Pathogenic variants in PIK3CA are associated with clinical phenotypes of kaposiform lymphangiomatosis, generalized lymphatic anomaly, and central conducting lymphatic anomaly.

2023

e30419

05/2023

1545-5017

Complex lymphatic anomalies are debilitating conditions characterized by aberrant development of the lymphatic vasculature (lymphangiogenesis). Diagnosis is typically made by history, examination, radiology, and histologic findings. However, there is significant overlap between conditions, making accurate diagnosis difficult. Recently, genetic analysis has been offered as an additional diagnostic modality. Here, we describe four cases of complex lymphatic anomalies, all with PIK3CA variants but with varying clinical phenotypes. Identification of PIK3CA resulted in transition to a targeted inhibitor, alpelisib. These cases highlight the genetic overlap between phenotypically diverse lymphatic anomalies.

10.1002/pbc.30419

Pediatr Blood Cancer

37194624

Relationship Between Serum Brain-Type Natriuretic Peptide and Biomarkers of Growth in Infants With Shunt-Dependent Single Cardiac Ventricle.

2022

2022 Mar 11

1879-1913

<p>For infants with shunt-dependent or ductal-dependent single ventricle heart disease, poor growth is common and associated with morbidity and impaired neurodevelopmental outcomes. Although attention has focused on nutrition to promote weight gain, little is known about the relation between heart failure and growth factors. A prospective observational pilot study was performed to assess the relation between heart failure, assessed by brain natriuretic peptide (BNP), and growth factors (insulin-like growth factor 1 [IGF-1] and insulin-like growth factor-binding protein 3) at 3 visits: (1) before discharge from neonatal intervention with the establishment of stable pulmonary blood flow, (2) immediately before superior cavopulmonary connection, and (3) before discharge after superior cavopulmonary connection operation. The relation between BNP and growth factors was analyzed using Spearman pairwise correlations at each visit and modeled over time with a linear mixed-effects model. Correlations were considered worthy of further exploration using a p &lt;0.10, given the exploratory nature of the study. The study included 38 infants (66% male, 68% hypoplastic left heart syndrome). Median BNP was elevated at visit 1 and decreased over time (287&nbsp;pg/dl [interquartile range 147 to 794], 85&nbsp;pg/dl [52 to 183], and 90&nbsp;pg/dl [70 to 138]). Median IGF-1 Z&nbsp;score was &lt;0 at each visit but increased over time (-0.9 [interquartile range -1.1 to 0.1], -0.7 [-1.2 to 0.1], and -0.5 [-1.2 to 0]). Inverse correlations were found between BNP and IGF-1 at visit 1 (r&nbsp;=&nbsp;-0.40, p&nbsp;=&nbsp;0.097), BNP and IGF-1 and insulin-like growth factor-binding protein 3 at visit 2 (r&nbsp;=&nbsp;-0.33, p&nbsp;=&nbsp;0.080 and r&nbsp;=&nbsp;-0.33, p&nbsp;=&nbsp;0.085, respectively) and BNP and IGF-1 Z&nbsp;score at visit 3 (r&nbsp;=&nbsp;-0.42, p&nbsp;=&nbsp;0.049). Significant relations were likewise found between the change in BNP and the change in IGF-1 between visits 1 and 3 (p&nbsp;=&nbsp;0.046) and between visits 2 and 3 (p&nbsp;=&nbsp;0.048). In conclusion, this pilot study demonstrates an inverse correlation between BNP and growth factors, suggesting that the heart failure state associated with this physiology may play a mechanistic role in impaired growth.</p>

10.1016/j.amjcard.2022.01.052

Am J Cardiol

35287945

Adipocytokines and Associations with Abnormal Body Composition in Rheumatoid Arthritis.

2021

2021 Sep 24

2151-4658

<p><strong>PURPOSE: </strong>We determined associations between adipokines and abnormal body composition in patients with rheumatoid arthritis (RA).</p>

<p><strong>METHODS: </strong>Combining data from three RA cohorts, whole-body dual-energy absorptiometry measures of appendicular lean mass and fat mass indices were converted to age, sex, and race-specific Z-Scores. Lean mass relative to fat mass was determined based on prior methods. Independent associations between body composition profiles and circulating levels of adiponectin, leptin, and fibroblast growth factor(FGF)-21 were assessed using linear and logistic regression models adjusting for demographics and study cohort. We also determined the improvement in the area-under-the-curve (AUC) for prediction of low lean mass when adipokines were added to predictive models that included clinical factors such as demographics, study, and body mass index (BMI).</p>

<p><strong>RESULTS: </strong>Among 419 participants, older age was associated with higher levels of all adipokines while higher C-reactive protein was associated with lower adiponectin levels and higher FGF-21 levels. Greater fat mass was strongly associated with lower adiponectin levels and higher leptin and FGF-21 levels. Higher levels of adiponectin, leptin, and FGF-21 were independently associated with low lean mass. The addition of adiponectin and leptin levels to regression models improved prediction of low lean mass when combined with demographics, study, and BMI (AUC 0.75 v. 0.66).</p>

<p><strong>CONCLUSIONS: </strong>Adipokines are associated with both excess adiposity and low lean mass in patients with RA. Improvements in the prediction of body composition abnormalities suggest that laboratory screening could help identify patients with altered body composition who may be at greater risk of adverse outcomes.</p>

10.1002/acr.24790

Arthritis Care Res (Hoboken)

34558809

Bone accrual in children and adolescents with type 1 diabetes: current knowledge and future directions.

2021

2021 May 06

1752-2978

<p><strong>PURPOSE OF REVIEW: </strong>Skeletal fragility is now recognized as a significant complication of type 1 diabetes (T1D). Many patients with T1D develop the disease in childhood and prior to the attainment of peak bone mass and strength. This manuscript will review recent studies investigating the effects of T1D on skeletal development.</p>

<p><strong>RECENT FINDINGS: </strong>Mild-to-moderate deficits in bone density, structure, and mineral accrual were reported early in the course of T1D in some but not all studies. Childhood-onset disease was associated with a more severe skeletal phenotype in some adult studies. Lower than expected bone mass for muscle size was been described. Hemoglobin A1c was negatively associated with bone density and structure in several studies, though the mechanism was not clear.</p>

<p><strong>SUMMARY: </strong>The use of advanced imaging techniques has shown that the adverse effects of T1D on the developing skeleton extend beyond bone density to include abnormalities in bone size, shape, microarchitecture, and strength. Despite these gains, a uniform understanding of the pathophysiology underlying skeletal fragility in this disorder remains elusive. Longitudinal studies, especially in association with interventions to reduce hyperglycemia or improve muscle strength, are needed to inform bone healthcare in T1D.</p>

10.1097/MED.0000000000000638

Curr Opin Endocrinol Diabetes Obes

33965967

A quality improvement project to address the challenges surrounding zoledronic acid use in children.

2021

2021 Apr 07

1435-5604

<p><strong>INTRODUCTION: </strong>Zoledronic acid (ZA) is an intravenous bisphosphonate used to treat pediatric osteoporosis. Adverse events including hypocalcemia and acute phase reaction (APR) are common following first-infusion. The purpose of this report is to describe implementation of a ZA clinical practice guideline and the subsequent process changes to improve adherence to aspects of the protocol related to safety and efficacy.</p>

<p><strong>METHODS: </strong>Quality assurance was evaluated by chart review over a 5-year period to compare the prevalence of hypocalcemia and APR to published data. A quality improvement (QI) initiative consisting of process changes including the addition of an endocrine RN to coordinate infusions and a shift to patient/family self-scheduling of infusions was conducted. The effect of the interventions on safety (completion of pre- and post-infusion bloodwork) and efficacy (receipt of all prescribed infusions) outcomes was evaluated.</p>

<p><strong>RESULTS: </strong>Seventy-two patients received 244 infusions over the period. The frequency of hypocalcemia (22%) and APR (31%) was consistent with prior reports. 99% of patients received pre-infusion bloodwork, 78% received post-first-infusion bloodwork, and 47% received all prescribed infusions. QI initiatives increased the percentage of patients receiving post-first-infusion bloodwork from 67 to 79% and those receiving all infusions from 62 to 74%, but fell short of the goal of 90%.</p>

<p><strong>CONCLUSIONS: </strong>The implementation of a standardized protocol for ZA use in children was successful in confirming patient eligibility with pre-infusion bloodwork but failed to ensure that patients obtained post-first-infusion bloodwork and received all prescribed infusions. Further efforts to systematize the management of children on ZA are needed.</p>

10.1007/s00774-021-01214-5

J Bone Miner Metab

33825940

Incidence and Risk of Celiac Disease after Type 1 Diabetes: A Population-Based Cohort Study Using The Health Improvement Network Database.

2018

2018 Sep 12

1399-5448

<p><strong>OBJECTIVE: </strong>To determine the incidence of and risk factors for development of celiac disese (CD) in individuals with type 1 diabetes.</p>

<p><strong>METHODS: </strong>Cohort study using The Health Improvement Network (THIN), a United Kingdom primary care database of &gt;13 million people. Individuals with incident type 1 diabetes diagnosed at 1-35 years of age between 1995 and 2015 with no previous diagnosis of CD were included. Cox regression was used to identify risk factors for CD, including age at diabetes diagnosis and sex, while adjusting for year of diagnosis to control for potential rising incidence in CD over time.</p>

<p><strong>RESULTS: </strong>Subjects (n=9,180; 43% female) had a median observation time of 5.1 years (IQR 2.0-10.1). CD was diagnosed in 196 (2%) during follow up. Median time to diagnosis was 2.1 years, but 25% were diagnosed more than 5 years after diabetes diagnosis. Incidence (per 10,000 person-years) was greater in females (43.0 [95%CI 35.2-52.0]) vs males (26.8 [95%CI 21.5-32.9]). In multivariable Cox regression stratified by childhood- versus young adult-onset diabetes, younger age at diabetes diagnosis within childhood (HR 0.91 [95% CI 0.88-0.94]) and female sex among the adult-onset diabetes group (HR 3.19 [95% CI 1.39-7.34]) were associated with greater risk of CD.</p>

<p><strong>CONCLUSIONS: </strong>As expected, incidence of CD was higher in individuals with childhood-onset diabetes versus those with adult-onset diabetes. However, individuals with diabetes are at risk of developing CD throughout childhood and adulthood, and prolonged screening after diagnosis may be warranted. Prospective studies are needed in order to guide risk-stratified approaches to screening. This article is protected by copyright. All rights reserved.</p>

10.1111/pedi.12770

Pediatr Diabetes

30209881

Emergency department utilization in pediatric heart transplant recipients.

2017

2017 Apr 29

1399-3046

<p>We used the NEDS database (2010) to evaluate ED utilization in PED HT recipients compared to other patient populations with focus on characteristics of ED visits, risk factors for admission, and charges. We analyzed 433 ED visits by PED HT recipients (median age 8 [range: 0-18] years). The most common primary diagnosis category was infectious (n=163, 37.6%), with pneumonia being the most common infectious etiology. When compared to all PED visits, HT visits were more likely to result in hospital admission (32.6% versus 3.9%, P&lt;.001), had greater hospital LOS (median of 3 days [IQR 2-4] versus 2 days [IQR 1-4], P=.001), and accumulated greater total hospital charges (median $26&nbsp;317 [IQR $11&nbsp;438-$46&nbsp;407] versus $12&nbsp;332 [IQR $7092-$22&nbsp;583], P&lt;.001). When compared to visits by other SOT recipients, results varied with similar rates of hospital admission for HT, LUNGT, and KT visits and similar LOS for HT and KT visits but differing total hospital charges. Although PED HT recipients account for a small percentage of overall ED visits, they are more likely to be hospitalized and require greater resource utilization compared to the general PED population, but not when compared to other SOT recipients.</p>

10.1111/petr.12936

Pediatr Transplant

28455909