Pharmacosimulation of delays and interruptions during administration of tirofiban: a systematic comparison between EU and US dosage regimens

Journal of Thrombosis and Thrombolysis - Tirofiban is a glycoproteine (GP) IIb/IIIa receptor antagonist, which inhibits platelet-platelet aggregation and is a potential adjunctive antithrombotic...     

Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia?

Clinical Rheumatology - The prevalence of sarcopenia with osteoporosis results in a higher risk of falling and fractures. It was noted that patients who had completed their planned 5-year denosumab...     

The diagnosis of Gestational Diabetes Mellitus and its impact on In Vitro Fertilization pregnancies. A pilot study

BackgroundIn Vitro Fertilization (IVF) is increasingly becoming a necessary mode of reproduction. This high risk group is prone to Gestational Diabetes Mellitus (GDM) which further exposes these pregnancies to an increased risk of adverse outcomes. In light of the limited data in the current literature, further investigation is needed regarding the time of GDM diagnosis in IVF pregnancies as well as the outcome of IVF pregnancies complicated by GDM.MethodsIn this three center pilot cross sectional study, the data of 101 singleton IVF pregnancies complicated by GDM were analyzed. Prompt GDM diagnosis in IVF pregnancies was accomplished by self-blood glucose monitoring (SMBG) from the first antenatal visit and confirmed by an OGTT. To evaluate pregnancy outcome, maternal and fetal complications in the 101 GDM IVF group was compared to 101 IVF as well as 101 spontaneous conceptions (SC). The three groups were matched by age. The effect of demographic and glycemic parameters on the outcome of GDM IVF pregnancies was investigated.ResultsGDM diagnosis was made before the 24th week in 37.6% of the GDM IVF group. The week of delivery was earlier for the GDM IVF group (37 ± 1.7) relative to the IVF (37.9 ± 0.9, p < 0.001) and the SC group (38.1 ± 0.8, p < 0.001). GDM IVF pregnancies exhibited greater preeclampsia rates and 84.8% underwent caesarian section. No significant difference regarding LGA and SGA birth weights was found. Complications of GDM IVF pregnancies were associated with the 1-h postprandial BG (r = 0.267, p = 0.007).ConclusionGDM screening in IVF pregnancies may be considered earlier than the 24th week. IVF pregnancies affected by GDM are prone to increased maternal and fetal complications which are associated with 1-h postprandial BG.     

Circulating intercellular adhesion molecule 1 predicts non-specific elevation of α1-fetoprotein

Molecules governing cellular interactions have been suggested to be involved in the spurious elevation of 1-fetoprotein (AFP) in non-neoplastic liver disease. To explore this controversial issue, we measured AFP, circulating intercellular adhesion molecule 1 (cICAM-1), and common liver function tests in 111 patients (71 male, 40 female). Eighty-four patients had non-neoplastic chronic liver disease and 27 had hepatocellular carcinoma. The concentration of cICAM-1 was determined immunoenzymatically. In patients with non-neoplastic chronic liver disease, univariate analysis demonstrated a significant correlation between AFP and cholinesterase (R=–0.397,P<0.001), aspartate aminotransferase (R=0.421,P<0.001), bilirubin (R=0.231,P<0.05) and cICAM-1 (R=0.430,P<0.001). Multivariate analysis among these variables and AFP indicated cICAM-1 to be the strongest independent predictor of AFP. We conclude that cICAM-1 compares favourably with liver function tests in predicting non-specific AFP variations in non-neoplastic chronic liver disease, suggesting a link between targeting of the inflammatory damage to the hepatocyte and development of neoplasia.Abbreviations AFP 1-fetoprotein - cICAM-1 circulating intercellular adhesion molecule 1     

Ectopic pregnancy: a resident’s guide to imaging findings and diagnostic pitfalls

Emergency Radiology - Ectopic pregnancy (EP) is a term used to describe any pregnancy which does not implant into the uterine cavity. There are several types of EPs: tubal, interstitial, ovarian,...     

Platelet phenotype changes associated with breast cancer and its treatment

Platelets and their granular contents influence both angiogenesis and breast cancer progression. This study was performed to assess the effect of breast cancer and its treatment on platelet biology and the response to inhibition of the platelet P2Y12 receptor. Receptor-specific platelet activation and inhibition was studied for three platelet-associated proteins important in cancer angiogenesis and progression, vascular endothelial growth factor (VEGF), thrombospondin1 (TSP1), and transforming growth factor beta 1 (TGF-β1).

Twenty-four women with active breast cancer and 10 healthy controls not receiving antiplatelet therapy participated in the study. Ex vivo activation of platelets in whole blood was accomplished using PAR1AP, PAR4AP, convulxin, and ADP. Platelet inhibition was accomplished using the P2Y12 receptor antagonist cangrelor (the in vitro equivalent of clopidogrel). VEGF, TSP1, and TGF-β1 were measured using standard ELISA.

Platelet activation by ADP, PAR1, PAR4, and collagen receptors increased VEGF, TSP1, and TGF-β1 secretion in patients with breast cancer. Agonist-induced release of VEGF was greater in cancer patients as compared to healthy controls (p = 0.02 for ADP, p < 0.001 for PAR1AP, PAR4AP, and convulxin) despite a decrease in the efficiency of VEGF secretion in patients with breast cancer. These differences were not observed for TSP1 and TGF-β1 secretion. P2Y12 receptor inhibition decreased VEGF, TSP1, and TGF-β1 secretion. In patients with cancer, cangrelor inhibited TSP1 release to a greater extent than VEGF and TGF-β1 release. In patients with breast cancer, the magnitude of platelet inhibition achieved by cangrelor was greater than that achieved with healthy controls for all agonists and platelet proteins studied.

While platelets are known to influence progression of breast cancer, our results show that breast cancer and its treatment influence the platelet phenotype by increasing the secretion of pro-angiogenic proteins following platelet activation, modulating the efficiency of platelet protein release as well as increasing the response to antiplatelet therapy.