Intramedullary Fixation for Pediatric Femoral Nonunion in Low- and Middle-Income Countries.

BACKGROUND: Pediatric femoral shaft nonunion after use of a plate or intramedullary nail (IMN) is uncommon in the United States. In low and middle-income countries, as defined by The World Bank, these complications may occur with greater frequency. We assessed the rates of union and painless weight-bearing after IMN fixation of pediatric femoral shaft nonunion in lower-resource settings. METHODS: We queried the SIGN (Surgical Implant Generation Network) Fracture Care International online database to identify all pediatric femoral shaft nonunions that had occurred since 2003 and had ≥3 months of follow-up after their treatment; our query identified 85 fractures in 83 patients. We defined nonunion as failure of initial instrumentation >90 days following its placement, lack of radiographic progression on radiographs made >3 months apart, or the absence of signs of radiographic healing >6 months after initial instrumentation. We evaluated the most recent follow-up radiograph to determine a Radiographic Union Scale in Tibial fractures (RUST) score. We also recorded rates of painless full weight-bearing as assessed by the treating surgeon. RESULTS: Fifty-seven patients with pediatric femoral shaft nonunions (including 42 male and 15 female patients from 18 countries) were included. The average age (and standard deviation) at the time of revision surgery was 13.8 ± 3.0 years (range, 6 to 17 years). The median duration of follow-up was 67 weeks (range, 13 weeks to 7.7 years). The initial instrumentation that went on to implant failure included plate constructs (56%), non-SIGN IMNs (40%), and SIGN IMNs (4%). At the time of the latest follow-up, 52 patients (91%) had a RUST score of ≥10 and 51 (89%) had painless full weight-bearing. No patient had radiographic evidence of femoral head osteonecrosis at the time of complete fracture-healing or the latest follow-up. CONCLUSIONS: Pediatric femoral shaft nonunion can occur after both plate and IMN fixation in low and middle-income countries. IMN fixation is an effective and safe treatment for these injuries. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Associations of Racial and Ethnic Category, Age, Comorbidities, and Socioeconomic Factors on Concordance to NCCN Guidelines for Patients With High-Risk Biliary Tract Cancers After Surgery.

Background: Biliary tract cancers (BTC) have a limited prognosis even for localized cancers, emphasizing the importance of multidisciplinary management. NCCN guidelines recommend adjuvant chemotherapy (CT) +/- radiotherapy (RT) for high-risk disease. We analyzed the association between racial and ethnic category along with other demographic factors and concordance to NCCN guidelines among patients following surgery for high-risk BTC. Methods: Subjects were identified from the National Cancer Database (NCDB) for BTC patients who underwent surgery and found to have metastatic lymph nodes (LN+) or positive surgical margins (M+) from 2004 to 2015. We defined concordance to NCCN guidelines as receiving surgery + CT +/- RT and non-concordance to the guidelines as surgery +/- RT. Descriptive studies and multivariate logistic regression analysis was performed. Results: A total of 3,792 patients were identified with approximately half being female (55.4%) and between the ages of 50-69 (52.8%). Most were White (76.3%) followed by Black (10.6%), Hispanic (8.5%), and Asian (5.3%). The BTC included extrahepatic cholangiocarcinoma (CCA) (48.6%), gallbladder cancer (43.5%), and intrahepatic CCA (7.9%). Most patients had an M- resection (71.9%) but also had LN+ disease (88.0%). There were no significant differences between racial groups in disease presentation (histological grade, tumor stage) and surgical outcomes (LN+, M+, hospital readmission, and 90 day post-surgery mortality). Hispanic patients as compared to White patients were less likely to be insured (85.7% vs 96.3%, p<0.001) and less likely to be treated at an academic facility (42.1% vs 52.1%, p=0.008). Overall, almost one-third (29.7%) of patients received non-concordant NCCN guideline care with Hispanic patients having the highest proportion of non-concordance as compared to Whites patients (36.1% vs 28.7%, p=0.029). On multivariate analysis, Hispanic ethnicity (HR=1.51, 95% CI: 1.15-1.99) remained significantly associated with non-concordance to NCCN guidelines. Conclusion: This study indicates that Hispanic patients with high-risk BTC are significantly less likely to receive NCCN-concordant treatment in comparison to White patients. More research is needed to confirm and understand the observed disparities and guide targeted interventions at the system-level.

Systematic Isolation of Key Parameters for Estimating Skeletal Maturity on Anteroposterior Wrist Radiographs.

BACKGROUND: The ability to make a continuous skeletal maturity estimate from a wrist radiograph would be useful in the treatment of adolescent forearm fractures, scoliosis, and other conditions. We attempted to create a reliable, rapid, and accurate method to do this. METHODS: Many anteroposterior wrist radiographic parameters from 3 skeletal maturity systems were simplified to 23 based on relevance to the peripubertal age range, univariate correlation with skeletal maturity, and reliability. These 23 parameters were evaluated on serial peripubertal anteroposterior hand-wrist radiographs. We determined the Greulich and Pyle (GP) skeletal age and Sanders hand system (SHS) stage. We used stepwise linear regression and generalized estimating equation (GEE) procedures to identify important radiographic and demographic parameters for estimating skeletal maturity, creating the "Modified Fels wrist skeletal maturity system." Its accuracy predicting skeletal maturity was evaluated and compared with that of 4 other systems: (1) GP system, (2) SHS, (3) GP parameters along with age and sex, and (4) SHS parameters along with age and sex. RESULTS: Three hundred and seventy-two radiographs of 42 girls (age range, 7 to 15 years) and 38 boys (age range, 9 to 16 years) were included. Fifteen radiographic parameters were excluded from the Modified Fels wrist system by stepwise regression and GEE analyses, leaving age, sex, and 8 radiographic parameters in the final model. Use of the Modified Fels wrist system resulted in more accurate skeletal maturity estimations (0.34-year mean discrepancy with actual skeletal maturity) than all other systems (p < 0.001 for all). The Modified Fels wrist system had a similar rate of outlier skeletal maturity estimations as the age, sex, and SHS model (1.9% versus 3.5%, p = 0.11) and fewer outliers than all other systems (p < 0.05 for all). CONCLUSIONS: A system that included demographic factors and 8 anteroposterior wrist radiographic parameters estimates skeletal maturity more accurately than the 2 most-used skeletal maturity systems in the United States. CLINICAL RELEVANCE: The Modified Fels wrist skeletal maturity system may allow for more accurate, reliable, and rapid skeletal maturity estimation than current systems, and also may be used when treating adolescent forearm fractures as it does not require imaging past the metacarpals. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Insights From Dynamic Neuro-Immune Imaging on Murine Immune Responses to CNS Damage.

Evolving technologies and increasing understanding of human physiology over the past century have afforded our ability to intervene on human diseases using implantable bio-materials. These bio-electronic devices present a unique challenge through the creation of an interface between the native tissue and implantable bio-materials: the generation of host immune response surrounding such devices. While recent developments in cancer immunology seek to stimulate the immune system against cancer, successful long-term application of implantable bio-material devices need to durably minimize reactive immune processes at involved anatomical sites. Peripheral immune system response has been studied extensively for implanted bio-materials at various body sites. Examples include tooth composites (Gitalis et al., 2019), inguinal hernia repair (Heymann et al., 2019), and cardiac stents and pacemaker leads (Slee et al., 2016). Studies have also been extended to less well-studied immune reactivity in response to CNS neural-electronic implant devices. Recent technological advances in 2-Photon Laser Scanning Microscopy (2P-LSM) have allowed novel insights into in vivo immune response in a variety of tissue microenvironments. While imaging of peripheral tissues has provided an abundance of data with regards to immune cell dynamics, central nervous system (CNS) imaging is comparatively complicated by tissue accessibility and manipulation. Despite these challenges, the results of dynamic intravital neuro-immune imaging thus far have provided foundational insights into basic CNS biology. Utilizing a combination of intravital and ex vivo 2P-LSM, we have observed novel pathways allowing immune cells, stromal cells, cancer cells and proteins to communicate between the CNS parenchyma and peripheral vasculature. Similar to what has been reported in the intestinal tract, we have visualized myeloid cells extend dendritic processes across the blood brain barrier (BBB) into pial blood vessels. Furthermore, transient vessel leaks seen during systemic inflammation provide opportunities for cellular protein to be exchanged between the periphery and CNS. These insights provide new, visual information regarding immune surveillance and antigen presentation within the CNS. Furthermore, when combining intravital 2P-LSM and microfluidic devices complexed with mathematical modeling, we are gaining new insights into the intravascular behavior of circulating immune cells. This new knowledge into the basic mechanisms by which cells migrate to and interact with the CNS provide important considerations for the design of neuro-electronic biomaterials that have the potential to connect the peripheral-neural microenvironments into a unique, artificial interface.