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SummaryBackgroundUlcerative colitis (UC) and Crohn's disease can sometimes relapse and be refractory to standard treatment following orthotopic liver transplantation (OLT) despite post‐transplantation immunosuppressive therapy.AimTo evaluate the efficacy and safety of anti‐tumour necrosis factor (anti‐TNF) agents for the management of IBD following OLT.MethodsWe reviewed the records of patients with a diagnosis of IBD who underwent OLT at Mayo Clinic Rochester between 1985 and 2009. Patients were included if they had received anti‐TNF therapy post‐OLT. Clinical response was defined as a physician's assessment of improvement after 12 weeks of anti‐TNF usage, and mucosal healing was defined as the absence of ulcerations on follow‐up endoscopy.ResultsThe median age of the eight study patients was 42.0 years and 37.5% were female patients. All had been diagnosed with IBD prior to OLT (UC in three and Crohn's disease in five). Indication for OLT was cirrhotic stage primary sclerosing cholangitis (PSC), and three concomitantly had cholangiocarcinoma. Clinical response was demonstrated in seven of eight patients (87.5%) and mucosal healing was demonstrated in three of seven (42.9%). Four infections (oral candidiasis, Clostridium difficile colitis, bacterial pneumonia and cryptosporidiosis) in three patients were reported. One patient developed an Epstein–Barr virus‐positive post‐transplant lympho‐proliferative disorder. One death occurred due to complications from recurrent PSC.ConclusionsStarting Anti‐TNF therapy following orthotopic liver transplantation appears to be a potential option for inflammatory bowel disease management. Additional studies are needed, however, to confirm these findings and to further assess risks associated with this treatment strategy.

Background —T cells are implicated in atherosclerosis, but little is known about the genetic control or molecular pathways, especially under conditions of mild hypercholesterolemia. Methods and Results —BALB/c mice, making a CD4+ Th2 (IL-4+) cell response, express both MHC class II antigens (IA d , IE d ) and are atherosclerosis-resistant. C57Bl/6 mice produce a CD4+ Th1 (interferon [IFN]γ+) response, express IA b but no IE, and are atherosclerosis-prone. To evaluate T helper–cell phenotype in fatty streak formation, wild-type C57Bl/6 mice (IA b +IE−) and transgenic mice, either AB o , IA b −IE−; ABEα, IA−IE k +; or Bl.Tg.Eα, IA b +IE k +, were fed a high-cholesterol diet for 16 weeks and evaluated histomorphometrically for aortic lesions. Lesion size in AB o , ABEα, and Bl.Tg.Eα strains was decreased by 54%, 79%, and 82%, respectively, compared with wild-type, correlating with decreased Th1 and increased Th2 expression and suggesting that T helper–cell phenotype is important in fatty lesion development. Decreasing Th1 cells by antibodies (α-CD4) or cytokines (IL-4) also caused ≥80% reductions in lesion size. Immunohistology revealed IFN-γ, but not IL-4, colocalized with activated macrophages. Confirming these findings in a different mouse strain, BALB/c Stat 6 knockout mice (Th2 cell–deficient) developed aortic lesions comparable to C57Bl/6 mice on the same diet. Conclusions —In mildly hypercholesterolemic C57Bl/6 mice, presence of IA b and absence of IE regulated CD4+ T helper–cell phenotype; fatty lesions were proportional to IFNγ+ Th1 cells in both C57Bl/6 and BALB/c strains. IFN-γ may participate through macrophage activation, whereas IL-4 may act to limit Th1-cell response.

Abstract Transmission of pathogens from donor to recipient is a potential complication of organ transplantation. Herein, we describe the clinical course and outcomes of 4 transplant recipients who received tissues from a donor with multi‐organ infection with Klebsiella pneumoniae carbapenemase ( KPC )‐producing K. pneumoniae . Recipient 1 underwent simultaneous liver and kidney transplantation for alpha‐1 antitrypsin deficiency and alcohol‐related cirrhosis, and acute tubular necrosis, respectively. Soon after transplantation, he developed an infected hematoma and peritonitis due to KPC ‐producing K. pneumoniae despite receiving tigecycline prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and meropenem, in conjunction with surgical evacuation and percutaneous drainage of the infected fluid collections. Recipient 2 underwent living‐donor liver transplantation for cholangiocarcinoma and primary sclerosing cholangitis using vein graft from the donor infected with KPC ‐producing K. pneumoniae . Culture of the preservation fluid containing the vein graft was positive for KPC ‐producing K. pneumoniae . The patient received preemptive amikacin and tigecycline, and he did not develop any infection (as evidenced by negative surveillance blood cultures). The isolates from the donor and Recipients 1 and 2 were indistinguishable by pulsed‐field gel electrophoresis. Recipients 3 and 4 underwent kidney and heart transplantation, respectively; both patients received perioperative tigecycline prophylaxis and did not develop infections due to KPC ‐producing K. pneumoniae . All transplant recipients had good short‐term outcomes. These cases highlight the importance of inter‐institutional communication and collaboration to ensure the successful management of recipients of organs from donors infected with multidrug‐resistant organisms.