Imbalances between the levels of tissue factor and tissue factor pathway inhibitor in ARDS patients

INTRODUCTION: To evaluate the pathogenetic role of tissue factor (TF), tissue factor pathway inhibitor (TFPI), and neutrophil elastase in acute respiratory distress syndrome (ARDS), as well as to test the hypothesis that TFPI levels modified by neutrophil activation are not sufficient to prevent TF-dependent intravascular coagulation, leading to sustained systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), which determine the prognosis of these patients. MATERIALS AND METHODS: The study subjects consisted of 55 patients with trauma and sepsis who were divided into three groups according to the Lung Injury Score. Ten normal healthy volunteers served as control. Plasma levels of TF, TFPI, and neutrophil elastase were measured on the day of injury or the day of diagnosis of sepsis (day 0) and days 1 through 4. The number of SIRS criteria that the patient met and the disseminated intravascular coagulation (DIC) score is determined daily. RESULTS: Patients (15) developed ARDS, 23 were at risk for but did not develop the syndrome, and 17 patients were without risk for ARDS. TF and neutrophil elastase levels in ARDS patients were persistently higher than those in other two groups and control subjects. However, the TFPI levels showed no difference among the three groups, which retained normal or slightly elevated levels compared to the control subjects. DIC scores did not improve and SIRS continued during the study period in patients with ARDS. The ARDS patients showed higher numbers of dysfunctioning organs and associated with poorer outcome than the other two groups. CONCLUSION: Systemic activation of the TF-dependent pathway not adequately balanced by TFPI is one of the aggravating factors of ARDS. High levels of neutrophil elastase released from activated neutrophils may explain the imbalance of TF and TFPI. Persistent DIC and sustained SIRS contribute to MODS, determining the prognosis of ARDS patients.     

Biological implications of thymectomy for myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies to the striated muscle tissue. It is often treated by thymectomy. We review recent studies to investigate the biological implications of thymectomy. In anti-acetylcholine receptor antibody (anti-AchR Ab)-positive patients without a thymoma, abnormal germinal center formation in the thymus seems to play an essential role in the pathogenesis of MG. Specific differentiation of B cells producing anti-AchR Ab takes place uniquely in the thymus, and thymectomy is thought to assist in terminating the provision of high-affinity anti-AchR antibody-producing cells to peripheral organs. Thymectomy is not indicated for anti-AchR Ab-negative MG patients who are antimuscle specific kinase antibody (anti-MuSK Ab)-positive, although some anti-MuSK Ab-negative patients may benefit from the procedure. A thymoma can be considered as an acquired thymus with insufficient function of negative selection. The resection of a thymoma is thought to terminate the production of selfreactive T cells. Thus, the biological implications of thymectomy for MG have been partially revealed. Nevertheless, additional studies are needed to elucidate the ontogeny of T cells that recognize AchR and the mechanism of the activation of anti-AchR antibodies producing B cells.     

Magnetic resonance plaque imaging to predict the occurrence of the slow-flow phenomenon in carotid artery stenting procedures

Introduction

The purpose is to investigate the feasibility of magnetic resonance (MR) plaque imaging in predicting the arterial flow impairment (slow-flow phenomenon) during carotid artery stenting (CAS) using a filter-type protection device.

Methods

Thirty-one carotid artery stenotic lesions in 30 patients (28 men and two women; mean age, 71.8 years) were evaluated by MR plaque imaging with black blood T1- and T2-weighted and time-of-flight sequences before CAS. Main plaque components were classified as vulnerable (intraplaque hemorrhage and lipid-rich/necrotic core) or stable (fibrous tissue and dense calcification) from the signal pattern. The plaque classification was statistically compared with the occurrence of slow-flow phenomenon.

Results

The slow-flow phenomenon was observed in ten CAS procedures (five flow arrests and five flow reductions). Flow arrests consisted of four vulnerable and one stable plaque, and flow reductions consisted of four vulnerable and one stable plaque. The slow-flow phenomenon occurred significantly (P?<?0.01) more frequently in patients with vulnerable plaque.

Conclusions

Vulnerable carotid plaques have a significantly higher risk of slow-flow phenomenon than stable plaques. The occurrence of the slow-flow phenomenon can be predicted by MR plaque imaging before CAS.     

Histology is a Prognostic Indicator After Pulmonary Metastasectomy from Renal Cell Carcinoma

Objectives

There are only a few detailed reports concerning the prognosticators following surgical resection of pulmonary metastases (PMs) from renal cell carcinoma (RCC). We investigated the prognosis of patients with RCC PMs undergoing pulmonary metastasectomy and identified prognostic factors in a multi-institutional retrospective study.

Methods

We retrospectively evaluated 84 patients who underwent resection of PMs from RCC between 1993 and 2014. We assessed the clinicopathological characteristics, focusing on the histological findings of PMs. We classified the histology into three types: pure clear cell carcinoma (N = 68), clear cell carcinoma combined with other histology type (N = 8), and non-clear cell carcinoma (N = 8). We examined the relationship between these histological types and the prognosis of patients with PMs from RCC.

Results

Complete resection was achieved in 78 patients (93%). The 5-year overall survival rate after metastasectomy was 59.7%. In multivariate analysis, three factors were found to be independent favorable prognostic factors of overall survival after lung metastasectomy [tumor size <2 cm, hazard ratio (HR) = 0.31, 95% confidence interval (CI) 0.13–0.78, P = 0.012; clear cell type, HR = 0.37, 95% CI 0.16–0.83, P = 0.025; and complete resection, HR = 0.27, 95% CI 0.10–0.78, P = 0.015].

Conclusions

This study indicates that a histological finding of the clear cell type is a significant favorable prognostic factor in addition to complete resection and a tumor size <2 cm. Histological evaluation of PM lesions is important for predicting survival after metastasectomy.

     

Outcome of surgical resection for recurrent pulmonary metastasis from colorectal carcinoma

Background

The outcomes after repeat pulmonary resection for colorectal cancer (CRC) and the factors associated with the prognosis of these patients remain uncharacterized.

Methods

Data on 156 patients who underwent curative resection of pulmonary metastasis from CRC were reviewed. Repeat pulmonary resection was performed in 25 patients; the present study examined the outcomes and factors associated with prognosis after repeat pulmonary resection.

Results

The 5-year survival rate after the first pulmonary resection was 56.2%. A multivariate analysis identified a histological type other than well-differentiated adenocarcinoma, a high prethoracotomy serum carcinoembryonic antigen (CEA) level, and the presence of hilar or mediastinal lymph node metastasis as poor prognostic factors for the first pulmonary resection. The 5-year survival rate after repeat pulmonary resection was 42.1%. Hilar or mediastinal lymph node metastasis at the time of the repeat resection was significantly associated with poor survival.

Conclusions

Repeat pulmonary resection for metastatic CRC provides satisfactory outcomes. Hilar or mediastinal lymph node involvement is consistently associated with a poor prognosis after the first and repeat pulmonary resections.     

A further study of the biological effects of lead on urban and suburban Tokyo school children

Summary There are few reports on lead exposure in children living in the center and the suburbs of large cities. As subjects of epidemiological investigations on the effects of lead exposure in ambient air, school children are very significant in that they have a relatively limited sphere of movement in their daily life. In a previous study the authors compared school children living in the center of Tokyo and those in a suburb of the city and reported that the blood lead levels (PbB) were significantly higher in children living in urban areas [12]. However, it was concluded that further investigation of factors other than ambient air was required to determine the cause of this difference. In the present study, the method used was the same as that of the previous study. However, the areas investigated in the present study were distant from those of the previous study. The results again indicated that the average PbB of school children in the city-center was approximately 2.5–4.8 mg/100 g higher than that of suburban school children, a statistically significant difference. An analysis made on the combined data from both studies according to age revealed that urban school children indicated the highest level among younger urban children, showing a gradual decrease in lead levels as age increased (from 10 to 15 years of age). Suburban children did not show this decline. As a result, it was concluded that these differences in PbB might not be attributable only to lead exposure in ambient air, but to lead exposure from sources such as street dust to which young children are more readily exposed than adults.     

Combined activation of coagulation and inflammation has an important role in multiple organ dysfunction and poor outcome after severe trauma

We tested the hypothesis that activated neutrophil-endothelial cell interaction in DIC can cause endothelial injury contributing to multiple organ dysfunction syndrome (MODS) and a poor outcome after trauma. Fifty-eight severe trauma patients, 29 with DIC and 29 without DIC were studied. Serial levels of soluble L-, P-, and E-selectins, ICAM-1, VCAM-1, thrombomodulin, and neutrophil elastase were measured on days 0-4 after trauma. The numbers of systemic inflammatory response syndrome (SIRS) criteria that patients met were determined, simultaneously. In the DIC patients, higher DIC scores, lower platelet counts, and a longer duration of SIRS were found compared with the non-DIC patients. The incidence of ARDS and MODS were higher in patients with DIC than in those patients without DIC, and the DIC patients had poor outcome. Soluble L-selectin (sL-selectin) level on Day 1 in the DIC patients who died was markedly lower than those in the non-DIC patients. The levels of sP- and sE-selectins, sICAM-1, and sVCAM-1 were more elevated in the patients with DIC than in those without DIC on days 2 to 4. Neutrophil elastase and sThrombomodulin levels in the DIC patients persistently increased during the study period compared to those in the non-DIC patients. Maximum DIC scores in the DIC group showed good correlations with peak levels of sICAM-1, sVCAM-1, neutrophil elastase, sThrombomodulin, and the number of dysfunctioning organs. Highly activated and sustained inflammation caused by neutrophil-endothelium interaction in DIC gives rise to MODS and poor outcome in patients with severe trauma. These results suggest a close relationship between inflammation and thrombosis in posttrauma DIC.