Recombinant activated factor VII decreases bleeding without increasing arterial thrombosis in rabbits

PURPOSE: To compare the effects of recombinant activated factor VII (rFVIIa) and platelet-rich plasma (PRP) in an experimental model of bleeding and arterial thrombosis. METHODS: The Folts model was used in 60 rabbits. After anesthesia, the carotid artery was exposed and a 75% stenosis was induced. A compression injury of the artery triggered a series of cyclic flow reductions (CFRs). After counting baseline CFRs, animals were assigned randomly to one of four groups (n = 15 in each): control, PRP, rFVIIa and placebo. Control animals received 10 mL.kg(-1) of saline while 10 mL.kg(-1) of a hydroxyethyl starch solution (200,000/6%/0.5) were infused in the three other groups. CFRs were measured again, followed by treatment with PRP, rFVIIa or placebo and by a final measurement of CFRs. At the end of each observation period, an ear immersion bleeding time (BT) was measured and a blood sample was drawn for the evaluation of hematological variables. Microvascular bleeding was evaluated at the end of the experiment in grams of blood shed from liver and spleen sections. Results are presented as median (range). RESULTS: rFVIIa shortened the BT and decreased microvascular bleeding as compared with placebo [60 (35-100) sec vs 110 (50-140) sec, P = 0.0019 and 9 (4-24) g vs 17 (5-28) g, P = 0.002, respectively]. rFVIIa did not increase CFRs [3(0-9) vs |(0-5), P = 0.11]. CONCLUSION: rFVIIa led to a decrease in BT and microvascular bleeding but did not significantly affect arterial thrombosis in rabbits.     

Starch digestibility modulation significantly improves glycemic variability in type 2 diabetic subjects: A pilot study

Background and aimsIn type 2 diabetes (T2D) patients, the reduction of glycemic variability and postprandial glucose excursions is essential to limit diabetes complications, beyond HbA1c level. This study aimed at determining whether increasing the content of Slowly Digestible Starch (SDS) in T2D patients’ diet could reduce postprandial hyperglycemia and glycemic variability compared with a conventional low-SDS diet.Methods and resultsFor this randomized cross-over pilot study, 8 subjects with T2D consumed a controlled diet for one week, containing starchy products high or low in SDS. Glycemic variability parameters were evaluated using a Continuous Glucose Monitoring System.Glycemic variability was significantly lower during High-SDS diet compared to Low-SDS diet for MAGE (Mean Amplitude of Glycemic Excursions, p < 0.01), SD (Standard Deviation, p < 0.05), and CV (Coefficient of Variation, p < 0.01). The TIR (Time In Range) [140–180 mg/dL[ was significantly higher during High-SDS diet (p < 0.0001) whereas TIRs ≥180 mg/dL were significantly lower during High-SDS diet. Post-meals tAUC (total Area Under the Curve) were significantly lower during High-SDS diet.ConclusionOne week of High-SDS Diet in T2D patients significantly improves glycemic variability and reduces postprandial glycemic excursions. Modulation of starch digestibility in the diet could be used as a simple nutritional tool in T2D patients to improve daily glycemic control.Registration numberin clinicaltrials.gov: NCT 03289494.     

Frequent expression of PD‐L1 on circulating breast cancer cells

Immune checkpoint regulators such as PD‐L1 have become exciting new therapeutic targets leading to long lasting remissions in patients with advanced malignancies. However, in view of the remarkable costs and the toxicity profiles of these therapies, predictive biomarkers able to discriminate responders from non‐responders are urgently needed. In the present paper, we provide evidence that PD‐L1 is frequently expressed on metastatic cells circulating in the blood of hormone receptor‐positive, HER2‐negative breast cancer patients. We performed western blot, flow cytometry and immunocytochemical analyses to demonstrate the specificity of the PDL1 antibody used in our study and established immunoscores for PDL1 expression on single tumor cells. We then selected sixteen patients with circulating tumor cells (CTCs) using the CellSearch® system and found PD‐L1(+) CTCs in 11 patients (68.8%). The fraction of PD‐L1(+) CTCs varied from 0.2 to 100% in individual patients. This is the first report demonstrating the expression of PD‐L1 on CTCs. The established CTC/PD‐L1 assay can be used for liquid biopsy in future clinical trials for stratification and monitoring of cancer patients undergoing immune checkpoint blockade.     

Conversion of oral alfacalcidol to oral calcitriol in the treatment of secondary hyperparathyroidism in chronic hemodialysis patients

International Urology and Nephrology - The optimal vitamin D3 therapy for the treatment of secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients is still controversial. Recent...     

Surgical and Nonsurgical Endodontic Treatment-induced Stress

This observational study compared physiologic and psychological indicators of stress between two groups of 30 healthy patients undergoing either surgical or nonsurgical endodontic treatments. Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure were monitored during care sessions. The patients were asked to score their anxiety before treatment and to report pain, stress, and/or discomfort experienced during care. Variations in HR and SBP were significantly dependent on treatment group (HR: F = 6, p < 0.001; SBP: F = 4, p = 0.05). Intergroup differences increased during the active steps of the treatment, such as local anesthesia, rotary instrumentation, periradicular curettage, root filling, and field removal. Moreover, the level of stress experienced during the care procedure was correlated to the level of anticipated anxiety in both groups. This study raises questions on the indications for anxiolysis or sedation in endodontic patients as a means of preventing the neurophysiologic consequences of stress.