Case Report: Hemophagocytic Lymphohistiocytosis and Non-Tuberculous Mycobacteriosis Caused by a Novel GATA2 Variant.

Hemophagocytic lymphohistiocytosis (HLH) is a disorder of uncontrolled immune activation with distinct clinical features including fever, cytopenia, splenomegaly, and sepsis-like symptoms. In a young adolescent patient a novel germline GATA2 variant (NM_032638.5 (GATA2): c.177C>G, p.Tyr59Ter) was discovered and had resulted in non-tuberculous mycobacterial (NTM) infection and aggressive HLH. Strikingly, impaired degranulation of cytotoxic T-lymphocytes (CTL) and natural killer (NK)-cells was detected in CD107a-analyses. The affected patient was treated with HLA-matched unrelated alloHSCT, and subsequently all hematologic and infectious abnormalities including HLH and NTM resolved. This case supports early alloHSCT in GATA2 deficiencies as curative approach regardless of active NTM infection. Future studies on GATA2 c.177C>G, p.Tyr59*Ter might unravel its potential role in cytotoxic effector cell function and its contribution to HLH pathogenesis.

Human beta-defensin 2 but not beta-defensin 1 is expressed preferentially in colonic mucosa of inflammatory bowel disease.

OBJECTIVE: Various antimicrobial peptides such as defensins are part of innate immunity and contribute to the intestinal barrier that may be defective in inflammatory bowel disease (IBD). This study investigated beta-defensin mRNA and peptide expression in the colon from controls and patients with Crohn's disease, ulcerative colitis or unspecific colitis as inflammatory controls. METHODS: Mucosal mRNA expression was measured by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) with primers for human beta-defensin 1 (HBD-1) and human beta-defensin 2 (HBD-2) in CaCo-2 cells and in biopsies from 103 patients (33 controls, 24 Crohn's disease patients, 36 ulcerative colitis patients, 10 unspecific colitis patients). Paraffin-embedded tissue from colonic resections was tested for HBD-1 and HBD-2 peptides by immunohistochemistry. RESULTS: HBD-1 mRNA was expressed constitutively whereas HBD-2 was induced by pro-inflammatory cytokines in CaCo-2 cells. HBD-1 mRNA was detectable in 61% of control and Crohn's disease biopsies and 53% of ulcerative colitis biopsies. HBD-2 transcript was expressed differentially, with 18% of control biopsies positive as opposed to 34% in Crohn's disease and 53% in ulcerative colitis. HBD-2 mRNA but not HBD-1 mRNA was expressed preferentially in inflamed areas. Immunohistochemical investigation demonstrated the presence of defensin peptides in colonic epithelium as well as the differential induction in IBD. CONCLUSIONS: HBD-1 is expressed constitutively in colonic tissue irrespective of inflammation. HBD-2 is barely present in uninflamed colon but it is induced in inflammation. The lower expression of HBD-2 in Crohn's disease compared with ulcerative colitis indicates different responses of the mucosal innate defence. Defensins may play a crucial role in controlling pathogen invasion in IBD, although the functional significance remains to be established.

Vascular closure staples-a new technique for biliary reconstruction: prospective randomized comparison with manual suture in an animal model.

BACKGROUND: In orthotopic liver transplantation the incidence of biliary complications is up to 49%. In view of the relative frequency of such complications despite seemingly good preconditions, method-related disadvantages of conventional suture must also be considered as a possible cause. These include perforating needle injury of the choledochal wall with at least temporary exposure of suture material in the lumen, suboptimal approximation of the mucosa, and an additional decrease in blood flow in the choledochal stumps as a result of suture-related tissue strangulation. Hence the search for alternative anastomosis techniques. METHODS: To evaluate the surgical suitability of extramucosal titanium clips (Vascular Closure Staples; VCS) in comparison with conventional manual suture, a study was performed in 36 pigs, which were randomly assigned to 4 groups, each containing 9 animals. Choledochal excision was performed in 18 pigs and transection in the other 18 pigs; end-to-end anastomosis was then carried out, using a VCS stapler in half of the animals in each of these two groups and conventional manual suture in the other half. Pre- and postanastomotic blood flow was measured during the surgery with the aid of a laser Doppler flow meter. The long-term behavior of the closure techniques was ascertained by regular laboratory checks over the ensuing 6-month observation period, after which the pigs were killed so that the specimens could be harvested. RESULTS: Using medium-sized VCS clips, we were able to create a tension-free, everted biliary anastomosis with exact mucosal approximation and no narrowing of the lumen, and without any technical problems during the performance of the procedure. Measurements with the laser Doppler flow meter showed well-preserved anastomotic blood flow after clip reconstruction, with significantly higher perfusion values than after manual suture. The postoperative courses of the investigated laboratory parameters did not reveal any significant differences between the two methods. In contrast, histomorphometric evaluation showed wall thickness and thus fibrosis in the anastomosis region to be less in the clip group than in the suture group (median: 510 microm versus 660 microm, P<0.001). In the pigs in which clip anastomosis was used, there were no detectable anastomotic stenoses; in the pigs in which conventional suture was used, however, ultrasonography revealed five anastomoses with varying degrees of narrowing. CONCLUSIONS: Extramucosal VCS clip anastomosis not only offers potential advantages with respect to nonpenetrating and optimal mucosal contact, investigations in animals also show it to be superior to conventional manual suture as regards anastomotic blood flow and medium-term fibrosis formation. We believe that our data and the available literature warrant a clinical evaluation of this technique in appropriate studies.