The Influence of Aspiration Volume on the Number of Osteoblastic Progenitors Obtained From Bone Marrow in Children.

BACKGROUND: Autologous bone marrow aspirates are utilized to treat various conditions in children. The biological value of bone marrow aspirate depends on the concentration of competent osteoblastic progenitors present in the aspirate. It has been shown in adults that increasing bone marrow aspiration volume beyond 2 mL decreases the concentration of osteoblast progenitor cells because of dilution of the sample with peripheral blood. The effect of varying bone marrow aspiration volumes on the osteoblast cell content has not been determined in children. METHODS: In total, 21 children (3 male and 18 female patients, age range 8 mo to 14 y) scheduled for pelvic osteotomy were included in the study. Three separate bone marrow aspirates of 1, 5, and 10 mL were obtained from the anterior superior iliac crest. Total number of nucleated cells was counted per aspirate and the prevalence of alkaline phosphatase-positive colony-forming units was determined per million nucleated cells. RESULTS: We measured a significant, proportional increase in the total number of nucleated bone marrow precursor cells between the 1 and 5 mL samples (mean±SD, 27±13 and 152±78 million nucleated cells, respectively; P<0.0001). When the aspiration volume doubled from 5 to 10 mL the total number of nucleated cells was 178±76 million (P=0.17). A proportional increase from 2214 alkaline phosphatase-positive colony-forming units in the 1 mL sample to 14,100 alkaline phosphatase-positive colony-forming units in the 5 mL sample was observed. However, the number of colony-forming units per aspirate decreased to 11,880 in the 10 mL sample. CONCLUSIONS: These data demonstrate that in children aspiration up to 5 mL bone marrow from the iliac crest yields a proportional increase in osteoblastic progenitor cells per aspirate. Increasing the aspiration volume beyond 5 mL results in hemodilution, rather than further selection of osteoblastic material. CLINICAL RELEVANCE: These data provide clinicians with a guideline for optimizing aspiration volume of bone marrow in children. LEVEL OF EVIDENCE: Level II-development of diagnostic criteria on basis of consecutive patients.

Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen.

Although biallelic mutations in non-collagen genes account for <10% of individuals with osteogenesis imperfecta, the characterization of these genes has identified new pathways and potential interventions that could benefit even those with mutations in type I collagen genes. We identified mutations in FKBP10, which encodes the 65 kDa prolyl cis-trans isomerase, FKBP65, in 38 members of 21 families with OI. These include 10 families from the Samoan Islands who share a founder mutation. Of the mutations, three are missense; the remainder either introduce premature termination codons or create frameshifts both of which result in mRNA instability. In four families missense mutations result in loss of most of the protein. The clinical effects of these mutations are short stature, a high incidence of joint contractures at birth and progressive scoliosis and fractures, but there is remarkable variability in phenotype even within families. The loss of the activity of FKBP65 has several effects: type I procollagen secretion is slightly delayed, the stabilization of the intact trimer is incomplete and there is diminished hydroxylation of the telopeptide lysyl residues involved in intermolecular cross-link formation in bone. The phenotype overlaps with that seen with mutations in PLOD2 (Bruck syndrome II), which encodes LH2, the enzyme that hydroxylates the telopeptide lysyl residues. These findings define a set of genes, FKBP10, PLOD2 and SERPINH1, that act during procollagen maturation to contribute to molecular stability and post-translational modification of type I procollagen, without which bone mass and quality are abnormal and fractures and contractures result.

Collaborative Multidisciplinary Incident Command at Seattle Children's Hospital for Rapid Preparatory Pediatric Surgery Countermeasures to the COVID-19 Pandemic.

Washington was the first US state to have a patient test positive for COVID-19. Before this, our children's hospital proactively implemented an incident command structure that allowed for collaborative creation of safety measures, policies, and procedures for patients, families, staff, and providers. Although the treatment and protective standards are continuously evolving, this commentary shares our thoughts on how an institution, and specifically, surgical services, may develop collaborative process improvement to accommodate for rapid and ongoing change. Specific changes outlined include early establishment of incident command; personal protective equipment conservation; workforce safety; surgical and ambulatory patient triage; and optimization of trainee education. Please note that the contents of this manuscript are shared in the interest of providing collaborative information and are under continuous development as our regional situation changes. We recognize the limitations of this commentary and do not suggest that our approaches represent validated best practices.

Precordial Doppler evaluation of simple bone cyst injection.

BACKGROUND: A randomized prospective trial of marrow-versus-steroids treatment of solitary bone cyst was ongoing. Protocol required contrast injection of the cyst. A subpopulation was noted to have large, rapid venous outflow of contrast material (omnipaque). Central embolization and resultant acute respiratory distress syndrome has been reported with bone marrow transplant. Particulate injection can result in bradycardia, low exhaled CO2, decreased SaO2 and voltage changes on electrocardiogram. METHODS: Precordial Doppler can measure flow and turbulence centrally after a peripheral cyst injection. Our cases were monitored with precordial Doppler as well as heart rate, ETCO2, blood pressure, electrocardiogram, and pulse oximetry. RESULTS: Five patients/7 injections were noted to have large and rapid outflow veins from solitary bone cyst. The Doppler showed increased signal in all 7 particulate injections (2 steroid injections, 5 bone marrow aspirates and cyst injections.) One marrow injection resulted in transient bradycardia and decreased blood pressure with no sequelae. One developed transient decrease in exhaled CO2. CONCLUSIONS: Rapid outflow has been reported in the past but precordial Doppler monitoring of injection into peripheral cysts is not reported. The potential for embolization with serious physiologic effects is a concern. Others have advocated injection of more particulate substances, such as calcium, sulfate, and demineralized bone matrix. This Doppler technique may be valuable for monitoring the potential harmful effects of these injections and lead to a better understanding of failure of cyst healing due to rapid outflow of material. LEVEL OF EVIDENCE: Level IV case series with poor reference standard.

Trevor's disease: the clinical manifestations and treatment of dysplasia epiphysealis hemimelica.

Trevor's disease is a rare abnormality characterized by aberrant osteocartilaginous growth from an epiphysis. We describe six new cases from our institution. A patient with isolated tibial tuberosity involvement is described for the first time. Each patient was classified according to Azouz into localized (three), classical (two) and generalized (one) form. We recommend that parents be counseled regarding the progressive nature of this disorder owing to the chance of worsening deformity with surgical excision alone, and the need to be followed until skeletal maturity.

Chronic osteomyelitis in children: Shriners Hospital Honolulu experience.

Chronic osteomyelitis incidence and severity in 55 hospitalized Pacific Island children between 1990 and 2002 were compared with the expected incidence and reports in the literature. Of these 55 cases, 87% were from Polynesia/Micronesia. The average length of hospital stay was 104 days. Staphylococcus aureus was cultured in 64% of the cases with 43% of those being methicillin resistant S. aureus. A total of 111 bones were involved. Average antibiotic treatment was 135 days. Each case required an average of 1.3 irrigations/debridements and 45% required a sequestrectomy. Ninety-two percent had elevated erythrocyte sedimentation rate on admission. Sixty-nine percent of the cases involved metaphyseal, diaphyseal and epiphyseal segments of the bone and 29% were multifocal. Results indicate that Pacific Island children have a higher incidence and increased severity of osteomyelitis when compared with non-Pacific Island children in the literature, requiring a high suspicion for multifocal osteomyelitis, extensive bone involvement, S. aureus positive cultures and a longer period of antibiotic treatment.

Perspective: One Health: a compelling convergence.

One Health has been defined as "the collaborative effort of multiple disciplines--working locally, nationally, and globally--to attain optimal health for people, animals, plants, and our environment." The broadly based One Health movement includes domains as diverse as agricultural and animal science, environmental science, climatology, veterinary medicine, human medicine, and public health. One Health, previously espoused by Virchow, Osler, and other pioneers in medical education, is not a new idea, but, as an approach for dealing with the many global health problems in an increasingly interconnected world, it has become more important than ever. The 1999 North American West Nile virus epidemic illustrates that pathogens can, and frequently do, have major effects on animal and human populations simultaneously and that the interface between humans and animals is frequently the source of new or resurgent diseases. Further, climate change will result in widespread alterations to environmental conditions worldwide. How humanity addresses the resulting challenges to human and animal health as well as to the world's water and food supplies will have a major impact on how, or even if, the global community survives.One Health touches on all the missions of academic health centers: population or public health, the care of individual patients, biomedical research, and health education. Texas A&M University is working to break down the barriers that have impeded collaboration among the scientific disciplines now encompassed under the One Health banner to create a whole greater than the sum of its component parts.

Transient monoparesis after blade plate removal in a Hutchinson-Gilford progeria syndrome patient: a case report.

Treatment of patients with Hutchinson-Gilford progeria syndrome (HGPS) is based on the abnormalities of accelerated aging that affect the healing processes, combined with a fragile cardiovascular status. A classic HGPS case, of Korean ancestry, previously treated for severe coxa valga with bilateral varus osteotomies using blade plate fixation is presented. Complications over the blade plate area required removal of the hardware, after which the patient showed right-sided hypertonicity--determined to be a cerebrovascular accident. Subsequently, the patient returned almost completely to her presurgical neurologic status. Perioperative planning for HGPS patients should include risks that are typically considered in the planning for geriatric patient care.

Cyst index: a nonpredictor of simple bone cyst fracture.

PURPOSE: Treatment is indicated for simple bone cysts (SBC) with high risk of fracture. The cyst index was described as a method to determine if a cyst is at high risk or low risk of fracture. STUDY DESIGN: The cyst index of 32 femoral and humeral SBCs was determined by 8 reviewers. The risk group cyst index was compared with whether a fracture took place. Sensitivities, specificities, and positive and negative predictive values were calculated across varying cutoff levels. Intraobserver and interobserver reliability testing for 10 cysts was made. RESULTS: Receiver operator curves demonstrate that no cutoff value gave an acceptable level of both sensitivity and specificity. The mean value for the cyst index was significantly different for different observers (P < 0.05). CONCLUSIONS: This study does not validate the cyst index to be an accurate predictor of fracture. The test has low intraobserver and interobserver reliability. CLINICAL RELEVANCE: The cyst index cannot reliably discriminate between the patients that will fracture and those that will not.

Pedicle rotation in scoliosis: a marker for occult intrathecal abnormalities.

STUDY DESIGN: The Perdriolle method was used to assess retrospectively radiographic pedicle rotation for association with occult intrathecal abnormalities in patients with scoliosis. OBJECTIVE: To determine if pedicle rotation can be predictive of underlying intrathecal abnormalities. SUMMARY OF BACKGROUND DATA: Scoliosis associated with intrathecal abnormalities is thought to produce less rotation than true idiopathic scoliosis. No supporting evidence was found in the literature. METHODS: A consecutive series of patients with a presenting diagnosis of idiopathic scoliosis were reviewed for anteroposterior radiographs and spinal magnetic resonance imaging (MRI). A blinded single examiner evaluated radiographic curve parameters. MRI reports were reviewed for the presence or absence of intrathecal abnormalities. RESULTS: A total of 78 MRIs included 15 intrathecal abnormalities and 63 normals. The abnormal MRI group had more males and apex left curves. Primary curve in the intrathecal abnormality group had a mean of 9.6 degrees of apical vertebrae rotation compared to 17.7 degrees in idiopathic curves (average 37 degrees and 40 degrees Cobb angles, respectively). Of angulation, 1 degrees correlated with 0.21 degrees and 0.34 degrees of rotation in intrathecal abnormality versus no abnormality groups, respectively. CONCLUSIONS: Curves with occult intrathecal pathology had significantly less rotation than those without. Pedicle rotation assessment is a useful adjuvant for identifying scoliosis with intrathecal abnormalities.

C-reactive protein response following pediatric orthopaedic surgery.

The purpose of this study was to describe the pediatric C-reactive protein (CRP) response following orthopaedic surgery, specifically addressing whether CRP values in children return to normal within 3 weeks as they do in adults. Children undergoing elective orthopaedic procedures had serum CRP values measured before surgery and then on days 3, 7, and 21 after surgery. These intervals were chosen to assess the rise, fall, and return to normal of CRP levels. Twenty-two children were studied. CRP levels on day 3 varied from normal to 22.2 mg/dL (mean 7.3 mg/dL), on day 7 they averaged 2.2 mg/dL, and at 3 weeks all values were normal. None of the patients had postoperative infections. The authors concluded that the CRP rise in children may be more varied than in adults. In children, CRP levels return to normal within 3 weeks after surgery. This information can be useful in identifying postoperative infections in children.