The Impact of Antiviral Therapy for Hepatitis C Virus on the Survival of Patients after Hepatocellular Carcinoma Treatment

Objective Owing to advances in direct-acting antiviral (DAA) therapy, a considerable number of patients with hepatitis C virus (HCV)-positive hepatocellular carcinoma (HCC) are now able to achieve a sustained viral response (SVR) after curative treatment of HCC. However, the beneficial effect of a DAA-SVR on the survival remains unclear. Methods A total of 205 patients with HCC who were HCV-positive with Child-Pugh A at the onset from 2008 to 2018 were categorized into 2 groups: 140 patients untreated for HCV throughout the entire course after HCC development (untreated group) and 65 patients treated for HCV with DAAs following HCC treatment who achieved an SVR (SVR group). After propensity score matching, 63 patients from each group were selected. Using these patients, the survival and maintenance of Child-Pugh A after HCC treatment were compared between the untreated group and SVR group. Results There was a significant difference in the overall survival (p<0.001) and the rate of maintaining Child-Pugh A (p<0.001) between the groups. The 5-year survival rates were 96% (SVR group) and 60% (untreated group), and the proportions of patients with Child-Pugh A at 5 years after HCC treatment were 96% (SVR group) and 38% (untreated group). Conclusion In patients with HCV-positive HCC, achieving a DAA-SVR after HCC treatment significantly improved the overall survival rate compared with HCV-untreated patients. The contribution of DAA-SVR during the course of HCC treatment to a longer survival is mainly due to the prevention of the progression of Child-Pugh A to B/C. Further research is needed to determine whether aggressive antiviral therapy is also effective for HCC patients with Child-Pugh B/C.     

Secondary Skin Cancer in a Case with Long-term Voriconazole after Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

Secondary malignancies that develop after allogeneic-hematopoietic stem cell transplantation (allo-HSCT) have become serious issues. A 47-year-old man who developed acute myeloid leukemia in 2009 and subsequently underwent allo-HSCT twice: in 2009 and 2011. In 2015, voriconazole for lung aspergillus was started. In 2018, chronic graft-versus-host disease (GVHD) and multiple actinic keratoses manifested at his head. In 2020, some lesions were diagnosed as squamous cell carcinoma, so voriconazole was withdrawn, and subsequent surgery and radiation led to remission. Long-term administration of voriconazole in addition to allo-HSCT and chronic GVHD may be closely related to secondary skin cancer.     

Delayed bowel necrosis due to inferior mesenteric artery occlusion in Stanford type A acute aortic dissection

Although inferior mesenteric artery occlusion due to acute aortic dissection sometimes occurs, it is usually not considered an important finding. Herein, we present an extremely rare case of delayed bowel ischaemia due to inferior mesenteric artery occlusion in Stanford type A acute aortic dissection that highlights the need for cardiac surgeons to be mindful of inferior mesenteric artery occlusion in patients with superior mesenteric artery dissection or vascular anomalies in the mesenteric arteries.     

25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) induces ectopic calcification

Vascular calcification is an important pathogenesis related to cardiovascular disease and high mortality rate in chronic kidney disease (CKD) patients. It has been well-known that hyper­phosphatemia induces osteochondrogenic transition of vascular smooth muscle cells (VSMCs) resulting ectopic calcification in aortic media, cardiac valve, and kidney. However, the detailed mechanism of the ectopic calcification has been not clarified yet. Here, we found that the co-localization of CYP27B1 with the calcified lesions of aorta and arteries in kidney of klotho mutant (kl/kl) mice, and then investigated the role of CYP27B1 in the mineralization of the VSMCs. Under high phosphate condition, overexpression of CYP27B1 induced calcification and osteocalcin mRNA expression in the VSMCs. Inversely, siRNA-CYP27B1 inhibited high phosphate-induced calcification of the VSMCs. We also found that the accumulated CYP27B1 protein was glycosylated in the kidney of kl/kl mice. Therefore, overexpression of CYP27B1-N310A and CYP27B1-T439A, which are a mutation for N-linked glycosylation site (N310A) and a mutation for O-linked glycosylation site (T439A) in CYP27B1, decreased calcium deposition and expression of RUNX2 induced by high phosphate medium in VSMCs compared with wild-type CYP27B1. These results suggest that extra-renal expression of glycosylated CYP27B1 would be required for ectopic calcification of VSMCs under hyperphosphatemia.     

Selective synthesis of 3-formylbenzofuran and 3-acylbenzofuran using a chalcone rearrangement strategy

We developed a method for highly selective synthesis of two benzofuran isomers, by rearranging and subsequently transforming 2-hydroxychalcones. Depending on the reaction conditions, synthesis of 3-formylbenzofurans, unconventional products, and 3-acylbenzofurans was achieved through cyclized 2,3-dihydrobenzofurans obtained from the rearranged products. The facile synthesis of 3-formylbenzofurans facilitated synthesis of the natural product, puerariafuran, from the corresponding chalcone.

A method for the highly selective synthesis of two benzofuran isomers, 3-formylbenzofurans and 3-acylbenzofurans, by rearranging and subsequently transforming 2-hydroxychalcones has been developed.     

Effects of tranexamic acid on coagulofibrinolytic markers during the early stage of severe trauma: A propensity score–matched analysis

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score–matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified.     

洛沙坦对人类正常系膜细胞及糖尿病肾病大鼠肾脏组织环氧化酶2的影响

目的:观察高糖及洛沙坦对正常人类系膜细胞(NHMCs)增殖及环氧化酶表达的影响,及洛沙坦对糖尿病肾病(DN)大鼠肾脏环氧化酶(COX2)及转化生长因子β1(TGF-β1)的影响.方法:体外实验采用高糖培养NHMCs,分二组(洛沙坦组,非干预组),用WST-1法检测NHMCs增殖,Western印迹和RT-PCR检测COX2表达.体内实验采用链脲菌素方法制备DN大鼠模型,洛沙坦干预4周后,分别检测大鼠肾脏病理改变、尿血栓素B2(TXB2)、24 h尿蛋白定量,同时采用免疫组织化学及RT-PCR方法检测大鼠肾脏COX2及TGF-β1表达.结果:洛沙坦呈剂量依赖性地抑制高糖引起的NHMCs增殖,同时还能减少高糖及低糖引起的NHMCa的COX2高表达;体内实验中,DN大鼠组肾体质量指数、尿TXB2和24 h尿蛋白均较正常对照组明显升高,洛沙坦能减少DN大鼠肾体质量指数、尿.TXB2、24小时尿蛋白,同时显著抑制肾组织COX2和TGF-β1表达.结论:洛沙坦能减少NHMCs的COX2表达,在高糖条件下更为明显.洛沙坦能抑制DN大鼠肾组织COX2和TGF-β1表达,从而改善DN肾损害.     

Reversible Periventricular Hyperintensity Lesions in Cerebral Amyloid Angiopathy: A Case Mimicking Cerebral Amyloid Angiopathy-related Inflammation

A 59-year-old man with progressive cognitive decline and mood disturbances was admitted to the hospital. Brain magnetic resonance imaging revealed marked white matter hyperintensity (WMH) and widespread lobar cerebral microbleeds. Because he had untreated hypertension, we started antihypertensive treatment and found a significantly improved cognitive function and WMH regression. We diagnosed him with cerebral amyloid angiopathy (CAA) based on the modified Boston Criteria with the rare apolipoprotein E (ApoE) ε2/ε4 genotype. The mechanism underlying reversible leukoencephalopathy in CAA may be related to the loss of autoregulation of brain circulation: cerebrovascular amyloid β deposits damaged the blood-brain barrier of the capillaries, which led to vasogenic edema induced by blood pressure surges.