Safety and efficacy of metallic stent for unresectable distal malignant biliary obstruction in elderly patients

AIM To study the safety of insertion of metallic stents in elderly patients with unresectable distal malignant biliary obstruction.METHODS Of 272 patients with unresectable distal malignant biliary obstruction, 184 patients under the age of 80 were classified into Group A, and 88 subjects aged 80 years or more were classified into Group B. The safety of metallic stent insertion, metal stent patency period, and the obstruction rate were examined in each group.RESULTS In Group B, patients had a significantly worse per-formance status, high blood pressure, heart disease, cerebrovascular disease, and dementia; besides the rate of patients orally administered antiplatelet drugs or anticoagulants tended to be higher(P 0.05). Metallic stents were successfully inserted in all patients. The median patency period was 265.000 ± 26.779(1-965) d; 252.000 ± 35.998(1-618) d in Group A and 269.000 ± 47.885(1-965) d in Group B, with no significant difference between the two groups. Metallic stent obstruction occurred in 82 of the 272(30.15%) patients; in 53/184(28.80%) patients in Group A and in 29/88(32.95%) of those in Group B, showing no significant difference between the two groups. Procedural accidents due to metal stent insertion occurred in 24/272(8.8%) patients; in 17/184(9.2%) of patients in Group A and in 7/88(8.0%) of those in Group B, with no significant difference between the two groups, either.CONCLUSION These results suggested that metallic stents can be safely inserted to treat unresectable distal malignant biliary obstruction even in elderly patients aged 80 years or more.     

Implementation of an educational program for pancreaticoduodenectomy in a university hospital: a retrospective observational study

Objective::No ideal training system exists for pancreaticoduodenectomy (PD). We developed an educational system that uses an objective structured assessment of ...     

Prediction of human pharmacokinetics for low‐clearance compounds using pharmacokinetic data from chimeric mice with humanized livers

Development of low‐clearance (CL) compounds that are slowly metabolized is a major goal in the pharmaceutical industry. However, the pursuit of low intrinsic CL (CL_int) often leads to significant challenges in evaluating the pharmacokinetics of such compounds. Although in vitro–in vivo extrapolation is widely used to predict human CL, its application has been limited for low‐CL_int compounds because of the low turnover of parent compounds in metabolic stability assays. To address this issue, we focused on chimeric mice with humanized livers (PXB‐mice), which have been increasingly reported to accurately predict human CL in recent years. The predictive accuracy for nine low‐CL_int compounds with no significant turnover in a human hepatocyte assay was investigated using PXB‐mouse methods, such as single‐species allometric scaling (PXB‐SSS) approach and a novel physiologically based scaling (PXB‐PBS) approach that assumes that the CL_int per hepatocyte is equal between humans and PXB‐mice. The percentages of compounds with predicted CL within 2‐ and 3‐fold ranges of the observed CL for low‐CL_int compounds were 89% and 100%, respectively, for both PXB‐SSS and PXB‐PBS approaches. Moreover, the predicted CL was mostly consistent among the methods. Conversely, the percentages of compounds with predicted CL within 2‐ and 3‐fold ranges of the observed CL for low‐CL_int compounds were 50% and 63%, respectively, for multispecies allometric (MA) scaling. Overall, these PXB‐mouse methods were much more accurate than conventional MA scaling approaches, suggesting that PXB‐mice are useful tools for predicting the human CL of low‐CL_int compounds that are slowly metabolized.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

It is important to identify low‐clearance (CL) compounds that are slowly metabolized during the drug discovery process, but the ability of in vitro–in vivo extrapolation to predict human CL decreases as the value of intrinsic CL (CL_int) decreases. Although chimeric mice with humanized livers (PXB‐mice) have been reported to be useful for predicting human CL, their applicability to low‐CL_int compounds with no significant turnover in human hepatocyte assays has not been clarified.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study examined the predictive accuracy of PXB‐mouse methods for low‐CL_int compounds.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

In addition to the previously reported single‐species allometric scaling approach, we proposed a novel physiologically based scaling approach. Both methods displayed much greater predictive accuracy for low‐CL_int compounds than conventional multispecies allometric scaling approaches.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

The findings should improve the accuracy of human pharmacokinetic prediction and enable efficient and safe first‐in‐human studies.     

Stents liberadores de rapamicina sin polímero frente a stents liberadores de paclitaxel con polímero: un análisis de datos de pacientes procedentes de ensayos aleatorizados

Introduction and objectives

The angiographic and clinical efficacy of polymer-free sirolimus-eluting stents vs polymer-based paclitaxel-eluting stents remain a matter of debate. We sought to investigate angiographic and clinical measures of efficacy of polymer-free sirolimus-eluting stents vs polymer-based paclitaxel-eluting stents.

Methods

Patient data from the randomized intracoronary stenting and angiographic restenosis-test equivalence between the 2 drug-eluting stents (ISAR-TEST) clinical trial and the LIPSIA Yukon clinical trial (randomized comparison of a polymer-free sirolimus-eluting stent vs a polymer-based paclitaxel-eluting stent in patients with diabetes mellitus) were pooled. The angiographic (primary) endpoint was in-stent late lumen loss at 6 months to 9 months. The clinical (secondary) endpoints were death or myocardial infarction, cardiac death or myocardial infarction, target lesion revascularization, and myocardial infarction.

Results

A total of 686 patients (polymer-free sirolimus-eluting stents, n=345 vs polymer-based paclitaxel-eluting stents, n=341) and 751 lesions (polymer-free sirolimus-eluting stents, n=383 vs polymer-based paclitaxel-eluting stents, n=368) were included in the study. Control angiography (606 lesions, 80.6%) showed comparable in-stent late lumen loss for polymer-free sirolimus-eluting stents vs polymer-based paclitaxel-eluting stents (0,53 [0,59] mm vs 0,46 [0,57] mm; P=.15). Median follow-up was 34.8 months. Polymer-free sirolimus-eluting stents and polymer-based paclitaxel-eluting stents were associated with comparable risk of death or myocardial infarction (relative risk=1.17; 95% confidence interval, 0,49-2.80; P=.71), cardiac death or myocardial infarction (relative risk=1.17; 95% confidence interval, 0,72-1.89; P=.50), target lesion revascularization (relative risk=0,98; 95% confidence interval, 0,65-1.47; P=.93), and myocardial infarction (relative risk=1.79; 95% confidence interval, 0,85-3.76; P=.12).

Conclusions

In this pooled analysis, polymer-free sirolimus-eluting stents were comparable to polymer-based paclitaxel-eluting stents with respect to both angiographic and clinical efficacy.Full English text available from:www.revespcardiol.org.     

Clinical features of emergency electrocardiography in patients with acute myocardial infarction caused by left main trunk obstruction.

BACKGROUND: To diagnose left main trunk (LMT) infarction by 12-lead standard electrocardiogram (ECG) is an important emergency technique, but the features in LMT infarctions have not been clarified. METHODS AND RESULTS: The study enrolled 140 subjects who were divided into 4 groups according to the location of the culprit artery: 35 with LMT, 35 with left anterior descending artery (LAD), 35 with right coronary artery and 35 with left circumflex artery. Various parameters obtained from the ECGs were analyzed. Average QTc interval (0.51 +/- 0.06 s) in LMT group was markedly longer than that in the 3 other groups. Average QRS axis (-10 +/- 77 degrees) in LMT infarction showed a remarkable left deviation. ST-segment elevation in lead aVR occurred in 28 patients (80.0%) in the LMT group. The ECG features of the LMT group could be classified into 2 main groups: right bundle branch block (RBBB) with a marked left axis deviation (RBBB + LADEV type) and ST-segment elevation in leads V2-5, I and aVL without abnormal axis deviation (LAD type). CONCLUSION: Either ST-segment elevation in lead aVR and marked prolongation of both the QRS width and QTc interval with a prominent abnormal axis deviation or ST-segment elevation in the broad anterior precordial lead with a normal QRS axis strongly suggests LMT infarction.     

Chronic hepatitis C virus infection and lipoprotein metabolism

Hepatitis C virus (HCV) is a hepatotrophic virus and a major cause of chronic liver disease, including hepatocellular carcinoma, worldwide. The life cycle of HCV is closely associated with the metabolism of lipids and lipoproteins. The main function of lipoproteins is transporting lipids throughout the body. Triglycerides, free cholesterol, cholesteryl esters, and phospholipids are the major components of the transported lipids. The pathway of HCV assembly and secretion is closely linked to lipoprotein production and secretion, and the infectivity of HCV particles largely depends on the interaction of lipoproteins. Moreover, HCV entry into hepatocytes is strongly influenced by lipoproteins. The key lipoprotein molecules mediating these interactions are apolipoproteins. Apolipoproteins are amphipathic proteins on the surface of a lipoprotein particle, which help stabilize lipoprotein structure. They perform a key role in lipoprotein metabolism by serving as receptor ligands, enzyme co-factors, and lipid transport carriers. Understanding the association between the life cycle of HCV and lipoprotein metabolism is important because each step of the life cycle of HCV that is associated with lipoprotein metabolism is a potential target for anti-HCV therapy. In this article, we first concisely review the nature of lipoprotein and its metabolism to better understand the complicated interaction of HCV with lipoprotein. Then, we review the outline of the processes of HCV assembly, secretion, and entry into hepatocytes, focusing on the association with lipoproteins. Finally, we discuss the clinical aspects of disturbed lipid/lipoprotein metabolism and the significance of dyslipoproteinemia in chronic HCV infection with regard to abnormal apolipoproteins.