Coagulofibrinolytic changes in patients with disseminated intravascular coagulation associated with post-cardiac arrest syndrome― Fibrinolytic shutdown and insufficient activation of fibrinolysis lead to organ dysfunction

Introduction

Post-cardiac arrest syndrome (PCAS) is often associated with disseminated intravascular coagulation (DIC), thus leading to the development of multiple organ dysfunction syndrome (MODS). The aim of this study was to examine the pathophysiological relationships between coagulation, fibrinolysis and fibrinolytic shutdown by evaluating the levels of coagulofibrinolytic markers, including soluble fibrin, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPAIC), plasmin-alpha2 plasmin inhibitor complex (PPIC), neutrophil elastase and fibrin degradation product by neutrophil elastase (EXDP).

Materials and Methods

Fifty-two resuscitated patients were divided into two groups: 22 DIC and 30 non-DIC patients.

Results

The levels of soluble fibrin, PPIC, tPAIC, EXDP and neutrophil elastase in the DIC patients with PCAS were significantly higher than those observed in the non-DIC patients. The values of the tPAIC and JAAM DIC scores were found to be independent predictors of increased SOFA scores in the DIC patients. The MODS patients demonstrated significantly higher levels of soluble fibrin and tPAIC; however, the levels of TAFI and EXDP were identical between the patients with and without MODS. In addition, positive correlations were observed between the levels of tPAIC and EXDP in the patients with non-MODS; however, no correlations were observed between these markers in the MODS patients.

Conclusions

Thrombin activation and fibrinolytic shutdown play important roles in the development of organ dysfunction in PCAS patients. Neutrophil elastase-mediated fibrinolysis cannot overcome the fibrinolytic shutdown that occurs in DIC patients with PCAS, thus resulting in the development of MODS.     

Outpatient treatment of symptomatic pulmonary embolism: A systematic review and meta-analysis

Background

Patients with acute deep vein thrombus (DVT) can safely be treated as outpatients. However the role of outpatient treatment in patients diagnosed with a pulmonary embolism (PE) is controversial. We sought to determine the safety of outpatient management of patients with acute symptomatic PE.

Materials and Methods

A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews. Pooled proportions for the different outcomes were calculated.

Results

A total of 1258 patients were included in the systematic review. The rate of recurrent venous thromboembolism (VTE) in patients with PE managed as outpatients was 1.47% (95% CI: 0.47 to 3.0%; I²: 65.4%) during the 3 month follow-up period. The rate of fatal PE was 0.47% (95% CI: 0.16 to 1.0%; I²: 0%). The rates of major bleeding and fatal intracranial hemorrhage were 0.81% (95% CI: 0.37 to 1.42%; I²: 0%) and 0.29% (95% CI: 0.06 to 0.68%; I²: 0%), respectively. The overall 3 month mortality rate was 1.58% (95% CI: 0.71 to 2.80%; I²: 45%). The event rates were similar if employing risk stratification models versus using clinical gestalt to select appropriate patients for outpatient management.

Conclusions

Independent of the risk stratification methods used, the rate of adverse events associated with outpatient PE treatment seems low. Based on our systematic review and pooled meta-analysis, low-risk patients with acute PE can safely be treated as outpatients if home circumstances are adequate.     

Elective EC-IC bypass for unclippable intracranial aneurysms

Ligation of the carotid artery in the neck has become part of the surgical armamentarium for treating inaccessible or technically difficult intracranial aneurysms. Obliteration of an aneurysm by sacrificing the parent vessel has also been employed for the treatment of unclippable posterior circulation and middle cerebral artery aneurysms. Because parent vessel occlusion is not well tolerated by all individuals, the use of an extracranial-intracranial bypass has been advocated in order to improve the safety of this procedure. The purpose of this report is to detail our methods and results with the use of extracranial-intracranial bypass for the treatment of giant internal carotid and middle cerebral artery aneurysms in 35 patients and review the litereture to determine the status of the use of the bypass for other intracranial aneurysms.     

Association between anatomical variations of the posterior communicating artery and the presence of aneurysms

Objectives: Posterior communicating artery aneurysms (PcoAA) account for 30–35% of intracranial aneurysms. The anatomical factors involved in the formation of PCoAA are poorly known. The study aimed to investigate the anatomical variations in the posterior communicating artery (PcoAs) and the presence of PCoAA.

Methods: All 154 patients hospitalized from January 2008 to December 2013 at the department of neurology of our hospital were included in this study; 76 were confirmed with PCoAA upon cerebral angiography and 78 were confirmed without cranial artery aneurysm (controls). According to the blood supply pattern, variations of the PCoAA were classified as Type P0, P-I, or P-II. The angles of C7 and C6 of the internal carotid artery on each side were analyzed.

Results: Compared with controls, patients with PCoAA had a higher frequency of abnormal posterior communicating artery (Types P-I and P-II) (p < 0.001). The angles of C7 and C6 on the contralateral side in the PCoAA group were significantly greater than on the affected side, and significantly lesser than in controls (p < 0.001). There was no difference in the angle between the culprit artery and the contralateral one.

Discussion: Abnormal PCoAs (Types P-I and P-II) might be more vulnerable to PCoAA development, and Type P-II was the most vulnerable. There was a correlation between the angles of C7 and C6 part of the internal carotid artery and the presence of symptomatic PCoAA, with smaller angles being associated with increased frequency of symptomatic PCoAA.     

Influence of internal-gap width and cement type on the retentive force of zirconia copings in pullout testing

Objectives

The purpose of this study was to evaluate the influence of internal-gap width and cement type on the retentive force of zirconia copings.

Methods

A CAD/CAM system was used to mill 48 identical abutments on extracted human molars and fabricate 48 zirconia copings. The internal-gap width for cement was set to 40 μm or 160 μm (n = 24 each). Three cement types (Panavia F, RelyX Unicem, and RelyX Luting) were used with each internal-gap width (n = 8/cement type). The intaglio surfaces of the copings were airborne-particle abraded, and each coping was cemented onto the corresponding abutment using the indicated luting agent. After 10,000 cycles of thermocycling, the retentive force was evaluated by pullout tests. Kruskal–Wallis and Wilcoxon Rank Sum tests were used for data analysis (α = 0.05).

Results

In the 40-μm gap groups, Panavia F had the highest mean retentive force compared to RelyX Unicem and RelyX Luting (P < 0.000). In 160-μm gap groups, RelyX Unicem had the highest mean retentive force compared to Panavia F and RelyX Luting (P < 0.000).

Conclusions

With the increase in internal gap width, a resin cement with self-etching agents as a co-initiator for autopolymerization resulted in significantly decreased retentive force, whereas a resin-modified glass ionomer cement or a self-adhesive resin cement did not. Use of resin cements rather than resin-modified glass ionomer cements improved the retentive force of zirconia copings regardless of the amount of internal gap width.     

Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs

In order to better explain, predict, or extrapolate to humans the developmental toxicity effects of chemicals to zebrafish (Danio rerio) embryos, we developed a physiologically-based pharmacokinetic (PBPK) model designed to predict organ concentrations of neutral or ionizable chemicals, up to 120 h post-fertilization. Chemicals’ distribution is modeled in the cells, lysosomes, and mitochondria of ten organs of the embryo. The model’s partition coefficients are calculated with sub-models using physicochemical properties of the chemicals of interest. The model accounts for organ growth and changes in metabolic clearance with time. We compared ab initio model predictions to data obtained on culture medium and embryo concentrations of valproic acid (VPA) and nine analogs during continuous dosing under the OECD test guideline 236. We further improved the predictions by estimating metabolic clearance and partition coefficients from the data by Bayesian calibration. We also assessed the performance of the model at reproducing data published by Brox et al. (2016) on VPA and 16 other chemicals. We finally compared dose-response relationships calculated for mortality and malformations on the basis of predicted whole embryo concentrations versus those based on nominal water concentrations. The use of target organ concentrations substantially shifted the magnitude of dose-response parameters and the relative toxicity ranking of chemicals studied.     

Dosimetric comparison of vaginal vault brachytherapy vs applicator-guided stereotactic body radiotherapy with volumetric modulated arc therapy and helical tomotherapy for endometrium cancer patients

We performed this dosimetric study to compare a nonstandard volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) techniques with high-dose rate (HDR) brachytherapy (BRT) plan of vaginal vault in patients with postoperative endometrial cancer (EC). Twelve postoperative patients with early stage EC were included in this study. Three plans were performed for each patient; dosimetric and radiobiological comparisons were made using dose-volume histograms and equivalent dose for determining the planning target volume (PTV) coverages in brachytherapy and external beam radiotherapy, and organs-at-risk (OARs) doses between three different delivery techniques. All the plans achieved adequate dose coverage for PTV; however, the VMAT plan yielded better dose conformity, and the HT plan showed better homogeneity for target volume. With respect to the OARs, the bladder D_2cc was significantly lower in the BRT plan than in the VMAT and HT plans, with the highest bladder D_2cc value being observed in the HT plan. However, no difference was observed in the rectum D_2cc of the three plans. Other major advantages of the BRT plan over the VMAT and HT plans were the relatively lower body integral doses and femoral head doses as well as the fact that the integral doses were significantly lower in the BRT plan than in the VMAT and HT plans. This is the first dosimetric comparison of vaginal vault treatment for EC with BRT, VMAT, and HT plans. Our analyses showed the feasibility of stereotactic body radiotherapy technique as an alternative to HDR-BRT for postoperative management of EC patients.     

How might financial pressures have impacted brachytherapy? A proposed narrative to explain the declines in cervical and prostate brachytherapy utilization

Rates of brachytherapy administration in the United States have declined for both cervical and prostate cancers, and we argue that the available facts suggest financial considerations are a major contributor to this issue. In this narrative, we discuss financial pressures that have existed for cervical and prostate brachytherapy and how they may have influenced their declining usage, consider other proposed influences, and provide suggestions for future research to understand the scope of the issue.     

Navigating Uncertainty in the Management of Incidental Findings

The lack of prospective outcomes studies for many types of incidental findings limits our understanding of both their natural history and the potential efficacy of treatment. To support decision making for the management of incidental findings, major sources of uncertainty in management pathways can be mapped and analyzed using mathematical models. This process yields important insights into how uncertainty influences the best treatment decision. Here, we consider a classification scheme, grounded in decision science, which exposes various levels and types of uncertainty in the management of incidental findings and addresses (1) disease-related risks, which are considered in context of a patient’s competing causes of mortality; (2) potential degrees of intervention; (3) strength of evidence; and (4) patients’ treatment-related preferences. Herein we describe how categorizing uncertainty by the sources, issues, and locus can build a framework from which to improve the management of incidental findings. Accurate and comprehensive handling of uncertainty will improve the quality of related decision making and will help guide future research priorities.