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Objective To evaluate institutional opioid prescribing patterns following percutaneous fixation of pediatric supracondylar humerus fractures before and after implementation of a standardized discharge order set. Design A retrospective review of patients who underwent closed reduction and percutaneous skeletal fixation of a Type II or III supracondylar humerus fracture in 2017 (prior to pain protocol implementation) and again in 2019 (after pain protocol implementation) Setting Single Tertiary Care Children's Hospital Participants In total, 106 patients met inclusion criteria between years 2017 (n = 49) and 2019 (n = 57). Exclusion criteria included miscoded patients, open fractures, patients who presented with vascular injury or nerve palsy, polytrauma patients with multiple fractures in the same upper extremity, and supracondylar humerus fractures that underwent an open procedure. Results There were no significant differences between inpatient pain scores (p = 0.91) and MDE prescribed (p = 0.75) between the 2 cohorts. In 2017, large variability was noted in day supply of opioids (0-11.4 days) and MDE (0-8.45 mg/kg), with significant differences between prescribing patterns of junior and senior level residents (mean day supply of opioids (p = 0.045), mean MDE prescribed on discharge (p = 0.001)). After implementation of a standardized opioid discharge order set, there was a tenfold increase in the number of patients discharged without an opioid prescription (2017: 4%, 2019: 44%). Additionally, any discrepancies between prescribing practices of junior and senior level residents were eliminated (mean day supply of opioids (p = 0.65), mean MDE prescribed on discharge (p = 0.69)). Conclusions The introduction of a standardized post-operative opioid discharge order set led to a 10-fold increase in the number of patients discharged without an opioid prescription. Additionally, the order set decreased the variability in the prescribing patterns of discharge opioid medications without change in pain control. The resident prescribing variability based upon level of experience resolved with the use of the order set.

Accessory ossicles are a common radiographic finding about the foot and ankle in children and adolescents. They are often noted incidentally during evaluation of foot and ankle injuries, and most can be managed nonsurgically. Although over 20 accessory ossicles have been described around the foot and ankle, five specific structures generate the most concern in pediatric patients. An accessory navicular presents commonly with medial midfoot pain and may require surgical intervention after failure of nonsurgical treatment. Although an accessory navicular can be treated surgically with simple excision, there is some recent evidence that supports concomitant reconstruction of associated flatfoot deformities. Os trigonum, an ossicle posterior to the talus, is also commonly asymptomatic. However, os trigonum may be associated with persistent posterior ankle pain, and open and endoscopic resection techniques are successful. Os subfibulare is an uncommon ossicle that may be associated with recurrent ankle sprains. Recent literature reports successful return to activities after ossicle excision and ligament reconstruction. Os subtibiale may be confused with a medial malleolar fracture in skeletally immature patients. Os peroneum may contribute to lateral midfoot pain.

Increasingly, patients with early onset scoliosis (EOS) are completing a growth friendly surgical program followed by observation, removal of implants or a definitive spinal fusion. These patients are colloquially referred to as “graduates”. A standardized definition of a graduate is needed for research and comparing the outcomes, family counseling, and a better understanding of the population. A 15-question electronic survey was completed by 39 experienced pediatric spine surgeons to identify factors salient to the definition of a graduate of EOS surgical programs. A Delphi/Nominal group technique session with nine questions was then performed face-to-face with 21 members of the Pediatric Spine Study Group to discuss and refine the definition. A follow-up electronic survey was then distributed to these same 21 members to gain consensus on the final definition. From the initial survey, it was identified that a graduate did not require definitive spinal fusion after a growing program. From the Delphi session, it was determined that skeletal maturity was the most important factor in defining a graduate. A strictly defined minimum length of follow-up was not felt to be a prerequisite for qualification of graduation. After the final electronic version was distributed, > 80% of respondents agreed upon the final definition, thereby achieving consensus. The Pediatric Spine Study Group recommends adoption of the following definition: a “graduate” is a patient who has undergone any surgical program to treat early onset scoliosis, and has reached skeletal maturity and does not have a planned surgical intervention for EOS in the future. V.

Introduction After discontinuation of growth friendly (GF) surgery for early onset scoliosis, patients undergo spinal fusion or continued observation. This last planned treatment is colloquially called "definitive" treatment, conferring these patients as "graduates" of a growing program. The 5-year radiographic and clinical outcomes of this cohort are unknown. Methods An international pediatric spine database was queried for patients from a GF program (spine or rib-based) with minimum 5-year follow-up from last planned surgery (GF or spinal fusion). Radiographs and charts were reviewed for main coronal curve angle and maximum kyphosis as well as occurrence of secondary surgery. Results Of 580 graduates, 170 (29%) had minimum 5-year follow-up (37% male). Scoliosis etiology was congenital in 41 (24%), idiopathic 36 (21%), neuromuscular 51 (30%), and syndromic 42 (25%). Index surgery consisted of spine-based growing rods in 122 (71%) and rib-based distraction in 48 (29%). Mean age at index surgery was 6.8 years, and patients underwent an average of 5.4 lengthenings over an average of 4.9 years (range, 6 mo to 11 y). Last planned treatment was at an average age of 11.8 years (range, 7 to 17 years). Last planned treatment consisted of spinal fusion in 114 patients, 47 had growing implants maintained, 9 had implants removed. Average follow-up was 7.3 years (range, 5 to 13 y).When compared from postdefinitive treatment to 2-year follow-up, there was noted progression of the coronal curve angle (46±19 to 51±21 degrees, P=0.046) and kyphosis (48±20 to 57±25 degrees, P=0.03). However, between 2 and 5 years, no further progression occurred in the coronal (51±21 to 53±21 degrees, P=0.26) or sagittal (57±25 to 54±28 degrees, P=0.93) planes. When stratified based on etiology, there was no significant coronal curve progression between 2- and 5-year follow-up. When comparing spinal fusion patients to those who had maintenance of their growing construct, there was also no significant curve progression.Thirty-seven (21%) underwent at least 1 (average, 1.7; range, 1 to 7) revision surgery following graduation, and 15 of 37 (41%) underwent 2 or more revision surgeries. Reason for revision was implant revision (either GF or spinal fusion) in 34 patients, and implant removal in 3. On an average, the first revision was 2.5 years after the definitive treatment plan (range, 0.02 to 7.4 y). In total, 15 of 37 (41%) revisions occurred over 2 years following the final decision for treatment plan, and 7 of 37 (19%) occurred 5 or more years after the definitive treatment.Patients who underwent spinal fusion as a definitive treatment strategy were more likely to undergo revision surgery (27%) than patients who had their GF implants maintained (11%) (P=0.04). Conclusions Five years following "graduation" from growing surgery for early onset scoliosis, there is progression of curve magnitude in both the coronal and sagittal planes up to 2 years, with no further progression at 5 years. A total of 21% of patients undergo at least 1 revision surgery, and average time to revision surgery is over 2 years from last planned surgery. Risk of revision surgery was higher in patients who underwent a spinal fusion as their definitive treatment strategy. Level evidence Level III-retrospective comparative. Type of evidence Therapeutic.

INTRODUCTION Pediatric venous thromboembolism (VTE) is a concern for orthopaedic surgeons. We sought to query the Pediatric Orthopaedic Society of North America (POSNA) members on current VTE prophylaxis practice and compare those results with those of a previous survey (2011). METHODS A 35-question survey was emailed to all active and candidate POSNA members. The survey consisted of questions on personal and practice demographics; knowledge and implementation of various VTE prophylaxis protocols, mechanical and chemical VTE prophylaxis agents, and risk factors; and utilization of scenarios VTE prophylaxis agents for various clinical scenarios. One- and two-way frequency tables were constructed comparing results from the current survey and those of the 2011 survey. RESULTS Two hundred thirty-nine surveys were completed (18% respondent rate), with most respondents from an academic/university practice reporting one or two partners (>60%). Half were in practice ≥15 years, and >90% reported an almost exclusive pediatric practice. One-third of the respondents reported familiarity with their institution-defined VTE prophylaxis protocol, and 20% were aware of an institutionally driven age at which all patients receive VTE prophylaxis. The most frequently recognized risk factors to guide VTE prophylaxis were oral contraceptive use, positive family history, and obesity. Respondents indicated a similar frequency of use of a VTE prophylaxis agent (either mechanical or chemical) for spinal fusion, hip reconstruction, and trauma (60% to 65%), with lower frequency for neuromuscular surgery (34%) (P < 0.001). One hundred thirty-seven respondents had a patient sustain a deep vein thrombosis, and 66 had a patient sustain a pulmonary embolism. Compared with responses from 2011, only 20 more respondents reported familiarity with their institution VTE prophylaxis protocol (75 versus 55). In 2018, aspirin was used more frequently than in 2011 (52% versus 19%; P < 0.0001) and enoxaparin was used less frequently (20% versus 41%; P < 0.0001). DISCUSSION Over the past 7 years since the first POSNA survey on VTE prophylaxis, most POSNA members are still unaware of their institution specific VTE prophylaxis protocol. Most respondents agree that either mechanical or chemical VTE prophylaxis should be used for spinal fusion, hip reconstruction, and trauma. The use of aspirin as an agent of chemical VTE prophylaxis has increased since 2011. LEVEL OF EVIDENCE Level IV. Type of evidence: therapeutic.

At some point after children with early-onset scoliosis (EOS) undergo implantation of a distraction construct to control deformity and promote growth, a decision is made to discontinue lengthening. The purpose of this study was to evaluate surgeon indications for discontinuation of a lengthening program and to evaluate patient outcomes. As a part of a multicenter database, surgeons prospectively completed a questionnaire at the completion of growth-friendly treatment. Surgeon indications for discontinuation included patient age, pain/functional status, implant status, and spinal deformity parameters. Patient demographics, scoliosis type, deformity parameters, and length of time in a growing program were queried. Patients were treated with a final fusion or observation, and rate of secondary surgeries was analyzed. Questionnaires were completed on 121 patients (61% female). EOS etiology was 31% neuromuscular, 43% congenital, 16% idiopathic, and 10% syndromic. Average age at initiation of growing program was 6.8 ± 3.1 years, and average age at discontinuation was 12.7 ± 2.5 years. The most commonly cited indications for discontinuation of a lengthening program included bone age/skeletal maturity (n = 46), patient age (n = 33), and diminishing returns with expansions (n = 33). A larger coronal Cobb angle was found in patients who underwent definitive fusion (65°) when compared with continued observation (55°, p = 0.001). Twenty-nine (24%) patients were initially treated with observation after completion of a growing construct. In this subgroup, at a minimum of 2 years’ (average 3.8 years’) follow-up, 26/29 (90%) patients remained stable with observation alone; whereas, three (10%) underwent delayed final fusion surgery. The most common surgeon-cited indications for discontinuation of a lengthening program in EOS patients are skeletal maturity and patient age. The majority of patients (76%) underwent definitive spinal fusion after discontinuation of a lengthening program; whereas, those treated with observation alone had a survivorship of 90% at a minimum follow-up of two years.

Objective/Background: No studies to date have evaluated the the effect of rib-based anchors on the translational relationship between the rib and spine. We hypothesized that there would be an increase in the translational distance between the rib anchor and anterior vertebral body in early onset spinal deformity patients managed with long-term rib-based anchors. Methods: All patients with EOSD from a single tertiary level institution treated with a growth-friendly technique surgery utilizing proximal rib-based anchors from 2006-2015 with a minimum of 2-year follow-up were included. Thoracic kyphosis and the translational distance from the rib anchor to the corresponding anterior vertebral body were measured. Results: Twenty-seven patients (13 female, 14 male) qualified for inclusion. Mean age at implantation of the index proximal rib-based construct was 5±1.9 years (range, 1-9). EOSD etiology was congenital: 3, neuromuscular: 17, syndromic: 3, and idiopathic: 4. Mean kyphosis improved from 31±33° preoperatively to 25±20° immediately post-operatively. No significant changes in kyphosis were noted over 1 and 2 year follow-up (p=0.3). Twenty-one (78%) patients demonstrated an increase in translational distance from the rib anchors to the adjacent anterior vertebral body. Immediately post-operatively, mean distance was 25±1 mm and increased at 1-year (26±1 mm) and significantly at 2-year (29±1 mm) follow-up (p=0.005). Conclusion: The use of long term rib-based anchors may lead to an increase in the distance between the rib utilized for proximal fixation and the associated vertebral body, generating what appears to be increased anterior translation of the spine. This translation, in conjunction with increased or increasing overall thoracic kyphosis, may be the source of unexpected obstacles at the time of future surgical procedures for revision or final fusion.

BACKGROUND Obesity rates continue to rise among children and adolescents across the globe. A multicenter research consortium composed of institutions in the Southern US, located in states endemic for childhood obesity, was formed to evaluate the effect of obesity on pediatric musculoskeletal disorders. This study evaluates the effect of body mass index (BMI) percentile and socioeconomic status (SES) on surgical site infections (SSIs) and perioperative complications in patients with adolescent idiopathic scoliosis (AIS) treated with posterior spinal fusion (PSF). METHODS Eleven centers in the Southern US retrospectively reviewed postoperative AIS patients after PSF between 2011 and 2017. Each center contributed data to a centralized database from patients in the following BMI-for-age groups: normal weight (NW, 5th to

Introduction: Surgical Site Infection (SSI) is a rare but serious complication following Posterior Spinal Fusion (PSF) for pediatric scoliosis. Several studies have identified patient risk factors for SSI following PSF, including high Body Mass Index (BMI). The purpose of this study was to determine whether Radiographic Skin-to-spine Distance (RSD) can be used as a surrogate for BMI when evaluating the pediatric patient’s risk of developing a SSI after PSF. Methods: This study was performed retrospectively and included patients ages 0-18 who underwent PSF for scoliosis over a four-year period. RSD, defined as the distance from the L5 spinous process to the skin, was measured using preoperative lateral radiographs. Results: Of the 176 included patients, we identified eight (4.5%) who suffered from surgical site infection following PSF. Logistic regression analysis revealed no statistically significant predictors for SSI. However, there was a strong, statistically significant linear regression prediction between RSD and BMI (r = 0.71, p=0.001). Discussion: RSD was not shown to be predictive of SSI in this patient cohort. However, the strong correlation found between RSD and BMI suggests that when assessing risk of SSI, RSD may be useful as a substitute for BMI when BMI cannot be easily ascertained.

The purpose of this study was to compare the efficacy of a single-sugar-tong splint (SSTS) to a long-arm cast (LAC) in maintaining reduction of pediatric forearm fractures, while avoiding secondary intervention. One hundred patients age 3-15 with a forearm fracture requiring a reduction and immobilization were evaluated (50 LAC and 50 SSTS). Medical records and radiographs were reviewed at injury, postreduction, and at 1, 2, and 4 weeks postinjury. Sagittal and coronal angular deformities were recorded. Any secondary intervention due to loss of reduction was documented. The groups were matched by age (P = 0.19), sex (P = 0.26), mechanism of injury (P = 0.66), average injury sagittal deformity (LAC 27.4°, SSTS 25.4°; P = 0.50), and average injury coronal deformity (LAC 15.5°, SSTS 16°; P = 0.80) At 4 weeks postinjury follow-up, there were no statistically significant differences between use of an SSTS or LAC when comparing postimmobilization sagittal alignment (LAC 10.3 ± 7.2, SSTS 8.4 ± 5.1°; P = 0.46), coronal alignment (LAC 6.9 ± 4.6, SSTS 7.6 ± 9.3°; P = 0.46), or need for repeat manipulation or surgery (LAC 4/50, SSTS 3/50; P = 0.70).

A 9-year-old boy sustained an ulnohumeral dislocation with a medial epicondyle fracture and experienced incomplete post-traumatic median nerve palsy in addition to post-traumatic stiffness following closed reduction and cast immobilization. When his motor palsy and stiffness did not improve, MRI and ultrasound were obtained, which demonstrated entrapment of the median nerve in an osseous tunnel at the fracture site, compatible with type 2 median nerve entrapment. Subsequently, the patient underwent surgery to mobilize the medial epicondyle and free the median nerve, resulting in improved range of motion, near complete restoration of motor function, and complete restoration of sensory function in the median nerve distribution within 6 months of surgery. Median nerve entrapment, particularly intraosseous, is a rare complication of posterior elbow dislocation and medial epicondyle fracture that may result in significant, sometimes irreversible, nerve damage if there is a delay in diagnosis and treatment. A high degree of clinical suspicion with early imaging is indicated in patients with persistent stiffness or nerve deficits following reduction of an elbow dislocation. Intra-articular entrapment diagnosed on ultrasound has been reported and intraosseous entrapment diagnosed clinically and on MR neurography have been reported; however, to our knowledge, this is the first reported case of intraosseous (type 2) median nerve entrapment clearly visualized and diagnosed on traditional MRI and ultrasound. The use of ultrasound for diagnosing median nerve entrapment is an accurate, accessible, and non-invasive imaging option for patients presenting with suspected nerve entrapment following elbow dislocation.

Displaced pediatric forearm fractures often are treated with closed reduction and immobilization. Recent literature demonstrates no difference in maintaining alignment or needing repeat intervention in patients immobilized with either a single sugar-tong splint or a long-arm cast, but most series include patients with distal fractures. This study included patients 3 to 15 years old who underwent closed reduction and immobilization for displaced midshaft or proximal forearm fractures. Radiographs from the time of injury, after reduction, and at 4-week follow-up were reviewed for coronal and sagittal plane angular alignment. Secondary interventions also were recorded. A total of 121 patients (70 long-arm cast, 51 simple sugar-tong splint) met inclusion criteria. Groups were matched in terms of age ( P =.95), sex ( P =.41), body mass index ( P =.12), and angular deformity prior to reduction in the sagittal ( P =.78) and coronal ( P =.83) planes. Following closed reduction, sagittal ( P =.003) and coronal ( P =.002) alignment improved significantly in all patients. At 4-week follow-up, there were no significant differences in sagittal ( P =.15) or coronal ( P =.68) alignment between the 2 groups. Nine patients underwent a secondary intervention after the index reduction (long-arm cast, n=7; simple sugar-tong splint, n=2), with no statistically significant difference between groups ( P =.30). There were no statistically significant differences between patients managed with long-arm cast or simple sugar-tong splint regarding residual sagittal or coronal plane deformity at 4-week follow-up or incidence of secondary intervention. These findings indicate simple sugar-tong splint and long-arm cast appear to be acceptable and equivalent methods of immobilization for these injuries. [ Orthopedics . 2021;44(2):e178–e182.]

Disk space infection (discitis) is an uncommon source of back pain in children. It occurs most frequently in children 1–5 years of age. Signs and symptoms may include back pain, abdominal pain, lethargy, and gait alterations. The non-specific nature of these findings may result in delayed presentation to a medical professional and subsequent diagnosis. Management predominantly includes antibiotic therapy, although short-term immobilization may be recommended in some cases. Biopsy or other surgical interventions are rarely indicated. Long-term sequelae, beyond radiographic changes, especially loss of disc space, are infrequent.

Patients with developmental dysplasia of the hip (DDH) who undergo periacetabular osteotomy (PAO) often have labral tears. The objective of this retrospective study was to compare PAO alone with PAO combined with arthrotomy or arthroscopy in DDH patients who had a full-thickness labral tear on magnetic resonance imaging. In total, 47 hips in the PAO group (PAO) were compared with 60 hips in the PAO with concomitant arthrotomy or arthroscopy (PAO-A) with respect to Hip Disability and Osteoarthritis Outcome Score (HOOS), modified Harris Hip Score (mHHS), Visual Analog Scale (VAS), clinical and radiographic outcomes at a median of 29 months. Reoperation rate and complications were compared between two groups of treatment. The PAO group was younger than the PAO-A group (25.2 ± 9.7 versus 31.3 ± 8.3). The PAO group was more likely to have worse dysplasia: lateral center edge angle (7.6°±9.63° versus 10.8°±6.85°) and anterior center edge angle (4°±12.92° versus 10.8°±9.92°). The PAO group had a higher preoperative mHHS (65.2 ± 15.3 versus 57.8 ± 14.8) and HOOS (66.3 ± 17.5 versus 55.8 ± 20.1). There were no significant differences in final functional outcome scores across treatment groups: mHHS (PAO; 86.8 ± 12.4 versus PAO-A, 83.3 ± 17.2), HOOS (86.5 ± 13.3 versus 82.5 ± 16.8) and VAS (2.5 ± 2.8 versus 2.5 ± 3.1). There was no difference in reoperation rate between two groups (6.4% versus 11.6%, P = 0.51). The overall complication rate was lower in the PAO group (26% versus 68%), but major complications were comparable. On the basis of our data, we were not able to conclusively demonstrate a clear benefit for the routine treatment of all labral tears; however, arthrotomy or arthroscopy may play a role in some conditions.

The crankshaft phenomenon, a progressive rotational and angular spinal deformity that can occur after posterior spinal surgery, has been reported in pediatric patients with idiopathic, congenital, and neuromuscular scoliosis. In the skeletally immature patient, the crankshaft phenomenon is thought to occur secondary to continued growth of the anterior elements of the spine after solid posterior spinal fusion. The condition has also been reported in the setting of newer, so-called growth-friendly posterior distraction-based spinal instrumentation. The clinical evidence of crankshaft phenomenon is often subtle, whereas radiographic findings are usually more apparent. However, objective measurement of radiographic signs may be complicated by instrumentation and postoperative changes. Treatment options for patients with the crankshaft phenomenon are limited; in those with problematic deformity and/or risk of progression, additional surgery may be indicated.

The use of freeze-dried allograft as a bone graft substitute for pediatric spine surgery is safe and efficacious in the thoracic and lumbar spines. Allograft bone use in segmental instrumented fusions in the subaxial cervical spine has not been well reported in the literature. We sought to describe our experience with allograft bone in this patient cohort, and to compare union rates to patients treated with autograft.Medical records were queried over a 10-year time period (2004 to 2014). Inclusion criteria were all pediatric patients (18 y old and below) who underwent subaxial cervical spine fusion with minimum follow-up of 24 months. Variables queried included demographics, type of graft material used, diagnosis, approach (anterior, posterior, combined), levels instrumented, placement of postoperative halo, surgical-related complications, and achievement of fusion.A total of 26 patients qualified for inclusion (18 allograft, 8 autograft). No differences existed between the 2 groups regarding age, sex, or number of fused levels. In the allograft cohort, average age at initial surgery was 13.3 years (range, 5 to 18 y). The most common reasons for surgery included trauma (6), tumor (3), and syndrome-associated kyphosis (3). The average number of instrumented levels was 4 (range, 2 to 13). Four patients (22%) developed a postoperative surgical complication. There were 2 asymptomatic pseudarthroses not requiring revision. At a minimum of 24-month follow-up (average, 45 mo; range, 24 to 121 mo), the allograft group demonstrated a fusion rate of 88%, which was comparable with a fusion rate of 87% in the autograft group.The use of allograft bone for pediatric subaxial instrumented cervical spine fusions is safe in a variety of conditions, with the same rate of fusion as autograft. Rates of complications are acceptable. To avoid donor-site morbidity from autogenous graft harvest, we recommend considering allograft bone in subaxial cervical spine fusions with modern segmental instrumentation.Level IV-case series; therapeutic.

PURPOSE OF REVIEW: Spinal deformity is a common issue in pediatric patients with an underlying neurological diagnosis or syndrome. Management of neuromuscular scoliosis (NMS) is a major part of the orthopedic care of such patients, as the deformity is often progressive, and may affect gait, seating and positioning. In addition, untreated large spinal deformities may be associated with pain and/or cardiopulmonary issues over time. RECENT FINDINGS: Recent changes in medical management of the underlying disease process appears to alter the natural history of certain neuromuscular conditions, and in the case of patients with Duchenne’s muscular dystrophy significantly diminish the incidence of spinal deformity. In the most common diagnosis associated with NMS, cerebral palsy, there is evidence that despite a high complication rate, surgical management of spinal deformity is associated with measurable improvements in validated health-related quality-of-life measures. SUMMARY: Spinal deformity is a common finding in patients with neurological diagnoses. It is important for those involved in the care of these patients to understand the natural history of NMS, as well as the potential risks and benefits to the patient and caregivers, of surgical and non-surgical interventions.

Septic arthritis of the hip (SAH) is a common condition encountered by pediatric orthopaedic surgeons and is treated with arthrotomy and irrigation. Depending on the response to initial treatment, some patients require surgical treatment beyond the index procedure. The purpose of this study was to investigate risk factors for repeat surgical intervention after initial arthrotomy for presumed SAH.A multicenter retrospective review of all children who underwent surgical arthrotomy for presumed SAH over a ten-year period was conducted. Variables queried included demographics, clinical presentation, laboratory parameters, imaging, infecting organism, presence of osteomyelitis, and surgical interventions performed. Logistic regression was used to predict the risk of a second procedure. Chi-square was used to compare patients who required further surgery and those who did not.One hundred and thirty-eight patients (139 hips) qualified for inclusion. The average age at initial surgery was 6.1 years (range, zero to 17 years), and 57% of the patients were male. Concomitant osteomyelitis was diagnosed in 55 cases (40%). An infecting organism was identified from 70 (50%) index intraoperative cultures, with Staphylococcus aureus infections (methicillin-resistant Staphylococcus aureus [MRSA], 27; methicillin-sensitive Staphylococcus aureus, 25) being the most frequent. Fifty-six patients (41%) underwent subsequent surgical intervention, at an average of 5.5 days (range, 2 to 95) from the index procedure. Independent risk factors for repeat surgical procedures included presenting C-reactive protein10 mg/dL (P = 0.002) and presenting erythrocyte sedimentation rate40 (P = 0.011). The odds of repeat surgical intervention were significantly increased by the presence of concomitant osteomyelitis (odds ratio, 3.4; P = 0.001) and positive index intraoperative cultures for MRSA (odds ratio, 1.19; P = 0.001). Preoperative MRI before the index procedure was not universal (73/138; 53%), and acquisition of preoperative MRI was not associated with secondary surgical intervention (P = 0.389).Forty-one percent of children in this multicenter cohort underwent at least one repeat surgical procedure after the index arthrotomy for management of presumed SAH. Risk factors for return to the operating room include elevated initial erythrocyte sedimentation rate and C-reactive protein, infection with MRSA, and presence of osteomyelitis.Level 3, case-cohort series. Type of evidence, therapeutic.

Complications following spine fusion for adolescent idiopathic scoliosis can be characterized as either intra-operative or post-operative. The most serious and feared complication is neurologic injury, both in the intra- and post-operative period. Other intra-operative complications include dural tears and ophthalmologic or peripheral nerve deficits, which may be related to positioning. Among the most common post-operative complications are surgical site infection, venous thromboembolism, gastrointestinal complications, and implant-related complications. Significant blood loss requiring transfusion, traditionally considered a known sequelae of spine fusion, is now being recognized as a “complication” in large national databases. Pediatric spine surgeons who care for patients with AIS must be thoroughly familiar with all potential complications and their management.

In children with bilateral Blount’s Disease, the vast majority of patients present with deformity of both legs concomitantly at the time of initial diagnosis. Although the severity of deformity may not be identical in each limb, it is generally present to some degree on both sides. Asynchronous presentation of bilateral Blount’s Disease has been reported in the Japanese literature8, but to our knowledge there are no reports of such a presentation in the English literature. We report this case due to its apparent rarity, and also as a reminder to maintain vigilance for the possible late development of contralateral deformity in patients with presumed unilateral tibia vara.

Over the past 35 years the health care community and in particular orthopaedic surgery, has undergone a transformation from retrospective case-series-based expert opinion to randomized prospective clinical trials. During this transition, orthopaedic surgeons have become very skilled in the measurement of physician-derived outcomes (radiographic angles, complications, recurrences, and mortality); however, these are not patient-centered outcomes and they are of little importance to our patients' satisfaction. Moving forward outcome measurement needs to be restructured to focus more on patient-reported outcomes. This paper outlines why outcome measurement is important, reviews outcome strategies that have been used historically, introduces a new outcome measurement tool and identifies strategies for future implementation and measurement of health care quality and value within pediatric orthopaedics.

BACKGROUND:: Limited data exist on pediatric subaxial cervical spine injuries. The goal of this study was to characterize the injuries and initial treatment of a large consecutive series of patients with injuries from C3 to C7. METHODS:: Medical records and radiographs of consecutive patients admitted with cervical spine fractures and/or dislocations at a single level 1 pediatric trauma center from 2003 to 2013 were reviewed. Data abstracted included age, injury type and level, mechanism of injury, associated nonspine injuries, neurological status, length of hospitalization, and initial treatment. RESULTS:: Fifty-one patients were grouped into 3 age ranges: infant, 0 to 3 years (2); youth, 4 to 12 years (13); and adolescent, 13 to 16 years (36). Isolated fractures were identified in both infants and accounted for most of injuries in youths (85%) and adolescents (86%). Single vertebra or single vertebral level injuries were present in 65% of patients, most commonly at C7 (36%) or C6 (29%). No correlation existed between cervical level injured and patient age. Multiple cervical spine injuries occurred in 1 infant, 3 youths, and 14 adolescents. Other concomitant thoracic and/or lumbar spine injuries were found in 1 infant and 3 adolescents. The most common mechanisms of injury were motor vehicle accidents (53%) and sports (14%). High-energy trauma was associated with higher rates of noncontiguous spinal injuries and associated nonspinal injuries, with a longer length of hospitalization. Neurological deficits were observed in 8 patients: 1 infant, 2 youths, and 5 adolescents, of which 5 resulted from high-energy trauma. One infant and all youth patients were treated nonoperatively; 26 adolescents (73%) were treated in a cervical collar or with observation, 1 was treated with halo-vest immobilization, and 9 had surgical treatment. CONCLUSIONS:: Most subaxial cervical spine injuries in pediatric and adolescent patients are isolated fractures at C6 and C7. High-energy mechanisms are associated with noncontiguous spinal injuries and other nonspine injuries. Most patients can be treated in a cervical collar, but adolescent patients are more likely to require halo placement or surgical intervention. LEVEL OF EVIDENCE:: Level IV-retrospective, diagnostic. Language: en

Background Based on pre-clinical and clinical activity in adult refractory tumors, and absence of significant neuro-, nephro-, or oto-toxicity, we conducted a pediatric phase 1 trial to determine the toxicities, maximum tolerated dose (MTD), and pharmacokinetics of satraplatin, an oral platinum analogue, in children and young adults with refractory solid tumors. Procedure Satraplatin was administered orally once daily on days 1–5 of a 28-day cycle at dose level (DL) 1 (60 mg/m2/dose), and DL2 (80 mg/m2/dose). Toxicities, responses, satraplatin pharmacokinetics, and pharmacogenomic expression of specific DNA repair genes were evaluated. Results Nine patients received 1–15 cycles (median = 2). The MTD was exceeded at DL2 with delayed prolonged myelosuppression as dose-limiting toxicity (DLT) in 2/4 patients. At DL1, 0/5 patients had DLTs. Common non-DLTs included myelosuppression, gastrointestinal toxicities, fatigue, headache, liver enzyme elevation, and electrolyte abnormalities. No significant neuro-, nephro-, or oto-toxicity was observed. No objective responses were observed but 2 patients experienced prolonged disease stabilization (­­­6–15 cycles). Satraplatin exposure (day 1 plasma ultrafiltrate area under the curve) was similar at DL1 and DL2. A strong correlation between estimated creatinine clearance and satraplatin pharmacokinetic parameters (clearance, area under the curve, and peak concentration) was observed. Conclusions The MTD of oral satraplatin in children with solid tumors was 60 mg/m2/dose daily ×5 days every 28 days, which is lower than the adult recommended dose of 80–120 mg/m2/dose. The toxicity profile was similar to adults and delayed myelosuppression was the DLT. No significant neuro-, nephro- or oto-toxicities were observed. Pediatr Blood Cancer 2015;62:603–610. © 2015 Wiley Periodicals, Inc.

BACKGROUND Pediatric orthopaedic fellowship applicants commonly use online-based resources for information on potential programs. Two primary sources are the San Francisco Match (SF Match) database and the Pediatric Orthopaedic Society of North America (POSNA) database. We sought to determine the accessibility and quality of information that could be obtained by using these 2 sources. METHODS The online databases of the SF Match and POSNA were reviewed to determine the availability of embedded program links or external links for the included programs. If not available in the SF Match or POSNA data, Web sites for listed programs were located with a Google search. All identified Web sites were analyzed for accessibility, content volume, and content quality. RESULTS At the time of online review, 50 programs, offering 68 positions, were listed in the SF Match database. Although 46 programs had links included with their information, 36 (72%) of them simply listed http://www.sfmatch.org as their unique Web site. Ten programs (20%) had external links listed, but only 2 (4%) linked directly to the fellowship web page. The POSNA database does not list any links to the 47 programs it lists, which offer 70 positions. On the basis of a Google search of the 50 programs listed in the SF Match database, web pages were found for 35. Of programs with independent web pages, all had a description of the program and 26 (74%) described their application process. Twenty-nine (83%) listed research requirements, 22 (63%) described the rotation schedule, and 12 (34%) discussed the on-call expectations. A contact telephone number and/or email address was provided by 97% of programs. Twenty (57%) listed both the coordinator and fellowship director, 9 (26%) listed the coordinator only, 5 (14%) listed the fellowship director only, and 1 (3%) had no contact information given. CONCLUSIONS The SF Match and POSNA databases provide few direct links to fellowship Web sites, and individual program Web sites either do not exist or do not effectively convey information about the programs. CLINICAL RELEVANCE Improved accessibility and accurate information online would allow potential applicants to obtain information about pediatric fellowships in a more efficient manner.

Ulnohumeral elbow dislocations are common in children. These injuries can be associated with fractures or soft tissue injuries that are often missed on radiographs, leading to delayed diagnosis and potential complications. In certain cases, magnetic resonance imaging (MRI) may assist clinicians by revealing underlying pathology and making a complete diagnosis. The purposes of this study were to assess the utility of MRI in diagnosing concomitant injuries in pediatric elbow dislocations and to identify associated risk factors for radiographically-occult injuries. A retrospective review was performed for all children (0-18 years) …

Orthobiologics are biologic devices or products used in orthopedic surgery to augment or enhance bone formation. The use of orthobiologics in pediatric orthopedics is less frequent than in other orthopedic subspecialties, mainly due to the naturally abundant healing potential and bone formation in children compared with adults. However, orthobiologics are used in certain situations in pediatric orthopedics, particularly in spine and foot surgery. Other uses have been reported in conjunction with specific procedures involving the tibia and pelvis. The use of bioabsorable implants to stabilize children's fractures is an emerging concept but has limited supporting data.

Almost half of growing rod (GR) patients that undergo final fusion (FF) have an extension of instrumented levels. The purpose of this study was to review sagittal plane radiographic parameters of patients with distal extension of instrumented levels at FF to those whose levels remained the same. Radiographs were assessed preoperatively, after GR insertion/first lengthening, following GR treatment before FFs, and after FF. Measurements included sagittal balance, lumbar lordosis, thoracic kyphosis, and distal junction angle (DJA). Twenty-one patients were included. There was no change in sagittal balance. There was a significant decrease in lordosis and kyphosis following initial GR implantation. Kyphosis and lordosis increased during the GR period, but remained unchanged at time of FF. DJA increased 8° on average. Seven patients had distal extension of instrumented levels at time of FF (average 2 levels, range: 1-4). Indication for distal extension was sagittal plane decompensation in four cases. When comparing patients who had distal extension at the time of FF to those whose levels remained the same, there was no difference in the change in sagittal balance, lordosis, or kyphosis. Final DJA was significantly smaller in those patients with distal extension. Most GR patients that undergo FF demonstrate acceptable correction of sagittal plane radiographic parameters. A small cohort of patients requires distal extension at FF due to sagittal plane decompensation. LEVEL OF EVIDENCE Level IV, Therapeutic.

Total hip arthroplasty (THA) continues to be one of the most successful surgical procedures in the medical field. However, over the last two decades, the use of modularity and alternative bearings in THA has become routine. Given the known problems associated with hard-on-hard bearing couples, including taper failures with more modular stem designs, local and systemic effects from metal-on-metal bearings, and fractures with ceramic-on-ceramic bearings, it is not known whether in aggregate the survivorship of these implants is better or worse than the metal-on-polyethylene bearings that they sought to replace.Have alternative bearings (metal-on-metal and ceramic-on-ceramic) and implant modularity decreased revision rates of primary THAs?In this systematic review of MEDLINE and EMBASE, we used several Boolean search strings for each topic and surveyed national registry data from English-speaking countries. Clinical research (Level IV or higher) with ≥ 5 years of followup was included; retrieval studies and case reports were excluded. We included registry data at ≥ 7 years followup. A total of 32 studies (and five registry reports) on metal-on-metal, 19 studies (and five registry reports) on ceramic-on-ceramic, and 20 studies (and one registry report) on modular stem designs met inclusion criteria and were evaluated in detail. Insufficient data were available on metal-on-ceramic and ceramic-on-metal implants, and monoblock acetabular designs were evaluated in another recent systematic review so these were not evaluated here.There was no evidence in the literature that alternative bearings (either metal-on-metal or ceramic-on-ceramic) in THA have decreased revision rates. Registry data, however, showed that large head metal-on-metal implants have lower 7- to 10-year survivorship than do standard bearings. In THA, modular exchangeable femoral neck implants had a lower 10-year survival rate in both literature reviews and in registry data compared with combined registry primary THA implant survivorship.Despite improvements in implant technology, there is no evidence that alternative bearings or modularity have resulted in decreased THA revision rates after 5 years. In fact, both large head metal-on-metal THA and added modularity may well lower survivorship and should only be used in select cases in which the mission cannot be achieved without it. Based on this experience, followup and/or postmarket surveillance studies should have a duration of at least 5 years before introducing new alternative bearings or modularity on a widespread scale.

In pediatric patients with developmental dysplasia of the hip with late presentation or failure of nonsurgical treatment, surgical management is indicated. The goal of surgery is to obtain a stable reduction to promote development of the femoral head and acetabulum while avoiding osteonecrosis of the femoral head and the need for further surgery. Treatment is related to the age of the patient and the degree of soft-tissue contracture or bony deformity present. As a general rule, in children aged12 months, closed reduction and spica casting is preferred. Children aged 12 to 18 months may require open reduction, which can be performed safely through a medial or anterior approach. In children aged 18 months to 3 years, residual bony deformity can be corrected with a femoral or pelvic osteotomy in addition to open reduction. In children with complex deformity or in children aged3 years, both pelvic and femoral osteotomies are commonly required to stabilize an open reduction.

INTRODUCTION Ulnohumeral elbow dislocation is a rare elbow injury in children. We reviewed a large cohort of pediatric ulnohumeral elbow dislocations and sought to identify risk factors associated with poor functional outcomes. METHODS Medical charts and radiographs were reviewed for all acute pediatric ulnohumeral elbow dislocations evaluated at our facility during a 7-year period. Charts were abstracted for demographics, injury characteristics, treatments, and complications. Functional outcomes were assessed at minimum 6-week follow-up using a combination of symptoms and elbow range of motion (Roberts criteria). RESULTS A total of 145 cases qualified for inclusion and were analyzed. The average age at injury was 11 years (range, 5 to 18 y), with equal distribution between male and female individuals. Concomitant elbow fractures were identified in 114 (80%) cases; the most common was the medial epicondyle (80/134, 60%). Treatment consisted of open reduction and fixation of associated fracture(s) in 59% of fracture cases. At an average follow-up of 3.7 months, the average range of motion was -5-degree extension to 126-degree flexion. Immobilization for longer than 2 weeks resulted in a loss of elbow extension (P

BACKGROUND Although the vertical expandable prosthetic titanium rib (VEPTR) has been shown to be useful in treating congenital scoliosis (CS) with fused ribs, no studies to date have specifically evaluated the efficacy of VEPTR in the treatment of CS without fused ribs. The purpose of this study was to determine the effectiveness of VEPTR in sagittal/coronal curve correction and spine growth and compare its complication rate to the use of VEPTR in other conditions and to other treatment methods used for CS. METHODS A multicenter database was queried for patients with CS without fused ribs treated with VEPTR. Anteroposterior (AP) and lateral radiographs were used to measure parameters at 3 timepoints (preoperative, immediate postoperative, and latest follow-up): coronal Cobb angle, sagittal kyphosis, and thoracic and lumbar spine heights. Clinical data included age, time to follow-up, and complications. RESULTS Twenty-five patients (13 females, 12 males) were identified. The average age at implantation was 5.7 years, with an average follow-up of 50 months. Several parameters improved from preoperative to latest follow-up: coronal Cobb angle (69 to 54 degrees, P

To determine the maximum tolerated dose and the toxicity profile of the PDGF receptor pathway inhibitor SU101 in pediatric patients with refractory solid tumors, and to define the plasma pharmacokinetics of SU101 and its active metabolite SU0020 in children.Patients between 3 and 21 years of age with CNS malignancy, neuroblastoma, or sarcoma refractory to standard therapy were eligible. The starting dose of SU101 was 230 mg/m(2) per day administered as a 96-h continuous infusion every 21 days. Blood for pharmacokinetic analysis was obtained during the first cycle.Entered into the trial were 27 patients, and 24 were fully evaluable for toxicity. Dose-limiting central nervous system toxicity was observed in two patients at the 440 mg/m(2) per day dose level. Non-dose-limiting toxicities included nausea, vomiting, headache, fatigue, abdominal discomfort, diarrhea, pruritus, anorexia, constipation, and paresthesias. There were no complete or partial responses. One patient with rapidly progressive desmoplastic small round-cell tumor experienced symptomatic improvement and prolonged stable disease. Steady-state concentrations of SU101 were rapidly achieved and proportional to dose. The concentration of SU0020 was 100- to 1000-fold greater than that of SU101. The median clearance of SU0020 was 0.19 l/day per m(2) and its terminal elimination half-life was 14 days.SU101 administered on this schedule was generally well tolerated. The maximum tolerated dose of SU101 is 390 mg/m(2) per day for 4 days repeated every 3 weeks. The neurotoxicity observed at the 440 mg/m(2) per day dose level suggests that patients receiving repetitive cycles must be monitored closely, as SU0020 may accumulate over time.

e14067 Background: Doxil, a pegylated liposomal doxorubicin (PLD) has excellent CNS penetration in rodent brain tumor models and is active in patients with lymphoma. The CNS penetration of doxil in humans is unknown. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics (PK) of doxil in adults primary CNS lymphoma (PCNSL) as a surrogate for CNS penetration. Methods: Adults with PCNSL enrolled on a NCI phase I study of ibrutinib and multi-agent immune-chemotherapy (NCT02203526) received doxil 50 mg/m2 IV over 1 hour on day 2 of 21-day cycles of chemotherapy. In 4 patients with indwelling Ommaya reservoirs serial blood and CSF samples were obtained prior to infusion and until a median of 345 hours, (range 72-477 hours) after doxil administration. Total doxorubicin concentration (liposome bound + protein bound + free) was quantified with a validated liquid chromatography/tandem mass spectrometry assay (lower limit of quantification plasma=0.29 ng/mL, and CSF=0.06 ng/mL). PK parameters were estimated using non-compartmental methods. CSF penetration was calculated from the AUCCSF:AUCplasma. Results:Total doxorubicin plasma concentration time curves were characterized by sustained drug exposure and a median terminal half-life of 64.5 hours. (range, 61.9-65.1 hours). Doxorubicin was measurable in CSF in all patients, but CSF penetration was low. The terminal half-life of doxorubicin in CSF could not be calculated due to persistently measurable concentrations throughout the sampling times. Conclusions: In patients with PCNSL doxorubicin was measurable in CSF for prolonged time periods after doxil administration, but CSF penetration is low. Clinical trial information: NCT02203526. [Table: see text]

Background Periodic review of the published research in pediatric orthopaedics is helpful to evaluate the state of scientific methodology. The purpose of this paper was to review the levels of evidence (LOE) and types of evidence (TOE) published in the Journal of Pediatric Orthopaedics (JPO) from 2009 to 2013 and to compare the percentage of articles with each LOE to pediatric orthopaedic articles published in the Journal of Bone and Joint Surgery-American Volume (JBJS) during the same time. Methods All articles published in JPO from January 1, 2009, to December 31, 2013, were reviewed. Articles were classified as scientific studies, case reports, commentaries/letters to editor, reviews, expert opinion, and basic science articles. All scientific articles in the pediatrics section of the online version of JBJS were reviewed. If listed, the LOE was recorded from all clinical scientific studies. In addition, articles were abstracted for self-reported TOE (therapeutic, diagnostic, prognostic, or economic analysis). Results We found 850 citations in JPO over the study period; 646 (76%) were identified as scientific articles and, of those, 552 (85%) had a LOE listed. There were 18 level I articles (3%), 101 level II (18%), 184 level III (34%), and 289 level IV (45%). The TOE was listed in 213 (39%) articles: 114 (54%) therapeutic, 37 (17%) prognostic, 55 diagnostic (26%), and 7 (3%) economic analysis. Comparing 2009 to 2013, the percentage of scientific studies with a self-reported LOE improved significantly (from 81% to 93%, P=0.001). Compared with JPO, JBJS had a significantly higher rate of level I (12% vs. 3%, P=0.006) and a significantly lower rate of level III (23% vs. 34%, P=0.01) articles. Conclusion From 2009 to 2013, 3% of articles in JPO were level I. Significantly more articles are now including a level of evidence designation. Approximately half of published studies are level IV, and most are therapeutic type. A higher percentage of level I studies were published in JBJS during the same time period.

PURPOSE In preclinical studies, thioguanine (TG) has been shown to be more potent than the standard acute lymphoblastic leukemia (ALL) maintenance agent, mercaptopurine (MP), suggesting that TG may be more efficacious than MP in the treatment of childhood ALL. As part of a pilot trial in which TG was used in place of MP, we studied the plasma pharmacokinetics of oral TG and measured steady-state plasma and CSF TG concentrations during a continuous intravenous infusion (CIVI) in children with newly diagnosed standard-risk ALL. METHODS Nine plasma samples were collected after each patient's first 60 mg/m2 oral TG dose during maintenance. CIVI TG (20 mg/m2/h over 24 h) was administered during the consolidation phase of therapy, and simultaneous plasma and CSF samples were collected near the end of the infusion. TG was measured by reverse-phase HPLC with ultraviolet detection. Erythrocyte TG nucleotide (TGN) concentrations were measured 7 days after a course of CIVI TG and prior to the start of each maintenance cycle. RESULTS After oral TG (n = 35), the mean (+/- SD) peak plasma concentration was 0.46 +/- 0.68 microM and the AUC ranged from 0.18 to 9.5 microM.h (mean 1.5 microM.h). Mean steady-state plasma and CSF TG concentrations during CIVI (n = 33) were 2.7 and 0.5 microM, respectively. The mean (+/- SD) TG clearance was 935 +/- 463 ml/min per m2. Plasma TG concentrations did not correlate with erythrocyte TGN concentrations after oral or CIVI TG. The 8-OH-TG metabolite was detected in plasma and CSF. CONCLUSIONS TG concentrations that are cytotoxic to human leukemia cell lines can be achieved in plasma after a 60 mg/m2 oral dose of TG and in plasma and CSF during CIVI of TG.

Purpose: Clinical toxicity associated with 5-fluorouracil (5-FU) is related to the area under the plasma concentration-time curve (AUC). Recently, short-term infusions of 5-FU given over 30 or 60 min have been substituted for conventional "bolus" 5-FU given over 3–5 min in randomized clinical trials, but there are only limited pharmacokinetic data for these altered infusion durations. We therefore wished to determine the pharmacokinetics and toxicity associated with 5-FU given as a 1-h intravenous (i.v.) infusion. Methods: A group of 22 adults with advanced gastrointestinal tract cancers and no prior systemic chemotherapy for advanced disease received interferon α-2a (5 MU/m2 s.c., days 1–7), leucovorin (500 mg/m2 i.v. over 30 min, days 2–6) and 5-FU (370 mg/m2 i.v. over 1 h, days 2–6). The doses of 5-FU and interferon-α were adjusted according to individual tolerance. The pharmacokinetics and clinical toxicity were retrospectively compared with patients receiving the same regimen under the same treatment guidelines except that 5-FU was given over 5 min. Results: The regimen was well tolerated, and 41% of the patients tolerated 5-FU dose escalations to 425–560 mg/m2 per day. Grade 3 or worse diarrhea and fatigue ultimately occurred in 14% of the patients each. Granulocytopenia, mucositis, and diarrhea appeared to be appreciably milder in the present trial compared with our prior phase II experience in colorectal cancer. The peak 5-FU plasma levels and AUC with 370 mg/m2 5-FU given over 1 h were 7.3-fold and 2.4-fold lower than previously measured in 31 patients who received 5-FU over 5 min. Conclusion: Increasing the length of 5-FU infusion to 1 h seemed to substantially reduce the clinical toxicity with this modulated 5-FU regimen, likely due to markedly lower peak 5-FU plasma levels and AUC. Changes in the duration of a short infusion of 5-FU clearly affects the clinical toxicity, but raises the concern of a potentially adverse impact on its antitumor activity. These results suggest the importance of including precise guidelines concerning the time over which 5-FU is given in clinical trials. Having a specified duration of 5-FU infusion is also important if 5-FU dose escalation is considered.

PURPOSE To determine the maximum-tolerated dose (MTD) of all-trans-retinoic acid (ATRA) administered on an intermittent oral schedule with interferon-alpha2a (IFN-alpha2a) in children with refractory cancer, and whether the marked reduction in plasma ATRA concentrations observed with chronic daily oral dosing could be circumvented with an intermittent dosing schedule. PATIENTS AND METHODS Thirty-three children with refractory cancer (stratified by age, < or = 12 and > 12 years) were treated with ATRA 3 consecutive days per week and IFN-alpha2a 3 x 10(6) U/m2 5 consecutive days per week, both repeated weekly. The starting dose of ATRA was 60 mg/m2/d divided into three doses, with planned escalations to 90 and 120 mg/m2/d. Because severe headaches have been noted to occur on the initial day of ATRA administration, only two of three doses of ATRA were administered on day 1 of each week. RESULTS Pseudotumor cerebri or dose-limiting headache was observed in two of five patients older than 12 years treated at the 120-mg/m2/d dose level and in one of six < or = 12 years at the 90-mg/m2/d level. Other non-dose-limiting toxicities of ATRA included reversible elevations in hepatic transaminases and triglycerides, dry skin, cheilitis, and nausea/vomiting. One child with recurrent neuroblastoma had an objective response of 6 months' duration, and one with recurrent Wilms' tumor had histologic maturation of multiple tumors. This intermittent schedule allowed for exposure to relatively high plasma concentrations of ATRA on a repetitive basis. Following 30-mg/m2 doses, the ATRA area under the concentration-time curve (AUC) decreased from 96 +/- 14 micromol/L/min on day 1 to 26 +/- 24 micromol/L/min by day 3 of drug administration, but on day 1 of the fourth consecutive week of therapy, the AUC averaged 110 +/- 16 micromol/L/min. The recommended pediatric phase II dose of ATRA administered on this schedule is 90 mg/m2/d. CONCLUSION An intermittent schedule of ATRA administration appears to circumvent the low plasma drug exposure that is a result of the sustained upregulation of metabolism when this drug is administered on a chronic daily schedule. Based on the results of this trial, a phase II trial of ATRA/IFN-alpha2a in neuroblastoma and Wilms' tumor using this schedule is in progress.

PURPOSE Methotrexate nephrotoxicity can lead to delayed methotrexate elimination and the development of life-threatening toxicity, which may not be preventable with the standard rescue agent leucovorin. In preclinical studies, we previously demonstrated that carboxypetidase-G2 (CPDG2) rapidly hydrolyzes methotrexate to nontoxic metabolites. A protocol for the compassionate use of CPDG2 in patients who develop nephrotoxicity while receiving high-dose methotrexate was therefore developed. The pharmacologic and clinical outcome of CPDG2 rescue administered with thymidine and leucovorin in 20 patients is presented here. METHODS Patients with high-dose methotrexate-induced renal dysfunction received one to three doses of CPDG2, 50 U/kg body weight intravenously (i.v.), thymidine 8 g/m2/d by continuous i.v. infusion, and standard pharmacokinetically guided leucovorin rescue. Plasma concentrations of methotrexate and its inactive metabolite 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) were measured before and after CPDG2 using high-pressure liquid chromatography (HPLC). Tolerance of CPDG2 and thymidine, development of methotrexate toxicities, and recovery of renal function were monitored. RESULTS Twenty patients who received high-dose methotrexate for osteosarcoma (n = 11), lymphoid cancers (n = 8), and gastric cancer (n = 1) developed nephrotoxicity (median serum creatinine, 3.2 mg/dL) and elevated plasma methotrexate concentrations (median, 201 mumol/L at hour 46). CPDG2 and thymidine rescue was well tolerated and resulted in a rapid 95.6% to 99.6% reduction in the plasma methotrexate concentration. Methotrexate-related toxicity was mild to moderate. Serum creatinine returned to normal values at a median of 22 days. CONCLUSION CPDG2, thymidine, and leucovorin rescue was highly effective in 20 patients at high risk for developing life-threatening methotrexate toxicity after the onset of methotrexate-induced nephrotoxicity and delayed methotrexate excretion.

Objective Because of the importance of current procedural terminology (CPT) coding in both resident education evaluation and practice management, this study was undertaken to evaluate the correlation and interrater reliability between residents and attending physicians in CPT coding for orthopedic foot and ankle surgeries as well as to determine attending surgeons’ and residents’ familiarity with and confidence in the coding process. Methods CPT codes from resident case logs were compared with those submitted by attending surgeons, and Pearson’s correlation coefficient and interrater reliability were calculated to examine coding congruency. An online survey was also used to examine attending surgeon and resident perceptions and habits regarding CPT codes and the coding process. Results CPT codes recorded by 20 residents (1164) were compared with those recorded by 3 attending foot and ankle surgeons (1259). Correlation between attending and resident codes was poor (r = −0.015). Interrater reliability demonstrated a kappa value of 0.04, indicating poor agreement. Compared with attending CPT coding, residents concordantly coded 42% of the time, with an individual resident range from 2% to 65%. Additionally, 43% of residents reported being uncomfortable about foot and ankle CPT coding, and they reported rarely or never discussing CPT codes with attending surgeons in the perioperative period. Conclusions Resident and attending surgeon concordance in CPT coding for foot and ankle procedures is poor, and residents have a low level of confidence in logging CPT codes, possibly because of a lack of training and preparation in coding. Because CPT coding is used not only for practice management but also has implications for evaluating institutions by accreditation bodies, educational initiatives to improve resident confidence and accuracy with CPT coding may be warranted.

PURPOSE A phase I/II study of oral all-trans-retinoic acid (ATRA; tretinoin), administered every other week alone and then in combination with interferon (IFN) alfa-2a, was undertaken to evaluate the activity, toxicity, and pharmacokinetics of this regimen in patients with human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). PATIENTS AND METHODS Thirteen patients with HIV-associated KS, eight of whom had more than 100 CD4 cells/microL, were entered. The protocol initially called for patients to receive 150 mg/m2/d of ATRA every other week. However, this regimen was associated with headaches, and the initial dose of ATRA was reduced to 40 mg/m2/d orally in three divided doses, increasing to a maximum of 100 mg/m2/d. After 12 weeks, IFN alfa-2a could be added. RESULTS The principal toxicities from ATRA were headaches (12 patients) and dry skin or lip (seven patients). Of 12 assessable patients, 10 had progressive disease and two had stable disease on ATRA alone. One of eight assessable patients who went on to receive ATRA plus IFN alfa-2a had partial response (PR). There were no overall changes in the serum HIV p24 antigen (Ag) level or CD4 count during treatment with ATRA alone. Peak ATRA levels decreased during the week of continuous ATRA therapy, but rebounded when treatment was resumed after a week without the drug. CONCLUSION Intermittent ATRA therapy was reasonably well tolerated and provided a means to circumvent the low plasma exposure found with continuous ATRA therapy. However, we were unable to document antitumor activity in patients with HIV-associated KS.