Publications by authors named "Lucy D Mastrandrea"

28 Publications

  • Page 1 of 1

Association of same-day discharge with hospital readmission after pediatric thyroidectomy.

Pediatr Surg Int 2021 Sep 20;37(9):1259-1264. Epub 2021 May 20.

Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, 1001 Main Street, Buffalo, NY, 14203, USA.

Background: Studies have demonstrated that same-day discharge (SDD) following thyroid resection is safe and feasible in adults but there are no similar studies in the pediatric age group. The purpose of this study is to evaluate the influence of SDD on 30-day readmission rates following thyroid surgery in pediatric patients.

Methods: This retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program-Pediatric database to evaluate 30-day readmission rates among patients < 19 years of age who underwent thyroid resection between 2012 and 2017. Patients excluded were those discharged more than 2 days after surgery. The main exposure variable was SDD and the primary outcome was 30-day readmission. Secondary outcomes included wound complications, unplanned reoperation and death. Patient characteristics were compared using chi-squared testing and odds ratios for readmission were calculated using multivariate logistic regression.

Results: Of the 1125 patients (79% female, median age 15 years), 122 (11%) were discharged on the day of surgery. Total or near-total thyroidectomy represented the majority of operations (714, 63.5%) and patients undergoing these operations were less likely to be discharged on the same day as surgery compared to those undergoing thyroid lobectomy (4.3 vs. 22.1%, P < 0.001). Twenty-nine patients were readmitted within 30 days (3 in the same day group, 26 in the later group). There was no difference in the odds of readmission between the two groups (adjusted odds ratio in SDD compared to later discharge 1.04 [95% CI 0.29-3.75, P = 0.96; readmission rate, 2.46 vs. 2.59%). Wound complications were reported in two patients, both in the later discharge group.

Conclusion: Same-day discharge in pediatric patients undergoing thyroidectomy is not associated with an increase in 30-day readmissions or wound complications when compared to patients discharged 1 or 2 days after surgery. In selected patients, SDD may be an appropriate alternative to traditional overnight stay.
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http://dx.doi.org/10.1007/s00383-021-04927-wDOI Listing
September 2021

Postnatal steroid management in preterm infants with evolving bronchopulmonary dysplasia.

J Perinatol 2021 May 19. Epub 2021 May 19.

Division of Neonatology, Department of Pediatrics, UH Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting extremely preterm infants. Although mechanical ventilation and oxygen requirements in premature infants are identified as inciting mechanisms for inflammation and the development of BPD over time, data now support an array of perinatal events that may stimulate the inflammatory cascade prior to delivery. Corticosteroids, such as dexamethasone and hydrocortisone, have proven beneficial for the prevention and management of BPD postnatally due to their anti-inflammatory characteristics. This review aims to examine the pharmacologic properties of several corticosteroids, appraise the existing evidence for postnatal corticosteroid use in preterm infants, and assess steroid management strategies to ameliorate BPD. Finally, we aim to provide guidance based on clinical experience for managing adrenal suppression resulting from prolonged steroid exposure since this is an area less well-studied.
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http://dx.doi.org/10.1038/s41372-021-01083-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133053PMC
May 2021

Evidence of Early Diabetic Nephropathy in Pediatric Type 1 Diabetes.

Front Endocrinol (Lausanne) 2021 28;12:669954. Epub 2021 Apr 28.

Section of Pediatric Nephrology, Dayton Children's Hospital, Dayton, OH, United States.

Background: Diabetic nephropathy (DN) is one of the most common microvascular complications in type 1 diabetes Mellitus (T1D). Urinary markers of renal damage or oxidative stress may signal early stages of DN. The association of these markers with blood pressure (BP) patterns and glycemic variability (GV) in children is yet to be explored.

Methods: Subjects between the ages of 10 and 21 years with T1D were enrolled. Continuous glucose monitoring (CGM) and ambulatory blood pressure monitoring (ABPM) were performed on each subject. Urine samples were collected and analyzed for albumin, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) and pentosidine.

Results: The study included 21 subjects (62% female) with median age of 16.8 (IQR: 14.5, 18.9). Median HbA1C was 8.4 (IQR: 7.5, 9.3). While microalbuminuria was negative in all but one case (4.8%), urinary NGAL/Cr and pentosidine/Cr ratios were significantly elevated (P<0.001) in diabetic patients despite having normal microalbuminuria, and they correlated significantly with level of microalbumin/Cr (r=0.56 [CI: 0.17, 0.8] and r=0.79 [CI: 0.54, 0.91], respectively). Using ABPM, none had hypertension, however, poor nocturnal systolic BP dipping was found in 48% of cases (95% CI: 28-68%). Urinary NGAL/Cr negatively correlated with nocturnal SBP dipping (r=-0.47, CI: -0.76, -0.03). Urine NGAL/Cr also showed a significant negative correlation with HbA1c measurements, mean blood glucose, and high blood glucose index (r=-0.51 [CI: -0.78, -0.09], r=-0.45 [CI: -0.74, -0.03], and r=-0.51 [CI: -0.77, -0.1], respectively). Median urinary NGAL/Cr and pentosidine/Cr ratios were higher in the high GV group but were not significantly different.

Discussion: This pilot study explores the role of ABPM and urinary markers of tubular health and oxidative stress in early detection of diabetic nephropathy. GV may play a role in the process of this diabetic complication.
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http://dx.doi.org/10.3389/fendo.2021.669954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113955PMC
April 2021

Liraglutide pharmacokinetics and exposure-response in adolescents with obesity.

Pediatr Obes 2021 May 7:e12799. Epub 2021 May 7.

Division of Pediatric Endocrinology/Diabetes, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.

Background: Obesity in adolescence presents a major public health challenge, often leading to obesity in adulthood with associated chronic disease.

Objectives: This study aimed to perform a population pharmacokinetic and exposure-response analysis of liraglutide by meta-analysis of data from trials conducted in children, adolescents and adults with obesity.

Methods: The population pharmacokinetic analysis investigated the effect of covariates body weight, age group (children, adolescents and adults) and sex on liraglutide exposure in adolescents compared with previous results in adults. The exposure-response relationship of liraglutide for the change from baseline in body mass index standard deviation score (BMI SDS) was evaluated in adolescents and compared to that in adults.

Results: Body weight was the main covariate affecting liraglutide exposure, with lower exposures at higher body weights, whereas age group was of no importance and sex was of little importance. An exposure-response relationship was demonstrated for liraglutide in both adolescents and adults as the decrease in BMI SDS from baseline increased in an exposure-dependent manner with increasing liraglutide exposure.

Conclusions: The population pharmacokinetic analysis supported similar liraglutide exposures in adolescents and adults; body weight was the most important covariate affecting exposure. An exposure-response relationship was established for liraglutide.
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http://dx.doi.org/10.1111/ijpo.12799DOI Listing
May 2021

Bleak present, bright future: II. Combined effects of episodic future thinking and scarcity on delay discounting in adults at risk for type 2 diabetes.

J Behav Med 2021 04 28;44(2):222-230. Epub 2020 Sep 28.

Center for Transformative Research on Health Behaviors, Fralin Biomedical Research Institute at VTC, 1 Riverside Circle, Roanoke, VA, 24016, USA.

The present study sought to determine if episodic future thinking (EFT) can decrease delay discounting (DD) and demand for fast food under simulations of economic scarcity in adults at risk for diabetes (i.e., overweight/obese and with hemoglobin A1c values in, or approaching, the prediabetic range). Across two sessions, participants completed assessments of DD and food demand at baseline and while prompted to: (1) engage in either EFT or control episodic recent thinking, and (2) while reading a brief narrative describing either economic scarcity or neutral income conditions. Results showed that EFT significantly reduced DD, whereas the economic scarcity narrative significantly increased DD; no significant interaction between EFT and scarcity was observed. No significant effect of either EFT or scarcity was observed on food demand. We conclude that EFT decreases DD even when challenged by simulated economic scarcity in adults at risk for diabetes. The absence of a significant interaction between EFT and scarcity suggests that these variables operate independently to influence DD in opposing directions. Effects of EFT and economic scarcity on food demand require further study. The present study was registered on clinicaltrials.gov (NCT03664726).
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http://dx.doi.org/10.1007/s10865-020-00178-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965228PMC
April 2021

Does Episodic Future Thinking Repair Immediacy Bias at Home and in the Laboratory in Patients With Prediabetes?

Psychosom Med 2020 09;82(7):699-707

From the Fralin Biomedical Research Institute at VTC (Bickel, Stein, Mellis, Athamneh, Greenawald, Gatchalian), Roanoke, Virginia; and University at Buffalo Jacobs School of Medicine and Biomedical Sciences (Paluch, Quattrin, Bree, Mastrandrea, Epstein), Buffalo, New York.

Objective: This study aimed to determine if episodic future thinking (EFT) can decrease delay discounting (DD) among adults with prediabetes both in and out of the laboratory. DD measures how much the value of a reinforcer decreases as a function of the delay to receive it.

Methods: Adults with prediabetes (n = 67) completed a three-session study. At session 1, baseline measures (including DD) were collected. At sessions 2 and 3, participants were prompted to engage in either EFT or control episodic thinking (CET) while completing DD and other measures. In addition, between the completion of sessions 2 and 3, participants engaged in EFT or CET at home and completed DD tasks remotely via smartphones or other Internet-connected devices.

Results: Results showed significant -1.2759 (-20.24%) reductions in DD in the EFT group compared with a + 0.0287 (+0.46%) DD increase in the CET group (p = .0149) in the laboratory; and -0.4095 (-8.85%) reduction in DD in the EFT group compared with a + 0.2619 (+5.64%) increase in the CET group (p = .011) at home. Working memory (measured by Backwards Corsi and Digit Span) was found to moderate the effects of EFT on some measures of DD. EFT did not change measures from the food purchase task or a food ad libitum procedure.

Conclusions: Results show that EFT decreases DD in and out of the laboratory and supports the further exploration of EFT as an intervention for prediabetes and related chronic diseases.

Clinical Trial Registration: NCT03664726.
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http://dx.doi.org/10.1097/PSY.0000000000000841DOI Listing
September 2020

Delay Discounting, Glycemic Regulation and Health Behaviors in Adults with Prediabetes.

Behav Med 2021 Jul-Sep;47(3):194-204. Epub 2020 Apr 10.

Virginia Tech Carilion Research Institute.

The majority of people with prediabetes transition to type 2 diabetes. Research has suggested that persons with type 2 diabetes are likely to discount the future and focus on immediate rewards. This study was designed to assess whether this process of delay discounting (DD) is associated with glycemic regulation, medication adherence and eating and exercise behaviors in adults with prediabetes. Participants included 81 adults with prediabetes who were also prescribed hypertension or dyslipidemia drugs, which is common for people with prediabetes. Participants completed adjusting amount DD $100 and $1000 tasks, as well assessments of glycemic control (Hemoglobin (Hb) A1c), medication adherence, diet quality, and objectively measured physical activity. Relationships between DD and these variables were assessed. Results showed higher rates of DD were related to higher HbA1c; as well as poorer medication adherence, lower diet quality and lower physical activity. Hierarchical regression showed that the association between minority status, a known risk factor for type 2 diabetes, was moderated by DD, as minorities with higher DD had greater HbA1c values. Delay discounting may represent a novel target to prevent progression from prediabetes to type 2 diabetes.
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http://dx.doi.org/10.1080/08964289.2020.1712581DOI Listing
April 2020

A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity.

N Engl J Med 2020 05 31;382(22):2117-2128. Epub 2020 Mar 31.

From the Department of Pediatrics and Center for Pediatric Obesity Medicine, University of Minnesota Medical School, Minneapolis (A.S.K.); Novo Nordisk, Søborg, Denmark (P.A.); Pediatric Endocrinology, Hospital Ángeles Puebla, Puebla City, Mexico (M.B.-P.); the Department of Pediatrics, Division of Pediatric Endocrinology, Universitair Ziekenhuis Brussel, Brussels (I.G.); Novo Nordisk, Plainsboro, NJ (P.M.H.); the Division of Pediatrics, Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm (C.M.); the Division of Pediatric Endocrinology and Diabetes, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY (L.D.M.); Novo Nordisk, Bengaluru, India (N.P.); and the Center for Pediatric Research in Obesity and Metabolism, Division of Pediatric Endocrinology, Metabolism, and Diabetes Mellitus, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh (S.A.).

Background: Obesity is a chronic disease with limited treatment options in pediatric patients. Liraglutide may be useful for weight management in adolescents with obesity.

Methods: In this randomized, double-blind trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we enrolled adolescents (12 to <18 years of age) with obesity and a poor response to lifestyle therapy alone. Participants were randomly assigned (1:1) to receive either liraglutide (3.0 mg) or placebo subcutaneously once daily, in addition to lifestyle therapy. The primary end point was the change from baseline in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) standard-deviation score at week 56.

Results: A total of 125 participants were assigned to the liraglutide group and 126 to the placebo group. Liraglutide was superior to placebo with regard to the change from baseline in the BMI standard-deviation score at week 56 (estimated difference, -0.22; 95% confidence interval [CI], -0.37 to -0.08; P = 0.002). A reduction in BMI of at least 5% was observed in 51 of 113 participants in the liraglutide group and in 20 of 105 participants in the placebo group (estimated percentage, 43.3% vs. 18.7%), and a reduction in BMI of at least 10% was observed in 33 and 9, respectively (estimated percentage, 26.1% vs. 8.1%). A greater reduction was observed with liraglutide than with placebo for BMI (estimated difference, -4.64 percentage points) and for body weight (estimated difference, -4.50 kg [for absolute change] and -5.01 percentage points [for relative change]). After discontinuation, a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (estimated difference, 0.15; 95% CI, 0.07 to 0.23). More participants in the liraglutide group than in the placebo group had gastrointestinal adverse events (81 of 125 [64.8%] vs. 46 of 126 [36.5%]) and adverse events that led to discontinuation of the trial treatment (13 [10.4%] vs. 0). Few participants in either group had serious adverse events (3 [2.4%] vs. 5 [4.0%]). One suicide, which occurred in the liraglutide group, was assessed by the investigator as unlikely to be related to the trial treatment.

Conclusions: In adolescents with obesity, the use of liraglutide (3.0 mg) plus lifestyle therapy led to a significantly greater reduction in the BMI standard-deviation score than placebo plus lifestyle therapy. (Funded by Novo Nordisk; NN8022-4180 ClinicalTrials.gov number, NCT02918279.).
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http://dx.doi.org/10.1056/NEJMoa1916038DOI Listing
May 2020

Neonatal Thyroid Function and Disorders.

Clin Obstet Gynecol 2019 06;62(2):373-387

Pediatric Endocrinology, Medical University of South Carolina (MUSC) Children's Hospital, Charleston, South Carolina.

Thyroid hormone is essential for normal fetal brain development in utero and for the first 2 years of life. The developing fetus is initially reliant upon maternal thyroid hormones that cross the placenta, until the fetal thyroid begins to supply thyroid hormone for the fetus. Maternal thyroid status affects fetal thyroid function and maternal thyroid dysfunction can have a significant impact on the fetus and neonate. There are also several neonatal factors that can influence thyroid function. Here, we describe thyroid function in the fetus and neonate and discuss the most common thyroid disorders seen in neonates.
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http://dx.doi.org/10.1097/GRF.0000000000000434DOI Listing
June 2019

Role of delay discounting in predicting change in HBA1c for individuals with prediabetes.

J Behav Med 2019 Oct 22;42(5):851-859. Epub 2019 Mar 22.

Virginia Tech Carilion Research Institute, Roanoke, USA.

The majority of people with prediabetes transition to type 2 diabetes. Weight gain is a known predictor of increasing the risk of diabetes, but another reason may be a focus on immediate rewards and discounting of the future. Delay discounting (DD: devaluation of future consequences) is related to obesity and poor glycemic control in persons with type 2 diabetes. This study was designed to assess whether changes in DD are associated with HbA1c change beyond BMI change in individuals with prediabetes. Hierarchical regression showed changes in BMI (p = 0.008) and the $1000 DD task (p = 0.04) were associated with HbA1c change beyond demographic characteristics, with the full model accounting for 25.8% of the variance. Those with greater BMI increases and greater increases in discounting of the future showed the greatest increases in HbA1c. DD represents a novel target to prevent progression from prediabetes to type 2 diabetes.
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http://dx.doi.org/10.1007/s10865-019-00026-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726498PMC
October 2019

Liraglutide effects in a paediatric (7-11 y) population with obesity: A randomized, double-blind, placebo-controlled, short-term trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics.

Pediatr Obes 2019 05 17;14(5):e12495. Epub 2019 Jan 17.

Atlanta Center for Medical Research, Atlanta, Georgia.

Background: Childhood obesity is a major public health concern with limited treatment options.

Objective: The aim of this study was to assess safety, tolerability, pharmacokinetics, and pharmacodynamics during short-term treatment with liraglutide in children (7-11 y) with obesity.

Methods: In this randomized, double-blind, placebo-controlled trial, 24 children received at least one dose of once-daily subcutaneous liraglutide (n = 16) or placebo (n = 8) starting at 0.3 mg with weekly dose escalations up to 3.0 mg or maximum tolerated dose, and 20 children completed the trial (14 in the liraglutide group and six in the placebo group). The primary endpoint was the number of adverse events.

Results: Baseline characteristics (mean ± standard deviation) included the following: age 9.9 ± 1.1 years, weight 71.5 ± 15.4 kg, and 62.5% male. Thirty-seven adverse events were reported in nine liraglutide-treated participants (56.3%) versus 12 events in five placebo-treated participants (62.5%). Most adverse events were mild in severity, three were of moderate severity, and none were severe. Gastrointestinal disorders were the most frequently reported events occurring in 37.5% of liraglutide-treated participants compared with placebo (12.5%). Six asymptomatic hypoglycaemic episodes occurred in five participants of whom four were liraglutide treated. Liraglutide exposure was consistent with dose proportionality. Body weight was the only covariate to significantly impact exposure. A significant reduction in body mass index (BMI) Z score from baseline to end of treatment (estimated treatment difference: -0.28; P = 0.0062) was observed.

Conclusion: Short-term treatment with liraglutide in children with obesity revealed a safety and tolerability profile similar to trials in adults and adolescents with obesity, with no new safety issues.
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http://dx.doi.org/10.1111/ijpo.12495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590663PMC
May 2019

Hematuria as an adverse outcome following provocative growth hormone stimulation testing in children.

J Pediatr Endocrinol Metab 2018 Apr;31(5):539-543

Division of Pediatric Endocrinology, Children's Hospital of Michigan, Detroit, MI, USA.

Background: Provocative growth hormone (GH) stimulation testing is used to evaluate short stature and growth failure in children. Agents commonly used for testing include clonidine, arginine and glucagon. While stimulation testing is generally considered safe, gross hematuria has been described as a rare idiopathic complication of GH stimulation testing. This study was designed to estimate the incidence of both microscopic and macroscopic hematuria following GH testing with different provocative agents.

Methods: Subjects undergoing GH stimulation testing were invited to participate in the study. Prior to testing, vital signs were measured and baseline point-of-care (POC) urinalysis was done. The subjects performed urine testing at home on days 1, 2, 3 and 7 following GH stimulation studies. Families notified the study team with any positive findings and returned the data collection tool by mail.

Results: In total, 34 subjects aged 11.14±2.71 years (91.2% male) completed the study. Agents used in provocative testing included arginine (73.5%), clonidine (94.1%) and glucagon (32.4%). Three subjects developed hematuria after GH stimulation testing (clonidine/arginine). The hematuria resolved by 7 days after testing. Additional adverse effects included nausea, vomiting and hypotension.

Conclusions: In this study of children undergoing GH testing, hematuria was identified in three subjects. This study demonstrates that side effects to agents used for GH testing are self-limited, yet not rare, and should be discussed with patients and families prior to stimulation testing.
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http://dx.doi.org/10.1515/jpem-2017-0458DOI Listing
April 2018

Salivary inflammatory markers and microbiome in normoglycemic lean and obese children compared to obese children with type 2 diabetes.

PLoS One 2017 2;12(3):e0172647. Epub 2017 Mar 2.

Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States of America.

Background: There is emerging evidence linking diabetes with periodontal disease. Diabetes is a well-recognized risk factor for periodontal disease. Conversely, pro-inflammatory molecules released by periodontally-diseased tissues may enter the circulation to induce insulin resistance. While this association has been demonstrated in adults, there is little information regarding periodontal status in obese children with and without type 2 diabetes (T2D). We hypothesized that children with T2D have higher rates of gingivitis, elevated salivary inflammatory markers, and an altered salivary microbiome compared to children without T2D.

Methods: Three pediatric cohorts ages 10-19 years were studied: lean (normal weight-C), obese (Ob), and obese with T2D (T2D). Each subject completed an oral health survey, received a clinical oral examination, and provided unstimulated saliva for measurement of inflammatory markers and microbiome analysis.

Results: The diabetes group was less likely to have had a dental visit within the last six months. Body mass index (BMI) Z-scores and waist circumference/height ratios were similar between Ob and T2D cohorts. The number of carious lesions and fillings were similar for all three groups. The gingival index was greater in the T2D group compared to the Ob and C groups. Although salivary microbial diversity was minimal between groups, a few differences in bacterial genus composition were noted.

Conclusions: Obese children with T2D show a trend toward poorer oral health compared to normal weight and obese children without T2D. This study characterizes the salivary microbiome of children with and without obesity and T2D. This study supports a modest link between T2D and periodontal inflammation in the pediatric population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172647PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333807PMC
August 2017

Evaluation of Pump Discontinuation and Associated Factors in the T1D Exchange Clinic Registry.

J Diabetes Sci Technol 2017 03 25;11(2):224-232. Epub 2016 Sep 25.

1 University of California, San Francisco, San Francisco, CA, USA.

Background: The objectives of this study were to examine factors associated with insulin pump discontinuation among children and adults followed longitudinally for 1 year in the multicenter T1D Exchange clinic registry, and to provide participant-reported reasons for stopping pump therapy.

Methods: We longitudinally followed 8935 participants of all ages using an insulin pump at the time of registry enrollment. Logistic regressions were used to identify demographic and clinical factors associated with pump discontinuation. Pump discontinuation was self-reported by participants on a first annual follow-up survey.

Results: The overall frequency of pump discontinuation was 3%. Discontinuation was higher in adolescents (4%) and young adults (4%) than in younger children (3%) or older adults (1%). In multivariate analysis of children between 6 and <13 and 13 and <18 years, participants who discontinued pump use were more likely to have higher HbA1c levels at baseline (adjusted P < .001 for both). The top participant-reported reasons for discontinuing the pump included problems with wearability (57%), disliking the pump or feeling anxious (44%), and problems with glycemic control (30%).

Conclusions: In T1D Exchange registry participants, insulin pump discontinuation is uncommon, but more prevalent among adolescents and young adults, and youth with poor glycemic control. Given the known benefits of pump therapy, these populations should be targeted for support and education on troubleshooting pump use. Common reasons for discontinuation should also be considered in future device design and technological improvement.
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http://dx.doi.org/10.1177/1932296816663963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478021PMC
March 2017

Testicular failure following severe diabetic ketoacidosis complicated by hypotensive shock.

Clin Case Rep 2016 Apr 4;4(4):396-8. Epub 2016 Mar 4.

Department of Pediatrics University at Buffalo Women and Children's Hospital of Buffalo 219 Bryant Street Buffalo New York 14222.

The stalling or regression of pubertal development may be the first sign of hypergonadotropic hypogonadism in adolescent males. We report here a case of pediatric hypergonadotropic hypogonadism that likely developed secondary to ischemic injury during severe diabetic ketoacidosis (DKA). This case highlights the importance of performing genital exams during all evaluations of pediatric patients.
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http://dx.doi.org/10.1002/ccr3.527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831392PMC
April 2016

An Overview of Organ-Specific Autoimmune Diseases Including Immunotherapy.

Immunol Invest 2015 ;44(8):803-16

a Division of Pediatric Endocrinology, Department of Pediatrics , School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo, NY , USA.

A significant number of individuals are affected by autoimmune diseases, which are caused by aberrant recognition of self by the immune system. A wide variety of cells and organ systems are targets of pathologic activation of the immune mediators. Effective and safe therapies aimed at managing the chronic inflammatory aspect of many autoimmune diseases remain elusive. This review will focus on the available interventions and discuss the future of the field to prevent organ destruction by the autoimmune process.
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http://dx.doi.org/10.3109/08820139.2015.1099409DOI Listing
August 2016

Disorders of sex development: management of gender assignment in a preterm infant with intrauterine growth restriction.

Case Rep Med 2012 21;2012:587484. Epub 2012 Mar 21.

Division of Pediatric Endocrinology, Women & Children's Hospital of Buffalo, School of Medicine and Biomedical Sciences, University at Buffalo, 219 Bryant Street, Buffalo, NY 14222, USA.

We describe how a gender specialist team managed the case of a disorder of sex development in a preterm infant where definitive diagnosis and gender assignment were delayed due to complications of prematurity, anemia, and severe intrauterine growth restriction.
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http://dx.doi.org/10.1155/2012/587484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318260PMC
August 2012

Does the dopamine transporter protein allele predict growth hormone testing results or response to growth hormone therapy?

Endocrine 2010 Apr 6;37(2):361-4. Epub 2010 Mar 6.

Department of Pediatrics, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.

Animal studies have shown dopamine transporter protein (DAT1) knock out mice are growth retarded and hyperactive. DAT1 has been researched in several human psychiatric studies with varying results regarding phenotype and DAT1 alleles. However, the relationship between DAT1 and short stature in humans has not been explored. Buccal swabs were collected from patients receiving growth hormone (GH) therapy and were genotyped for variable number tandem repeat (VNTR) by polymerase chain reaction. Forty subjects were included; twenty-three patients had the 10/10 DAT1 genotype and thirteen had the 9/10 genotype. Fifteen of the patients with the 10/10 genotype tested GH deficient. Seven patients with the 9/10 genotype tested GH sufficient. The linear growth rate during the first year of GH therapy was equivalent in both genotypes. In conclusion, polymorphisms in the DAT1 40 base pair (bp) VNTR genotype do not predict GH deficiency or response to GH therapy in short children.
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http://dx.doi.org/10.1007/s12020-010-9313-9DOI Listing
April 2010

Lingual thyroid as a cause of primary hypothyroidism: congenital hypothyroidism in the neonatal period and beyond.

Clin Pediatr (Phila) 2010 Sep 31;49(9):885-8. Epub 2010 Mar 31.

Division of Pediatric Endocrinology, Women and Children's Hospital of Buffalo, 219 Bryant Street, Buffalo, NY 14222, USA.

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http://dx.doi.org/10.1177/0009922810364660DOI Listing
September 2010

Inhaled insulin: overview of a novel route of insulin administration.

Vasc Health Risk Manag 2010 Mar 3;6:47-58. Epub 2010 Mar 3.

Department of Pediatrics, School of Medicine and Biochemical Sciences, University at Buffalo, Buffalo, NY, USA.

Diabetes is a chronic disease characterized by inadequate insulin secretion with resulting hyperglycemia. Diabetes complications include both microvascular and macrovascular disease, both of which are affected by optimal diabetes control. Many individuals with diabetes rely on subcutaneous insulin administration by injection or continuous infusion to control glucose levels. Novel routes of insulin administration are an area of interest in the diabetes field, given that insulin injection therapy is burdensome for many patients. This review will discuss pulmonary delivery of insulin via inhalation. The safety of inhaled insulin as well as the efficacy in comparison to subcutaneous insulin in the various populations with diabetes are covered. In addition, the experience and pitfalls that face the development and marketing of inhaled insulin are discussed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835554PMC
http://dx.doi.org/10.2147/vhrm.s6098DOI Listing
March 2010

Young women with type 1 diabetes have lower bone mineral density that persists over time.

Diabetes Care 2008 Sep 30;31(9):1729-35. Epub 2008 Jun 30.

Department of Pediatrics, University at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, New York, USA.

Objective: Individuals with type 1 diabetes have decreased bone mineral density (BMD), yet the natural history and pathogenesis of osteopenia are unclear. We have previously shown that women with type 1 diabetes (aged 13-35 years) have lower BMD than community age-matched nondiabetic control subjects. We here report 2-year follow-up BMD data in this cohort to determine the natural history of BMD in young women with and without diabetes.

Research Design And Methods: BMD was measured by dual-energy X-ray absorptiometry at baseline and 2 years later in 63 women with type 1 diabetes and in 85 age-matched community control subjects. A1C, IGF-1, IGF binding protein-3, serum osteocalcin, and urine N-teleopeptide were measured at follow-up.

Results: After adjusting for age, BMI, and oral contraceptive use, BMD at year 2 continued to be lower in women >or=20 years of age with type 1 diabetes compared with control subjects at the total hip, femoral neck, and whole body. Lower BMD values were observed in cases <20 years of age compared with control subjects; however, the differences were not statistically significant. Lower BMD did not correlate with diabetes control, growth factors, or metabolic bone markers.

Conclusions: This study confirms our previous findings that young women with type 1 diabetes have lower BMD than control subjects and that these differences persist over time, particularly in women >or=20 years of age. Persistence of low BMD as well as failure to accrue bone density after age 20 years may contribute to the increased incidence of osteoporotic hip fractures seen in postmenopausal women with type 1 diabetes.
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http://dx.doi.org/10.2337/dc07-2426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518333PMC
September 2008

Bisphosphonate treatment of tumor-induced hypercalcemia in a toddler: case report and review of related literature.

Endocr Pract 2006 Nov-Dec;12(6):670-5

Division of Pediatric Endocrinology, Women's and Children's Hospital of Buffalo, The State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, New York 14222, USA.

Objective: To describe the initial manifestations and treatment of parathyroid hormone-related peptide (PTH-rP)-induced hypercalcemia in a toddler with a malignant rhabdoid tumor.

Methods: We report a case of a 2-year-old boy presenting with poor appetite, lethargy, and a 1.5-kg weight loss during a 2-week period. On examination, the child was found to have a right upper quadrant abdominal mass. Laboratory studies revealed severe hypercalcemia. We review the patients' clinical course and management of hypercalcemia.

Results: Initial evaluation revealed no cardiovascular instability. An abdominal mass was identified on physical examination. Initial laboratory studies revealed elevated levels of total and ionized calcium, low phosphorus, microcytic anemia, and elevated erythrocyte sedimentation rate. Saline diuresis with furosemide was begun. Abdominal ultrasonography revealed a large right renal tumor. Because of refractory hypercalcemia, intravenously administered bisphosphonate was used. Within 12 hours after bisphosphonate infusion, the serum calcium level declined from 14.9 mg/dL to 10.9 mg/dL. The furosemide dose was decreased and finally discontinued 2 days after bisphosphonate administration. Because of development of a femoral thrombosis, definitive surgical intervention was delayed. During that time, serum calcium levels again increased and necessitated administration of a second bisphosphonate dose. At surgical treatment, a right renal tumor was identified, and frozen section pathology revealed a rhabdoid tumor. After tumor resection, calcium levels were stable. Other laboratory studies performed at admission revealed suppressed PTH, normal vitamin D and calcitonin levels, and elevated PTH-rP.

Conclusion: Hypercalcemia in a toddler is a rare event and can be attributable to humoral factors released by malignant tumors. Hypercalcemia in the pediatric population can be treated effectively with bisphosphonates when conservative measures fail.
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http://dx.doi.org/10.4158/EP.12.6.670DOI Listing
March 2007

Clinical evaluation of inhaled insulin.

Adv Drug Deliv Rev 2006 Oct 17;58(9-10):1061-75. Epub 2006 Aug 17.

Division of Endocrinology-Diabetes, Department of Pediatrics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, The Women's and Children's Hospital, 219 Bryant Street, Buffalo, New York 14222, USA.

Diabetes affects over 18.2 million individuals in the United States alone. Current therapy to treat type 1 diabetes relies on subcutaneous insulin administration either by injection or continuous infusion. In addition, patients with type 2 diabetes who fail lifestyle intervention and oral therapy require subcutaneous insulin. Optimal injection protocols to achieve tight metabolic control often prove burdensome to patients. Thus, development of pulmonary insulin delivery to supplement and/or replace subcutaneous insulin injections may be an effective alternative, allowing patients to achieve intensive diabetes management. This review will discuss the devices in development for the delivery of inhaled insulin. In addition, the efficacy of inhaled insulin in both type 1 and type 2 diabetic populations will be discussed. Finally, the available safety data with respect to the unique pulmonary effects of inhaled insulin will be covered.
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http://dx.doi.org/10.1016/j.addr.2006.07.019DOI Listing
October 2006

Sphingosine 1-phosphate affects cytokine-induced apoptosis in rat pancreatic islet beta-cells.

Endocrinology 2006 Oct 22;147(10):4705-12. Epub 2006 Jun 22.

102 Farber Hall, Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, The University at Buffalo, New York 14214, USA.

Cytokines mediate pancreatic islet beta-cell apoptosis and necrosis, leading to loss of insulin secretory capacity and type 1 diabetes mellitus. The cytokines, IL-1beta and interferon-gamma, induced terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining of rat islet cells within 48 h by about 25-30%, indicative of apoptosis and/or necrosis. Sphingosine 1-phosphate (S1P) at nanomolar concentrations significantly reduced islet cell cytokine-induced TUNEL staining. Similar effects were observed in INS-1 cells. The dihydro analog of S1P also reduced the percentage of TUNEL stained islet and INS-1 cells, whereas the S1P receptor antagonist BML-241 blocked the protective effects. Pertussis toxin did not affect the S1P protective response. In the presence of a phospholipase C antagonist, U73122, there was significant inhibition of the S1P protective effects against apoptosis/necrosis. S1P stimulated INS-1 cell protein kinase C activity. Carbamylcholine chloride acting through muscarinic receptors also inhibited cytokine-induced TUNEL staining in pancreatic islet cells. S1P and/or dihydro-S1P also antagonized cytokine-induced increases in cytochrome c release from mitochondria and caspase-3 activity in INS-1 cells, which are indicative of cell apoptosis vs. necrosis. S1P failed to affect nitric oxide synthase activity after 48 h. Thus, the evidence suggests that S1P acting on S1P receptors coupled to G(q) mediates protective effects on islet beta-cells against cytokine-induced apoptosis.
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http://dx.doi.org/10.1210/en.2006-0456DOI Listing
October 2006

Clinical and biochemical similarities between reflux/obstructive uropathy and salt-wasting congenital adrenal hyperplasia.

Clin Pediatr (Phila) 2005 Nov-Dec;44(9):809-12

Department of Pediatrics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, and The Women's and Children's Hospital, Buffalo, New York, NY 14222, USA.

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http://dx.doi.org/10.1177/000992280504400911DOI Listing
March 2006

Sphingosine kinase activity and sphingosine-1 phosphate production in rat pancreatic islets and INS-1 cells: response to cytokines.

Diabetes 2005 May;54(5):1429-36

Department of Pharmacology and Toxicology, The State University of New York at Buffalo, Buffalo, NY, USA.

Sphingosine-1 phosphate (S1P) is a bioactive sphingolipid with the potential to mobilize Ca2+, to inhibit apoptosis, and to promote mitogenesis. Sphingosine kinase (SPHK) and S1P were characterized in INS-1 insulinoma cells and isolated rat islets of Langerhans. SPHK activity increased in INS-1 cell homogenates treated with interleukin-1beta (IL-1beta) or tumor necrosis factor-alpha (TNF-alpha), and responses were additive. IL-1beta or TNF-alpha increased islet SPHK activity within 15 min to 1 h; activity remained elevated after 8 h. SPHK2 was the predominant active isoform in INS-1 cells; little or no SPHK1 activity was detected. Cytokines increased endogenous S1P biosynthesis in 32P(i)-prelabeled INS-1 cells, and cycloheximide inhibited the response after 8 h, suggesting that protein synthesis mediated the response. There was no [32P]S1P release from cells. Compared with basal values, IL-1beta and TNF-alpha induced increases in SPHK1a mRNA levels relative to 18S ribosomal RNA in INS-1 cells within 1 h; relative SPHK2 mRNA levels were unchanged after cytokine treatment. IL-1beta, but not TNF-alpha, induced relative SPHK1a mRNA expression levels within 1 h in islets, whereas SPHK2 mRNA levels were unchanged. Thus, IL-1beta and TNF-alpha induced an early and sustained increase in SPHK activity in INS-1 cells and isolated islets, suggesting that S1P plays a role in the pathological response of pancreatic beta-cells to cytokines.
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http://dx.doi.org/10.2337/diabetes.54.5.1429DOI Listing
May 2005
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