Does adding hydroxychloroquine to empiric treatment improve the live birth rate in refractory obstetrical antiphospholipid syndrome? A systematic review.

PROBLEM: The current standard prevention of obstetric complications in patients with antiphospholipid antibody syndrome (APS) is the use of combination low-dose aspirin and low molecular weight heparin. However, 20-30% of women still experience refractory obstetrical APS. Hydroxychloroquine (HCQ) is an immunomodulatory agent that has been shown in laboratory studies to decrease thrombosis risk, support placentation, and minimize the destructive effects of antiphospholipid antibodies. The objective of this study was to evaluate the risk of pregnancy loss upon treatment with HCQ among women with refractory obstetrical APS. METHOD OF STUDY: A systematic review was conducted according to PRISMA guidelines. Studies that evaluated the use of HCQ during pregnancy in women with primary APS were included. The primary outcomes of interest were live birth and pregnancy losses after treatment with HCQ. RESULTS: Twelve studies met inclusion criteria. Three retrospective cohort studies demonstrated improved live birth rate, and four studies demonstrated a reduction in pregnancy loss rate. Two case reports also demonstrated a benefit in the use of HCQ compared to previous obstetrical outcomes. CONCLUSIONS: Our findings suggest a significant benefit of HCQ in addition to aspirin and heparin for patients with APS to mitigate the risk of antiphospholipid antibody mediated obstetrical complications. Randomized controlled trials with standardized patient selection criteria need to be conducted to corroborate these findings.

Beyond Cartilage Repair: The Role of the Osteochondral Unit in Joint Health and Disease.

IMPACT STATEMENT: In this comprehensive review, we are providing a holistic overview of osteochondral tissue development, disease, pain localization, as well as structural evaluation and current repair strategies. This review is intended to serve as a broad introduction to this multidisciplinary research area. It is a thorough examination of the biological aspects of the osteochondral unit from a tissue engineering perspective, highlighting the importance of the subchondral bone in chondral and osteochondral lesion repair and pain relief.

Low-dose metronomic delivery of cyclophosphamide is less detrimental to granulosa cell viability, ovarian function, and fertility than maximum tolerated dose delivery in the mouse.

Chemotherapy can cause early menopause or infertility in women and have a profound negative impact on the quality of life of young female cancer survivors. Various factors are known to influence the risk of chemotherapy-induced ovarian failure, including the drug dose and treatment duration; however, the scheduling of dose administration has not yet been evaluated as an independent risk factor. We hypothesized that low-dose metronomic (LDM) chemotherapy scheduling would be less detrimental to ovarian function than the traditional maximum tolerated dose (MTD) strategy. In vitro, MTD cyclophosphamide exposure resulted in decreased proliferation and increased granulosa cell apoptosis, while cells treated with LDM cyclophosphamide were not different from untreated controls. Treatments of MTD cyclophosphamide induced high levels of follicle atresia and enhanced follicle recruitment in mice. In contrast, LDM delivery of an equivalent dose of cyclophosphamide reduced growing follicle numbers, but was not associated with higher levels of follicle atresia or recruitment. MTD cyclophosphamide induced significant vascular disruption and DNA damage in vivo, while LDM chemotherapy with equal cumulative amounts of cyclophosphamide was not different from controls. MTD chemotherapy also had a negative effect on mouse-fertility outcomes. Our findings suggest that LDM scheduling could potentially minimize the long-term effects of cyclophosphamide on female fertility by preventing follicle depletion from enhanced activation.