Long-term Continuous Glucose Monitor Use in Very Young Children With Type 1 Diabetes: One-Year Results From the SENCE Study.

OBJECTIVES: Achieving optimal glycemic outcomes in young children with type 1 diabetes (T1D) is challenging. This study examined the durability of continuous glucose monitoring (CGM) coupled with a family behavioral intervention (FBI) to improve glycemia. STUDY DESIGN: This one-year study included an initial 26-week randomized controlled trial of CGM with FBI (CGM+FBI) and CGM alone (Standard-CGM) compared with blood glucose monitoring (BGM), followed by a 26-week extension phase wherein the BGM Group received the CGM+FBI (BGM-Crossover) and both original CGM groups continued this technology. RESULTS: Time in range (70-180 mg/dL) did not improve with CGM use (CGM+FBI: baseline 37%, 52 weeks 41%; Standard-CGM: baseline 41%, 52 weeks 44%; BGM-Crossover: 26 weeks 38%, 52 weeks 40%). All three groups sustained decreases in hypoglycemia (<70 mg/dL) with CGM use (CGM+FBI: baseline 3.4%, 52 weeks 2.0%; Standard-CGM: baseline 4.1%, 52 weeks 2.1%; BGM-Crossover: 26 weeks 4.5%, 52 weeks 1.7%, P-values <.001). Hemoglobin A1c was unchanged with CGM use (CGM+FBI: baseline 8.3%, 52 weeks 8.2%; Standard-CGM: baseline 8.2%, 52 weeks 8.0%; BGM-Crossover: 26 weeks 8.1%, 52 weeks 8.3%). Sensor use remained high (52-week study visit: CGM+FBI 91%, Standard-CGM 92%, BGM-Crossover 88%). CONCLUSION: Over 12 months young children with T1D using newer CGM technology sustained reductions in hypoglycemia and, in contrast to prior studies, persistently wore CGM. However, pervasive hyperglycemia remained unmitigated. This indicates an urgent need for further advances in diabetes technology, behavioral support, and diabetes management educational approaches to optimize glycemia in young children.

Treatment of cystic fibrosis related bone disease.

The advent of highly effective CFTR modulator therapies has slowed the progression of pulmonary complications in people with cystic fibrosis. There is increased interest in cystic fibrosis bone disease (CFBD) due to the increasing longevity of people with cystic fibrosis. CFBD is a complex and multifactorial disease. CFBD is a result of hypomineralized bone leading to poor strength, structure and quality leading to susceptibility to fractures. The development of CFBD spans different age groups. The management must be tailored to each group with nuance and based on available guidelines while balancing therapeutic benefits to risks of long-term use of bone-active medication. For now, the mainstay of treatment includes bisphosphonates. However, the long-term effects of bisphosphonate treatment in people with CF are not fully understood. We describe newer agents available for osteoporosis treatment. Still, the lack of data behooves trials of monoclonal antibodies treatments such as Denosumab and Romozosumab and anabolic bone therapy such as teriparatide and Abaloparatide. In this review, we also summarize screening and non-pharmacologic treatment of CFBD and describe the various options available for the pharmacotherapy of CFBD. We address the prospect of CFTR modulators on bone health while awaiting long-term trials to describe the effects of these medications on bone health.

An update on methods for assessing bone quality and health in Cystic fibrosis.

With increasing life expectancy in people with Cystic fibrosis (CF), the focus of clinical care has shifted to management and prevention of non-pulmonary comorbidities. CF related bone disease, defined by low bone mineral density (BMD), is prevalent across all age groups and acknowledges the increased fractures rates that negatively impact lung function and quality of life. Dual energy X-ray absorptiometry (DXA) measurement of bone mineral content (BMC) and "areal" BMD (aBMD) is recommended for identifying and monitoring bone health in children and adults due to its low cost, low radiation exposure, and widespread availability. Recent studies in children and adolescents with chronic illness focus on adjustment of BMC and aBMD measurements for height due to the effects of short stature and delayed maturation on bone size. Expanded reference databases for alternate imaging sites such as the ultradistal radius and hip present opportunities for research and long-term monitoring. As the two-dimensional nature of DXA imposes limitations, we highlight other imaging modalities including peripheral quantitative computed tomography QCT (pQCT), magnetic resonance imaging, and quantitative ultrasound (QUS). These tools, while primarily used in a research setting, can impart information on true volumetric bone density and bone microarchitecture as well as contribute to fracture assessment and prediction. Due to the high morbidity and mortality associated with vertebral and hip fracture, we will present on vertebral fracture assessment (VFA) in both children and adults as well as applied analyses including hip structural analysis (HSA), trabecular bone score (TBS), and fracture risk assessment (FRAX) for high risk groups. Questions remain on the future clinical applicability and accessibility of these assessment and prediction tools, longitudinal monitoring through adolescence and adulthood, and how outcome measures may guide bone modifying therapies.

Practical aspects of diabetes technology use: Continuous glucose monitors, insulin pumps, and automated insulin delivery systems.

There have been tremendous advances in diabetes technology in the last decade. Continuous glucose monitors (CGM), insulin pumps, and automated insulin delivery (AID) systems aim to improve glycemic control while simultaneously decreasing the burden of diabetes management. Although diabetes technologies have been shown to decrease both hypoglycemia and hyperglycemia and to improve health-related quality of life in individuals with type 1 diabetes, the impact of these devices in individuals with cystic fibrosis-related diabetes (CFRD) is less clear. There are unique aspects of CFRD, including the different underlying pathophysiology and unique lived health care experience and comorbidities, that likely affect the use, efficacy, and uptake of diabetes technology in this population. Small studies suggest that CGM is accurate and may be helpful in guiding insulin therapy for individuals with CFRD. Insulin pump use has been linked to improvements in lean body mass and hemoglobin A1c among adults with CFRD. A recent pilot study highlighted the promise of AID systems in this population. This article provides an overview of practical aspects of diabetes technology use and device limitations that clinicians must be aware of in caring for individuals with CF and CFRD. Cost and limited insurance coverage remain significant barriers to wider implementation of diabetes technology use among patients with CFRD. Future studies exploring strategies to improve patient and CF provider education about these devices and studies showing the effectiveness of these technologies on health and patient-reported outcomes may lead to improved insurance coverage and increased rates of uptake and sustained use of these technologies in the CFRD community.

Resuscitation of the Traumatically Injured Patient.

Trauma is a leading cause of death. Optimal outcomes depend on a coordinated effort. Providers must be prepared to act in an organized and methodical manner. Recognizing and immediately treating causes of shock after trauma offer the best chance of survival to the patient. Incorporating evidence-based knowledge and resuscitation techniques learned from the military, the trauma victim experiencing acute hypovolemia has better outcomes because of advances in the clinical management of blood loss than ever before. Treatment focuses primarily on stopping the bleeding, providing damage control resuscitation, and monitoring and treating the patient for signs of shock. If the patient can be stabilized and avoid the lethal trauma triad, definitive surgical care can be achieved.

Cutaneous Reactions to Continuous Glucose Monitoring and Continuous Subcutaneous Insulin Infusion Devices in Type 1 Diabetes Mellitus.

BACKGROUND: Continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) are the standard of care for type 1 diabetes in children. There is little reported on device-related skin complications and treatment options. This study documents cutaneous reactions to CGM and CSII devices in children and young adults with type 1 diabetes. METHODS: One hundred and twenty-one subjects (3-25 years) with type 1 diabetes and CGM and/or CSII use were recruited over a three-month period from the Naomi Berrie Diabetes Center at Columbia University Irving Medical Center. A five-question survey was completed for each subject detailing demographic data, diabetes management, and device-related skin complications. RESULTS: Sixty percent of subjects reported skin complications related to CGM and/or CSII use. Terms most frequently used to describe cutaneous reactions were "red," "itchy," "painful," and "rash." Subjects who used both CGM and CSII were more likely to report skin problems than those who used only CSII (odds ratio 2.9, [95% confidence interval: 1.2-6.7]; P = .015). There were no associations between skin complications and sex or race/ethnicity. Twenty-two percent of subjects with adverse skin event(s) discontinued use of a device due to their skin problem. Seven percent were evaluated by a dermatologist. Eighty-one percent used a range of products to treat their symptoms, with variable perceived clinical outcomes. CONCLUSIONS: Skin complications related to CSII or CGM devices are commonly reported in pediatric patients with type 1 diabetes and may lead to interruption or discontinuation of device use. Future studies are needed to elucidate the causes of these reactions and determine the best methods for prevention.

A newly described cutaneous reaction at sites of insulin pump use in a child with Type 1 diabetes.

Continuous subcutaneous insulin infusion (CSII), or insulin pumps, with or without continuous glucose monitoring (CGM) devices have become the standard of care for patients with type 1 diabetes. While increasingly popular, a wide range of reported skin reactions to CSII and CGM devices was found. We present this case of a pyogenic granuloma-like neutrophilic and granulomatous response to an insulin pump to increase awareness of a previously uncharacterized cutaneous adverse reaction at insulin pump infusion sites.

The Unique Role of 11-Oxygenated C19 Steroids in Both Premature Adrenarche and Premature Pubarche.

INTRODUCTION: Recent studies have shown 11-oxygenated androgens (11oAs) are the dominant androgens in premature adrenarche (PA). Our objective was to compare 11oAs and conventional androgens in a well-defined cohort of children with PA or premature pubarche (PP) and correlate these androgens with metabolic markers. METHODS: A prospective cross-sectional study was conducted at a university hospital. Fasting early morning serum steroids (including 11oAs) and metabolic biomarkers were compared and their correlations determined in children ages 3-8 years (F) or 3-9 years (M) with PA or PP (5 M and 15 F) and healthy controls (3 M and 8 F). RESULTS: There were no differences between PA, PP, and controls or between PA and PP subgroups for sex, BMI z-score, or criteria for childhood metabolic syndrome. Dehydroepiandrosterone sulfate (DHEAS) was elevated only in the PA subgroup, as defined. 11oAs were elevated versus controls in PA and PP although no differences in 11oAs were noted between PA and PP. Within the case cohort, there was high correlation of T and A4 with 11-ketotestosterone and 11ß-hydroxyandrostenedione. While lipids did not differ, median insulin and HOMA-IR were higher but not statistically different in PA and PP. CONCLUSIONS: PA and PP differ only by DHEAS and not by 11oAs or insulin sensitivity, consistent with 11oAs - rather than DHEAS - mediating the phenotypic changes of pubarche. Case correlations suggest association of 11oAs with T and A4. These data are the first to report the early morning steroid profiles including 11oAs in a well-defined group of PA, PP, and healthy children.

Response to Long-term Vitamin D Therapy for Bone Disease in Children With Sickle Cell Disease.

Patients with sickle cell disease (SCD) are at risk for bone fragility from multiple factors including vitamin D deficiency. To date, no studies have evaluated the efficacy and safety of long-term vitamin D therapy for bone disease in children with SCD. We report a cohort of 4 children with SCD found to have severe vitamin D deficiency, secondary hyperparathyroidism, and abnormal bone mineral density treated with monthly high-dose oral cholecalciferol over 2 years. All patients exhibited a positive response to therapy without hypervitaminosis D or hypercalcemia. Further studies are needed to standardize guidelines for optimal vitamin D dosing and prevention of toxicity.

Bariatric Surgery in Adolescents: Is Routine Nutrient Supplementation Sufficient to Avoid Anemia Following Bariatric Surgery?

BACKGROUND: Anemia following bariatric surgery is a known complication. To prevent nutrient deficiencies, adolescents require multivitamin/mineral supplementation following bariatric surgery. The purpose of this study was to investigate if routine multivitamin/mineral supplementation is sufficient to prevent anemia in adolescents undergoing bariatric surgery, particularly sleeve gastrectomy (SG), a procedure that may induce nutrient malabsorption. METHODS: We conducted a retrospective review of pediatric patients who underwent SG (34 patients) and laparoscopic adjustable gastric banding (LAGB) (141 patients) (January 2006 through December 2013). We examined anemia marker levels (iron, ferritin, folate, B12, hemoglobin, and hematocrit) at first visit and 3, 6, and 12 months postsurgery by repeated-measures analysis adjusting for weight loss. RESULTS: Following SG, folate levels decreased 3 and 6 months postsurgery but returned to baseline levels at 12 months. Furthermore, the SG group demonstrated lower folate levels compared with LAGB at 3 and 6 months. B12 levels decreased 6 months post-SG but returned to baseline at 12 months. Following LAGB, B12 levels decreased 12 months postsurgery compared with baseline. Ferritin levels decreased 3 months post-LAGB but returned to baseline levels at 6 months. There were no changes within groups or differences between groups in iron, hemoglobin, or hematocrit. CONCLUSIONS: While anemia did not occur in any patients while on recommended routine supplementation, folate levels were significantly reduced following SG and were lower in SG compared with LAGB patients. Additional folate supplementation seemed to improve folate levels, which highlights the importance of ongoing surveillance by primary care providers and the need for additional folate supplementation following SG.

Cortisol Levels in Children With Diabetic Ketoacidosis Associated With New-Onset Type 1 Diabetes Mellitus.

There is little data documenting cortisol levels in children with diabetic ketoacidosis (DKA), despite the fact that untreated adrenal insufficiency (AI) could worsen the outcome of DKA. In this cross-sectional study, we assessed serum cortisol levels in 28 children with DKA and new onset type 1 diabetes mellitus evaluated at our center over a 5-year period. Average duration of diabetes-related symptoms was positively associated with age ( P = .002), and significantly lower hemoglobin A1c levels were observed in the youngest children. The mean cortisol level was 40.9 µg/dL, with a range of 7.8 to 119 µg/dL. Cortisol levels were found to be inversely associated with serum pH ( P = .007). There was no difference in the clinical outcome of the 4 patients who had cortisol levels less than 18 µg/dL. Overall, we did not find clinical or laboratory evidence of diminished cortisol reserve; however, the possibility of AI must be kept in mind when treating children with DKA.

Usefulness of repeat review of head magnetic resonance images during presurgical epilepsy conferences.

Surgical epilepsy conferences are an important part of the process of determining whether a patient is a candidate for resective epilepsy surgery. At these conferences, repeat review (re-review) of the magnetic resonance images (MRIs) of the patient's head often occurs. This study assessed how often radiologic re-review at a presurgical epilepsy conference resulted in a changed interpretation of the head MRI. Charts were reviewed for 239 patients who had been presented at presurgical epilepsy conferences between 2008 and 2012. Of the 233 patients whose MRIs were re-reviewed, resective surgery was performed in 94 patients (40.3%). Forty-one patients (17.6%) had a previously undiagnosed finding, and 18 of the 41 (43.9%) underwent resective surgery. For 4 of the 41 patients (9.8%) with a previously undiagnosed pertinent finding, re-review detected abnormalities that were not amenable to surgical resection (autoimmunity or significant bilateral pathology).

Double Inversion Recovery Magnetic Resonance Imaging in Identifying Focal Cortical Dysplasia.

BACKGROUND: Focal cortical dysplasia is commonly recognized in pediatric epilepsy surgery. Despite characteristic radiographic features, focal cortical dysplasia can be subtle on magnetic resonance imaging. Double inversion recovery acquisition suppresses the white matter signal, which may enhance visualization of abnormal features at the gray-white matter interface. We assessed the ability of double inversion recovery to distinguish focal cortical dysplasia from periventricular nodular heterotopia and normal brain. METHODS: Patients with focal cortical dysplasia were identified from our patient database, as was a control group comprising patients with periventricular nodular heterotopia and healthy persons. A senior neuroradiologist reviewed all clinical images and classified them as patients with focal cortical dysplasia (n = 16) or control subjects (periventricular nodular heterotopia, n = 13; normal, n = 20). Four neuroradiologists reviewed the de-identified and randomized double inversion recovery and magnetization prepared rapid acquired gradient echoes (MPRAGE) sequences for each person and scored them as normal, focal cortical dysplasia, or periventricular nodular heterotopia. RESULTS: Among individual reviewers, double inversion recovery showed sensitivity from 50% to 88% and specificity from 67% to 91% in detecting focal cortical dysplasia. The sensitivity was notably higher in reviewers with more clinical experience with the technique. Consensus agreement among the three most experienced reviewers gave a sensitivity of 88% (95% confidence interval [CI], 72% to 97%) and specificity of 88% (95% CI, 62% to 98%) for double inversion recovery and sensitivity of 44% (95% CI, 20% to 70%) and specificity of 100% (95% CI, 89% to 100%) for MPRAGE. CONCLUSIONS: Double inversion recovery is sensitive for detection of focal cortical dysplasia with experienced users, particularly when there is consensus agreement. The use of two clinically available magnetic resonance imaging acquisitions-double inversion recovery and another sequence with high specificity such as MPRAGE-would be complementary in the evaluation of lesional epilepsy.

Update on Bone Health in Pediatric Chronic Disease.

Children and adolescents with chronic disease are predisposed to impaired bone health. Pediatric illness, including type 1 diabetes mellitus, celiac disease, and cystic fibrosis, have significant risk of low bone mineralization and fracture due to underlying inflammation, malabsorption, lack of physical activity, and delayed puberty. Dual-energy x-ray absorptiometry is the primary imaging method to assess bone health in this population. The purpose of this review is to update readers about the assessment and management of bone health in children with common pediatric chronic illnesses and review recent advances in the prevention and treatment of impaired bone health.

Routine vs extended outpatient EEG for the detection of interictal epileptiform discharges.

OBJECTIVE: To compare the yield of epileptiform abnormalities on 30-minute recordings with those greater than 45 minutes. METHODS: We performed a prospective observational cross-sectional study of all outpatient routine EEGs comparing the rate of interictal epileptiform discharges (IEDs) and clinical events during the initial 30 minutes (routine) with those occurring in the remaining 30-60 minutes (extended). A relative increase of 10% was considered clinically significant. RESULTS: EEGs from 1,803 patients were included; overall EEG duration was 59.4 minutes (SD ±6.5). Of 426 patients with IEDs at any time during the EEG, 81 (19.1%, 95% confidence interval 15.6-23) occurred only after the initial 30 minutes. The rate of late IEDs was not associated with age, indication, IED type, or sleep deprivation. Longer recording times also increased event capture rate by approximately 30%. CONCLUSIONS: The yield of IED and event detection is increased in extended outpatient EEGs compared to 30-minute studies.

The Relationship of Metabolic Syndrome and Body Composition in Children with Premature Adrenarche: Is It Age Related?

BACKGROUND: Studies that evaluate both body composition and metabolic syndrome (MeS) risk in prepubertal children with premature adrenarche (PA) are limited. METHODS: Fifty-eight prepubertal children (aged 5-9 years, 33 female and 25 male), 30 with PA and 28 controls, were evaluated for the presence of MeS as defined by age-modified National Cholesterol Education Program Adult Treatment Panel III criteria. A subset had dual-energy X-ray absorptiometry and bone markers (n = 23/58) to evaluate the effect of hyperandrogenism on metabolic abnormalities and body composition. RESULTS: There was no difference in the prevalence of MeS between PA and controls (p = 0.138). Children with MeS were obese with an increased waist circumference (WC) and decreased high-density lipoprotein levels. Androgens were not associated with having more than one criterion for MeS (p = 0.08) but were associated with triglycerides and WC (p = 0.029 and p = 0.041, respectively). Lean mass was greater in PA subjects (p = 0.039), and androgens correlated with bone mineral density (p = 0.029) and total body fat (p = 0.008). Subjects with a higher percent of body fat were more likely to have more than one MeS risk factor (p = 0.005). CONCLUSIONS: MeS was seen only in obese subjects whether or not they had PA. Thus, it appears that obesity drives metabolic risk in the prepubertal population rather than PA. Our findings are important in determining how the prepubertal patient with PA should be evaluated for metabolic risk.

Autoimmune thyroid disease following alemtuzumab therapy and hematopoietic cell transplantation in pediatric patients with sickle cell disease.

Allogenic hematopoietic cell transplantation (alloHCT) is currently the only curative treatment option for patients with sickle cell disease. Alemtuzumab is a monoclonal antibody directed against CD52 positive cells used in myeloablative conditioning regimens for alloHCT. Its use has been associated with development of autoimmune disease in adult patients with rheumatologic conditions. We report on three cases of new onset autoimmune thyroid disease after alloHCT treatment with alemtuzumab in pediatric patients with sickle cell disease.

A retrospective review of newborn screening for congenital hypothyroidism and newborn thyroid disease at a major medical center.

Objective. To study the frequency of congenital hypothyroidism (CH)/thyroid disorders at a major, urban medical center. Methods. We conducted a retrospective review of a preexisting database for 2007 to 2011. Infants were classified as having CH, secondary/tertiary hypothyroidism, thyroid-binding globulin deficiency, and other types of newborn thyroid dysfunctions. Results. A total of 353 (50%) abnormal newborn screens were found to be normal and 42% were abnormal on repeat. Of the latter, 14% had true CH, 1% had thyroid-binding globulin deficiency, and 27% had other causes of thyroid dysfunction. The 5-year incidence of CH at NYP Morgan Stanley Children's Hospital was significantly greater than in New York City, New York State, and Upstate New York. Conclusion. The incidence of CH and other thyroid dysfunctions were greater in our population for 2007 to 2010, after which there was an unexplained decline. The study underlines the importance of continued newborn screening for thyroid dysfunction.