The Accuracy of Incident Vertebral Fracture Detection in Children Using Targeted Case-Finding Approaches

Vertebral fractures are clinically important sequelae of a wide array of pediatric diseases. In this study, we examined the accuracy of case-finding strategies for detecting incident vertebral fractures (IVF) over 2 years in glucocorticoid-treated children (n = 343) with leukemia, rheumatic disorders, or nephrotic syndrome. Two clinical situations were addressed: the prevalent vertebral fracture (PVF) scenario (when baseline PVF status was known), which assessed the utility of PVF and low lumbar spine bone mineral density (LS BMD; Z-score <−1.4), and the non-PVF scenario (when PVF status was unknown), which evaluated low LS BMD and back pain. LS BMD was measured by dual-energy X-ray absorptiometry, vertebral fractures were quantified on spine radiographs using the modified Genant semiquantitative method, and back pain was assessed by patient report. Forty-four patients (12.8%) had IVF. In the PVF scenario, both low LS BMD and PVF were significant predictors of IVF. Using PVF to determine which patients should have radiographs, 11% would undergo radiography (95% confidence interval [CI] 8–15) with 46% of IVF (95% CI 30–61) detected. Sensitivity would be higher with a strategy of PVF or low LS BMD at baseline (73%; 95% CI 57–85) but would require radiographs in 37% of children (95% CI 32–42). In the non-PVF scenario, the strategy of low LS BMD and back pain produced the highest specificity of any non-PVF model at 87% (95% CI 83–91), the greatest overall accuracy at 82% (95% CI 78–86), and the lowest radiography rate at 17% (95% CI 14–22). Low LS BMD or back pain in the non-PVF scenario produced the highest sensitivity at 82% (95% CI 67–92), but required radiographs in 65% (95% CI 60–70). These results provide guidance for targeting spine radiography in children at risk for IVF. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Impact of Parent Practices of Infant Positioning on Head Orientation Profile and Development of Positional Plagiocephaly in Healthy Term Infants

Aims: The influence of infant positioning on the development of head orientation and plagiocephaly is not clear. This study explored the relationship between infant body and head positioning, with the development of asymmetrical head orientation and/or positional plagiocephaly. Methods: Clinician measurement of head orientation profile and parent-reported infant positioning data were collected for 94 healthy term infants at 3, 6, and 9 weeks of age. Plagiocephaly was measured at 9 weeks with the modified Cranial Vault Asymmetry Index. Results: More severe plagiocephaly was associated with longer supine-sleep-maximum (p = 0.001) and longer supine-lying-total (p = 0.014) at 6 weeks. Prone positioning was not associated with plagiocephaly. Parent-reported head asymmetry during awake and sleep time at 3 weeks identified infants with clinician-measured head asymmetry at 9 weeks. Better symmetry in head turning was associated with more side-lying-total time by 9 weeks (p = 0.013). Conclusions: Our results showed that infant positioning is associated with early head orientation and plagiocephaly development. Early parent-reported asymmetry during awake and sleep time is an important indicator for the need for professional assessment and advice. A Plagiocephaly Prevention Strategy and Plagiocephaly Screening Pathway are provided for clinicians and parents.     

Contractile dysfunction in hypertrophied hearts with deficient insulin receptor signaling: possible role of reduced capillary density

Diabetics have worse outcomes than nondiabetics after a variety of cardiac insults. We tested the hypothesis that impaired insulin receptor signaling in myocytes worsens cardiac remodeling and function following injury, even in the absence of hyperglycemia. Mice with cardiomyocyte-restricted knock out of the insulin receptor (CIRKO) and wild type (WT) mice were treated with isoproterenol (ISO) for 2 or 5 days. Heart rates and cardiac mass increased comparably following ISO in WT and CIRKO mice. After 5 days, WT hearts were hyperdynamic by echocardiographic and left ventricular pressure measurements. However, CIRKO hearts had a blunted increase in contractility and relaxation following ISO. Interestingly, single myocytes isolated from both CIRKO ISO and WT ISO hearts had increased cellular shortening with prolonged time to peak shortening vs. respective shams. Thus, loss of myocytes or extramyocyte factors, rather than intrinsic dysfunction of surviving myocytes, caused the blunted inotropic response in ISO treated CIRKO hearts. Indeed, CIRKO ISO mice had increased troponin release after 2 days and greater interstitial and sub-endocardial fibrosis at 5 days than did ISO WT. Apoptosis assessed by TUNEL and caspase staining was increased in CIRKO ISO compared to WT ISO hearts; however, very few of the apoptotic nuclei were clearly in cardiac myocytes. After 5 days of ISO treatment, VEGF expression was increased in WT but not in CIRKO hearts. In keeping with this finding, capillary density was reduced in CIRKO ISO relative to WT ISO. Basal expression of hypoxia-inducible factor-1alpha was lower in CIRKO vs. WT hearts and may explain the blunted VEGF response. Thus, absence of insulin receptor signaling in the cardiac myocyte worsens catecholamine-mediated myocardial injury, at least in part, via mechanisms that tend to impair myocardial blood flow and increase ischemic injury.