCr time constants, oxidative phosphorylation, maximal mitochondrial function) or the related measures of creatine kinase reaction or anaerobic glycolysis.
In summary, metformin improves peripheral IS in T1D youth, but likely not via muscle mitochondrial-mediated mechanisms. Further research is needed to understand mitochondrial dysfunction and metformin-induced improvements in IS in T1D.

Disclosure
K.L. Tommerdahl: None. M. Cree-Green: None. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. A. Carreau: Advisory Panel; Self; Pfizer Inc. Y. Garcia Reyes: None. A.D. Baumgartner: None. M.S. Brown: None. B. Newcomer: None. J.E.B. Reusch: Board Member; Self; American Diabetes Association. Other Relationship; Self; Merck & Co., Inc. K.J. Nadeau: None.

Funding
American Diabetes Association (7-11-CD-08 to K.J.N.)
1349-P: Sociodemographic and Clinical Factors Associate with Parental Fear of Hypoglycemia: Italian Nationwide Cross-Sectional Survey
Authors: CHERUBINI VALENTINO , PJETRAJ DORINA , BONFANTI RICCARDO , MARINO MONICA , IANNILLI ANTONIO ,   ISPED, CARLE FLAVIA , GESUITA ROSARIA 
Published: June 2019

Aim of this study was to evaluate the association of socio-demographic and clinical factors, including technologies used for diabetes management, and parental fear of hypoglycaemia (FOH) in parents of children (&lt;18y) with T1D. A cross-sectional, nationwide electronic survey, supported by the Italian Society of Paediatric Endocrinology and Family Associations of children with diabetes, was conducted during September-November 2018. The Hypoglycaemia Fear Survey for Parents (HFS-P), a 25-item questionnaire, was used to assess FOH. Quintile regression analysis was performed to estimate factors associated to FOH. Out of 1450 questionnaires, 1106 (873 mothers) reported a complete HFS-P in both the worry and behavior subscales. Children median age was 11 y (IQR: 8-14), median diabetes duration 6 y (IQR: 3-10); median HbA1c 7.2% (IQR: 6.7-7.8). Glucose Sensor (including CGM and FGM) was used in 79% of patients and insulin pump in 45%. Median HFS-P worry score was 36 (IQR: 29-46), behavior score 29 (IQR: 24-33). Parental FOH was associated with parental modifiable and non-modifiable factors (Table 1). The use of insulin pump does not seem to impact worries and behaviors, while glucose sensor do influence parental behaviors. As the use of diabetes-advanced technologies is today increasingly widespread, the impact on parental FOH requires more analyses.

Disclosure
V. Cherubini: None. D. Pjetraj: None. R. Bonfanti: Advisory Panel; Self; Abbott, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Roche Diabetes Care, Sanofi. M. Marino: None. A. Iannilli: None. F. Carle: None. R. Gesuita: None.
1356-P: Comparison of Serum Adipokines and Anthropometric Measures in Children with Type 1 Diabetes (T1D) and Obesity
Authors: REDONDO MARIA JOSE , GU XIANGJUN , SISLEY STEPHANIE , TOSUR MUSTAFA , SILLER ALEJANDRO F. , BONDY MELISSA , DEVARAJ SRIDEVI 
Published: June 2019

Obesity or overweight occur in 40% of U.S. youth with T1D. While BMI is used to define obesity, it may not accurately reflect excess adiposity, which correlates better with metabolic dysfunction. However, it is difficult to measure adiposity without a research setting. In contrast, adipokines, which are produced by the adipose tissue, can be measured in serum. We aimed to analyze, in youth with T1D and obesity, the relationships of serum adipokines with measures of adiposity and cardiovascular risk factors.
We studied participants in the T1D Exchange Metformin Study with a serum sample obtained before randomization (n=61, mean age=8.0 years [SD=3.0], 27.9% male, 82.0% non-Hispanic white, mean BMI percentile=99.0 ([SD=1.0], mean BMI Z-score=2.7 [SD=0.78], mean % of the 95th BMI percentile (%95th BMI pctle)=134.6 [SD=20.0]). We measured serum levels of adipokines and inflammatory markers. We studied the correlations between DEXA scan-derived measures of adiposity (e.g., % body fat) with adipokines (e.g., leptin, adiponectin) or anthropometric measures (e.g., % 95th BMI pctle [recommended measure for extreme obesity], BMI-Z score).
DEXA % body fat was significantly correlated with % 95th BMI pctle (r=0.494, p&lt;0.0001) or leptin (r=0.467, p=0.0002), without statistical difference between these two correlations (p = 0.857). The correlation between % body fat and BMI Z-score was weaker (r=0.29, p=0.0270). Higher adiponectin was correlated with cardiovascular protective factors, such as lower systolic blood pressure (p=0.039) and higher HDL cholesterol (p=0.001), while neither % 95th BMI pctle nor BMI Z-score were. Children with high adiponectin (&gt;26.5 mg/L, distribution mean) were less likely to have high CRP &gt;6 mg/L (1.6%) vs. children with low adiponectin (23.0%, p&lt;0.05).
Serum adipokines levels could be used as more convenient markers of adiposity than BMI measures, and potentially become therapeutic targets to improve clinical outcomes in children with T1D and obesity.

Disclosure
M.J. Redondo: None. X. Gu: None. S. Sisley: Advisory Panel; Self; Rhythm Pharmaceuticals, Inc. M. Tosur: None. A.F. Siller: None. M. Bondy: None. S. Devaraj: None.