Our functional evaluation of AIP mutations is consistent with a tumor-suppressor role for AIP and its involvement in familial acromegaly. The abnormal expression and subcellular localization of AIP in sporadic pituitary adenomas indicate deranged regulation of this protein during tumorigenesis.
SummaryThrombotic microangiopathies (TMAs) are frequently difficult to differentiate clinically, and measurement of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) remains vital in thrombotic thrombocytopenic purpura (TTP) diagnosis. We retrospectively reviewed cases referred for ADAMTS13 testing, using UK TTP Registry screening data. Of a total 810 cases, 350 were confirmed as TTP. The 460 non-TTP cases comprised secondary TMAs (24Á57%) and haemolytic uraemic syndrome (HUS) (27Á17% aHUS, 2Á83% Shiga-like toxin-producing E. coli [STEC]-HUS); the remainder were TMAs with no clear association, not TMAs, or had no confirmed diagnosis. ADAMTS13 levels were significantly lower in TTP than STEC-HUS, aHUS and other TMAs. TTP patients had significantly lower platelet count (15 9 10 9 /l; range 0-96) than aHUS (57 9 10 9 /l; range 13-145, P < 0Á0001) or STEC-HUS (35 9 10 9 /l; range 14-106, P < 0Á0001); they also had lower creatinine levels (92 lmol/l; range 43-374) than aHUS (255 lmol/l; range 23-941, P < 0Á0001) and STEC-HUS (324 lmol/l; range 117-639, P < 0Á0001). However, 12/34 (35Á3%) aHUS patients had a platelet count <30 9 10 9 /l and 26/150 (17Á3%) of TTP patients had a platelet count >30 9 10 9 /l; 23/ 150 (15Á3%) of TTP patients had a creatinine level >150 lmol/l. This study highlights the wide variety of TMA presentations, and confirms the utility of ADAMTS13 testing in TTP diagnosis.
De novo HLA donor specific antibodies (DSA) following transplantation are associated with alloimmune injury and allograft failure. Blood transfusions are allogeneic, and when given posttransplant (PTBT) they may independently increase the risk of HLA antibody development. This study aims to analyse the development of HLA transfusion specific antibodies (TSA) to blood donors of transfusions given post-transplant and examine the impact on clinical outcomes. 244 blood donors of transfusions received by 86 transplant patients (46 who developed a DSA post transfusion and 40 who remained DSA negative) were HLA typed. De novo TSA developed against 150/244(61.5%) blood donors. In 70/150(46.7%) cases the TSA was of shared HLA antibody specificity with a DSA response in the recipient (DSA+=TSA+). This occurred when there was a greater overall HLA match between the blood and transplant donor. DSA+=TSA+ patients had increased risk of allograft failure [p=0•0025] and AMR [p=0•02] compared with the DSA+≠TSA+ patients. To conclude, PTBT may elicit de novo HLA antibodies. Enhanced HLA matching between the blood and transplant donor is more likely to result in a DSA and TSA of shared antibody specificities. Transfusion avoidance or the use of HLA matched or selected blood may reduce this risk and improve outcomes.
Preoperative DM and RI were important predictors of 5-year mortality after CABG. Patients with RI alone had a higher mortality rate than patients with DM alone, but this difference was largely accounted for by age and other comorbidities. The combination of DM and RI doubled the 5-year mortality rate after CABG independently of potential confounding factors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.