Vena caval filter placement by intravascular ultrasound

OBJECTIVE: Placement of vena caval filters under fluoroscopic surveillance incurs significant expense and potential risks associated with the transportation of critically ill patients. Intravascular ultrasound (IVUS) allows direct intraluminal visualization of the vena cava and the renal veins. The purpose of this study is to evaluate the accuracy of vena caval filter placement under IVUS in an animal model. METHODS: Fifteen Simon-Nitinol venal cava filters (C.R. Bard, Inc., Covington, GA) were placed under IVUS guidance into four anesthetized sheep. Twelve were placed transfemorally, and three were placed transjugularly. Accuracy of placement was confirmed with fluoroscopy by measurement between the filter tip and the targeted side branch. RESULTS: The vena caval filters placed femorally averaged 0.33+/-0.42 cm distance from the target vein side branch. Jugular approach filter placement was less accurate. Although two out of three filters placed from the jugular vein were correctly positioned, the distance from the target vein side branch was much greater averaging 2.5+/-1.04 cm. CONCLUSION: Femoral placement of vena caval filters under IVUS is extremely accurate. The transjugular route, however, was technically challenging and standard fluoroscopic vena caval filter placement appears to be more appropriate. Our success with the femoral approach merits further clinical investigation in the use of IVUS for critically ill patients that would benefit from bedside vena caval filter placement.     

Expression and cellular localization of p8 protein in thyroid neoplasms

OBJECTIVES: p8 protein has mitogenic activity and is linked to the development of pancreatic carcinoma. However, little is known about the expression and physiological significance of this protein in other human carcinomas. METHODS: In this study, we immunohistochemically investigated p8 expression in thyroid neoplasms as well as in the normal thyroid gland. RESULTS: p8 was expressed in normal follicular cells, but no normal thyroid was regarded as overexpressing p8. On the other hand, 44.3% of papillary carcinoma overexpressed p8 and the incidence was directly linked to the tumor size (p=0.0340) and lymph node metastasis (p=0.0145). In follicular tumors, the incidence of p8 overexpression did not depend on histological type. In anaplastic (undifferentiated) carcinoma, p8 was overexpressed only in 5.0%, which was significantly lower than in papillary (p=0.0006) and follicular carcinomas (p=0.0049). In normal follicules and follicular tumors, p8 was localized mainly in the nucleus except for two adenomas. On the other hand, p8 localization was more cytoplasmic in papillary carcinoma larger than 1.0 cm (p=0.0186) and with a poorly differentiated lesion (p=0.0313). CONCLUSIONS: These results suggest that the overexpression and cytoplasmic localization of p8 protein may reflect disease progression of papillary carcinoma, whereas this protein plays little part in thyroid carcinoma after anaplastic transformation.     

Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4α transduction

Hepatocyte-like cells from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are expected to be a useful source of cells drug discovery. Although we recently reported that hepatic commitment is promoted by transduction of SOX17 and HEX into human ESC- and iPSC-derived cells, these hepatocyte-like cells were not sufficiently mature for drug screening. To promote hepatic maturation, we utilized transduction of the hepatocyte nuclear factor 4α (HNF4α) gene, which is known as a master regulator of liver-specific gene expression. Adenovirus vector-mediated overexpression of HNF4α in hepatoblasts induced by SOX17 and HEX transduction led to upregulation of epithelial and mature hepatic markers such as cytochrome P450 (CYP) enzymes, and promoted hepatic maturation by activating the mesenchymal-to-epithelial transition (MET). Thus HNF4α might play an important role in the hepatic differentiation from human ESC-derived hepatoblasts by activating the MET. Furthermore, the hepatocyte like-cells could catalyze the toxication of several compounds. Our method would be a valuable tool for the efficient generation of functional hepatocytes derived from human ESCs and iPSCs, and the hepatocyte-like cells could be used for predicting drug toxicity.     

The learning curve of thoracoscopic surgery in a single surgeon and successful implementation of uniportal approach

BackgroundIn some institutions, a recently introduced uniportal approach has replaced the multiportal approach for thoracoscopic major pulmonary resection. This study investigated the effect of this change on the surgical learning curve by examining the perioperative results of a single surgeon.MethodsBetween April 2012 and August 2020, 376 patients with primary lung cancer underwent thoracoscopic lobectomy with ND2a-1/2 lymphadenectomy in the authors’ hospital. Surgery was performed by one of the authors in 189 of these patients, who were thus enrolled in this retrospective study. The surgeries were classified chronologically into five phases and the operative time, rate of intraoperative massive bleeding, and rate of postoperative prolonged air leak (PAL) were then compared. The learning curve (i.e., operative time) was assessed by Spearman’s rank correlation test. The perioperative results achieved with the uniportal and multiportal approaches were also compared before and after the patients were matched for their characteristics based on the propensity score.ResultsThe five phases differed significantly with respect to the operative time and rate of postoperative PAL (P<0.0001, P=0.0061). The correlation between operative time and number of consecutive cases was also significant (r=−0.579, P<0.0001). Superior results in terms of operative time (P<0.0001), duration of postoperative drainage (P<0.0001), and rate of postoperative PAL (P=0.0034) were obtained using a uniportal rather than multiportal approach.ConclusionsThe transition from a multiportal to a uniportal approach did not cause a decline in the learning curve of thoracoscopic lobectomy with ND2a-1/2 lymphadenectomy.     

Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice

Cardiac progenitor cells are a potential source of cell therapy for heart failure. Although recent studies have shown that transplantation of cardiac stem/progenitor cells improves function of infarcted hearts, the precise mechanisms of the improvement in function remain poorly understood. The present study demonstrates that transplantation of sheets of clonally expanded stem cell antigen 1–positive (Sca-1–positive) cells (CPCs) ameliorates cardiac dysfunction after myocardial infarction in mice. CPC efficiently differentiated into cardiomyocytes and secreted various cytokines, including soluble VCAM-1 (sVCAM-1). Secreted sVCAM-1 induced migration of endothelial cells and CPCs and prevented cardiomyocyte death from oxidative stress through activation of Akt, ERK, and p38 MAPK. Treatment with antibodies specific for very late antigen-4 (VLA-4), a receptor of sVCAM-1, abolished the effects of CPC-derived conditioned medium on cardiomyocytes and CPCs in vitro and inhibited angiogenesis, CPC migration, and survival in vivo, which led to attenuation of improved cardiac function following transplantation of CPC sheets. These results suggest that CPC transplantation improves cardiac function after myocardial infarction through cardiomyocyte differentiation and paracrine mechanisms mediated via the sVCAM-1/VLA-4 signaling pathway.