Contemporary Unplanned Readmission Trends Following Management of Type B Aortic Dissection.

Purpose: Large studies have demonstrated improved survival outcomes with thoracic endovascular aortic repair (TEVAR) at two and five years compared to medical therapy; however, early TEVAR for acute type B aortic dissection (TBAD) remains controversial. We aimed to evaluate trends and clinical predictors of hospital readmissions in patients undergoing medical management and TEVAR for acute TBADs. Materials and Methods: The Nationwide Readmissions Database was queried for all 30-day and 90-day index readmissions (30D-IR and 90D-IR, respectively) after a diagnosis of a TBAD from January 2012 to September 2015. Data on readmission diagnosis, patient demographics, and hospital characteristics were collected from readmitted patients and analyzed. Multivariable logistic regression models were used to identify the predictors of readmission after TEVAR or medical medical management of TBAD. Results: We identified 53,117 patients with acute TBAD. Medical management was the initial treatment modality in 46,985 (88.4%) patients, while 6,132 (11.5%) underwent TEVAR. Factors including older patient age, lower household income, severity of comorbidities, initial hospital length of stay, and urgent procedure demonstrated an increased likelihood of experiencing 30D-IR and 90D-IR (P<0.05). The rate of unplanned readmission for patients undergoing medical management remained stable (11.3% vs. 10.0% for 30D-IR; 19.1% vs. 15.5% for 90D-IR). Reasons for unplanned readmission in the TEVAR cohort were largely related to technical complications. There was no significant difference in readmission costs between medical management and TEVAR. Conclusion: Number of unplanned readmissions in the TEVAR arm decreased significantly over time, whereas the number of readmissions for medical management remained stable.

Enterococcus faecalis promotes a migratory and invasive phenotype in colon cancer cells.

Much about the role of intestinal microbes at the site of colon cancer development and tumor progression following curative resection remains to be understood. We have recently shown that collagenolytic bacteria such as Enterococcus faecalis predominate within the colon postoperatively, particularly at the site of the colon reconnection (i.e. anastomosis) in the early period of post-surgical recovery. The presence of collagenolytic bacteria at this site correlates with the tumor progression in a mouse model of post-surgical tumor development. In the present study we hypothesized, that collagenolytic bacteria, such as E. faecalis, play an important yet to be discovered role in tumor formation and progression. Therefore the aims of this study were to assess the role of collagenolytic E. faecalis on the migration and invasion of a murine colon cancer cell line. Results demonstrated that both migration and invasion were induced by E. faecalis with collagenolytic activity being required for only invasion. Bidirectional signaling in the E. faecalis-cancer cell interaction was observed by the discovering that the expression of gelE in E. faecalis, the gene required for collagenase production, is expressed in response to exposure to CT26 cells. The mechanism by which migration enhancement via E. faecalis occurs appears to be dependent on its ability to activate pro-uPA, a key element of the urokinase-plasminogen system, a pathway that is well - known to be important in cancer cell invasion and migration. Finally, we demonstrated that collagenase producing microbes preferentially colonize human colon cancer specimens.

Fenestrated Endovascular Aortic Repair With Chimney Graft for Thoracoabdominal Aneurysm.

Thoracoabdominal aneurysms pose technical challenges for endovascular repair due to involvement of visceral and renal vessels. We report a case series of four patients diagnosed with thoracoabdominal aneurysm who underwent complex endovascular repair with Fenestrated Device and chimney grafts (FEVARCh). FEVARCh is a technically feasible approach for repair of thoracoabdominal aneurysms that involve renal, superior mesenteric, and celiac arteries for patients not appropriate for open surgical repair. Further studies are needed to understand the implications of resultant Type 1a endoleaks and strategies to minimize the displacement of the main body graft with adjunct chimneys.

Prevention of Anastomotic Leak Via Local Application of Tranexamic Acid to Target Bacterial-mediated Plasminogen Activation: A Practical Solution to a Complex Problem.

OBJECTIVE: To investigate the role of bacterial- mediated plasminogen (PLG) activation in the pathogenesis of anastomotic leak (AL) and its mitigation by tranexamic acid (TXA). BACKGROUND: AL is the most feared complication of colorectal resections. The pathobiology of AL in the setting of a technically optimal procedure involves excessive submucosal collagen degradation by resident microbes. We hypothesized that activation of the host PLG system by pathogens is a central and targetable pathway in AL. METHODS: We employed kinetic analysis of binding and activation of human PLG by microbes known to cause AL, and collagen degradation assays to test the impact of PLG on bacterial collagenolysis. Further, we measured the ability of the antifibrinolytic drug TXA to inhibit this process. Finally, using mouse models of pathogen-induced AL, we locally applied TXA via enema and measured its ability to prevent a clinically relevant AL. RESULTS: PLG is deposited rapidly and specifically at the site of colorectal anastomoses. TXA inhibited PLG activation and downstream collagenolysis by pathogens known to have a causal role in AL. TXA enema reduced collagenolytic bacteria counts and PLG deposition at anastomotic sites. Postoperative PLG inhibition with TXA enema prevented clinically and pathologically apparent pathogen-mediated AL in mice. CONCLUSIONS: Bacterial activation of host PLG is central to collagenolysis and pathogen-mediated AL. TXA inhibits this process both in vitro and in vivo. TXA enema represents a promising method to prevent AL in high-risk sites such as the colorectal anastomoses.

Infliximab Does Not Promote the Presence of Collagenolytic Bacteria in a Mouse Model of Colorectal Anastomosis.

BACKGROUND: Previous work from our group has suggested a pivotal role for collagenolytic bacteria in the development of anastomotic complications. Tumor necrosis factor antagonists are a mainstay of treatment for patients with inflammatory bowel disease. The reported impact of these agents on key surgical outcomes such as anastomotic leak has been inconsistent. The objective of this study is to assess the impact of infliximab on the anastomotic microbiome in a mouse model of colon resection. DESIGN: BALB/c mice underwent colon resection with primary anastomosis. Mice were randomly assigned to receive either an intraperitoneal dose of saline (control) or 10 mg/kg of infliximab for 8 weeks prior to surgery. On postoperative day 7, the animals were sacrificed. Anastomotic tissues were analyzed by histology with TUNNEL staining as a marker of epithelial apoptosis. In order to assess compositional and functional changes of the local microbiome, anastomotic tissues were further analyzed by 16S rRNA V4 region sequencing and for the presence of collagenolytic strains that may impair anastomotic healing. The main outcome measures were microbiome community structure and the presence of collagenolytic bacteria. RESULTS: Infliximab-treated mice demonstrated an increase in epithelial apoptosis, consistent with the expected drug effect. Although infliximab modified the perianastomotic microbiome, no increase in the presence of collagenolytic bacteria was observed. CONCLUSIONS: Infliximab did not promote the emergence of collagenolytic bacteria or demonstrably impair anastomotic healing in a mouse model of colon resection and anastomosis.

Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets.

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa-mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing.NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.

Western Diet Promotes Intestinal Colonization by Collagenolytic Microbes and Promotes Tumor Formation After Colorectal Surgery.

BACKGROUND & AIMS: The Western diet, which is high in fat, is a modifiable risk factor for colorectal recurrence after curative resection. We investigated the mechanisms by which the Western diet promotes tumor recurrence, including changes in the microbiome, in mice that underwent colorectal resection. METHODS: BALB/c male mice were fed either standard chow diet or Western-type diet (characterized by high fat, no fiber, and decreased minerals and vitamins) for 4 weeks; some mice were given antibiotics or ABA-PEG20k-Pi20 (Pi-PEG), which inhibits collagenase production by bacteria, but not bacterial growth, in drinking water. Colorectal resections and anastomoses were then performed. The first day after surgery, mice were given enemas containing a collagenolytic rodent-derived strain of Enterococcus faecalis (strain E2), and on the second day they were given mouse colon carcinoma cells (CT26). Twenty-one days later, distal colons were removed, and colon contents (feces, distal colon, and tumor) were collected. Colon tissues were analyzed by histology for the presence of collagenolytic colonies and by 16S ribosomal RNA sequencing, which determined the anatomic distribution of E faecalis at the site of the anastomosis and within tumors using in situ hybridization. Mouse imaging analyses were used to identify metastases. RESULTS: Colorectal tumors were found in 88% of mice fed the Western diet and given antibiotics, surgery, and E faecalis compared with only 30% of mice fed the standard diet followed by the same procedures. Colon tumor formation correlated with the presence of collagenolytic E faecalis and Proteus mirabilis. Antibiotics eliminated collagenolytic E faecalis and P mirabilis but did not reduce tumor formation. However, antibiotics promoted emergence of Candida parapsilosis, a collagenase-producing microorganism. Administration of a Pi-PEG reduced tumor formation and maintained diversity of the colon microbiome. CONCLUSIONS: We identified a mechanisms by which diet and antibiotic use can promote tumorigenesis by colon cancer cells at the anastomosis after colorectal surgery. Strategies to prevent emergence of these microbe communities or their enzymatic activities might be used to reduce the risk of tumor recurrence in patients undergoing colorectal cancer surgery.

Axillary Surgery for Early-Stage, Node-Positive Mastectomy Patients and the Use of Postmastectomy Chest Wall Radiation Therapy.

BACKGROUND: We examined axillary surgery in mastectomy patients with tumor-positive nodes and how the type of axillary surgery impacted use of postmastectomy chest wall radiation therapy (PMRT). METHODS: Using the National Cancer Data Base, we selected patients with AJCC cT1/T2c N0 breast cancer with one to three tumor-positive lymph nodes treated between 2013 and 2014. Type of axillary surgery was analyzed using the FORDS scope of regional lymph node surgery variable. Multivariable logistic regression modeling was used to identify independent predictors associated with SNB alone and the use of PMRT. RESULTS: Of 8089 patients, 2482 (30.7%) underwent SNB alone, 1339 (16.6%) underwent axillary dissection (ALND) alone, and 4268 (52.7%) underwent SNB followed by ALND. Fifty-seven percent of patients with micrometastases underwent SNB alone compared with 22.6% of patients with macrometastases. Independent predictors of SNB alone for patients with micrometastases were African American race, number of nodes positive, and PMRT. For patients with macrometastases, age, facility type and location, and PMRT were independent predictors for SNB alone. Of 2449 patients who underwent SNB alone, 1538 (62.8%) had no PMRT, 261 (10.7%) had PMRT alone, and 650 (26.5%) had PMRT with regional nodal irradiation. Patients undergoing SNB alone were 1.70 times [96% confidence interval (CI) 1.45-2.00] more likely to undergo PMRT than upfront ALND and 1.51 times (96% CI 1.34-1.71) more likely than SNB followed by ALND. CONCLUSIONS: Surgeons are omitting completion ALND in a third of early-stage, node-positive mastectomy patients. SNB alone patients are more likely to undergo PMRT than patients undergoing ALND.

Optimum Operating Room Environment for the Prevention of Surgical Site Infections.

BACKGROUND: Surgical site infections (SSI), whether they be incisional or deep, can entail major morbidity and death to patients and additional cost to the healthcare system. A significant amount of effort has gone into optimizing the surgical patient and the operating room environment to reduce SSI. METHODS: Relevant guidelines and literature were reviewed. RESULTS: The modern practice of surgical antisepsis involves the employment of strict sterile techniques inside the operating room. Extensive guidelines are available regarding the proper operating room antisepsis as well as pre-operative preparation. The use of pre-operative antimicrobial prophylaxis has become increasingly prevalent, which also presents the challenge of opportunistic and nosocomial infections. Ongoing investigative efforts have brought about a greater appreciation of the surgical patient's endogenous microflora, use of non-bactericidal small molecules, and pre-operative microbial screening. CONCLUSIONS: Systematic protocols exist for optimizing the surgical sterility of the operating room to prevent SSIs. Ongoing research efforts aim to improve the precision of peri-operative antisepsis measures and personalize these measures to tailor the patient's unique microbial environment.

Nasal tip infantile hemangioma, a case of mistaken identity.

Infantile hemangioma is the most common vascular tumor in the pediatric population, and the majority of cases are diagnosed only on history and physical examination. This report highlights a case in which a 3-year-old girl undergoes surgical removal of what was thought to be an infantile hemangioma. Immunohistochemical staining, however, showed the absence of GLUT-1 marker, which discredited the original diagnosis. The vascular tumor was found to be a unique presentation of a pyogenic granuloma. When the clinical diagnosis is in question, referral for biopsy may prevent unnecessary medical interventions.

Real world efficacy of alvimopan on elective bowel resection patients: an analysis of statistical versus clinical significance.

BACKGROUND: Alvimopan has been shown to shorten time to return of bowel function (RBF), thereby decreasing length of stay (LOS). The aim of this study was to assess the clinical significance of this effect on actual practice. METJODS: A retrospective and prospective study of elective bowel resection patients was performed. Surgeons were assigned to alvimopan users (treatment) or nonusers (control). Primary outcome measures included LOS, RBF, and total hospital cost (THC). RESULTS: Mean RBF was 2.93 ± 1.22 days in the treatment group and 4.22 ± 1.81 days in the control group (P < .001). Mean LOS was 7 ± 2.6 days in the treatment group and 7.2 ± 2.2 days in the control group. Mean THC was $7,584 ± $4,770 in the treatment group and $7,310 ± $5,471 in the control group (P > .81). LOS decreased by 2.5 days compared with the historical controls, independent of alvimopan use. CONCLUSIONS: Alvimopan improved RBF but not LOS or THC. Reductions in average LOS of 1 day for ≤6 doses and 2 days if patients received >6 doses were needed to decrease THC.