Cleaved TMEM106B forms amyloid aggregates in central and peripheral nervous systems.

Filaments made of residues 120-254 of transmembrane protein 106B (TMEM106B) form in an age-dependent manner and can be extracted from the brains of neurologically normal individuals and those of subjects with a variety of neurodegenerative diseases. TMEM106B filament formation requires cleavage at residue 120 of the 274 amino acid protein; at present, it is not known if residues 255-274 form the fuzzy coat of TMEM106B filaments. Here we show that a second cleavage appears likely, based on staining with an antibody raised against residues 263-274 of TMEM106B. We also show that besides the brain TMEM106B inclusions form in dorsal root ganglia and spinal cord, where they were mostly found in non-neuronal cells. We confirm that in the brain, inclusions were most abundant in astrocytes. No inclusions were detected in heart, liver, spleen or hilar lymph nodes. Based on their staining with luminescent conjugated oligothiophenes, we confirm that TMEM106B inclusions are amyloids. By in situ immunoelectron microscopy, TMEM106B assemblies were often found in structures resembling endosomes and lysosomes.

Increase in Tau Pathology in P290S Mapt Knock-In Mice Crossed with App NL-G-F Mice.

Alzheimer's Disease (AD) is characterized by the pathologic assembly of amyloid ß (Aß) peptide, which deposits into extracellular plaques, and tau, which accumulates in intraneuronal inclusions. To investigate the link between Aß and tau pathologies, experimental models featuring both pathologies are needed. We developed a mouse model featuring both tau and Aß pathologies by knocking the P290S mutation into murine Mapt and crossing these Mapt P290S knock-in (KI) mice with the App NL-G-F KI line. Mapt P290S KI mice developed a small number of tau inclusions, which increased with age. The amount of tau pathology was significantly larger in App NL-G-F xMapt P290S KI mice from 18 months of age onward. Tau pathology was higher in limbic areas, including hippocampus, amygdala, and piriform/entorhinal cortex. We also observed AT100-positive and Gallyas-Braak-silver-positive dystrophic neurites containing assembled filamentous tau, as visualized by in situ electron microscopy. Using a cell-based tau seeding assay, we showed that Sarkosyl-insoluble brain extracts from both 18-month-old Mapt P290S KI and App NL-G-F xMapt P290S KI mice were seed competent, with brain extracts from double-KI mice seeding significantly more than those from the Mapt P290S KI mice. Finally, we showed that App NL-G-F xMapt P290S KI mice had neurodegeneration in the piriform cortex from 18 months of age. We suggest that App NL-G-F xMapt P290S KI mice provide a good model for studying the interactions of aggregation-prone tau, Aß, neuritic plaques, neurodegeneration, and aging.

Epicardial ultrasound in a case of myocardial bridge and apical hypertrophic cardiomyopathy.

A 59-year-old male with a history of unstable angina was diagnosed with a myocardial bridge of the left anterior descending artery (LAD) and apical variant hypertrophic cardiomyopathy (AHCM). He underwent unroofing of the myocardial bridge and a left ventricular apical myectomy. Intraoperatively, epicardial ultrasound was used to identify the myocardial bridge with systolic compression of the LAD and confirm resolution of this compression postoperatively. Furthermore, epicardial ultrasound was used for guiding the degree of apical resection of the decompressed heart. This novel use of intraoperative epicardial ultrasound can help guide surgeons preoperatively and confirm results immediately after an operation.

Increased risk of atrial fibrillation among patients undergoing coronary artery bypass graft surgery while receiving nitrates and antiplatelet agents.

Background Postoperative atrial fibrillation (POAF) is a frequent complication of coronary artery bypass graft (CABG) surgery. This arrhythmia occurs more frequently among patients who receive perioperative inotropic therapy (PINOT). Administration of nitrates with antiplatelet agents reduces the conversion rate of cyclic guanosine monophosphate to guanosine monophosphate. This process is associated with increased concentrations of free radicals, catecholamines, and blood plasma volume. We hypothesized that patients undergoing CABG surgery who receive PINOT may be more susceptible to POAF when nitrates are administered with antiplatelet agents. Methods Clinical records were examined from a prospectively maintained cohort of 4,124 patients undergoing primary isolated CABG surgery to identify POAF-associated factors. Results POAF risk was increased among patients receiving PINOT, and the greatest effect was observed when nitrates were administered with antiplatelet therapy. Adjustment for comorbidities did not substantively change the study results. Conclusions Administration of nitrates with certain antiplatelet agents was associated with an increased POAF risk among patients undergoing CABG surgery. Additional studies are needed to determine whether preventive strategies such as administration of antioxidants will reduce this risk.

Effect of hypothermia on splenic leukocyte modulation and survival duration in severely septic rats.

BACKGROUND: Therapeutic hypothermia (HT) in severe septic shock is associated with prolonged survival. We hypothesized that moderate HT would prolong survival and modulate the inflammatory response in rats with septic shock by exerting its therapeutic effect on splenic leukocytes. MATERIALS AND METHODS: Severe septic shock was created in rats by cecal ligation and incision (CLI). One hour after CLI or laparotomy, rats were randomized to sham, normothermia (NT), or 4 h of HT followed by 2 h of rewarming. HT (31 ± 1°C) was induced using a cooling blanket and monitored via a rectal temperature probe. RESULTS: Survival duration was 2.78 ± 1.0 h in NT rats and 8.33 ± 0.32 h in HT rats (n = 8/group, P < 0.0001). In separate groups, 3 h after CLI, the spleen weight was significantly smaller in NT rats (769 ± 100 mg) than in HT rats (947 ± 157 mg, P = 0.04). Fluorescent immunostaining of formyl peptide receptors on leukocytes in spleen tissue showed considerably higher formyl peptide receptor expression in HT rats than in NT rats. Significantly elevated proinflammatory cytokines and myeloperoxidase enzyme in plasma were found in NT rats compared with HT rats. Anti-inflammatory cytokine, interleukin-10, was significantly higher in HT rats. Both proinflammatory cytokines and plasma myeloperoxidase were significantly reduced in splenectomized NT rats. CONCLUSIONS: Moderate hypothermic therapy significantly prolongs the survival duration of rats with severe septic shock. HT dampens the inflammatory response during septic shock by modulating the spleen to an anti-inflammatory mode and preventing the spleen from releasing activated splenic leukocytes into the blood.

Perioperative Inotrope Therapy and Atrial Fibrillation Following Coronary Artery Bypass Graft Surgery: Evidence of a Racial Disparity.

BACKGROUND AND OBJECTIVE: Following coronary artery bypass graft (CABG) surgery, mortality rates are significantly higher among black patients who experience postoperative atrial fibrillation (POAF). Perioperative inotropic therapy (PINOT) was associated with POAF in previous reports, but the extent to which race influences this association is unknown. In the present study, the relationship between PINOT, race, and POAF was examined in patients undergoing CABG surgery. METHODS AND SETTING: Clinical records were examined from a prospectively maintained cohort of 11,855 patients (median age 64 yrs; 70% male; 16% black) undergoing primary isolated CABG at a large cardiovascular institute in the southeastern region of the United States. Relative risk (RR) and 95% confidence intervals (CIs) were computed using log-binomial regression. MAIN RESULTS: The association between PINOT and POAF was significantly increased among black patients (adjusted RR 1.7, CI 1.4-2.0) compared with white patients (adjusted RR 1.3, CI 1.2-1.4) (pinteraction  = 0.013). CONCLUSIONS: These findings suggest that PINOT may be disproportionately associated with POAF among black patients undergoing CABG surgery. Additional studies are needed to examine further the potential underlying mechanisms of this association.

Long-Term Survival after Cardiac Surgery in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Although many patients with chronic obstructive pulmonary disease (COPD) require a prolonged length of stay (PLOS) following coronary artery bypass grafting (CABG), the impact of PLOS on long-term survival has not been examined in this population. OBJECTIVES: To determine the association between PLOS and long-term survival among COPD and non-COPD patients after CABG and to examine consequent policy and practice-based implications. METHODS: A retrospective cohort study of CABG patients was conducted between 2002 and 2011. Long-term survival was compared in patients with and without COPD and stratified by PLOS. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. RESULTS: A total of 203 patients (4.2%) had PLOS after nonemergent CABG (N = 4801). PLOS was an important independent predictor of decreased long-term survival (no COPD, no PLOS: HR = 1.0; COPD, no PLOS: adjusted HR [95% CI], 1.8 [1.5-2.1]; no COPD, PLOS: 3.3 [2.5-4.4]; COPD, PLOS: 6.0 [4.4-8.2]; PTrend < .001). CONCLUSIONS: COPD and PLOS are 2 of many factors that affect long-term mortality in postoperative CABG patients. Aggressive treatment strategies aimed at early weaning off of mechanical ventilation and prevention of reintubation among COPD patients must be considered carefully as a means to reduce length of stay after CABG. Our results also have important implications for the long-term management of these patients and strategies for containing costs over the life course of the patient.

Seasonal Incidence of Emergent Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Emergent coronary artery bypass grafting (CABG) surgery is often required in the case of severe coronary artery disease, which is refractory to traditional management. The objective of our study was to test the hypothesis that there is seasonal variation in the incidence of emergent CABG. METHODS: A sinusoidal logistic regression model was used to analyze operative data at our cardiovascular institute of 270 cases spanning 5939 calendar days. RESULTS: A cyclic peak risk for emergent CABG was observed for late winter (calendar day 66; P = .036). The odds ratios for the 1-, 2- and 3-month window surrounding this peak were 1.8 (95% CI = 0.94-3.5, P = .072), 1.6 (95% CI = 1.06-2.5, P = .024) and 1.4 (95% CI = 0.9-1.8, P = .066), respectively. CONCLUSION: Our results suggest that a seasonal variation may exist in the incidence of patients presenting with severe coronary artery disease requiring emergent CABG. This information is useful in the scheduling of hospital resources and staff. It also provides important etiology clues underlying coronary artery disease that may lead to future interventions or targeted therapies.

Operative Start Time Does Not Affect Post-Operative Infection Risk.

BACKGROUND: Surgical care is delivered 24 h a day at most institutions. Alarmingly, some authors have found that certain operative start times are associated with greater morbidity and mortality rates. This effect has been noted in both the public and private sector. Although some of these differences may be related to process, they may also be caused by the human circadian rhythm and corresponding changes in host defenses. We hypothesized that the time of day of an operation would impact the frequency of certain post-operative outcomes significantly. METHODS: Cases at a single tertiary-care center reported to the American College of Surgeons National Surgical Quality Improvement Program over a 10-year period were identified. Operative start times were divided into six-hour blocks, with 6 am to noon serving as the reference. Standard univariable techniques were applied. Multivariable logistic regression with mixed effects modeling then was used to determine the relation between operative start times and infectious outcomes, controlling for surgeon clustering. Statistical significance was set at p < 0.01. RESULTS: A total of 21,985 cases were identified, of which 2,764 (12.6%) were emergency procedures. Overall, 9.7% (n = 2,142) of patients experienced some post-operative infectious complication. Seventy percent of these infections (n = 1,506) were surgical site infections. On univariable analysis considering all cases, nighttime and evening operations had higher rates of post-operative infections than those in performed during the day (9.1% from 6 am to noon; 9.7% from noon to 6 pm; 14.8% from 6 pm to midnight; and 14.4% from midnight to 6 am; p < 0.001). On multivariable analysis, operative start time was not associated with the risk of post-operative infection, even when emergency cases were considered independently. CONCLUSION: Our data suggest that operative start times have no correlation with post-operative infectious complications. Further work is required to identify the source of the time-dependent outcome variability observed in previous studies.

Obesity Is Not Associated with Antimicrobial Treatment Failure for Intra-Abdominal Infection.

BACKGROUND: Obesity and commonly associated comorbidities are known risk factors for the development of infections. However, the intensity and duration of antimicrobial treatment are rarely conditioned on body mass index (BMI). In particular, the influence of obesity on failure of antimicrobial treatment for intra-abdominal infection (IAI) remains unknown. We hypothesized that obesity is associated with recurrent infectious complications in patients treated for IAI. METHODS: Five hundred eighteen patients randomized to treatment in the Surgical Infection Society Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial were evaluated. Patients were stratified by obese (BMI ≥30) versus non-obese (BMI≥30) status. Descriptive comparisons were performed using Chi-square test, Fisher exact test, or Wilcoxon rank-sum tests as appropriate. Multivariable logistic regression using a priori selected variables was performed to assess the independent association between obesity and treatment failure in patients with IAI. RESULTS: Overall, 198 (38.3%) of patients were obese (BMI ≥30) versus 319 (61.7%) who were non-obese. Mean antibiotic d and total hospital d were similar between both groups. Unadjusted outcomes of surgical site infection (9.1% vs. 6.9%, p = 0.36), recurrent intra-abdominal infection (16.2% vs. 13.8, p = 0.46), death (1.0% vs. 0.9%, p = 1.0), and a composite of all complications (25.3% vs. 19.8%, p = 0.14) were also similar between both groups. After controlling for appropriate demographics, comorbidities, severity of illness, treatment group, and duration of antimicrobial therapy, obesity was not independently associated with treatment failure (c-statistic: 0.64). CONCLUSIONS: Obesity is not associated with antimicrobial treatment failure among patients with IAI. These results suggest that obesity may not independently influence the need for longer duration of antimicrobial therapy in treatment of IAI versus non-obese patients.

Ventilator-Associated Pneumonia in Trauma Patients: Different Criteria, Different Rates.

BACKGROUND: No consensus exists regarding the definition of ventilator-associated pneumonia (VAP). Even within a single institution, inconsistent diagnostic criteria result in conflicting rates of VAP. As a Level 1 trauma center participating in the Trauma Quality Improvement Project (TQIP) and the National Healthcare Safety Network (NHSN), our institution showed inconsistencies in VAP rates depending on which criteria was applied. The purpose of this study was to compare VAP definitions, defined by culture-based criteria, National Trauma Data Bank (NTDB) and NHSN, using incidence in trauma patients. METHODS: A retrospective chart review of consecutive trauma patients who were diagnosed with VAP and met pre-determined inclusion and exclusion criteria admitted to our rural, 861-bed, Level 1 trauma and tertiary care center between January 2008 and December 2011 was performed. These patients were identified from the National Trauma Registry of the American College of Surgeons (NTRACS) database and an in-house infection control database. Ventilator-associated pneumonia diagnosis criteria defined by the U.S. Center for Disease Control and Prevention (used by the NHSN), the NTDB, and our institutional, culture-based criteria gold standard were compared among patients. RESULTS: Two hundred seventy-nine patients were diagnosed with VAP (25.4% met NHSN criteria, 88.2% met NTDB, and 76.3% met culture-based criteria). Only 58 (20.1%) patients met all three criteria. When NHSN criteria were compared with culture-based criteria, NHSN showed a high specificity (92.5%) and low sensitivity (28.2%). The positive predictive value (PPV) was 84.5%, but the negative predictive value (NPV) was 47.1%. The agreement between the NHSN and the culture-based criteria was poor (κ = 0.18). Conversely, the NTDB showed a lower specificity (57.8%), but greater sensitivity (86.4%) compared with culture-based criteria. The PPV and NPV were both 74% and the two criteria showed fair agreement (κ = 0.41). CONCLUSIONS: The lack of standard diagnostic criteria for VAP resulted in variable reporting to different agencies. Emphasis on establishing a consensus VAP definition should be undertaken.

Comparison of Risk of Atrial Fibrillation in Black Versus White Patients After Coronary Artery Bypass Grafting.

Obesity has been identified as a risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). However, no studies have addressed the influence of race on this association. A total of 13,594 patients undergoing first-time, isolated CABG without preoperative AF between 1992 and 2011 were included in our study. The association between body mass index and POAF was compared by race. Relative risk and 95% CIs were computed using maximum likelihood log-binomial regression. Increasing levels of body mass index were associated with higher POAF risk after CABG in black but not white patients (pinteraction = 0.0009).

Top Guns: The "Maverick" and "Goose" of Empiric Therapy.

BACKGROUND: Vancomycin and piperacillin-tazobactam are commonly used first guns in the empiric management of critically ill patients. Current studies suggest an increased prevalence of acute kidney injury with concomitant use, however, these studies are few and limited by small sample size. The purpose of this study was to compare the prevalence of nephrotoxicity after treatment with vancomycin alone and concomitant vancomycin and piperacillin-tazobactam treatment at our institution. HYPOTHESIS: Concomitant vancomycin and piperacillin-tazobactam-treated patients will experience greater prevalence of nephrotoxicity compared with vancomycin-only treated patients. METHODS: This was a retrospective cohort of patients treated with vancomycin for gram-positive or mixed infections in our facility from 2005 to 2009 who were not receiving hemodialysis at the time of admission. Included patients were stratified by treatment with vancomycin, vancomycin/piperacillin-tazobactam, or vancomycin/an alternative gram-negative rod (GNR) antibiotic. p values for categorical variables were computed using χ(2) while continuous variables were computed using Kruskal-Wallis. Variables deemed statistically significant (< 0.05) were included in the multivariable, log-binomial regression model. Relative risk (RR) and 95% confidence intervals (CI), and p values were computed using a generalized estimating equation (GEE) approach with robust standard errors (i.e., Huber White "sandwich variance" estimates) to accommodate a correlated data structure corresponding to multiple episodes of infection per individual. RESULTS: A total of 530 patients with 1,007 episodes of infection, were treated with vancomycin (150 patients/302 episodes of infection), vancomycin/piperacillin-tazobactam (213 patients/372 episodes of infection), or vancomycin/GNR alternative (167 patients/333 episodes of infection). Patient demographics, comorbidities, sites of infection, and organisms of infection were compared among groups. After adjusting for statistically significant variables, neither vancomycin/piperacillin-tazobactam (RR = 1.1, 95% CI = 0.99-1.2; p = 0.073) nor vancomycin/GNR alternative (RR = 1.1, 95% CI = 0.98-1.2; p = 0.097) were found to be associated with an increased risk for nephrotoxicity compared with vancomycin alone. CONCLUSION: A difference in nephrotoxicity was not observed between vancomycin and vancomycin/piperacillin-tazobactam-treated patients at our institution. Concomitant use as empiric therapy is appropriate, although larger sample sizes are needed to analyze closely this relation among at-risk subsets of this population.

Do Polymicrobial Intra-Abdominal Infections Have Worse Outcomes than Monomicrobial Intra-Abdominal Infections?

BACKGROUND: Numerous studies have demonstrated microorganism interaction through signaling molecules, some of which are recognized by other bacterial species. This interspecies synergy can prove detrimental to the human host in polymicrobial infections. We hypothesized that polymicrobial intra-abdominal infections (IAI) have worse outcomes than monomicrobial infections. METHODS: Data from the Study to Optimize Peritoneal Infection Therapy (STOP-IT), a prospective, multicenter, randomized controlled trial, were reviewed for all occurrences of IAI having culture results available. Patients in STOP-IT had been randomized to receive four days of antibiotics vs. antibiotics until two days after clinical symptom resolution. Patients with polymicrobial and monomicrobial infections were compared by univariable analysis using the Wilcoxon rank sum, χ(2), and Fisher exact tests. RESULTS: Culture results were available for 336 of 518 patients (65%). The durations of antibiotic therapy in polymicrobial (n = 225) and monomicrobial IAI (n = 111) were equal (p = 0.78). Univariable analysis demonstrated similar demographics in the two populations. The 37 patients (11%) with inflammatory bowel disease were more likely to have polymicrobial IAI (p = 0.05). Polymicrobial infections were not associated with a higher risk of surgical site infection, recurrent IAI, or death. CONCLUSION: Contrary to our hypothesis, polymicrobial IAI do not have worse outcomes than monomicrobial infections. These results suggest polymicrobial IAI can be treated the same as monomicrobial IAI.

Conditional long-term survival following minimally invasive robotic mitral valve repair: a health services perspective.

BACKGROUND: Conditional survival is defined as the probability of surviving an additional number of years beyond that already survived. The aim of this study was to compute conditional survival in patients who received a robotically assisted, minimally invasive mitral valve repair procedure (RMVP). METHODS: Patients who received RMVP with annuloplasty band from May 2000 through April 2011 were included. A 5- and 10-year conditional survival model was computed using a multivariable product-limit method. RESULTS: Non-smoking men (≤65 years) who presented in sinus rhythm had a 96% probability of surviving at least 10 years if they survived their first year following surgery. In contrast, recent female smokers (>65 years) with preoperative atrial fibrillation only had an 11% probability of surviving beyond 10 years if alive after one year post-surgery. CONCLUSIONS: In the context of an increasingly managed healthcare environment, conditional survival provides useful information for patients needing to make important treatment decisions, physicians seeking to select patients most likely to benefit long-term following RMVP, and hospital administrators needing to comparatively assess the life-course economic value of high-tech surgical procedures.

Vancomycin-Associated Nephrotoxicity: The Obesity Factor.

BACKGROUND: Current recommendations suggest that vancomycin dosing utilize actual rather than ideal body weight in obese patients. Thus, obese patients may be at greater risk for nephrotoxicity. The purpose of this study was to compare the incidence of nephrotoxicity in vancomycin-treated obese and lean patients at our institution, where unadjusted, actual body weight-based dosing (capped at 2 g per dose twice daily) is used. We expected obese patients to experience a greater incidence of nephrotoxicity than lean patients. METHODS: This study examined a retrospective cohort of patients treated with vancomycin for gram-positive or mixed infections in our facility from 2005-2009 who were not receiving hemodialysis at the time of admission. Patients were stratified by body mass index (BMI; obese ≥30 kg/m(2) vs. lean <30 kg/m(2)). Relative risk (RR), 95% confidence intervals (CIs), and p values were computed using a generalized estimating equation to accommodate a correlated data structure corresponding to multiple episodes of infection per individual. Multivariable analysis was performed. RESULTS: A total of 530 patients (207 obese; 323 lean) with 1,007 episodes of infection were treated with vancomycin. Patient demographics, co-morbidities, sites of infection, and infecting organisms were similar in the two groups. Female gender (p=0.042), diabetes mellitus (DM) (p=0.018), and hypertension (HTN) (p=0.0009) were more often associated with obesity, whereas allografts (p=0.022) and peripheral vascular disease (p=0.036) were more often present in lean patients. The Acute Physiology and Chronic Health Evaluation II score >21 was the only variable associated with nephrotoxicity (p=0.039). After adjusting for statistically significant variables, obesity was found not to be associated with a greater risk of nephrotoxicity (RR=0.98; 95% CI=0.93-1.04; p=0.59). CONCLUSION: No difference in nephrotoxicity was observed between lean and obese patients treated with vancomycin at our institution.

Whence Resistance?

BACKGROUND: Antimicrobial resistance results from a complex interaction between pathogenic and non-pathogenic bacteria, antimicrobial pressure, and genes, which together comprise the total body of potential resistance elements. The purpose of this study is to review and evaluate the importance of antimicrobial pressure on the development of resistance in a single surgical intensive care unit. METHODS: We reviewed a prospectively collected dataset of all intensive care unit (ICU)-acquired infections in surgical and trauma patients over a 6-y period at a single hospital. Resistant gram-negative pathogens (rGNR) included those resistant to all aminoglycosides, quinolones, penicillins, cephalosporins, or carbapenems; resistant gram-positive infections (rGPC) included methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE). Each resistant infection was evaluated for prior or concomitant antibiotic use, previous treatment for the same (non-resistant) organism, and concurrent infection with the same organism (genus and species, although not necessarily resistant) in another ICU patient. RESULTS: Three hundred and thirty resistant infections were identified: 237 rGNR and 93 rGPC. Infections with rGNR occurred frequently while receiving antibiotic therapy (65%), including the sensitive form of the subsequent resistant pathogen (42.2%). Infections with rGPC were also likely to occur on antimicrobial therapy (50.6%). Treatment of a different patient for an infection with the same resistant pathogen in the ICU at the time of diagnosis, implying potential patient-to-patient transmission occurred more frequently with rGNR infections (38.8%). CONCLUSION: Antimicrobial pressure exerts a substantial effect on the development of subsequent infection. Our data demonstrate a high estimated rate of de novo emergence of resistance after treatment, which appears to be more common than patient-to-patient transmission. These data support the concept that efforts to limit antimicrobial usage will be more efficacious than enhanced isolation procedures when trying to reduce antimicrobial resistance.

Increased Long-Term Mortality among Black CABG Patients Receiving Preoperative Inotropic Agents.

The aim of this study was to examine racial differences in long-term mortality after coronary artery bypass grafting (CABG), stratified by preoperative use of inotropic agents. Black and white patients who required preoperative inotropic support prior to undergoing CABG procedures between 1992 and 2011 were compared. Mortality probabilities were computed using the Kaplan-Meier product-limit method. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. A total of 15,765 patients underwent CABG, of whom 211 received preoperative inotropic agents within 48 hours of surgery. Long-term mortality differed by race (black versus white) among preoperative inotropic category (inotropes: adjusted HR = 1.6, 95% CI = 1.009-2.4; no inotropes: adjusted HR = 1.15, 95% CI = 1.08-1.2; P(interaction) < 0.0001). Our study identified an independent preoperative risk-factor for long-term mortality among blacks receiving CABG. This outcome provides information that may be useful for surgeons, primary care providers, and their patients.

Predictors of Monomicrobial Necrotizing Soft Tissue Infections.

BACKGROUND: Broad-spectrum antibiotic therapy is critical in the management of necrotizing soft tissue infections (NSTI) in the emergency setting. Clindamycin often is included empirically to cover monomicrobial gram-positive pathogens but probably is of little value for polymicrobial infections and is associated with significant side effects, including the induction of Clostridium difficile colitis. However, there have been no studies predicting monomicrobial infections prior to obtaining cultures. The purpose of this study was to identify independent predictors of monomicrobial NSTI where the use of clindamycin would be most beneficial. We hypothesized that monomicrobial infections are characterized by involvement of the upper extremities and fewer co-morbid diseases. METHODS: We reviewed all cases of potential NSTI occurring between 1996 and 2013 in a single tertiary-care center. The infection was diagnosed by the finding of rapidly progressing necrotic fascia during debridement with positive cultures of tissue. Univariable analysis was performed using the Student t-, Wilcoxon rank sum, χ2, and Fisher exact tests as appropriate. Multivariable logistic regression was used to identify independent variables associated with outcomes. RESULTS: A group of 151 patients with confirmed NSTI with complete data was used. Of the monomicrobial infections, 61.8% were caused by Group A streptococci, 20.1% by Staphylococcus aureus, and 12.7% by Escherichia coli. Of the polymicrobial infections, E. coli was involved 13.7% of the time, followed by Candida spp. at 12.9%, and Bacteroides fragilis at 11.3%. On univariable analysis, immunosuppression, upper extremity infection, and elevated serum sodium concentration were associated with monomicrobial infection, whereas morbid obesity and a perineal infection site were associated with polymicrobial infection. On multivariable analysis, the strongest predictor of monomicrobial infection was immunosuppression (odds ratio [OR] 7.0; 95% confidence interval [CI] 2.2-22.3) followed by initial serum sodium concentration (OR 1.1; 95% CI 1.0-1.2). Morbid obesity (OR 0.1; 95% CI 0.0-0.5) and perineal infection (OR 0.3; 95% CI 0.1-0.8) were independently associated with polymicrobial infection. CONCLUSION: We identified independent risk factors that may be helpful in differentiating monomicrobial from polymicrobial NSTI. We suggest empiric clindamycin coverage be limited to patients who are immunosuppressed, have an elevated serum sodium concentration, or have upper extremity involvement and be avoided in obese patients or those with perineal disease.