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© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Activated protein C (APC) downregulates thrombin generation by inactivating procoagulant cofactors Va and VIIIa by limited proteolysis. We identified two protein C-deficient patients both of whom carry a heterozygous Gly197 to Arg (G197R) mutation in PROC and experience venous thrombosis. OBJECTIVE The objective of this study was to determine the molecular basis of the clotting defect in patients carrying the G197R mutation. METHODS We expressed protein C-G197R in mammalian cells and characterized its properties in established coagulation and antiinflammatory assay systems. RESULTS The activation of protein C-G197R by thrombin was improved ~10-fold, however, its activation by thrombin was not promoted by thrombomodulin (TM). In a tissue factor-mediated thrombin generation assay, the addition of soluble TM to protein C-deficient plasma, supplemented with protein C-G197R, did not have a significant inhibitory effect on thrombin generation parameters. APC-G197R did not exhibit a significant anticoagulant activity in either purified or plasma-based assay systems. Guanosine APC-G197R was essentially inactive since it showed no activity in an aPTT assay. Antiinflammatory activity of APC-G197R was also dramatically impaired as determined by an endothelial cell permeability assay. Structural modeling predicted that the side-chain of Arg cannot be accommodated at this site of APC without a major distortion of the local structure that appears to propagate and adversely affect the reactivity/folding of the catalytic pocket. CONCLUSION The G197R mutation in patients appears to be functionally equivalent to a heterozygous protein C knockout with half of the protein having no significant activity and thus causing thrombosis. This article is protected by copyright. All rights reserved.PURPOSE To evaluate the cost-effectiveness of the triple procedure (phacovitrectomy + posterior capsulotomy, PhacoPPVc) compared to the double- (phacovitrectomy, PhacoPPV) or single sequential procedures. METHODS Prospective study on 31 eyes from 31 patients (mean age 72.1 ± 9.1 years; 55% females) was performed with a preoperative decision to undergo only pars plana vitrectomy (PPV) (26%) or PhacoPPV (74%) and/or posterior capsulotomy based upon presence or absence of lens opacification or pseudophakia. Time during and between surgeries, surgical procedure codes, medical and transport costs, outcome and likelihood of complications after surgery were all included in the analysis. Societal perspectives and visual acuity were considered as measures of quality of adjusted life years (QALYs). RESULTS About 23 eyes underwent triple procedure and eight eyes underwent vitrectomy only (mean surgery times 35.9 and 24.0 min, respectively). Posterior capsulotomy took on average 30 s, while preparation and cataract procelished by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.INTRODUCTION The expression of forkhead box N3 (FOXN3), also known as checkpoint suppressor 1 (CHES1), is reduced in many types of tumours. However, the clinical significance of FOXN3 and its potential role in acute myeloid leukaemia (AML) remain largely unknown. METHODS A total of 117 de novo AML patients newly diagnosed between December 2015 and January 2018 were included in this study. The expression of FOXN3 and its clinical significance were analysed in these AML patients. RESULTS The expression of FOXN3 was significantly downregulated in AML. In addition, lower FOXN3 expression was associated with older age and higher white blood cell counts. Moreover, a close correlation was observed between lower FOXN3 expression and a lower complete remission (CR) rate and shorter overall survival (OS), which was further analysed by multivariate analysis. CONCLUSION These data suggest that FOXN3 is a novel biomarker in AML and that lower FOXN3 expression predicts poor chemotherapy response and prognosis in AML. © 2020 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.INTRODUCTION The differentiation of benign and malignant sub-centimetre (≤10 mm) lung nodules (SCLNs) is challenging. Computed tomography (CT)-guided biopsy has been widely used for the diagnosis of lung nodules or masses. However, studies regarding CT-guided biopsies for SCLNs are still lacking. OBJECTIVES To evaluate the feasibility and diagnostic accuracy of CT-guided biopsies for SCLNs. METHODS From December 2011 to October 2017, 102 patients with SCLNs underwent CT-guided lung biopsies. Data on technical success, diagnostic performance and procedure-related complications were collected and analysed. RESULTS The technical success rate of CT-guided biopsy for SCLNs was 99% (101/102). One patient failed to undergo the procedure. A total of 101 SCLNs in 101 patients were examined. The biopsy diagnostic results included 38 malignant cases, 1 suspected malignant case, 5 specific benign cases and 57 non-specific benign cases. The final diagnoses included 49 malignant cases, 49 benign cases and 3 cases of undiagnosed lesions. The sensitivity, specificity and overall diagnostic accuracy were 80% (39/49), 100% (49/49) and 90% (88/98), respectively. Based on the univariate and multivariate logistic regression analyses, the independent risk factors for diagnostic failure were small tissue sample numbers (P = 0.048) and procedure-related hemoptysis (P = 0.004). Pneumothorax was found in 13 patients (13%). Based on the univariate and multivariate logistic regression analyses, the independent risk factor for pneumothorax was the decubitus position (P = 0.011). Hemoptysis was found in seven patients (7%). CONCLUSIONS CT-guided biopsy is a safe and highly accurate diagnostic method for SCLNs. © 2020 John Wiley & Sons Ltd.Portal vein thrombosis (PVT) is a common complication in patients with cirrhosis awaiting a liver transplantation (LT), with the incidence ranging from 2% to 26%. Risk factors associated with this complication are male sex; previous treatment for portal hypertension (sclerotherapy, transjugular intrahepatic portosystemic shunt [TIPS], shunt surgery, previous splenectomy); Child-Pugh class C and alcoholic liver disease. This article is protected by copyright. All rights reserved.
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