Publications by authors named "Phillip M Kemp Bohan"

26 Publications

  • Page 1 of 1

Impact of Hepatic Metastasectomy in the Multimodal Treatment of Metastatic Breast Cancer.

J Surg Res 2021 Aug 30;268:650-659. Epub 2021 Aug 30.

General Surgery Department, William Beaumont Army Medical Center, El Paso, Texas. Electronic address:

Background: Surgical management of hepatic metastases in patients with stage IV breast cancer remains controversial. The purpose of this study was to examine the impact of hepatic metastasectomy on long-term outcomes.

Methods: The 2004-2015 National Cancer Database was queried for all patients diagnosed with stage IV breast cancer with metastases isolated to the liver. Patient demographics, disease-, treatment- and outcome-related data were analyzed.

Results: Of 2,895 patients, only 90 (3.1%) underwent hepatic resection. Compared to patients who did not undergo metastasectomy, patients treated with metastasectomy tended to be younger (52 ± 12.7 versus 59.2 ± 14.6; P < 0.001) and have private insurance (74.4% versus 45.3%; P < 0.001). Independent predictors of metastasectomy included younger age (OR 0.98; CI 0.96-0.99; P = 0.01), lobular carcinoma (OR 2.26; CI 1.06-4.82; P = 0.03), and prior surgery of the primary site (partial mastectomy (OR 6.96; CI 3.47-13.95; P < 0.001) or total mastectomy (OR 5.74; CI 3.06-10.76; P < 0.001)). Compared to no metastasectomy, hepatic metastasectomy was independently associated with a 37% reduction in the risk of death (HR 0.63; CI 0.44-0.91; P = 0.01).

Conclusions: Stage IV breast cancer with metastases to the liver is rare and few patients undergo hepatic resection. However, in this select patient population, hepatic metastasectomy was associated with a significant survival advantage when included in the multimodal treatment of synchronous stage IV breast cancer.
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http://dx.doi.org/10.1016/j.jss.2021.07.032DOI Listing
August 2021

Impact of dermal matrix thickness on split-thickness skin graft survival and wound contraction in a single-stage procedure.

Int Wound J 2021 Jul 9. Epub 2021 Jul 9.

Department of Surgery, Brooke Army Medical Center, San Antonio, Texas, USA.

Optimal treatment of full-thickness skin injuries requires dermal and epidermal replacement. To spare donor dermis, dermal substitutes can be used ahead of split-thickness skin graft (STSG) application. However, this two-stage procedure requires an additional general anaesthetic, often prolongs hospitalisation, and increases outpatient services. Although a few case series have described successful single-stage reconstructions, with application of both STSG and dermal substitute at the index operation, we have little understanding of how the physical characteristics of dermal substitutes affects the success of a single-stage procedure. Here, we evaluated several dermal substitutes to optimise single-stage skin replacement in a preclinical porcine model. A porcine full-thickness excisional wound model was used to evaluate the following dermal substitutes: autologous dermal graft (ADG; thicknesses 0.15-0.60 mm), Integra (0.4-0.8 mm), Alloderm (0.9-1.6 mm), and chitosan-based hydrogel (0.1-0.2 mm). After excision, each wound was treated with either a dermal substitute followed by STSG or STSG alone (control). Endpoints included graft take at postoperative days (PODs) 7 and 14, wound closure at POD 28, and wound contracture from POD 28-120. Graft take was highest in the STSG alone and hydrogel groups at POD 14 (86.9% ± 19.5% and 81.3% ± 12.3%, respectively; P < .001). There were no differences in graft take at POD 7 or in wound closure at POD 28, though highest rates of wound closure were seen in the STSG alone and hydrogel groups (93.6% ± 9.1% and 99.8% ± 0.5%, respectively). ADG-treated wounds demonstrated the least amount of wound contracture at each time point. Increase dermal substitute thickness was associated with worse percent graft take at PODs 14 and 28 (Spearman ρ of -0.50 and -0.45, respectively; P < .001). In this preclinical single-stage skin reconstruction model, thinner ADG and hydrogel dermal substitutes outperformed thicker dermal substitutes. Both substitute thickness and composition affect treatment success. Further preclinical and clinical studies to optimise this treatment modality are warranted.
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http://dx.doi.org/10.1111/iwj.13637DOI Listing
July 2021

Safety and efficacy of autologous tumor lysate particle-loaded dendritic cell vaccination in combination with systemic therapies in patients with recurrent and metastatic melanoma.

Melanoma Res 2021 08;31(4):378-388

Cancer Vaccine Development Program, San Antonio, Texas, USA.

Immunotherapy has revolutionized the treatment of melanoma, yet survival remains poor for patients with metastatic disease. The autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine has been shown to be safe adjuvant therapy for patients with resected stage III/IV melanoma who complete the primary vaccine series. Here, we describe an open-label trial of patients with metastatic melanoma treated with TLPLDC vaccine in addition to standard of care (SoC) therapies. The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles, which are phagocytosed by autologous dendritic cells ex vivo. Patients who recurred while enrolled in a phase IIb trial of adjuvant TLPLDC vaccine (crossover cohort) and patients with measurable metastatic melanoma cohort were offered TLPLDC vaccine along with SoC therapies. Tumor response was measured by RECIST 1.1 criteria. Overall survival (OS) and progression-free survival (PFS) were estimated by intention-to-treat analysis. Fifty-four patients were enrolled (28 in crossover cohort; 26 in metastatic melanoma cohort). The vaccine was well-tolerated with no grade ≥3 adverse events when given with SoC therapies to include checkpoint inhibitors, BRAF/MEK inhibitors, tyrosine kinase inhibitors, intralesional therapy and/or radiation. In the crossover arm, OS was 76.5% and PFS was 57.1% (median follow-up of 13.9 months). In the metastatic melanoma arm, OS was 85.7% and PFS was 52.2% (median follow-up 8.5 months). The TLPLDC vaccine is well-tolerated and safe in combination with SoC therapies. Future trials will determine the efficacy of TLPLDC in combination with SoC therapies in metastatic melanoma.
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http://dx.doi.org/10.1097/CMR.0000000000000758DOI Listing
August 2021

Safety and efficacy of low-titer O whole blood resuscitation in a civilian level I trauma center.

J Trauma Acute Care Surg 2021 08;91(2S Suppl 2):S162-S168

From the Department of Surgery (P.M.K.B., P.M.M., A.M.A., R.C.C.), Brooke Army Medical Center, Fort Sam Houston, Texas; Uniformed Services University of the Health Sciences (M.E.W.), Bethesda, Maryland; and Department of Trauma and Acute Care Surgery (J.E.F., J.S.R., R.A.H., V.G.S.), Brooke Army Medical Center, Fort Sam Houston, Texas.

Background: Military experience has shown low-titer O whole blood (LTOWB) to be safe and beneficial in the resuscitation of hemorrhaging trauma patients. However, few civilian centers use LTOWB for trauma resuscitation. We evaluated the early experience and safety of a LTOWB program at a level 1 civilian trauma center.

Methods: We retrospectively reviewed our trauma registry from January 2018 to June 2020 for patients admitted in shock (defined as ≥1 of the following: heart rate, >120 beats per minute; systolic blood pressure, <90 mm Hg; or shock index, >0.9) who received blood products within 24 hours. Patients were grouped by resuscitation provided: LTOWB (group 1), component therapy (CT; group 2), and LTOWB-CT (group 3). Safety, outcomes, and variables associated with LTOWB transfusion and mortality were analyzed.

Results: 216 patients were included: 34 in Group 1, 95 in Group 2, and 87 in Group 3. Patientsreceiving LTOWB were more commonly male (p<0.001) and had a penetrating injury (p=0.005). Groups 1 and 3 had higher median ISS scores compared to Group 2 (19 and 20 vs 17; p=0.01). Group 3 received more median units of blood product in the first 4h (p<0.001) and in the first 24h (p<0.001). There was no difference between groups in 24h mortality or transfusion-related complications (all p>0.05). Arrival ED SBP was associated with LTOWB transfusion (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.95-1.00, p=0.03). ED lactate was independently associated with 24h mortality. (OR 1.27, CI 1.02-1.58, p=0.03). LTOWB transfusion was not associated with mortality (p=0.49). Abstract.

Conclusion: Severely injured patients received LTOWB-CT and more overall product units but had similar 24 h mortality when compared with the LTOWB or CT groups. No increase in transfusion-related complications was seen after LTOWB transfusion. Low-titer O whole blood should be strongly considered in the resuscitation of trauma patients at civilian centers.

Level Of Evidence: Retrospective, therapeutic, level IV.
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http://dx.doi.org/10.1097/TA.0000000000003289DOI Listing
August 2021

Multi-institutional, prospective, randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine to prevent recurrence in high-risk melanoma patients: A subgroup analysis.

Cancer Med 2021 07 12;10(13):4302-4311. Epub 2021 May 12.

Cancer Vaccine Development Program, San Antonio, TX, USA.

Background: Checkpoint inhibitors (CPI) in combination with cell-based vaccines may produce synergistic antitumor immunity. The primary analysis of the randomized and blinded phase IIb trial in resected stage III/IV melanoma demonstrated TLPLDC is safe and improved 24-month disease-free survival (DFS) in the per treatment (PT) analysis. Here, we examine efficacy within pre-specified and exploratory subgroups.

Methods: Stage III/IV patients rendered disease-free by surgery were randomized 2:1 to TLPLDC vaccine versus placebo. The pre-specified PT analysis included only patients completing the primary vaccine/placebo series at 6 months. Kaplan-Meier analysis was used to compare 24-month DFS among subgroups.

Results: There were no clinicopathologic differences between subgroups except stage IV patients were more likely to receive CPI. In stage IV patients, 24-month DFS was 43% for vaccine versus 0% for placebo (p = 0.098) in the ITT analysis and 73% versus 0% (p = 0.002) in the PT analysis. There was no significant difference in 24-month DFS when stratified by use of immunotherapy or CPI. For patients with resected recurrent disease, 24-month DFS was 88.9% versus 33.3% (p = 0.013) in the PT analysis. All benefit from vaccination was in the PT analysis; no benefit was found in patients receiving up to three doses.

Conclusion: The TLPLDC vaccine improved DFS in patients completing the primary vaccine series, particularly in the resected stage IV patients. The efficacy of the TLPLDC vaccine will be confirmed in a phase III study evaluating adjuvant TLPLDC + CPI versus Placebo + CPI in resected stage IV melanoma patients.
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http://dx.doi.org/10.1002/cam4.3969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267143PMC
July 2021

A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis.

Ann Surg Oncol 2021 Oct 27;28(11):6126-6137. Epub 2021 Feb 27.

The Angeles Clinic, Santa Monica, CA, USA.

Background: Melanoma therapy has changed dramatically over the last decade with improvements in immunotherapy, yet many patients do not respond to current therapies. This novel vaccine strategy may prime a patient's immune system against their tumor and work synergistically with immunotherapy against advanced-stage melanoma.

Methods: This was a prospective, randomized, double-blind, placebo-controlled, phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine administered to prevent recurrence in patients with resected stage III/IV melanoma. Patients were enrolled and randomized 2:1 to the TLPLDC vaccine or placebo (empty yeast cell wall particles and autologous dendritic cells). Both intention-to-treat (ITT) and per treatment (PT) analyses were predefined, with PT analysis including patients who remained disease-free through the primary vaccine/placebo series (6 months).

Results: A total of 144 patients were randomized (103 vaccine, 41 control). Therapy was well-tolerated with similar toxicity between treatment arms; one patient in each group experienced related serious adverse events. While disease-free survival (DFS) was not different between groups in ITT analysis, in PT analysis the vaccine group showed improved 24-month DFS (62.9% vs. 34.8%, p = 0.041).

Conclusions: This phase IIb trial of TLPLDC vaccine administered to patients with resected stage III/IV melanoma shows TLPLDC is well-tolerated and improves DFS in patients who complete the primary vaccine series. This suggests patients who do not recur early benefit from TLPLDC in preventing future recurrence from melanoma. A phase III trial of TLPLDC + checkpoint inhibitor versus checkpoint inhibitor alone in patients with advanced, surgically resected melanoma is under development.

Trial Registration: NCT02301611.
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http://dx.doi.org/10.1245/s10434-021-09709-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914039PMC
October 2021

Rates, Predictors, and Outcomes of Portal Lymphadenectomy for Resectable Gallbladder Cancer.

Ann Surg Oncol 2021 Jun 10;28(6):2960-2972. Epub 2021 Feb 10.

Department of Surgery, Brooke Army Medical Center, Ft. Sam Houston, TX, USA.

Introduction: Lymphadenectomy (LND) is recommended following surgical resection of ≥ T1b gallbladder cancer (GBC). However, frequency and stage-specific survival benefits of LND remain unclear.

Patients And Methods: The National Cancer Database (NCDB; 2006-15) was queried for resected pathologic stage I-III GBC. LND performance, predictors of receiving LND, and LND association with overall survival (OS) were assessed.

Results: Of 2302 total patients, 1343 (58.3%) underwent LND. Patients who underwent LND were younger and more frequently had private health insurance, a negative surgical margin, higher pathologic T stage, and received adjuvant chemotherapy (all p < 0.001). LND rates were highest at academic centers (70.1%) relative to all other facility types (p < 0.001). LND was independently associated with improved OS [hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.44-0.61]. LND was associated with improved OS for pT1b, pT2, and pT3 patients (all p < 0.05) on univariate analysis. LND was independently associated with improved OS in pT2 (HR 0.44, CI 0.35-0.56) and pT3 (HR 0.54, CI 0.43-0.69) patients.

Conclusions: LND is associated with a 48% reduction in risk of death in patients with resectable non-metastatic GBC, with greatest impact in pT2-3 patients. Patients without LND have similar OS to patients with node-positive disease, highlighting the importance of LND. Underutilization of LND likely results in undertreatment of patients with undiagnosed nodal disease, which may contribute to unfavorable oncologic outcomes.
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http://dx.doi.org/10.1245/s10434-021-09667-8DOI Listing
June 2021

ASO Author Reflections: Contemporary Analysis of Impact of Lymphadenectomy on Survival in Nonmetastatic Gallbladder Cancer.

Ann Surg Oncol 2021 06 9;28(6):2973-2974. Epub 2021 Feb 9.

Department of Surgery, Brooke Army Medical Center, Ft. Sam Houston, TX, USA.

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http://dx.doi.org/10.1245/s10434-021-09668-7DOI Listing
June 2021

Phase I Trial of Encapsulated Rapamycin in Patients with Prostate Cancer Under Active Surveillance to Prevent Progression.

Cancer Prev Res (Phila) 2021 May 29;14(5):551-562. Epub 2021 Jan 29.

Department of Urology, UT Health-San Antonio, San Antonio, Texas.

No approved medical therapies prevent progression of low-grade prostate cancer. Rapamycin inhibits cell proliferation and augments immune responses, producing an antitumor effect. Encapsulated rapamycin (eRapa) incorporates rapamycin into a pH-sensitive polymer, ensuring consistent dosing. Here, we present results from a phase I trial evaluating the safety and tolerability of eRapa in patients with prostate cancer. Patients with Gleason ≤7 (3+4) disease (low and intermediate risk) under active surveillance were enrolled in a 3+3 study with three eRapa dosing cohorts (cohort 1, 0.5 mg/week; cohort 2, 1 mg/week; and cohort 3, 0.5 mg/day). Patients were treated for 3 months and followed for an additional 3 months to assess safety, pharmacokinetics, quality of life (QoL), immune response, and disease progression. Fourteen patients (cohort 1, = 3; cohort 2, = 3; and cohort 3, = 8) were enrolled. In cohort 3, one dose-limiting toxicity (DLT; neutropenia) and two non-DLT grade 1-2 adverse events (AE) occurred that resulted in patient withdrawal. All AEs in cohorts 1 and 2 were grade 1. Peak serum rapamycin concentration was 7.1 ng/mL after a 1 mg dose. Stable trough levels (∼2 ng/mL) developed after 48-72 hours. Daily dosing mildly worsened QoL, although QoL recovered after treatment cessation in all categories, except fatigue. Weekly dosing increased naïve T-cell populations. Daily dosing increased central memory cell populations and exhaustion markers. No disease progression was observed. In conclusion, treatment with eRapa was safe and well-tolerated. Daily dosing produced higher frequencies of lower grade toxicities and transient worsening of QoL, while weekly dosing impacted immune response. Future studies will verify clinical benefit and long-term tolerability. There is an unmet medical need for a well-tolerated treatment capable of delaying progression of newly diagnosed low-grade prostate cancer. This treatment would potentially obviate the need for future surgical intervention and improve the perception of active surveillance as a more acceptable option among this patient population.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0383DOI Listing
May 2021

Subgroup analysis of nelipepimut-S plus GM-CSF combined with trastuzumab versus trastuzumab alone to prevent recurrences in patients with high-risk, HER2 low-expressing breast cancer.

Clin Immunol 2021 04 22;225:108679. Epub 2021 Jan 22.

Cancer Vaccine Development Program, 1422 E. Grayson, 3rd Floor, San Antonio, TX 78208, USA.

HER2-targeted therapy has not benefited patients with low levels of HER2 expression; however, combination therapy may be effective. Primary analysis of a phase IIb trial investigating the HER2-derived vaccine nelipepimut-S (NPS) did not benefit the intention-to-treat population, but subset analysis showed a benefit in triple-negative breast cancer (TNBC) patients. The subset analysis of this multicenter, randomized, single-blind, phase IIb trial identified significant improvement in 36-month disease-free survival (DFS) between NPS (n = 55) and placebo (n = 44) in TNBC (HR 0.25, p = 0.01) and those who express HLA-A24 (HR 0.41, p = 0.05). The TNBC cohort demonstrated improved 36-month DFS in those with HER2 1+ expression (HR 0.17, p = 0.01), HLA-A24 positivity (HR 0.08, p < 0.01), or in those who received neoadjuvant chemotherapy (HR 0.21, p < 0.01). NPS vaccination with trastuzumab was associated with improved 36-month DFS among patients with TNBC. The observed benefit to this high-risk subgroup warrants confirmation in a phase III trial.
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http://dx.doi.org/10.1016/j.clim.2021.108679DOI Listing
April 2021

Lymph node sampling in resectable hepatocellular carcinoma: national practice patterns and predictors of positive lymph nodes.

Surg Oncol 2021 Mar 30;36:138-146. Epub 2020 Dec 30.

Department of Surgery, Brooke Army Medical Center, Ft. Sam Houston, TX, USA; Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. Electronic address:

Background And Objectives: Routine lymphadenectomy (LND) for resectable hepatocellular carcinoma (HCC) remains controversial. We evaluated national LND trends to identify pre-operative factors associated with node-positive disease to determine which patients might benefit from LND.

Methods: We identified HCC patients in the National Cancer Database (NCDB) treated with surgical resection between 2004 and 2015. Demographic, operative, pathologic, and survival data were compared. Multivariable regression was performed to determine preoperative predictors of pathologic nodal disease.

Results: Of 8095 total resected patients, 1442 (17.8%) underwent hepatectomy with LND. Patients who received LND had higher preoperative clinical T (T3-T4: 20.0% vs 12.1%, p < 0.001) and N (N1: 3.3% vs 0.6%, p < 0.001) stages. The strongest independent predictor of pathologic nodal disease was clinical N stage (OR 106.54, CI 44.10-257.42). Survival was highest in patients whose surgeons omitted LND or were found with LND to be node-negative on final pathology (p < 0.001). Clinical node positivity had high negative predictive value (97.9%) but moderate positive predictive value (56.3%) in estimating pathologic nodal status.

Conclusions: Defining preoperative clinical nodal status is imperative in HCC patients. Clinical node positivity was the strongest predictor of pathologic nodal disease and its associated worse prognosis. LND can be considered selectively in clinically node-positive patients.
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http://dx.doi.org/10.1016/j.suronc.2020.12.011DOI Listing
March 2021

Correlation of tumor microenvironment from biopsy and resection specimens in untreated colorectal cancer patients: a surprising lack of agreement.

Cancer Immunol Immunother 2021 May 12;70(5):1465-1474. Epub 2020 Nov 12.

Department of Surgery, Brooke Army Medical Center, 3551 Roger Brooke Dr., Ft. Sam Houston, TX, 78234, USA.

Background: Colorectal cancer (CRC) tumor microenvironment (TME) characteristics, such as tumor infiltrating lymphocyte (TIL) densities and PD-L1 status, are predictive of recurrence, disease-free survival, and overall survival. In many malignancies, TME characteristics are also predictive of response to immunotherapy. As window of opportunity studies using neoadjuvant immunotherapy become more common and treatment guidelines incorporate TME features, accurate assessment of the pre-treatment TME using the biopsy specimen is critical. However, no study has thoroughly evaluated the correlation between the TMEs of the biopsy and resection specimens.

Methods: We conducted a retrospective analysis of patients with stage I-III CRC with matched biopsy and resection specimens. CD3+, CD4+, CD8+, and FoxP3+ lymphocyte populations at the center of tumor (CT) and invasive margin (IM) and tumor PD-L1 status in the biopsy and resection specimens were evaluated. TIL populations were compared using Mann-Whitney U tests or Student's t tests and correlated using Pearson r.

Results: CD3+ and CD4+ densities were significantly higher in the CT of the biopsy relative to the resection specimen Comparing biopsy and resection specimens, no TIL population at either the CT or IM had a correlation coefficient > 0.5. Determining PD-L1 status based on biopsy tissue resulted in a sensitivity of 37.1%, specificity of 81.4%, and accuracy of 61.5%.

Conclusions: These findings demonstrate significant discordance between the TME of the biopsy and resection specimens. Caution should be used when basing treatment decisions on pre-treatment endoscopic biopsy findings and when interpreting changes in the TME between pre-treatment biopsy and resection specimens after neoadjuvant therapy.
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http://dx.doi.org/10.1007/s00262-020-02784-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658304PMC
May 2021

Examining Perioperative Risk Associated with Simultaneous Resection of Primary Neuroendocrine Tumors and Synchronous Hepatic Metastases.

World J Surg 2021 Feb 5;45(2):531-542. Epub 2020 Nov 5.

Department of Surgery, William Beaumont Army Medical Center, 5005 N. Piedras St, El Paso, TX, 79920, USA.

Background: Surgical debulking of primary neuroendocrine tumors (NETs) and hepatic resection of metastatic NET disease may each independently improve overall survival. However, evidence for combined primary site debulking and metastasectomy on survival and impact on short-term perioperative outcomes is limited.

Methods: The 2014-2016 ACS-NSQIP targeted hepatectomy database was queried for all patients undergoing liver resection for metastatic NET. Secondary procedure codes were evaluated for major concurrent operations. Multivariable analysis was performed to determine risk factors for 30-day morbidity and mortality.

Results: A total of 472 patients were identified, of whom 153 (32.4%) underwent ≥1 additional concurrent major operation. The most common concurrent procedures were small bowel resection (14.6%), partial colectomy (8.9%), and radical lymphadenectomy (7.4%). Among all patients, overall 30-day mortality and morbidity were 1.5% and 25.6%, respectively. Modifiable and treatment-related factors associated with increased major postoperative morbidity risk included >10% weight loss within six months of surgery (p = 0.05), increasing number of hepatic lesions treated (p = 0.05), and biliary reconstruction (p = 0.001). No major concurrent procedure was associated with increased 30-day morbidity (all p > 0.05).

Conclusions: Approximately one-third of patients with stage IV NET underwent combined hepatic and multi-organ resection. Although modifiable and treatment-related factors predictive of perioperative morbidity were identified, performance of concurrent major procedures did not increase perioperative morbidity. These results support consideration of multi-organ resection in carefully selected patients with metastatic NET.
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http://dx.doi.org/10.1007/s00268-020-05847-xDOI Listing
February 2021

Reply to "Comment on: Adjuvant Chemotherapy in Resectable Gallbladder Cancer is Underutilized Despite Benefits in Node-Positive Patients".

Ann Surg Oncol 2020 12 25;27(Suppl 3):942-943. Epub 2020 Sep 25.

Department of Surgery, William Beaumont Army Medical Center, 5005 N. Piedras St., El Paso, TX, 79920, USA.

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http://dx.doi.org/10.1245/s10434-020-09170-6DOI Listing
December 2020

An Educational Intervention Reduces Opioids Prescribed Following General Surgery Procedures.

J Surg Res 2021 01 3;257:399-405. Epub 2020 Sep 3.

Brooke Army Medical Center, Ft Sam Houston, Texas; Uniformed Services University of the Health Sciences, Bethesda, Maryland. Electronic address:

Background: Variability exists in opioid prescribing practices among surgeons, frequently resulting in the prescription of excessive opioids. This study evaluated the ability of a single educational intervention targeted toward general surgery residents to reduce the quantity of postoperative opioids prescribed.

Materials And Methods: This retrospective cohort study evaluated opioid prescribing practices 12 mo prior to and 6 mo following a 30-min lecture for general surgery residents that discussed prescribing guidelines and multimodal analgesia. Opioid volumes (normalized to oral morphine equivalents, OME), opioid type, nonopioid pain medications, and refills requested were analyzed for opioid-naïve adult patients undergoing excisional breast biopsy (EB), mastectomy (M), laparoscopic appendectomy (LA), laparoscopic cholecystectomy (LC), open umbilical hernia repair (OUHR), open inguinal hernia repair (OIHR), or laparoscopic inguinal hernia repair (LIHR).

Results: 695 and 376 patients preintervention and postintervention were included, respectively. Median OME prescribed decreased for EB (150 mg to 75 mg, P < 0.001), M (225 mg to 150 mg, P = 0.85), LA (150 mg to 94 mg, P < 0.001), LC (150 mg to 82 mg, P < 0.001), OUHR (150 mg to 103 mg, P < 0.001), OIHR (175 mg to 100 mg, P = 0.001), and LIHR (200 mg to 113 mg, P < 0.001). Fewer patients received opioids alone and more patients received an opioid with two nonopioid adjuncts (P < 0.001). More patients received oxycodone as fewer received acetaminophen-containing opioid combinations (P < 0.001). Patients requiring refills decreased (11.9% to 7.2%) (P = 0.014).

Conclusions: Following this targeted intervention, patients were discharged with fewer OME and more nonopioid analgesics, even as refill requests decreased. Educating residents on opioid prescription guidelines and multimodal therapy is effective and should be part of the annual didactic curriculum.
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http://dx.doi.org/10.1016/j.jss.2020.08.012DOI Listing
January 2021

Fractionated Ablative Carbon Dioxide Laser Therapy Decreases Ultrasound Thickness of Hypertrophic Burn Scar: A Prospective Process Improvement Initiative.

Ann Plast Surg 2021 03;86(3):273-278

US Army Institute of Surgical Research.

Introduction: Carbon dioxide (CO2) laser treatment is routinely used to treat hypertrophic burn scars (HBS). Although prior research has documented subjective improvement in HBS after treatment, there is little data evaluating objective changes in scar characteristics after therapy. The aim of our process improvement project was to evaluate changes to scar thickness (ST) using high-frequency ultrasound in patients with HBS undergoing CO2 laser therapy.

Methods: Ultrasound measurements of ST were obtained from patients with HBS before initial and at each subsequent treatment. ST, reduction in ST per treatment, and percentage reduction in ST from baseline were tabulated. Post hoc analyses examining the effect of initial ST and scar maturity on outcome were performed. First, patients were grouped by baseline ST into thicker (group 1, initial ST ≥ median value) and thinner (group 2, initial ST < median value) scar groups. Second, patients were divided into quartiles based on time from injury to treatment. Outcomes at each time point were compared with either Mann-Whitney U or Kruskal-Wallis tests, with Bonferonni corrections performed for post hoc subgroup analyses. Significance was set at P < 0.05.

Results: Twenty-one consecutive patients with HBS treated with CO2 laser were included. All patients completed 1 or more treatment, 48% completed 2 or more treatments, and 28% completed 3 treatments. Median initial ST was 0.71 cm (0.44-0.98 cm), and median scar maturity was 7.5 months (4.9-9.8 months). Overall, ST decreased over the treatment course (P < 0.001), with post hoc analysis demonstrating that 2 treatments were required to achieve a significant ST reduction (P < 0.01). On subgroup analysis comparing initial ST, ST decreased significantly in group 1 (thicker scars) overall (P < 0.001) but not in group 2 (P = 0.109). ST reduction was greatest after 1 treatment in group 1 (P = 0.022) and group 2 (P = 0.061). Percent reduction was greater in group 1 relative to group 2 after 1 treatment (P = 0.016). On subgroup analysis of scar maturity, there were no significant differences in either baseline ST or ST at any subsequent visit.

Conclusions: Fractionated ablative CO2 laser treatment improved ST after 1 to 2 treatments. Patients with thicker scars demonstrated greater ST reduction than those with thinner scars. Ultrasound adequately assessed treatment response.
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http://dx.doi.org/10.1097/SAP.0000000000002517DOI Listing
March 2021

ASO Author Reflection: Trends and Impact of Adjuvant Chemotherapy in Resected Gallbladder Cancer: Going Beyond Trial Data.

Ann Surg Oncol 2021 Mar 5;28(3):1481-1482. Epub 2020 Aug 5.

Department of Surgery, William Beaumont Army Medical Center, 5005 N. Piedras St., El Paso, TX, 79920, USA.

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http://dx.doi.org/10.1245/s10434-020-08979-5DOI Listing
March 2021

Adjuvant Chemotherapy in Resectable Gallbladder Cancer is Underutilized Despite Benefits in Node-Positive Patients.

Ann Surg Oncol 2021 Mar 4;28(3):1466-1480. Epub 2020 Aug 4.

Department of Surgery, William Beaumont Army Medical Center, El Paso, TX, USA.

Background: Adjuvant chemotherapy (AC) is recommended following surgical resection of gallbladder cancer regardless of stage. However, stage-specific benefits of AC in gallbladder cancer are unclear.

Patients And Methods: Patients with resected pathologic stage I-III gallbladder cancer were identified using the 2006-2015 National Cancer Database. Utilization trends, predictors of use, and impact of AC on overall survival (OS) were determined.

Results: A total of 5656 patients were included. Use of AC increased from 9.9% in 2006 to 24.2% in 2015 (OR 2.91; 95% CI 2.06-4.09; p < 0.001). However, only 17.5% of patients overall and only 32.4% of node-positive (stage IIIb) patients received AC. Patients receiving AC were younger and had fewer comorbidities, shorter hospitalizations, more advanced disease, and more margin-positive resections (all p < 0.01). Higher pathologic T stage and positive nodal status represented the greatest independent predictors of receipt of AC. While AC demonstrated no OS advantage for stage I patients (p = 0.83), AC was associated with improved OS among stage II patients (p = 0.003), though this impact was not independently associated with improved OS on multivariable analysis. AC was independently associated with improved OS among stage IIIb patients, with a 30% reduction in risk of death (HR 0.70; 95% CI 0.58-0.83; p < 0.001). Younger age, fewer comorbidities, and shorter hospitalization all predicted receipt of AC among stage IIIb patients (all p < 0.05).

Conclusions: Systemic therapy remains underprescribed, in particular among patients that would seem to benefit most. Adjuvant chemotherapy likely improves survival in node-positive gallbladder cancer, but its utility in the treatment of node-negative disease has not been demonstrated.
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http://dx.doi.org/10.1245/s10434-020-08973-xDOI Listing
March 2021

Anti-human Leukocyte Antigen Immune Sensitization Effects of Cryopreserved Allograft and Blood Transfusion.

J Burn Care Res 2020 11;41(6):1216-1223

Department of Surgery, Brooke Army Medical Center, Ft. Sam Houston, Texas.

Vascularized composite allotransplantation (VCA) is the most advanced reconstructive technique available to patients who suffer devastating burns to the limbs or face. However, VCA requires donor-recipient matching. Burn patients have been reported to experience sensitization, or the development of anti-human leukocyte antigen antibodies, during resuscitation and wound coverage, potentially precluding them from future VCA. This study sought to investigate the contributions of both blood and allograft to sensitization in burn patients. Four groups were compared: burn patients who received blood products and allograft (group 1), burn patients who received blood products only (group 2), trauma patients who received blood products only (group 3), and healthy volunteer controls (group 4). The average calculated panel-reactive antibody (indicating sensitization) was higher in group 1 compared to group 4 (P = .035). Additionally, the incidence of severe sensitization was higher in group 1 relative to the other groups (P = .049). When comparing groups of patients who had no sensitization, mild sensitization, moderate sensitization, and severe sensitization, there were no significant differences in age, sex, blood products received, total body surface area burned, or allograft used between groups, though severely sensitized patients tended to have greater total body surface area involvement and received more units of packed red blood cells and allograft (P = .079, P = .196, and P = .072, respectively). We therefore conclude that while burn patients who received allograft and blood demonstrated a higher incidence of anti-human leukocyte antigen sensitization relative to healthy controls, this difference cannot solely be attributed to either allograft use or transfusion.
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http://dx.doi.org/10.1093/jbcr/iraa070DOI Listing
November 2020

Chemoprevention in familial adenomatous polyposis: past, present and future.

Fam Cancer 2021 01 8;20(1):23-33. Epub 2020 Jun 8.

Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, OH, USA.

Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome characterized by colorectal adenomas and a near 100% lifetime risk of colorectal cancer (CRC). Prophylactic colectomy, usually by age 40, is the gold-standard therapy to mitigate this risk. However, colectomy is associated with morbidity and fails to prevent extra-colonic disease manifestations, including gastric polyposis, duodenal polyposis and cancer, thyroid cancer, and desmoid disease. Substantial research has investigated chemoprevention medications in an aim to prevent disease progression, postponing the need for colectomy and temporizing the development of extracolonic disease. An ideal chemoprevention agent should have a biologically plausible mechanism of action, be safe and easily tolerated over a prolonged treatment period, and produce a durable and clinically meaningful effect. To date, no chemoprevention agent tested has fulfilled these criteria. New agents targeting novel pathways in FAP are needed. Substantial preclinical literature exists linking the molecular target of rapamycin (mTOR) pathway to FAP. A single case report of rapamycin, an mTOR inhibitor, used as chemoprevention in FAP patients exists, but no formal clinical studies have been conducted. Here, we review the prior literature on chemoprevention in FAP, discuss the rationale for rapamycin in FAP, and outline a proposed clinical trial testing rapamycin as a chemoprevention agent in patients with FAP.
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http://dx.doi.org/10.1007/s10689-020-00189-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276278PMC
January 2021

Optimizing physician skill development for medical students: The four-part assessment.

Am J Surg 2017 May 5;213(5):906-909. Epub 2017 Apr 5.

Oregon Health & Science University, Department of Surgery, Division of Trauma, Critical Care & Acute Care Surgery, USA. Electronic address:

Background: Medical student performance has been poorly correlated with residency performance and warrants further investigation. We propose a novel surgical assessment tool to determine correlations with clinical aptitude.

Methods: Retrospective review of medical student assessments from 2013 to 2015. Faculty rating of student performance was evaluated by: 1) case presentation, 2) problem definition, 3) question response and 4) use of literature and correlated to final exam assessment. A Likert scale interrater reliability was evaluated.

Results: Sixty student presentations were scored (4.8 assessors/presentation). A student's case presentation, problem definition, and question response was correlated with performance (r = 0.49 to 0.61, p ≤ 0.003). Moderate correlations for either question response or use of literature was demonstrated (0.3 and 0.26, p < 0.05).

Conclusion: Our four-part assessment tool identified correlations with course and examination grades for medical students. As surgical education evolves, validated performance and reliable testing measures are required.
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http://dx.doi.org/10.1016/j.amjsurg.2017.03.026DOI Listing
May 2017

Early analysis of laparoscopic common bile duct exploration simulation.

Am J Surg 2017 May 23;213(5):888-894. Epub 2017 Mar 23.

Oregon Health & Science University, Department of Surgery, Portland, OR, USA.

Background: We developed a laparoscopic common bile duct exploration (LCBDE) simulation course for resident surgeons (RS) and practicing surgeons (PS). We hypothesized that course completion would provide LCBDE procedural skills and increase procedure utilization.

Methods: RS and PS were prospectively enrolled. Pre- and post-course ability were assessed with written examinations and LCBDE simulations. PS completed pre-course, post-course, and 1-year follow-up surveys (5-point Likert-type scale).

Results: 17 RS and 8 PS were enrolled. Median written test scores improved (70.0%-80.0%, p < 0.001) and median LCBDE simulation times (seconds) improved (585-314, p = 0.001) among all participants. Comparing RS and PS, median written assessment scores pre-course (70% vs 72.5%, p = 0.953) and post-course (77.5% vs 80.0%, p = 0.198) were not significantly different. Simulation completion times (seconds) improved similarly from pre-course (608.0 vs 521.5, p = 0.885) to post-course (314.0 vs 373.0, p = 0.287) between groups. PS comfort with LCBDE improved (2-4, p = 0.03). All PS reported LCBDE utilization 1 year post-course.

Conclusions: The LCBDE course is appropriate for RS and PS. PS also reported increased comfort with LCBDE and procedure utilization.
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http://dx.doi.org/10.1016/j.amjsurg.2017.03.011DOI Listing
May 2017

Damage control laparotomy utilization rates are highly variable among Level I trauma centers: Pragmatic, Randomized Optimal Platelet and Plasma Ratios findings.

J Trauma Acute Care Surg 2017 03;82(3):481-488

From the Oregon Health Science University, Portland, Oregon (J. J. W. J. N., K. H., J. D. Y., C. R. N., P. M. K. B., H. S., P. S., K. J. B., M. Sie, division, department. Etc, University of Texas Health Science Center at Houston, Houston, Texas (B. C. T., B. A. C., J. B. H.), University of Washington, Seattle, Washington (G. v. B., E. M. B.), and University of Arizona, Tucson, Arizona (T. S. O.).

Background: Damage control laparotomy (DCL) is intended to limit deleterious effects from trauma-induced coagulopathy. DCL has been associated with mortality reduction, but may increase complications including sepsis, abscess, respiratory failure, hernia, and gastrointestinal fistula. We hypothesized that (1) DCL incidence would vary between institutions; (2) mortality rates would vary with DCL rates; (3) standard DCL criteria of pH, international normalized ratio, temperature and major intra-abdominal vascular injury would not adequately capture all patients.

Methods: Trauma patients at 12 Level 1 North American trauma centers were randomized based on transfusion ratios as described in the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. We analyzed outcomes after emergent laparotomy using a mixed-effects logistic model comparing DCL versus definitive surgical management with random effect for study site. Primary outcomes were 24-hour and 30-day mortality.

Results: Three hundred twenty-nine patients underwent emergent laparotomy: 213 (65%) DCL and 116 (35%) definitive surgical management. DCL rates varied between institutions (33-83%), (p = 0.002). Median Injury Severity Score (ISS) was higher in the DCL group, 29 (interquartile range, 13-34) versus 21 (interquartile range, 22-41) (p < 0.001). Twenty-four-hour mortality was 19% with DCL versus 4% (p < 0.001); 30-day mortality was 28% with DCL versus 19% (p < 0.001). In a mixed-effects model, ISS and major intra-abdominal vascular injury were correlates of DCL (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02-1.07 and OR, 2.7; 95% CI, 1.4-5.2). DCL was not associated with 30-day mortality (OR, 2.33; 95% CI, 0.97-5.60). Correlates included ISS (OR, 1.06; 95% CI, 1.02-1.09), PRBCs in 24 hours (OR, 1.10; 95% CI, 1.03-1.18), and age (OR, 1.04; 95% CI, 1.01-1.06). No significant mortality difference was detected between institutions (p = 0.63). Sepsis and VAP occurred more frequently with DCL (p < 0.05). Eighty percent (135/213) of DCL patients met standard criteria.

Conclusion: Although DCL utilization varied significantly between institutions, there was no significant mortality difference between centers. This finding suggests tempering DCL use may not decrease mortality, but could decrease related complications.

Level Of Evidence: Therapeutic study, level III.
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http://dx.doi.org/10.1097/TA.0000000000001357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325087PMC
March 2017

Performance improvement and patient safety program-guided quality improvement initiatives can significantly reduce computed tomography imaging in pediatric trauma patients.

J Trauma Acute Care Surg 2016 08;81(2):278-84

From the Division of Trauma, Critical Care, and Acute Care Surgery, Department of Surgery (C.R.C., J.D.Y., L.E.E., P.E.B., P.M.K.B., M.A.S., J.M.W.), Oregon Health & Science University, Portland, Oregon; Division of Pediatric Surgery, Department of Surgery (K.S.A., M.A.J.), Oregon Health & Science University, Portland, Oregon; Doernbecher Children's Hospital, Randall Children's Hospital (M.A.J.), Oregon Health & Science University, Portland, Oregon.

Background: Morbidity and mortality of cervical spine (C-spine) injury in pediatric trauma patients are high, necessitating quick and accurate diagnosis. Best practices emphasize minimizing radiation exposure through decreased reliance on computed tomography (CT), instead using clinical assessment, physical examination, and alternate imaging techniques. We implemented an institutional performance improvement and patient safety (PIPS) program initiative for C-spine clearance in 2010 because of high rates of CT scans among pediatric trauma patients.

Methods: A retrospective review of pediatric trauma patients, aged 0 years to 14 years, in the pre- and post-PIPS implementation periods was conducted. Rates of C-spine CT, overall CT, other imaging modalities, radiation exposure, patient characteristics, and injury severity were compared, and compliance with PIPS protocol was reviewed.

Results: Patient characteristics and injury severity were similar before and after PIPS implementation. C-spine CT rates decreased significantly between groups (30% vs. 13%, p < 0.001), whereas C-spine plain x-ray rates increased significantly (7% vs. 25%, p < 0.001). There was no difference in C-spine magnetic resonance imaging between groups (12% vs. 10%, p = 0.11). In 2007, 71% of patients received a CT scan for any reason. However, the overall CT rate decreased significantly between groups (60% vs. 45%, p < 0.001). There was an estimated 22% decrease in lifetime attributable risk (LAR) for any cancer due to ionizing imaging exposure in males and 38% decrease in females between the pre- and post-PIPS groups. There was a 54% decrease in LAR for thyroid cancer in males and females between groups; 2014 compliance with the protocol was excellent (82-90% per quarter).

Conclusions: Performance improvement and patient safety program-generated protocol can significantly decrease ionizing radiation exposure. We demonstrate that a simple protocol focused on C-spine imaging has high compliance, decreased C-spine CT scans, and decreased LAR for thyroid cancer. A secondary benefit is a reduction in total CT imaging, with an associated decrease in LAR for all cancers.

Level Of Evidence: Therapeutic study, level IV; diagnostic study, level III.
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http://dx.doi.org/10.1097/TA.0000000000001071DOI Listing
August 2016

A night float week in a surgical clerkship improves student team cohesion.

Am J Surg 2016 May 23;211(5):913-8. Epub 2016 Feb 23.

Division of Trauma, Critical Care, and Acute Care Surgery, Department of Surgery, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Mail Code: L611, Portland, OR 97239, USA.

Background: We hypothesize that night float rotations in the third-year surgical clerkship improve student learning and perceptions of team cohesion.

Methods: A 1-week night float (NF) system was implemented during the 2013 to 2014 academic year for students. Each student completed 1 week of NF with the Trauma/Emergency General Surgery service. The Perceived Cohesion Scale survey was prospectively administered and National Board of Medical Examiners academic performance retrospectively reviewed.

Results: We surveyed 70 medical students, 37 traditional call and 33 NF students, with 91% response rate. Perception of team cohesion increased significantly, without perceived loss of educational benefit. Examination scores increased significantly comparing pre- and postintervention groups, with this trend continuing in the following academic year.

Conclusions: A week-long student NF experience significantly improved perception of team cohesion and standardized examination results. A dedicated period of NF during the surgical clerkship may improve its overall educational value.
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http://dx.doi.org/10.1016/j.amjsurg.2016.01.011DOI Listing
May 2016

The found down patient: A Western Trauma Association multicenter study.

J Trauma Acute Care Surg 2015 Dec;79(6):976-82; discussion 982

From the Department of Surgery (B.M.H., L.Z.K., A.S.C., M.F.N., R.A.C., M.J.C.), San Francisco General Hospital, University of California San Francisco, San Francisco; and Division of Trauma Surgery and Surgical Critical Care (K.C., J.R.H.), University of Southern California, Los Angeles, California; Department of Surgery (C.C.B., A.E.W.), Denver Health Medical Center, University of Colorado, Denver, Colorado; Acute Care Surgery Specialty (M.M.C., G.R.M.), Medical Center of Plano, Plano; and Methodist Dallas Medical Center (J.R.W., M.S.T.), Dallas, Texas; Department of Surgery (D.J.C., J.A.D.), University of South Florida College of Medicine, Tampa, Florida; Duke University Medical Center (C.J.V., P.M.K.B.), Durham, North Carolina.

Background: Unconscious patients who present after being "found down" represent a unique triage challenge. These patients are selected for either trauma or medical evaluation based on limited information and have been shown in a single-center study to have significant occult injuries and/or missed medical diagnoses. We sought to further characterize this population in a multicenter study and to identify predictors of mistriage.

Methods: The Western Trauma Association Multicenter Trials Committee conducted a retrospective study of patients categorized as found down by emergency department triage diagnosis at seven major trauma centers. Demographic, clinical, and outcome data were collected. Mistriage was defined as patients being admitted to a non-triage-activated service. Logistic regression was used to assess predictors of specified outcomes.

Results: Of 661 patients, 33% were triaged to trauma evaluations, and 67% were triaged to medical evaluations; 56% of all patients had traumatic injuries. Trauma-triaged patients had significantly higher rates of combined injury and a medical diagnosis and underwent more computed tomographic imaging; they had lower rates of intoxication and homelessness. Among the 432 admitted patients, 17% of them were initially mistriaged. Even among properly triaged patients, 23% required cross-consultation from the non-triage-activated service after admission. Age was an independent predictor of mistriage, with a doubling of the rate for groups older than 70 years. Combined medical diagnosis and injury was also predictive of mistriage. Mistriaged patients had a trend toward increased late-identified injuries, but mistriage was not associated with increased length of stay or mortality.

Conclusion: Patients who are found down experience significant rates of mistriage and triage discordance requiring cross-consultation. Although the majority of found down patients are triaged to nontrauma evaluation, more than half have traumatic injuries. Characteristics associated with increased rates of mistriage, including advanced age, may be used to improve resource use and minimize missed injury in this vulnerable patient population.

Level Of Evidence: Epidemiologic study, level III.
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http://dx.doi.org/10.1097/TA.0000000000000862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684961PMC
December 2015
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