Publications by authors named "Liam Harris"

21 Publications

  • Page 1 of 1

Defining the volume of consultations for musculoskeletal infection encountered by pediatric orthopaedic services in the United States.

PLoS One 2020 4;15(6):e0234055. Epub 2020 Jun 4.

Nationwide Children’s Hospital, Columbus, OH, United States of America,

Objective: Adequate resources are required to rapidly diagnose and treat pediatric musculoskeletal infection (MSKI). The workload MSKI consults contribute to pediatric orthopaedic services is unknown as prior epidemiologic studies are variable and negative work-ups are not included in national discharge databases. The hypothesis was tested that MSKI consults constitute a substantial volume of total consultations for pediatric orthopaedic services across the United States.

Study Design: Eighteen institutions from the Children's ORthopaedic Trauma and Infection Consortium for Evidence-based Study (CORTICES) group retrospectively reviewed a minimum of 1 year of hospital data, reporting the total number of surgeons, total consultations, and MSKI-related consultations. Consultations were classified by the location of consultation (emergency department or inpatient). Culture positivity rate and pathogens were also reported.

Results: 87,449 total orthopaedic consultations and 7,814 MSKI-related consultations performed by 229 pediatric orthopaedic surgeons were reviewed. There was an average of 13 orthopaedic surgeons per site each performing an average of 154 consultations per year. On average, 9% of consultations were MSKI related and 37% of these consults yielded positive cultures. Finally, a weak inverse monotonic relationship was noted between percent culture positivity and percent of total orthopedic consults for MSKI.

Conclusion: At large, academic pediatric tertiary care centers, pediatric orthopaedic services consult on an average of ~3,000 'rule-out' MSKI cases annually. These patients account for nearly 1 in 10 orthopaedic consultations, of which 1 in 3 are culture positive. Considering that 2 in 3 consultations were culture negative, estimating resources required for pediatric orthopaedic consult services to work up and treat children based on culture positive administrative discharge data underestimates clinical need. Finally, ascertainment bias must be considered when comparing differences in culture rates from different institution's pediatric orthopaedics services, given the variability in when orthopaedic physicians become involved in a MSKI workup.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234055PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272072PMC
August 2020

Five or more proximal anchors and including upper end vertebra protects against reoperation in distraction-based growing rods.

Spine Deform 2020 08 3;8(4):781-786. Epub 2020 Mar 3.

Children's Orthopaedic Center, Children's Hospital Los Angeles, Los Angeles, CA, USA.

Study Design: Retrospective multi-center enrollment.

Objective: To examine the impact of patient and surgical factors on proximal complication and revision rates of early onset scoliosis patients using a multicenter database. Proximal anchor pullout and junctional kyphosis are common causes necessitating revision surgery during growth friendly treatment of early onset scoliosis (EOS). Many options exist for proximal fixation and may impact the rate of these complications.

Methods: Retrospective review of multicenter database of patients with growth friendly constructs for EOS. Inclusion criteria were patients with index instrumentation < 10 years of age and minimum of 2 year follow-up.

Results: 353 patients met the inclusion criteria and had the following constructs: growing rods with spine anchors = 303; growing rods with rib anchors = 15 and VEPTR = 35. Mean age at index instrumentation was 6.0 years. Mean preoperative Cobb angle was 76° and mean kyphosis was 54°. Mean follow-up was 6.0 years. 21.8% of patients (77/353) experienced anchor pullout. Lower anchor pullout rates were associated with a higher numbers of proximal anchors (p = 0.003, r = - 0.157), and 5 or more anchors were associated with lower rates of anchor pullout (p = 0.014). Anchor type (rib hooks vs spine anchors vs rib cradle) did not impact rate of anchor pullout (p = 0.853). Kyphosis data was available for 198 patients. 23.2% (46/198) of these patients required proximal extension of their construct after index surgery. Initial instrumentation below the upper end vertebrae (UEV) of kyphosis was associated with higher rates of subsequent proximal revision; 28.9% (20/69) compared to 20.1% (26/129) for those instrumented at or above the UEV (p = 0.035). Preoperative kyphosis and change in thoracic kyphosis were not associated with anchor pullout (p = 0.436, p = 0.115) or proximal revision rates (p = 0.486, p = 0.401).

Conclusion: Five or more anchors are associated with lower rates of anchor pullout. Proximal anchor placement at or above the UEV resulted in a significant decrease in rates of proximal extension of the construct.
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http://dx.doi.org/10.1007/s43390-020-00064-xDOI Listing
August 2020

Socioeconomic Risk Factors for Poor Outcomes of Developmental Dysplasia of the Hip.

J Pediatr 2019 08 10;211:159-163. Epub 2019 May 10.

Children's Orthopaedic Center, Children's Hospital Los Angeles, Los Angeles, CA. Electronic address:

Objective: To examine the relationship between socioeconomic factors and outcomes of developmental dysplasia of the hip (DDH).

Study Design: A retrospective review of patients with DDH at a tertiary pediatric hospital from 2003 to 2012 with 2 years minimum follow-up was conducted. The relationship between socioeconomic factors with late presentation, treatment, and outcomes was examined. Socioeconomic factors included insurance status, language, and ethnicity.

Results: In total, 188 patients met criteria. Patients with late presentations were more likely to be Hispanic (P = .02). However, public insurance and a non-English language were not associated with late presentation. Hispanic patients (P = .01) and patients with a non-English language (P = .01) had a lower nonoperative treatment success rate. Hispanic patients had more surgical procedures performed than non-Hispanic patients (P = .04). Patients with range of motion limitations were more likely to have public insurance (P = .05) and be Hispanic (P = .04). On multiple logistic regression analysis controlling for late presentation, patients with public insurance had increased odds of range of motion limitations (OR 2.22, P = .04). Patients with public insurance (OR 0.44, P = .04), a non-English primary language (OR 0.30, P < .01), and Hispanic ethnicity (OR 0.37, P = .01) had decreased odds of successful nonoperative treatment.

Conclusions: Public insurance, a non-English language, and Hispanic ethnicity are risk factors for inferior outcomes for DDH. When controlling for late presentation, these were significant risk factors for nonoperative treatment failure.
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http://dx.doi.org/10.1016/j.jpeds.2019.04.029DOI Listing
August 2019

Transfer Time After Acceptance to a Level I Trauma Center.

J Am Acad Orthop Surg Glob Res Rev 2018 Feb 2;2(2):e081. Epub 2018 Feb 2.

Children's Orthopedic Center, Children's Hospital Los Angeles, Los Angeles, CA.

Background: Timely treatment of pediatric orthopaedic emergencies at level I trauma centers is frequently dependent on transfers from neighboring centers.

Methods: Records were collected from our level I trauma center for patients with isolated orthopaedic issues accepted for transfer in 2015. Open fractures, compartment syndrome, septic arthritis, and supracondylar humerus fractures with ecchymosis or neurovascular compromise were emergent. The rush hour was 6 am to 10 am and 3 pm to 7 pm.

Results: Ninety-six patients met the inclusion criteria; 19% (18/96) were orthopaedic emergencies and 37% (35/96) occurred during the rush hour. The average time from transfer acceptance to accepting hospital admission was 203 minutes (range, 68 to 584 minutes; SD, 85.8 minutes). The average time from transfer acceptance to departure from the transferring facility was 114 minutes (range, 7 to 391 minutes; SD, 71.9 minutes). There was no correlation between the transfer time and rush hour ( = 0.40), emergent versus nonemergent ( = 0.42), or routed distance from the hospital ( = 0.46).

Conclusion: The average transfer time exceeded 3 hours and was independent of the distance, the rush hour, or urgency of patient condition. An average 2-hour delay was encountered for patients while leaving a medical facility after acceptance of transfer.
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http://dx.doi.org/10.5435/JAAOSGlobal-D-17-00081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132317PMC
February 2018

Pulseless Supracondylar Humerus Fracture With Anterior Interosseous Nerve or Median Nerve Injury-An Absolute Indication for Open Reduction?

J Pediatr Orthop 2019 Jan;39(1):e1-e7

Children's Hospital Los Angeles, Los Angeles, CA.

Background: Optimal management for a pulseless supracondylar humerus fracture associated with anterior interosseous nerve (AIN) or median nerve injury is unclear. The purpose of this study was to determine the incidence of pulseless supracondylar humerus fractures associated with AIN or median nerve injury, to assess open versus closed surgical management, to determine factors associated with the need for neurovascular intervention, and to report the outcome.

Methods: A retrospective review was performed at 4 pediatric trauma hospitals on all patients who sustained a Gartland III or IV supracondylar humerus fracture with the combination of absent distal palpable pulses and AIN or median nerve injury between 2000 and 2014. Choice of treatment, details regarding preoperative and postoperative exam findings, follow-up course, and outcome were recorded.

Results: A total of 71 patients met inclusion criteria; 52 patients (73%) underwent closed reduction (CR); 19 patients (27%) underwent open reduction (OR) and early antecubital fossa exploration. The index procedure of CR plus percutaneous pinning was sufficient treatment in 50 (of 52, 96%) patients with only 2 requiring reoperation. One patient developed compartment syndrome approximately 9 hours after CRPP (13.5 h after time of injury) and underwent emergent fasciotomies. Of the 19 patients who underwent OR and early exploration, 6 needed vascular procedures, 5 required detethering of entrapped surrounding fibrous tissues. Forty patients were diagnosed with median nerve palsy versus 31 diagnosed with AIN palsy. There was no significant difference between patients presenting with median nerve versus AIN palsy, with similar rates of need for OR (10/40; 25% vs. 9/31; 29%), rate of compartment syndrome (3/40; 7.5% vs. 3/31; 9.7%), need for reoperation (4/40; 10% vs. 6.5%), and ultimate resolution of nerve palsy (4/36; 20.1% vs. 3/30; 10%). Compartment syndrome developed in 6 (of 71, 8.5%) patients and was associated with poor perfusion status on presentation and delayed time from injury to surgery. In patients with at least 3-month neurological follow-up, 59 (of 61, 97%) patients had complete resolution of nerve palsy.

Conclusions: Although previous authors have suggested a pulseless SCH fx with an associated AIN or median nerve injury should be treated with exploration and OR, 70% (50/71) of the patients in this series were treated with a CR. In this series, both AIN and median nerve palsies among patients presenting with pulseless extremity and Gartland III or IV SCH fracture, offer similar rates of OR, risk of compartment syndrome, and resolution of nerve palsy.

Level Of Evidence: Level IV.
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http://dx.doi.org/10.1097/BPO.0000000000001238DOI Listing
January 2019

Methicillin-resistant Staphylococcus aureus Swab Results Did Not Change Treatment or Outcome in Pediatric Spinal Fusion Patients.

J Am Acad Orthop Surg 2018 Sep;26(17):617-623

From the Children's Orthopaedic Center, Children's Hospital of Los Angeles, Los Angeles, CA.

Introduction: The aim of this study was to investigate whether preoperative methicillin-resistant Staphylococcus aureus (MRSA) swab results were predictive of surgical site infections (SSIs) in pediatric patients who have undergone spinal fusion.

Methods: We conducted a retrospective chart review of patients who underwent posterior spinal fusion between 2004 and 2014 to determine preoperative MRSA colonization status and SSI rates and organisms. Before October 1, 2012, we administered vancomycin to the patients for infection prophylaxis; beginning October 1, 2012, patients received ceftazidime and Ancef (cefazolin for injection; GlaxoSmithKline). We added powdered vancomycin to all bone grafts.

Results: A total of 1,200 patients met inclusion criteria. Of the patients, 2.3% (n = 28 of 1,200) were positive for MRSA, and an SSI developed in 3.1% (n = 37 of 1,200). No significant difference in infection rates was found between patients whose MRSA swab was positive and negative (positive swab = 1 SSI, negative swab = 36 SSIs; P = 0.88). Three SSIs were caused by MRSA.

Conclusion: The results of a preoperative MRSA nasal swab had no correlation with SSI rates.

Level Of Evidence: Level III.
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http://dx.doi.org/10.5435/JAAOS-D-17-00010DOI Listing
September 2018

Comparison of Percentile Weight Gain of Growth-Friendly Constructs in Early-Onset Scoliosis.

Spine Deform 2018 01;6(1):43-47

Growing Spine Study Group, Growing Spine Foundation, 555 East Wells Street, Suite 1100, Milwaukee, WI 53202, USA.

Study Design: Multicenter retrospective cohort.

Objective: To compare improvement in nutritional status seen in early-onset scoliosis (EOS) patients following treatment with various growth-friendly techniques, especially in underweight patients (<20th weight percentile).

Background: Thoracic insufficiency resulting from EOS can lead to severe cardiopulmonary disease. In this age group, pulmonary function tests are often difficult or impossible to perform. Weight gain has been used in prior studies as a proxy for improvement and has been demonstrated following VEPTR and growing rod implantation. In this study, we aim to analyze weight gain of EOS patients treated with four different spinal implants to evaluate if significant differences in weight percentile change exist between them.

Methods: Retrospective review of patients treated surgically for EOS was performed from a multicenter database. Exclusion criteria were index instrumentation at >10 years old and <2 years' follow-up.

Results: 287 patients met the inclusion criteria and etiologies were as follows: congenital = 85; syndromic = 79; neuromuscular = 69; and idiopathic = 52. Average patient age at surgery was 5.41 years, with an average follow-up of 5.8 years. Preoperatively, 55.4% (162/287) fell below the 20th weight percentile. There was no significant difference in preoperative weight between implants (p = .77), or diagnoses (p = .25). Among this group, the mean change in weight percentile was 10.5% (range: -16.7% to 88.7%) and all implant groups increased in mean weight percentile at final follow-up. There were no significant differences in weight percentile change between the groups when divided by implant type (p = .17).

Conclusions: Treatment of EOS with growth-friendly constructs resulted in an increase in weight percentile for underweight patients (<20th percentile), with no significant difference between constructs.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1016/j.jspd.2017.05.005DOI Listing
January 2018

Motivating participation in open science by examining researcher incentives.

Elife 2017 10 30;6. Epub 2017 Oct 30.

Centre for Intellectual Property Policy, Faculty of Law, McGill University, Montreal, Canada.

Support for open science is growing, but motivating researchers to participate in open science can be challenging. This in-depth qualitative study draws on interviews with researchers and staff at the Montreal Neurological Institute and Hospital during the development of its open science policy. Using thematic content analysis, we explore attitudes toward open science, the motivations and disincentives to participate, the role of patients, and attitudes to the eschewal of intellectual property rights. To be successful, an open science policy must clearly lay out expectations, boundaries and mechanisms by which researchers can engage, and must be shaped to explicitly support their values and those of key partners, including patients, research participants and industry collaborators.
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http://dx.doi.org/10.7554/eLife.29319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662284PMC
October 2017

Mesenchymal Stem Cell Levels of Human Spinal Tissues.

Spine (Phila Pa 1976) 2018 May;43(9):E545-E550

Keck School of Medicine of USC, Los Angeles, CA.

Study Design: Systematic review.

Objective: The aim of this study was to investigate, quantify, compare, and compile the various mesenchymal stem cell (MSC) tissue sources within human spinal tissues to act as a compendium for clinical and research application.

Summary Of Background Data: Recent years have seen a dramatic increase in academic and clinical understanding of human MSCs. Previously limited to cells isolated from bone marrow, the past decade has illicited the characterization and isolation of human MSCs from adipose, bone marrow, synovium, muscle, periosteum, peripheral blood, umbilical cord, placenta, and numerous other tissues. As researchers explore practical applications of cells in these tissues, the absolute levels of MSCs in specific spinal tissue will be critical to guide future research.

Methods: The PubMED, MEDLINE, EMBASE, and Cochrane databases were searched for articles relating to the harvest, characterization, isolation, and quantification of human MSCs from spinal tissues. Selected articles were examined for relevant data, categorized according to type of spinal tissue, and when possible, standardized to facilitate comparisons between sites.

Results: Human MSC levels varied widely between spinal tissues. Yields for intervertebral disc demonstrated roughly 5% of viable cells to be positive for MSC surface markers. Cartilage endplate cells yielded 18,500 to 61,875 cells/0.8 mm thick sample of cartilage end plate. Ligamentum flavum yielded 250,000 to 500,000 cells/g of tissue. Annulus fibrosus fluorescence activated cell sorting treatment found 29% of cells positive for MSC marker Stro-1. Nucleus pulposus yielded mean tissue samples of 40,584 to 234,137 MSCs per gram of tissue.

Conclusion: Numerous tissues within and surrounding the spine represent a consistent and reliable source for the harvest and isolation of human MSCs. Among the tissues of the spine, the annulus fibrosus and ligamentum flavum each offer considerable levels of MSCs, and may prove comparable to that of bone marrow.

Level Of Evidence: 5.
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http://dx.doi.org/10.1097/BRS.0000000000002401DOI Listing
May 2018

Periosteal turndown flap for posterior occipitocervical fusion: a technique review.

Eur Spine J 2017 09 2;26(9):2303-2307. Epub 2017 May 2.

Children's Hospital Los Angeles, 4650 Sunset Blvd, MS#69, Los Angeles, CA, 90027, USA.

Purpose: Recently, several authors have proposed techniques for improving the fusion rate in pediatric posterior occipitocervical fusion including a variety of implants and the use of bone morphogenetic protein. A technique by Koop et al. using a periosteal flap for occipitocervical arthrodesis was described in 1984.

Methods: A straight incision is made about the posterior neck to expose the occipitocervical region from the inion superiorly to the lowest cervical vertebrae to be fused inferiorly. The occiput is exposed superficial to the periosteum, which is then reflected and elevated from the occiput. The attachment is preserved at the caudal base of the flap and reflected over the intended area of fusion. When possible, fixation is then performed with cables, wires, screws, hooks, or plates.

Case Example: A 6-year-old male with an occiput to C2 distraction injury underwent posterior spinal fusion from occiput to C3 using sublaminar wires, periosteal turndown flap, and autologous iliac crest bone graft.

Conclusion: In small children with traumatic upper cervical spine instability, the periosteal turndown technique may be used as a safe adjunct for occipitocervical fusions.
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http://dx.doi.org/10.1007/s00586-017-5085-8DOI Listing
September 2017

Removal of Infected Posterior Spinal Implants: Be Prepared to Transfuse.

Spine Deform 2016 Jul 16;4(4):283-287. Epub 2016 Jun 16.

Children's Orthopaedic Center, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA, 90027, USA. Electronic address:

Study Design: Single-center retrospective review of spinal deformity patients undergoing removal of infected posterior spinal fusion implants over a 10-year period.

Objective: To evaluate the intraoperative blood loss and perioperative complications of implant removal in posterior spinal fusions.

Summary Of Background Data: To our knowledge, no studies examine blood loss or complications associated with removal of infected spinal implants in spinal deformity.

Methods: A retrospective review of 28 consecutive cases of infected posterior spinal fusion implant removal from 2003 to 2012 was performed. Exclusion criteria were patients with ≤6 levels of instrumentation, a partial removal of implants or a bleeding disorder.

Results: The average estimated blood loss was 465 mL (range 100-1,505 mL). Average estimated blood volume was 3,814 mL (range 1,840-9,264 mL). The average percentage of estimated blood loss was 14.2% (range 1.9%-43.5%). On postoperative labs obtained at the conclusion of the procedure, there was an average loss in hematocrit of 6.6 from preoperative values. Seventy-one percent of patients (20/28) received a blood transfusion; 39% (11/28) of these received a transfusion intraoperatively and 54% (15/28) received a transfusion postoperatively. Forty-six percent of patients (13/28) experienced an associated medical complication in the postoperative period. Among these 13, there were 16 total complications, with the most common being seizures (4/16), pneumonia (2/16), and sepsis (2/16). Average hospital stay was 14 days (range 4-52).

Conclusion: Seventy-one percent of patients undergoing removal of infected spinal implants received a blood transfusion. We recommend having blood products available when removing posterior spinal instrumentation >6 levels. Patients and families should be counseled on the high risk of complications and expected hospital stay in these cases.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1016/j.jspd.2016.01.002DOI Listing
July 2016

A Complete Fossil-Calibrated Phylogeny of Seed Plant Families as a Tool for Comparative Analyses: Testing the 'Time for Speciation' Hypothesis.

PLoS One 2016 5;11(10):e0162907. Epub 2016 Oct 5.

Department of Biology, McGill University, 1205 Docteur-Penfield Avenue, Montreal, Quebec, Canada, H3A 1B1.

Explaining the uneven distribution of species richness across the branches of the tree of life has been a major challenge for evolutionary biologists. Advances in phylogenetic reconstruction, allowing the generation of large, well-sampled, phylogenetic trees have provided an opportunity to contrast competing hypotheses. Here, we present a new time-calibrated phylogeny of seed plant families using Bayesian methods and 26 fossil calibrations. While there are various published phylogenetic trees for plants which have a greater density of species sampling, we are still a long way from generating a complete phylogeny for all ~300,000+ plants. Our phylogeny samples all seed plant families and is a useful tool for comparative analyses. We use this new phylogenetic hypothesis to contrast two alternative explanations for differences in species richness among higher taxa: time for speciation versus ecological limits. We calculated net diversification rate for each clade in the phylogeny and assessed the relationship between clade age and species richness. We then fit models of speciation and extinction to individual branches in the tree to identify major rate-shifts. Our data suggest that the majority of lineages are diversifying very slowly while a few lineages, distributed throughout the tree, are diversifying rapidly. Diversification is unrelated to clade age, no matter the age range of the clades being examined, contrary to both the assumption of an unbounded lineage increase through time, and the paradigm of fixed ecological limits. These findings are consistent with the idea that ecology plays a role in diversification, but rather than imposing a fixed limit, it may have variable effects on per lineage diversification rates through time.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162907PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051821PMC
June 2017

Sacral Alar Iliac (SAI) Screws Fail 75% Less Frequently Than Iliac Screws in Neuromuscular Scoliosis.

J Pediatr Orthop 2017 Dec;37(8):e470-e475

Children's Orthopedic Center, Children's Hospital Los Angeles, Los Angeles, CA.

Background: Despite recent popularity of sacral alar iliac (SAI) screws for fusion to the pelvis for neuromuscular scoliosis, there are little data regarding the failure rate of this technique compared with traditional modes of iliac fixation. Theoretical advantages of the SAI screws are obviating the need for a rod to iliac screw connector and a lower implant profile. The purpose of this study is to determine whether SAI screws have fewer failures than iliac screws in neuromuscular scoliosis.

Methods: Review of neuromuscular patients treated with posterior spinal fusion with pelvic fixation from 2004 to 2012 with minimum 2-year follow-up was conducted. Medical records and imaging studies were reviewed. Patients were divided into 2 groups based on the type of pelvic fixation (SAI or iliac screws), and implant failures were compared between the groups.

Results: A total of 101 patients were reviewed, including 55 patients with iliac screws and 46 patients with SAI screws. Implant failures included: disengagement of the rod to iliac screw connector (10%, 10/101), separation of screw head from screw shaft (4%, 4/101), and set screw disengagement (2%, 2/101). The SAI group had a lower implant failure rate (7%, 3/46) compared with the iliac screw group (24%, 13/55) (P=0.031). Rod to iliac screw connectors failed in 18% (10/55) of patients. There were significantly less surgical revisions in the SAI group (2%, 1/46) for pelvic screw prominence compared with the iliac screw group (11%, 6/55) (P=0.027).

Conclusions: SAI screws had a lower rate of implant failure and revision surgery compared with iliac screws. If rod to screw connector failures are excluded, the failure rate of SAI screws of 6.5% (3/46) is similar to that of iliac screws 5.5% (3/55); therefore, the most important advantage of the SAI technique may be obviating the need for a screw to rod connector.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1097/BPO.0000000000000720DOI Listing
December 2017

Umbilical Cord Tissue Offers the Greatest Number of Harvestable Mesenchymal Stem Cells for Research and Clinical Application: A Literature Review of Different Harvest Sites.

Arthroscopy 2015 Sep;31(9):1836-43

Keck School of Medicine, University of Southern California, Los Angeles, California, U.S.A.

Purpose: Recent years have seen dramatic increases in the techniques used to harvest and isolate human mesenchymal stem cells. As the potential therapeutic aspects of these cells further develop, informative data on the differences in yields between tissue harvest sites and methods will become increasingly valuable. We collected and compared data on cell yields from multiple tissue harvest sites to provide insight into the varying levels of mesenchymal stem cells by tissue and offer primary and alternative tissue types for harvest and clinical application.

Methods: The PubMed and Medline databases were searched for articles relating to the harvest, isolation, and quantification of human mesenchymal stem cells. Selected articles were analyzed for relevant data, which were categorized according to tissue site and, if possible, standardized to facilitate comparison between sites.

Results: Human mesenchymal stem cell levels in tissue varied widely according to tissue site and harvest method. Yields for adipose tissue ranged from 4,737 cells/mL of tissue to 1,550,000 cells/mL of tissue. Yields for bone marrow ranged from 1 to 30 cells/mL to 317,400 cells/mL. Yields for umbilical cord tissue ranged from 10,000 cells/mL to 4,700,000 cells/cm of umbilical cord. Secondary tissue harvest sites such as placental tissue and synovium yielded results ranging from 1,000 cells/mL to 30,000 cells/mL.

Conclusions: Variations in allogeneic mesenchymal stem cell harvest levels from human tissues reflect the evolving nature of the field, patient demographic characteristics, and differences in harvest and isolation techniques. At present, Wharton's jelly tissue yields the highest concentration of allogeneic mesenchymal stem cells whereas adipose tissue yields the highest levels of autologous mesenchymal stem cells per milliliter of tissue.

Clinical Relevance: This comparison of stem cell levels from the literature offers a primer and guide for harvesting mesenchymal stem cells. Larger mesenchymal stem cell yields are more desirable for research and clinical application.
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http://dx.doi.org/10.1016/j.arthro.2015.03.014DOI Listing
September 2015

Biogeological Analysis of Desert Varnish Using Portable Raman Spectrometers.

Astrobiology 2015 Jun 27;15(6):442-52. Epub 2015 May 27.

3 Department of Geography, University of Leicester , Leicester, UK .

Desert varnishes are thin, dark mineral coatings found on some rocks in arid or semi-arid environments on Earth. Microorganisms may play an active role in their formation, which takes many hundreds of years. Their mineral matrix may facilitate the preservation of organic matter and is therefore of great relevance to martian exploration. Miniaturized Raman spectrometers (which allow nondestructive analysis of the molecular composition of a specimen) will equip rovers in forthcoming planetary exploration missions. In that context, and for the first time, portable Raman spectrometers operating in the green visible (532 nm as currently baselined for flight) and in the near-infrared (785 nm) were used in this study to investigate the composition (and substrate) of several samples of desert varnish. Rock samples that were suspected (and later confirmed) to be coated with desert varnish were recovered from two sites in the Mojave Desert, USA. The portable spectrometers were operated in flight-representative acquisition modes to identify the key molecular components of the varnish. The results demonstrate that the coatings typically comprise silicate minerals such as quartz, plagioclase feldspars, clays, ferric oxides, and hydroxides and that successful characterization of the samples can be achieved by using flightlike portable spectrometers for both the 532 and 785 nm excitation sources. In the context of searching for spectral signatures and identifying molecules that indicate the presence of extant and/or extinct life, we also report the detection of β-carotene in some of the samples. Analysis complications caused by the presence of rare earth element photoluminescence (which overlaps with and overwhelms the organic Raman signal when a 785 nm laser is employed) are also discussed.
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http://dx.doi.org/10.1089/ast.2014.1265DOI Listing
June 2015

Selection of Portable Spectrometers for Planetary Exploration: A Comparison of 532 nm and 785 nm Raman Spectroscopy of Reduced Carbon in Archean Cherts.

Astrobiology 2015 Jun 29;15(6):420-9. Epub 2015 May 29.

1 Department of Physics and Astronomy, University of Leicester , Leicester, UK .

Knowledge and understanding of the martian environment has advanced greatly over the past two decades, beginning with NASA's return to the surface of Mars with the Pathfinder mission and its rover Sojourner in 1997 and continuing today with data being returned by the Curiosity rover. Reduced carbon, however, is yet to be detected on the martian surface, despite its abundance in meteorites originating from the planet. If carbon is detected on Mars, it could be a remnant of extinct life, although an abiotic source is much more likely. If the latter is the case, environmental carbonaceous material would still provide a source of carbon that could be utilized by microbial life for biochemical synthesis and could therefore act as a marker for potential habitats, indicating regions that should be investigated further. For this reason, the detection and characterization of reduced or organic carbon is a top priority for both the ESA/Roscosmos ExoMars rover, currently due for launch in 2018, and for NASA's Mars 2020 mission. Here, we present a Raman spectroscopic study of Archean chert Mars analog samples from the Pilbara Craton, Western Australia. Raman spectra were acquired with a flight-representative 532 nm instrument and a 785 nm instrument with similar operating parameters. Reduced carbon was successfully detected with both instruments; however, its Raman bands were detected more readily with 785 nm excitation, and the corresponding spectra exhibited superior signal-to-noise ratios and reduced background levels.
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http://dx.doi.org/10.1089/ast.2014.1220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490632PMC
June 2015

Accessory Navicular is Associated With Wider and More Prominent Navicular Bone in Pediatric Patients by Radiographic Measurement.

J Pediatr Orthop 2016 Jul-Aug;36(5):521-5

*Children's Orthopaedic Center, Children's Hospital Los Angeles †Keck School of Medicine, University of Southern California, Los Angeles, CA.

Background: Accessory navicular (AN) is a common anatomic variant that is known to cause medial foot pain. Surgery may be required for excision if conservative measures fail. Often, the medial border of the navicular is excised in addition to the AN during surgery. The purpose of this radiographic study is to determine if the presence of an AN is associated with a wider or more prominent navicular in pediatric patients compared with normal controls.

Methods: This study included pediatric patients who received an initial plain anteroposterior foot radiograph between January 1, 2004 and December 31, 2012 and were between the ages of 10 and 20 years. Feet with an AN were compared with those without, while controlling for age. Male and female patients were analyzed independently. Feet with fractures, deformities, or previous surgeries were excluded. Radiographic measurements included the navicular width and the protrusion of the navicular bone medially.

Results: A total of 592 feet were included. An AN was identified in 73 feet. Male patients were analyzed separately from females. Cases with 1 AN bone had similar-sized native navicular bones in the contralateral normal foot compared with controls with 2 normal feet (P>0.05). The presence of an AN was associated with a larger navicular width (male: P=0.02, female: P=0.02) and a larger medial protrusion percent (male: P<0.01, female: P<0.01). Age was controlled for.

Conclusion: On radiographic examination, feet with an AN had wider native navicular bones that protruded more medially than feet without an AN.

Level Of Evidence: Level IV-diagnostic.
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http://dx.doi.org/10.1097/BPO.0000000000000489DOI Listing
April 2017

Fever is common postoperatively following posterior spinal fusion: infection is an uncommon cause.

J Pediatr 2015 Mar 6;166(3):751-5. Epub 2015 Jan 6.

Children's Orthopaedic Center, Children's Hospital Los Angeles, Los Angeles, CA. Electronic address:

Objective: To determine the frequency and clinical significance of postoperative fever in pediatric patients undergoing posterior spinal fusion (PSF).

Study Design: A retrospective chart review was performed for consecutive patients undergoing PSF at a single institution between June 2005 and April 2011, with a minimum of 2-year follow up. Exclusion criteria were previous spine surgery, a combined anterior-posterior approach, and delayed wound closure at the time of surgery.

Results: Two hundred and seventy-eight patients with an average age of 13 years (1-22 years) met inclusion criteria, with the following diagnoses: adolescent idiopathic scoliosis 43%, neuromuscular/syndromic scoliosis 39%, congenital scoliosis 11%, spondylolisthesis 4%, and Scheuermann kyphosis 3%. Seventy-two percent (201/278) of patients had a maximum temperature (Tmax) >38(°) postoperatively, and 9% (27/278) Tmax >39(°). The percentage of febrile patients trended down following the first postoperative day. Infection rate was 4% (12/278). There was no correlation between Tmax >38(°) or Tmax >39(°), and timing of fever, positive blood or urine cultures, pneumonia, or surgical site infection.

Conclusion: Seventy-two percent of pediatric patients undergoing PSF experienced postoperative fever, and 9% of patients had Tmax>39(°). There was no significant correlation between fever and positive blood culture, urine culture, pneumonia, or surgical site infection. This information may help relieve stress for families and healthcare providers, and obviate routine laboratory evaluation for fever alone.
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http://dx.doi.org/10.1016/j.jpeds.2014.11.033DOI Listing
March 2015

Raman spectroscopy on Mars: identification of geological and bio-geological signatures in Martian analogues using miniaturized Raman spectrometers.

Philos Trans A Math Phys Eng Sci 2014 Dec;372(2030)

Department of Geology & Petroleum Geology, University of Aberdeen, King's College, Aberdeen AB24 3UE, UK.

The first Raman spectrometers to be used for in situ analysis of planetary material will be launched as part of powerful, rover-based analytical laboratories within the next 6 years. There are a number of significant challenges associated with building spectrometers for space applications, including limited volume, power and mass budgets, the need to operate in harsh environments and the need to operate independently and intelligently for long periods of time (due to communication limitations). Here, we give an overview of the technical capabilities of the Raman instruments planned for future planetary missions and give a review of the preparatory work being pursued to ensure that such instruments are operated successfully and optimally. This includes analysis of extremophile samples containing pigments associated with biological processes, synthetic materials which incorporate biological material within a mineral matrix, planetary analogues containing low levels of reduced carbon and samples coated with desert varnish that incorporate both geo-markers and biomarkers. We discuss the scientific importance of each sample type and the challenges using portable/flight-prototype instrumentation. We also report on technical development work undertaken to enable the next generation of Raman instruments to reach higher levels of sensitivity and operational efficiency.
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http://dx.doi.org/10.1098/rsta.2014.0204DOI Listing
December 2014

Heterologous expression of mycobacterial Esx complexes in Escherichia coli for structural studies is facilitated by the use of maltose binding protein fusions.

PLoS One 2013 29;8(11):e81753. Epub 2013 Nov 29.

UCLA-DOE Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, California, United States of America.

The expression of heteroligomeric protein complexes for structural studies often requires a special coexpression strategy. The reason is that the solubility and proper folding of each subunit of the complex requires physical association with other subunits of the complex. The genomes of pathogenic mycobacteria encode many small protein complexes, implicated in bacterial fitness and pathogenicity, whose characterization may be further complicated by insolubility upon expression in Escherichia coli, the most common heterologous protein expression host. As protein fusions have been shown to dramatically affect the solubility of the proteins to which they are fused, we evaluated the ability of maltose binding protein fusions to produce mycobacterial Esx protein complexes. A single plasmid expression strategy using an N-terminal maltose binding protein fusion to the CFP-10 homolog proved effective in producing soluble Esx protein complexes, as determined by a small-scale expression and affinity purification screen, and coupled with intracellular proteolytic cleavage of the maltose binding protein moiety produced protein complexes of sufficient purity for structural studies. In comparison, the expression of complexes with hexahistidine affinity tags alone on the CFP-10 subunits failed to express in amounts sufficient for biochemical characterization. Using this strategy, six mycobacterial Esx complexes were expressed, purified to homogeneity, and subjected to crystallization screening and the crystal structures of the Mycobacterium abscessus EsxEF, M. smegmatis EsxGH, and M. tuberculosis EsxOP complexes were determined. Maltose binding protein fusions are thus an effective method for production of Esx complexes and this strategy may be applicable for production of other protein complexes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081753PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843698PMC
December 2014
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