Subcutaneous Heparin Therapy for Patients with Cancer-Associated Stroke

Background

Anticoagulation therapy, particularly subcutaneous heparin therapy, is recommended for cancer-associated thrombosis. However, not starting or discontinuing anticoagulation was not rare. The aim of the present study was to examine the practical issues related to anticoagulation therapy and effects of subcutaneous heparin therapy for cancer-associated stroke.

No clear survival benefit of azacitidine for lower‐risk myelodysplastic syndromes: A retrospective study of Nagasaki

The efficacy of azacitidine (AZA) on survival of lower risk (LR) ‐ myelodysplastic syndromes (MDS) is controversial. To address this issue, we retrospectively evaluated the long‐term survival benefit of AZA for patients with LR‐MDS defined by International Prognostic Scoring System (IPSS). Using data from 489 patients with LR‐MDS in Nagasaki, hematologic responses according to International Working Group 2006 and overall survival (OS) were compared among patients that received best supportive care (BSC), immunosuppressive therapy (IST), erythropoiesis‐stimulating agents (ESA), and AZA. Patients treated with AZA showed complete remission (CR) rate at 11.3%, marrow CR at 1.9%, and any hematologic improvement at 34.0%, with transfusion independence (TI) of red blood cells in 27.3% of patients. and platelet in 20% of patients, respectively. Median OS for patients received IST, ESA, BSC, and AZA (not reached, 91 months, 58 months, and 29 months, respectively) differed significantly (P < .001). Infection‐related severe adverse events were observed in more than 20% of patients treated with AZA. Multivariate analysis showed age, sex, IPSS score at diagnosis, and transfusion dependence were significant for OS, but AZA treatment was not, which maintained even response to AZA, and IPSS risk status at AZA administration was added as factors. We could not find significant survival benefit of AZA treatment for LR‐MDS patients.     

Comprehensive preclinical pharmacokinetic evaluations of trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate,in cynomolgus monkeys

1. Trastuzumab deruxtecan (DS-8201a) is an antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) conjugated to a topoisomerase I inhibitor (DXd) at a drug-to-antibody ratio (DAR) of 7-8. Here, we examined the pharmacokinetic (PK) profiles of DS-8201a and DXd in cynomolgus monkeys, a cross-reactive species.

2. Following intravenous (iv) administration of DS-8201a, the linker was stable in plasma, and systemic DXd exposure was low. DXd was rapidly cleared following iv dosing. Biodistribution studies revealed that intact DS-8201a was present mostly in the blood without tissue-specific retention. The major pathway of excretion for DXd was the faecal route following iv administration of radiolabelled DS-8201a. The only detectable metabolite in the urine and faeces was unmetabolized DXd. DXd is a substrate of organic anion transporting polypeptides, P-gp, and breast cancer resistance protein.

3. In conclusion, the stable linker in circulation and the high clearance of DXd upon release resulted in the low systemic exposure to DXd. Furthermore, the minimal tissue-specific retention and rapid excretion of DXd into faeces as its unmetabolized form with potentially limited impact on drug???drug interaction as a victim were also critical elements of the PK profile of DS-8201a.

     

The correlation between toe flexor strength and performance-based measures of physical fitness in the elderly

[Purpose] To examine the correlation between toe flexor strength (TFS) and physical fitness performance measurements and their gender differences in the elderly. [Participants and Methods] Japanese males (n=50) and females (n=121), aged 65–88 years, participated in this study. We measured TFS, handgrip strength (HGS), knee extensor strength (KES), sit-and-reach distance (SR), and functional reach (FR). [Results] The female participants had significantly lower TFS, KES, and HGS than the male participants; however, the female participants had a significantly higher SR than that the male participants. FR was not significantly different between males and females. In males, TFS was significantly correlated with HGS, KES, SR, and FR. In females, TFS had correlations with HGS, KES, and FR; however, no correlation with SR was found. We could observe these correlations even after adjustment for age and body weight. [Conclusion] Elderly male had higher TFS than elderly females. In addition, TFS was correlated with all the physical fitness measurements in the male participants and all the measurements except for SR in the female participants. Gender and aging may explain the inconsistent results between SR and other physical fitness performance measurements.Key words: Toe grip, Aging, Physical fitness