Microparticles as a circulating source of procoagulant and fibrinolytic activities in the circulation

Circulating microparticles (MP) are small membrane vesicles derived from a variety of cell types including platelets, erythrocytes, leukocytes, and endothelial cells. They harbor a large repertoire of cell surface receptors, mRNA and biological activities that are related to their involvement in many biological functions. MP subpopulations are well known for their procoagulant activity that relies mainly on the expression of phosphatidylserine and of tissue factor, the major cellular activator of the clotting system. In this review, we will discuss a new vision of MP as complex and ambivalent structures, expressing both activators and inhibitors of coagulation, but also conveying fibrinolytic properties, counteracting their procoagulant activities and identifying MP as integrative systems tuning the hemostatic balance.     

Maintenance chemotherapy in children with ALL exerts metronomic-like thrombospondin-1 associated anti-endothelial effect

Maintenance chemotherapy is an important part of the treatment of ALL in children. It relies on the long-term oral administration of daily low-dose mercaptopurin and weekly low-dose methotrexate. Although it has been used in the clinic for decades, its mechanisms of action remain unclear. Here, we investigated different angiogenic and immune biomarkers to gain insights into the mechanisms of action of maintenance therapy in children with ALL. We thus monitored circulating endothelial cells (CEC), endothelial progenitor cells (EPC) and endothelial microparticles (EMP), pro-angiogenic factors (VEGF, VEGFR-1 and Ang-2), anti-angiogenic factor thrombospondin-1 (THBS1) and regulatory T lymphocytes (Treg) in 47 children with ALL during the maintenance phase of their treatment (at treatment initiation and after 6, 12 and 18 months). We observed a statistically significant decrease in EPC and EMP counts throughout the maintenance phase associated with a significant increase in THBS1 levels. No significant change was detected in other angiogenic markers or in Treg numbers.The results presented here indicate that maintenance therapy in children with ALL exerts its antitumor activity at least in part through anti-angiogenic effects, similar to those induced by metronomic chemotherapy. Larger studies are now warranted to validate these findings and determine their clinical implications.     

Total Synthesis of Thiaplakortone A: Derivatives as Metabolically Stable Leads for the Treatment of Malaria

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Macroscopic heterogeneity of liver fat: an MR-based study in type-2 diabetic patients

Objective

To assess the heterogeneity of liver fat deposition with MR of the liver in type-2 diabetic (T2D) patients.

Methods

We enrolled 121 consecutive T2D patients. The reference standard was 3.0-T ¹H-MR spectroscopy. Hepatic steatosis was defined as liver fat content (LFC) ≥5.56?%. A triple-echo gradient-echo sequence corrected for T1 recovery and T2* decay was used to calculate LFC in left and right livers and hepatic segments. Analyses were performed using a linear mixed model.

Results

Fifty-nine (48.8?%) patients had liver steatosis, whereas 62 (51.2?%) did not. Steatosis was greater in the right than in the left liver (P?P?P?P?P?=?0.0002 respectively) patients [mean maximum difference: 3.98?% (range: 0.74–19.32?%)]. In 23 patients (19?%), LFC was <5.56?% in one segment, whereas it was ≥5.56?% in at least one other.

Conclusion

Overall, the mean segmental/lobar variability of steatosis is low. However, segmental variability can sometimes lead to a misdiagnosis.

Key Points

• There is a need for methods quantifying steatosis over a large region.
• Steatosis is usually greater in the right than left lobe of the liver.
• Steatosis within both left and right hepatic lobes is segmentally heterogeneous.
• Segmental variability of steatosis can result in misdiagnosis.

     

Mapping of liver fat with triple-echo gradient echo imaging: validation against 3.0-T proton MR spectroscopy

The purpose of this study was to validate a magnetic resonance imaging (MRI) technique for mapping liver fat, using ¹H magnetic resonance spectroscopy (¹H-MRS) as the reference standard. In 91 patients with type 2 diabetes, 3.0-T single-voxel point-resolved ¹H-MRS was used to calculate the liver fat fraction (LFF) from the water (4.76 ppm) and methylene (1.33 ppm) peaks, corrected for T1 and T2 decays. LFF (corrected for T1 and T2* decays) was also obtained from the mean signal intensity on a map built from a triple-echo (consecutive in-phase, opposed-phase, and in-phase echo times) breath-hold gradient echo sequence, using basic image calculation functions (arithmetic mean, subtraction, division, multiplication by a numerical factor). Mean LFF was 8.9% (range, 0.9–33.5) by MRI and 8.8% (range, 0–34.1) by ¹H-MRS. Pearson’s coefficient was 0.976 (P < 0.0001) and Lin’s coefficient was 0.975 (P < 0.0001). Liver segment had no significant influence. With Bland–Altman analysis, 95.6% (87/91) of data points were within the limits of agreement. Given its excellent agreement with ¹H-MRS, our mapping technique can be used for visual and quantitative evaluation of liver fat in everyday practice.     

Efficacy,safety and outcomes of transcatheter arterial embolization with N-butyl cyanoacrylate glue for non-variceal gastrointestinal bleeding: A systematic review and meta-analysis

PurposeTo perform a systematic review and meta-analysis to determine the safety, efficacy, and outcomes of transcatheter arterial embolization (TAE) with N-butyl cyanoacrylate (NBCA) as the single embolic agent for the management of non-variceal upper and lower gastrointestinal bleeding (GIB).Materials and methodsA literature search using MEDLINE/PubMed, EMBASE, and SCOPUS databases was performed for studies published from January 1980 to December 2019. Data from eligible studies were extracted and evaluated by two independent reviewers. Exclusion criteria were sample size < 5, article reporting the use of NBCA with other embolic agents, no extractable data, and duplicate reports. Technical success, clinical success, 30-day rebleeding, 30-day overall and major complications, and 30-day mortality were evaluated. The estimated overall rates were calculated with their 95% confidence intervals, based on each study rate, weighted by the number of patients involved in each study. Heterogeneity across studies was assessed using the Q test and I² statistic.ResultsFifteen studies with 574 patients were included. For upper GIB (331 patients), the technical and clinical success rates, and 30-day rebleeding and mortality rates, were 98.8% (328 of 331 patients) and 88.0% (237 of 300 patients), and 12.5% (69 of 314 patients) and 15.9% (68 of 331 patients), respectively. Thirty-day overall and major complications occurred in 14.3% (28 of 331 patients) and 2.7% (7 of 331 patients) of patients, respectively. For lower GIB (243 patients), the technical and clinical success rates, and 30-day rebleeding and mortality rates, were 98.8% (78 of 78 patients) and 78.0% (145 of 189 patients), and 15.7% (33 of 218 patients) and 12.7% (14 of 78 patients), respectively. Thirty-day overall and major complications occurred in 13.0% (25 of 228 patients) and 8.6% (19 of 228 patients) of patients, respectively.ConclusionTAE with NBCA is safe and effective for treating non-variceal GIB, with high clinical success and very low major complication rates.