Community-acquired methicillin-resistant Staphylococcus aureus in surgically treated hand infections.

PURPOSE: An increase in the incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections has been observed. The purpose of this study is to determine the change in proportion of surgically treated CA-MRSA hand infections over the last decade and to identify associated risk factors. METHODS: A retrospective review was performed of all 159 hand infections treated in the operating room over an 11-year period (1997-2007). Mean age overall was 40 years, mean inpatient length of stay was 4.9 days, and 115 of the 159 patients were male. Examined data included known risk factors for MRSA, including human immunodeficiency virus infection, diabetes mellitus, intravenous drug use, incarceration, and homelessness. RESULTS: Forty-eight patients had surgery for hand infections due to CA-MRSA. The yearly proportion of CA-MRSA increased over the study period, and the risk of having an MRSA infection was 41% higher with each progressive calendar year during the study period relative to the apparent incidence of non-MRSA hand infections. Other factors associated with CA-MRSA were intravenous drug use, felon-type infection, and prior hand infection. Multivariable logistic regression identified intravenous drug use as a significant, independent risk factor for CA-MRSA hand infection. CONCLUSIONS: The proportion of surgically treated hand infections due to CA-MRSA has increased during the last decade. Intravenous drug use was the only independent risk factor for CA-MRSA infections treated in the operating room at our institution.

Career plans of graduating plastic surgery trainees in 2009: the impact of an uncertain economic climate.

BACKGROUND: Trainees in plastic surgery graduating in the midst of the current economic recession face unique financial challenges. These issues have the potential to affect future training and practice plans. METHODS: A 13-item questionnaire regarding issues influencing career plans was administered to senior plastic and reconstructive surgery trainees attending the 2009 American Society of Plastic Surgery Senior Residents Conference, in Austin, Texas. RESULTS: Of 97 conference attendees, 57 (58.7 percent) completed the survey representing all regions of the United States (33.3 percent of trainees nationwide). Trainees in the traditional training model (i.e., plastic surgery fellowship after surgery residency) were significantly less likely to pursue additional subspecialty training (29.6 percent) compared with trainees in integrated (76.9 percent) or combined programs (58.8 percent) (p = 0.012). Trainees who have dependents were significantly more likely to go into practice without fellowship (69 versus 38.2 percent, p = 0.031). Outstanding educational debt (>$50,000 or >$100,000) did not influence future practice plans. Trainees who are concerned about the national economic recession trended toward entering practice without fellowship training (70.0 versus 40.5 percent, p = 0.052). Of the factors surveyed, only anticipated fellowship training was significantly associated with plans to pursue academic practice (p = 0.002). CONCLUSIONS: The majority of graduating trainees enter private practice without additional subspecialty fellowship training. Neither exceptional debt nor concern about the current economic recession was the primary determinant of future career plans, whereas trainees in a traditional model of plastic surgery and trainees with dependents were more likely to enter practice without further fellowship training.

Variation in the TLR4 gene influences the risk of organ failure and shock posttrauma: a cohort study.

BACKGROUND: Genetic variation contributes to risk and outcomes of sepsis. We sought to determine whether variation in inflammation related genes is associated with severity of sepsis in trauma patients. METHODS: A cohort of severely injured Caucasian patients was studied and genotyped for candidate single nucleotide polymorphisms (SNPs). These were toll-like receptor 4 (TLR4) A896G, tumor necrosis factor-alpha G-308A, interleukin-6 G-174C, interleukin-1beta C-31T, and cluster of differentiation marker 14C-159T. SNP genotypes among patients with sepsis and complicated sepsis were analyzed by chi2 and logistic regression. Six haplotype-tagging SNPs in the TLR4 gene were subsequently examined to analyze their influence on TLR4 A896G SNPs relationship to sepsis severity. RESULTS: We enrolled 598 patients. Complicated sepsis developed in 147 (25%). Adjusting for independent risk factors, carriage of the variant TLR4 896 G allele was associated with decreased risk of complicated sepsis (odds ratio = 0.3, 95% confidence interval, 0.1-0.7, p = 0.008). Furthermore, two haplotypes seemed to better characterize this risk than the variant TLR4 896G allele. The variant TLR4 896G allele is linked to one common haplotype, which seems to confer a considerably reduced risk of complicated sepsis. (aOR = 0.2 95% confidence interval, 0.05-0.7, p = 0.01). CONCLUSIONS: Variation within TLR4 gene is associated with severity of posttraumatic sepsis. This risk may not be solely related to TLR4 A896G SNP. It is likely that other, uncharacterized variations in the TLR4 gene contribute to sepsis severity. A thorough evaluation of variability within the TLR4 gene is needed to characterize sepsis risk.

The influence of gender on human innate immunity.

BACKGROUND: Several experimental, clinical, and epidemiologic studies indicate a better prognosis in women after an infectious challenge. The monocyte/macrophage, as coordinators of the innate immune response to sepsis, secrete plasma inflammatory cytokines. Elevated plasma cytokine levels are inversely correlated with outcome. In addition, single-nucleotide polymorphisms related to these cytokine genes and in genes important for lipopolysaccharide (LPS) detection, particularly toll-like receptor-4, have been associated with variations in clinical outcome. We hypothesize that the gender differences in clinical outcome are due to measurable differences in cytokine responses and intracellular signaling, and these differences are independent of polymorphism carrier status. METHODS: Venous blood samples from healthy subjects (56 men, 23 women) were incubated with LPS, and supernatant cytokine levels were determined by enzyme-linked immunosorbent assay. In a randomly chosen subgroup, (8 men, 4 women), peripheral blood mononuclear cells were isolated, and LPS-mediated intracellular mitogen-activated protein kinase (MAPK) phosphorylation was assayed via Western blot analysis. Each subject was screened for the following SNPs: tumor necrosis factor alpha (TNF-alpha) -308G/A, interleukin (IL)-6 -174G/C, IL-1beta -31C/T, and toll-like receptor-4 (TLR4) +896A/G. RESULTS: Women produced significantly less LPS-induced TNF-alpha and IL-1beta but not IL-6. When the analysis was adjusted for the presence of each polymorphism, the differences in TNF-alpha and IL-1beta accumulation persisted. Female gender was associated with lower MAPK phosphorylation at each LPS concentration but was not statistically significant. CONCLUSIONS: Gender-specific differences in LPS-induced TNF-alpha and IL-1beta were observed, possibly attributed to alterations in MAPK phosphorylation. Furthermore, studies investigating the influence of genomic variation on the innate immune response should address potential gender-related differences.

Genetic determinants of the inflammatory response.

PURPOSE OF REVIEW: Despite substantial advances in our understanding of the biology of sepsis and inflammation, improvements in clinical outcomes have been more sporadic and, with few notable exceptions, are related to improvements in supportive care rather than to specific therapies. As a result, morbidity, mortality, and cost remain high. Investigation into the genetic determinants of this response span a broad spectrum and include those aimed at deciphering the mechanisms and involved pathways on a molecular level, to those aiming to identify how genetic variation may be clinically important. While it is clear that gene sequencing and manipulation of experimental models have provided insight into the biology of the inflammatory response to infection, these technologies and their application to the study of naturally occurring human genetic variation have yet to provide the same insight or clinical benefit. The purpose of this review is to summarize what is known about the genetic determinants of the inflammatory response. We make particular reference to this broad scope of investigation introduced above but with a focus on the present status of studies examining the role of human genetic variation in the risk for and outcome from severe bacterial infection, or sepsis. RECENT FINDINGS: Using the examples of two candidate genes tumor necrosis factor-alpha (TNF-alpha) and toll-like receptor 4 (TLR4), we illustrate the spectrum of studies concerning the genetic determinants of the inflammatory response. We highlight recent literature across this spectrum, focusing on genetic association studies examining the relationships between SNPs in these genes and sepsis risk and outcome. We then review the literature addressing discordant findings in basic experimental observations and studies of clinical association. SUMMARY: Naturally occurring genetic variants in important inflammatory mediators such as TNF-alpha and TLR4 appear to alter inflammatory responses in numerous experimental and a few clinical models of inflammation. However, inconsistencies exist in the literature regarding the association between these genetic variants and disease (eg, sepsis) susceptibility and prognosis. The main limitations relate to the translation of experimental observations into reproducible genotype-phenotype associations. The reasons for these are multifactorial and include deficiencies in study design (insufficient sample size), and the complexities introduced by background genetic heterogeneity.

The effect of the maze procedure on the secretion of arginine-vasopressin and aldosterone.

BACKGROUND: Excessive fluid retention is a serious complication after the maze procedure that cannot be totally explained by changes in levels of atrial natriuretic peptide. We therefore measured circulating levels of arginine vasopressin and aldosterone in patients undergoing the maze procedure to study their possible role in this postoperative complication. METHODS: Serial arginine vasopressin and aldosterone levels were monitored for 72 hours in 11 patients after coronary artery bypass grafting and in 13 patients after the maze procedure. Hemodynamic data, urine output, fluid balance, and complications were recorded prospectively during the same period of time. RESULTS: Plasma levels of arginine vasopressin and aldosterone were significantly higher in patients after the maze procedure when compared with patients after coronary artery bypass grafting. CONCLUSIONS: This study documents that the maze procedure results in increased plasma arginine vasopressin and aldosterone levels and indicates that they, rather than atrial natriuretic peptide alone, participate in the excessive postoperative fluid retention that follows the maze procedure. We believe that these hormone elevations are most likely secondary to a temporary lack of response of the atrial baroreceptors. These results may explain the effectiveness of spironolactone therapy after the maze procedure.

Antimicrobial strategies in surgical critical care.

There is clear evidence that early and appropriate empiric antimicrobial therapy for suspected nosocomial infections reduces the rate of adverse outcomes. This approach necessitates a liberal antimicrobial policy, whereas observational and experimental data also suggest that excessive antibiotic use promotes the emergence of antimicrobial resistance, creating a dilemma for the intensivists and begging the question as to whether minimization of antimicrobial resistance and maximization of individual patient outcomes are mutually exclusive. Contemporary strategies are outlined for the antimicrobial management of ventilator-associated pneumonia, the most common nosocomial infection in the intensive care unit, and the use of institution-specific guidelines, invasive diagnostic approaches, and other objective criteria to ensure adequate, yet not excessive use of antimicrobials are discussed. The focus is then on relative merits of routine antifungal prophylaxis as an example of an attempt to reduce the incidence and adverse consequences of late diagnoses of fungal sepsis. Finally, the advantages and disadvantages of antimicrobial cycling as a means of reducing antimicrobial resistance in the intensive care unit are outlined.