The systemic inflammatory response that occurs in the septic patient as a result of an infectious insult affects multiple organs and systems, causing numerous physiological derangements. Alterations in phagocytic, lymphocytic and endothelial cell function and immune regulation are evident, leading to heterogeneity in a host’s response to a septic challenge. In addition, the normal hemostatic balance shifts toward a procoagulant state through alterations in tissue factor, antithrombin, protein C and the inhibition of fibinolysis, which can result in thrombus formation and paradoxical hemostatic failure. In an effort to diagnose sepsis and predict outcomes, biomarkers such as C-reactive protein, pro-calcitonin, pro- and anti-inflammatory cytokines have been investigated with varying results. Targeted therapies for sepsis, most notably Xigris (recombinant human activated protein C), have proven unsuccessful and treatment continues to remain reliant on source control, antibiotics and supportive interventions, specifically early goal-directed therapy. This brief review gives an overview of the immunopathologic and coagulopathic alterations that occur in sepsis, soluble inflammatory mediators as potential diagnostic and prognostic biomarkers, and the clinical management of the septic patient.

Sepsis, a leading cause of death in the U.S., has poorly understood mechanisms of mortality. To address this, our model of Cecal Ligation and Puncture (CLP) induced sepsis stratifies mice as predicted to Live (Live-P) or Die (Die-P) based on plasma IL-6. Six hours post-CLP, both Live-P and Die-P groups have equivalent peritoneal bacterial colony forming units and recruitment of phagocytes. By 24hr, however, Die-P mice have increased bacterial burden, despite increased neutrophil recruitment, suggesting Die-P phagocytes have impaired bacterial killing. Peritoneal cells were used to study multiple bactericidal processes: bacterial killing, Reactive Oxygen Species (ROS) generation, and phagocytosis. Total phagocytosis and intra-phagosomal processes were determined with triple-labeled E.coli, covalently labeled with ROS and pH sensitive probes, and an ROS/pH insensitive probe for normalization. While similar proportions of Live-P and Die-P phagocytes responded to exogenous stimuli, Die-P phagocytes showed marked deficits in all parameters measured, thus suggesting immunosuppression rather than exhaustion. This contradicts the prevailing sepsis paradigm that acute phase sepsis deaths (<5 days) result from excessive inflammation, whereas chronic phase deaths (>5 days) are characterized by insufficient inflammation and immunosuppression. These data suggest that suppression of cellular innate immunity in sepsis occurs within the first six hours.

Dupuytren's contracture, a benign condition characterized by fibrosis of the palmar and digital fascia, may be a debilitating condition that limits daily function. Several techniques exist for managing symptomatic contractures of the hand related to Dupuytren's. These techniques include the more invasive open fasciotomy or fasciectomy. More recently, less invasive techniques including administration of collagenase Clostridium histolyticum (CCH) or percutaneous needle aponeurotomy (PNA) have become part of the treatment armamentarium. A comprehensive review of the literature is performed and an algorithm for management of Dupuytren's contracture is proposed.

The acute-phase response is characteristic of perhaps all infections, including bacterial pneumonia. In conjunction with the acute-phase response, additional biological pathways are induced in the liver and are dependent on the transcription factors STAT3 and NF-B, but these responses are poorly understood. Here, we demonstrate that pneumococcal pneumonia and other severe infections increase expression of multiple components of the cellular secretory machinery in the mouse liver, including the endoplasmic reticulum (ER) translocon complex, which mediates protein translation into the ER, and the coat protein complexes (COPI and COPII), which mediate vesicular transport of proteins to and from the ER. Hepatocyte-specific mutation of STAT3 prevented the induction of these secretory pathways during pneumonia, with similar results observed following pharmacological activation of ER stress by using tunicamycin. These findings implicate STAT3 in the unfolded protein response and suggest that STAT3-dependent optimization of secretion may apply broadly. Pneumonia also stimulated the binding of phosphorylated STAT3 to promoter regions of secretion-related genes in the liver, supporting a direct role for STAT3 in their transcription. Altogether, these results identify a novel function of STAT3 during the acute-phase response, namely, the induction of secretory machinery in hepatocytes. This may facilitate the processing and delivery of newly synthesized loads of acute-phase proteins, enhancing innate immunity and preventing liver injury during infection.

Background Chest radiography is routinely used post-tracheostomy to evaluate for complications. Often, the chest X-ray findings do not change clinical management. The present study was conducted to evaluate the utility of post-tracheostomy X-rays. Method This retrospective review of 255 patients was performed at a single-center, university, level I trauma center. All patients underwent tracheostomy and were evaluated for postprocedure complications. Results Of the 255 patients, 95.7% had no change in postprocedure chest X-ray findings. New significant chest X-ray findings were found in 4.3% of patients, including subcutaneous emphysema, pneumothorax, and new significant consolidation. Only three of these patients required change in clinical management, and all changes were based on clinical presentation alone. Conclusions Routine chest X-ray following tracheostomy fails to provide additional information beyond clinical examination. Therefore radiographic examination should be performed only after technically difficult procedures or if the patient experiences clinical deterioration. Significant cost savings and minimization of radiation exposure can be achieved when chest radiography after tracheostomy is performed exclusively for clinical indications.

Background Sepsis remains a serious clinical problem despite intensive research efforts and numerous attempts to improve outcome by modifying the inflammatory response. Substance P, the principal ligand for the neurokinin-1 receptor (NK-1R), is a potent pro-inflammatory mediator that exacerbates inflammatory responses and cardiovascular parameters in sepsis. Location University basic science research laboratory. Methods The current study examined whether inhibition of the NK-1R with a specific antagonist (CJ-12,255) would improve survival in the cecal ligation and puncture (CLP) model of sepsis in adult female outbred mice. NK-1R treatment at the initiation of sepsis improved survival in CLP sepsis (NK-1RA survival = 79% vs. vehicle = 54%). Delaying therapy for as little as 8 hours post CLP failed to provide a survival benefit. NK-1RA treatment did not prevent the sepsis induced decrease in circulating white blood cells, augment the early (6 h post CLP) recruitment of inflammatory cells to the peritoneum or improve phagocytic cell killing of pathogens. However, the NK-1R antagonist significantly reduced both circulating and peritoneal cytokine concentrations. Additionally, the cardiovascular parameter pulse distension (a surrogate for stroke volume) was improved in the NK-1RA group during the first six hours of sepsis and there was a significant reduction in loss of fluid into the intestine. Conclusion These data show that early activation of the NK-1R by substance P decreases sepsis survival through multiple mechanisms including depressing stroke volume, increasing fluid loss into the intestine and increasing inflammatory cytokine production.

The latissimus dorsi flap has been used to reconstruct mastectomy defects for more than 100 years. It has remained relevant in breast reconstruction because of its consistent anatomy, robust vascular supply, congruent vector, and ability to cover large surface areas. With the evolution of oncologic and reconstructive techniques as well as improvements in prosthetic devices, however, this myocutaneous flap has largely fallen out of favor in primary breast reconstruction. Our experience demonstrates that the latissimus dorsi flap remains a versatile flap that may be tailored to reconstruct various oncologic breast defects and deformities in an expeditious fashion.

Background:Patients undergoing incisional/ventral hernia repair are at risk of developing several postoperative complications particularly venous thromboembolism (VTE), which is a major cause of morbidity and mortality. The aim of this study was to assess 30-day postoperative morbidity and mortality of patients undergoing incisional/ventral hernia repair and to determine the association between component separation and VTE.Methods:We reviewed the 2005–2011 American College of Surgeons National Surgical Quality Improvement Program databases to identify patients undergoing incisional/ventral hernia repair. Preoperative variables and postoperative outcomes were compared between a component separation group and a non–component separation group. The χ2 tests and Fisher’s exact test were used for categorical variables and t tests for continuous variables. Logistic regression analysis was performed to determine preoperative predictors for complications in both groups.Results:Thirty-four thousand five hundred forty-one patients were included in our study; 501 patients underwent a component separation procedure. A higher rate of wound complications, minor/major morbidity, mortality, and return to the operating room occurred in the component separation group. However, there was no statistically significant difference in deep vein thrombosis/thrombophlebitis and pulmonary embolism rates between the 2 groups (P = 0.780 and P = 0.591, respectively). Several risk factors were significantly associated with postoperative complications in both groups.Conclusions:Component separation is used for large and complex incisional/ventral hernia repairs to achieve tension-free midline closure. Although component separation hernia repair is associated with higher incidence of wound complication, morbidity, and mortality, perhaps because of the complexity of the defects, it does not seem to be associated with increased VTE rates.