Surgical Timing and Neurocognitive Development among Patients with Craniosynostosis: Analysis of Confounders.

BACKGROUND: In 1988, Renier and Marchac asserted that children with craniosynostosis who undergo cranial vault remodeling (CVR) after 12 months of age experience delayed neurocognitive development compared to children who undergo CVR before 12 months of age. The purpose of this study was to identify factors potentially confounding this cause-and-effect relationship. The authors hypothesize that children with socioeconomic disadvantages or comorbid conditions are more likely to undergo CVR after 12 months and may represent a selection bias toward delayed neurocognitive development. METHODS: Patients with nonsyndromic single-suture craniosynostosis who underwent CVR between 2009 and 2020 at Michigan Medicine were included ( n = 227). Sociodemographic and clinical variables were documented. The sample was dichotomized to compare patients who underwent CVR before (early) and after (late) 12 months of age. Statistical analysis was performed at P < 0.05 significance. RESULTS: The early and late groups contained 157 patients and 70 patients, respectively. Compared to the early group, the late group contained a larger proportion of patients who identified as non-White ( P = 0.03), qualified for need-based financial assistance ( P = 0.03), were born preterm ( P < 0.01), or had a comorbid condition ( P < 0.01). Based on preoperative testing, the late group contained a larger proportion of patients with baseline cognitive ( P < 0.001) and language ( P = 0.008) delays relative to the early group. CONCLUSIONS: This study demonstrates that socioeconomic disadvantages and comorbid conditions are prevalent among patients who undergo delayed CVR and may represent a selection bias toward delayed neurocognitive development. Future studies evaluating the relationship between surgical timing and neurocognitive development must control for these factors. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Longitudinal Assessment of Neurodevelopment in Patients With Nonsyndromic Single-Suture Craniosynostosis: A Retrospective Review of 66 Patients.

The neurodevelopmental consequences of nonsyndromic single-suture (NSS) craniosynostosis are the subject of continued debate. Although the predictive validity of the Bayley Scales of Infant and Toddler Development (Third Edition) (BSID-III) have been questioned, this neurodevelopmental testing battery continues to be widely utilized among multidisciplinary craniofacial teams. The purpose of this study is to evaluate the neurodevelopmental functioning of patients with NSS craniosynostosis before and after surgical correction and the impact of surgical correction on neurodevelopmental trajectory based on BSID-III testing. All patients with NSS craniosynostosis who underwent cranial vault remodeling between 2009 and 2020 were considered for inclusion. Patients who failed to complete BSID-III testing within 2 months of surgery preoperatively and 2 years of surgery postoperatively were excluded. A total of 66 patients met criteria for the study. On language testing, both the preoperative mean score ( P =0.007) and postoperative mean score ( P =0.003) were significantly lower than the population norm. Furthermore, on motor testing, both the preoperative mean score ( P =0.005) and postoperative mean score ( P =0.001) were significantly lower than the population norm. Bayley Scales of Infant and Toddler Development (Third Edition) testing revealed no significant change between preoperative and postoperative neurodevelopmental functioning. Overall, this study suggests that patients with NSS craniosynostosis experience modest delays in language and motor development, which are present before and after cranial vault remodeling. In addition, this study provides evidence that cranial vault remodeling does not significantly impact the neurodevelopmental trajectory. Multicenter st udies and refined neurodevelopmental testing methods are necessary to definitively establish the neurodevelopmental implications of NSS craniosynostosis.

Amifostine Prophylaxis in Irradiated Breast Reconstruction: A Study of Oncologic Safety In Vitro.

BACKGROUND: Indications for adjuvant radiation therapy (XRT) in breast cancer have expanded. Although highly effective, XRT damages surrounding tissues and vasculature, often resulting in delayed or compromised breast reconstruction. Thus, effective yet safe methods of radiation injury prophylaxis would be desirable. Amifostine is a Food and Drug Administration-approved radioprotectant; however, concerns about its potential to also protect cancer remain. The purpose of this study was to evaluate the oncologic safety of amifostine (AMF) in vitro and determine its effect on human breast cancer cells in the setting of XRT. METHODS: One ER+/PR+/Her2- (MCF-7) and two ER-/PR-Her2- (MDA-MB-231, MDA-MB-468) breast cancer cell lines were investigated. Female fibroblasts were used as controls. Cells were treated with WR-1065, the active metabolite of AMF, 20 minutes before 0Gy, 10Gy, or 20Gy XRT. Live and dead cells were quantified; percent cell death was calculated. RESULTS: WR-1065 treatment significantly preserved viability and reduced healthy female fibroblasts death after XRT compared with untreated controls. All three breast cancer cells lines exhibited radiosensitivity with substantial cell death. Cancer cells retained their radiosensitivity despite WR-1065 pretreatment, achieving the same degree of cell death as untreated controls. CONCLUSIONS: This study demonstrated the proficiency of AMF to selectively protect healthy cells from XRT while breast cancer cells remained radiosensitive. These results support the oncologic safety of AMF in breast cancer in vitro. Further investigation is now warranted in vivo to ascertain the translational potential of using AMF as a radioprotectant to improve breast reconstruction after radiation treatment.