Outcomes of Selective Strategies for Distal Entry Tears After Thoracic Endovascular Aortic Repair in Type B Aortic Dissection.

BACKGROUND: Distal entry tears have undesirable influence in type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR), including inhibition of aortic remolding and increase of late aortic events. Therefore, distal entry tears should be managed. Nowadays, main strategies for managing distal entry tears included total and selective strategies. However, which strategy is better still remains controversial. The objective of the study is to investigate the outcomes of selective strategy for distal entry tears after TEVAR in TBAD. METHODS: A total of 43 consecutive patients with TBAD with distal entry tears after TEVAR were administered with selective strategy for distal entry tears, including occlusion of the tear in the thoracic aortic segment, thrombosis of the reverse blood flow channel in the false lumen, and selective occlusion of distal entry tears. Mortality, complications, and aortic remolding in early follow-up (12 months after operation) were analyzed. RESULTS: All 43 patients survived during the follow-up period. Operation was performed again for femoral artery reconstruction in 1 patient who had occlusion of the approach vessel during the follow-up period, and the remaining 42 patients had no uncomfortable symptoms and operation-related complications. The maximum diameter of the aorta was 32.03 ± 6.35 mm and 27.36 ± 4.92 mm, respectively, for before and after reintervention, and the difference was significant (t = 5.899, P < 0.001). The unthrombotic range of the false lumen after reintervention was significantly shrunken in all patients, compared with the range before reintervention. CONCLUSIONS: Selective strategy was safe and effective, at least in early follow-up. Its effectiveness should be further verified by more clinical observation results and long-term follow-up results.

Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for Treatment of Aplastic Anemia: A Multicenter Phase II Trial.

We conducted a phase II, noncomparative, multicenter study to assess the efficacy and safety of allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSCs) expanded in vitro for patients with aplastic anemia (AA) refractory to immunosuppressive therapy. Seventy-four patients from seven centers received allogeneic BM-MSCs at a dose of 1-2 × 106 cells/kg per week for 4 weeks. Responses were assessed at 0.5, 1, 2, 3, 6, 9, and 12 months after the first cells infusion. Patients with response at 1 month continued to receive four infusions. All patients were evaluable. The overall response rate was 28.4% (95% confidence interval, 19%-40%), with 6.8% complete response and 21.6% partial response. The median times to response of leukocytic, erythrocytic, and megakaryocytic linages were 19 (range, 11-29), 17 (range, 12-25), and 31 (range, 26-84) days, respectively. After median follow-up of 17 months, overall survival was 87.8%. Seven patients developed transitory and mild headache and fever, but no other adverse events were observed. Antithymocyte globulin used in previous treatment and no activated infection throughout treatment were predictors for response. Allogeneic BM-MSCs infusion is a feasible and effective treatment option for refractory AA. The trial was registered at www.clinicaltrials.gov as NCT00195624. Stem Cells Translational Medicine 2017;6:1569-1575.

Association Between Three SNPs and Thromboangiitis Obliterans in Xinjiang Uyghur Population.

BACKGROUND: Thromboangiitis obliterans (TAO), also called Buerger's disease, is a chronic peripheral vascular occlusive disease. It is an obliterative vasculitis characterized by arterial thrombosis and strongly associated with tobacco exposure. The pathogenesis and etiology of TAO are not well understood, but genetic factors may be important in its development. A case-control study was undertaken to identify genetic factors potentially involved in the pathogenesis of TAO in a Xinjiang Uyghur population of China, where TAO is common. METHODS: We ascertained 177 TAO patients by clinical screening and 86 healthy individuals from the HAPMAP database. The genotypes of single-nucleotide polymorphisms (SNPs) of the participants were identified using the Affymetrix Genome-Wide Human SNP Array 6.0 to perform a genome wide association study (GWAS). The association between the SNPs and incidence of TAO was quantified using race stratification exposure. RESULTS: Through a case-control GWAS study 26 SNPs were significantly associated with incidence of TAO following a Bonferroni correction. However, after genomic control correction for population stratification only three of these SNPS were highly significantly associated with TAO: rs376511 in IL17RC (OR = 24.4, 95% CI:8.68 - 68.62, p < 0.0001), rs7632505 in SEMA5B (OR = 29.47, 95% CI:7.16 - 121.3, p < 0.0001), and rs10178082 (OR = 18.09, 95% CI: 6.56 - 49.92, p < 0.0001) showed a significant risk of TAO in the Uyghur population. CONCLUSIONS: This study shows an association between these 3 SNPs and susceptibility to TAO in the Uyghur population, suggesting that polymorphisms in the IL-17RC and Sema 5B genes may pre-dispose individuals in this population to development of TAO. These findings require replication.

Association between prothrombin gene polymorphisms and hereditary thrombophilia in Xinjiang Kazakhs population.

To assess the association between polymorphisms of prothrombin gene and hereditary thrombophilia in Xinjiang Kazakhs population. Through cross-sectional investigation, permanent Kazakh population of Ili Kazakh Autonomous Prefecture was selected as the study object to measure their antithrombin III (AT-III), protein C, protein S activity and activated C protein resistance value, thus defining the situation of the crowd's hereditary thrombophilia. Sequenom Massarray detection technology was used to conduct a genotype test of the six sites selected by the case and control groups. Haploview software was used to perform linkage disequilibrium analysis of the six sites, and the impact of the interaction between genetic variations and environment on hereditary thrombophilia was researched by the use of sum model. A total of 1005 Kazakh volunteers participated in the test (332 men and 673 women), average age (41.13 ±â€Š11.50) years; the prevalence of hereditary thrombophilia in Xinjiang Kazakh population was 31.0%, and the prevalence of AT-III deficiency, protein C deficiency, protein S deficiency and activated protein C resistance was 16.4, 14.9, 20.6 and 7.8%, respectively. The difference in allele frequency of the hereditary thrombophilia patient group at rs3136447 and rs5896 sites was statistically significant (P = 0.0483 and P = 0.0302, respectively). rs5896 and rs2070852 had high linkage disequilibrium (r = 0.99), and constituted a single-domain block 1. The rs3136447 and the rs5896 polymorphisms located in the region of the prothrombin gene may be associated with hereditary thrombophilia in the Xinjiang Kazakhs population. There is additive interactive effect of rs5896 polymorphism (CT + TT) and smoke on hereditary thrombophilia.

[A study on causes of re-admission to surgical intensive care unit and risk factors analysis of their prognosis].

OBJECTIVE: To evaluate the causes of readmission of patients to surgical intensive care unit (SICU), and the risk factors involved in their prognosis. METHODS: Among 7381 SICU patients admitted between January 2009 and February 2012, clinical data of 178 patients readmitted to the SICU were analyzed retrospectively and assessed by univariate and multiple step wise regression analysis. RESULTS: The SICU readmission rate was 2.41% (178/7381). Among 178 patients readmitted to SICU, 39.89% (71/178) of them were over 70 years old in age, and 46.07% (82/178) of readmission to SICU occurred within 48 hours after their first SICU discharge. The death rate of readmitted patients was 37.08% (66/178). At discharge from SICU and at readmission, the acute physiology and chronic health evaluation II (APACHEII) score in death group (n=66) was higher than that in survivor group (n=112, 9.15±4.13 vs. 7.74±3.62, 18.47±5.67 vs. 12.99±6.32, P<0.05 and P<0.01). At readmission, Glasgow coma score (GCS) was lower than that in survive group (10.88±4.37 vs. 12.37±2.68, P<0.01). Respiratory and operation related complications were the most common causes of SICU readmission. The incidence of sepsis, septic shock and multiple organ dysfunction syndrome(MODS) in death group was obviously higher than that in survivor group (22.7% vs. 7.1%, 19.7% vs. 7.1%, 10.6% to 0 respectively, all P<0.05). The APACHEII score and complicating MODS at time of SICU readmission were found to be the independent risk factors of death as shown by multiple step wise regression analysis (t=5.0163, P=0.0000; t=2.3641, P=0.0192). CONCLUSIONS: The study indicated that the criteria for discharge of patients from SICU should be strictly controlled in line with patients' condition. It is very important to actively monitor the APACHEII score and GCS score, to control both respiratory and operation related complications in order to reduce the re-admission rate of the patients to SICU.

The iron regulatory hormone hepcidin reduces ferroportin 1 content and iron release in H9C2 cardiomyocytes.

Iron plays a key pathophysiological role in a number of cardiac diseases. Studies on the mechanisms of heart iron homeostasis are therefore crucial for understanding the causes of excessive heart iron. In addition to iron uptake, cellular iron balance in the heart also depends on iron export. We provided evidence for the existence of iron exporter ferroportin 1 (Fpn1) in the heart in a recent study. The presence of hepcidin, a recently discovered iron regulatory hormone, was also confirmed in the heart recently. Based on these findings and the inhibiting role of hepcidin on Fpn1 in other tissues, we speculated that hepcidin might be able to bind with, internalize and degrade Fpn1 and then decrease iron export in heart cells, leading to an abnormal increase in heart iron and iron mediated cell injury. We therefore investigated the effects of hepcidin on the contents of Fpn1 and iron release in H9C2 cardiomyocyte cell line. We demonstrated that hepcidin has the ability to reduce Fpn1 content as well as iron release in this cell. The similar regulation patterns of hepcidin on the Fpn1 and iron release suggested that the decreased iron release resulted from the decreased content of Fpn1 induced by hepcidin. We also found that hepcidin has no significant effects on ceruloplasmin (CP) and hephaestin (Heph)--two proteins required for iron release from mammalian cells. The data imply that Fpn1, rather than Heph and CP, is the limited factor in the regulation of iron release from heart cells under physiological conditions.

Lipopolysaccharide induces a significant increase in expression of iron regulatory hormone hepcidin in the cortex and substantia nigra in rat brain.

Hepcidin plays an essential role in maintaining normal iron homeostasis outside the brain. This recently discovered iron regulation hormone is predominantly expressed in the liver, and regulated by iron and hypoxia. As an antimicrobial peptide, this hormone is also elevated during infections and inflammation. In this study we investigated the expression of hepcidin mRNA and protein in different brain regions, including the cortex, hippocampus, striatum, and substantia nigra, and the effects of lipopolysaccharide (LPS) on the expression of hepcidin using quantitative real-time RT-PCR and immunofluorescence analysis. Our data provided further evidence for the existence of hepcidin in all the regions we examined. We also demonstrated for the first time that LPS administration by iv injection can regulate the expression of hepcidin mRNA and protein not only in peripheral organs such as the liver, but also in the brain. LPS induced a significant increase in the expression of hepcidin mRNA and protein in the cortex and substantia nigra, but not in the hippocampus and striatum, indicating a regionally specific regulation of LPS on hepcidin in the brain. The relevant mechanisms and the functions of hepcidin in the brain remain to be elucidated.

Ceruloplasmin expression and its role in iron transport in C6 cells.

Ceruloplasmin (CP) is essential for brain iron homeostasis. However, little is known about the effect of iron on CP expression in the brain. Also, the role of CP in brain iron transport has not been well determined. In this study, we investigated the effects of iron on CP expression and the role of CP in iron transport in the C6 rat glioma cells. Our data showed that treatment of the cells with iron (cell iron overload) or iron chelators (cell iron deficiency) did not induce a significant change in the expression of CP mRNA. However, western blotting analysis demonstrated that cell iron overload induced a significant decrease in CP protein content in the cells and that treatment with iron chelators led to a significant increase in CP protein level in the cells. These findings suggest a translational regulation of CP expression by iron in the cells. We also examined the effects of CP on iron transport in the cells. We found that glycosylphosphatidylinositol-anchored CP did not have any impact on iron uptake by normal iron or iron-deficient cells nor on iron release from normal iron or iron-sufficient cells. However, low concentrations of soluble CP (2-8 microg/ml) increased iron uptake by iron-deficient C6 glioma cells, while the same concentrations of CP had no effect on iron uptake by normal iron cells and iron release from normal iron and iron-sufficient cells. The possible reason for the difference between our results in vitro and those obtained from in vivo studies was discussed.

Pancreatoduodenectomy with vascular reconstruction in treating carcinoma of the pancreatic head.

BACKGROUND: The incidence of carcinoma of the pancreas is increasing in the world. Pancreatic carcinoma is characterized by early local extension to contiguous structures and metastases to regional lymph nodes and the liver. This study was conducted to increase the rate of pancreatoduodenectomy combined with vascular reconstruction. METHODS: Pancreatoduodenectomy with vascular reconstruction was performed for 79 patients at a number of hospitals in Fujian Province, Zhejiang Province, Shanghai and Xinjiang Uyghur Autonomous Region from April 1994 to December 2003. One of these patients also underwent right hemicolectomy; but all received through superior mesenteric vein (SMV)-portal vein (PV) reconstruction. The reconstructions of the superior mesenteric artery (SMA) and hepatic artery (HA) were performed in 4 patients, and reconstructions of the SMA or HA were carried out in 7 and 4 patients respectively. Partial reconstruction of the inferior vena cava (ICV) was done in 2 patients when the tumor was adhering to the wall of the inferior caval vein. RESULTS: Four patients died during the peri-operative period, with a mortality rate of 5%. No complications such as biliary or pancreatic fistulae or artificial blood vessel infection were noted. Histological examination showed one patient with neuroendocrine cancer and the other 78 patients with adenocarcinoma of the pancreatic head. Resected endothelia and vascular margins proved to be microscopically tumor-free. Follow-up for 3 months to 10 years for all except two patients showed 7 of the 9 patients who had undergone resection and reconstruction of the SMA and HA died 7 months or 4 years after operation and 37 survived for over 3 years and 12 for more than 5 years. The rest are still under follow-up. CONCLUSION: Pancreatoduodenectomy with vascular reconstruction for carefully selected patients with carcinoma of the pancreatic head has proved to be a safe and reliable treatment, capable of raising the rates of tumor resection and survival.