Publications by authors named "Robert Tisherman"

16 Publications

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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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March 2021

Under Disclosure of Conflicts of Interest is less Frequent in Senior Authors: A Cross-Sectional Review of all Authors Submitting to JAAOS Between 2014 and 2018.

J Am Acad Orthop Surg 2021 Feb 22. Epub 2021 Feb 22.

From the Department of Orthopaedic Surgery (Tisherman, Musahl, and Lesniak), University of Pittsburgh Medical Center, Pittsburgh, PA, and the Georgetown University Hospital Orthopedics (Murray), Washington, DC.

The interactions between physicians and industry are necessary for advancement of clinical practice and improvement in medical devices. Physician-industry relationships also introduces financial conflicts of interest into research publications. Payments to physicians do not inherently introduce bias in research, but failure to disclose potential conflicts of interest can negatively impact the perceived integrity of authors, editors, and journals. The conflict of interest disclosure statement in all articles published in the Journal of the American Academy of Orthopaedic Surgery between 2014 and 2018 were compared to the financial payments indexed in the Center for Open Payments Database. Payment type, magnitude, and payer were obtained for each payment meeting inclusion criteria. Statistical comparisons were made using Mann-Whitney comparisons due to non-normal distribution of payment amounts. 704 articles involving 2596 authors were reviewed, with 1268 authors meeting inclusion criteria. 634 authors had accurate disclosure statements. The total amount of disclosed payments was $169 million, whereas undisclosed payments were $14.2 million. The amount of disclosed payments on a per-author basis, $55,844 ($12,559, $186,129), was significantly greater than undisclosed payments, $2,171 ($568, $7,238). The lowest rates of correct disclosure were in education (29.2%), gifts (38.7%) and honoraria (57.8%). First and middle authors disclosed correctly at a significantly lower rate than last authors. The magnitude of undisclosed payments was significantly lower than disclosed payments, indicating that these payments do not register with authors as significant enough to disclose.
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February 2021

Distal locking of short cephalomedullary nails decreases varus collapse in unstable intertrochanteric fractures - a biomechanical analysis.

Injury 2021 Mar 6;52(3):414-418. Epub 2021 Feb 6.

Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh PA, USA.

Introduction: Peritrochanteric fractures are a growing problem and complications relating to operative fixation of these fracture, including varus collapse and screw cutout, are common in elderly osteoporotic patients. We hypothesize that unlocked nails will demonstrate increased varus collapse and inferior construct stiffness in specimens with increased diaphyseal medullary diameter.

Materials And Methods: Sixteen non-cadaveric osteoporotic biomechanical femur specimens were utilized in this study, with eight specimens having an artificially large femoral canal to represent Dorr C femurs. All femurs were instrumented with a short cephalomedullary nail with and without distal cross-lock screw fixation and had an unstable intertrochanteric fracture created in a repeatable pattern. Specimens underwent cyclic compression to a maximal load of 1000N with segmental motion quantified through the use of visual tracking markers. Statistical comparisons were performed using one-way ANOVA with Tukey post-hoc analysis to determine differences between specific groups. Significance was defined as p<0.05.

Results: Unlocked short cephalomedullary nails showed increased varus collapse due to motion of the nail within the femoral canal in capacious femoral canals compared with narrow femoral canals and distally cross-locked nails. The coronal deformation of the wide canal unlocked group (17.9 ±2.6) was significantly greater in the varus direction than any other fixation under compressive load of 1000N. There was no significant difference in varus angulation between the wide canal or narrow canal locked groups (11.1±8.7 vs. 8.2±1.7 respectively, p=0.267). The narrow canal unlocked group (13.7±2.4) showed significantly greater varus angulation than the narrow canal locked (p=0.015). The wide canal unlocked group showed significantly greater varus angulation than the wide canal locked group (p=0.003). Motion between the femoral shaft and the cephalomedullary nail (toggling of the nail within the shaft) was significantly greater in narrow or wide canal unlocked specimens, 7.94±2.13 and 10.2±1.7 respectively, than in the narrow or wide canal locked specimens, 2.4±0.2 and 4.2±0.5 respectively (p<0.05) CONCLUSION: Unlocked short intramedullary fixation for unstable peritrochanteric fractures results in increased varus collapse under axial compression. This study supports the use of distal cross-locking of short intramedullary fixation for unstable peritrochanteric fractures in patients with capacious femoral canals secondary to osteoporosis who might otherwise be as risk for varus collapse, device failure, and malunion.
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March 2021

Association of Bacteremia with Vaccination Status in Children Aged 2 to 36 Months.

J Pediatr 2021 May 13;232:207-213.e2. Epub 2021 Jan 13.

Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH; Division of Emergency Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Objective: To determine the association between bacteremia and vaccination status in children aged 2-36 months presenting to a pediatric emergency department.

Study Design: Retrospective cohort study of children aged 2-36 months with blood cultures obtained in the pediatric emergency department between January 2013 and December 2017. The exposure of interest was immunization status, defined as number of Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae vaccinations, and the main outcome positive blood culture. Subjects with high-risk medical conditions were excluded.

Results: Of 5534 encounters, 4742 met inclusion criteria. The incidence of bacteremia was 1.5%. The incidence of contaminated blood culture was 5.0%. The relative risk of bacteremia was 0.79 (95% CI 0.39-1.59) for unvaccinated and 1.20 (95% CI 0.52-2.75) for undervaccinated children relative to those who had received age-appropriate vaccines. Five children were found to have S pneumoniae bacteremia and 1 child had Hib bacteremia; all of these subjects had at least 3 sets of vaccinations. No vaccine preventable pathogens were isolated from blood cultures of unvaccinated children. We found no S pneumoniae or Hib in children 2-6 months of age who were not fully vaccinated due to age (95% CI 0-0.13%) and the contamination rate in this group was high compared with children 7-36 months (6.6% vs 3.7%).

Conclusions: Bacteremia in young children is an uncommon event. Contaminated blood cultures were more common than pathogens. Bacteremia from S pneumoniae or Hib is uncommon and, in this cohort, was independent of vaccine status.
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May 2021

Augmentation of Anatomic Anterior Cruciate Ligament Reconstruction With Lateral Extra-articular Tenodesis Does Not Significantly Affect Rotatory Knee Laxity: A Time Zero, In Vivo Kinematic Analysis.

Am J Sports Med 2020 12 11;48(14):3495-3502. Epub 2020 Nov 11.

Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Background: The pivot-shift test is used to assess for rotatory knee laxity in the anterior cruciate ligament (ACL)-deficient knee and ACL-reconstructed knee; however, the pivot shift uses a subjective grading system that is limited by variability between examiners. Consequently, quantified pivot shift (QPS) test software (PIVOT iPad application) has been developed and validated to measure the magnitude of rotatory knee laxity during the positive pivot-shift test.

Purpose: To employ intraoperative QPS (iQPS) to assess for differences in residual rotatory knee laxity after ACL reconstruction (ACLR) versus ACLR augmented with lateral extra-articular tenodesis (ACLR + LET), and to employ iQPS to determine if ACLR and/or ACLR + LET result in overconstrained knee kinematics when compared with the contralateral knee.

Study Design: Cohort study; Level of evidence, 2.

Methods: iQPS was performed in 20 patients by a single surgeon on both the operative and contralateral knees before ACLR. ACLR was augmented with a LET if the lateral compartment tibial translation measured during QPS was greater than or equal to double the amount of lateral tibial compartment translation measured for the contralateral knee. After each reconstruction (ACLR or ACLR + LET), iQPS measurements were performed. iQPS data were compared with the preoperative QPS measurements of the operative and contralateral knees. Postoperative iQPS data were compared with both the preoperative QPS measurements of the operative and contralateral knees with paired samples tests. Categorical variables were compared using the Fisher exact test.

Results: The mean age in the cohort was 17.3 years (range, 15-24 years). There were no significant differences between the groups in terms of the proportion of male patients (ACLR: 5 male, 5 female vs ACLR + LET: 4 male, 6 female) or age (ACLR: 17.7 ± 3.3 years; 95% CI, 15.4-24.0 vs ACLR + LET: 16.8 ± 2.8 years, 95% CI, 14.8-22.0; .999). There were no significant differences between the groups with respect to preoperative QPS performed during examination under anesthesia (ACLR: 4.7 ± 2.0 mm; 95% CI, 3.3-6.1 vs ACLR + LET: 3.6 ± 1.8 mm; 95% CI, 2.3-4.9; = .2). Both ACLR and ACLR + LET resulted in significant decreases in rotatory knee laxity when compared with preoperative QPS measurements (ACLR: -3.4 ± 1.7 mm; 95% CI, -4.6 to -2.2; < .001: ACLR + LET: -2.6 ± 1.9 mm; 95% CI, -3.9 to -1.3; < .002). Moreover, when compared with isolated ACLR, ACLR + LET did not result in a significantly smaller magnitude of change in iQPS between the pre- and postoperative states ( = .3).

Conclusion: Both ACLR and ACLR + LET resulted in significant decreases in rotatory knee laxity. The augmentation of ACLR with LET did not change the constraint of the knee with respect to lateral compartment translation as measured during iQPS.
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December 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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November 2020

Anterior Cruciate Ligament Reconstruction With a Partial-Thickness Quadriceps Tendon Graft Secured With a Continuous-Loop Fixation Device.

Arthrosc Tech 2020 May 3;9(5):e603-e609. Epub 2020 Apr 3.

Division of Sports Medicine, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.

Anterior cruciate ligament reconstruction using quadriceps tendon (QT) autograft has recently gained popularity because newer techniques allow harvest of a robust graft with little soft-tissue dissection or donor-site morbidity. The QT graft can provide a safe, reproducible, and versatile option for primary and revision anterior cruciate ligament reconstruction with equivalent outcomes and failure rates to those of bone-patellar tendon-bone and hamstring tendon grafts. Therefore, continued improvement in surgical technique may help to further improve patient outcomes. This study introduces a modification of current QT techniques using a partial-thickness graft with continuous-loop EndoButton fixation (Smith & Nephew, Andover, MA).
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May 2020

Biomechanical contribution of the alar ligaments to upper cervical stability.

J Biomech 2020 01 23;99:109508. Epub 2019 Nov 23.

Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, United States; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States. Electronic address:

Acute and chronic whiplash-associated disorders pose a significant healthcare burden due to chronic pain, which is associated with upper cervical instability resulting from ligamentous injury. No standard measure exists for diagnosing alar ligament injury and imaging findings vary widely. Multiple physical examination maneuvers are used to diagnose alar ligament injury including the C2 Spinous Kick, Flexion-Rotation, and Bending-Rotation tests. The objective of the current study was to determine the mechanical contribution of the alar ligaments to upper cervical stability and quantify the biomechanical changes seen during simulated clinical examinations after alar ligament injury. Eight cadaveric C0-C3 specimens were evaluated using a robotic testing system. Range of motion and moment at the end of intact specimen replay were the primary outcomes. Clinical examinations were simulated by rotation through two axes as performed during physical examination. Intact, unilateral and bilateral alar ligament injury states were tested. Unilateral alar ligament injury led to significant increases in lateral bending (12.0 ± 7.2%, p < 0.05), axial rotation (4.1 ± 2.4%, p < 0.05), and flexion-extension (5.3 ± 4.3%, p < 0.05) compared with intact specimens. The alar ligaments also contributed to resistance to intact motion in extension (13.4 ± 6.6%, p < 0.05), flexion (4.4 ± 2.2%, p < 0.05), axial rotation (19.3 ± 2.7%, p < 0.05), and lateral bending (16.0 ± 2.8%, p < 0.05). The C2 Spinous Kick Test showed the largest percentage change (-23.0 ± 14.8%), and the Bending-Rotation Test towards the side of injury significantly increased axial rotation by the largest absolute magnitude (5.5° ± 5.1°). Overall, quantifiable changes to motion measured during simulated physical examinations were found, but the ability of a clinician to feel these changes remains unknown.
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January 2020

Anterior Cruciate Ligament Injury and the Anterolateral Complex of the Knee-Importance in Rotatory Knee Instability?

Curr Rev Musculoskelet Med 2019 Dec;12(4):472-478

Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Freddie Fu Sports Medicine Building, 3200 South Water Street, Pittsburgh, PA, 15203, USA.

Purpose Of Review: In the setting of rotatory knee instability following anterior cruciate ligament (ACL) reconstruction, there has been a resurgence of interest in knee's anterolateral complex (ALC). Reconstruction or augmentation of the ALC with procedures such as a lateral extra-articular tenodesis (LET) has been proposed to reduce rotatory knee instability in conjunction with ACL reconstruction. The current review investigates the recent literature surrounding the role of the ALC in preventing rotatory knee instability.

Recent Findings: The knee's anterolateral complex (ALC) is a complex structure composed of the superficial and deep portions of the iliotibial band, the capsulo-osseous layer, and the anterolateral capsule. Distally, these various layers merge to form a single functional unit which imparts stability to the lateral knee. While the iliotibial band and the capsule-osseous layer have been shown to be primary restraints to rotatory motion after ACL injury, the biomechanical role of the anterolateral capsule remains unclear. Biomechanical studies have shown that the anterolateral capsule and the anterolateral thickening of this capsule act as a sheet of fibrous tissue which does not resist motion around the knee as other longitudinally oriented ligaments do. Augmentation of the ALC, with LET, has been performed globally for over 30 years. This procedure can decrease rotatory knee instability, but long-term studies have found little difference in patient-reported outcomes, osteoarthritis, or ACL reconstruction failure with the addition of LET. Further research is needed to clarify indications for the clinical use of ALC-based procedures.
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December 2019

Novel use of telescoping growth rods in treatment of early onset scoliosis: An and study in a porcine model.

JOR Spine 2018 Dec 8;1(4):e1035. Epub 2018 Oct 8.

Department of Orthopaedic Surgery, School of Medicine University of Pittsburgh Pittsburgh Pennsylvania.

Introduction: Treatment of early-onset scoliosis (EOS) can be difficult. Various forms of growing rods exist to correct deformity while delaying definitive spinal fusion. The disadvantage of traditional growing rods is need for repeated surgical lengthening procedures. Telescoping growth rods (TelGR) are a prototype new, guided growth technology with a rod mechanism that allows spontaneous longitudinal growth over time without manual lengthening. We hypothesized that the TelGR system will permit unrestricted growth with limited complications through 12 weeks , and that the range of motion (RoM) in each of three directions and stiffness of the TelGR system would not be significantly different than the rigid rod system .

Materials And Methods: : Six immature pigs were surgically implanted with TelGR with cephalad fixation at T6-7 and caudal fixation at T14-L1. Radiographs of the involved vertebral segments were measured postoperatively and after 12 weeks. : A robotic testing system was utilized for flexibility tests in flexion-extension (FE), lateral bending (LB), and axial rotation (AR) of eight immature porcine specimens (T3-T15). Testing was performed on both dual rigid rods and bilateral TelGR with instrumentation at T4-5 and T13-14.

Results: : Over the 12-week period, the rod length of the TelGR increased an average of 65 mm. : TelGR demonstrated significantly increased motion in LB and AR RoM compared with rigid rods. No difference was noted in FE RoM.

Discussion: The results in this study showed expected skeletal growth with spines instrumented with TelGR. findings of increased RoM in AR and LB suggest that the TelGR system may be less rigid than traditional growing rods. Treatment with TelGR might, if proven efficacious in the clinical setting, decrease the need for repeated surgical intervention compared with traditional growing rods. This study adds to the limited body of biomechanical evidence examining guided growth technology.
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December 2018

Biomechanical Analysis of a Growing Rod with Sliding Pedicle Screw System for Early-Onset Scoliosis.

J Healthc Eng 2019 12;2019:9535070. Epub 2019 Jun 12.

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

Early-onset scoliosis (EOS) remains a challenging condition for which current nonfusion surgeries require iterative lengthening surgeries. A growing rod with sliding pedicle screw system (GRSPSS) was developed to treat spinal deformities without repeated operative lengthening. This study was performed to evaluate whether GRSPSS had similar stability as a conventional pedicle screw system to maintain deformity correction. A serial-linkage robotic manipulator with a six-axis load cell positioned on the end-effector was utilized to evaluate the mechanical stability of the GRSPSS versus conventional fixed scoliosis instrumentation. Ten skeletally mature thoracic female Katahdin sheep spines (T4-L1) were subjected to 2.5 Nm of flexion-extension (FE), lateral bending (LB), and axial rotation (AR) in 2° increments for each state. The overall range of motion (ROM), apical segment ROM, and stiffness were calculated and reported. A two-tailed paired -test was used to detect significant differences ( < 0.05) between the fixed group and GRSPSS fixation. There were no significant differences in overall range of motion (ROM), apical segment ROM, or stiffness for FE or LB between the GRSPSS group and fixed group. In AR, the GRSPSS group showed increased ROM compared to the fixed group for the overall spine (36.0° versus 19.2°, < 0.01) and for the instrumented T8-T10 segments (7.0° versus 2.9°, =0.02). Similarly, the fixed rod elastic zone (EZ) stiffness was significantly greater than the GRSPSS EZ stiffness (0.29 N/m versus 0.17 N/m, < 0.001). The space around the rod allows for the increased AR observed with the GRSPSS fusion technique and is necessary for axial growth. The GRSPSS fusion model shows equivalent flexion and LB stability to current fusion models and represents a stable fusion technique and may allow for longitudinal growth during childhood.
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September 2020

Allograft for knee ligament surgery: an American perspective.

Knee Surg Sports Traumatol Arthrosc 2019 Jun 19;27(6):1882-1890. Epub 2019 Mar 19.

Department of Orthopaedic Surgery, University of Pittsburgh, 3471 Fifth Avenue Suite 1010, Pittsburgh, PA, 15213, USA.

Purpose: Allografts are frequently use for ligamentous reconstruction at the knee. In the United States, tissue donation and distribution are highly regulated processes with thorough oversight from private and government entities. Allograft is widely available in the United States and allograft procurement is a large industry with varying procurement, sterilization, processing, and distribution procedures. It is important to understand allograft regulation and processing which may affect graft mechanical properties and biological graft integration.

Methods: English-language literature, United States government and regulatory agency statues pertaining to allograft procurement, distribution, and usage were reviewed and the findings summarized.

Results: During the processing of allograft, multiple factors including sterilization procedures, irradiation, storage conditions, and graft type all affect the biomechanical properties of the allograft tissue. Biological incorporation and ligamentization of allograft does occur, but at a slower rate compared with autograft. For ligamentous reconstruction around the knee, allograft offers shorter operative time, no donor-site morbidity, but has shown an increased risk for graft failure compared to autograft.

Conclusion: This article reviews the regulations on graft tissue within the United States, factors affecting the biomechanics of allograft tissue, differences in allograft tissue choices, and the use of allograft for anterior cruciate ligament reconstruction and multiligamentous knee injury reconstruction.

Level Of Evidence: V.
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June 2019

Biomechanical contributions of upper cervical ligamentous structures in Type II odontoid fractures.

J Biomech 2019 01 22;83:28-33. Epub 2018 Nov 22.

Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:

Fractures of the odontoid present frequently in spinal trauma, and Type II odontoid fractures, occurring at the junction of the odontoid process and C2 vertebrae, represent the bulk of all traumatic odontoid fractures. It is currently unclear what soft-tissue stabilizers contribute to upper cervical motion in the setting of a Type II odontoid fracture, and evaluation of how concomitant injury contributes to cervical stability may inform surgical decision-making as well as allow for the creation of future, accurate, biomechanical models of the upper cervical spine. The objective of the current study was to determine the contribution of soft-tissue stabilizers in the upper cervical spine following a Type II odontoid fracture. Eight cadaveric C0-C2 specimens were evaluated using a robotic testing system with motion tracking. The unilateral facet capsule (UFC) and anterior longitudinal ligament (ALL) were serially resected to determine their biomechanical role following odontoid fracture. Range of motion (ROM) and moment at the end of intact specimen replay were the primary outcomes. We determined that fracture of the odontoid significantly increases motion and decreases resistance to intact motion for flexion-extension (FE), axial rotation (AR), and lateral bending (LB). Injury to the UFC increased AR by 3.2° and FE by 3.2°. ALL resection did not significantly increase ROM or decrease end-point moment. The UFC was determined to contribute to 19% of intact flexion resistance and 24% of intact AR resistance. Overall, we determined that Type II fracture of the odontoid is a significant biomechanical destabilizer and that concurrent injury to the UFC further increases upper cervical ROM and decreases resistance to motion in a cadaveric model of traumatic Type II odontoid fractures.
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January 2019

Mechanical role of the posterior column components in the cervical spine.

Eur Spine J 2016 07 6;25(7):2129-38. Epub 2016 Apr 6.

Department of Orthopaedic Surgery, University of Pittsburgh, 200 Lothrop Street, E1641 Biomedical Science Tower, Pittsburgh, PA, 15261, USA.

Purpose: To quantify the mechanical role of posterior column components in human cervical spine segments.

Methods: Twelve C6-7 segments were subjected to resection of (1) suprasinous/interspinous ligaments (SSL/ISL), (2) ligamenta flavum (LF), (3) facet capsules, and (4) facets. A robot-based testing system performed repeated flexibility testing of flexion-extension (FE), axial rotation (AR), and lateral bending (LB) to 2.5Nm and replayed kinematics from intact flexibility tests for each state. Range-of-motion, stiffness, moment resistance and resultant forces were calculated.

Results: The LF contributes largely to moment resistance, particularly in flexion. Facet joints were primary contributors to AR and LB mechanics. Moment/force responses were more sensitive and precise than kinematic outcomes.

Conclusions: The LF is mechanically important in the cervical spine; its injury could negatively impact load distribution. Damage to facets in a flexion injury could lead to AR or LB hypermobility. Quantifying the contribution of spinal structures to moment resistance is a sensitive, precise process for characterizing structural mechanics.
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July 2016

NF-κB Signaling Pathway in Controlling Intervertebral Disk Cell Response to Inflammatory and Mechanical Stressors.

Phys Ther 2016 05 18;96(5):704-11. Epub 2016 Feb 18.

G. Sowa, MD, PhD, Department of Physical Medicine and Rehabilitation, University of Pittsburgh, 3471 5th Ave, Suite 201, Pittsburgh, PA 15213 (USA).

Background: Intervertebral disk degeneration (IDD) has a greater than 90% lifetime incidence and is one of the leading causes of chronic back pain in the United States. Despite the high societal cost of IDD, there is limited understanding of the biological effects of mechanical overloading on further degeneration. The transcription factor NF-κB (nuclear factor κB) has been implicated as a key mediator of disk cell response to inflammatory and mechanical stresses and represents a potential control point.

Objective: The study objective was to measure the effect of NF-κB signaling pathway inhibition on annulus fibrosus (AF) cell matrix synthesis and gene expression under conditions of combined inflammatory and mechanical stimulation.

Methods: Annulus fibrosus cells were harvested from rabbit intervertebral disks and grown in vitro on flexible plates. The cells were exposed to inflammatory and mechanical stimulation for 24 hours with and without NF-κB inhibition. Nuclear translocation of NF-κB was measured via immunofluorescent staining. Intervertebral disk cell homeostasis was assessed via inflammatory, anabolic, and catabolic gene expression and via matrix synthetic ability.

Results: NF-κB nuclear translocation in response to interleukin-1 beta (IL-1β) was reversed with exposure to NF-κB inhibition. NF-κB inhibition decreased matrix metalloproteinase-3, inducible nitric oxide synthase, and cyclooxygenase-2 gene expression and prostaglandin E2 production response to combined inflammatory and mechanical stimulation. Proteoglycan and collagen synthesis were decreased by combined stimulation, but this effect was not reversed by NF-κB inhibition.

Limitations: In vitro modeling of conditions within the disk may not fully reflect the response that AF cells have in native matrix.

Conclusions: NF-κB signaling mediates catabolic and inflammatory responses to inflammatory and mechanical stimulation but does not mediate the decrease in matrix synthesis under combined harmful stimulation. Identification of key control points in the cellular responses to inflammatory and mechanical stimuli will facilitate rational design of exercise-based therapies and facilitate synergistic treatments of novel biochemical treatments with rehabilitation regimens.
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May 2016

Alpha-actinin-4 and CLP36 protein deficiencies contribute to podocyte defects in multiple human glomerulopathies.

J Biol Chem 2011 Sep 16;286(35):30795-30805. Epub 2011 Jun 16.

Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261. Electronic address:

Genetic alterations of α-actinin-4 can cause podocyte injury through multiple mechanisms. Although a mechanism involving gain-of-α-actinin-4 function was well described and is responsible for a dominantly inherited form of human focal segmental glomerulosclerosis (FSGS), evidence supporting mechanisms involving loss-of-α-actinin-4 function in human glomerular diseases remains elusive. Here we show that α-actinin-4 deficiency occurs in multiple human primary glomerulopathies including sporadic FSGS, minimal change disease, and IgA nephropathy. Furthermore, we identify a close correlation between the levels of α-actinin-4 and CLP36, which form a complex in normal podocytes, in human glomerular diseases. siRNA-mediated depletion of α-actinin-4 in human podocytes resulted in a marked reduction of the CLP36 level. Additionally, two FSGS-associated α-actinin-4 mutations (R310Q and Q348R) inhibited the complex formation between α-actinin-4 and CLP36. Inhibition of the α-actinin-4-CLP36 complex, like loss of α-actinin-4, markedly reduced the level of CLP36 in podocytes. Finally, reduction of the CLP36 level or disruption of the α-actinin-4-CLP36 complex significantly inhibited RhoA activity and generation of traction force in podocytes. Our studies reveal a critical role of the α-actinin-4-CLP36 complex in podocytes and provide an explanation as to how α-actinin-4 deficiency or mutations found in human patients could contribute to podocyte defects and glomerular failure through a loss-of-function mechanism.
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September 2011