Challenges in closing the gap between evidence and practice: International survey of institutional surgical stabilization of rib fractures guidelines.

BACKGROUND: Surgical stabilization of rib fractures (SSRF) has gained increasing interest over the past decade, yet few candidates who could benefit from SSRF undergo operative management. We conducted an international survey of institutional SSRF guidelines comparing congruence between practice and contemporary evidence. We hypothesized that few guidelines reflect comprehensive evidence to facilitate standardized patient selection, operation, and postoperative management. METHODS: A request for institutional rib fracture guidelines was distributed from the Chest Wall Injury Society. Surgical stabilization of rib fractures-specific guideline contents were extracted using a priori-designed extraction sheets and compared against 28 SSRF evidence-based recommendations outlined by a panel of 14 international experts. Fisher's exact test compared the proportion of strong and weak evidence-based recommendations specified within a majority of institutional guidelines to evaluate whether strength of evidence is associated with implementation. RESULTS: A total of 36 institutions from 3 countries submitted institutional rib fracture management guidelines, among which 30 had SSRF-specific guidance. Twenty-eight guidelines (93%) listed at least one injury pattern criteria as an indication for SSRF, while 22 (73%) listed pain and 21 (70%) listed impaired respiratory function as other indications. Quantitative pain and respiratory function impairment thresholds that warrant SSRF varied across institutions. Few guidelines specified nonacute indications for SSRF or perioperative considerations. Seven guidelines (23%) detailed postoperative management but recommended timing and interval for follow-up varied. Overall, only 3 of the 28 evidence-based SSRF recommendations were specified within a majority of institutional practice guidelines. There was no statistically significant association ( p = 0.99) between the strength of recommendation and implementation within institutional guidelines. CONCLUSION: Institutional SSRF guidelines do not reflect the totality of evidence available in contemporary literature. Guidelines are especially important for emerging interventions to ensure standardized care delivery and minimize low-value care. Consensus effort is needed to facilitate adoption and dissemination of evidence-based SSRF practices. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Malformation of the Posterior Cerebellar Vermis Is a Common Neuroanatomical Phenotype of Genetically Engineered Mice on the C57BL/6 Background.

C57BL/6 mice exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the posterior vermis, indicative of neuronal migration defect during cerebellar development. Recognizing that many genetically engineered (GE) mouse lines are produced from C57BL/6 ES cells or backcrossed to this strain, we performed histological analyses and found that cerebellar heterotopia were a common feature present in the majority of GE lines on this background. Furthermore, we identify GE mouse lines that will be valuable in the study of cerebellar malformations including diverse driver, reporter, and optogenetic lines. Finally, we discuss the implications that these data have on the use of C57BL/6 mice and GE mice on this background in studies of cerebellar development or as models of disease.

Divergence and inheritance of neocortical heterotopia in inbred and genetically-engineered mice.

Cortical function emerges from the intrinsic properties of neocortical neurons and their synaptic connections within and across lamina. Neurodevelopmental disorders affecting migration and lamination of the neocortex result in cognitive delay/disability and epilepsy. Molecular layer heterotopia (MLH), a dysplasia characterized by over-migration of neurons into layer I, are associated with cognitive deficits and neuronal hyperexcitability in humans and mice. The breadth of different inbred mouse strains that exhibit MLH and inheritance patterns of heterotopia remain unknown. A neuroanatomical survey of numerous different inbred mouse strains, 2 first filial generation (F1) hybrids, and one consomic strain (C57BL/6J-Chr 1A/J/NaJ) revealed MLH only in C57BL/6 mice and the consomic strain. Heterotopia were observed in numerous genetically-engineered mouse lines on a congenic C57BL/6 background. These data indicate that heterotopia formation is a weakly penetrant trait requiring homozygosity of one or more C57BL/6 alleles outside of chromosome 1. These data are relevant toward understanding neocortical development and disorders affecting neocortical lamination.

Neuroanatomical characterization of the cellular and axonal architecture of subcortical band heterotopia in the BXD29-Tlr4lps-2J/J mouse cortex.

Subcortical band heterotopia (SBH) are malformations of the human cerebral cortex typically associated with epilepsy and cognitive delay/disability. Rodent models of SBH have demonstrated strong face validity as they are accompanied by both cognitive deficits and spontaneous seizures or reduced seizure threshold. BXD29-Tlr4lps-2J/J recombinant inbred mice display striking bilateral SBH, partial callosal agenesis, morphological changes in subcortical structures of the auditory pathway, and display sensory deficits in behavioral tests (Rosen et al., 2013; Truong et al., 2013, 2015). Surprisingly, these mice show no cognitive deficits and have a higher seizure threshold to chemi-convulsive treatment (Gabel et al., 2013) making them different than other rodent SBH models described previously. In the present report, we perform a detailed characterization of the cellular and axonal constituents of SBH in BXD29-Tlr4lps-2J/J mice and demonstrate that various types of interneurons and glia as well as cortical and subcortical projections are found in SBH. In addition, the length of neuronal cilia was reduced in SBH compared to neurons in the overlying and adjacent normotopic cortex. Finally, we describe additional and novel malformations of the hippocampus and neocortex present in BXD29-Tlr4lps-2J/J mice. Together, our findings in BXD29-Tlr4lps-2J/J mice are discussed in the context of the known neuroanatomy and phenotype of other SBH rodent models.