Comparative in vitro efficacy of different platelet glycoprotein IIb/IIIa antagonists on platelet-mediated clot strength induced by tissue factor with use of thromboelastography: differentiation among glycoprotein IIb/IIIa antagonists

In the present study, the in vitro efficacy of different platelet glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists on platelet-fibrin-mediated clot strength under shear was compared with the antiaggregatory efficacy by using tissue factor (TF) thromboelastography (TEG). The ability of platelets to augment the elastic properties of blood clots under shear conditions was measured by computerized TEG under conditions of maximal platelet activation accelerated by recombinant TF. Under these conditions, platelets significantly enhance clot strength 8-fold (relative to platelet-free fibrin clots). This effect was inhibited to a different extent by various platelet GPIIb/IIIa receptor antagonists; this inhibition appears to be dependent on the transmission of platelet contractile force to fibrin via the GPIIb/IIIa receptors. The GPIIb/IIIa antagonists with high binding affinity for resting and activated platelets and slow platelet dissociation rates (class I) but not those with fast platelet dissociation rates (class II) demonstrated potent and comparable inhibition of platelet aggregation and TF-TEG clot strength. Platelet GPIIb/IIIa antagonists of class I, such as XV459 (free-acid form of roxifiban), DMP802, XV454, and c7E3, demonstrated comparable inhibitory dose responses of TF-TEG clot strength and platelet aggregation, with an IC(50) of 50 to 70 nmol/L. In contrast, platelet GPIIb/IIIa antagonists from class II, with comparable antiaggregatory efficacy, such as DMP728, YZ202 (free-acid form of orbofiban), YZ211 (free-acid form of sibrafiban), YZ751, and other antagonists, have a much lower efficacy in altering the strength of TF-mediated clot formation (IC(50) >1.0 micromol/L). These data suggest differential efficacy among different GPIIb/IIIa antagonists in inhibiting platelet-fibrin clot retraction despite of equivalent antiaggregatory potency.     

The Low Molecular Weight Heparin,Tinzaparin, in Thrombosis and Beyond

Standard unfractionated heparin (UFH) has been in clinical use for over 50 years. The commercial use of low molecular weight heparins (LMWHs) began in the mid 1980s for hemodialysis and the prophylaxis of deep vein thrombosis (DVT). Initially, the clinical development of LMWHs was concentrated on the European continent. Subsequently, LMWHs were introduced in North America as well. In the initial stages of development of these drugs only nadroparin, dalteparin and enoxaparin were used. Subsequently, several other LMWHs such as ardeparin, tinzaparin, reviparin and parnaparin were introduced. LMWHs constitute a group of important medications with total sales reaching nearly 2.5 billion dollars with expanded indications reaching far beyond the initial indications for the prophylaxis of post‐surgical DVT. This review highlights the pharmacology of tinzaparin. Unlike other LMWHs, tinzaparin is prepared by enzymatic hydrolysis with heparinase, while various chemical depolymerization methods are used for the synthesis of other LMWHs. As compared with the standard heparin, LMWHs have different pharmacodynamic, and pharmacokinetic properties; they also differ in clinical benefits.     

Diagnostic yield of CT pulmonary angiography for pulmonary embolism in clinically suspected patients

Pulmonary embolism (PE) is a common medical problem. Its diagnostic criteria must be reviewed to determine the need for confirmatory testing. Computed tomography pulmonary angiography (CTPA) is the current standard of care, which provides accurate diagnosis with rapid turnaround. This study aimed to estimate the diagnostic yield of CTPA in clinically suspected PE patients in a tertiary care hospital in Saudi Arabia.Radiology records of all patients with clinically suspected PE who underwent CTPA between January 1, 2012 and September 30, 2018 were reviewed retrospectively. A radiologist with 10 years of professional experience interpreted and reported all cases. The Wells score with 2 tiers (likely and unlikely) was used to raise the clinical suspicion of PE.Positive results for PE were reported in 177 out of 534 clinically suspected cases (33%). Among the positive PE cases, 143 were acute (81%) and 34 (19%) were chronic. Bilateral, right-sided, and left-sided PE were found in 115 (65%), 37 (21%), and 25 (14%) cases, respectively. Involvement of the segmental branches, subsegmental branches, and the pulmonary trunk were noted in 152 (86%), 70 (40%), and 9 cases (5%), respectively. Saddle PE was found in (4%) of the cases. The lower lobe branches (right 55%, left 53%) and the upper lobe branches (right 47%, left 41%) were the most common sites of involvement.CTPA had a higher positive detection rate for PE among clinically suspected cases than its published diagnostic yield. Adequate clinical evaluation when selecting patients for CTPA is emphasized to minimize unjustified exposure of the patients to radiation and intravenous contrast administration. It is crucial for radiologists to provide detailed reports commenting on all relevant findings, including pertinent negatives. A template for reporting radiological findings for CTPA can be recommended for this purpose.     

Vitamin D and cardiometabolic disorders: a review of current evidence,genetic determinants and pathomechanisms

Vitamin D deficiency has been implicated in the pathophysiology of cardiometabolic disorders including obesity, type 2 diabetes mellitus, cardiovascular diseases and polycystic ovary syndrome. Despite a large number of experimental and observational studies supporting a role for vitamin D in these pathologies, randomized controlled trials have reported little to no effect of vitamin D supplementation in the prevention or treatment of these disorders, although some results remain ambiguous. Polymorphisms in genes related to vitamin D metabolism, particularly in the vitamin D receptor and binding protein and the metabolizing enzyme 1‐α‐hydroxylase, have emerged as potential contributors to these divergent results. It is now becoming increasingly recognized that the effects and potential benefits of vitamin D supplementation may vary by several factors including vitamin D deficiency status, ethnicity and/or the presence of genetic variants, which affect individual responses to supplementation. However, these factors have seldom been explored in the available literature. Future trials should consider inter‐individual differences and, in particular, should aim to clarify whether certain subgroups of individuals may benefit from vitamin D supplementation in the context of cardiometabolic health.     

Would gestational age and presence of brain anomalies affect interobserver reliability of fetal head biometry? Using off-line analysis of 3-D dataset

The objective was to assess interobserver reliability of fetal head biometry using archived three-dimensional (3-D) volumes and the impact of gestational age and presence of brain anomalies on examiners’ performance. Seventy nine 3-D volume datasets of fetal head were examined: 27 were normal and 52 had brain abnormalities. Off-line analysis was done by three fetal medicine experts (E1, E2 and E2), all were blinded to history and patient details. Measurements of the biparietal diameter (BPD), head circumference (HC), lateral ventricle (Vp) and transcerebellar diameter (TCD) were compared between examiners and to two-dimensional (2-D) measurements. Comparisons were made at two gestational age groups (≤22 and >22 weeks) and in presence and absence of brain anomalies. The intraclass coefficient showed a significantly high level of measurement agreement between 3-D examiners and 2-D, with values >0.9 throughout (p < 0.001). Bias was evident between 3-D examiners. E2 produced smaller measurements. The mean percentage difference between this examiner and the other two in BPD, HC, Vp and TCD measurements was significant, of 1.6%, 1%, 4.9% and 1.8%, respectively. E1 measured statistically larger for HC and TCD. E3 measured significantly larger for only BPD. The presence of anomalies was of no influence on the 3-D examiners’ performance except for E3 who showed bias in BPD measurements only in cases with brain anomalies. Unlike other examiners, bias of E2 was only seen at gestational age group ≤22 weeks. Limits of agreement in measurements between observers were narrow for all parameters but were widest for the Vp measurements, being ±23% of the mean difference. Despite the above bias, the actual mean difference between examiners was small and unlikely to be of any clinical significance. Off-line measurement of fetal head biometry using 3-D volumes is reliable. In our study, presence of brain anomalies was unlikely to influence the reproducibility of measurements. Gestational age seemed to be of an impact on examiners’ bias. Among experts this bias may be of no clinical significance.     

Antiplatelet Therapies: Recent Advances in the Development of Platelet Glycoprotein IIb/IIIa Antagonists

This article reviews recent advances in antiplatelet therapies, compares the antiplatelet/antithrombotic efficacy of various antiplatelet strategies to that of platelet glycoprotein (GP) IIb/IIIa receptor antagonists, and discusses issues in the development of long-term anti-GP IIb/IIIa therapy, and the potential adjunct strategies with GP IIb/IIIa antagonists.     

Comparative antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist (XV454) and abciximab (c7E3) in flow models of thrombosis

Glycoprotein (GP) IIb/IIIa is pivotal in homotypic platelet aggregation and may also be involved in the heterotypic adhesion of leukocytes and tumor cells to platelets. This study was primarily undertaken to compare the antiplatelet efficacy of a novel, nonpeptide GPIIb/IIIa antagonist, XV454, to that of abciximab in 2 flow models of platelet thrombus formation: (1) direct shear-induced platelet aggregation imposed by a cone-and-plate rheometer and (2) platelet adhesion onto von Willebrand factor (vWF)/collagen I followed by aggregation in a perfusion system. XV454 inhibited platelet aggregation in a concentration-dependent manner in both experimental models. Maximal inhibition of aggregation was achieved by XV454 at approximately 70% receptor occupancy, which is lower than the >/=85% previously reported for abciximab. At similar levels of receptor blockade (approximately 45%), XV454 appeared to be relatively more effective than abciximab in suppressing platelet aggregation. Neither XV454 nor abciximab inhibited platelet adhesion to collagen. Pretreatment of surface-adherent platelets with either XV454 or abciximab inhibited the attachment of monocytic THP-1 cells under flow. In contrast, the rapidly reversible GPIIb/IIIa inhibitor orbofiban failed to suppress these heterotypic interactions. These findings demonstrate that XV454 is a potent GPIIb/IIIa antagonist with a long receptor-bound lifetime like abciximab and may be beneficial for the treatment/prevention of thrombotic complications.     

Predicting falls among Egyptian nursing home residents: A 1-year longitudinal study

Background/PurposeFalls and their related complications are serious health problems among the institutionalized older population. This study aimed to evaluate the incidence of falls and the risk factors among nursing home residents in Cairo, Egypt.MethodsA one-year prospective cohort study was done in three nursing homes in Cairo. Overall, 84 residents aged over 60 years participated in this study. Baseline demographic characteristics and results of comprehensive geriatric assessments, e.g. cognition, depression, functional and nutritional status, previous falls, fear of falling, assistive device use, and assessment by the timed up-and-go test (TUG) test were collected. All falling accidents were recorded by the nursing home staff during the study period.ResultsDuring the study period, 163 incident falls (1940 falls/ 1000 resident-years) were identified in 53 fallers (631 fallers/1000 resident-years) were recorded. On average, fallers may fall twice a year (mean ± SD 2.0 ± 2.1 episodes, range 1–6). Compared to nonfallers, fallers were older, more likely to have hadprevious falls, fear of falling, frailty, impaired instrumental activities of daily living, poor cognitive status, malnutrition or its risk, assistive device use, and slower TUG. The most sensitive (86.8%) and specific (90.3%) predictor for falls in this study was TUG >14 seconds.ConclusionSixty-three percent of Egyptian nursing home residents may fall during one year follow-up with the incidence of 1019 falls/1000 resident-years. The most important predictive factor for falls in this study was the TUG >14 seconds.     

Low‐grade papillary cystadenocarcinoma of the parotid gland: Presentation of a case with cytological,histopathological, and immunohistochemical features and pertinent literature review

Cystadenocarcinoma of the salivary glands is a very rare, slow growing, low‐grade malignant neoplasm. However, when it occurs, it poses a diagnostic challenge. They are usually well circumscribed and exhibit multicystic appearance. The cytological features of fine‐needle aspirates show bland appearing papillary and micropapillary neoplasm with variable cellularity and absence of cytological atypia. The cells are small to medium in size with abundant and occasionally vacuolated cytoplasm. The nuclei are eccentric, bland appearing, round, and at the most part uniform in size without anaplasia or mitotic activity. The background is commonly mucoid. Histologically, the neoplasm is usually well circumscribed and contains variably sized multicystic spaces with papillary structures. Foci of definite stromal invasion by tumor cells have to be present to justify the diagnosis of carcinoma. The remainders of the cytological features are similar to these seen on cytological smears. Typically, they are slow growing and conservative, but complete surgical excision is considered adequate. We present a case in a 57‐year‐old Saudi man that we believe the first from our region demonstrating the clinical and pathological features. Diagn. Cytopathol. 2009. © 2008 Wiley‐Liss, Inc.     

Implementation of 3D Printing in Medical Care for Preoperative Planning of Complex Ventricular Septal Defect

Three-dimensional (3D) modeling and printing in medicine have emerged to encompass every aspect of medical applications. This ranges from education, illustration, and treatment, as well as patient care whether for purposes of diagnosis or treatment and surgical planning. In the past few decades, these novel tools have shown promising utility to help radiologists and the medical team to improve quality of patient care and outcomes via 3D printing application and utilization. This workflow will be illustrated through a ventricular septal defect (VSD) case at which 3D analysis was critical in the assessment and treatment planning of the patient’s underlying medical condition.