Publications by authors named "Jeremy D Shaw"

25 Publications

  • Page 1 of 1

Surgery Related Factors Do Not Affect Short-Term Adjacent Segment Kinematics After Anterior Cervical Arthrodesis.

Spine (Phila Pa 1976) 2021 Apr 23. Epub 2021 Apr 23.

Department of Orthopaedic Surgery, University of Pittsburgh Medical Center Department of Neurosurgery, University of Pittsburgh Medical Center.

Study Design: Prospective cohort study.

Objective: To identify surgical factors that affect adjacent segment kinematics after anterior cervical discectomy and fusion (ACDF) as measured by biplane radiography.

Summary Of Background Data: Previous studies investigated the effect of surgical factors on spine kinematics as a potential etiology for adjacent segment disease (ASD). Those studies used static flexion-extension radiographs to evaluate range of motion. However, measurements from static radiographs are known to be unreliable. Furthermore, those studies were unable to evaluate the effect of ACDF on adjacent segment axial rotation.

Methods: Patients had continuous cervical spine flexion/extension and axial rotation movements captured at 30 images per second in a dynamic biplane radiography system preoperatively and 1 year after ACDF. Digitally reconstructed radiographs generated from subject-specific CT scans were matched to biplane radiographs using a previously validated tracking process. Dynamic kinematics, postoperative segmental kyphosis, and disc distraction were calculated from this tracking process. Plate-to-disc distance was measured on postoperative radiographs. Graft type was collected from the medical record. Multivariate linear regression was performed to identify surgical factors associated with 1-year post-surgery changes in adjacent segment kinematics. A secondary analysis was also performed to compare adjacent segment kinematics between each of the surgical factors and previously defined thresholds believed to be associated with adjacent segment degeneration.

Results: Fifty-nine patients completed preoperative and postoperative testing. No association was found between any of the surgical factors and change in adjacent segment flexion/extension or axial rotation range of motion (all p > 0.09). The secondary analysis also did not identify differences between adjacent segment kinematics and surgical factors (all p > 0.07).

Conclusions: Following ACDF for cervical spondylosis, factors related to surgical technique were not associated with short-term changes in adjacent segment kinematics that reflect the hypermobility hypothesized to lead to the development of ASD.Level of Evidence: 2.
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http://dx.doi.org/10.1097/BRS.0000000000004080DOI Listing
April 2021

Pre-Operative Bariatric Surgery Imparts An Increased Risk of Infection, Re-Admission and Operative Intervention Following Elective Instrumented Lumbar Fusion.

Global Spine J 2021 Apr 28:21925682211011601. Epub 2021 Apr 28.

Department of Orthopaedic Surgery, 6595University of Pittsburgh Medical Center, PA, USA.

Study Design: Retrospective cohort study.

Objectives: To evaluate the impact of bariatric surgery on patient outcomes following elective instrumented lumbar fusion.

Methods: A retrospective review of a prospectively collected database was performed. Patients who underwent a bariatric procedure prior to an elective instrumented lumbar fusion were evaluated. Lumbar procedures were performed at a large academic medical center from 1/1/2012 to 1/1/2018. The primary outcome was surgical site infection (SSI) requiring surgical debridement. Secondary outcomes were prolonged wound drainage requiring treatment, implant failure requiring revision, revision secondary to adjacent segment disease (ASD), and chronic pain states. A randomly selected, surgeon and comorbidity-matched group of 59 patients that underwent an elective lumbar fusion during that period was used as a control. Statistical analysis was performed using Student's two-way t-tests for continuous data, with significance defined as < .05.

Results: Twenty-five patients were identified who underwent bariatric surgery prior to elective lumbar fusion. Mean follow-up was 2.4 ± 1.9 years in the bariatric group vs. 1.5 ± 1.3 years in the control group. Patients with a history of bariatric surgery had an increased incidence of SSI that required operative debridement, revision surgery due to ASD, and a higher incidence of chronic pain. Prolonged wound drainage and implant failure were equivalent between groups.

Conclusion: In the present study, bariatric surgery prior to elective instrumented lumbar fusion was associated increased risk of surgical site infection, adjacent segment disease and chronic pain when compared to non-bariatric patients.
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http://dx.doi.org/10.1177/21925682211011601DOI Listing
April 2021

Conflict of interest disclosure in orthopaedic and general surgical trauma literature.

Injury 2021 Mar 7. Epub 2021 Mar 7.

Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, 3471 Fifth Avenue, Suite 1010, Pittsburgh, PA 15213, United States. Electronic address:

Significance: Financial relationships between industry and physicians are a key aspect for the advancement of surgical practice and training, but these relationships also result in a conflict of interest with respect to research. Financial payments to physicians are public within the United States in the Open Payments Database, but the rate of accurate financial disclosure of payments has not previously been studied in trauma surgery publications.

Objective: To determine the rate of accurate financial disclosure in major surgical trauma journals compared with the Open Payments Database.

Materials And Methods: The names of all authors publishing in The Journal of Orthopaedic Trauma, Injury, and The Journal of Trauma and Acute Care Surgery between 2015 and 2018 were obtained from MEDLINE. Non-physicians, physicians outside of the United States, physicians without payments in the Open Payments Database, and physicians with payments types of only "Food and Drink" were excluded. Financial disclosure statements were obtained from the journal websites and manually compared against Open Payments Database entries the year prior to submission and during the year of submission up until 3 months prior to publication for each individual physician. Main outcomes were accuracy of disclosure published with each article, total amount of payments received (disclosure or undisclosed), surgical subspecialty of the reporting physician. Statistical comparisons were made using Chi-square testing with significance defined as p<0.05.

Results: Between 2015 and 2018, 5070 articles were published involving 28,948 authors. 2945 authors met inclusion criteria. 490 authors accurately disclosed their financial relationships with industry (16.6%). The median value of undisclosed payments was $22,140 [IQR $6465, $77,221] which was significantly less than the medial value of disclosed payment of $66,433 [IQR $24,624, $161,886], p<0.001 Orthopaedic surgeons disclosed at a higher rate (26.3%, 479/1818) than general surgeons (4.8%, 47/971), p<0.001.

Conclusions: Physician-industry relationships are key for advancing surgical practice and providing training to physicians. These relationships are not inherently unethical, but there is consistently high inaccuracy of financial disclosure across multiple trauma surgery journals which may indicate the need for further education on financial disclosures during surgical training or active obtainment of publicly available financial disclosures by journals.
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http://dx.doi.org/10.1016/j.injury.2021.03.011DOI Listing
March 2021

What Does Your PROMIS Score Mean? Improving the Utility of Patient-Reported Outcomes at the Point of Care.

Global Spine J 2020 Oct 14:2192568220958670. Epub 2020 Oct 14.

14358University of Utah, Salt Lake City, UT, USA.

Study Design: Prospective cohort.

Objectives: Patient-Reported Outcome Measurement Information System (PROMIS) has been validated for lumbar spine. Use of patient-reported outcome (PRO) measures can improve clinical decision making and health literacy at the point of care. Use of PROMIS, however, has been limited in part because clinicians and patients lack plain language understanding of the meaning of scores and it remains unclear how best to use them at the point of care. The purpose was to develop plain language descriptions to apply to PROMIS Physical Function (PF) and Pain Interference (PI) scores and to assess patient understanding and preferences in presentation of their individualized PRO information.

Methods: Retrospective analysis of prospectively collected PROMIS PF v1.2 and PI v1.1 for patients presenting to a tertiary spine center for back/lower extremity complaints was performed. Patients with missing scores, standard error >0.32, and assessments with <4 or >12 questions were excluded. Scores were categorized into score groups, specifically PROMIS PF groups were: <18, 20 ± 2, 25 ± 2, 30 ± 2, 35 ± 2, 40 ± 2, 45 ± 2, 50 ± 2, 55 ± 2, 60 ± 2, and >62; and PROMIS PI groups were: <48, 50 ± 2, 55 ± 2, 60 ± 2, 65 ± 2, 70 ± 2, 75 ± 2, 80 ± 2, and >82. Representative questions and answers from the PROMIS PI and PROMIS PF were selected for each score group, where questions with <25 assessments or representing <15% of assessments were excluded. Two fellowship-trained spine surgeons further trimmed the questions to create a streamlined clinical tool using a consensus process. Plain language descriptions for PROMIS PF were then used in a prospective assessment of 100 consecutive patients. Patient preference for consuming the score data was recorded and analyzed.

Results: In total, 12 712 assessments/5524 unique patients were included for PF and 14 823 assessments/6582 unique patients for PI. More than 90% of assessments were completed in 4 questions. The number of assessments and patients per scoring group were normally distributed. The mean PF score was 37.2 ± 8.2 and the mean PI was 63.3 ± 7.4. Plain language descriptions and compact clinical tool was were generated. Prospectively 100 consecutive patients were surveyed for their preference in receiving their -score versus plain language description versus graphical presentation. A total of 78% of patients found receiving personalized PRO data helpful, while only 1% found this specifically not helpful. Overall, 80% of patients found either graphical or plain language more helpful than -score alone, and half of these preferred plain language and graphical descriptions together. In total, 89% of patients found the plain language descriptions to be accurate.

Conclusions: Patients at the point of care are interested in receiving the results of their PRO measures. Plain language descriptions of PROMIS scores enhance patient understanding of PROMIS numerical scores. Patients preferred plain language and/or graphical representation rather than a numerical score alone. While PROs are commonly used for assessing outcomes in research, use at point of care is a growing interest and this study clarifies how they might be utilized in physician-patient communication.
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http://dx.doi.org/10.1177/2192568220958670DOI Listing
October 2020

Correction to: ISSLS prize in basic science 2021: a novel inducible system to regulate transgene expression of TIMP1.

Eur Spine J 2021 Mar 7. Epub 2021 Mar 7.

Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

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http://dx.doi.org/10.1007/s00586-021-06783-7DOI Listing
March 2021

ISSLS prize in basic science 2021: a novel inducible system to regulate transgene expression of TIMP1.

Eur Spine J 2021 Feb 1. Epub 2021 Feb 1.

Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Purpose: Inflammatory and oxidative stress upregulates matrix metalloproteinase (MMP) activity, leading to intervertebral disc degeneration (IDD). Gene therapy using human tissue inhibitor of metalloproteinase 1 (hTIMP1) has effectively treated IDD in animal models. However, persistent unregulated transgene expression may have negative side effects. We developed a recombinant adeno-associated viral (AAV) gene vector, AAV-NFκB-hTIMP1, that only expresses the hTIMP1 transgene under conditions of stress.

Methods: Rabbit disc cells were transfected or transduced with AAV-CMV-hTIMP1, which constitutively expresses hTIMP1, or AAV-NFκB-hTIMP1. Disc cells were selectively treated with IL-1β. NFκB activation was verified by nuclear translocation. hTIMP1 mRNA and protein expression were measured by RT-PCR and ELISA, respectively. MMP activity was measured by following cleavage of a fluorogenic substrate.

Results: IL-1β stimulation activated NFκB demonstrating that IL-1β was a surrogate for inflammatory stress. Stimulating AAV-NFκB-hTIMP1 cells with IL-1β increased hTIMP1 expression compared to unstimulated cells. AAV-CMV-hTIMP1 cells demonstrated high levels of hTIMP1 expression regardless of IL-1β stimulation. hTIMP1 expression was comparable between IL-1β stimulated AAV-NFκB-hTIMP1 cells and AAV-CMV-hTIMP1 cells. MMP activity was decreased in AAV-NFκB-hTIMP1 cells compared to baseline levels or cells exposed to IL-1β.

Conclusion: AAV-NFκB-hTIMP1 is a novel inducible transgene delivery system. NFκB regulatory elements ensure that hTIMP1 expression occurs only with inflammation, which is central to IDD development. Unlike previous inducible systems, the AAV-NFκB-hTIMP1 construct is dependent on endogenous factors, which minimizes potential side effects caused by constitutive transgene overexpression. It also prevents the unnecessary production of transgene products in cells that do not require therapy.
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http://dx.doi.org/10.1007/s00586-021-06728-0DOI Listing
February 2021

What is the predictive value of intraoperative somatosensory evoked potential monitoring for postoperative neurological deficit in cervical spine surgery?-a meta-analysis.

Spine J 2021 Apr 16;21(4):555-570. Epub 2021 Jan 16.

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Electronic address:

Background Context: Cervical decompression and fusion surgery remains a mainstay of treatment for a variety of cervical pathologies. Potential intraoperative injury to the spinal cord and nerve roots poses nontrivial risk for consequent postoperative neurologic deficits. Although neuromonitoring with intraoperative somatosensory evoked potentials (SSEPs) is often used in cervical spine surgery, its therapeutic value remains controversial.

Purpose: The purpose of the present study was to evaluate whether significant SSEP changes can predict postoperative neurologic complications in cervical spine surgery. A subgroup analysis was performed to compare the predictive power of SSEP changes in both anterior and posterior approaches.

Study Design: The present study was a meta-analysis of the literature from PubMed, Web of Science, and Embase to identify prospective/retrospective studies with outcomes of patients who underwent cervical spine surgeries with intraoperative SSEP monitoring.

Patient Sample: The total cohort consisted of 7,747 patients who underwent cervical spine surgery with intraoperative SSEP monitoring.

Methods: Inclusion criteria for study selection were as follows: (1) prospective or retrospective cohort studies, (2) studies conducted in patients undergoing elective cervical spine surgery not due to aneurysm, tumor, or trauma with intraoperative SSEP monitoring, (3) studies that reported postoperative neurologic outcomes, (4) studies conducted with a sample size ≥20 patients, (5) studies with only adult patients ≥18 years of age, (6) studies published in English, (7) studies inclusive of an abstract.

Outcome Measures: The sensitivity, specificity, diagnostic odds ratio (DOR), and likelihood ratios of overall SSEP changes, reversible SSEP changes, irreversible SSEP changes, and SSEP loss for predicting postoperative neurological deficit were calculated.

Results: The total rate of postoperative neurological deficits was 2.50% (194/7,747) and the total rate of SSEP changes was 7.36% (570/7,747). The incidence of postoperative neurological deficit in patients with intraoperative SSEP changes was 16.49% (94/570) while only 1.39% (100/7,177) in patients without. All significant intraoperative SSEP changes had a sensitivity of 46.0% and specificity of 96.7% with a DOR of 27.32. Reversible and irreversible SSEP changes had sensitivities of 17.7% and 37.1% and specificities of 97.5% and 99.5%, respectively. The DORs for reversible and irreversible SSEP changes were 9.01 and 167.90, respectively. SSEP loss had a DOR of 51.39, sensitivity of 17.3% and specificity 99.6%. In anterior procedures, SSEP changes had a DOR of 9.60, sensitivity of 34.2%, and specificity of 94.7%. In posterior procedures, SSEP changes had a DOR of 13.27, sensitivity of 42.6%, and specificity of 94.0%.

Conclusions: SSEP monitoring is highly specific but weakly sensitive for postoperative neurological deficit following cervical spine surgery. The analysis found that patients with new postoperative neurological deficits were nearly 27 times more likely to have had significant intraoperative SSEP change. Loss of SSEP signals and irreversible SSEP changes seem to indicate a much higher risk of injury than reversible SSEP changes.
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http://dx.doi.org/10.1016/j.spinee.2021.01.010DOI Listing
April 2021

Chronic Subdural Hematoma as a Complication of Cerebrospinal Fluid Leak During Revision Lumbar Spine Surgery: A Case Report and Review of the Literature.

HSS J 2020 Dec 5;16(Suppl 2):482-484. Epub 2019 Aug 5.

Department of Orthopaedic Surgery, Ferguson Lab for Orthopaedic Research, University of Pittsburgh Medical Center, E1643 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213 USA.

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http://dx.doi.org/10.1007/s11420-019-09709-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749911PMC
December 2020

The Impact of Obesity on Risk Factors for Adverse Outcomes in Patients Undergoing Elective Posterior Lumbar Spine Fusion.

Spine (Phila Pa 1976) 2021 Apr;46(7):457-463

Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA.

Study Design: Retrospective case-control study.

Objective: The aim of this study was to determine the influence of obesity on risk factors for adverse outcome after lumbar spine fusion (LSF).

Summary Of Background Data: Obesity is risk factor for complications after LSF and poses unique challenges regarding optimization of care. Nonetheless, this patient population is not well-studied.

Methods: Adult patients undergoing LSF were identified the State Inpatient Database. Patients were identified as obese or nonobese using ICD-9 codes. Outcome variables were 90-day readmission, major medical complication, infection, and revision rates. Data were queried for demographics, comorbidities, surgery characteristics, and outcome variables. Logistic multivariate regression was utilized, serially testing interactions between obesity and other independent variables in separate models for each outcome. The Benjamini-Hochberg procedure was used to adjust statistical significance for multiple comparisons.

Results: A total of 262,153 patients were included: 31,062 obese and 231, 091 nonobese. For major complications, obese patients had lower odds ratios (ORs) versus nonobese patients for cerebrovascular accident, diabetes with chronic complications, age ≥65, congestive heart failure, history of myocardial infarction, renal disease, chronic pulmonary disease, Medicare/Medicaid payor, more than two levels fused, transforaminal/posterior lumbar interbody fusion, and female sex, and higher OR for non-White race. For readmission, obese patients had lower OR for age ≥65, history of MI, renal disease, and mental health disease, and higher OR for female sex. For revision, obese patients had higher OR for female sex and TLIF/PLIF. For infection, obese patients had lower OR for diabetes with and without chronic complications, and higher OR for female sex.

Conclusion: Many medical comorbidities have less impact in obese patients than nonobese patients in predicting adverse outcomes despite increased rates of adverse outcomes in obese patients. These findings reflect the impact of obesity as an independent risk factor and have important implications for preoperative optimization.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003812DOI Listing
April 2021

Methylene Blue Is an Effective Disclosing Agent for Identifying Bacterial Biofilms on Orthopaedic Implants.

J Bone Joint Surg Am 2020 Oct;102(20):1784-1791

Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, Utah.

Background: Bacterial biofilms pose a challenge in treating implant-associated infections. Biofilms provide bacteria with protection against antimicrobial agents and the immune response and often are invisible to the naked eye. As a biofilm-disclosing agent, methylene blue (MB) has shown promise, but lacks rigorous in vitro evaluation. The purposes of the present study were to assess MB as a biofilm-disclosing agent in vitro for common biofilm-forming organisms and to determine performance characteristics across implant materials and healthy tissue types.

Methods: Staphylococcus aureus (ATCC 6538) and Pseudomonas aeruginosa (ATCC 27853) biofilms were grown on culture for 2 days in CDC biofilm reactors on titanium, cobalt chromium, polyethylene, and polyether ether ketone (PEEK) coupons. Biofilms were stained with MB solutions of either 0.005% or 0.01% and then were washed with normal saline solution. Digital photographs were obtained to compare the visual sensitivity of the blue dye at these dilutions. Scanning electron microscopy (SEM) was performed to confirm the absence or presence of biofilm on MB-stained areas. Uninoculated controls were also assessed. Healthy adult sheep tissues were also stained to determine the staining characteristics of the host tissue. ImageJ was used to determine the relative blue intensity of stained implants and tissues compared with standard curves.

Results: S. aureus and P. aeruginosa biofilms stained avidly on titanium, cobalt chromium, polyethylene, and PEEK coupons. There was visible dose-dependent staining based on dye concentration. MB was visible only where biofilms were present as confirmed by SEM. MB did not stain uninoculated controls. Articular cartilage and meniscus demonstrated appreciable staining; bone, tendon, muscle, nerve, and fat did not. Bacterial biofilms demonstrated both dose-dependent and species-specific staining.

Conclusions: MB is an effective disclosing agent for S. aureus and P. aeruginosa biofilms in vitro. MB did not stain implant materials, nor did it stain most healthy tissues in vitro. MB may allow surgeons to see biofilms and may allow for enhanced debridement once visualized.
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http://dx.doi.org/10.2106/JBJS.20.00091DOI Listing
October 2020

Use of Fondaparinux Following Elective Lumbar Spine Surgery Is Associated With a Reduction in Symptomatic Venous Thromboembolism.

Global Spine J 2020 Oct 30;10(7):844-850. Epub 2019 Sep 30.

6595University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Study Design: Retrospective cohort study.

Objective: To assess the impact of fondaparinux on venous thromboembolism (VTE) following elective lumbar spine surgery in high-risk patients.

Methods: Matched patient cohorts who did or did not receive inpatient fondaparinux starting postoperative day 2 following elective lumbar spine surgery were compared. All patients received 1 month of acetyl salicylic acid 325 mg following discharge. The primary outcome was a symptomatic DVT (deep vein thrombosis) or PE (pulmonary embolus) within 30 days of surgery. Secondary outcomes included prolonged wound drainage, epidural hematoma, and transfusion.

Results: A significantly higher number of DVTs were diagnosed in the group that did not receive inpatient VTE prophylaxis (3/102, 2.9%) compared with the fondaparinux group (0/275, 0%, = .02). Increased wound drainage was seen in 18.5% of patients administered fondaparinux, compared with 25.5% of untreated patients ( = .15). Deep infections were equivalent (2.2% with fondaparinux vs 4.9% control, = .18). No epidural hematomas were noted, and the number of transfusions after postoperative day 2 and 90-day return to operating room rates were equivalent.

Conclusions: Patients receiving fondaparinux had lower rates of symptomatic DVT and PE and a favorable complication profile when compared with matched controls. The retrospective nature of this work limits the safety and efficacy claims that can be made about the use of fondaparinux to prevent VTE in elective lumbar spine surgery patients. Importantly, this work highlights the potential safety of this regimen, permitting future high-quality trials.
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http://dx.doi.org/10.1177/2192568219878418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485070PMC
October 2020

Undisclosed Conflict of Interest Is Prevalent in Spine Literature.

Spine (Phila Pa 1976) 2020 Nov;45(21):1524-1529

Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.

Study Design: Cohort study.

Objective: The aim of this study was to determine the rate of accurate conflict of interest (COI) disclosure within three prominent subspecialty Spine journals during a 4-year period.

Summary Of Background Data: Industry-physician relationships are crucial for technological advancement in spine surgery but serve as a source of bias in biomedical research. The Open Payments Database (OPD) was established after 2010 to increase financial transparency.

Methods: All research articles published from 2014 to 2017 in Spine, The Spine Journal (TSJ), and the Journal of Neurosurgery: Spine (JNS) were reviewed in this study. In these articles, all author's COI statements were recorded. The OPD was queried for all author entries within the disclose period of the journal. Discrepancies between the author's self-reported COIs and the documented COIs from OPD were recorded.

Results: A total of 6816 articles meeting inclusion criteria between 2014 and 2017 in Spine, TSJ, and JNS with 39,869 contributing authors. Overall, 15.8% of all authors were found to have an OPD financial relationship. Of 2633 authors in Spine with financial disclosures, 77.1% had accurate financial disclosures; 42.5% and 41.0% of authors with financial relationships in the OPD had accurate financial disclosures in TSJ and JNS, respectively. The total value of undisclosed conflicts of interest between 2014 and 2017 was $421 million with $1.48 billion in accurate disclosures. Of undisclosed payments, 68.7% were <$1000 and only 7.2% were >$10,000. Undisclosed payments included $180 million in research funding and $188 million in royalties.

Conclusion: This study demonstrates that undisclosed COI is highly prevalent for authors in major Spine journals. This study indicates that there remains a need to standardize definitions and financial thresholds for significant COI as well as to shift the reporting burden for COI to journals who actively review potential COIs instead of relying on self-reporting.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003589DOI Listing
November 2020

Assessing the biofidelity of in vitro biomechanical testing of the human cervical spine.

J Orthop Res 2020 Apr 25. Epub 2020 Apr 25.

Ferguson Lab for Orthopaedic Research, Department of Orthopaedic Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.

In vitro biomechanical studies of the osteoligamentous spine are widely used to characterize normal biomechanics, identify injury mechanisms, and assess the effects of degeneration and surgical instrumentation on spine mechanics. The objective of this study was to determine how well four standards in vitro loading paradigms replicate in vivo kinematics with regards to the instantaneous center of rotation and arthrokinematics in relation to disc deformation. In vivo data were previously collected from 20 asymptomatic participants (45.5 ± 5.8 years) who performed full range of motion neck flexion-extension (FE) within a biplane x-ray system. Intervertebral kinematics were determined with sub-millimeter precision using a validated model-based tracking process. Ten cadaveric spines (51.8 ± 7.3 years) were tested in FE within a robotic testing system. Each specimen was tested under four loading conditions: pure moment, axial loading, follower loading, and combined loading. The in vivo and in vitro bone motion data were directly compared. The average in vitro instant center of rotation was significantly more anterior in all four loading paradigms for all levels. In general, the anterior and posterior disc heights were larger in the in vitro models than in vivo. However, after adjusting for gender, the observed differences in disc height were not statistically significant. This data suggests that in vitro biomechanical testing alone may fail to replicate in vivo conditions, with significant implications for novel motion preservation devices such as cervical disc arthroplasty implants.
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http://dx.doi.org/10.1002/jor.24702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606317PMC
April 2020

In vivo changes in adjacent segment kinematics after lumbar decompression and fusion.

J Biomech 2020 03 14;102:109515. Epub 2019 Nov 14.

Department of Orthopaedic Surgery, Orthopaedic Biodynamics Laboratory, University of Pittsburgh, Pittsburgh, USA; EMPA (Swiss Federal Laboratories for Materials Science and Research), Mechanical Systems Engineering (Lab 304), Duebendorf, Switzerland.

The pathogenesis of lumbar adjacent segment disease is thought to be secondary to altered biomechanics resulting from fusion. Direct in vivo evidence for altered biomechanics following lumbar fusion is lacking. This study's aim was to describe in vivo kinematics of the superior adjacent segment relative to the fused segment before and after lumbar fusion. This study analyzed seven patients with symptomatic lumbar degenerative spondylolisthesis (5 M, 2F; age 65 ± 5.1 years) using a biplane radiographic imaging system. Each subject performed two to three trials of continuous flexion of their torso according to established protocols. Synchronized biplane radiographs were acquired at 20 images per second one month before and six months after single-level fusion at L4-L5 or L5-S1, or two-level fusion at L3-L5 or L4-S1. A previously validated volumetric model-based tracking process was used to track the position and orientation of vertebrae in the radiographic images. Intervertebral flexion/extension and AP translation (slip) at the superior adjacent segment were calculated over the entire dynamic flexion activity. Skin-mounted surface markers were tracked using conventional motion analysis and used to determine torso flexion. Change in adjacent segment kinematics after fusion was determined at corresponding angles of dynamic torso flexion. Changes in adjacent segment motion varied across patients, however, all patients maintained or increased the amount of adjacent segment slip or intervertebral flexion/extension. No patients demonstrated both decreased adjacent segment slip and decreased rotation. This study suggests that short-term changes in kinematics at the superior adjacent segment after lumbar fusion appear to be patient-specific.
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http://dx.doi.org/10.1016/j.jbiomech.2019.109515DOI Listing
March 2020

Cervical Spine Fractures: Who Really Needs CT Angiography?

Spine (Phila Pa 1976) 2019 Dec;44(23):1661-1667

Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.

Study Design: Retrospective cohort study.

Objective: Compare a novel two-step algorithm for indicating a computed tomography angiography (CTA) in the setting of a cervical spine fracture with established gold standard criteria.

Summary Of Background Data: As CTA permits the rapid detection of blunt cerebrovascular injuries (BCVI), screening criteria for its use have broadened. However, more recent work warns of the potential for the overdiagnosis of BCVI, which must be considered with the adoption of broad criteria.

Methods: A novel two-step metric for indicating CTA screening was compared with the American College of Surgeons guidelines and the expanded Denver Criteria using patients who presented with cervical spine fractures to a tertiary-level 1 trauma center from January 1, 2012 to January 1, 2016. The ability for each metric to identify BCVI and posterior circulation strokes that occurred during this period was assessed.

Results: A total of 721 patients with cervical fractures were included, of whom 417 underwent CTAs (57.8%). Sixty-eight BCVIs and seven strokes were diagnosed in this cohort. All algorithms detected an equivalent number of BCVIs (52 with the novel metric, 54 with the ACS and Denver Criteria, P = 0.84) and strokes (7/7, 100% with the novel metric, 6/7, 85.7% with the ACS and Denver Criteria, P = 1.0). However, 63% fewer scans would have been needed with the proposed screening algorithm compared with the ACS or Denver Criteria (261/721, 36.2% of all patients with our criteria vs. 413/721, 57.3% with the ACS standard and 417/721, 57.8%) with the Denver Criteria, P < 0.0002 for each).

Conclusion: A two-step criterion based on mechanism of injury and patient factors is a potentially useful guide for identifying patients at risk of BCVI and stroke after cervical spine fractures. Further prospective analyses are required prior to widespread clinical adoption.

Level Of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000003163DOI Listing
December 2019

No relationship between mild limb length discrepancy and spine, hip or knee degenerative disease in a large cadaveric collection.

Orthop Traumatol Surg Res 2018 09 27;104(5):603-607. Epub 2018 Apr 27.

Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut, USA.

Background: Although asymptomatic mild limb length discrepancy (LLD) in children is generally treated non-operatively, there is limited high quality follow up data to support this recommendation.

Hypothesis: We hypothesized that there would be no association between LLD and arthritic changes with mild limb length discrepancy.

Materials And Methods: We studied 576 well-preserved cadaveric skeletons ranging from 40 to 79 years of age. Limb length discrepancy was based on combined femoral and tibial lengths measured using digital calipers. Degenerative disease was hand graded in the spine, hips and knees using a previously described classification system. Power was set at 90%.

Results: Average age was 56±10 years and average LLD was 4.8±4.0mm. Multiple regression analysis did not demonstrate any correlation between LLD and degenerative disease. After screening to find 26 additional specimens with LLD 10mm or greater, and assessing a potentially quadratic relationship, we still did not find any detrimental effects of LLD.

Discussion: Our data support the general clinical recommendation of observation for mild asymptomatic LLD. These results do not apply to larger LLD nor LLD associated with other deformities or clinical symptoms.

Level Of Evidence: Not applicable, anatomic basic science study.
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http://dx.doi.org/10.1016/j.otsr.2017.11.025DOI Listing
September 2018

Spine deformity surgery in the elderly: risk factors and 30-day outcomes are comparable in posterior versus combined approaches.

Neurol Res 2017 Dec 19;39(12):1066-1072. Epub 2017 Sep 19.

a Department of Orthopedic Surgery , University of California San Francisco , San Francisco , CA , USA.

Objectives Risk factors portending poor outcome following elective spine deformity fusion remain in need of characterization and stratification in the elderly population. Methods Cases aged ≥60 years who underwent elective posterior or anterior-posterior ('combined') fusion were extracted from the American College of Surgeons National Surgical Quality Improvement Program years 2007-2013 and analyzed by surgical cohort (posterior vs. combined). The 30-day outcomes included operation time, hospital length of stay (HLOS), perioperative complications, and discharge destination. Multivariable regressions controlling for demographic/clinical variables were performed. Odds ratios (OR) and mean differences (B) were reported with 95% confidence intervals (CI). Results A total of 881 cases (18.2% combined; 81.8% posterior) aged 70 ± 6.2 years, 32.8% male, and 87.2% Caucasian were included. Posterior fusions associated with extreme body habitus (obese class II/III and underweight; P = 0.027), functional independence (97.5% vs. 91.8%; P = 0.010), and multi-level fusions (7-12 levels: 24.8% vs. 18.1%; ≥13 levels: 8.9% vs. 3.1%; P = 0.004). Overall operation time was 338.0 ± 150.2-min and HLOS 7.4 ± 6.6-days; 17.1% suffered early complications and 54.5% were discharged home. On multivariable analysis, combined (B = 63.8-min; P < 0.001), and multi-level fusions (7-12: 61.0-min; P < 0.001; ≥13: 133.8-min; p < 0.001) associated with increased operation time. HLOS increased for multi-level fusions (7-12 levels: 1.3-days; P = 0.012; ≥13 levels: 2.2-days; P = 0.008). Overall complications did not differ by cohort or levels; on post hoc analysis combined fusions associated with pneumonia (OR = 3.05; P = 0.008). Multi-level fusions showed decreased odds of discharge home (7-12 levels: OR = 0.57; P = 0.003; ≥13-levels: OR = 0.41; P = 0.003). Conclusions The 30-day outcomes and early perioperative complications are comparable for posterior vs. combined approaches to correct deformity in the elderly. Multi-level fusions are associated with increased operation time, HLOS, and discharge to higher level of care.
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http://dx.doi.org/10.1080/01616412.2017.1378298DOI Listing
December 2017

Methylene Blue-Guided Debridement as an Intraoperative Adjunct for the Surgical Treatment of Periprosthetic Joint Infection.

J Arthroplasty 2017 12 21;32(12):3718-3723. Epub 2017 Jul 21.

Department of Orthopaedic Surgery, University of California, San Francisco (UCSF), San Francisco, California.

Background: Current methods to identify infected tissue in periprosthetic joint infection (PJI) are inadequate. The purpose of this study was (1) to assess methylene blue-guided surgical debridement as a novel technique in PJI using quantitative microbiology and (2) to evaluate clinical success based on eradication of infection and infection-free survival.

Methods: Sixteen total knee arthroplasty patients meeting Musculoskeletal Infection Society criteria for PJI undergoing the first stage of 2-stage exchange arthroplasty were included in this prospective study. Dilute methylene blue (0.1%) was instilled in the knee before debridement, residual dye was removed, and stained tissue was debrided. Paired tissue samples, stained and unstained, were collected from the femur, tibia, and capsule during debridement. Samples were analyzed by neutrophil count, semiquantitative culture, and quantitative polymerase chain reaction (PCR). Clinical success was a secondary outcome.

Results: The mean age was 64.0 ± 6.0 years, and follow-up was 24.4 ± 3.5 months. More bacteria were found in methylene blue-stained vs unstained tissue-based on semiquantitative culture (P = .001). PCR for staphylococcal species showed 9-fold greater bioburden in methylene blue-stained vs unstained tissue (P = .02). Tissue pathology found 53 ± 46 polymorphonuclear leukocytes per high-power field in methylene blue-stained vs 4 ± 13 in unstained tissue (P = .0001). All subjects cleared their primary infection and underwent reimplantation. At mean 2-year follow-up, 25% of patients failed secondary to new infection with a different organism.

Conclusion: These results suggest a role for methylene blue in providing a visual index of surgical debridement in the treatment of PJI.
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http://dx.doi.org/10.1016/j.arth.2017.07.019DOI Listing
December 2017

Increasing Rates of Surgical Management of Multilevel Spinal Curvature in Elderly Patients.

Spine Deform 2016 09 21;4(5):365-372. Epub 2016 Aug 21.

Department of Orthopaedic Surgery, University of California-San Francisco, 1500 Owens St. Box 3004, San Francisco, CA 94158, USA. Electronic address:

Study Design: Retrospective analysis of Nationwide Inpatient Sample (NIS) database.

Objective: To analyze trends in utilization and hospital charges for multilevel spinal curvature surgery in patients over 60 from 2004 to 2011.

Summary Of Background Data: Multilevel spinal curvature has been increasingly recognized as a major source of morbidity in patients over sixty years of age. The economic burden of non-operative management for spinal curvature is elusive and likely underestimated. Though patient reported outcomes suggest that surgical treatment of spinal curvature may be superior to non-operative treatment in selected patients, surgical utilization trends remain unclear.

Methods: Data were obtained from the NIS between 2004 and 2011. The NIS is the largest all-payer inpatient care database with approximately eight million annual patient discharges throughout the United States. Analysis included patients over age 60 with a spinal curvature diagnosis treated with a multi-level spinal fusion (≥3 levels fused) determined by ICD-9-CM diagnosis and procedure codes. Population-based utilization rates were calculated from US census data.

Results: A total of 84,302 adult patients underwent multilevel spinal curvature surgery from 2004 to 2011. The annual number of ≥3 level spinal curvature fusions in patients over age 60 increased from 6,571 to 16,526, representing a 107.8% increase from 13.4 cases per 100,000 people in 2004 to 27.9 in 2011 (p < .001). Utilization rates in patients 65-69 years old experienced the greatest growth, increasing by 122% from 15.8 cases per 100,000 people to 35.1. Average hospital charges increased 108% from $90,557 in 2007 to $188,727 in 2011 (p < .001).

Conclusions: Rates of surgical management of multilevel spinal curvature increased from 2004 to 2011, exceeding growth of the 60+ age demographic during the same period. Growth was observed in all age demographics, and hospital charges consistently increased from 2004 to 2011 reflecting a per-user increase in expenditure.

Level Of Evidence: III.
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http://dx.doi.org/10.1016/j.jspd.2016.03.005DOI Listing
September 2016

Sexual function after cervical spine surgery: Independent predictors of functional impairment.

J Clin Neurosci 2017 Feb 4;36:94-101. Epub 2016 Nov 4.

Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Avenue, Rm 779M, CA 94143, USA. Electronic address:

Sexual function (SF) is an important component of patient-focused health related quality of life (HRQoL), but it has not been well studied in spine surgery. This study aims to assess SF after cervical spine surgery and identify predictors of SF. This single-center retrospective study evaluates SF of adults who underwent cervical spine surgery 2007-2012. Predictor variables included demographics, medical/surgical history, operative information, HRQoL measures (Neck Disability Index, SF-12), validated SF surveys [Female Sexual Function Index (FSFI) and Brief Sexual Function Inventory (BSFI) for males], and a study-specific SF questionnaire. 59 patients (31M, 28F; mean age=56±8.4) had significantly lower SF scores compared to age-matched peers: average BSFI = 2.26±1.22 (vs. 06±0.74), average FSFI=13.05±11.42 (<26.55 indicating sexual dysfunction). In men, lower mental SF-12 and higher NDI, back pain, and number of operated levels were associated with lower BSFI scores (all p<0.05). In women, higher total number of medications and pain medications were associated with lower FSFI scores (both p<0.05). 46% of patients reported difficulty performing a sexual position after surgery that they had previously enjoyed. 39% of men had difficulty on top during intercourse, and 32% of participants reported difficulty performing oral sex. 39% of patients reported worse SF, while only 5% reported an improvement in postoperative SF. Men and women who underwent cervical spine surgery had lower SF scores than age-matched peers, likely attributable to general mental health, regional neck disability, back pain, and medications. A large portion of patients reported subjectively worsened SF after surgery.
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http://dx.doi.org/10.1016/j.jocn.2016.10.017DOI Listing
February 2017

The role of the hospital and health care system characteristics in readmissions after major surgery in California.

Surgery 2016 Feb 21;159(2):381-8. Epub 2015 Jul 21.

Department of Surgery, Stanford University, Stanford, CA.

Background: Hospital readmission after major surgery is a costly problem that has been associated with patient characteristics. Because hospitals are incentivized to join accountable care organizations, interventions on a hospital or health care system level may help reduce readmissions. Our objective was to identify hospital- and systems-level characteristics associated with readmissions after major operative procedures.

Methods: Retrospective analysis of California discharge abstracts with record linkage numbers for adult patients undergoing coronary artery bypass graft (CABG), colectomy or total hip/knee arthroplasty (TJA) in California acute, nonfederal hospitals in 2011. The record linkage number showed where patients were readmitted. Hierarchic logistic regression estimated the odds of readmission by hospital characteristics.

Results: There were 91,205 records analyzed: CABG (6.4%), colectomy (12.0%), and TJA (82.3%). There were 120 hospitals that performed CABG surgery; 296 performed colectomy; and 298 performed TJA. Readmission rates after CABG was 9.7%, colectomy 7.7%, and TJA 3.9%. After adjustment for patient factors, rural location was predictive of readmission after colectomy (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.40-3.08). Low-volume (OR 1.54, 95% CI 1.13-2.10) and minority-serving hospitals (OR 1.18, 95% CI 1.05-1.33) were associated with greater odds of readmission after TJA.

Conclusion: Select hospital characteristics are associated with readmissions after major operative procedures. Because financial penalties may worsen performance in vulnerable or low-resource settings, policies aimed at reducing readmissions should be attentive to the potential unintended consequences.
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http://dx.doi.org/10.1016/j.surg.2015.06.016DOI Listing
February 2016

Characterization of lumbar spinous process morphology: a cadaveric study of 2,955 human lumbar vertebrae.

Spine J 2015 Jul 14;15(7):1645-52. Epub 2015 Mar 14.

Department of Orthopedics, New England Baptist Hospital, 125 Parker Hill Ave, Boston, MA 02120, USA.

Background Context: Despite the interest in lumbar spinous process (SP)-based surgical innovation, there are no large published studies that have characterized the morphometry of lumbar SPs.

Purpose: To provide accurate level-specific morphometric data with respect to human lumbar SPs using a human cadaveric lumbar spine model and to describe the morphometric variation of lumbar SPs with respect to gender, race, and age.

Study Design: An anatomic observational study.

Methods: This study used 2,955 cadaveric lumbar vertebrae from 591 adult spines at the Hamann-Todd Human Osteological Collection. Specimens were aged 20 to 79 years. Each vertebra was photographed in standardized positions and measured using ImageJ software. Direct measurements were made for the SP length, width, height, slope, and caudal morphology. Gender, race, and age were recorded and analyzed.

Results: Spinous process length was 24.8±4.6 mm (L5) to 33.9±3.9 mm (L3). Effective length varied from 19.5±2.6 mm (L1) to 24.6±3.3 mm (L4). Height was shortest at L5 (18.2±2.7 mm). Caudal width was greater than the cranial width. Slope, caudal morphology, and radius measures showed large interspecimen variation. Slope at L5 was steeper than other levels (23.7°±10.5°, p<.0001). Most specimens demonstrated convex caudal morphology. L4 had the highest proportion of convexity (80.7%). L1 was the only level with predominantly concave morphology. Measurements for female SPs were smaller, but the slope was steeper. Anatomic and effective SP lengths were longer for specimens from white individuals. Specimens from black individuals had larger width and height, as well as steeper slope. Black specimens had more convex morphology at L4 and L5. With increasing age, the SP length, effective length, and width increased. Height increased with age only at L4 and L5. Slope and caudal radius of curvature decreased with age, and increasingly convex morphology was noted at most levels.

Conclusions: This large cadaveric study provides level-specific morphometric data regarding the osseous dimensions of lumbar SPs relevant to techniques and devices targeting the lumbar SPs or the interspinous space. Of particular importance is the recognition that L5 has relatively different morphology when compared with more cranial levels. Potentially important differences were noted comparing women with men, black with white, and aging populations.
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http://dx.doi.org/10.1016/j.spinee.2015.03.007DOI Listing
July 2015

Association between degenerative spondylolisthesis and spinous process fracture after interspinous process spacer surgery.

Spine J 2012 Jun 22;12(6):466-72. Epub 2012 May 22.

Department of Orthopaedic Surgery, New England Baptist Hospital and Tufts University School of Medicine, 125 Parker Hill Ave., Boston, MA 02120, USA.

Background Context: Spinous process fracture is a recognized complication associated with interspinous process spacer (IPS) surgery. Although occasionally identified by plain radiographs, computed tomography (CT) appears to identify a higher rate of such fractures. Although osteoporotic insufficiency fracture is considered a contraindication for IPS surgery, a formal risk factor analysis for this complication has not previously been reported.

Purpose: To identify risk factor(s) associated with early spinous process fracture after IPS surgery.

Study Design/setting: Prospective cohort study of 39 consecutive patients with lumbar stenosis and neurogenic claudication undergoing IPS surgery at a single institution.

Methods: Patients underwent preoperative dual-energy X-ray absorptiometry (DXA) scans, lumbar spine CT, and plain radiographs. Postoperatively, patients underwent repeat CT imaging within 6 months of surgery and serial radiographs at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year. Preoperative CT scans were analyzed by calculating average Hounsfield units for a 1 cm(2) area of the midsagittal reconstructed image for four separate locations: midvertebral body, subcortical bone subjacent to the superior margin of the midspinous process, subcortical bone above the inferior margin of the midspinous process, and the midspinous process.

Results: Thirty-eight patients underwent IPS surgery at a total of 50 levels (38 L4-L5, 12 L3-L4; 26 one-level, 12 two-level). One patient underwent laminectomy at index surgery and was excluded from the analysis. Implants included 34 titanium X-STOP (Medtronic, Memphis, TN, USA), 8 polyaryletheretherketone X-STOP (Medtronic, Memphis, TN, USA), and 8 Aspen (Lanx, Broomfield, CO, USA) devices. Eleven spinous process fractures were identified by CT in 11 patients (22.0% of levels). No fractures were apparent on plain radiographs. The rate of spondylolisthesis observed on preoperative radiographs was 100% (11 of 11) among patients with fractures compared with 33.3% (9 of 27) of patients without fracture (p=.0001). Overall, 21 of 39 patients in this series had spondylolisthesis, and the rate of fracture in this group was 52%. Among patients without spondylolisthesis, the fracture rate was 0%. A trend was observed toward decreased DXA lumbar spine and hip T-scores among fracture patients versus nonfracture patients (0.2 ± 1.7 vs. 0.8 ± 1.7; p=.389; -1.1 ± 1.4 vs. -0.3 ± 1.4; p=.201), but these differences were not significant. Similarly, bone density based on CT measurements at four different locations revealed a trend toward decreased density among fracture patients, but these differences were not significant.

Conclusions: Degenerative spondylolisthesis appears strongly associated with the occurrence of spinous process fracture after IPS surgery. There is a trend toward increased fracture risk in patients with decreased bone mineral density as measured by both DXA scan and CT-based volume averaging of Hounsfield units, but osteoporosis appears to be a relatively weaker risk factor. The association between spondylolisthesis and fracture observed in this study may account for the relatively poorer outcome of IPS surgery in patients with spondylolisthesis that has been reported in previous series.
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http://dx.doi.org/10.1016/j.spinee.2012.03.034DOI Listing
June 2012

Institutional prescreening for detection and eradication of methicillin-resistant Staphylococcus aureus in patients undergoing elective orthopaedic surgery.

J Bone Joint Surg Am 2010 Aug 7;92(9):1820-6. Epub 2010 Jul 7.

Department of Orthopaedic Surgery, New England Baptist Hospital, 125 Parker Hill Avenue, Boston, MA 02120, USA.

Background: Surgical site infection has been identified as one of the most important preventable sources of morbidity and mortality associated with medical treatment. The purpose of the present study was to evaluate the feasibility and efficacy of an institutional prescreening program for the preoperative detection and eradication of both methicillin-resistant and methicillin-sensitive Staphylococcus aureus in patients undergoing elective orthopaedic surgery.

Methods: Data were collected prospectively during a single-center study. A universal prescreening program, employing rapid polymerase chain reaction analysis of nasal swabs followed by an eradication protocol of intranasal mupirocin and chlorhexidine showers for identified carriers, was implemented. Surgical site infection rates were calculated and compared with a historical control period immediately preceding the start of the screening program.

Results: During the study period, 7019 of 7338 patients underwent preoperative screening before elective surgery, for a successful screening rate of 95.7%. One thousand five hundred and eighty-eight (22.6%) of the patients were identified as Staphylococcus aureus carriers, and 309 (4.4%) were identified as methicillin-resistant Staphylococcus aureus carriers. A significantly higher rate of surgical site infection was observed among methicillin-resistant Staphylococcus aureus carriers (0.97%; three of 309) compared with noncarriers (0.14%; seven of 5122) (p = 0.0162). Although a higher rate of surgical site infection was also observed among methicillin-sensitive Staphylococcus aureus carriers (0.19%; three of 1588) compared with noncarriers, this difference did not achieve significance (p = 0.709). Overall, thirteen cases of surgical site infection were identified during the study period, for an institutional infection rate of 0.19%. This rate was significantly lower than that observed during the control period (0.45%; twenty-four cases of surgical site infection among 5293 patients) (p = 0.0093).

Conclusions: Implementation of an institution-wide prescreening program for the identification and eradication of methicillin-resistant and methicillin-sensitive Staphylococcus aureus carrier status among patients undergoing elective orthopaedic surgery is feasible and can lead to significant reductions in postoperative rates of surgical site infection.

Level Of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.I.01050DOI Listing
August 2010

Genome-wide characterization of the SloR metalloregulome in Streptococcus mutans.

J Bacteriol 2010 Mar 13;192(5):1433-43. Epub 2009 Nov 13.

Department of Biology, Middlebury College, 276 Bicentennial Way, MBH354, Middlebury, VT 05753.

Streptococcus mutans is the primary causative agent of human dental caries, a ubiquitous infectious disease for which effective treatment strategies remain elusive. We investigated a 25-kDa SloR metalloregulatory protein in this oral pathogen, along with its target genes that contribute to cariogenesis. Previous studies have demonstrated manganese- and SloR-dependent repression of the sloABCR metal ion transport operon in S. mutans. In the present study, we demonstrate that S. mutans coordinates this repression with that of certain virulence attributes. Specifically, we noted virulence gene repression in a manganese-containing medium when SloR binds to promoter-proximal sequence palindromes on the S. mutans chromosome. We applied a genome-wide approach to elucidate the sequences to which SloR binds and to reveal additional "class I" genes that are subject to SloR- and manganese-dependent repression. These analyses identified 204 S. mutans genes that are preceded by one or more conserved palindromic SloR recognition elements (SREs). We cross-referenced these genes with those that we had identified previously as SloR and/or manganese modulated in microarray and real-time quantitative reverse transcription-PCR (qRT-PCR) experiments. From this analysis, we identified a number of S. mutans virulence genes that are subject to transcriptional upregulation by SloR and noted that such "class II"-type regulation is dependent on direct SloR binding to promoter-distal SREs. These observations are consistent with a bifunctional role for the SloR metalloregulator and implicate it as a target for the development of therapies aimed at alleviating S. mutans-induced caries formation.
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http://dx.doi.org/10.1128/JB.01161-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820837PMC
March 2010