Brian Brigman

Positions:

Professor of Orthopaedic Surgery

Orthopaedics
School of Medicine

Professor in Pediatrics

Pediatrics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1994

University of North Carolina - Chapel Hill

Intern, Surgery

University of Nebraska, Lincoln

Resident, Orthopaedic Surgery

University of Nebraska, Lincoln

Fellow, Orthopaedic Oncology

Boston University

Grants:

Fresh Tissue Lab Agreement

Administered By
Orthopaedics
Awarded By
DePuy Synthes Companies
Role
Principal Investigator
Start Date
End Date

Protocol Number: 14-03-PATHOLHUM-02

Administered By
Orthopaedics
Awarded By
IlluminOss Medical, Inc.
Role
Principal Investigator
Start Date
End Date

Publications:

Wound Surface Area as a Risk Factor for Flap Complications among Patients with Open Fractures.

BACKGROUND: Soft-tissue complications often dictate the success of limb salvage and the overall outcome of open fractures. Based on prior work at the R Adams Cowley Shock Trauma Center, the authors hypothesize that wounds larger than 200 cm are associated with a greater likelihood of both flap-related reoperation and wound complications among patients requiring soft-tissue reconstruction with a rotational flap or free tissue transfer. METHODS: This study was a secondary analysis of Fluid Lavage in Open Wounds trial data that included all patients who received a rotational or free tissue flap transfer for an open fracture. The primary outcome was flap-related reoperation within 12 months of injury. The secondary outcome was wound complication, which included events treated operatively or nonoperatively. Multivariable logistic regression was used to assess the association between wound size and outcomes, adjusting for confounders. RESULTS: Seventeen percent of the 112 patients required a flap-related reoperation. A wound size greater than 200 cm(2) was not associated with reoperation in an unadjusted model (p = 0.64) or adjusting for Gustilo type (p = 0.70). The sample had an overall wound complication rate of 47.3 percent. Patients with a wound size of greater than 200 cm(2) were three times more likely to experience wound complications (OR, 3.05; 95 percent CI, 1.08 to 8.62; p = 0.04) when adjusting for moderate to severe wound contamination and wound closure in the operating room. CONCLUSION: The findings of this study demonstrate that wound surface area is an integral determinant for wound complication following soft-tissue flap treatment, but found no association between wound surface area and flap-related reoperation rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.
Authors
Shea, P; O'Hara, NN; Sprague, SA; Bhandari, M; Petrisor, BA; Jeray, KJ; Zhan, M; Slobogean, GP; Pensy, RA; Fluid Lavage in Open Wounds Investigators,
MLA Citation
Shea, Phelan, et al. “Wound Surface Area as a Risk Factor for Flap Complications among Patients with Open Fractures.Plast Reconstr Surg, vol. 142, no. 1, July 2018, pp. 228–36. Pubmed, doi:10.1097/PRS.0000000000004418.
URI
https://scholars.duke.edu/individual/pub1436576
PMID
29608532
Source
pubmed
Published In
Plast Reconstr Surg
Volume
142
Published Date
Start Page
228
End Page
236
DOI
10.1097/PRS.0000000000004418

Cerebrospinal Fluid Proteome Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD), a syndrome of cognitive deficits occurring 1-12 months after surgery primarily in older patients, is associated with poor postoperative outcomes. POCD is hypothesized to result from neuroinflammation; however, the pathways involved remain unclear. Unbiased proteomic analyses have been used to identify neuroinflammatory pathways in multiple neurologic diseases and syndromes but have not yet been applied to POCD. OBJECTIVE: To utilize unbiased mass spectrometry-based proteomics to identify potential neuroinflammatory pathways underlying POCD. METHODS: Unbiased LC-MS/MS proteomics was performed on immunodepleted cerebrospinal fluid (CSF) samples obtained before, 24 hours after, and 6 weeks after major non-cardiac surgery in older adults who did (n = 8) or did not develop POCD (n = 6). Linear mixed models were used to select peptides and proteins with intensity differences for pathway analysis. RESULTS: Mass spectrometry quantified 8,258 peptides from 1,222 proteins in > 50%of patient samples at all three time points. Twelve peptides from 11 proteins showed differences in expression over time between patients with versus withoutPOCD (q < 0.05), including proteins previously implicated in neurodegenerative disease pathophysiology. Additionally, 283 peptides from 182 proteins were identified with trend-level differences (q < 0.25) in expression over time between these groups. Among these, pathway analysis revealed that 50 were from 17 proteins mapping to complement and coagulation pathways (q = 2.44*10-13). CONCLUSION: These data demonstrate the feasibility of performing unbiased mass spectrometry on perioperative CSF samples to identify pathways associated with POCD. Additionally, they provide hypothesis-generating evidence for CSF complement and coagulation pathway changes in patients with POCD.
Authors
VanDusen, KW; Li, Y-J; Cai, V; Hall, A; Hiles, S; Thompson, JW; Moseley, MA; Cooter, M; Acker, L; Levy, JH; Ghadimi, K; Quiñones, QJ; Devinney, MJ; Chung, S; Terrando, N; Moretti, EW; Browndyke, JN; Mathew, JP; Berger, M; MADCO-PC Investigators,
MLA Citation
VanDusen, Keith W., et al. “Cerebrospinal Fluid Proteome Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction.J Alzheimers Dis, vol. 80, no. 3, 2021, pp. 1281–97. Pubmed, doi:10.3233/JAD-201544.
URI
https://scholars.duke.edu/individual/pub1475476
PMID
33682719
Source
pubmed
Published In
J Alzheimers Dis
Volume
80
Published Date
Start Page
1281
End Page
1297
DOI
10.3233/JAD-201544

Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY): a multi-center randomized controlled study comparing alternative antibiotic regimens in patients undergoing tumor resections with endoprosthetic replacements-a statistical analysis plan.

BACKGROUND: Limb salvage with endoprosthetic reconstruction is the current standard practice for the surgical management of lower extremity bone tumors in skeletally mature patients and typically includes tumor resection followed by the functional limb reconstruction with modular metallic and polyethylene endoprosthetic implants. However, owing to the complexity and length of these procedures, as well as the immunocompromised nature of patients treated with chemotherapy, the risk of surgical site infection (SSI) is high. The primary research objective of the Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY) trial is to assess whether a 5-day regimen of post-operative antibiotics decreases the risk of SSI at 1 year post-operatively compared to a 1-day regimen. This article describes the statistical analysis plan for the PARITY trial. METHODS/DESIGN: The PARITY trial is an ongoing multi-center, blinded parallel two-arm randomized controlled trial (RCT) of 600 participants who have been diagnosed with a primary bone tumor, a soft tissue sarcoma that has invaded the bone or oligometastatic bone disease of the femur or tibia that requires surgical resection and endoprosthetic reconstruction. This article describes the overall analysis principles, including how participants will be included in each analysis, the presentation of results, adjustments for covariates, the primary and secondary outcomes, and their respective analyses. Additionally, we will present the planned sensitivity and sub-group analyses. DISCUSSION: Our prior work has demonstrated (1) high rates of SSI after the treatment of lower extremity tumors by surgical excision and endoprosthetic reconstruction, (2) highly varied opinion and practice among orthopedic oncologists with respect to prophylactic antibiotic regimens, (3) an absence of applicable RCT evidence, (4) extensive support from international investigators to participate in a RCT, and (5) the feasibility of conducting a definitive RCT to evaluate a 5-day regimen of post-operative antibiotics in comparison with a 1-day regimen. TRIAL REGISTRATION: ClinicalTrials.gov NCT01479283 . Registered on 24 November 2011.
Authors
Schneider, P; Heels-Ansdell, D; Thabane, L; Ghert, M; PARITY Investigators,
URI
https://scholars.duke.edu/individual/pub1478261
PMID
33752752
Source
pubmed
Published In
Trials
Volume
22
Published Date
Start Page
223
DOI
10.1186/s13063-021-05147-2

Humeral Shaft Fracture With Placement of an Intramedullary Nail Through an Unrecognized Sarcoma.

CASE: A 72-year-old man underwent intramedullary nailing of a humeral diaphysis fracture with passage through an unrecognized pathologic fracture. Four months later, a biopsy of a soft-tissue mass in the arm revealed pleomorphic undifferentiated sarcoma. Only after local recurrence and forequarter amputation was the story of a pathologic fracture through undifferentiated pleomorphic sarcomas of bone clear. The patient developed metastatic disease and died after 2 years postoperatively. DISCUSSION: Orthopaedic surgeons should consider sarcoma when assessing patients with fractures of unknown etiology and an inappropriate mechanism because the placement of an intramedullary device through a sarcoma of bone has consequences.
Authors
Cullen, MM; Okwumabua, E; Flamant, EM; Ferlauto, HR; Brigman, BE; Eward, WC
MLA Citation
Cullen, Mark M., et al. “Humeral Shaft Fracture With Placement of an Intramedullary Nail Through an Unrecognized Sarcoma.J Am Acad Orthop Surg Glob Res Rev, vol. 5, no. 2, Feb. 2021. Pubmed, doi:10.5435/JAAOSGlobal-D-20-00142.
URI
https://scholars.duke.edu/individual/pub1474547
PMID
33620175
Source
pubmed
Published In
Journal of the American Academy of Orthopaedic Surgeons. Global Research & Reviews
Volume
5
Published Date
DOI
10.5435/JAAOSGlobal-D-20-00142

Immunomodulatory lipid mediator profiling of cerebrospinal fluid following surgery in older adults.

Arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) derived lipids play key roles in initiating and resolving inflammation. Neuro-inflammation is thought to play a causal role in perioperative neurocognitive disorders, yet the role of these lipids in the human central nervous system in such disorders is unclear. Here we used liquid chromatography-mass spectrometry to quantify AA, DHA, and EPA derived lipid levels in non-centrifuged cerebrospinal fluid (CSF), centrifuged CSF pellets, and centrifuged CSF supernatants of older adults obtained before, 24 h and 6 weeks after surgery. GAGE analysis was used to determine AA, DHA and EPA metabolite pathway changes over time. Lipid mediators derived from AA, DHA and EPA were detected in all sample types. Postoperative lipid mediator changes were not significant in non-centrifuged CSF (p > 0.05 for all three pathways). The AA metabolite pathway showed significant changes in centrifuged CSF pellets and supernatants from before to 24 h after surgery (p = 0.0000247, p = 0.0155 respectively), from before to 6 weeks after surgery (p = 0.0000497, p = 0.0155, respectively), and from 24 h to 6 weeks after surgery (p = 0.0000499, p = 0.00363, respectively). These findings indicate that AA, DHA, and EPA derived lipids are detectable in human CSF, and the AA metabolite pathway shows postoperative changes in centrifuged CSF pellets and supernatants.
Authors
Terrando, N; Park, JJ; Devinney, M; Chan, C; Cooter, M; Avasarala, P; Mathew, JP; Quinones, QJ; Maddipati, KR; Berger, M; MADCO-PC Study Team,
MLA Citation
Terrando, Niccolò, et al. “Immunomodulatory lipid mediator profiling of cerebrospinal fluid following surgery in older adults.Sci Rep, vol. 11, no. 1, Feb. 2021, p. 3047. Pubmed, doi:10.1038/s41598-021-82606-5.
URI
https://scholars.duke.edu/individual/pub1473574
PMID
33542362
Source
pubmed
Published In
Scientific Reports
Volume
11
Published Date
Start Page
3047
DOI
10.1038/s41598-021-82606-5