Citrobacter rodentium possesses a functional type II secretion system necessary for successful host infection.

Infectious diarrheal diseases are the third leading cause of mortality in young children, many of which are driven by Gram-negative bacterial pathogens. To establish successful host infections these pathogens employ a plethora of virulence factors necessary to compete with the resident microbiota, and evade and subvert the host defenses. The type II secretion system (T2SS) is one such conserved molecular machine that allows for the delivery of effector proteins into the extracellular milieu. To explore the role of the T2SS during natural host infection, we used Citrobacter rodentium, a murine enteric pathogen, as a model of human intestinal disease caused by pathogenic Escherichia coli such as Enteropathogenic and Enterohemorrhagic E. coli (EPEC and EHEC). In this study, we determined that the C. rodentium genome encodes one T2SS and 22 potential T2SS-secreted protein effectors, as predicted via sequence homology. We demonstrated that this system was functional in vitro, identifying a role in intestinal mucin degradation allowing for its utilization as a carbon source, and promoting C. rodentium attachment to a mucus-producing colon cell line. During host infection, loss of the T2SS or associated effectors led to a significant colonization defect and lack of systemic spread. In mice susceptible to lethal infection, T2SS-deficient C. rodentium was strongly attenuated, resulting in reduced morbidity and mortality in infected hosts. Together these data highlight the important role of the T2SS and its effector repertoire during C. rodentium pathogenesis, aiding in successful host mucosal colonization.

Beneficial Effect of Extracorporeal Membrane Oxygenation on Organ Perfusion During Management of the Unstable Brain-dead Donor: A Case Series.

It is well known that the quality of organs retrieved from brain-dead donors (DBDs) is better than those retrieved from circulatory death donors. However, in situations of organ retrieval from marginal DBDs, who are unstable despite intensive care, transplantation outcomes are not good. Organ ischemia is the most important determining factor in decreased organ quality in circulatory death donors and in some DBDs. Extracorporeal membrane oxygenation (ECMO) for management of DBDs can be an emergency countermeasure. The purpose of this report is to relay our experience with four cases of ECMO for DBD management. In all four cases, the donors were unstable and showed clear signs of ischemia despite intensive care, including ventilator use and administration of inotropic agents. Two donors had acute respiratory distress syndrome, and two exhibited dysfunctional oxygen delivery. ECMO was used to improve organ perfusion. ECMO resulted in an increased partial pressure of arterial oxygen increased and decreased lactic acid levels. Vital signs were stabilized, especially in the donors who were bleeding. The organ was successfully retrieved from each donor. Two livers (one of them was split), eight kidneys, and one pancreas were retrieved from four DBDs. All other organs were transplanted successfully, and there were no cases of primary nonfunction or delayed graft function. The ECMO machine is the most powerful supportive device for management of unstable DBDs. The use of ECMO in unstable DBDs can be beneficial in expanding the donor pool as well as improving the quality of retrieved organs.

Conservative management of symptomatic spontaneous isolated dissection of the superior mesenteric artery.

BACKGROUND: Spontaneous isolated dissection of the superior mesenteric artery (SMA) is uncommon. Because of its rarity, the risk factors, aetiology and natural history are unclear, and there is no consensus on the optimal treatment strategy. METHODS: Seven consecutive patients with symptomatic spontaneous isolated SMA dissection who received conservative treatment between March 2003 and February 2008 were included in this study. Their clinical characteristics, treatment methods and outcomes were analysed retrospectively. RESULTS: Acute abdominal pain was the most common clinical manifestation. Initial contrast-enhanced dynamic computed tomography (CT) showed isolated SMA dissection with partial thrombosis in all seven patients. Full anticoagulation was carried out immediately after the diagnosis. Clinical symptoms disappeared within 14 days and follow-up CT showed complete resolution of the dissection in four patients. After a mean follow-up of 23 months, there was no mortality or morbidity related to the dissection. CONCLUSION: In patients with symptomatic spontaneous isolated dissection of the SMA, conservative management is feasible if there is no evidence of bowel infarction or bleeding.

Small-sized liver graft does not increase the risk of hepatocellular carcinoma recurrence after living donor liver transplantation.

PURPOSE: Following implantation into adult recipients, living donor liver grafts usually undergo liver regeneration. This regeneration process may provoke the growth of occult hepatocellular carcinoma (HCC) cells in the recipient body. To assess the risk of HCC recurrence, we analyzed the influence of graft-recipient weight ratio (GRWR). METHODS: The 181 recipients with HCC within the University of California at San Francisco (UCSF) criteria were divided into four groups according to GRWR: low GRWR (<0.8; n = 30), mid GRWR (0.8-1.0; n = 65), high GRWR (>1.0; n = 64), and whole liver graft group (>1.5; n = 22). RESULTS: There were no differences in overall patient survival (P = .105) and recurrence-free survival (P = .406) among these four groups. GRWR <0.8 was not a significant risk factor for HCC recurrence. Similar outcomes were obtained in HCC patients who met the Milan criteria (n = 170). CONCLUSIONS: We think that small living donor liver graft and subsequent liver regeneration do not increase the risk of posttransplant HCC recurrence when HCC is within the Milan or UCSF criteria.

Suitable whole blood levels 2 hours after neoral in liver transplant patients: experiences at a single center.

UNLABELLED: Whole blood levels 2 hours after Neoral (C2) administration were observed to correlate better with area under the curve (AUC(0-4)) than trough levels (C0), suggesting that C2 may be the best single time point predictor of Neoral absorption. Owing to concerns about drug toxicity due to excessive immunosuppression, C2 adjustments to target blood levels may represent an advance. The present study measured C2 and levels to determine which correlated more closely with AUC(0-4). METHODS: Between August 2003 and July 2004, 40 adult liver transplantations were performed in our center. All patients received Neoral twice daily. They were maintained at a C0 level of about 200 ng/mL. C0 levels were measured daily. C2 levels were estimated on postoperative days 3, 5, 7, 14, and 28. AUC(0-4) performed on postoperative days 3, 7, and 28 was calculated using the trapezoidal rule. RESULTS: The mean AUC(0-4), C0, C1, C2, C3, and C4 were 1100.3 +/- 484.8 ng/mL, 197.1 +/- 84.7 ng/mL, 240.7 +/- 166.2 ng/mL, 307.8 +/- 162.6 ng/mL, 302.8 +/- 138.9 ng/mL, and 300.3 +/- 142.8 ng/mL, respectively. C2 correlated with AUC(0-4) (R2 = 0.868: P < .05) better than C0 (R2 = 0.245: P < .05), C1 (R2 = 0.604: P < .05), or C4 (R2 = 0.583: P < .05). CONCLUSIONS: Neoral dose monitoring according to a mean C2 range of 307.8 +/- 162.6 ng/mL correlated better with AUC(0-4). Further studies are required to determine suitable C2 levels in liver transplant patients.