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1.
J Surg Educ ; 78(6): 1878-1884, 2021.
Article in English | MEDLINE | ID: mdl-34266790

ABSTRACT

OBJECTIVE: The Public Service Loan Forgiveness (PSLF) program is an option to trainees to help alleviate federal education debt. The prevalence of PSLF utilization and how this may impact career decisions of trainees is unknown. The purpose of this study was to understand the prevalence, impact, and understanding of PSLF participation on trainees. DESIGN: IRB-approved anonymous survey asking study subjects to report demographics, financial status, and reliance on PSLF. In addition, study subjects were asked to report their participation in PSLF, the possible impact of PSLF participation on career decisions, and to identify the qualifications needed to complete PSLF. SETTING: Online anonymous survey. PARTICIPANTS: The survey was offered to all physician trainees in all specialties at the University of Texas, Southwestern, University of Wisconsin, Madison, and University of Michigan, Ann Arbor. RESULTS: There were 934 respondents, yielding a 37.6% response rate. A total of 416/934 (44.5%) respondents were actively or planning on participating in the PSLF program with 175/934 (18.7%) belonging to a surgical specialty. Those belonging to a surgical specialty were more likely to be PSLF participants compared to medical specialties (53.1% versus 42.6%, p = 0.01). For those participating in PSLF, 82/416 (19.7%) stated this participation impacted career decisions. A total of 275/934 (29.4%) respondents obtained and 437/934 (46.8%) wanted to receive formal training/lectures in regards to the PSLF program. Of those actively or planning on participating in the PSLF program, only 58/416 (13.9%) were able to correctly identify all of the qualifications/criteria to complete the program. CONCLUSIONS: A large proportion of trainees rely on the PSLF program for education loan forgiveness with approximately 20% reporting participation impacted career decisions. Additionally, the majority may not fully understand PSLF criteria. Programs should strongly consider providing a formal education regarding PSLF to their trainees.


Subject(s)
Education, Medical , Forgiveness , Internship and Residency , Career Choice , Humans , Surveys and Questionnaires , Training Support
2.
Ann Surg ; 273(6): e255-e261, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33979313

ABSTRACT

OBJECTIVE: The purpose of this study was to measure the efficacy of a novel faculty and resident educational bundle focused on development of faculty-resident behaviors and entrustment in the operating room. SUMMARY BACKGROUND DATA: As surgical training environments are orienting to entrustable professional activities (EPAs), successful transitions to this model will require significant faculty and resident development. Identifying an effective educational initiative which prepares faculty and residents for optimizing assessment, teaching, learning, and interacting in this model is critical. METHODS: From September 2015 to June 2017, an experimental study was conducted in the Department of Surgery at the University of Michigan Health System (UMHS). Case observations took place across general, plastic, thoracic, and vascular surgical specialties. A total of 117 operating room observations were conducted during Phase I of the study and 108 operating room observations were conducted during Phase II following the educational intervention. Entrustment behaviors were rated for 56 faculty and 73 resident participants using OpTrust, a validated intraoperative entrustment instrument. RESULTS: Multiple regression analysis showed a significant increase in faculty entrustment (Phase I = 2.32 vs Phase II = 2.56, P < 0.027) and resident entrustability (Phase I = 2.16 vs Phase II = 2.40, P < 0.029) scores following exposure to the educational intervention. CONCLUSIONS: Our study shows improved intraoperative entrustment following implementation of faculty and resident development, indicating the efficacy of this innovative educational bundle. This represents a crucial component in the implementation of a competency-based assessment framework like EPAs.


Subject(s)
Faculty, Medical , Internship and Residency/methods , Interprofessional Relations , Specialties, Surgical/education , Trust , Intraoperative Period
3.
J Vasc Surg Venous Lymphat Disord ; 9(1): 187-192, 2021 01.
Article in English | MEDLINE | ID: mdl-32446005

ABSTRACT

BACKGROUND: Popliteal vein aneurysms are a rare vascular anomaly first reported in the 1980s. Degeneration of elastic fibers and smooth muscle cell reduction, possibly secondary to inflammation, are implicated as integral steps in the development of these aneurysms. Given the rarity of this clinical entity, significant controversy exists regarding ideal treatment strategies, including the role of observation, medical management with anticoagulation, and surgical intervention. Retrospective reviews have demonstrated a failure rate of >40% with anticoagulation alone, with patients often presenting with pulmonary embolism. This has prompted our institutional preference for surgical management once the aneurysm is identified. Surgical management involves tangential repair with lateral venorrhaphy most commonly, followed in prevalence by aneurysm resection and end-to-end anastomosis either primarily or with vein interposition. Herein, we report our results with venous plications, through both closed and open techniques. METHODS: We performed a retrospective review of prospectively collected data for 10 patients undergoing popliteal vein plication for treatment of popliteal vein aneurysms. Patient-level characteristics and operative details were examined from periprocedural and follow-up records. RESULTS: We identified 10 patients undergoing popliteal vein plication, including 9 closed plications and 1 open plication. The average aneurysm size at presentation was 2.35 ± 0.69 cm for closed plication and 4.74 cm for the one open plication. After treatment, the average popliteal vein size was significantly reduced to 1.12 ± 0.45 cm for the closed plications (P < .001 from preprocedural size) and 1.13 cm for the open plication with 100% primary patency. Average follow-up for patients treated with closed plication was 35.0 ± 25.2 months, during which seven (78%) patients had a stable, normal popliteal vein size. One patient with recurrence was diagnosed with Klippel-Trénaunay syndrome. The other had degeneration of the popliteal vein cranial to the previous repair at 39 months after the original operation that required additional plication. The open plication patient experienced a hematoma requiring washout and resulting in a transient peroneal mononeuropathy. There was one case of cellulitis after closed plication but no hematomas within this group. CONCLUSIONS: Closed plication demonstrated favorable primary patency rates and low recurrence rates, avoiding technical issues or need for early institution of systemic anticoagulation associated with tangential repair and venorrhaphy or resection methods. Closed plication represents an attractive option in patients without luminal thrombus to limit the risk of these postoperative complications and obviates the need for bypass conduit and postoperative anticoagulation.


Subject(s)
Aneurysm/surgery , Popliteal Vein/surgery , Suture Techniques , Vascular Surgical Procedures , Adolescent , Adult , Aged , Aneurysm/diagnostic imaging , Aneurysm/physiopathology , Female , Humans , Male , Middle Aged , Popliteal Vein/diagnostic imaging , Popliteal Vein/physiopathology , Postoperative Complications/etiology , Recurrence , Registries , Retrospective Studies , Suture Techniques/adverse effects , Time Factors , Treatment Outcome , Vascular Patency , Vascular Surgical Procedures/adverse effects
4.
Am J Surg ; 219(4): 608-612, 2020 04.
Article in English | MEDLINE | ID: mdl-31221455

ABSTRACT

BACKGROUND: Longitudinal contact between faculty and residents facilitates greater faculty entrustment. The purpose of this study is to assess the relationship between faculty familiarity with residents and faculty entrustment. MATERIALS AND METHODS: Researchers observed and rated entrustment behaviors using OpTrust, September 2015-June 2017 at Michigan Medicine. Faculty familiarity with resident was measured on a 1-4 scale (1 = not familiar, 4 = extremely familiar). ANOVA and Sidak adjusted multiple comparisons were used to assess the relationship between faculty familiarity and faculty entrustment. RESULTS: 56 faculty and 73 residents were observed across 225 surgical cases. Faculty entrustment scores increased to 2.48 when resident familiarity was reported as "slightly familiar". Faculty entrustment scores for "moderately familiar" increased to 2.57. Faculty entrustment scores for "extremely familiar" increased to 2.84. CONCLUSIONS: We found a positive relationship between faculty familiarity and entrustment. These findings support greater continuity in faculty/resident relationships. Longitudinal contact allows learners to be granted progressive entrustment. SUMMARY: This study demonstrates a positive relationship between faculty familiarity with residents and an increase in intraoperative entrustment. These findings support greater continuity in faculty/resident relationships.


Subject(s)
Faculty, Medical , Internship and Residency , Interpersonal Relations , Professional Autonomy , Specialties, Surgical/education , Clinical Competence , Female , Humans , Male , Michigan
5.
Ann Vasc Surg ; 64: 285-291, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31200040

ABSTRACT

BACKGROUND: Mentoring relationships have been encouraged for medical students interested in surgical specialties. We investigated the role of mentoring relationships of integrated vascular surgery residents, while in medical school. We hypothesized that mentoring relationships between medical students and vascular surgeons would have a positive effect on match outcome in the integrated vascular surgery residency match. METHODS: We used an online survey that respondents completed on a smartphone, tablet, or computer. This was created with Qualtrics Software. The survey was circulated to all North American Integrated Vascular Surgery residents, with the support of the Association of Program Directors in Vascular Surgery Recruitment Committee and the Society for Vascular Surgery Resident/Student Outreach Committee. Questions were posed either as Likert Scale or as multiple choice. Data were analyzed in Stata. RESULTS: Response rate (67 total responses of 241 polled residents) was 28%. Earlier postgraduate year residents were more likely to have had vascular surgeon mentors (P = 0.033). There was no association between having a mentor and match rank; however, those with vascular surgeon mentors matched higher on their rank list (P = 0.022). 50% of respondents indicated that mentoring was influential in the choice of integrated residency. Respondents with nonvascular surgeon mentors were more likely to answer negatively regarding their mentor's knowledge about other integrated (P < 0.0001) and traditional programs (P < 0.0001) while residents with a vascular surgeon mentor were more likely to respond positively to this question (P < 0.0001). Regarding the effectiveness of mentorship, 81% indicated their mentor was accessible, 92% responded that their mentor demonstrated professional integrity, and 76% responded that their mentor prioritized their success. CONCLUSIONS: Integrated vascular surgery residents were generally positive about their medical school mentors. Our data indicate that surgical mentorship in medical school is effective, both in influencing medical students to choose the vascular surgery specialty and in improving match rank-vascular surgeons were more knowledgeable and mentees with vascular surgeon mentors tended to be more successful in the match.


Subject(s)
Attitude of Health Personnel , Career Choice , Education, Medical , Internship and Residency , Mentors , Students, Medical/psychology , Surgeons/psychology , Vascular Surgical Procedures , Adult , Female , Humans , Male , Surgeons/education , Surveys and Questionnaires , Young Adult
6.
J Vasc Surg ; 71(4): 1371-1377, 2020 04.
Article in English | MEDLINE | ID: mdl-31564586

ABSTRACT

OBJECTIVE: In the past decade, treatment of abdominal aortic aneurysm (AAA) has dramatically shifted from open repair to an endovascular approach. The decreasing number of open AAA repairs (OAR) has raised concerns regarding future vascular surgeons' competence to perform this complex and high-risk procedure. Prior work has documented decreasing open aortic volume among surgical residents. However, these studies report average national case volume with a limited understanding of the variation in OAR exposure among training programs and trainees. We sought to evaluate the current open AAA repair trends among individual accredited vascular surgery training programs and vascular surgery residents to better evaluate trainees' exposure to OAR. METHODS: We identified elderly Medicare beneficiaries undergoing OAR and endovascular aneurysm repair (EVAR) between 2010 and 2014. Accredited vascular surgery training program hospitals were identified. OAR and EVAR volume was aggregated at the program level and the number of senior vascular surgery trainees per year at each program was captured. The training program all-payer total AAA repair volume was calculated based on the national proportion of patients undergoing AAA covered by Medicare in the Vascular Quality Initiative. Temporal trends in program and vascular surgery trainee OAR and EVAR volume were calculated. RESULTS: A total of 119,408 (77%) EVAR and 35,042 (23%) were identified in the Medicare database between 2010 and 2014. Of these, 21% were performed among the 111 training programs, including 22,227 (73%) EVAR and 8416 (27%) OAR. The total OAR volume among training programs decreased by 38% during the study period, from a median of 29.1 to 18.2 OAR. In 2014, 25% of programs performed fewer than 10 OARs annually. Among senior vascular surgery trainees, the median number of OAR decreased from 10.0 in 2010 to 6.4 in 2014 and approximately one-half of senior trainees had exposure to fewer than five OAR in 2014. CONCLUSIONS: Exposure to OAR among vascular surgery training programs has dramatically decreased, with nearly one-half of senior trainees performing fewer than five OAR in 2014. The variable and diminishing OAR exposure among vascular surgery training program highlights growing concerns surrounding competence in complex open repairs and suggest that only a small proportion of current trainees have ample opportunity to develop confidence and proficiency in this high-risk operation.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Vascular Surgical Procedures/education , Vascular Surgical Procedures/methods , Adult , Education, Medical, Graduate , Endovascular Procedures/education , Endovascular Procedures/methods , Female , Humans , Male , Medicare , United States , Workload
7.
J Invest Dermatol ; 139(12): 2528-2537.e2, 2019 12.
Article in English | MEDLINE | ID: mdl-31207226

ABSTRACT

Control of inflammation is critical for the treatment of nonhealing wounds, but a delicate balance exists between early inflammation that is essential for normal tissue repair and the pathologic inflammation that can occur later in the repair process. This necessitates the development of novel therapies that can target inflammation at the appropriate time during repair. Here, we found that SIRT3 is essential for normal healing and regulates inflammation in wound macrophages after injury. Under prediabetic conditions, SIRT3 was decreased in wound macrophages and resulted in dysregulated inflammation. In addition, we found that FABP4 regulates SIRT3 in human blood monocytes, and inhibition of FABP4 in wound macrophages decreases inflammatory cytokine expression, making FABP4 a viable target for the regulation of excess inflammation and wound repair in diabetes. Using a series of ex vivo and in vivo studies with genetically engineered mouse models and diabetic human monocytes, we showed that FABP4 expression is epigenetically upregulated in diabetic wound macrophages and, in turn, diminishes SIRT3 expression, thereby promoting inflammation. These findings have significant implications for controlling inflammation and promoting tissue repair in diabetic wounds.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Sirtuin 3/pharmacology , Wound Healing/drug effects , Animals , Cells, Cultured , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Macrophages/metabolism , Macrophages/pathology , Mice , Mice, Inbred C57BL
8.
J Immunol ; 202(6): 1777-1785, 2019 03 15.
Article in English | MEDLINE | ID: mdl-30710046

ABSTRACT

Myeloid cells are critical for orchestrating regulated inflammation during wound healing. TLRs, particularly TLR4, and its downstream-signaling MyD88 pathway play an important role in regulating myeloid-mediated inflammation. Because an initial inflammatory phase is vital for tissue repair, we investigated the role of TLR4-regulated, myeloid-mediated inflammation in wound healing. In a cutaneous tissue injury murine model, we found that TLR4 expression is dynamic in wound myeloid cells during the course of normal wound healing. We identified that changes in myeloid TLR4 during tissue repair correlated with increased expression of the histone methyltransferase, mixed-lineage leukemia 1 (MLL1), which specifically trimethylates the histone 3 lysine 4 (H3K4me3) position of the TLR4 promoter. Furthermore, we used a myeloid-specific Mll1 knockout (Mll1f/fLyz2Cre+ ) to determine MLL1 drives Tlr4 expression during wound healing. To understand the critical role of myeloid-specific TLR4 signaling, we used mice deficient in Tlr4 (Tlr4-/- ), Myd88 (Myd88 -/-), and myeloid-specific Tlr4 (Tlr4f/fLyz2Cre+) to demonstrate delayed wound healing at early time points postinjury. Furthermore, in vivo wound myeloid cells isolated from Tlr4-/- and Myd88 -/- wounds demonstrated decreased inflammatory cytokine production. Importantly, adoptive transfer of monocyte/macrophages from wild-type mice trafficked to wounds with restoration of normal healing and myeloid cell function in Tlr4-deficient mice. These results define a role for myeloid-specific, MyD88-dependent TLR4 signaling in the inflammatory response following cutaneous tissue injury and suggest that MLL1 regulates TLR4 expression in wound myeloid cells.


Subject(s)
Histone-Lysine N-Methyltransferase/metabolism , Histones/metabolism , Myeloid-Lymphoid Leukemia Protein/metabolism , Skin/metabolism , Toll-Like Receptor 4/biosynthesis , Wound Healing/physiology , Animals , DNA Methylation/physiology , Female , Gene Expression Regulation/physiology , Inflammation/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Myeloid Cells/metabolism , Myeloid Differentiation Factor 88/metabolism , Signal Transduction/physiology , Skin/injuries
9.
Ann Vasc Surg ; 58: 309-316, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30742889

ABSTRACT

BACKGROUND: Free digital platforms are smartphone-compatible and permit self-directed curriculum development based on learners' interests and educational needs. We developed a free mobile vascular surgery handbook initiated, authored, and edited by surgical house officers and surveyed on the content and users. METHODS: Using a free digital platform, house officers developed a vascular surgery handbook. Initiated by a single user for conference preparation and clinical care, the use expanded through sharing among residents. The handbook was then deployed at a second medical center, with free access granted to users after completing a survey. Handbook and content use were evaluated based on user ratings ≥4 on a Likert scale from 1 to 5, where 1 = "strongly disagree" and 5 = "completely agree." Domains assessed included handbook ease of use, content, and relevance to a variety of learning environments and goals (e.g., preparation for the operating room, rounds, clinic, teaching conferences, and examinations). Analytic methods included qualitative analysis, graphical evaluation, and categorical tests. RESULTS: The handbook is organized into sections, with each consisting of multiple pages and/or posts related to the section topic. Sections with the most content included lower extremity arterial disease, endovascular aneurysm repair/thoracic endovascular aortic repair, venous disease, anticoagulation, and anatomy/exposures. Fifty-four users participated in the evaluation phase, including different types of surgical residents (35%), medical students (30%), and anesthesia residents (22%). Sixty-nine percent of participants were in their position for <2 years. The average age was 29.1 years, and 57% were women. Preferred learning styles among users at the time of enrollment primarily included question banks (52%), followed by slide-based lectures (15%) and "chalk talk" lectures (13%). Of the users who participated in the presurvey, 43 users participated in the postsurvey with a general agreement on the handbook being an easy-to-use resource that was useful for gaining overall knowledge and contained accurate information. Users generally agreed they would recommend the handbook to a colleague. CONCLUSIONS: References customized to user needs can be developed through crowdsourcing and published with free digital resources. These approaches allow mobile access to useful information during conferences and clinical care. House officers' self-perceived educational needs can be targeted for tailored educational initiatives.


Subject(s)
Cell Phone , Computer-Assisted Instruction/instrumentation , Crowdsourcing , Education, Medical, Graduate/methods , Education, Medical, Undergraduate/methods , Internship and Residency , Mobile Applications , Students, Medical , Surgeons/education , Vascular Surgical Procedures/education , Adult , Attitude of Health Personnel , Curriculum , Female , Health Knowledge, Attitudes, Practice , Humans , Information Dissemination , Male , Students, Medical/psychology , Surgeons/psychology , Writing , Young Adult
10.
Ann Surg ; 270(6): 1058-1064, 2019 12.
Article in English | MEDLINE | ID: mdl-29794849

ABSTRACT

OBJECTIVE: To determine the association between intraoperative entrustment and personality alignment. SUMMARY BACKGROUND DATA: For surgical residents, achieving operative autonomy has become increasingly difficult. The impact of faculty-resident operative interactions in accomplishing this goal is not well understood. We hypothesized that if operative dyads (faculty and resident) had personality alignment or congruency, then resident entrustment in the operating room would increase. METHODS: We completed a retrospective analysis of 63 operations performed from September 2015 to August 2016. Operations were scored using OpTrust, a validated tool that assesses progressive entrustment of responsibility to surgical residents in the operating room. All dyads were classified as having congruent or incongruent personality alignment as measured by promotion or prevention orientation using the regulatory focus questionnaire. The association between personality congruence and OpTrust scores was identified using multivariable linear regression. RESULTS: A total of 35 congruent dyads and 28 incongruent dyads were identified. Congruent dyads had a higher percentage of "very difficult" cases (33.3 vs. 7.4%, P = 0.017), female residents (37.1 vs. 14.3%, P = 0.042) and faculty with fewer years of experience (10.4 vs. 14.8%, P = 0.028) than incongruent dyads. In addition to post-graduate year level, dyad congruency was independently associated with a 0.88 increase (95% CI [0.27-1.49], P = 0.006) in OpTrust scores (overall range 2-8), after adjusting for case difficulty, faculty experience, and post-graduate year. CONCLUSIONS: Congruent operative dyads are associated with increased operative entrustment as demonstrated by increased OpTrust scores. Developing awareness and strategies for addressing incongruence in personality in the operative dyad is needed.


Subject(s)
Clinical Competence , General Surgery/education , Internship and Residency , Personality , Professional Autonomy , Trust , Adult , Female , Humans , Interprofessional Relations , Male , Retrospective Studies
11.
Am J Surg ; 217(2): 276-280, 2019 02.
Article in English | MEDLINE | ID: mdl-30177241

ABSTRACT

BACKGROUND: Faculty entrustment decisions affect resident entrustability behaviors and surgical autonomy. The relationship between entrustability and autonomy is not well understood. This pilot study explores that relationship. METHODS: 108 case observations were completed. Entrustment behaviors were rated using OpTrust. Residents completed a Zwisch self-assessment to measure surgical autonomy. Resident perceived autonomy was collected for 67 cases used for this pilot study. RESULTS: Full entrustability was observed in 5 of the 108 observed cases. Residents in our study did not report full autonomy. Spearman's rank correlation coefficient identified that resident entrustability was positively correlated with perceived resident autonomy (ρ = 0.66, p < 0.05). Ordinal logistic regression assessed the relationship between resident entrustability and autonomy. The relationship persisted while controlling for PGY level, gender, and case complexity (OR = 8.42, SEM = 4.54, p < 0.000). CONCLUSIONS: Resident entrustability is positively associated with perceived autonomy, yet full entrustability is not translating to the perception of full autonomy for residents.


Subject(s)
Clinical Competence , Educational Measurement/methods , Faculty, Medical/standards , General Surgery/education , Internship and Residency/methods , Professional Autonomy , Self-Assessment , Adult , Decision Making , Female , Humans , Male , Pilot Projects , Retrospective Studies
12.
Surgery ; 164(3): 583-588, 2018 09.
Article in English | MEDLINE | ID: mdl-30041964

ABSTRACT

BACKGROUND: Optimizing intraoperative education is critical for development of autonomous residents. Faculty decisions concerning intraoperative entrustment determine the degree to which a resident gains intraoperative responsibility. Accordingly, residents exhibit entrustable behaviors that further faculty entrustment in the operating room. Little empiric evidence exists evaluating how the sex of a resident influences faculty-resident decisions of entrustment. Studies involving perception-based measurements of autonomy report inequities for women residents. We sought to assess faculty behaviors in entrustment in relation to resident sex using OpTrust, a third-party objective measurement tool. METHODS: From September 2015 to June 2017 at the University of Michigan, surgical cases were observed and entrustment behaviors were rated using OpTrust. Critical case sampling was used to generate variation in operation type, case difficulty, faculty-resident pairings, faculty experience, and the level of the resident's training. Independent sample t-tests were conducted to compare faculty entrustment scores, as well as resident entrustability scores. RESULTS: A total of 56 faculty and 73 residents were observed across 223 surgical cases from 4 surgical specialties: general, plastic, thoracic, and vascular. There was no difference in faculty entrustment or entrustability scores between women and men (2.54 vs 2.35, P = .117 and 2.32 vs 2.22, P = .393, respectively). CONCLUSION: Using OpTrust scores, we found that a resident's sex does not appear to influence faculty entrustment in the OR. Faculty entrustment scores for women and men residents are similar across cases. This observation suggests that during the intraoperative interaction, faculty are not extending entrustment or opportunities for autonomy differently to women or men. Future research is needed to identify and measure perioperative elements that inform resident autonomy, which may contribute to inequities for women residents.


Subject(s)
Attitude of Health Personnel , General Surgery/education , Internship and Residency , Professional Autonomy , Adult , Clinical Competence , Decision Making , Faculty, Medical , Female , Humans , Male , Middle Aged , Sex Factors
13.
Eur J Immunol ; 48(9): 1445-1455, 2018 09.
Article in English | MEDLINE | ID: mdl-29879295

ABSTRACT

Macrophages play a critical role in the establishment of a regulated inflammatory response following tissue injury. Following injury, CCR2+ monocytes are recruited from peripheral blood to wound tissue, and direct the initiation and resolution of inflammation that is essential for tissue repair. In pathologic states where chronic inflammation prevents healing, macrophages fail to transition to a reparative phenotype. Using a murine model of cutaneous wound healing, we found that CCR2-deficient mice (CCR2-/- ) demonstrate significantly impaired wound healing at all time points postinjury. Flow cytometry analysis of wounds from CCR2-/- and WT mice revealed a significant decrease in inflammatory, Ly6CHi recruited monocyte/macrophages in CCR2-/- wounds. We further show that wound macrophage inflammatory cytokine production is decreased in CCR2-/- wounds. Adoptive transfer of mT/mG monocyte/macrophages into CCR2+/+ and CCR2-/- mice demonstrated that labeled cells on days 2 and 4 traveled to wounds in both CCR2+/+ and CCR2-/- mice. Further, adoptive transfer of monocyte/macrophages from WT mice restored normal healing, likely through a restored inflammatory response in the CCR2-deficient mice. Taken together, these data suggest that CCR2 plays a critical role in the recruitment and inflammatory response following injury, and that wound repair may be therapeutically manipulated through modulation of CCR2.


Subject(s)
Macrophages/transplantation , Receptors, CCR2/genetics , Wound Healing/genetics , Wound Healing/physiology , Animals , Inflammation/immunology , Macrophages/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, CCR2/metabolism
14.
Arterioscler Thromb Vasc Biol ; 38(5): 1102-1114, 2018 05.
Article in English | MEDLINE | ID: mdl-29496661

ABSTRACT

OBJECTIVE: Wound monocyte-derived macrophage plasticity controls the initiation and resolution of inflammation that is critical for proper healing, however, in diabetes mellitus, the resolution of inflammation fails to occur. In diabetic wounds, the kinetics of blood monocyte recruitment and the mechanisms that control in vivo monocyte/macrophage differentiation remain unknown. APPROACH AND RESULTS: Here, we characterized the kinetics and function of Ly6CHi [Lin- (CD3-CD19-NK1.1-Ter-119-) Ly6G-CD11b+] and Ly6CLo [Lin- (CD3-CD19-NK1.1-Ter-119-) Ly6G-CD11b+] monocyte/macrophage subsets in normal and diabetic wounds. Using flow-sorted tdTomato-labeled Ly6CHi monocyte/macrophages, we show Ly6CHi cells transition to a Ly6CLo phenotype in normal wounds, whereas in diabetic wounds, there is a late, second influx of Ly6CHi cells that fail transition to Ly6CLo. The second wave of Ly6CHi cells in diabetic wounds corresponded to a spike in MCP-1 (monocyte chemoattractant protein-1) and selective administration of anti-MCP-1 reversed the second Ly6CHi influx and improved wound healing. To examine the in vivo phenotype of wound monocyte/macrophages, RNA-seq-based transcriptome profiling was performed on flow-sorted Ly6CHi [Lin-Ly6G-CD11b+] and Ly6CLo [Lin-Ly6G-CD11b+] cells from normal and diabetic wounds. Gene transcriptome profiling of diabetic wound Ly6CHi cells demonstrated differences in proinflammatory and profibrotic genes compared with controls. CONCLUSIONS: Collectively, these data identify kinetic and functional differences in diabetic wound monocyte/macrophages and demonstrate that selective targeting of CD11b+Ly6CHi monocyte/macrophages is a viable therapeutic strategy for inflammation in diabetic wounds.


Subject(s)
Antigens, Ly/metabolism , Diabetes Mellitus, Type 2/blood , Diabetic Angiopathies/blood , Inflammation/blood , Macrophages/metabolism , Monocytes/metabolism , Skin Ulcer/blood , Wound Healing , Animals , Cell Plasticity , Chemokine CCL2/metabolism , Chronic Disease , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/pathology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Angiopathies/genetics , Diabetic Angiopathies/pathology , Diabetic Angiopathies/physiopathology , Diet, High-Fat , Disease Models, Animal , Fibrosis , Inflammation/genetics , Inflammation/pathology , Inflammation/physiopathology , Inflammation Mediators/metabolism , Kinetics , Male , Mice, Inbred C57BL , Mice, Transgenic , Phenotype , Signal Transduction , Skin Ulcer/genetics , Skin Ulcer/pathology
15.
Curr Diab Rep ; 18(1): 2, 2018 01 23.
Article in English | MEDLINE | ID: mdl-29362914

ABSTRACT

PURPOSE OF REVIEW: Diabetic foot ulcerations (DFU) affect 25% of patients with diabetes mellitus during their lifetime and constitute a major health problem as they are often recalcitrant to healing due to a constellation of both intrinsic and extrinsic factors. The purpose of this review is to (1) detail the current mechanistic understanding of DFU formation and (2) highlight future therapeutic targets. RECENT FINDINGS: From a molecular perspective, DFUs exhibit a chronic inflammatory predisposition. In addition, increased local hypoxic conditions and impaired cellular responses to hypoxia are pathogenic factors that contribute to delayed wound healing. Finally, recent evidence suggests a role for epigenetic alterations, including microRNAs, in delayed DFU healing due to the complex interplay between genes and the environment. In this regard, notable progress has been made in the molecular and genetic understanding of DFU formation. However, further studies are needed to translate preclinical investigations into clinical therapies.


Subject(s)
Diabetic Foot/genetics , Diabetic Foot/physiopathology , Wound Healing/physiology , Diabetic Foot/therapy , Epigenesis, Genetic , Extracellular Matrix/physiology , Gene-Environment Interaction , Humans , Hypoxia/physiopathology , Inflammation/physiopathology , MicroRNAs/physiology , Peripheral Arterial Disease/physiopathology
16.
Ann Surg ; 267(1): 189-195, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29240607

ABSTRACT

OBJECTIVE: To understand statewide variation in preoperative cardiology consultation prior to major vascular surgery and to determine whether consultation was associated with differences in perioperative myocardial infarction (poMI). SUMMARY BACKGROUND DATA: Medical consultation prior to major vascular surgery is obtained to reduce perioperative risk. Despite perceived benefit of preoperative consultation, evidence is lacking specifically for major vascular surgery on the effect of preoperative cardiac consultation. METHODS: Patient and clinical data were obtained from a statewide vascular surgery registry between January 2012 and December 2014. Patients were risk stratified by revised cardiac risk index category and compared poMI between patients who did or did not receive a preoperative cardiology consultation. We then used logistic regression analysis to compare the rate of poMI across hospitals grouped into quartiles by rate of preoperative cardiology consultation. RESULTS: Our study population comprised 5191 patients undergoing open peripheral arterial bypass (n = 3037), open abdominal aortic aneurysm repair (n = 332), or endovascular aneurysm repair (n = 1822) at 29 hospitals. At the patient level, after risk-stratification by revised cardiac risk index category, there was no association between cardiac consultation and poMI. At the hospital level, preoperative cardiac consultation varied substantially between hospitals (6.9%-87.5%, P <0.001). High preoperative consulting hospitals (rate >66%) had a reduction in poMI (OR, 0.52; confidence interval: 0.28-0.98; P <0.05) compared with all other hospitals. These hospitals also had a statistically greater consultation rate with a variety of medical specialties. CONCLUSIONS: Preoperative cardiology consultation for vascular surgery varies greatly between institutions, and does not appear to impact poMI at the patient level. However, reduction of poMI was noted at the hospitals with the highest rate of preoperative cardiology consultation as well as a variety of medical services, suggesting that other hospital culture effects play a role.


Subject(s)
Cardiology/methods , Postoperative Complications/prevention & control , Preoperative Care/methods , Referral and Consultation , Vascular Surgical Procedures , Aged , Female , Humans , Male , Prospective Studies
17.
Am J Surg ; 216(1): 13-18, 2018 07.
Article in English | MEDLINE | ID: mdl-29128100

ABSTRACT

BACKGROUND: Changes in the surgical training landscape have sparked an interest in developing new educational models anchored on entrustment assessment. We sought to optimize the validated OpTrust entrustment assessment tool by comparing ratings from short-course video reviews to previously validated intraoperative assessments. METHODS: Entrustment assessment scores for video-based and 1-h (short-course) observations were compared to previously validated intraoperative assessment scores. Faculty and residents were surveyed for their perceptions related to operative observation. RESULTS: There was a strong association between entrustment scores when comparing in-person to video-based observations (R2 = 0.76-0.84, p < 0.01) as well as short-course to full-duration observations (R2 = 0.65-0.76, p < 0.01). The majority of faculty and residents (>97%) felt observation did not negatively impact operative experience. CONCLUSIONS: Assessment of entrustment behaviors using short-course video review provides a feasible approach to intraoperative assessment. This latest application of OpTrust allows for the tool to be incorporated into surgical training programs across a variety of environments.


Subject(s)
Clinical Competence , Education, Medical, Graduate/standards , Educational Measurement/methods , Faculty, Medical/standards , General Surgery/education , Internship and Residency/methods , Professional Autonomy , Feasibility Studies , Humans , Internship and Residency/standards , Intraoperative Period , Reproducibility of Results , Surveys and Questionnaires
18.
Diabetes ; 66(9): 2459-2471, 2017 09.
Article in English | MEDLINE | ID: mdl-28663191

ABSTRACT

Macrophages are critical for the initiation and resolution of the inflammatory phase of wound repair. In diabetes, macrophages display a prolonged inflammatory phenotype in late wound healing. Mixed-lineage leukemia-1 (MLL1) has been shown to direct gene expression by regulating nuclear factor-κB (NF-κB)-mediated inflammatory gene transcription. Thus, we hypothesized that MLL1 influences macrophage-mediated inflammation in wound repair. We used a myeloid-specific Mll1 knockout (Mll1f/fLyz2Cre+ ) to determine the function of MLL1 in wound healing. Mll1f/fLyz2Cre+ mice display delayed wound healing and decreased wound macrophage inflammatory cytokine production compared with control animals. Furthermore, wound macrophages from Mll1f/fLyz2Cre+ mice demonstrated decreased histone H3 lysine 4 trimethylation (H3K4me3) (activation mark) at NF-κB binding sites on inflammatory gene promoters. Of note, early wound macrophages from prediabetic mice displayed similarly decreased MLL1, H3K4me3 at inflammatory gene promoters, and inflammatory cytokines compared with controls. Late wound macrophages from prediabetic mice demonstrated an increase in MLL1, H3K4me3 at inflammatory gene promoters, and inflammatory cytokines. Prediabetic macrophages treated with an MLL1 inhibitor demonstrated reduced inflammation. Finally, monocytes from patients with type 2 diabetes had increased Mll1 compared with control subjects without diabetes. These results define an important role for MLL1 in regulating macrophage-mediated inflammation in wound repair and identify a potential target for the treatment of chronic inflammation in diabetic wounds.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Histone-Lysine N-Methyltransferase/metabolism , Macrophages/physiology , Myeloid-Lymphoid Leukemia Protein/metabolism , Obesity/metabolism , Wound Healing/physiology , Animals , Cells, Cultured , Diet, High-Fat , Histone-Lysine N-Methyltransferase/genetics , Humans , Inflammation/metabolism , Mice , Mice, Knockout , Myeloid-Lymphoid Leukemia Protein/genetics , Prediabetic State/metabolism
19.
Front Immunol ; 8: 635, 2017.
Article in English | MEDLINE | ID: mdl-28620387

ABSTRACT

Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (DNMAMLfloxedLyz2Cre+ ) demonstrated delayed early healing (days 1-3) and wound macrophages had decreased inflammatory gene expression. In our physiologic murine model of type 2 diabetes (T2D), Notch receptor expression was significantly increased in wound macrophages on day 6, following the initial inflammatory phase of wound healing, corresponding to increased inflammatory cytokine expression. This increase in Notch1 and Notch2 was also observed in human monocytes from patients with T2D. Further, in prediabetic mice with a genetic Notch signaling defect (DNMAMLfloxedLyz2Cre+ on a high-fat diet), improved wound healing was seen at late time points (days 6-7). These findings suggest that Notch is critical for the early inflammatory phase of wound healing and directs production of macrophage-dependent inflammatory mediators. These results identify that canonical Notch signaling is important in directing macrophage function in wound repair and define a translational target for the treatment of non-healing diabetic wounds.

20.
J Immunol ; 199(1): 17-24, 2017 07 01.
Article in English | MEDLINE | ID: mdl-28630109

ABSTRACT

The healing of cutaneous wounds is dependent on the progression through distinct, yet overlapping phases of wound healing, including hemostasis, inflammation, proliferation, and resolution/remodeling. The failure of these phases to occur in a timely, progressive fashion promotes pathologic wound healing. The macrophage (MΦ) has been demonstrated to play a critical role in the inflammatory phase of tissue repair, where its dynamic plasticity allows this cell to mediate both tissue-destructive and -reparative functions. The ability to understand and control both the initiation and the resolution of inflammation is critical for treating pathologic wound healing. There are now a host of studies demonstrating that metabolic and epigenetic regulation of gene transcription can influence MΦ plasticity in wounds. In this review, we highlight the molecular and epigenetic factors that influence MΦ polarization in both physiologic and pathologic wound healing, with particular attention to diabetic wounds.


Subject(s)
Diabetes Mellitus/immunology , Inflammation/immunology , Macrophages/immunology , Wound Healing/immunology , Animals , Cell Differentiation , Diabetes Complications/immunology , Epigenesis, Genetic , Gene Expression Regulation , Humans , Inflammation Mediators/immunology , Mice
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