Surprising neutral effect of shorter staple cartridges in laparoscopic sleeve gastrectomy.

BACKGROUND: Consensus agreements regarding laparoscopic sleeve gastrectomy (LSG) advise against using staple loads less than 1.5 mm in closed staple height. However, few data exist to support this recommendation. We hypothesized that using staples with a shorter closed height would actually decrease incidence of intraoperative and postoperative bleeding during LSG, while not increasing the incidence of leak. METHODS: All LSG cases for a single institution from 1/1/2014 to 12/31/2019 were exported for analysis. Two cohorts were established: 1. 'Green/Blue' group was cases in which no white cartridges were used and 2. 'White' group was cases in which any white cartridges were used. Demographic variables, procedural characteristics, hospital length of stay, and postoperative outcomes were compared between groups. RESULTS: The study populations included 1710 patients, 974 in the green/blue group and 736 in the white cartridge group. There were no significant differences in postoperative leak, bleed, stricture, readmission, or death while using white staple loads as compared with the standard combination of blue and green loads. CONCLUSION: Using staples with a shorter closed height during LSG did not impact the postoperative bleeding or leak rate. The impact from selection of shorter staples to achieve more tissue compression may be limited.

Multisite study of Titan SGS stapler in longitudinal gastric resection.

BACKGROUND: Standardization of the laparoscopic sleeve gastrectomy procedure is needed to improve patient outcomes. A single-fire 23 cm stapler was developed to streamline the operation. Comparative testing conducted on excised human tissue has demonstrated the superiority of the novel Titan SGS stapler to two commonly utilized commercial devices in both staple line integrity and burst pressure. We hypothesized that the stapler would be safe and effective in creating longitudinal gastric resections in human patients. METHODS: 61 patients were enrolled to undergo gastric resection with the Titan SGS stapler. Perioperative interventions and post-operative adverse events were recorded. Upper GI study was completed on post-operative day 1, and patients were followed for 6 weeks post-operatively to determine any subacute device-related adverse events. RESULTS: Surgeon feedback for intraoperative device utilization and post-operative gastric pouch shape were positive. Adverse events were found to be mild, limited, and generally well-known effects of bariatric surgery. One episode of post-operative hemorrhage required surgical takeback, with no criminal bleeding vessel identified. CONCLUSION: The Titan SGS stapler is both safe and effective in sleeve gastrectomy pouch creation.

Burn injury influences the T cell homeostasis in a butyrate-acid sphingomyelinase dependent manner.

Following burn injury, a key factor for patients susceptible to opportunistic infections is immune suppression. Butyrate levels are important in maintaining a functional immune system and these levels can be altered after injury. The acid sphingomyelinase (Asm) lipid signaling system has been implicated in a T cell actions with some evidence of being influenced by butyrate. Here, we hypothesized that burn-injury changes in butyrate levels would mediate Asm activity and, consequently, T cell homeostasis. We demonstrate that burn injury temporally decreases butyrate levels. We further determined that T cell Asm activity is increased by butyrate and decreased after burn injury. We additionally observed decreased T cell numbers in Asm-deficient, burn-injured, and microbiota-depleted mice. Finally, we demonstrate that butyrate reduced T cell death in an Asm-dependent manner. These data suggest that restoration of butyrate after burn injury may ameliorate the T cell lost observed in burn-injured patients by Asm regulation.

Matrix Metalloproteinase-8 Augments Bacterial Clearance in a Juvenile Sepsis Model.

Genetic ablation or pharmacologic inhibition of matrix metalloproteinase-8 (MMP8) improves survival in an adult murine sepsis model. Because developmental age influences the host inflammatory response, we hypothesized that developmental age influences the role of MMP8 in sepsis. First, we compared sepsis survival between wild type (WT, C57BL/6) and MMP8 null juvenile-aged mice (12-14 days) after intraperitoneal injection of a standardized cecal slurry. Second, peritoneal lavages collected at 6 and 18 hours after cecal slurry injection were analyzed for bacterial burden, leukocyte subsets, and inflammatory cytokines. Third, juvenile WT mice were pretreated with an MMP8 inhibitor prior to cecal slurry injection; analysis of their bacterial burden was compared to vehicle-injected animals. Fourth, the phagocytic capacity of WT and MMP8 null peritoneal macrophages was compared. Finally, peritoneal neutrophil extracellular traps (NETs) were compared using immunofluorescent imaging and quantitative image analysis. We found that juvenile MMP8 null mice had greater mortality and higher bacterial burden than WT mice. Leukocyte counts and cytokine concentrations in the peritoneal fluid were increased in the MMP8 null mice, relative to the wild type mice. Peritoneal macrophages from MMP8 null mice had reduced phagocytic capacity compared to WT macrophages. There was no quantitative difference in NET formation, but fewer bacteria were adherent to NETs from MMP8 null animals. In conclusion, in contrast to septic adult mice, genetic ablation of MMP8 increased mortality following bacterial peritonitis in juvenile mice. The increase in mortality in MMP8 null juvenile mice was associated with reduced bacterial clearance and reduced NET efficiency. We conclude that developmental age influences the role of MMP8 in sepsis.

Laparoscopic sigmoid colectomy: Are all laparoscopic techniques created equal?

BACKGROUND: Laparoscopic colectomy has been associated with improved postoperative pain control, earlier return to work, and shorter hospital stays compared to open colectomy. However, there are varied technical approaches to laparoscopic resections. We therefore sought to determine whether the straight laparoscopic approach was associated with shorter length of stay compared to hand-assisted and laparoscopic-assisted techniques for sigmoid colectomies. METHODS: A retrospective review of laparoscopic sigmoid colectomies performed by five colorectal surgeons from 2010 to 2014 was performed. Approaches were defined as: (1) straight laparoscopic if colon mobilization, inferior mesenteric artery transection and intra-corporeal anastomosis were performed laparoscopically, (2) hand assisted if a hand port was utilized to assist with mobilization and vessel transection, and (3) laparoscopic assisted if only the colon mobilization was performed intra-corporeally. Poisson regression was performed to determine the impact of surgical technique on LOS while controlling for differences in patient factors. RESULTS: A total of 191 patients were identified with 71 straight laparoscopic, 57 hand-assisted, and 63 laparoscopic-assisted cases. Substantial variability in choice of surgical technique was seen across surgeons. Patient populations were similar, with the exception of hand-assisted procedures being more often used in obese patients. Unadjusted average postoperative days to discharge were 3.6 days for straight laparoscopic and 4.1 and 4.0 days for hand-assisted and laparoscopic-assisted approaches, respectively. While controlling for factors associated with longer hospital stay, the straight laparoscopic approach was associated with a 14 % shorter stay compared to laparoscopic-assisted colectomy and a 15 % shorter stay compared to hand-assisted colectomy. The straight laparoscopic approach was also associated with earlier return of bowel function compared to other approaches. CONCLUSIONS: The straight laparoscopic approach to sigmoid colectomy is associated with substantially shorter postoperative stay and earlier return of bowel function when compared to hand-assisted and laparoscopic-assisted techniques. When technically feasible, the straight laparoscopic approach is preferred.

CXC chemokine receptor-4 signaling limits hepatocyte proliferation after hepatic ischemia-reperfusion in mice.

The role of stromal cell-derived factor-1 (SDF-1 or CXCL12) and its receptor CXC chemokine receptor-4 (CXCR4) in ischemic liver injury and recovery has not been studied. Some reports suggest that this chemokine may aid in liver regeneration, but others suggest that it may be profibrotic through its activation of hepatic stellate cells. In this study we sought to elucidate the role of SDF-1 and its receptor CXCR4 during liver injury, recovery, and regeneration after ischemia-reperfusion (I/R). A murine model of partial (70%) I/R was used to induce liver injury and study the reparative and regenerative response. CXCR4 was expressed constitutively in the liver, and hepatic levels of SDF-1 peaked 8 h after reperfusion but remained significantly increased for 96 h. Treatment of mice with the CXCR4 antagonist AMD3100 or agonist SDF-1 had no effect on acute liver injury assessed 8 h after I/R. However, treatment with AMD3100 increased hepatocyte proliferation after 72 and 96 h of reperfusion and reduced the amount of liver necrosis. In contrast, treatment with SDF-1 significantly decreased hepatocyte proliferation. These effects appeared to be dependent on the presence of liver injury, as AMD3100 and SDF-1 had no effect on hepatocyte proliferation or liver mass in mice undergoing 70% partial hepatectomy. The data suggest that signaling through CXCR4 is detrimental to liver recovery and regeneration after I/R and that clinical therapy with a CXCR4 antagonist may improve hepatic recovery following acute liver injury.

Peritoneal wash contents used to predict mortality in a murine sepsis model.

BACKGROUND: Cecal ligation and puncture (CLP) is considered the gold standard for inducing abdominal sepsis in mice. However, the model lacks source control, a component of sepsis management in humans. Using a CLP-excision model, we characterized peritoneal cytokines and cells and hypothesized these analyses would allow us to predict survival. METHODS: Fifty-eight mice were first subjected to CLP. Twenty hours later, the necrotic cecums were debrided, abdominal cavity lavaged, and intraperitoneal antibiotics administered. Peritoneal cytokines and leukocytes collected from the peritoneal lavage were analyzed. These immune parameters were used to generate receiver operator characteristic curves. In separate experiments, the accuracy of the model was verified with a survival cohort. Finally, we collected the peritoneal lavage and analyzed both serum and peritoneal cytokines, bacterial load, and leukocyte functionality. RESULTS: Peritoneal interleukin (IL)-6 levels and neutrophil CD11b intensity were observed to be significantly different in mice that lived versus those who died. In separate experiments, mice predicted to live (P-LIVE) had decreased bacterial loads, systemic IL-10, and neutrophil oxidative burst and increased peritoneal inflammatory monocyte numbers and phagocytosis. CONCLUSIONS: This study couples a clinically relevant sepsis model with methodology to limit pathogen spread. Using surgical waste, stratification of the mice into groups P-LIVE and predicted to die was possible with a high degree of accuracy and specificity. In mice P-LIVE, increased inflammatory monocyte recruitment and phagocytosis were associated with decreased systemic IL-10 and bacterial loads.

Microparticles impact coagulation after traumatic brain injury.

BACKGROUND: The pathophysiology that drives the subacute hypercoagulable state commonly seen after traumatic brain injury (TBI) is not well understood. Alterations caused by TBI in platelet and microparticle (MP) numbers and function have been suggested as possible causes; however, the contributions of platelets and MPs are currently unknown. MATERIALS AND METHODS: A weight-drop technique of TBI using a murine model of moderate head injury was used. Blood was collected at intervals after injury. MP enumeration and characterization were performed using Nanoparticle Tracking Analysis, and platelet counts and coagulation parameters were determined using thromboelastometry. A MP procoagulant assay was used to compare activity between injured and sham mice. RESULTS: At 24 h after injury, there were no changes in circulating platelet numbers. However, there was a decrease in platelet contribution to clot formation. In contrast, there was a decline in circulating total MP numbers. When MPs from sham mice were added to the blood from head-injured animals, there was a normalization of platelet contribution to clot formation. Conversely, when MPs from TBI mice were added to sham blood, there was a significant decrease in platelet contribution to clot formation. Notably, there was an increase in MP procoagulant activity in head-injured mice. CONCLUSIONS: MPs generated after TBI likely contribute to altered coagulation after head injury and may play a key role in the development of a posttraumatic hypercoagulable state in TBI patients.

Thymic stromal lymphopoietin mediates the host response and increases mortality during sepsis.

BACKGROUND: Sepsis and subsequent multiorgan system failure is associated with high rates of mortality and morbidity. Thymic stromal lymphopoietin (TSLP) is a cytokine that can be produced by keratinocytes and epithelial cells. Primarily, TSLP has been shown to promote counter-inflammatory processes. However, its potential expression or role in the pathogenesis of sepsis is largely unexplored. We hypothesized that TSLP is expressed during sepsis and TSLP blockade would alter the immune response and mortality. MATERIALS AND METHODS: Mice underwent cecal ligation and puncture (CLP) to produce a physiologically relevant murine model for sepsis. Cohorts were either treated with neutralizing TSLP antibodies or isotype controls before the CLP to determine changes in survival, bacterial loads, cytokine levels, and neutrophil function. RESULTS: It was observed that TSLP levels peaked at 6 h and remained detectable up to 48 h after CLP. Mice pretreated with neutralizing TSLP showed decreased mortality and bacterial load after CLP. Additionally, we determined that septic mice pretreated with the anti-TSLP antibody had increased tumor necrosis factor alpha and oxidative burst as well as increased interleukin 17 and neutrophil numbers compared with mice pretreated with isotype controls. CONCLUSIONS: TSLP levels peak early but are sustained during the first 48 h of sepsis. We speculate that TSLP blunts the neutrophil response resulting in increased bacterial load and mortality.

Assessing the immune status of critically ill trauma patients by flow cytometry.

BACKGROUND: Unintentional injury or trauma remains the leading cause of death among young adults. About one fifth of these trauma patients require care in an intensive care unit (ICU) because of severity of injuries and comorbidities. Patients hospitalized in an ICU are at increased risk for nosocomial infections, such as urinary tract infections, pneumonia, bacteremia, and wound infections. Many of these patients will develop sepsis or septic shock, and some will progress to multiple organ failure and death. The balance between the proinflammatory and counterinflammatory immune response appears to be a driving factor in this progression. At present, there is no proposed method for the timely detection of the immune status in trauma patients, making rational decisions to use immune-altering therapies difficult. OBJECTIVE: We demonstrate that flow cytometry, with its capabilities to characterize and/or enumerate (a) leukocyte subtypes, (b) leukocyte activation markers, (c) leukocyte-derived cytokines and microvesicles, and (d) leukocyte function is well suited to monitor the immune status of critically ill trauma patients. METHODS: Information for the review was obtained from the extant literature. DISCUSSION: We suggest that flow cytometry is a research method that might aid nurse scientists in investigating the immune status of critically ill patients, the recovery status of conditions such as hemorrhagic shock and tissue injury and the relationship between cancer disease progression and symptoms. Therefore, flow cytometry has the potential to broaden nursing research priority areas so that a comprehensive approach to understanding the cellular response is attained.

The impact of medical student interest in surgery on clerkship performance and career choice.

BACKGROUND: Interest in surgery has declined for two decades. This study aimed to evaluate the impact of one's interest in surgery on career choice. METHODS: Students who completed the surgical clerkship (2016-2017) were invited to complete surveys assessing rotation experience, learning style, burnout, and grit. Students were grouped according to interest or no interest in surgery after the clerkship. RESULTS: Surveys were completed by 62 students of whom 51.6% reported an interest in surgery. No minority students expressed interest compared with Caucasian (51.1%) and Asian (71.4%) students (p = 0.02). Disinterested students had higher emotional exhaustion (EE, 20 vs 25, p = 0.03). There was no difference in clerkship grade between groups (86.3% vs 85.3%, p = 0.56). Students who matched into surgery had lower EE and higher grit. CONCLUSIONS: Interest in surgery was not associated with improved clerkship performance. Disinterested students had higher EE, suggesting interest may play a role in adapting to clerkship challenges.

Exploring the relationship between burnout and grit during general surgery residency: A longitudinal, single-institution analysis.

BACKGROUND: How burnout changes during general surgery residency remains unknown. METHODS: From 2015 to 2018, general surgery residents completed the Maslach Burnout Inventory and Grit Scale. Statistical analyses were adjusted for repeated measures and compared to the incoming intern level. RESULTS: Fifty-five residents participated in this study. Burnout rates varied by program level, with an increased risk occuring in the third clinical year (OR = 11.7, p = 0.03). Emotional exhaustion (EE) peaked during the first and third clinical years, depersonalization (DP) peaked during the first and second clinical years, and personal achievement (PA) reached a nadir during the third clinical year (all p < 0.05). Residents with burnout had lower grit scores compared to those without burnout (3.71 vs 4.02, p < 0.01). Increasing grit was linearly associated with decreasing EE, decreasing DP, and increasing PA (all p < 0.05). CONCLUSIONS: Burnout varies throughout surgical residency, and grit is inversely related to burnout.

The Impact of Medical Student Burnout on Surgery Clerkship Performance.

OBJECTIVE: Increasing reports on resident burnout have resulted in efforts to improve trainee well-being. Medical student burnout, however, is not well understood. We set out to evaluate burnout among third-year medical students and explore its impact on clerkship performance. DESIGN: Analysis of prospectively-collected survey data from medical students on the third-year surgery clerkship was performed. Surveys included an institution-specific pre- and postclerkship survey, the 12-item Grit Scale, and the Maslach Burnout Inventory. SETTING: University of Cincinnati College of Medicine. PARTICIPANTS: Between 2016 and 2017, 166 students completed the surgery clerkship and were asked to complete the surveys. Sixty-two students (37.4%) completed all surveys and were included in this study. RESULTS: Among the third-year medical student participants, there was no difference in burnout before vs after the clerkship (22.6% vs 17.7%, p = 0.41). Students with burnout had significantly lower grit scores (3.10 ± 0.66) compared to those without burnout (3.63 ± 0.50, p = 0.01). Linear regression analysis demonstrated that increasing grit was associated with decreasing emotional exhaustion (p = 0.01), decreasing depersonalization (p = 0.04), and increasing personal achievement (p = 0.03). Finally, 75% of students with resolution of burnout developed an interest in surgery, whereas all students who developed burnout after the clerkship had no interest in surgery (p = 0.03). Upon completion of the rotation, burnout was not associated with poorer quality of clerkship experience or decreased clerkship performance (p > 0.05 for each). CONCLUSIONS: Although traditionally considered a difficult rotation, we found no increase in medical student burnout following the surgery clerkship. Higher grit scores were associated with decreased burnout, though burnout did not have a negative impact on student experience or performance. Clerkships should continue to set high expectations and maximize educational opportunities without significant apprehension that it may have a negative impact on students.

The Impact of a Comprehensive Resident Curriculum and Required Participation in "This Week in SCORE" on General Surgery ABSITE Performance and Well-Being.

OBJECTIVE: This Week in SCORE (TWIS) is a biennial, general surgery curriculum comprised of weekly online modules, readings, and multiple-choice quizzes. In this study, we examined the impact of required TWIS on American Board of Surgery In-Training Examination (ABSITE) scores and well-being among categorical general surgery residents. DESIGN, SETTING, AND PARTICIPANTS: TWIS quiz completion became required in 2017. Residents attended weekly lectures, and ABSITE performance was incentivized with educational stipends. Surveys were distributed to assess study preferences, learning styles, burnout, and grit. Thirty-six categorical general surgery residents who took ABSITE in both 2017 and 2018 were evaluated in a paired-sample, retrospective analysis. RESULTS: After requiring TWIS, median ABSITE percentile increased by 12% (65%-77%, p = 0.001). Weekly TWIS completion (59% vs 89%, p < 0.001) and quiz results (62% vs 69%, p = 0.005) also improved. During this time, emotional exhaustion and depersonalization declined significantly, yet overall burnout scores did not change. Of 21 survey respondents, 66.7% (n = 14) increased weekly study time by a median of 2.5 hours. However, less than half used Surgical Council on Resident Education as their primary study tool. Only 23.8% (n = 5) reported that mandatory TWIS modified their study behavior, while 90.4% (n = 19) felt the culture of education had improved. CONCLUSIONS: After TWIS participation became required, ABSITE performances improved. Formalized curriculum with frequent assessment may foster accountability among residents, enhancing educational climate, well-being, and test performance.

Gas off, room lights on: Shedding light on the surgical resident's experience in open and laparoscopic surgery.

BACKGROUND: The operative experience of today's surgery residents is different than years past. Although overall volume remains stable, the composition is changing. As such, trends in open versus laparoscopic surgery for general surgery residents were examined. METHODS: The Accreditation Council for Graduate Medical Education national operative log reports from 1994 to 2018 were analyzed for the 15 operations recorded as both open and laparoscopic. Operative volume was examined for total major, surgeon chief, and surgeon junior cases. RESULTS: From 1994 to 2018, 26,258 residents graduated with 955.2 ± 31.7 total major cases. The 15 identified operations comprised 38.4% of this volume. During the 25-year study period, laparoscopic volume increased (+9.67 cases per year), whereas open volume decreased (-3.25 cases per year, P < .0001 for each). Similar trends were seen for both chief and surgeon junior cases (P < .05 for both). For 2 of the 4 core general surgery operations examined (hernia and proctocolectomy), the open approach was still the dominant approach, providing residents an opportunity to perform open surgery in an era of increasing minimally invasive approaches. CONCLUSION: For select procedures, the frequency of laparoscopy has surpassed open surgery for general surgery residents. These trends raise the concern that when necessary, general surgery graduates may not have adequate experience converting to open.

See None, Do Some, Teach None: An Analysis of the Contemporary Operative Experience as Nonprimary Surgeon.

OBJECTIVE: The operative experience of today's general surgery resident has changed, but little is known about the modern experience as nonprimary surgeon. We set out to explore changes in the operative experience of general surgery residents as first assistant (FA) and teaching assistant (TA). DESIGN, SETTING, AND PARTICIPANTS: This is a review of ACGME national operative log reports from 1990 to 2018. TA and FA cases were analyzed. Statistical analysis was performed using polynomial regression analysis and Kruskal-Wallis test. Statistical significance was set at p < 0.05. RESULTS: 30,260 individuals completed general surgery residency during the study period with medians of 951 (interquartile range: 929-974) total major, 63 (31-184) FA, and 32 (25-48) TA cases. As a proportion of total cases completed, FA cases decreased from 21.8% of the total operative experience in 1990 to 2.5% in 2018, and TA cases declined from 7.4% of the total operative experience in 1990 to 3.5% in 2018. Regression modeling demonstrated that both operative roles decreased over time, but at a progressively decreasing rate, with FA cases reaching a "floor" around 2010 and TA cases reaching a "breakpoint" in 2008 at which time operative volume rebounded and began to increase. Among the core general surgery domains of abdomen and alimentary tract, compositional analysis revealed a decrease across each of the 11 operative subcategories (all p < 0.05) for FA, and for TA, a decrease in 6 of the 11 operative subcategories (stomach, small intestine, large intestine, anorectal, hernia, and biliary, all p < 0.05). CONCLUSIONS: Over the past 3 decades, the resident operative experience as nonprimary surgeon has decreased dramatically, with today's residents graduating with fewer FA and TA cases. As surgical training has traditionally relied heavily on an apprenticeship model for learning technical skills, it is essential that surgical educators recognize and rectify these trends.

Impact of Platelets and Platelet-Derived Microparticles on Hypercoagulability Following Burn Injury.

An acute burn induced coagulopathy develops after scald injury, which evolves into a subacute, hypercoagulable state. Microparticles, specifically platelet-derived MPs (PMPs), have been suggested as possible contributors. We first developed a model of burn-induced coagulopathy and then sought to investigate the role of platelets and PMPs in coagulation after burn. We hypothesized that changes in circulating platelet and PMP populations after injury would contribute to the post-burn, hypercoagulable state. A murine scald model with 28% TBSA full thickness burn injury was utilized and blood samples were collected at intervals after injury. Circulating MP populations, platelet counts, overall coagulation, and platelet function were determined. Burn injury led to hypercoagulability on post-burn day one (PBD1), which persisted 6 days after injury (PBD6). On PBD1, there was a significant decrease in platelet numbers and a decline in platelet contribution to clot formation with a concomitant increase in circulating procoagulant PMPs. On PBD6, there was a significant increase in platelet numbers and in platelet activation with no change in PMPs compared with sham. Further, on PBD1 decreased ADP-induced platelet activation was observed with a contrasting increase in ADP-induced platelet activation on PBD6. We therefore concluded that there was a temporal change in the mechanisms leading to a hypercoagulable state after scald injury, that PMPs are responsible for changes seen on PBD1, and finally that ADP-induced platelet activation was key to the augmented clotting mechanisms 6 days after burn.

Fecal Microbiota Transplant Restores Mucosal Integrity in a Murine Model of Burn Injury.

The gut microbiome is a community of commensal organisms that are known to play a role in nutrient production as well as gut homeostasis. The composition of the gut flora can be affected by many factors; however, the impact of burn injury on the microbiome is not fully known. Here, we hypothesized that burn-induced changes to the microbiome would impact overall colon health. After scald-burn injury, cecal samples were analyzed for aerobic and anaerobic colony forming units, bacterial community, and butyrate levels. In addition, colon and total intestinal permeabilities were determined. These parameters were further determined in a germ-reduced murine model. Following both burn injury and germ reduction, we observed decreases in aerobic and anaerobic bacteria, increased colon permeability and no change to small intestinal permeability. After burn injury, we further observed a significant decrease in the butyrate producing bacteria R. Gnavus, C. Eutactus, and Roseburia species as well as decreases in colonic butyrate. Finally, in mice that underwent burn followed by fecal microbiota transplant, bacteria levels and mucosal integrity were restored. Altogether our data demonstrate that burn injury can alter the microbiome leading to decreased butyrate levels and increased colon permeability. Of interest, fecal microbiota transplant treatment was able to ameliorate the burn-induced changes in colon permeability. Thus, fecal transplantation may represent a novel therapy in restoring colon health after burn injury.

Novel approaches to the development of anti-sepsis drugs.

INTRODUCTION: Sepsis is the dysregulated systemic immune response to an infection. Experimental and clinical research provided detailed insight into the pathophysiology of the disease, but no pathway explored, so far, has been exploited to deliver effective therapies with regard to significant outcome improvement. Increasing incidence and high mortality of sepsis require novel approaches for the development of anti-sepsis drugs. AREAS COVERED: Since accurate assessment of the patient's condition in sepsis is the basis for the success of novel anti-sepsis drugs, the authors first review briefly biomarkers for improved diagnostics in sepsis. The authors then discuss specific pharmacological approaches with a focus on immune modulation, for example, Toll-like receptor 4 inhibition and modulation of the endocannabinoid system. The authors also cover iron chelation and uncoupling of the nitric oxide pathway. EXPERT OPINION: The failure of anti-sepsis treatments in the past is most likely related to wrong timing of the drugs due to missing reliable biomarkers to assess the condition of the patients. The authors believe that the development of anti-sepsis drugs using time-critical ('vertical') and continuous ('horizontal') approaches may provide the answer for future novel therapeutics.