Not your Mother's MAPKs: Apicomplexan MAPK function in daughter cell budding.

Reversible phosphorylation by protein kinases is one of the core mechanisms by which biological signals are propagated and processed. Mitogen-activated protein kinases, or MAPKs, are conserved throughout eukaryotes where they regulate cell cycle, development, and stress response. Here, we review advances in our understanding of the function and biochemistry of MAPK signaling in apicomplexan parasites. As expected for well-conserved signaling modules, MAPKs have been found to have multiple essential roles regulating both Toxoplasma tachyzoite replication and sexual differentiation in Plasmodium. However, apicomplexan MAPK signaling is notable for the lack of the canonical kinase cascade that normally regulates the networks, and therefore must be regulated by a distinct mechanism. We highlight what few regulatory relationships have been established to date, and discuss the challenges to the field in elucidating the complete MAPK signaling networks in these parasites.

Ancient MAPK ERK7 is regulated by an unusual inhibitory scaffold required for Toxoplasma apical complex biogenesis.

Apicomplexan parasites use a specialized cilium structure called the apical complex to organize their secretory organelles and invasion machinery. The apical complex is integrally associated with both the parasite plasma membrane and an intermediate filament cytoskeleton called the inner-membrane complex (IMC). While the apical complex is essential to the parasitic lifestyle, little is known about the regulation of apical complex biogenesis. Here, we identify AC9 (apical cap protein 9), a largely intrinsically disordered component of the Toxoplasma gondii IMC, as essential for apical complex development, and therefore for host cell invasion and egress. Parasites lacking AC9 fail to successfully assemble the tubulin-rich core of their apical complex, called the conoid. We use proximity biotinylation to identify the AC9 interaction network, which includes the kinase extracellular signal-regulated kinase 7 (ERK7). Like AC9, ERK7 is required for apical complex biogenesis. We demonstrate that AC9 directly binds ERK7 through a conserved C-terminal motif and that this interaction is essential for ERK7 localization and function at the apical cap. The crystal structure of the ERK7-AC9 complex reveals that AC9 is not only a scaffold but also inhibits ERK7 through an unusual set of contacts that displaces nucleotide from the kinase active site. ERK7 is an ancient and autoactivating member of the mitogen-activated kinase (MAPK) family and its regulation is poorly understood in all organisms. We propose that AC9 dually regulates ERK7 by scaffolding and concentrating it at its site of action while maintaining it in an "off" state until the specific binding of a true substrate.

Does Shorter Time to Treatment of Pediatric Supracondylar Humerus Fractures Impact Clinical Outcomes?

BACKGROUND: Treatment of supracondylar humerus (SCH) fractures within 18 hours of presentation is a tracked quality metric for ranking of pediatric hospitals. This is in contrast with literature that shows time to treatment does not impact outcomes in SCH fractures. We aim to determine whether an 18-hour cutoff for pediatric supracondylar humerus fracture treatment is clinically significant by comparing the complication risks ofpatients on either side of this timepoint. Our hypothesis is that there will be no statistically significant differences based on time to treatment. METHODS: A retrospective review of clinical outcomes was performed for 472 pediatric patients who underwent surgical management of isolated supracondylar humerus fractures between 1997 and 2022 at a single level I pediatric trauma hospital. The cohort was split based on time to surgery (within or ≥18 h from Emergency Department admission). RESULTS: Surgical treatment occurred within 18 hours of arrival in 435 (92.2%) patients and after 18 hours in 37 (7.8%) patients. Mean age was 5.6±2.2 years and 51.5% of patients were female. Gartland fracture classification was type II [n=152 (32.3%)], type III [n=284 (60.3%)], type IV [n=13 (2.8%)], or flexion-type [n=18 (3.8%)]. There were no differences in demographic characteristics or fracture classification between cohorts. Fractures in the ≥18-hour cohort were treated more commonly with 2 pins (62.2% vs. 38.5%, P =0.04). There were no statistically significant differences in open versus closed reduction, utilization of medial pins, or postoperative immobilization between cohorts. We were unable to detect any differences in postoperative complications, including non-union, delayed union, stiffness, malunion, loss of reduction, iatrogenic nerve injury, or infection. This remained true when type II fractures were excluded. CONCLUSIONS: Using an arbitrary time cutoff of <18 hours does not influence clinical outcomes in the surgical treatment of SCH fractures. This held true when type II fractures were excluded. For this reason, we recommend modification to the USNWR guidelines to decrease emphasis on time-to-treatment of SCH fractures. LEVEL OF EVIDENCE: Level III.

Comparison of Fixation Techniques for Lower Extremity Rotationplasty.

BACKGROUND: Rotationplasty is a reconstructive, limb-sparing surgery indicated for patients with lower extremity musculoskeletal tumors. The procedure involves rotation of the distal lower extremity to allow the ankle to function as the new knee joint and provide an optimum weight-bearing surface for prosthetic use. Historically there is limited data comparing fixation techniques. The purpose of this study is to compare clinical outcomes between intramedullary nailing (IMN) and compression plating (CP) in young patients undergoing rotationplasty. METHODS: A retrospective review of 28 patients with a mean age of 10±4 years undergoing a rotationplasty for either a femoral (n=19), tibial (n=7), or popliteal fossa (n=2) tumor was performed. The most common diagnosis was osteosarcoma (n=24). Fixation was obtained with either an IMN (n=6) or CP (n=22). Clinical outcomes of patients undergoing rotationplasty were compared between the IMN and CP groups. RESULTS: Surgical margins were negative in all patients. The mean time to union was 24 months (range 6 to 93). There was no difference in the meantime to the union between patients treated with an IMN versus those with a CP (14±16 vs. 27±26 mo, P =0.26). Patients undergoing fixation with an IMN were less likely to have a nonunion (odds ratio: 0.35, 95% confidence interval: 0.03-3.54, P =0.62). Postoperative fracture of the residual limb only occurred in patients undergoing CP fixation (n=7, 33% vs. n=0, 0%, P =0.28). Postoperative fixation complications occurred in 13 (48%) patients, most commonly a nonunion (n=9, 33%). Patients undergoing fixation with a CP were more likely to have a postoperative fixation complication (odds ratio: 20, 95% CI: 2.14-186.88, P <0.01). CONCLUSIONS: Rotationplasty is an option for limb salvage for young patients with lower extremity tumors. The results of this study reveal fewer fixation complications when an IMN can be used. As such, IMN fixation should be considered for patients undergoing a rotationplasty, though equipoise should be shown by surgeons when determining technique.

Divergent kinase regulates membrane ultrastructure of the Toxoplasma parasitophorous vacuole.

Apicomplexan parasites replicate within a protective organelle, called the parasitophorous vacuole (PV). The Toxoplasma gondii PV is filled with a network of tubulated membranes, which are thought to facilitate trafficking of effectors and nutrients. Despite being critical to parasite virulence, there is scant mechanistic understanding of the network's functions. Here, we identify the parasite-secreted kinase WNG1 (With-No-Gly-loop) as a critical regulator of tubular membrane biogenesis. WNG1 family members adopt an atypical protein kinase fold lacking the glycine rich ATP-binding loop that is required for catalysis in canonical kinases. Unexpectedly, we find that WNG1 is an active protein kinase that localizes to the PV lumen and phosphorylates PV-resident proteins, several of which are essential for the formation of a functional intravacuolar network. Moreover, we show that WNG1-dependent phosphorylation of these proteins is required for their membrane association, and thus their ability to tubulate membranes. Consequently, WNG1 knockout parasites have an aberrant PV membrane ultrastructure. Collectively, our results describe a unique family of Toxoplasma kinases and implicate phosphorylation of secreted proteins as a mechanism of regulating PV development during parasite infection.

Noninvasive Hemoglobin Monitoring for Postoperative Pediatric Orthopaedic Patients: A Preliminary Study.

BACKGROUND: Hemoglobin (Hgb) levels are frequently checked through venipuncture [invasive hemoglobin (iHgb)] in pediatric orthopaedic patients after high blood loss procedures. This needlestick may causes further anxiety and fear in hospitalized children. Noninvasive hemoglobin (nHgb) monitoring has been effectively utilized in the adult intensive care and postoperative total joint arthroplasty setting. nHgb monitoring has not yet been validated in children for routine postoperative Hgb assessment in pediatric orthopaedics. METHODS: In this prospective study, 46 pediatric orthopaedic patients were enrolled who were undergoing surgery and postoperative standard of care iHgb testing. On postoperative day 1, Hgb levels were obtained through venipuncture and nHgb monitor (Pronto-7; Masimo) within a 2-hour period. Patient preferences, iHgb and nHgb values, time to result, and provider preferences were recorded. Cost data were estimated based on the standard Medicare payment rates for lab services versus the cost of nHgb probe. RESULTS: nHgb results were obtained after 1 attempt in 38 patients (83%), after multiple attempts in 7 patients (15%), and could not be obtained in 1 patient. The mean time to obtain nHgb value was significantly shorter than that to obtain iHgb results (1.3±1.5 vs. 40±18.1 min; P <0.0001). The mean nHgb value was significantly higher than the mean iHgb value (11.7±1.5 vs. 10.6±1.1 g/dL, P <0.0001). nHgb exceeded iHgb by 2 g/dL or more in 12 (26%) patients (2.64±0.9 vs. 0.54±0.84 g/dL; P <0.0001). The concordance correlation coefficient between the 2 Hgb methods was 0.59, indicating moderate agreement. Forty-three (93%) of our patients and 34 (74%) of the care providers preferred nHgb over iHgb if results were equivalent. At our institution, the cost per iHgb monitoring is approximately $28 per blood draw as compared with $5 for nHgb monitoring. Interestingly, no patients required postoperative transfusion during the study period, as asymptomatic patients with no cardiac disease are typically observed unless the Hgb is <6. CONCLUSIONS: nHgb monitoring in postoperative pediatric patients overestimated Hgb levels compared with the standard of care methods; however, nHgb had high patient and provider satisfaction and had moderate agreement with iHgb. As no patients required transfusion, postoperative Hgb checks could likely be discontinued in some portion of our population. LEVEL OF EVIDENCE: Level Ib-Diagnostic study.

Tiered Guidelines in a Pediatric Orthopaedic Practice Reduce Opioids Prescribed at Discharge.

BACKGROUND: Data regarding opioid prescribing patterns following pediatric orthopaedic procedures is limited. The aim of this work was to evaluate the effects of tiered guidelines for discharge opioid prescriptions following common pediatric orthopaedic procedures. METHODS: Quality improvement project conducted at a single academic institution. Guidelines for discharge opioid prescriptions were implemented January 2018 and established 4 tiers of increasing invasiveness for 28 common pediatric orthopaedic procedures. Patients who underwent these procedures in 2017 comprised the preguideline cohort (N=258), while patients treated in 2019 comprised the postguideline cohort (N=212). Opioid prescriptions were reported as oral morphine equivalents (OMEs). Univariate tests were performed to assess statistically significant differences before and after implementation of the guidelines. RESULTS: There was a significant decrease in OME prescribed between preguideline and postguideline cohorts (median OME 97.5 vs. 37.5). When analyzed according to procedure tiers, tiers 1, 2, and 4 showed significant decreases in OME prescribed between 2017 and 2019. The rate of no opioids prescribed at discharge increased from 13% to 23% between preguideline and postguideline cohorts. The 30-day refill rate did not significantly change. After implementation of guidelines, 91% of all prescriptions were within the guideline parameters, and there was a significant reduction in prescription variability. In tier 4 procedures, median OME prescribed decreased from 375 preguideline to 188 postguideline, but was associated with greater opioid refills within 30 days of discharge (10.2% preguideline vs. 28.8% postguideline). CONCLUSIONS: Tiered guidelines for discharge opioid prescriptions following pediatric orthopaedic procedures can significantly decrease the quantity of opioids prescribed. Furthermore, we noted excellent adherence and no overall increase in the rates of narcotic refills. Such guidelines may improve pediatric orthopaedists' ability to responsibly treat postoperative pain while limiting the distribution of unneeded opioids. LEVEL OF EVIDENCE: Level IV-quality improvement project.

The Open Triradiate Cartilage: How Young Is Too Young for Total Hip Arthroplasty?

BACKGROUND: There is, to our knowledge, no published literature regarding primary total hip arthroplasty (THA) in pediatric patients with an open triradiate cartilage. The purpose of this study was to report the outcomes following primary THA in pediatric patients with open triradiate cartilage at a single intuition. METHODS: Using a single institution's Total Joint Registry, 12 patients (13 hips) were identified as having undergone primary THA with open triradiate cartilage between the years of 2000 and 2019. The mean age and body mass index of this group were 13.1 years and 25.5 kg/m2, respectively. The cohort was composed of 10 males, and the mean follow up was 5.5 years. Indications for surgery, functional outcomes, and radiographic signs of stable fixation were analyzed. RESULTS: The most common indication for surgery was avascular necrosis secondary to corticosteroid use (31%), followed by avascular necrosis after operative management of slipped capital femoral epiphysis (23%). The proportion of patients able to achieve independent, gait-aid free, ambulation improved from 23% to 100%. Mean postoperative Harris Hip Score was 92.3. All constructs were cementless, and bearing surfaces included ceramic-on-ceramic in 62% and ceramic on highly crosslinked polyethylene bearings in the remainder. Radiographic review at final follow up demonstrated osseointegration in 12 of 13 (92%) acetabular components. Although 1 patient experienced both acetabular component loosening and instability, on separate occasions, there were no incidences of infection, wound dehiscence, thromboembolic events, or failure secondary to wear. CONCLUSIONS: In this study, THA in patients with an open triradiate cartilage yielded significant clinical improvement, low complication rates and good initial implant survivorship at early follow up. Awaiting closure of the triradiate cartilage for concerns of decreased fixation and implant survivorship may be unnecessary. LEVEL OF EVIDENCE: Level IV-case series.

Trends in Incidence of Adolescent Idiopathic Scoliosis: A Modern US Population-based Study.

BACKGROUND: A successful disease screening strategy requires a high incidence of the condition, efficacy of early treatment, and efficient detection. There is limited population-based data describing trends in incidence of adolescent idiopathic scoliosis (AIS) in the United States and potential role of school screening programs on the incidence of AIS. Thus, we sought to evaluate the incidence of AIS over a 20-year period between 1994 and 2013 using a population-based cohort. METHODS: The study population comprised 1782 adolescents (aged 10 to 18 y) with AIS first diagnosed between January 1, 1994 and December 31, 2013. The complete medical records and radiographs were reviewed to confirm diagnosis and coronal Cobb angles at first diagnosis. Age-specific and sex-specific incidence rates were calculated and adjusted to the 2010 United States population. Poisson regression analyses were performed to examine incidence trends by age, sex, and calendar period. RESULTS: The overall age-adjusted and sex-adjusted annual incidence of AIS was 522.5 [95% confidence interval (CI): 498.2, 546.8] per 100,000 person-years. Incidence was about 2-fold higher in females than in males (732.3 vs. 338.8/100,000, P<0.05). The incidence of newly diagnosed AIS cases with radiographs showing a Cobb angle >10 degrees was 181.7 (95% CI: 167.5, 196.0) per 100,000 person-years. The overall incidence of AIS decreased significantly after discontinuation of school screening in 2004 (P<0.001). The incidence of bracing and surgery at initial diagnosis was 16.6 (95% CI: 12.3, 20.9) and 2.0 (95% CI: 0.5, 3.4) per 100,000 person-years, respectively. CONCLUSIONS: Overall population-based incidence of AIS decreased after school screening was discontinued. However, incidence of patients with a Cobb angle >10 degrees, initiation of bracing and surgery did not change significantly over time. This provides further data to help determine the role of scoliosis screening. LEVEL OF EVIDENCE: Level III.

Does Shorter Time to Treatment of Pediatric Femur Shaft Fractures Impact Clinical Outcomes?

BACKGROUND: Annual rankings by US News and World Report are a widely utilized metric by both health care leaders and patients. One longstanding measure is time to treatment of femur shaft fractures. Hospitals able to provide at least 80% of pediatric patients with an operating room start time within 18 hours of admission to the emergency department score better as part of the overall pediatric orthopaedic ranking. Therefore, it is important to determine whether the 18-hour treatment time for pediatric femur shaft fractures is a clinically meaningful metric. METHODS: A retrospective review of clinical outcomes of 174 pediatric patients (aged below 16 y) with isolated femur shaft fractures (Injury Severity Score=9) was conducted from 1997 to 2017 at a single level I pediatric trauma center. The 2 comparison groups were patients receiving fracture reduction within 18 hours of emergency department admission (N=87) or >18 hours (N=87). RESULTS: Patient, injury, and surgical characteristics were similar between the 2 groups. Both groups had a similar mean age (treatment <18 h=7.5 y; treatment >18 h=8.1 y). Patients who received treatment within 18 hours were more often immobilized postoperatively (70.1% vs. 53.5%; P=0.0362) and had a shorter median hospital length of stay (2 vs. 3 d; P=0.0047). There were no statistically significant differences in any outcomes including surgical site infection, time to weight-bearing (treatment <18 h mean=48.1 d vs. 52.5 d), time to complete radiographic fracture healing (treatment <18 h mean=258.9 d vs. 232.0 d), decreased range of motion, genu varus/valgus, limb length discrepancy, loss of reduction, or persistent pain. CONCLUSIONS: Treatment of pediatric femur shaft fractures within 18 hours does not impact clinical outcomes. National quality measures should therefore use evidence-based metrics to help improve the standard of care. LEVEL OF EVIDENCE: Therapeutic level III.

Intercalary Allograft Reconstruction of the Proximal Tibia With and Without a Free Fibula Flap in Pediatric Patients.

BACKGROUND: Limb salvage of the proximal tibia can be difficult due to the growth potential of and functional demands of the pediatric patients. Multiple reconstruction techniques exist, however, the ideal form of reconstruction is yet to be elucidated. The purpose of the current study is to evaluate outcomes in patients with an intercalary resection of the proximal tibia reconstructed with an allograft with or without a free vascularized fibula flap (FVF). METHODS: Seventeen pediatric patients (9 males, 8 females) underwent lower extremity limb salvage with the use of intercalary cadaveric allograft at a mean age of 12±4 years. The most common diagnoses were osteosarcoma (n=6) and Ewing sarcoma (n=6). Patients were reconstructed with an allograft alone (n=6) or supplemented with an FVF (n=11). RESULTS: All surviving patients had at least 2 years of clinical follow-up, with the mean follow-up of 12±7 years. The mean time to union of the allograft was 11±4 months, with 6 patients requiring additional bone grafting. There was no difference in the need for an additional bone graft (odds ratio=1.14, P=1.0) between patients with an FVF and those without. Four patients underwent an amputation, all with an allograft alone, due to disease recurrence (n=2) and due to infection (n=2). As such, there was a higher 10-year overall limb-salvage rate when the allograft was combined with an FVF compared with an allograft alone (100% vs. 33%, P=0.001). At last follow-up, the mean Mankin and Musculoskeletal Tumor Society rating was 86%, with a higher mean score in patients reconstructed with an FVF (94% vs. 70%, P=0.002). CONCLUSION: Use of an intercalary allograft supplemented with an FVF to reconstruct the proximal tibia provides a durable means of reconstruction with an excellent functional outcome following oncologic proximal tibia resection in a pediatric population. LEVEL OF EVIDENCE: Level III-therapeutic level.

Derotational Pronation-producing Osteotomy of the Radius and Biceps Tendon Rerouting for Supination Contractures in Neonatal Brachial Plexus Palsy Patients: A Review of 20 Cases.

BACKGROUND: Forearm supination contractures can occur as a result of neurological derangement of the upper extremity in patients with neonatal brachial plexus birth palsy. The contractures become problematic in childhood as patients begin requiring forearm pronation for activities of daily living including typing on a keyboard and writing. There have been several techniques described to remedy this deformity. We present a case series describing the early clinical results of combined radial osteotomy and intraosseous biceps rerouting to realign the forearm in resting pronation and convert the biceps from a supinator to a pronator. METHODS: A retrospective review identified patients who had a radial osteotomy and biceps rerouting for supination contracture between 2006 and 2016. Inclusion criteria required a fixed forearm supination contracture, patients below 18 years of age and at least 1 year of clinical and radiographic follow-up. Demographic and surgical variables, early clinical results, complications, reoperations, and revisions were documented. RESULTS: Twenty patients were identified who met inclusion criteria. The mean follow-up was 3 years (range, 1 to 9 y). We observed a statistically significant difference in the mean resting position of the forearm from 56 degrees of supination preoperatively to 17 degrees of pronation postoperatively. Correspondingly, there was an increase in passive forearm pronation from 0 degree preoperatively to 66 degrees postoperatively and an expected decrease in passive forearm supination from 78 degrees preoperatively to 41 degrees postoperatively. There were 2 complications which were both radial osteotomy nonunions. Excluding revisions, there were 14 reoperations in 14 patients (63%) for hardware removal. Hardware removal was considered an expected return to the operating room, not an unplanned reoperation. There were 2 revisions for osteotomy nonunion, both of which went on to eventual union. Overall survivorship from the need for revision surgery was 95% at 12 months, 88% at 24 months, and 88% at 60 months. There were no recurrences of the supination contracture. CONCLUSIONS: We present results of a novel surgical solution to forearm supination contractures through the combination of a derotational osteotomy of the radius and biceps tendon rerouting. The results show a significant benefit in forearm positioning and passive pronation with excellent survivorship and maintenance of correction. LEVEL OF EVIDENCE: Level IV-therapeutic.

Total Knee Arthroplasty Is Safe and Successful in Patients With Klippel-Trénaunay Syndrome.

BACKGROUND: Klippel-Trénaunay syndrome (KTS) is a severe vascular malformation that can lead to hypertrophic osteoarthritis. Total knee arthroplasty (TKA) performed in extremities affected with KTS is challenging given the high-risk vascular considerations and occasionally poor bone quality. METHODS: We identified 12 patients with KTS who underwent TKA between 1998 and 2017. There were 7 men, mean age 42 years, and mean follow-up was 7 years. Before arthroplasty, 2 patients (17%) had preoperative sclerotherapy. Preoperative vascular studies were done for 9 patients (75%) and included magnetic resonance imaging (n = 7), magnetic resonance angiography (n = 1), and computed tomography angiography (n = 1). A preoperative blood conservation protocol was used for all operations and included the use of tranexamic acid (TXA) in later years. Posterior-stabilized TKA was used in 10 cases and cruciate-retaining TKA was used in 2 cases. RESULTS: At final follow-up, 2 patients (17%) had undergone revision surgery: 1 for infection and 1 for tibial loosening with subsequent arthrofibrosis. Knee Society Scores (36-83, P < .0001) and functional scores (48-84, P = .0007) significantly increased between the preoperative and postoperative period. Likewise at last follow-up, the mean knee range of motion significantly increased (82°-104°, P = .04). Median blood loss for patients who received TXA was 200 mL compared to 275 mL in patients who did not receive TXA (P = .66). Likewise there was no difference (P = .5) in the proportion of patients who required a transfusion between those who received TXA (2/6, 33%) and those who did not (3/6, 50%). CONCLUSION: In this small series, TKA can lead to significant clinical improvement for patients with KTS. Modern blood management techniques and a careful multidisciplinary care approach render TKA a reasonable option for select patients with KTS. LEVEL OF EVIDENCE: Level IV case series, therapeutic.

Distal Junctional Failure Following Pediatric Spinal Fusion.

BACKGROUND: Adjacent segment pathology is a known complication after spinal fusion, but little has been reported on junctional failure. A series of adolescent patients presented with acute distal junctional failure (DJF). We sought to determine any common features of these patients to develop a prevention strategy. METHODS: A retrospective review was conducted of pediatric patients who developed DJF after instrumented spinal fusion performed at 2 institutions from 1999 to 2013. Patients with proximal junctional failure or junctional kyphosis without failure were excluded. RESULTS: Fifteen subjects were identified with mean follow-up of 38 months. Distal failure occurred a mean of 60 days after index surgery, with history of minor trauma in 4 patients. Failures included 3-column Chance fracture (11) or instrumentation failure (4). Thirteen patients presented with back pain and/or acute kyphosis, whereas 2 asymptomatic patients presented with healed fractures. Two patients also developed new onset of severe lower extremity neurological deficit after fracture, which improved but never resolved after revision. A total of 13/15 subjects required revision surgery, typically within 1 week. Complications associated with revision surgery were encountered in 8 patients (62%). Major complications that required return to the operating room included 2 deep infections, 2 instrumentation failures, and dense lower extremity paralysis that improved after medial screw revision and decompression. At final follow-up, 10 patients are asymptomatic, 2 have persistent neurological deficit, 2 have chronic pain, and 1 has altered gait with gait aid requirement. CONCLUSIONS: This study analyzes a heterogenous cohort of spinal fusion patients who developed DJF from 3-column Chance fracture or instrumentation failure. Revision surgery is typically required, but has a high complication rate and can result in severe neurological deficit, highlighting the morbidity of this complication. It is unclear whether level of the lowest instrumented vertebra contributes to DJF. Increased awareness of junctional failure in children may prompt additional studies to further characterize risk factors and preventative strategies. LEVEL OF EVIDENCE: Level IV-study-type case series.

Treatment of Pediatric Osteoid Osteomas Not Amenable to Radiofrequency Ablation: A Retrospective Review of Surgical Outcomes.

The purpose of this study is to describe the surgical treatment of osteoid osteomas in a pediatric cohort of patients who were found not to be candidates for percutaneous ablative therapies. Medical records for 29 pediatric patients who were treated surgically for osteoid osteomas were reviewed. Reasons for surgical management included diagnostic uncertainty or lesions that were in close proximity to an articular surface or neurovascular structure. Twenty-eight patients experienced complete symptom resolution. Surgical treatment may still be indicated in a select group of osteoid osteoma patients who are not candidates for percutaneous treatment. (Journal of Surgical Orthopaedic Advances 27(4):299-302, 2018).

Is There a Deficit After Nonoperative Versus Operative Treatment of Shortened Midshaft Clavicular Fractures in Adolescents?

BACKGROUND: Recent clinical studies in adults have reported a higher incidence of symptomatic malunions and functional deficits in nonoperatively treated shortened midshaft clavicular fractures. We sought to determine whether functional or subjective deficits are found in adolescents after operative versus nonoperative treatment of clavicle fractures. METHODS: Adolescents with displaced midshaft clavicle fractures, >15 mm of shortening, and a minimum of 9 months of follow-up were recruited. Exclusion criteria included concomitant upper extremity injuries or abnormalities that would affect biomechanical strength testing. Sixteen patients, equally divided between nonoperative and operative plate fixation, met inclusion criteria and consented to testing. The average age (±SD) at the time of injury was 14±2 years (range, 10 to 16 y), time from injury was 22±10 months (range, 10 to 41 mo), and shortening was 24±6 mm (range, 16 to 35 mm). Consenting subjects completed a QuickDASH Score, Constant Shoulder Score, and questions regarding satisfaction with treatment. Quantitative isometric strength, range of motion, and abduction fatigue testing was performed on the involved and uninvolved sides for comparison. RESULTS: Treatment groups did not differ in age, time from injury, or fracture shortening. QuickDASH and Constant Shoulder Scores were perfect in all but 1 patient in the operative group who actively complained of persistent symptomatic hardware. This patient and one other in the operative group underwent symptomatic hardware removal. There were no cases of symptomatic malunions in the nonoperative group. All patients expressed satisfaction with their treatment. Two in each treatment group were unsatisfied with the appearance of the clavicle. With the exception of a 3% decrease in abduction strength in the operative group (P=0.03) there were no differences in range of motion, isometric strength, or abduction fatigue of the involved shoulder in either treatment group. CONCLUSIONS: Shortened midshaft clavicular fractures had excellent outcomes after both operative and nonoperative treatments. No subjective or objective differences were observed between treatment groups. LEVEL OF EVIDENCE: Level III-therapeutic, retrospective comparative study.

Long-Term Outcomes at Skeletal Maturity of Combined Pelvic and Femoral Osteotomy for the Treatment of Legg-Calve-Perthes Disease.

Surgical treatment for Legg-Calve-Perthes disease (LCPD) is recommended for older children with moderate to severe disease. We sought to determine whether double osteotomies lead to improved radiologic outcomes compared to reported non-operative outcomes. Patients older than 6 years of age diagnosed with LCPD lateral pillar B or C who were treated with pelvic and femoral osteotomies were included. Radiologic outcomes and leg-length discrepancies were assessed using the Stulberg classification and were compared with the current literature. Fifteen hips in fourteen patients were treated with double osteotomy for LCPD, and seven had lateral pillar C disease (47%). The mean age at surgery was 8.6 years (range, 7.2-10.4) and the mean age at follow-up was 20.2 years (range, 14.2-35.6). At a mean 11.6-year follow-up (range: 6.3-25.2), double osteotomy resulted in 40% of patients having Stulberg I/II scores, 27% having Stulberg III scores, and 33% having Stulberg IV/V scores. The mean leg-length discrepancy was 1.4 cm in lateral pillar C patients compared to 0.8 cm in lateral pillar B patients. Four patients underwent additional surgeries, including two who required total hip arthroplasty. Double osteotomy as an alternative surgical procedure for the treatment of LCPD did not show improved outcomes when compared to historic non-operative cohorts.

Toxoplasma ERK7 protects the apical complex from premature degradation.

Accurate cellular replication balances the biogenesis and turnover of complex structures. In the apicomplexan parasite Toxoplasma gondii, daughter cells form within an intact mother cell, creating additional challenges to ensuring fidelity of division. The apical complex is critical to parasite infectivity and consists of apical secretory organelles and specialized cytoskeletal structures. We previously identified the kinase ERK7 as required for maturation of the apical complex in Toxoplasma. Here, we define the Toxoplasma ERK7 interactome, including a putative E3 ligase, CSAR1. Genetic disruption of CSAR1 fully suppresses loss of the apical complex upon ERK7 knockdown. Furthermore, we show that CSAR1 is normally responsible for turnover of maternal cytoskeleton during cytokinesis, and that its aberrant function is driven by mislocalization from the parasite residual body to the apical complex. These data identify a protein homeostasis pathway critical for Toxoplasma replication and fitness and suggest an unappreciated role for the parasite residual body in compartmentalizing processes that threaten the fidelity of parasite development.

Cryo-tomography reveals rigid-body motion and organization of apicomplexan invasion machinery.

The apical complex is a specialized collection of cytoskeletal and secretory machinery in apicomplexan parasites, which include the pathogens that cause malaria and toxoplasmosis. Its structure and mechanism of motion are poorly understood. We used cryo-FIB-milling and cryo-electron tomography to visualize the 3D-structure of the apical complex in its protruded and retracted states. Averages of conoid-fibers revealed their polarity and unusual nine-protofilament arrangement with associated proteins connecting and likely stabilizing the fibers. Neither the structure of the conoid-fibers nor the architecture of the spiral-shaped conoid complex change during protrusion or retraction. Thus, the conoid moves as a rigid body, and is not spring-like and compressible, as previously suggested. Instead, the apical-polar-rings (APR), previously considered rigid, dilate during conoid protrusion. We identified actin-like filaments connecting the conoid and APR during protrusion, suggesting a role during conoid movements. Furthermore, our data capture the parasites in the act of secretion during conoid protrusion.