Publications by authors named "Sean T Campbell"

48 Publications

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Qualitative IgG Assays: The Value of Numeric Reporting.

Arch Pathol Lab Med 2021 Apr 5. Epub 2021 Apr 5.

Department of Pathology (Forest, Orner, Goldstein, Campbell, Cadoff, Weiss, Fox, Prystowsky, Wolgast), Department of Microbiology and Immunology (Wirchnianski, Bortz III, Laudermilch, Florez, Chandran), Department of Biochemistry (Malonis, Georgiev, Vergnolle, Lai), and the Department of Epidemiology and Population Medicine (Lo), at Albert Einstein College of Medicine, Bronx, NY; Department of Chemistry and Life Sciences, United States Military Academy, West Point, NY (Florez, Barnhill); Department of Radiology, Uniformed Services University of Health Science, Bethesda, MD (Barnhill).

Context: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG testing is used for serosurveillance and will be important to evaluate vaccination status. Given the urgency to release coronavirus disease 2019 (COVID-19) serology tests, most manufacturers have developed qualitative tests.

Objective: To evaluate clinical performance of six different SARS-CoV-2 IgG assays and their quantitative results to better elucidate the clinical role of serology testing in COVID-19.

Design: Six SARS-CoV-2 IgG assays were tested using remnant specimens from 190 patients. Sensitivity and specificity were evaluated for each assay with the current manufacturer's cutoff and a lower cutoff. A numeric result analysis and discrepancy analysis were performed Results: The specificity was >93% for all assays, and sensitivity was >80% for all assays (≥ 7 days post-polymerase chain reaction [PCR] testing). Inpatients with more severe disease had higher numeric values compared to health care workers with mild or moderate disease. Several discrepant serology results were those just below the manufacturers cutoff.

Conclusions: SARS-CoV-2 IgG antibody testing can aid in the diagnosis of COVID-19 especially with negative PCR. Quantitative COVID-19 IgG results are important to better understand the immunological response and disease course of this novel virus and to assess immunity as part of future vaccination programs.
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http://dx.doi.org/10.5858/arpa.2020-0851-SADOI Listing
April 2021

Delayed Displacement of a Subtle Sacral Insufficiency Fracture Unmasking Lumbopelvic Instability: A Case Report.

JBJS Case Connect 2021 Mar 25;11(1). Epub 2021 Mar 25.

Department of Orthopaedic Surgery, Harborview Medical Center, Seattle, Washington.

Case: There is limited literature reporting on sacral insufficiency fractures as a cause of lumbopelvic instability. We describe the presentation, treatment, and clinical outcome with a 2-year follow-up of a woman who sustained a low-energy spinopelvic dissociation diagnosed with magnetic resonance imaging. There was significant delayed displacement, and the patient was treated surgically with percutaneous iliosacral and trans-sacral screws.

Conclusion: U-type sacral insufficiency fractures may be subtle on advanced imaging and must be followed closely if nonoperative treatment is chosen. These patients may require surgical intervention. Iliosacral screws and lumbopelvic fixation are treatment options, each with advantages and disadvantages.
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http://dx.doi.org/10.2106/JBJS.CC.20.00329DOI Listing
March 2021

Research methodologic quality varies significantly by subspecialty: An analysis of AAOS meeting abstracts.

J Clin Orthop Trauma 2021 Apr 11;15:37-41. Epub 2020 Nov 11.

Department of Orthopaedic Surgery, Stanford University, Stanford, CA, (JAB), United States.

Background: The purpose of this study was to compare the level of evidence and study type of clinical abstracts accepted to the 2017 AAOS Annual Meeting based on subspecialty.

Methods: All clinical abstracts presented at the 2017 AAOS Annual Meeting were assessed by two independent raters for LOE and study type. Nonparametric statistics and chi-square test were used to compare LOE and study types between subspecialties.

Results: A total of 1083 abstracts met inclusion criteria. There was a significant difference in LOE of abstracts by subspecialty ( < 0.001). Shoulder/elbow, adult reconstruction knee, hand/wrist, and sports had the highest percentage of level I and II studies. The type of study also varied significantly by subspecialty ( = 0.005).

Discussion: Methodologic quality of clinical studies presented at the 2017 AAOS Annual Meeting differed significantly among subspecialties. Orthopedic researchers should look to the fields producing the highest quality studies in an effort to improve methodological quality.
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http://dx.doi.org/10.1016/j.jcot.2020.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920098PMC
April 2021

Do-Not-Resuscitate status is an independent risk factor for medical complications and mortality among geriatric patients sustaining hip fractures.

J Clin Orthop Trauma 2021 Mar 22;14:65-68. Epub 2020 Sep 22.

Stanford Medicine, Department of Orthopaedic Surgery, Stanford, CA, 94305, USA.

Background: The purpose of this study was to compare outcomes after hip fracture surgery between DNR/DNI and full code cohorts to determine whether DNR/DNI status is an independent predictor of complications and mortality within one year. A significant number of geriatric hip fracture patients carry a code status designation of DNR/DNI (Do-Not-Resuscitate/Do-Not-Intubate). There is limited data addressing how this designation may influence prognosis.

Methods: A retrospective chart review of all geriatric hip fractures treated between 2002 and 2017 at a single level-I academic trauma center was performed. 434 patients were eligible for this study with 209 in the DNR/DNI cohort and 225 in the full code cohort. The independent variable was code-status and dependent variables included patient demographics, surgery performed, American Society of Anesthesiologists, score, Charlson Comorbidity Index, significant medical and surgical complications within one year of surgery, duration of follow-up by an orthopaedic surgeon, duration of follow-up by any physician, and mortality within 1 year of surgery. One-year complication rates were compared, and multiple logistic regression analyses were performed to analyze the relationship between independent and dependent variables.

Results: The DNR/DNI cohort experienced significantly more surgical complications compared to the full code cohort (14.8% vs 7.6%, p = 0.024). There was a significantly higher rate of medical complications and mortality in the DNR/DNI cohort (57.9% vs 36%, p < 0.001 and 19.1% vs 3.1%, p = 0.037, respectively). In the regression analysis, DNR/DNI status was an independent predictor of a medical complication (odds ratio 2.33, p = 0.004) and one-year mortality (odds ratio 9.69, p < 0.001), but was not for a surgical complication (OR 1.95, p = 0.892).

Conclusions: In our analysis, DNR/DNI code status was an independent risk factor for postoperative medical complications and mortality within one year following hip fracture surgery. The results of our study highlight the need to recognize the relationship between DNR/DNI designation and medical frailty when treating hip fractures in the elderly population.
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http://dx.doi.org/10.1016/j.jcot.2020.09.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920119PMC
March 2021

Frame-Assisted Reduction of a B-Type Pilon Fracture Dislocation: Talar Body Incarceration on an Intact Fibula: A Case Report.

JBJS Case Connect 2021 Feb 11;11(1):e20.00436. Epub 2021 Feb 11.

Department of Orthoapedic Surgery, Harborview Medical Center, Seattle, Washington.

Case: We describe an irreducible anterolateral tibiotalar dislocation with an AO/OTA (Arbeitsgemeinschaft fur Osteosynthesefragen/Orthopaedic Trauma Association) B-type pilon fracture. The injury was initially treated with closed reduction, using a medializing force achieved with an external fixator to unhinge the talar body from the fibula, followed by temporary stabilization. Definitive fixation was performed once the soft tissues had recovered.

Conclusion: This unique irreducible pilon fracture dislocation pattern is important to recognize to prevent iatrogenic complications associated with multiple failed closed reduction attempts. Frame-assisted, percutaneous, or open maneuvers may be required to facilitate a reduction. Staged treatment with temporization in an external fixator may be required.
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http://dx.doi.org/10.2106/JBJS.CC.20.00436DOI Listing
February 2021

Long-term sequelae of septic arthritis after tibial plateau fracture fixation: does timing matter?

Arch Orthop Trauma Surg 2021 Jan 8. Epub 2021 Jan 8.

Department of Orthopaedic Surgery, Harborview Medical Center, 325 9th Ave, Box 359798, Seattle, WA, 98104, USA.

Introduction: Septic arthritis following surgical treatment of a tibial plateau fracture is a rare complication, but it does occur, and the impact on long-term function is relatively unknown. The purpose of this study was to determine the long-term sequelae of septic arthritis among patients treated with internal fixation for a tibial plateau fracture and to determine the effect of timing (early or late infection) on the rate of such sequela.

Materials And Methods: A retrospective comparative study was designed using the trauma database of a single level I academic trauma center. Patients who developed culture-positive septic knee arthritis after internal fixation of a tibial plateau fracture, with 1-year follow-up, were included in the study. The number of debridement procedures required was recorded. Rates of long-term complications and implant removal were identified. Complications rates were compared between patients who developed early (within 30 days of definitive fixation) and late (more than 30 days) septic arthritis.

Results: The mean number of debridement procedures per patient was six. Fourteen patients (88%) required implant removal, and thirteen (81%) developed knee arthritis. There was a significantly lower rate of complications in the early septic arthritis group compared to the late group (3 of 6 patients or 50%, vs 10 of 10 patients or 100%; p = 0.036).

Conclusions: Patients who developed septic arthritis following internal fixation of a tibial plateau fracture were likely to endure long-term sequelae. Early infection and detection led to fewer complications. Surgeons treating infectious complications in tibial plateau fracture patients should specifically seek to rule out septic arthritis, anticipate that implant removal may be necessary, and counsel these patients appropriately regarding the anticipated natural history of their condition.

Level Of Evidence: III.
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http://dx.doi.org/10.1007/s00402-020-03730-xDOI Listing
January 2021

Metaphyseal callus formation in pilon fractures is associated with loss of alignment: Is stiffer better?

Injury 2020 Oct 17. Epub 2020 Oct 17.

Stanford University Department of Orthopaedic Surgery, 300 Pasteur Dr, Edwards Building, R144, Stanford, CA, 94305, USA.

Objective: To assess the relationship between metaphyseal callus formation and preservation of distal tibial alignment in pilon fractures treated with internal plate fixation.

Design: Retrospective Review SETTING: Academic Level I Trauma Center PATIENTS: Forty-two patients with AO/OTA type C2 or C3 pilon fractures treated with plate fixation.

Intervention: Internal fixation with anterolateral plating, medial plating, or both. Modified Radiographic Union Score in Tibial fracture (mRUST) scores were determined from six-month radiographs.

Main Outcome Measurements: Change in lateral and anterior distal tibial angles (LDTA and ADTA) at six months post-operatively.

Results: High callus formation (mRUST ≥ 11 at six months) was associated with a greater loss of coronal reduction as measured by LDTA compared to low callus formation (mRUST < 11): 3.8 vs 2.1° (p = .019), with no difference in ADTA change between groups. In a multivariable logistic regression controlling for age, smoking, obesity, and open fracture, higher mRUST scores were a predictor of coronal reduction loss of five or more degrees (OR 1.71, p=.039). Dual column plating did not independently predict maintenance of alignment.

Conclusions: Recent literature has popularized dual column fixation for pilon fractures, but it remains unknown whether increased metaphyseal stiffness enhances or impairs healing. In this series, decreased metaphyseal callus formation was associated with maintained coronal alignment, suggesting that a stiffer mechanical environment may be preferable to prevent short term reduction loss in these complex injuries.

Level Of Evidence: III.
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http://dx.doi.org/10.1016/j.injury.2020.10.080DOI Listing
October 2020

Development, clinical translation, and utility of a COVID-19 antibody test with qualitative and quantitative readouts.

medRxiv 2020 Sep 11. Epub 2020 Sep 11.

The COVID-19 global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to place an immense burden on societies and healthcare systems. A key component of COVID-19 control efforts is serologic testing to determine the community prevalence of SARS-CoV-2 exposure and quantify individual immune responses to prior infection or vaccination. Here, we describe a laboratory-developed antibody test that uses readily available research-grade reagents to detect SARS-CoV-2 exposure in patient blood samples with high sensitivity and specificity. We further show that this test affords the estimation of viral spike-specific IgG titers from a single sample measurement, thereby providing a simple and scalable method to measure the strength of an individual's immune response. The accuracy, adaptability, and cost-effectiveness of this test makes it an excellent option for clinical deployment in the ongoing COVID-19 pandemic.
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http://dx.doi.org/10.1101/2020.09.10.20192187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491531PMC
September 2020

White-Light Body Scanning Captures Three-Dimensional Shoulder Deformity After Displaced Diaphyseal Clavicle Fracture.

J Orthop Trauma 2021 04;35(4):e142-e147

Stanford University Department of Orthopaedic Surgery, Stanford, CA.

Objective: We sought to determine if white-light three-dimensional (3D) body scanning can identify clinically relevant shoulder girdle deformity after displaced diaphyseal clavicle fracture (DCF).

Methods: Adult patients with DCF (OTA/AO 15A) were prospectively enrolled. Four subcutaneous osseous landmarks were used to measure shoulder girdle morphology of the injured and uninjured shoulder. Measurements were made both manually with a tape measure and digitally with a white-light 3D scanner. Bilateral radiographs were obtained, and clavicle length was recorded. Quick-Disabilities of the Arm, Shoulder, and Hand surveys were administered at injury and at 6 and 12 weeks.

Results: Twenty-two patients were included in the study. At the initial visit, all patients had significant differences in deformity measurements between injured and uninjured shoulders as measured by 3D scanning. There was no difference between shoulders measured using manual measurements. At 6 and 12 weeks, shoulder asymmetry was significantly less in patients treated with surgery compared with nonoperative patients as measured by the 3D scanner alone. Clavicle shortening measured on 3D scanning had weak and moderate positive correlations to radiographs (R = 0.27) and manual measurements (R = 0.53), respectively. Patients treated with surgery had significant functional improvements by 6 weeks, and a similar improvement was not seen until 12 weeks in nonsurgical patients.

Conclusion: White-light 3D scanning was able to identify and monitor clinically relevant shoulder girdle deformity after DCF. This tool may become a useful adjunct to clinical examination and radiographic assessment, when determining clinically relevant deformity thresholds. In the future, quantifying and understanding shoulder deformity may inform clinical decision making in these patients.

Level Of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.1097/BOT.0000000000001957DOI Listing
April 2021

How are peri-implant fractures below short versus long cephalomedullary nails different?

Eur J Orthop Surg Traumatol 2021 Apr 9;31(3):421-427. Epub 2020 Sep 9.

Department of Orthopaedic Surgery, Stanford University School of Medicine, 300 Pasteur Drive Room R144, Stanford, CA, 94305, USA.

Background: Cephalomedullary nails are a commonly used implant for the treatment of many pertrochanteric femur fractures and are available in short and long configurations. There is no consensus on ideal nail length. Relative advantages can be ascribed to short and long intramedullary nails, yet both implant styles share the potentially devastating complication of peri-implant fracture. Determining the clinical sequelae after fractures below nails of different lengths would provide valuable information for surgeons choosing between short or long nails. Thus, the purpose of the study was to compare injury patterns and treatment outcomes following peri-implant fractures below short or long cephalomedullary nails.

Methods: This was a multicenter retrospective cohort study that identified 33 patients referred for treatment of peri-implant fractures below short and long cephalomedullary nails (n = 19 short, n = 14 long). We compared fracture pattern, treatment strategy, complications, and outcomes between these two groups.

Results: Short nails were associated with more diaphyseal fractures (odds ratio [OR] 13.75, CI 2.2-57.9, p 0.002), which were treated more commonly with revision intramedullary nailing (OR, infinity; p 0.01), while long nails were associated with distal metaphyseal fractures (OR 13.75, CI 2.2-57.9, p 0.002), which were treated with plate and screw fixation (p 0.002). After peri-implant fracture, there were no differences in blood loss, operative time, weight bearing status, or complication rates based on the length of the initial nail. In patients treated with revision nailing, there was greater estimated blood loss (EBL, median 300 cc, interquartile range [IQR] 250-1200 vs median 200 cc, IQR 100-300, p 0.03), blood product utilization and complication rates (OR 11.1, CI 1.1-135.7, p 0.03), but a trend toward unrestricted post-operative weight-bearing compared to patients treated with plate and screw constructs.

Conclusion: Understanding fracture patterns and patient outcomes after fractures below nails of different lengths will help surgeons make more informed implant choices when treating intertrochanteric hip fractures. Revision to a long nail for the treatment of fractures at the tip of a short nail may be associated with increased patient morbidity.
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http://dx.doi.org/10.1007/s00590-020-02785-1DOI Listing
April 2021

Is percutaneous screw fixation really superior to non-operative management after valgus-impacted femoral neck fracture: a retrospective cohort study.

Eur J Orthop Surg Traumatol 2021 Jan 24;31(1):65-70. Epub 2020 Jul 24.

Department of Orthopaedic Surgery, 450 Broadway Ave, Pavilion A, Redwood City, CA, 94063, USA.

Purpose: The optimal management of valgus-impacted femoral neck fractures remains controversial. Internal fixation is associated with significant rates of re-operation, while historical non-operative management strategies consisting of prolonged bed rest also resulted in patient morbidity. Our hypothesis was that screw fixation would have comparable failure rates to non-operative treatment and immediate mobilization for valgus-impacted femoral neck fractures.

Methods: Retrospective cohort at a single academic Level I trauma center of patients with valgus-impacted femoral neck fractures (AO/OTA 31-B1) treated with percutaneous screw fixation (n = 97) or non-operatively (n = 28). Operative treatment consisted of percutaneous screw fixation. Non-operative treatment consisted of early mobilization. The primary outcome was a salvage operation. Patient demographics were assessed between groups.

Results: More non-operatively treated patients were permitted unrestricted weight-bearing (WBAT; p = 0.002). There was no increase in complication rates or mortality, and return to previous ambulatory status was comparable between operatively and non-operatively treated patients. 35.7% (10/28) of non-operatively treated patients underwent a subsequent operation, compared to 15.5% (15/97) of patients with screw fixation (p = 0.03). Only WBAT was independently associated with treatment failure (OR 3.1, 95%CI 1.2-8.3, p =0.02). WBAT was predictive of treatment failure only in the non-operatively treated group (64.3%, 9/14 WBAT vs 8.3%, 1/12 partial, p =0.005).

Conclusion: After controlling for weight-bearing restrictions, we found no difference in failure rates between non-operative treatment and screw fixation. Non-operative treatment with partial weight-bearing had low failure rates, comparable complication and mortality rates, and equivalent functional outcomes to operative treatment and is reasonable if a patient would like to avoid surgery and accepts the risk of subsequent arthroplasty. Overall, there were relatively high failure rates in all groups.
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http://dx.doi.org/10.1007/s00590-020-02742-yDOI Listing
January 2021

Contouring Plates in Fracture Surgery: Indications and Pitfalls.

J Am Acad Orthop Surg 2020 Jul;28(14):585-595

From the Department of Orthopaedic Surgery, Stanford University, Stanford, CA (Dr. Bishop, Dr. Campbell, and Dr. Gardner), and the Department of Orthopaedic Surgery, University of Mississippi, Oxford, MS (Dr. Graves).

Effective fracture surgery requires contouring orthopaedic implants in multiple planes. The amount of force required for contouring is dependent on the amount and type of material contained within the plane to be altered. The type of contouring used depends on the desired plate function; for example, buttress mode often requires some degree of undercontouring, whereas compression plating may require prebending. Other reasons to contour a plate include matching patient anatomy either to maximize fixation options or to reduce implant prominence. Precontoured plates can be convenient and help to facilitate soft-tissue friendly techniques but have the potential to introduce malreduction if the plate position and fit are not carefully monitored.
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http://dx.doi.org/10.5435/JAAOS-D-19-00462DOI Listing
July 2020

The Impact of Subspecialty Fellows on Orthopaedic Resident Surgical Experience: A Multicenter Study of 51,111 Cases.

J Am Acad Orthop Surg 2021 Mar;29(6):263-270

From the Stanford University School of Medicine (Dr. Jiang), Stanford, CA, the New York University School of Medicine (Dr. Carlock), New York, NY, the Department of Orthopaedic Surgery (Dr. Campbell, Dr. Vorhies, Dr. Gardner, Dr. Bishop), Stanford University Medical Center, Stanford, CA, and the Department of Orthopaedic Surgery (Dr. Leucht), New York University Langone Health, New York, NY.

Introduction: Meaningful participation in surgery is important for orthopaedic resident education. This study aimed to quantify the effect of fellows on resident surgical experience. We hypothesized that as fellowship programs expanded, resident caseload would decrease, whereas "double-scrubbed" cases would increase.

Methods: This multicenter retrospective study included 9 years of surgical caselog data from two orthopaedic residency programs. Six subspecialty services on which fellow number varied over time were included (trauma, spine, foot and ankle, adult reconstruction, and hand). Case volume and personnel composition per case were extracted. Statistical analysis was performed with two-sample equal variance Student t-tests.

Results: A total of 51,111 cases were assessed. Surgical volume increased across all sites/services over time. Fellow numbers did not affect average resident caseload. However, in years with more fellows, an 11% decrease in one-on-one resident-attending cases (P = 0.002) and a 17% increase in resident-fellow-attending "double-scrubbed" cases was observed (P < 0.001).

Discussion: Increasing orthopaedic fellows did not affect resident case volume but resulted in fewer one-on-one cases with the attending and more "double-scrubbed" cases with a fellow. The implications of these findings to resident education require further study, but orthopaedic educators should be aware of these findings to try to maximize educational opportunities.

Level Of Evidence: Level III.
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http://dx.doi.org/10.5435/JAAOS-D-20-00233DOI Listing
March 2021

Surgical and Nonoperative Management of Olecranon Fractures in the Elderly: A Systematic Review and Meta-Analysis.

J Orthop Trauma 2021 01;35(1):10-16

Department of Orthopaedic Surgery, Stanford University Medical Center, Stanford, CA; and.

Objectives: The aim of this comparative effectiveness study was to perform a meta-analysis of adverse events and outcomes in closed geriatric olecranon fractures, without elbow instability, after treatment with surgical or nonoperative management.

Data Sources: PubMed, Web of Science, and Embase databases.

Study Selection: Articles were included if they contained clinical data evaluating outcomes in patients ≥65 years of age with closed olecranon fractures, without elbow instability, treated surgically, or with nonoperative management.

Data Extraction: Data regarding patient age, olecranon fracture type, fracture union, adverse events, reoperation, elbow range of motion, and surgeon and patient reported outcome measures were recorded according to intervention. The interventions included for analysis were tension band wire fixation, plate fixation, or nonoperative management.

Data Synthesis: Separate random effects meta-analyses were conducted for each outcome according to intervention. Prevalence and 95% confidence intervals were calculated for dichotomous variables, whereas weighted means and confidence intervals were calculated for continuous variables.

Conclusions: Comparable outcomes were achieved with surgical or nonoperative management of olecranon fractures in geriatric patients. Surgical intervention carried a high risk of reoperation regardless of whether plate or tension band wire fixation was used. Functional nonunion can be anticipated if nonoperative treatment is elected in low-demand elderly patients.

Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.1097/BOT.0000000000001865DOI Listing
January 2021

Voxelotor Treatment Interferes With Quantitative and Qualitative Hemoglobin Variant Analysis in Multiple Sickle Cell Disease Genotypes.

Am J Clin Pathol 2020 10;154(5):627-634

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN.

Objectives: Voxelotor was recently approved for use in the United States as a treatment for sickle cell disease (SCD) and has been shown to interfere with the quantitation of hemoglobin (Hb) S percentage. This study aimed to determine the effect of voxelotor on the quantitation of hemoglobin variant levels in patients with multiple SCD genotypes.

Methods: In vitro experiments were performed to assess the impact of voxelotor treatment on hemoglobin variant testing. Whole blood samples were incubated with voxelotor and then analyzed by routinely used quantitative and qualitative clinical laboratory methods (high-performance liquid chromatography [HPLC], capillary zone electrophoresis [CZE], and acid and alkaline electrophoresis).

Results: Voxelotor modified the α-globin chain of multiple hemoglobins, including HbA, HbS, HbC, HbD-Punjab, HbE, HbA2, and HbF. These voxelotor-hemoglobin complexes prevented accurate quantitation of multiple hemoglobin species, including HbS, by HPLC and CZE.

Conclusions: Technical limitations in quantifying HbS percentage may preclude the use of HPLC or CZE for monitoring patients treated with voxelotor. Furthermore, it is unclear whether HbS-voxelotor complexes are clinically equivalent to HbS. Consensus guidelines for reporting hemoglobin variant percentages for patients taking voxelotor are needed, as these values are necessary for determining the number of RBC units to exchange in acute situations.
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http://dx.doi.org/10.1093/ajcp/aqaa067DOI Listing
October 2020

Complication Rates after Lateral Plate Fixation of Periprosthetic Distal Femur Fractures: A Multicenter Study.

Injury 2020 Aug 22;51(8):1858-1862. Epub 2020 May 22.

Department of Orthopaedic Surgery, Stanford University, Stanford, CA.

Objective: Periprosthetic fractures of the distal femur can be challenging injuries to treat; nonunion rates of up to 22% have been reported. The purpose of this study was to determine the rate of complications and nonunion in a multicenter series, and to identify patient or surgical factors that were associated with nonunion.

Design: Retrospective comparative study SETTING: Three Level 1 trauma centers PATIENTS: Fifty-five patients with a periprosthetic distal femur fracture proximal to a total knee arthroplasty. Minimum follow up for inclusion was six months or until union or failure.

Intervention: Surgical fixation using a precontoured lateral locking plate MAIN OUTCOME MEASUREMENT: Fracture union was the primary outcome. Patient demographic and injury variables (age, comorbidities, fracture classification and characteristics) and surgical technique factors (mode of plate fixation, plate material, working length, screw density, and proximal screw type) were identified and compared between patients who developed a nonunion and those who did not. Regression analysis was performed to identify independent risk factors for nonunion.

Results: The overall rate of nonunion was 18% and the total complication rate was 24%. After additional surgery, 49 of 55 patients went on to heal (89%). There were no statistical differences in patient demographic or injury variables between the union and nonunion groups, and none of the variables studied were independent risk factors for nonunion in the regression analysis.

Conclusions: In this series of 55 patients with periprosthetic distal femur fractures treated with precontoured lateral locking plates, 18% developed nonunion and the overall complication rate was 24%. No patient or surgical variables were identified as risk factors. Future research should seek to identify patients at high risk for complication and nonunion who could benefit from alternative fixation strategies or distal femoral replacement.
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http://dx.doi.org/10.1016/j.injury.2020.05.009DOI Listing
August 2020

How do pilon fractures heal? An analysis of dual plating and bridging callus formation.

Injury 2020 Jul 12;51(7):1655-1661. Epub 2020 May 12.

Department of Orthopaedic Surgery, Stanford University Hospital, 300 Pasteur Drive Room R144, Stanford, CA, USA.

Objectives: 1) To determine the effect of single versus dual plate metaphyseal fixation for pilon fractures on callus formation and reoperation rates, 2) to determine the effect of biomechanically matched versus unmatched fixation, and 3) to determine whether patient or surgical factors were independent predictors of bridging callus formation or need for reoperation.

Design: Retrospective comparative study.

Setting: Single level one trauma center.

Patients: Fifty patients with AO/OTA type C2 or C3 pilon fractures treated with plate fixation.

Intervention: Internal fixation with a plate and screw construct, with comparisons made between patients with single versus dual plate fixation, and patients treated with biomechanically matched or unmatched fixation.

Main Outcome Measurements: Modified RUST (mRUST) scores at three and six months and reoperation rate.

Results: At six months, mean mRUST scores were significantly lower in patients treated with dual metaphyseal plates compared to a single plate (8.7 vs 10.4, p=0.046) There were 15 open fractures; eight were treated with supplemental fixation, while seven were treated with single-column fixation. Open fracture (OR 51.05, p=0.008) was a risk factor for reoperation. Screw density between 0.4 and 0.5 was a protective factor against reoperation (OR 0.03, p=0.026). Biomechanically unmatched fixation did not affect mRUST scores or reoperation rates.

Conclusions: Pilon fractures treated with a single plate had more callus formation six months after surgery compared to those treated with dual plate fixation, and there was no difference in reoperation rates. Screw density between 0.4-0.5 was protective against reoperation. These data may serve as the basis of future work to determine the ideal fixation construct for the frequently comminuted metaphysis in pilon fractures. Further work is necessary to determine whether callus formation in these injuries is desirable.

Level Of Evidence: Three.
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http://dx.doi.org/10.1016/j.injury.2020.04.023DOI Listing
July 2020

Contouring Plates in Fracture Surgery: Indications and Pitfalls.

J Am Acad Orthop Surg 2020 Apr 23. Epub 2020 Apr 23.

From the Department of Orthopaedic Surgery, Stanford University, Stanford, CA (Dr. Bishop, Dr. Campbell, and Dr. Gardner), and the Department of Orthopaedic Surgery, University of Mississippi, Oxford, MS (Dr. Graves).

Effective fracture surgery requires contouring orthopaedic implants in multiple planes. The amount of force required for contouring is dependent on the amount and type of material contained within the plane to be altered. The type of contouring used depends on the desired plate function; for example, buttress mode often requires some degree of undercontouring, whereas compression plating may require prebending. Other reasons to contour a plate include matching patient anatomy either to maximize fixation options or to reduce implant prominence. Precontoured plates can be convenient and help to facilitate soft-tissue friendly techniques but have the potential to introduce malreduction if the plate position and fit are not carefully monitored.
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http://dx.doi.org/10.5435/JAAOS-D-19-00462DOI Listing
April 2020

Dual Mini-Fragment Plating Is Comparable With Precontoured Small Fragment Plating for Operative Diaphyseal Clavicle Fractures: A Retrospective Cohort Study.

J Orthop Trauma 2020 Jul;34(7):e229-e232

Department of Orthopaedic Surgery, Stanford University, Redwood City, CA.

Objectives: To compare precontoured (Pc) small fragment plating to dual mini-fragment plating (DmF) for open reduction and internal fixation of diaphyseal clavicle fractures.

Design: Retrospective cohort.

Setting: Level 1 trauma center.

Patients/participants: A total of 133 patients with displaced fractures of the diaphyseal clavicle (OTA/AO 15-B1, -2, and -3) treated with open reduction and internal fixation with a minimum of 1 year follow-up or until radiographic and clinical union.

Intervention: Two patient cohorts were identified: (1) patients treated with orthogonal DmF plate constructs and (2) patients treated with Pc clavicle-specific plates.

Outcome Measurements: Union rate and implant removal were assessed using standard descriptive statistics. Odds ratios, 95% confidence intervals, and P values (P) were calculated.

Results: There were 60 DmF and 74 Pc patients. There were no significant differences between groups with respect to age, sex, surgeon, body mass index, or mode of fixation. There was no significant difference in union (98.3% DmF; 100% Pc, P = 0.45) or maintenance of reduction (98.3% DmF; 100% Pc, P = 0.45). A total of 8% of DmF patients had symptomatic implant removal compared with 20% of Pc patients (odds ratio 0.36, confidence interval 0.12-1.05, P = 0.061).

Conclusions: This retrospective comparative study found no difference in union or maintenance of reduction for diaphyseal clavicle fractures fixed with DmF compared with Pc plating. Patients treated with DmF plates may have lower rates of symptomatic implant removal.

Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.1097/BOT.0000000000001727DOI Listing
July 2020

Intramedullary Cage Fixation for Proximal Humerus Fractures Has Low Reoperation Rates at 1 Year: Results of a Multicenter Study.

J Orthop Trauma 2020 Apr;34(4):193-198

Department of Orthopaedic Surgery, Stanford Hospitals and Clinics, Redwood City, CA.

Objectives: To determine reoperation rates after treatment of a proximal humerus fracture with cage fixation.

Design: Retrospective case series.

Setting: Eleven U.S. hospitals.

Patients: Fifty-two patients undergoing surgical treatment of proximal humerus fractures.

Intervention: Open reduction and internal fixation of a proximal humerus fracture with a proximal humerus cage.

Main Outcome Measurements: Reoperation rate at 1 year.

Results: At a minimum follow-up of 1 year, reoperations occurred in 4/52 patients (7.7%). Avascular necrosis (2/41) occurred in 4.9% of patients.

Conclusion: Standard locked plating remains an imperfect solution for proximal humerus fractures. Proximal humerus cage fixation had low rates of revision surgery at 1 year. Proximal humerus cage fixation may offer reduced rates of complication and reoperation when compared with conventional locked plating for the management of proximal humerus fractures.

Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.1097/BOT.0000000000001712DOI Listing
April 2020

Understanding the Radiographic Anatomy of the Proximal Ulna and Avoiding Inadvertent Intraarticular Screw Placement.

J Orthop Trauma 2020 Feb;34(2):102-107

Department of Orthopaedic Surgery, Stanford University Hospital, Palo Alto, CA.

Objectives: To map the proximal ulnar articular margins and ensure safe extraarticular placement of implants.

Methods: Ten fresh frozen adult elbow cadaver specimens were obtained. Radiopaque wire was applied to the articular margin of the articular facets and the central trochlear ridge of the proximal ulna. Fluoroscopic images were obtained demonstrating the articular facet margins. Radiographic measurements were performed and used to identify relative safe screw zones.

Results: All specimens demonstrated marked extension of the ulnar and radial facets dorsal to the central trochlear ridge. The dorsal extent of the ulnar facets from the central trochlear ridge averaged 9.7 mm (range, 7.9-13 mm; SD, 1.5 mm) and 6.2 mm (range, 3.4-9.4 mm; SD, 1.9 mm), respectively. The average footprint of the posterior ulnar facet occupied 44% (±4.9%) of the total ulnar height from the dorsal cortex to the trochlear ridge.

Conclusions: The articular margins of the anterior and posterior facets of the proximal ulna are challenging to identify radiographically. A surgical "at-risk zone" exists within 9.7 mm from the radiographic margin of the central trochlear ridge. Implants placed within this zone have the potential to violate the articular surface.
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http://dx.doi.org/10.1097/BOT.0000000000001638DOI Listing
February 2020

What have animals taught us about total joint arthroplasty ? A review of the literature.

Acta Orthop Belg 2019 Sep;85(3):261-268

Animal models for total joint arthroplasty (TJA) have been reported on extensively in the literature. This work seeks to objectively review the most relevant and recent studies performed using these models, and to provide insight into the strengths and weaknesses of each. The terms joint arthroplasty and animal model were searched on Pubmed on March 1, 2015. Animal models included bovine, canine, ovine, goat, rat, and rabbit. Much of the work in animal models for TJA has focused on the biologic response to novel materials, biologics, and surgical techniques ; as interest grows the use of animal models may increase.
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September 2019

Complete Atlantoaxial Dislocation After Odontoid Synchondrosis Fracture: A 2-Year Follow-up Study: A Case Report.

JBJS Case Connect 2019 Apr-Jun;9(2):e0327

Department of Orthopaedic Surgery, Stanford University, Stanford, California.

Case: Spine injuries are rare in children, but when they do occur, the synchondrosis of C2 may be involved. A 5-year-old boy presented to our clinic complaining of neck pain for 6 weeks, which started after wrestling with peers. He had slight upper extremity weakness, clonus, and diminished reflexes. Imaging, including computed tomography and magnetic resonance imaging scans, showed a fracture dislocation through the synchondrosis of the odontoid. The patient was initially treated with admission to the hospital, awake halo placement, and gradual traction over a few days. Subsequently, he was taken for transoral reduction and posterior instrumented fusion of C1-C3 using a combination of sublaminar suture, screws, and rods. Most recently, he was doing well over 2 years later, with no residual neurologic symptoms.

Conclusions: The case presented demonstrates one option for an otherwise nonreducible odontoid synchondrosis fracture with complete atlantoaxial dislocation: transoral reduction and open posterior instrumentation. This proved to be a practical technique and provided a good clinical result in this case. These injuries are rare, but when they do occur, the examination can be surprisingly subtle given the severity of the injury. Plain films should be scrutinized carefully and advanced imaging obtained when necessary to confirm the diagnosis.
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http://dx.doi.org/10.2106/JBJS.CC.18.00327DOI Listing
June 2020

Rates of Perioperative Complications Among Patients Undergoing Orthopedic Trauma Surgery Despite Having Positive Results for Methamphetamine.

Orthopedics 2019 Jul 28;42(4):192-196. Epub 2019 May 28.

The burden of psychosocial problems, including substance abuse, is high among trauma patients. Use of illicit substances is often noted during urine toxicology screening on admission and can delay surgery because of concerns for an interaction with anesthesia. Methamphetamine theoretically has potential to increase perioperative anesthetic risks. However, the authors are unaware of any studies documenting increased rates of cardiovascular complications in the perioperative period among orthopedic trauma patients. This study sought to determine the rate of cardiovascular complications in these patients. The authors reviewed the medical records of all patients between 2013 and 2018 who underwent orthopedic trauma surgery at two level I trauma centers in the setting of a methamphetamine-positive urine toxicology screening prior to surgery. Information on demographics, injury, type of surgical intervention, and incidence of perioperative cardiovascular and overall medical complications prior to discharge was recorded. Ninety-four patients were included in the study (mean age, 44 years; range, 16-78 years). Twenty-six (28%) patients had multiple injuries. Thirteen (14%) patients had debridement and/or provisional stabilization of an open or unstable fracture, 18 (19%) had treatment for an infection, and 63 (67%) had definitive fracture surgery. The overall rates of perioperative cardiovascular complications and perioperative medical complications were 2.1% and 3.2%, respectively. This study provides both a baseline understanding of the complication rate for methamphetamine-positive orthopedic trauma patients during general anesthesia and justification for larger multicenter studies to further investigate this topic. [Orthopedics. 2019; 42(4):192-196.].
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http://dx.doi.org/10.3928/01477447-20190523-01DOI Listing
July 2019

Optimizing the Orthopaedic Medical Student Rotation: Keys to Success for Students, Faculty, and Residency Programs.

J Am Acad Orthop Surg 2019 Aug;27(15):542-550

From the Department of Orthopaedic Surgery, Stanford University, Stanford, CA.

Senior medical students interested in pursuing careers in orthopaedic surgery participate in orthopaedic rotations around the country. These rotations are an important part of the application process because they allow students to demonstrate their work ethic and knowledge and learn more about the fit and culture of the residency program. Although knowledge and technical ability are important, several less tangible factors also contribute to success. These include maintaining situational awareness and a positive attitude, putting forth an appropriate effort, preparing effectively, and critically evaluating one's own performance. Attention to these details can help maximize the student's chance for a successful rotation. The hosting program and faculty can further facilitate a successful rotation by setting appropriate expectations, orienting the student to the program, carefully selecting appropriate services and faculty, and providing dedicated education to the student.
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http://dx.doi.org/10.5435/JAAOS-D-19-00096DOI Listing
August 2019

Distal Femur Locking Plates Fit Poorly Before and After Total Knee Arthroplasty.

J Orthop Trauma 2019 May;33(5):239-243

Department of Orthopaedic Surgery, Stanford University Hospital, Stanford, CA.

Objective: To evaluate the fit of distal femur locking plates. Secondarily, we sought to compare plate fit among patients with and without a total knee arthroplasty (TKA).

Design: Retrospective.

Setting: University hospital.

Intervention: Standard length precontoured distal femur locking plates from 4 manufacturers were digitally templated onto each patient's pre-TKA and post-TKA radiographs.

Main Outcome Measurements: The maximum distance from the plate to the lateral femoral cortex (plate-bone distance) was measured in the metaphyseal region. Mean plate-bone distances were compared between manufacturers and between pre-TKA and post-TKA radiographs.

Results: All implants tested were undercontoured in all patients. Plate-bone distances ranged from 6.6 ± 0.4 mm to 8.0 ± 0.4 mm (mean ± SE) pre-TKA and 8.2 ± 0.3 mm to 8.6 ± 0.3 mm after TKA, indicating worse fit after arthroplasty (P < 0.001). There were also intermanufacturer differences, with Synthes and Smith & Nephew implants demonstrating the lowest plate-bone distances in the pre-TKA and post-TKA groups, respectively. Proportionally, plate-bone increase was greater in the female cohort (16%) compared with the male cohort (8%).

Conclusions: There was plate-bone mismatch for the distal femur locking plates tested in this study, due to undercontouring of the implants. After patients underwent TKA, poor implant fit was exacerbated. Surgeons must be aware of the potential for deformity if the proximal segment is brought into contact with the implant. These finding may help optimize implant design for the treatment of periprosthetic distal femur fractures.
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http://dx.doi.org/10.1097/BOT.0000000000001431DOI Listing
May 2019

Chemoproteomic Discovery of a Ritanserin-Targeted Kinase Network Mediating Apoptotic Cell Death of Lung Tumor Cells.

Mol Pharmacol 2018 11 29;94(5):1246-1255. Epub 2018 Aug 29.

Departments of Chemistry (S.T.C., C.E.F., M.S., L.Z., K.-L.H.), Pathology (S.T.C.), and Pharmacology (A.L.B., K.-L.H.), University of Virginia Cancer Center (K.-L.H.), University of Virginia, Charlottesville, Virginia

Ritanserin was tested in the clinic as a serotonin receptor inverse agonist but recently emerged as a novel kinase inhibitor with potential applications in cancer. Here, we discovered that ritanserin induced apoptotic cell death of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cells via a serotonin-independent mechanism. We used quantitative chemical proteomics to reveal a ritanserin-dependent kinase network that includes key mediators of lipid [diacylglycerol kinase , phosphatidylinositol 4-kinase ] and protein [feline encephalitis virus-related kinase, rapidly accelerated fibrosarcoma (RAF)] signaling, metabolism [eukaryotic elongation factor 2 kinase, eukaryotic translation initiation factor 2- kinase 4], and DNA damage response [tousled-like kinase 2] to broadly kill lung tumor cell types. Whereas ritanserin exhibited polypharmacology in NSCLC proteomes, this compound showed unexpected specificity for c-RAF in the SCLC subtype, with negligible activity against other kinases mediating mitogen-activated protein kinase signaling. Here we show that ritanserin blocks c-RAF but not B-RAF activation of established oncogenic signaling pathways in live cells, providing evidence in support of c-RAF as a key target mediating its anticancer activity. Given the role of c-RAF activation in RAS-mutated cancers resistant to clinical B-RAF inhibitors, our findings may have implications in overcoming resistance mechanisms associated with c-RAF biology. The unique target landscape combined with acceptable safety profiles in humans provides new opportunities for repositioning ritanserin in cancer.
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http://dx.doi.org/10.1124/mol.118.113001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160665PMC
November 2018

Knee Pain After Intramedullary Nailing of Tibia Fractures: Prevalence, Etiology, and Treatment.

J Am Acad Orthop Surg 2018 Sep;26(18):e381-e387

From the Department of Orthopaedic Surgery, Stanford University, Stanford, CA (Dr. Bishop, Dr. Campbell, and Dr. Gardner), and the Department of Sports Medicine and Shoulder Surgery, Hospital for Special Surgery, New York City, NY (Dr. Eno).

Intramedullary nailing is often the treatment of choice for fractures of the tibia, but postoperative knee pain is common after this procedure. Potential etiologies include implant prominence, injury to intra-articular structures, patellar tendon or fat pad injury, damage to the infrapatellar branch of the saphenous nerve, and altered biomechanics. Depending on the etiology, described treatment options include observation, implant removal, assessment and treatment of injured intra-articular structures, and selective denervation. Careful attention to appropriate starting point and implant selection combined with more recently described semiextended nailing techniques may aid in prevention of knee pain.
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http://dx.doi.org/10.5435/JAAOS-D-18-00076DOI Listing
September 2018

A Structured Review Instrument Improves the Quality of Orthopaedic Journal Club.

J Surg Educ 2019 Jan - Feb;76(1):294-300. Epub 2018 Aug 7.

Department of Orthopaedic Surgery, Stanford University, Stanford, California. Electronic address:

Objective: We asked the following questions: 1. Does the use of an structured review instrument (SRI) at journal club increase presentation quality, as measured objectively by a standardized evaluation rubric? 2. Does SRI use increase the time required to prepare for journal club? 3. Does SRI use positively impact presenter perceptions about confidence while presenting, satisfaction, and journal club effectiveness, as measured by postparticipation surveys?

Design: A prospective study was designed in which a grading rubric was developed to evaluate journal club presentations. The rubric was applied to 24 presentations at journal clubs prior to introduction of the SRI. An SRI was developed and distributed to journal club participants, who were instructed to use it to prepare for journal club. The grading rubric was then used to assess 25 post-SRI presentations and scores were compared between the pre- and post-SRI groups. Presentations occurred at either trauma, pediatrics, or spine subspecialty journal clubs. Participants were also surveyed regarding time requirements for preparation, perceptions of confidence while presenting, satisfaction, and perceptions of overall club effectiveness.

Setting: A single academic center with an orthopaedic surgery residency program.

Participants: Resident physicians in the department of orthopaedic surgery.

Results: Mean presentation scores increased from 14.0 ± 5.9 (mean ± standard deviation) to 24.4 ± 5.2 after introduction of the SRI (p < 0.001). Preparation time decreased from a mean of 47 minutes to 40 minutes after SRI introduction (p = 0.22). Perceptions of confidence, satisfaction, and club effectiveness among trainees trended toward more positive responses after SRI introduction (confidence: 63% positive responses pre-SRI vs 72% post-SRI, p = 0.73; satisfaction: 64% vs 91%, p = 0.18; effectiveness: 64% vs 91%, p = 0.19).

Conclusions: The use of a structured review instrument to guide presentations at orthopaedic journal club increased presentation quality, and there was no difference in preparation time. There were trends toward improved presenter confidence, satisfaction, and perception of journal club effectiveness. SRI utilization at orthopaedic journal club may be an effective method for increasing the quality of journal club presentations. Future work should examine the relationship between presentation quality and overall club effectiveness.
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http://dx.doi.org/10.1016/j.jsurg.2018.06.017DOI Listing
June 2020

DNA Sequencing in the Clinical Laboratory: A Ladder to the Future.

Clin Chem 2018 Apr;64(4):757

Division of Laboratory Medicine, Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA.

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http://dx.doi.org/10.1373/clinchem.2017.285221DOI Listing
April 2018