Concomitant Use of Direct Oral Anticoagulants with Antiplatelet Agents and the Risk of Major Bleeding in Patients with Nonvalvular Atrial Fibrillation

Purpose

Patients with nonvalvular atrial fibrillation commonly have comorbidities requiring concurrent use of oral anticoagulants and antiplatelets. There are no real-world data on the comparative safety of concomitant antithrombotic treatments in the era of direct oral anticoagulant (DOACs). Thus, we compared the incidence of intracranial hemorrhage, gastrointestinal bleeding, and other major bleeding between concomitant DOAC-antiplatelet use and concomitant vitamin K antagonist (VKA)-antiplatelet use in patients with nonvalvular atrial fibrillation.

The frontotemporal-orbitozygomatic approach: reconstructive technique and outcome

Background  

The frontotemporal-orbitozygomatic (FTOZ) approach, also known as “the workhorse of skull base surgery,” has captured the interest of many researchers throughout the years. Most of the studies published have focused on the surgical technique and the gained exposure. However, few studies have described reconstructive techniques or functional and cosmetic outcomes. The goal of this study was to describe the surgical reconstruction after the FTOZ approach and analyze the functional and cosmetic outcomes.     

Cerebellopontine angle tumor composed of Schwann and meningeal proliferations.

Tumors found in the cerebellopontine angle are predominantly vestibular schwannomas. Mixed tumors found within the cerebellopontine angle are thought to be exceedingly rare and exclusively associated with neurofibromatosis 2. We report a case of a mixed tumor composed of Schwann and meningeal cell proliferations in a patient who was not diagnosed as having neurofibromatosis 2. Mixed tumors composed of neoplastic Schwann and meningeal cells have rarely been reported. However, new evidence indicates that these mixed tumors may be more common than was previously thought and may have an interrelated mechanism of pathogenesis. Although the case we describe does not fulfill the current diagnostic criteria for neurofibromatosis 2, a presumptive diagnosis was given, suggesting that the current diagnostic criteria for neurofibromatosis 2 may be too narrow.     

Radioimmunoassay of neocarzinostatin, an antitumor protein.

Antibodies directed toward the antitumor protein neocarzinostatin (NCS) have been produced in a rabbit by immunization with a highly purified NCS preparation. The antiserum was monospecific and reversed the antibacterial activity of NCS against Sarcina lutea. It cross-reacted with chemically modified derivatives of NCS and mitomalcin but failed to cross-react with macromomycin. A radioimmunoassay procedure has been developed utilizing the antiserum and a biologically active 125I-labeled derivative of NCS. The lower limit of detection by this radioimmunoassay, which involves a double antibody technique for the separation of antibody-bound and free antigen, was 1 X 10(-13) mole. The sensitivity of the assay is such that serum levels of NCS can be determined accurately after administration of the drug to rats at a single dose of 2 mg/kg. Since NCS is now undergoing clinical trial, the radioimmunoassay of the drug will be a valuable tool in clinical pharmacological studies.     

Orthogonal extraction/chromatography and UPLC, two powerful new techniques for bioanalytical quantitation of desloratadine and 3-hydroxydesloratadine at 25 pg/mL

Validation of the bioanalytical method for determination of desloratadine and 3-hydroxydesloratadine was conducted using ultra high pressure liquid chromatography (UPLC) in conjunction with mix mode solid phase extraction. The dynamic range of the assay was from 0.025 ng/mL to 10 ng/mL using 96-well solid phase extraction. On an UPLC system, the inter-run accuracy was better than 94.7% for desloratadine (n = 18) and 94.0% for 3-hydroxydesloratadine (n = 18). The between-run precision (%CV) ranged from 2.6% to 9.8% for desloratadine (n = 18) and 3.1% to 11.1% for 3-hydroxydesloratadine (n = 18). The limit of quantitation represented 0.478 pg and 0.525 pg of extracted material injected on-column for desloratadine and 3-hydroxydesloratadine, respectively. The total run time was slightly over 2 min per sample. The approach of orthogonal extraction/chromatography and UPLC significantly improves assay performance while also increasing sample throughput for drug development studies.     

Uterine response to prostaglandin E2 under oral contraceptives

The effect of prostaglandin E₂ (PGE₂) on the non-pregnant human uterus was evaluated in 35 patients. The compound was administered both by the i.v. and intra-uterine routes. Two groups of volunteers were studied; fifteen cases who were under oral contraceptives and twenty women with normal ovulatory cycles. The latter group served as the control group. The uterus under the influence of oral contraceptives showed a markedly reduced response to i.v. injections of PGE₂ at all phases of the menstrual cycles. However, the response at mid-cycle to local instillation of the compound was contradictory in the two groups, i.e. local intra-uterine instillation of PGE₂ induced uterine stimulation in pill users as compared to the usually observed uterine inhibition in ovulatory (control) cases around mid-cycle. In the proliferative and luteal phases (early and late in the cycle), the response to intra-uterine injections was qualitatively similar in the two groups but greatly reduced quantitatively in the pill user group. The implications of these findings in certain physiological processes and pathological conditions related to reproduction are discussed.