Oxylipins and metabolites from pyroptotic cells act as promoters of tissue repair.

Pyroptosis is a lytic cell death mode that helps limit the spread of infections and is also linked to pathology in sterile inflammatory diseases and autoimmune diseases1-4. During pyroptosis, inflammasome activation and the engagement of caspase-1 lead to cell death, along with the maturation and secretion of the inflammatory cytokine interleukin-1ß (IL-1ß). The dominant effect of IL-1ß in promoting tissue inflammation has clouded the potential influence of other factors released from pyroptotic cells. Here, using a system in which macrophages are induced to undergo pyroptosis without IL-1ß or IL-1α release (denoted Pyro-1), we identify unexpected beneficial effects of the Pyro-1 secretome. First, we noted that the Pyro-1 supernatants upregulated gene signatures linked to migration, cellular proliferation and wound healing. Consistent with this gene signature, Pyro-1 supernatants boosted migration of primary fibroblasts and macrophages, and promoted faster wound closure in vitro and improved tissue repair in vivo. In mechanistic studies, lipidomics and metabolomics of the Pyro-1 supernatants identified the presence of both oxylipins and metabolites, linking them to pro-wound-healing effects. Focusing specifically on the oxylipin prostaglandin E2 (PGE2), we find that its synthesis is induced de novo during pyroptosis, downstream of caspase-1 activation and cyclooxygenase-2 activity; further, PGE2 synthesis occurs late in pyroptosis, with its release dependent on gasdermin D pores opened during pyroptosis. As for the pyroptotic metabolites, they link to immune cell infiltration into the wounds, and polarization to CD301+ macrophages. Collectively, these data advance the concept that the pyroptotic secretome possesses oxylipins and metabolites with tissue repair properties that may be harnessed therapeutically.

Reverse translation approach generates a signature of penetrating fibrosis in Crohn's disease that is associated with anti-TNF response.

OBJECTIVE: Fibrosis is a common feature of Crohn's disease (CD) which can involve the mesenteric fat. However, the molecular signature of this process remains unclear. Our goal was to define the transcriptional signature of mesenteric fibrosis in CD subjects and to model mesenteric fibrosis in mice to improve our understanding of CD pathogenesis. DESIGN: We performed histological and transcriptional analysis of fibrosis in CD samples. We modelled a CD-like fibrosis phenotype by performing repeated colonic biopsies in mice and analysed the model by histology, type I collagen-targeted positron emission tomography (PET) and global gene expression. We generated a gene set list of essential features of mesenteric fibrosis and compared it to mucosal biopsy datasets from inflammatory bowel disease patients to identify a refined gene set that correlated with clinical outcomes. RESULTS: Mesenteric fibrosis in CD was interconnected to areas of fibrosis in all layers of the intestine, defined as penetrating fibrosis. We found a transcriptional signature of differentially expressed genes enriched in areas of the mesenteric fat of CD subjects with high levels of fibrosis. Mice subjected to repeated colonic biopsies showed penetrating fibrosis as shown by histology, PET imaging and transcriptional analysis. Finally, we composed a composite 24-gene set list that was linked to inflammatory fibroblasts and correlated with treatment response. CONCLUSION: We linked histopathological and molecular features of CD penetrating fibrosis to a mouse model of repeated biopsy injuries. This experimental system provides an innovative approach for functional investigations of underlying profibrotic mechanisms and therapeutic concepts in CD.

Debaryomyces is enriched in Crohn's disease intestinal tissue and impairs healing in mice.

Alterations of the mycobiota composition associated with Crohn's disease (CD) are challenging to link to defining elements of pathophysiology, such as poor injury repair. Using culture-dependent and -independent methods, we discovered that Debaryomyces hansenii preferentially localized to and was abundant within incompletely healed intestinal wounds of mice and inflamed mucosal tissues of CD human subjects. D. hansenii cultures from injured mice and inflamed CD tissues impaired colonic healing when introduced into injured conventionally raised or gnotobiotic mice. We reisolated D. hansenii from injured areas of these mice, fulfilling Koch's postulates. Mechanistically, D. hansenii impaired mucosal healing through the myeloid cell-specific type 1 interferon-CCL5 axis. Taken together, we have identified a fungus that inhabits inflamed CD tissue and can lead to dysregulated mucosal healing.

PAI-1 augments mucosal damage in colitis.

There is a major unmet clinical need to identify pathways in inflammatory bowel disease (IBD) to classify patient disease activity, stratify patients that will benefit from targeted therapies such as anti-tumor necrosis factor (TNF), and identify new therapeutic targets. In this study, we conducted global transcriptome analysis to identify IBD-related pathways using colon biopsies, which highlighted the coagulation gene pathway as one of the most enriched gene sets in patients with IBD. Using this gene-network analysis across 14 independent cohorts and 1800 intestinal biopsies, we found that, among the coagulation pathway genes, plasminogen activator inhibitor-1 (PAI-1) expression was highly enriched in active disease and in patients with IBD who did not respond to anti-TNF biologic therapy and that PAI-1 is a key link between the epithelium and inflammation. Functionally, PAI-1 and its direct target, the fibrinolytic protease tissue plasminogen activator (tPA), played an important role in regulating intestinal inflammation. Intestinal epithelial cells produced tPA, which was protective against chemical and mechanical-mediated colonic injury in mice. In contrast, PAI-1 exacerbated mucosal damage by blocking tPA-mediated cleavage and activation of anti-inflammatory TGF-ß, whereas the inhibition of PAI-1 reduced both mucosal damage and inflammation. This study identifies an immune-coagulation gene axis in IBD where elevated PAI-1 may contribute to more aggressive disease.

Temporal Regulation of the Bacterial Metabolite Deoxycholate during Colonic Repair Is Critical for Crypt Regeneration.

Colonic wound repair is an orchestrated process, beginning with barrier re-establishment and followed by wound channel formation and crypt regeneration. Elevated levels of prostaglandin E2 (PGE2) promote barrier re-establishment; however, we found that persistently elevated PGE2 hinders subsequent repair phases. The bacterial metabolite deoxycholate (DCA) promotes transition through repair phases via PGE2 regulation. During barrier re-establishment, DCA levels are locally diminished in the wound, allowing enhanced PGE2 production and barrier re-establishment. However, during transition to the wound channel formation phase, DCA levels increase to inhibit PGE2 production and promote crypt regeneration. Altering DCA levels via antibiotic treatment enhances PGE2 levels but impairs wound repair, which is rescued with DCA treatment. DCA acts via its receptor, farnesoid X receptor, to inhibit the enzyme cPLA2 required for PGE2 synthesis. Thus, colonic wound repair requires temporally regulated signals from microbial metabolites to coordinate host-associated signaling cascades. VIDEO ABSTRACT.

Tandem tyrosine phosphosites in the Enteropathogenic Escherichia coli chaperone CesT are required for differential type III effector translocation and virulence.

Enteropathogenic Escherichia coli (EPEC) use a type 3 secretion system (T3SS) for injection of effectors into host cells and intestinal colonization. Here, we demonstrate that the multicargo chaperone CesT has two strictly conserved tyrosine phosphosites, Y152 and Y153 that regulate differential effector secretion in EPEC. Conservative substitution of both tyrosine residues to phenylalanine strongly attenuated EPEC type 3 effector injection into host cells, and limited Tir effector mediated intimate adherence during infection. EPEC expressing a CesT Y152F variant were deficient for NleA effector expression and exhibited significantly reduced translocation of NleA into host cells during infection. Other effectors were observed to be dependent on CesT Y152 for maximal translocation efficiency. Unexpectedly, EPEC expressing a CesT Y153F variant exhibited significantly enhanced effector translocation of many CesT-interacting effectors, further implicating phosphosites Y152 and Y153 in CesT functionality. A mouse infection model of intestinal disease using Citrobacter rodentium revealed that CesT tyrosine substitution variants displayed delayed colonization and were more rapidly cleared from the intestine. These data demonstrate genetically separable functions for tandem tyrosine phosphosites within CesT. Therefore, CesT via its C-terminal tyrosine phosphosites, has relevant roles beyond typical type III secretion chaperones that interact and stabilize effector proteins.

Erdheim-Chester Disease presenting with histiocytic colitis and cytokine storm.

BACKGROUND: Non-Langerhans histiocytosis is a group of inflammatory lymphoproliferative disorders originating from non-clonal expansion of hematopoietic stem cells into cytokine-secreting dendritic cells or macrophages. Erdheim-Chester Disease (ECD) is a rare type of non-Langerhans cell histiocytosis characterized by tissue inflammation and injury caused by macrophage infiltration and histologic findings of foamy histiocytes. Often ECD involves the skeleton, retroperitoneum and the orbits. This is the first report documenting ECD manifesting as segmental colitis and causing cytokine-release syndrome. CASE PRESENTATION: A 68-year old woman presented with persistent fever without infectious etiology and hematochezia. Endoscopy showed segmental colitis and pathology revealed infiltration of large foamy histiocytes CD3-/CD20-/CD68+/CD163+/S100- consistent with ECD. The patient was empirically treated with steroids but continued to have fever and developed progressive distributive shock. CONCLUSION: This case report describes the differential diagnosis of infectious and immune-mediated inflammatory and rheumatologic segmental colitis. Non-Langerhans histiocytosis and ECD are rare causes of gastrointestinal inflammation. Prompt diagnosis is imperative for the appropriate treatment to prevent hemodynamic compromise due to distributive shock or gastrointestinal bleeding. Importantly, gastrointestinal ECD might exhibit poor response to steroid treatment and other potential treatments including chemotherapy, and biologic treatments targeting IL-1 and TNF-alpha signalling should be considered.

Predictors of adverse events after neck dissection: An analysis of the 2006-2011 National Surgical Quality Improvement Program (NSQIP) Database.

While neck dissection is an important primary and adjunctive procedure in the treatment of head and neck cancer, there is a paucity of studies evaluating outcomes. A retrospective review of the National Surgical Quality Improvement Program (NSQIP) database was performed to identify factors associated with adverse events (AEs) in patients undergoing neck dissection. A total of 619 patients were identified, using CPT codes specific to neck dissection. Of the 619 patients undergoing neck dissection, 142 (22.9%) experienced an AE within 30 days of the surgical procedure. Risk factors on multivariate regression analysis associated with increased AEs included dyspnea (odds ratio [OR] 2.57; 95% confidence interval [CI] 1.06 to 6.22; p = 0.037), previous cardiac surgery (OR 3.38; 95% CI 1.08 to 10.52; p = 0.036), increasing anesthesia time (OR 1.005; 95% CI 1 to 1.009; p = 0.036), and increasing total work relative value units (OR 1.09; CI 1.04 to 1.13; p < 0.001). The current study is the largest, most robust analysis to identify specific risk factors associated with AEs after neck dissection. This information will assist with preoperative optimization, patient counseling, and appropriate risk stratification, and it can serve as benchmarking for institutions comparing surgical outcomes.

ASA class is a reliable independent predictor of medical complications and mortality following surgery.

METHODS: The American Society of Anesthesiologists Physical Status classification system (ASA PS) is a method of characterizing patient operative risk on a scale of 1-5, where 1 is normal health and 5 is moribund. Every anesthesiologist is trained in this measure, and it is performed before every procedure in which a patient undergoes anesthesia. We measured the independent predictive value of ASA-PS for complications and mortality in the ACS-NSQIP database by multivariate regression. We conducted analogous regressions after standardizing ASA-PS to control for interprocedural variations in risk in the overall model and sub-analyses by surgical specialty and the most common procedures. RESULTS: For 2,297,629 cases (2005-2012; median age 55, min = 16, max > 90 [90 and above are coded as 90+]), at increasing levels of ASA-PS (2-5), odds ratios (OR's) from 2.05 to 63.25 (complications, p < 0.001) and 5.77-2011.92 (mortality, p < 0.001) were observed, with non-overlapping 95% confidence intervals. Standardization of ASA-PS (OR = 1.426 [per standard deviation above the mean ASA-PS per procedure], p < .001) and subgroup analyses yielded similar results. DISCUSSION: ASA PS was not only found to be associated with increased morbidity and mortality, but independently predictive when controlling for other comorbidities. Even after standardization based on procedure type, increases in ASA predicted significant increases in complication rates for morbidity and mortality post-operatively. CONCLUSIONS: ASA PS has strong, independent associations with post-operative medical complications and mortality across procedures. This capability, along with its simplicity, makes it a valuable prognostic metric.

Oropharyngeal Contamination Predisposes to Complications after Neck Dissection: An Analysis of 9462 Patients.

OBJECTIVE: While neck dissection is important in the treatment of head and neck cancer, there is a paucity of studies evaluating outcomes. We sought to compare preoperative variables and outcomes between clean and contaminated neck dissections, using the 2006-2011 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data sets. STUDY DESIGN: Retrospective review of prospectively maintained database. SETTING: Multicenter (university hospitals; tertiary referral centers). SUBJECTS AND METHODS: A retrospective review was performed of the NSQIP database to identify patients undergoing neck dissection in clean vs oropharyngeal contaminated cases. Clinical factors, comorbidities, epidemiologic factors, and procedural characteristics were analyzed to identify factors associated with 30-day postoperative adverse events, including medical and surgical complications, unplanned reoperation, and mortality. Bivariate and multivariable analyses were performed for the outcome of one or more adverse events. RESULTS: In total, 8890 patients had clean neck dissections, while 572 patients had neck wound contamination with oropharyngeal flora. On multivariable regression analysis, oropharyngeal contamination was a significant risk factor for surgical complications (odds ratio [OR], 3.42; 95% confidence interval [CI], 1.96-5.96; P < .001). However, medical complications and mortality were not significantly different between the 2 cohorts. This finding persisted after subgroup analysis, with removal of all thyroidectomy patients from analysis (OR, 2.33; 95% CI, 1.25-4.36; P = .008). CONCLUSION: Using the ACS-NSQIP data set, this study found an increased risk of surgical complications in the setting of contaminated neck dissections. These data should be used for patient risk stratification, informed consent, and to guide further research.

Properdin provides protection from Citrobacter rodentium-induced intestinal inflammation in a C5a/IL-6-dependent manner.

Citrobacter rodentium is an attaching and effacing mouse pathogen that models enteropathogenic and enterohemorrhagic Escherichia coli in humans. The complement system is an important innate defense mechanism; however, only scant information is available about the role of complement proteins during enteric infections. In this study, we examined the impact of the lack of properdin, a positive regulator of complement, in C. rodentium-induced colitis. Following infection, properdin knockout (P(KO)) mice had increased diarrhea and exacerbated inflammation combined with defective epithelial cell-derived IL-6 and greater numbers of colonizing bacteria. The defect in the mucosal response was reversed by administering exogenous properdin to P(KO) mice. Then, using in vitro and in vivo approaches, we show that the mechanism behind the exacerbated inflammation of P(KO) mice is due to a failure to increase local C5a levels. We show that C5a directly stimulates IL-6 production from colonic epithelial cells and that inhibiting C5a in infected wild-type mice resulted in defective epithelial IL-6 production and exacerbated inflammation. These outcomes position properdin early in the response to an infectious challenge in the colon, leading to complement activation and C5a, which in turn provides protection through IL-6 expression by the epithelium. Our results unveil a previously unappreciated mechanism of intestinal homeostasis involving complement, C5a, and IL-6 during bacteria-triggered epithelial injury.

Venous thromboembolism in reconstructive pelvic surgery.

OBJECTIVE: We sought to determine the incidence and risk factors for venous thromboembolism (VTE) in women undergoing reconstructive pelvic surgery (RPS). STUDY DESIGN: Using the American College of Surgeons National Surgical Quality Improvement Program registry, we identified patients who underwent RPS from 2006 through 2010 based on Current Procedural Terminology codes. We defined 2 cohorts: women with any RPS performed, with concomitant surgery from other specialties allowed (RPS + other), and women whose only procedure was RPS. VTE was defined as deep vein thrombosis or pulmonary embolism diagnosed within 30 days of surgery. Demographic characteristics, comorbidities, and operative characteristics were extracted from the database. Variables were analyzed using χ(2) tests and Student t tests for categorical and continuous variables. We performed a multiple logistic regression to control for confounding variables. RESULTS: In all, 20,687 women underwent RPS + other, with 69 cases of VTE for a rate of 0.3%. Multivariate analysis demonstrated predictors for postoperative VTE including inpatient hospital status (odds ratio [OR], 7.69; P < .001), higher American Society of Anesthesiology Physical Status classification (OR, 2.70; P < .001), and emergency intervention (OR, 3.65; P = .008). When women undergoing only RPS were analyzed, there were 14 cases of VTE, with an incidence of 0.1% and the only specific predictor for postoperative VTE was length of stay (P < .037). CONCLUSION: The incidence of VTE following RPS is very low, but it is increased in women undergoing concomitant surgeries. Patients undergoing inpatient surgery with higher American Society of Anesthesiology Physical Status classifications and requiring emergency intervention were at highest risk for VTE.

Predictors of readmission after inpatient plastic surgery.

BACKGROUND: Understanding risk factors that increase readmission rates may help enhance patient education and set system-wide expectations. We aimed to provide benchmark data on causes and predictors of readmission following inpatient plastic surgery. METHODS: The 2011 National Surgical Quality Improvement Program dataset was reviewed for patients with both "Plastics" as their recorded surgical specialty and inpatient status. Readmission was tracked through the "Unplanned Readmission" variable. Patient characteristics and outcomes were compared using chi-squared analysis and Student's t-tests for categorical and continuous variables, respectively. Multivariate regression analysis was used for identifying predictors of readmission. RESULTS: A total of 3,671 inpatient plastic surgery patients were included. The unplanned readmission rate was 7.11%. Multivariate regression analysis revealed a history of chronic obstructive pulmonary disease (COPD) (odds ratio [OR], 2.01; confidence interval [CI], 1.12-3.60; P=0.020), previous percutaneous coronary intervention (PCI) (OR, 2.69; CI, 1.21-5.97; P=0.015), hypertension requiring medication (OR, 1.65; CI, 1.22-2.24; P<0.001), bleeding disorders (OR, 1.70; CI, 1.01-2.87; P=0.046), American Society of Anesthesiologists (ASA) class 3 or 4 (OR, 1.57; CI, 1.15-2.15; P=0.004), and obesity (body mass index ≥30) (OR, 1.43; CI, 1.09-1.88, P=0.011) to be significant predictors of readmission. CONCLUSIONS: Inpatient plastic surgery has an associated 7.11% unplanned readmission rate. History of COPD, previous PCI, hypertension, ASA class 3 or 4, bleeding disorders, and obesity all proved to be significant risk factors for readmission. These findings will help to benchmark inpatient readmission rates and manage patient and hospital system expectations.

Predictors and causes of unplanned re-operations in outpatient plastic surgery: a multi-institutional analysis of 6749 patients using the 2011 NSQIP database.

Studies that evaluate the predictors and causes of unplanned re-operation in outpatient plastic surgery. This study retrospectively reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and identified all plastic surgery outpatient cases performed in 2011. Multiple logistic regression analysis was utilised to identify independent risk factors and causes of unplanned reoperations. Of the 6749 outpatient plastic surgery cases identified, there were 125 (1.9%) unplanned re-operations (UR). Regression analysis demonstrated that body mass index (BMI, OR = 1.041, 95% CI = 1.019-1.065), preoperative open wound/wound infection (OR = 3.498, 95% CI = 1.593-7.678), American Society of Anesthesiologists (ASA) class 3 (OR = 2.235, 95% CI = 1.048-4.765), and total work relative value units (RVU, OR = 1.014, 95% CI = 1.005-1.024) were significantly predictive of UR. Additionally, the presence of any complication was significantly associated with UR (OR = 15.065, 95% CI = 5.705-39.781). In an era of outcomes-driven medicine, unplanned re-operation is a critical quality indicator for ambulatory plastic surgery facilities. The identified risk factors will aid in surgical planning and risk adjustment.

Predictors of readmission after outpatient otolaryngologic surgery.

OBJECTIVES/HYPOTHESIS: Hospital readmissions increase costs to hospitals and patients. There is a paucity of data on benchmark rates of readmission for otolaryngological surgery. Understanding the risk factors that increase readmission rates may help enhance patient education and set system-wide expectations. We aimed to provide benchmark data on causes and predictors of readmission following outpatient otolaryngological surgery. STUDY DESIGN: This study is a retrospective analysis of the 2011 National Surgical Quality Improvement Program (NSQIP) dataset. METHODS: NSQIP was reviewed for outpatients with "Otolaryngology (ENT)" as their recorded surgical specialty. Readmission was tracked through the "Unplanned Readmission" variable. Patient characteristics and outcomes were compared using chi-square analysis and student t tests for categorical and continuous variables, respectively. Multivariate regression analysis investigated predictors of readmission. RESULTS: A total of 6,788 outpatient otolaryngological surgery patients were isolated. The unplanned readmission rate was 2.01%. Multivariate regression analysis revealed superficial surgical site infection (odds ratio [OR] 2.672, confidence interval [CI] 1.133-6.304, P = .025) and work relative value units (RVU) (OR .972, CI .944-1, P = .049) to be significant predictors of readmission. CONCLUSION: Outpatient otolaryngological surgery has an associated 2.01% unplanned readmission rate. Superficial surgical site infection and work RVUs proved to be significant positive and negative risk factors, respectively, for readmission. These findings will help to benchmark outpatient readmission rates and manage patient and hospital system expectations.

National multi-institutional comparison of 30-day postoperative complication and readmission rates between open retropubic radical prostatectomy and robot-assisted laparoscopic prostatectomy using NSQIP.

BACKGROUND: Many American hospitals will soon face readmission penalties deducted from Medicare reimbursements, which will place further scrutiny on techniques that may offer reduced postoperative morbidity. We aimed to perform the first multi-institutional study using the National Surgical Quality Improvement Program (NSQIP) database, to compare predictors of readmission within cohorts of open radical retropubic prostatectomy (RRP) and robot-assisted laparoscopic radical prostatectomy (RALRP) in a contemporary nationwide series of radical prostatectomy. METHODS: All patients who underwent radical prostatectomy in 2011 were identified in the NSQIP database using procedural codes. As no patients in the analysis underwent LRP, patients were grouped as RRP or RALRP for analysis. Perioperative variables were analyzed using chi-squared and Student's t-tests as appropriate. Multiple logistic regression was used to identify readmission risk factors. RESULTS: Of 5471 patient cases analyzed, 4374 (79.9%) and 1097 (20.1%) underwent RALRP and RRP, respectively. RRP and RALRP cohorts experienced different readmission rates (5.47% vs 3.48%, respectively; p=0.002). In addition, RRP experienced a higher rate of overall complications than RALRP (23.25% vs 5.62%, respectively; p<0.001), but not higher rates of reoperation (1.09% vs 0.96%, respectively; p=0.689). Overall predictors of readmission included operative time, dyspnea, and RRP or RALRP procedure type. Current smoking and patient age were predictive of readmission for RRP only, while dyspnea was predictive of readmission following RALRP only. CONCLUSION: This is the first multi-institutional retrospective study that examines readmission rates and procedural intracohort predictors of readmission for RRP in the contemporary United States. We report a significant difference in postoperative complication and readmission rates in RRP compared with RALRP. Further prospective analysis is warranted.

Post-mastectomy reconstruction: a risk-stratified comparative analysis of outcomes.

INTRODUCTION: Although breast reconstruction following mastectomy plays a role in the psychological impact of breast cancer, only one in three women undergo reconstruction. Few multi-institutional studies have compared complication profiles of reconstructive patients to non-reconstructive. METHODS: Using the National Surgical Quality Improvement database, all patients undergoing mastectomy from 2006 to 2010, with or without reconstruction, were identified and risk-stratified using propensity scored quintiles. The incidence of complications and comorbidities were compared. RESULTS: Of 37,723 mastectomies identified, 30% received immediate breast reconstruction. After quintile matching for comorbidities, complications rates between reconstructive and non-reconstructives were similar. This trend was echoed across all quintiles, except in the sub-group with highest comorbidities. Here, the reconstructive patients had significantly more complications than the non-reconstructive (22.8% versus 7.0%, p < 0.001). CONCLUSION: Immediate breast reconstruction is a well-tolerated surgical procedure. However, in patients with high comorbidities, surgeons must carefully counterbalance surgical risks with psychosocial benefits to maximize patient outcomes. LEVEL OF EVIDENCE: Level 3.

Impact of preoperative myocardial infarction on surgical outcomes in inpatient orthopaedic surgery.

PURPOSE: The purpose of this study was to evaluate the impact of a preoperative myocardial infarction (MI) on outcomes of inpatient orthopaedic operations. METHODS: The National Surgical Quality Improvement Program database was used to identify patients who underwent common orthopaedic operations from 2006 to 2010. Patient demographic data, comorbidities, complications, and lengths of stay were collected. Multivariate logistic regression and linear regression models were used to compare outcomes for patients with and without a history of MI in the six months prior to surgery. RESULTS: Of the 32,462 patients identified, 86 had sustained an MI in the six months prior to surgery. The MI cohort had no cardiac complications but had increased incidences of superficial surgical site infection, unplanned re-intubation, ventilator-assisted respiration for more than 48 hours, pneumonia, sepsis or septic shock, and postoperative mortality within 30 days of surgery, as well as prolonged lengths of stay. Following logistic regression to adjust for baseline differences, a history of MI showed no association with cardiac complications and was significantly associated with superficial surgical site infection (OR 3.6, 95% CI 1.1-11.8), ventilator dependence for over 48 hours (OR 4.0, 95% CI 1.1-14.0), and extended length of stay (median with interquartile range 4 [4-4] vs. 5 [5-5] days). CONCLUSIONS: A myocardial infarction within six months prior to orthopaedic surgery is not associated with a higher risk of 30-day perioperative cardiac complications; however, it is associated with increased rates of surgical site infection, prolonged ventilator dependence, and longer hospital stay.