Quantifying Intraoperative Blood Loss In Osteogenesis Imperfecta Patients

Background: Osteogenesis Imperfecta (OI) is a collagen disorder with numerous multisystemic manifestations, including potential for increased vascular fragility and, consequently, increased bleeding. Since these patients are prone to fractures and multiple surgeries, the associated risk of increased intraoperative blood loss is potentially elevated compared to the general population. Significance: Knowing if OI type, bone, or the number of bones operated on simultaneously is associated with more intraoperative blood loss can aid in preoperative planning in this population. Hypothesis: We aim to investigate intraoperative blood loss in OI patients undergoing intramedullary rodding of lower extremity long bones to assess quantitative differences in intraoperative estimated blood loss (EBL). We hypothesize that more severe OI types, surgeries involving femurs, and/or surgeries with more bones operated on simultaneously will have a higher EBL. Experimental Design: A retrospective review of OI patients\u27 first surgeries between 2003-2018 at a single hospital was completed. We identified 127 patients with OI who had undergone intramedullary rodding of a lower extremity long bone. Variables included OI type, EBL per surgery (in mL), length of surgery, which bone was operated on, number of bones operated on per procedure, and whether they required a blood transfusion. Statistical analyses were performed using Chi-Square, Kruskal Wallis, and Wilcoxon Rank Sum tests. Results/Data: Among patients with the three most common OI types, there was no significant difference in median EBL/hour (type I = 41.9, type III = 11.2, and type IV = 10.3; p = 0.10), nor in percentage who required transfusions, p = 0.94. Patients who had one bone operated on had significantly higher median EBL/hour (40.7) relative to patients who had 2 or 3 bones operated on (11.0 and 9.3, respectively; p = 0.01 for both). Which bones were operated on was statistically significant, with unilateral femurs alone having significantly higher median EBL/hour (50.9) versus bilateral femurs with (10.9) or without (10.3) other bones operated on simultaneously (p = 0.01 and 0.002, respectively). Conclusions: EBL, both total blood loss and blood loss per hour, and the need for a blood transfusion are not significantly associated with OI type. EBL/hour is, however, associated with how many and which bones are being operated on simultaneously, with unilateral femurs having the highest median EBL/hour.https://digitalcommons.unmc.edu/chri_forum/1046/thumbnail.jp

Assessing Body Fat in Pediatric Osteogenesis Imperfecta: A Preliminary Comparison of Anthropometric Techniques

Background: Osteogenesis Imperfecta (OI) is a genetic disorder causing brittle bones, extremity deformities, short stature, and scoliosis, resulting in decreased physical function. Body Mass Index (BMI) is used as a proxy for body fat in the general population, however, it is particularly inaccurate measure to gauge body fat in OI patients due to skeletal deformities and short stature. There is a critical need to identify the anthropometric and body composition characteristics that contribute to important health outcomes and improve disease management in patients with OI. Current literature is lacking data on percent body fat (% BF) composition in patients with OI due to several of the current methods to estimate % BF cannot be safely performed. The purpose of this study is to compare two safe measures using air displacement plethysmography (ADP) via the BOD POD® (COSMED USA Inc. Concord, CA) and 3D Body Scanner Styku™ (Styku, LLC, Los Angeles, CA) precision to one another to evaluate body fat percentage in OI patients. Our hypothesis is %BF and BMI percentiles measured between these two devices will not be statistically dissimilar. Methods: Patients were recruited from Children’s Omaha multidisciplinary OI clinic and underwent anthropometric measures using BOD POD® and Styku™. Air displacement plethysmography (ADP) via the BOD POD® and 3D Body Scanner with Styku™ associations between continuous variables were assessed using Spearman correlations. Difference scores between Styku and BodPod measurements were calculated, and were assessed to see if they significantly differed from zero (i.e. no difference) using a Signed Rank test All analyses were performed using SAS software version 9.4 (SAS Institute Inc., Cary, NC). Results: Higher body fat percentages as measured by the Styku™ and BOD POD® tended to be associated with higher BMI percentiles (rho = 0.56; 0.45), however this was not significant (p = 0.07; 0.09). The median difference between Styku and BodPod % BF measurements was 3.4 (-2.2, 8.7), however, this was not significantly different from zero (p = 0.21). Conclusion: More patients are needed to increase the power of the study in order to determine if there truly is a difference between Styku™ and BOD POD® measurements in %BF and BMI percentiles. If there is not a difference between these measures it is foreseeable to use either Styku™ and BOD POD® to assess %BF in OI patients as an overall measure of health.https://digitalcommons.unmc.edu/chri_forum/1044/thumbnail.jp

Femoral and Tibial Indications for Initial and Reoperation Surgeries with Fassier-Duval Intramedullary Rods for Children with Osteogenesis Imperfecta

Background: Osteogenesis imperfecta (OI) is a genetic connective tissue disorder affecting quantity and integrity of collagen type I, which is integral for the strength of osseus tissue. OI has a heterogenous molecular inheritance pattern – divided into four major subgroups (I-IV). Defects in collagen protein products lead to poor development of skeletal structures and increased fracture rates. Children with OI suffer from multiple fractures and bone deformities often requiring surgical intervention with osteotomies and intramedullary telescoping rods, most often with Fassier-Duval (FD) rods. Our study–updated cohort from 2018 paper Azzam et al.–looked at the relationship between initial and reoperation indications for femur and tibia FD rodding surgeries based on age, bone, and OI type. Methods: Retrospective chart review of initial surgeries included 197 bones (femurs and tibias) from 58 patients. Reoperations included 140 bones from 45 patients. Variables included age at first operation (0-24, 24.1-48, 48.1+ months), time to reoperation, operation indications, bone, and OI type. Spearman correlations were used separately for each bone-type to assess associations between age at first surgery and total number of surgeries. To assess dichotomous outcomes (i.e. specific indication), generalized estimating equations were utilized and adjusted for bone-type and side. Hazard ratios and associated 95% confidence intervals were derived from frailty survival models for the time to first reoperation outcome. Kaplan-Meier curves were generated to display time to reoperation, stratified by age at first operation and bone-type. Data was collected from 2003-2018. Analyses were performed using SAS software v9.4. Results: There was a statistically significant correlation between age at first surgery and indication (bowing and fracture) for initial (p\u3c0.0001, p=0.01) and reoperation surgeries (p=0.004, p=0.03), respectively. All bones, except left tibias, showed significant negative correlation between age at first surgery and total number of surgeries. Both older age at first surgery groups (24.1-48, 48.1+ months) had significantly lower risks of needing reoperation relative to the 0-24 months group (p=0.0003, p=0.0004). Descriptive analyses suggest median survival of FD rods in OI type III was decreased relative to type IV, XV or unknown when initial surgery was between 0-24 months. Conclusion: Bowing and fractures are the most common causes for initial and reoperation surgeries in children with OI. Patients in older age groups at first surgery need fewer reoperation surgeries. Median survival probabilities of FD rods increased when age at first surgery was after 48.1+ months. OI type may impact median survival of FD rods.https://digitalcommons.unmc.edu/chri_forum/1004/thumbnail.jp

Long Days Enhance Recognition Memory and Increase Insulin-like Growth Factor 2 in the Hippocampus

Light improves cognitive function in humans; however, the neurobiological mechanisms underlying positive effects of light remain unclear. One obstacle is that most rodent models have employed lighting conditions that cause cognitive deficits rather than improvements. Here we have developed a mouse model where light improves cognitive function, which provides insight into mechanisms underlying positive effects of light. To increase light exposure without eliminating daily rhythms, we exposed mice to either a standard photoperiod or a long day photoperiod. Long days enhanced long-term recognition memory, and this effect was abolished by loss of the photopigment melanopsin. Further, long days markedly altered hippocampal clock function and elevated transcription of Insulin-like Growth Factor2 (Igf2). Up-regulation of Igf2 occurred in tandem with suppression of its transcriptional repressor Wilm’s tumor1. Consistent with molecular de-repression of Igf2, IGF2 expression was increased in the hippocampus before and after memory training. Lastly, long days occluded IGF2-induced improvements in recognition memory. Collectively, these results suggest that light changes hippocampal clock function to alter memory, highlighting novel mechanisms that may contribute to the positive effects of light. Furthermore, this study provides insight into how the circadian clock can regulate hippocampus-dependent learning by controlling molecular processes required for memory consolidation