Background: Slipped capital femoral epiphysis (SCFE) occurs at a rate of 1 in 10,000 to 20,000 children. Methods: A PubMed search was undertaken to evaluate recent SCFE literature. A convenience sample of articles were selected and summarized. Results: Most slips appear well tolerated long-term with ∼5% resulting in total hip arthroplasty (THA) at 20-year follow-up. Classic data reveals poor outcomes following closed reduction for treatment of SCFE. Improvements in intraoperative fluoroscopy and avoidance of pin penetration have reduced the rates of chondrolysis. Unfortunately, avascular necrosis remains a known risk in patients, occurring in 15% to 50% of patients following acute, unstable slips. This is the most common cause of THA in patients with SCFE. Rate of THA due to degenerative arthritis secondary to SCFE is more difficult to determine and occurs at a later age. Although realignment procedures to address anatomic abnormalities from SCFE have increased in popularity, it is unclear if this prevents degenerative arthritis and subsequently reduces the rate of THA. SCFE patients face an increased risk of disability and death due to their underlying medical comorbidities. Interventions for weight loss, blood pressure management, and lifestyle adjustments should be considered at the time of SCFE diagnosis. Conclusions: SCFE remains a challenging and common condition for pediatric orthopedists. Although innovative techniques have been proposed, long-term outcome data still supports in situ pinning for stable slips, and in situ pinning with capsular decompression for unstable slips to minimize the risk of avascular necrosis.

The fibroblast growth factor (FGF) family has an important role in processes such as angiogenesis, wound healing, and development in which precise control of proteinase activity is important. The human plasma proteinase inhibitor ␣ 2 -macroglobulin (␣ 2 M) regulates cellular growth by binding and modulating the activity of many cytokines and growth factors. These studies investigate the ability of native and activated ␣ 2 M (␣ 2 M*) to bind to members of the FGF family. Both ␣ 2 M and ␣ 2 M* bind specifically and saturably to FGF-1, -2, -4, and -6, although the binding to ␣ 2 M* is of significantly higher affinity. Neither ␣ 2 M nor ␣ 2 M* bind to FGF-5, -7, -9, or -10. FGF-2 was chosen for more extensive study in view of its important role in angiogenesis. It was demonstrated that FGF-2 binds to the previously identified TGF-␤ binding site. The ␣ 2 M* inhibits FGF-2-dependent fetal bovine heart endothelial cell proliferation in a dose-dependent manner. Unexpectedly, IntroductionFibroblast growth factors (FGF) constitute a family of heparinbinding proteins that exert pleiotropic effects on cells from all embryonic lineages. 1,2 Sequencing of FGF-1 and FGF-2 has led to the identification of at least 19 proteins that are members of this mammalian family. 3,4 The FGFs are expressed during both embryogenesis and in mature organisms. 5 They play important roles in angiogenesis, mitogenesis, embryonic pattern formation and development, cellular differentiation, and wound healing. 1,[6][7][8][9][10] Only FGF-1 and FGF-2 are expressed at high levels in adults. FGF-1 expression is predominantly confined to the central nervous system, but FGF-2 is ubiquitously expressed throughout all adult tissues. 5 FGF-2 is a potent mitogen for mesoderm-derived cells, such as endothelial cells. 1,11 FGF-2 induces cell proliferation in endothelial cells derived from large vessels or capillaries with a median effective concentration of 1.5 to 2.6 pM. 12 In model systems of angiogenesis, such as the rabbit cornea, the chick chorioallantoic membrane, and the hamster cheek pouch, FGF-2 exerts a potent angiogenic effect. 6,13-15 FGF-1 and -2 are both involved in vasculogenesis, because epiblast cells can be induced to differentiate into endothelial cells by incubation with either of these FGFs. 8 FGF-2 up-regulates the urinary plasminogen activator receptor and stimulates the release of urinary plasminogen activator and collagenase in endothelial cells. [16][17][18] Additionally, FGFs act as chemoattractants for endothelial cells. 19 The ability of the FGFs to exert their effects depends on their interaction with both cellsurface receptor tyrosine kinases and extracellular and cell-surfacebound heparan sulfate proteoglycans. 20,21 However, the nature of the interactions of the FGFs with proteins and molecules that are predominantly fluid-phase has not been extensively investigated.The plasma protein ␣ 2 -macroglobulin (␣ 2 M) is a 718-kd homotetrameric glycoprotein that inactivates proteinases from all 4 mechanistic classes. 22 Proteinase i...

Background:Anterior vertebral body tethering is an alternative to fusion surgery for the treatment of adolescent idiopathic scoliosis (AIS) that is purported to preserve spinal motion. There is limited information regarding the measurable motion that is maintained over the instrumented levels following thoracic anterior vertebral body tethering surgery in humans. The purpose of the present study was to assess radiographic spinal motion 1 year after anterior vertebral body tethering.Methods:As part of a prospective U.S. Food and Drug Administration investigational device exemption study, 32 patients were treated with thoracic anterior vertebral body tethering. At 1 year postoperatively, patients were evaluated with standing flexion-extension and side-bending radiographs in a microdose biplanar slot scanning imaging system. The angle subtended by the screws at the upper instrumented vertebra (UIV) and lower instrumented vertebra (LIV) was measured on left and right-bending radiographs to evaluate the coronal arc of motion and was compared with preoperative values over the same levels. At 1 year postoperatively, the sagittal Cobb angle was measured over the instrumented levels on flexion and extension radiographs.Results:Side-bending radiographs revealed that the mean angle subtended by the screws changed from 15° ± 8° on left-bending radiographs to 8° ± 6° on right-bending radiographs. The mean coronal arc of motion on bending was 7° ± 6°, with 20 (62.5%) of 32 patients having a coronal arc of motion of >5°. The mean preoperative coronal arc of motion over the instrumented segments was 30° ± 9°. On flexion-extension lateral radiographs made at 1 year postoperatively, the mean kyphotic angle over the instrumented segments was 33° ± 13° in flexion and 11° ± 14° in extension, for a mean postoperative arc of motion of 21° ± 12° between flexion and extension radiographs.Conclusions:At 1 year following thoracic anterior vertebral body tethering for the treatment of AIS, the thoracic spine showed a measurable range of coronal and sagittal plane motion over the instrumented levels without evidence of complete autofusion. Motion in the coronal plane decreased by 77% following anterior vertebral body tethering. These findings provide proof of concept that sagittal spinal motion is preserved after thoracic anterior vertebral body tethering, although the functional importance remains to be determined.Level of Evidence:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Basic fibroblast growth factor (FGF-2) is important in development, wound healing and angiogenesis. The human plasma proteinase inhibitor alpha2-macroglobulin (alpha2M) binds to and regulates the biological activity of various growth factors, including FGF-2. FGF-2 binds specifically and saturably to native alpha2M and conformationally modified alpha2M (alpha2M*); however, the KD for FGF-2 binding to alpha2M* is 10-fold lower. This study investigates the biochemical nature of the interaction between FGF-2 and alpha2M* and localizes a possible FGF-2 binding site in the alpha2M subunit. FGF-2 binding to alpha2M* was not affected by shifts in pH between 6.5 and 10; however, increasing temperature decreased the KD for this interaction. The binding affinity of FGF-2 for alpha2M* also increased with increasing ionic strength. These results are consistent with the hypothesis that hydrophobic interactions predominate in promoting FGF-2 association with alpha2M*. Consistent with this hypothesis, FGF-2 bound to a glutathione S-transferase fusion protein containing amino acids 591-774 of the alpha2M subunit (FP3) and to a hydrophobic 16-amino-acid peptide (amino acids 718-733) within FP3. Specific binding of FGF-2 to the 16-amino-acid peptide was inhibited by excess transforming growth factor-beta1. When the 16-amino-acid peptide was chemically modified to neutralize the only two charged amino acids, FGF-2-binding activity was unaffected, supporting the predominant role of hydrophobic interactions. FGF-2 presentation to signalling receptors is influenced by growth factor binding to heparan sulphate proteoglycans (HSPGs), which is electrostatic in nature. Our results demonstrate that the interactions of FGF-2 with alpha2M* and HSPGs are biochemically distinct, suggesting that different FGF-2 sequences are involved.

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Purpose Tarsal coalitions are congenital fusions of two or more tarsal bones and can lead to foot pain and stiffness. Few studies examine the long-term reoperation rates following paediatric tarsal coalition surgery. Methods A population-based database, linking medical records at all medical centres to capture the entire medical history of the full population of a Midwest county, was used to identify tarsal coalitions in children between 1966 and 2018. Records were reviewed for clinical data, surgical records and followed up to identify any subsequent surgical interventions. Results A total of 58 patients (85 coalitions) were identified; 46 calcaneonavicular (CN) coalitions, 30 talocalcaneal (TC) coalitions and nine other coalitions (seven talonavicular, one naviculocuboid, one naviculocuneiform). In all, 46 coalitions were treated surgically (43 coalition resections, three arthrodeses) and 39 were treated nonoperatively. Patients treated surgically were less likely to report ongoing symptoms at final follow-up compared with patients managed nonoperatively (33% versus 67%; p = 0.0017). With a median 14.4 years (interquartile range 9.3 to 19.7) follow-up, there was an overall re-operation rate of 8.7% (4/46). Differences in reoperation rates by initial surgery (resection versus arthrodesis; p = 0.2936), coalition type (CN versus TC versus Other; p = 0.6487) or composition (osseous versus fibrocartilaginous; p = 0.29) did not reach statistical significance. Conclusion This is the first population-based study demonstrating the durability of surgical management of tarsal coalitions in a paediatric population. At final follow-up, patients treated surgically are less likely to report persistent symptoms compared with patients managed nonoperatively. Long-term reoperation rates appear to be low (8.7%). Level of evidence: III

Severe coronavirus disease 2019 (COVID-19) is known to be associated with a heightened risk of thromboembolism. However, the risk associated with mild and moderate illness from COVID-19 is unknown, and there is no current recommendation for prophylaxis against thromboembolism in patients after hospital treatment, unless there are established thrombophilic risk factors. We report the case of a 52-year-old woman who presented with massive saddle pulmonary embolism 1 week after initial hospital discharge, which was treated successfully with thrombolysis. This case raises the question of whether extended prophylactic anticoagulation should be considered even in low-risk COVID-19 cases.