Refining the Latissimus Dorsi Flap: A Useful Tool to Salvage Complex Breast Defects.

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.

A Deceptive Diagnosis: Pyoderma Gangrenosum After Breast Surgery-A Case Series and Literature Review.

Postsurgical pyoderma gangrenosum is a rare neutrophilic dermatosis that presents with characteristic ulcerative lesions and systemic signs and symptoms of inflammation. It has been well documented after both cosmetic and reconstructive breast surgeries. Given its similarity to postoperative infectious processes, a high index of suspicion is necessary to initiate treatment with immunosuppression and avoid unnecessary and potentially disfiguring debridements. We present our experience with 4 cases of pyoderma gangrenosum after breast reconstruction and review the existing literature regarding pyoderma gangrenosum after breast surgery.

Dupuytren's Contracture: An Evidence Based Review.

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.

Antagonism of the Neurokinin-1 Receptor Improves Survival in a Mouse Model of Sepsis by Decreasing Inflammation and Increasing Early Cardiovascular Function.

OBJECTIVES: 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, is a potent proinflammatory mediator that exacerbates inflammatory responses and cardiovascular variables in sepsis. DESIGN: The current study examined whether inhibition of the neurokinin-1 receptor with a specific antagonist (CJ-12,255) would improve survival in the cecal ligation and puncture model of sepsis in adult female outbred mice. SETTING: University basic science research laboratory. MEASUREMENTS AND MAIN RESULTS: Neurokinin-1 receptor treatment at the initiation of sepsis improved survival in cecal ligation and puncture sepsis (neurokinin-1 receptor antagonist survival = 79% vs vehicle = 54%). Delaying therapy for as little as 8 hours postcecal ligation and puncture failed to provide a survival benefit. Neurokinin-1 receptor antagonist treatment did not prevent the sepsis-induced decrease in circulating WBCs, augment the early (6 hr postcecal ligation and puncture) recruitment of inflammatory cells to the peritoneum, or improve phagocytic cell killing of pathogens. However, the neurokinin-1 receptor antagonist significantly reduced both circulating and peritoneal cytokine concentrations. In addition, the cardiovascular variable, pulse distension (a surrogate for stroke volume) was improved in the neurokinin-1 receptor antagonist group during the first 6 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 neurokinin-1 receptor by substance P decreases sepsis survival through multiple mechanisms including depressing stroke volume, increasing fluid loss into the intestine, and increasing inflammatory cytokine production.

Acute-Phase Deaths from Murine Polymicrobial Sepsis Are Characterized by Innate Immune Suppression Rather Than Exhaustion.

Sepsis, a leading cause of death in the United States, 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 24 h, 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 intraphagosomal processes were determined with triple-labeled Escherichia coli, covalently labeled with ROS- and pH-sensitive probes, and an ROS/pH-insensitive probe for normalization. Although 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 d) result from excessive inflammation, whereas chronic-phase deaths (>5 d) are characterized by insufficient inflammation and immunosuppression. These data suggest that suppression of cellular innate immunity in sepsis occurs within the first 6 h.

Pathophysiologic mechanisms in septic shock.

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.

The initial response to the Boston marathon bombing: lessons learned to prepare for the next disaster.

OBJECTIVE: We discuss the strengths of the medical response to the Boston Marathon bombings that led to the excellent outcomes. Potential shortcomings were recognized, and lessons learned will provide a foundation for further improvements applicable to all institutions. BACKGROUND: Multiple casualty incidents from natural or man-made incidents remain a constant global threat. Adequate preparation and the appropriate alignment of resources with immediate needs remain the key to optimal outcomes. METHODS: A collaborative effort among Boston's trauma centers (2 level I adult, 3 combined level I adult/pediatric, 1 freestanding level I pediatric) examined the details and outcomes of the initial response. Each center entered its respective data into a central database (REDCap), and the data were analyzed to determine various prehospital and early in-hospital clinical and logistical parameters that collectively define the citywide medical response to the terrorist attack. RESULTS: A total of 281 people were injured, and 127 patients received care at the participating trauma centers on that day. There were 3 (1%) immediate fatalities at the scene and no in-hospital mortality. A majority of the patients admitted (66.6%) suffered lower extremity soft tissue and bony injuries, and 31 had evidence for exsanguinating hemorrhage, with field tourniquets in place in 26 patients. Of the 75 patients admitted, 54 underwent urgent surgical intervention and 12 (22%) underwent amputation of a lower extremity. CONCLUSIONS: Adequate preparation, rapid logistical response, short transport times, immediate access to operating rooms, methodical multidisciplinary care delivery, and good fortune contributed to excellent outcomes.

Roles of STAT3 in protein secretion pathways during the acute-phase response.

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-κB, 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.

Chest X-ray after tracheostomy is not necessary unless clinically indicated.

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.

Neurokinin-1 Receptor Deficiency Improves Survival in Murine Polymicrobial Sepsis Through Multiple Mechanisms in Aged Mice.

OBJECTIVE: Substance P (SP) is a neuropeptide that contributes to a proinflammatory state by binding to the neurokinin 1 receptor (NK-1R). Limiting this interaction has been shown to attenuate the acute inflammation. Our hypothesis was that NK-1R activation would contribute to the morbidity and mortality of sepsis in a model using mice genetically deficient in the NK-1R. METHODS: To investigate the role of the SP/NK-1R axis in a murine model of sepsis, cecal ligation and puncture (CLP) in NK-1R deficient and wild type (WT) aged mice was performed. Acute inflammation was assessed by measuring circulating cytokines and clinical parameters. RESULTS: Deletion of the NK-1R results in improved survival following CLP (NK-1R knockout mice survival = 100% vs. WT = 14%). A reduction in the inflammatory cytokines interleukin (IL) 6, macrophage inflammatory peptide 2, and IL-1 receptor antagonist, improved hemodynamic parameters, and increased neutrophilia were present in the NK-1R-deficient mice after CLP compared with WT mice. CONCLUSIONS: These data confirm the hypothesis that eliminating the SP/NK-1R interaction in a highly lethal murine model of sepsis leads to decreased morbidity and mortality through multiple mechanisms.

Puerto Rico experience with plugs in the treatment of anal fistulas.

BACKGROUND: Anorectal fistula is a common problem that affects quality of life. Main objective of therapy has been to eradicate the fistula tract while preserving fecal continence. Latest good results for anal fistula treatment have been an anal fistula plug. This study was undertaken to determine if these results could be reproduced in Puerto Rico. METHOD: From January 2003 to January 2008, two experienced colorectal surgeons performed this new operation in 23 consecutive patients. A multivariable analysis was undertaken including age, sex, location of the fistula, previous surgeries, Seton placement before the insertion of the plug, continence pre and post operation, as well as close follow up. No patient with inflammatory bowel disease was included. RESULTS: We had a good result or healing of the fistula in 14 of 23 patients for a success rate of 60%. We had a subgroup of patients who did slightly better and had a healing rate of 66% compared to the 60% of the whole group. It appears to be a trend in favor of the Seton group but is not statically significant. We had 9 failures of 23 patients or 39%. Suppuration was noticed in three patients and all three had failures of the plug with recurrences. CONCLUSIONS: This new operation is another alternative to add to our armamentarium but we need to search for an operation that decreases the incidence of recurrences we had in our study while maintaining function of the sphincters.

Hermansky Pudlak syndrome: an unusual form of procto-colitis.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder consisting of oculocutaneous albinism, platelet dysfunction and systemic complications associated with lipofuscin deposition in the reticuloendothelial system. HPS has been associated with a granulomatous enterocolitis with pathologic features suggestive of Crohn's disease. It remains uncertain if HPS represents a truly distinct form of granulomatous enterocolitis. We report a series of two patients with HPS treated in Puerto Rico, and the results from medical and surgical intervention for gastrointestinal disease. Our experience with HPS patients has shown the difficult management of perineal disease similar in the management of Crohn's. However, complications from the bleeding diathesis necessitate caution during surgery and potential anesthesia complications. Furthermore, avoidance of a perineal wound is preferred, and when possible, ileostomies have fewer complications than colostomies as they do not involve the small bowel.

Cutaneous Breast Radiation-associated Angiosarcoma: Anterior Chest Wall Reconstruction Options Following Extra-radical Resection.

BACKGROUND: Radiation-associated angiosarcoma (RAAS) of the breast is a rare complication following breast irradiation with high rates of recurrence and death. To improve survival, we have advocated for an extra-radical resection where the entire irradiated skin and subcutaneous tissue is excised. This results in very large chest defects for which we describe our reconstructive experience. METHODS: We performed a retrospective review of patients diagnosed with RAAS and treated with extra-radical resection followed by immediate reconstruction between 1999 and 2017. We analyzed reconstructive options, complications rates, length of stay, and operative times. RESULTS: Extra-radical resections were performed in 35 patients. We reconstructed these large defects with abdominal advancement flaps with split-thickness skin grafting in 25 patients and added a pedicled latissimus dorsi or omental flap in the 10 other patients. Skin grafts took well over the irradiated pectoralis major muscle with a median take rate of over 90%. Average operative times were 150 minutes for those treated with an abdominal advancement flap and skin grafting with a median length of stay of 5 days for all patients. CONCLUSION: Large anterior chest soft-tissue defects caused by extra-radical resections leaves defects too large to be covered by traditional breast reconstruction flaps. Abdominal advancement, latissimus dorsi muscle, and omental flaps along with skin grafts can be safely performed while leaving other traditional options open for future breast reconstruction.

Is There an Association between Component Separation and Venous Thromboembolism? Analysis of the NSQIP.

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 χ(2) 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.

Location, location, location: cytokine concentrations are dependent on blood sampling site.

OBJECTIVE: Considerable breakthroughs in the field of sepsis have been made using animal models. Sepsis exhibits a wide array of derangements that may be evaluated in the blood, including the release of proinflammatory and anti-inflammatory cytokines. The Shock journal adheres to the ARRIVE guidelines regarding reporting in vivo results to allow reproducibility of data findings. It is generally assumed that blood cytokine concentrations collected from typical sampling sites will be similar, but there are no data validating that this is true. The main purpose of the present study was to determine if the location of blood sampling results in cytokine concentration differences following inflammatory insults. METHODS: Two different models of acute inflammation were studied. Adult, female ICR (Institute of Cancer Research) mice were injected with Escherichia coli lipopolysaccharide (n = 28) or subjected to cecal ligation and puncture (n = 16). They were killed at early time points following these inflammatory challenges for the collection of blood from the facial vein, retro-orbital sinus, and heart. Additional samples were collected in EDTA and heparin. Plasma cytokines from the same mouse were collected from each sampling site and evaluated by enzyme-linked immunosorbent assay. Clinical chemical parameters including plasma blood urea nitrogen and total protein were also analyzed. RESULTS: Regardless of model, time of collection, or cytokine measured, cytokine values from heart blood were higher than facial vein values from the same mouse. Interleukin (IL-6) collected from the heart relative to the facial vein demonstrated elevated concentrations following injection of lipopolysaccharide. In a similar manner, higher concentrations of IL-6, macrophage inflammatory protein 2, IL-10, and IL-1 receptor antagonist were found in cardiac puncture samples compared with other sampling sites 24 h after sepsis induced by cecal ligation and puncture. Similar differences were not seen when comparing blood urea nitrogen and total protein values from the two different sites. Using plasma IL-6 collected from the heart would incorrectly stratify predicted-to-live mice into the predicted-to-die category. Therefore, a simple linear regression model was developed to correctly restratify mice to their predicted fate. These data demonstrate that proinflammatory and anti-inflammatory cytokine concentrations are dramatically elevated when drawn centrally from the heart compared with collection from peripheral locations such as the facial vein. It is critical for publications to document the sampling location when evaluating plasma cytokines and attempting to compare studies.

Genetic evidence that apolipoprotein E4 is not a relevant susceptibility factor for cholelithiasis in two high-risk populations.

Apolipoprotein E (apoE) isoforms are genetic determinants of interindividual variations in lipid metabolism. To assess whether apoE is a genetic risk factor for cholesterol gallstone disease (GD), we analyzed apoE variants in populations from Chile and Germany, two countries with very high prevalence rates of this disease. ApoE genotypes were determined in Chilean gallstone patients (n = 117) and control subjects (n = 122) as well as in German gallstone patients (n = 184) and matched controls (n = 184). In addition, we studied apoE variants in subgroups of Chilean patients with strong differences in their susceptibility to acquire gallstones: 50 elderly subjects without gallstones in spite of well-known risk factors for this disease (gallstone-resistant) and 32 young individuals with gallstones but without risk factors (gallstone-susceptible). Furthermore, correlation analysis of apoE genotypes with cholesterol crystal formation times, biliary cholesterol saturation index (CSI), and gallstone cholesterol contents was performed in 81 cholecystectomized patients. In this study analyzing the largest sample set available, apoE4 genotype was not associated with an increased frequency of GD in either population. Moreover, in the Chilean population after adjusting for risk factors such as gender, age, body mass index, serum lipids, and glucose, the odds ratio for the association of the apoE4 allele and GD was significantly (P < 0.05) <1. Also, genotypes were not correlated with cholesterol crystal formation time, CSI, or gallstone cholesterol content. In contrast to previous smaller studies, apoE polymorphisms were not associated with susceptibility to cholesterol GD in high-risk populations.