Uterine Artery Embolization and Methotrexate Infusion as Sole Management for Caesarean Scar and Cervical Ectopic Pregnancies: A Single-Center Experience and Literature Review.

INTRODUCTION: The incidence of caesarean scar pregnancy (CSP) and cervical pregnancy (CP) has increased significantly in recent years. The related hemorrhage can be lethal and often needs hysterectomy. This study aims to assess the technical and clinical results of uterine artery embolization (UAE) combined with intra-arterial methotrexate (MTX) infusion for CSP and CP. METHODS: A retrospective study was conducted for 11 patients (age range from 25-40 years, mean; 31.8 y) with CSP (7/11) and CP (4/11). The diagnosis was confirmed by elevated b-hCG levels (mean 31.245 mIU/mL) with sonography and/or magnetic resonance imaging. They were treated with UAE using particulate embolic material. In all patients, the infusion of MTX (50 mg/m2) was performed before UAE. Follow-up periods after UAE ranged between 6-24 months included weekly sonography and b-hCG level assessment. A literature review was performed using standard online search tools. RESULTS: In 10 patients, UAE controlled active vaginal bleeding and reduced post-procedural b-hCG levels significantly by the second week. One patient presented with persistent elevated b-hCG level and vaginal rebleeding. The rebleeding was successfully controlled by second UAE procedure. The ectopic pregnancies were resolved, and the uterus was preserved in all patients. No major complications were detected. Normal menses resumed within 2 months after UAE. Two patients had subsequent natural successful intrauterine pregnancies. CONCLUSION: UAE combined with intra-arterial MTX infusion resulted in resolution of ectopic pregnancies with control of hemorrhage and without hysterectomy in this small group of patients.

Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies.

OBJECTIVES.: The SpAs are genetically and therapeutically linked to IL-23, which in turn regulates IL-22, a cytokine that has been implicated in the regulation of new bone formation in experimental models. We hypothesize that IL-22, a master regulator of stem cells in other niches, might also regulate human mesenchymal stem cell (MSC) osteogenesis. METHODS.: The effects of IL-22 on in vitro MSC proliferation, migration and osteogenic differentiation were evaluated in the presence or absence of IFN-γ and TNF (to ascertain IL-22 activity in pro-inflammatory environments). Colorimetric XTT assay, trans-well migration assays, quantitative real-time PCR (qRT-PCR) for MSC lineage markers and osteogenesis assays were used. RESULTS.: Combined treatment of MSC with IL-22, IFN-γ and TNF resulted in increased MSC proliferation ( P = 0.008) and migration ( P = 0.04), an effect that was not seen in cells treated with IL-22 alone and untreated cells. Osteogenic and adipogenic, but not chondrogenic, transcription factors were upregulated by IL-22 alone ( P < 0.05). MSC osteogenesis was enhanced following IL-22 exposure ( P = 0.03, measured by calcium production). The combination of IFN-γ and TNF with or without IL-22 suppressed MSC osteogenesis ( P = 0.03). CONCLUSION.: This work shows that IL-22 is involved in human MSC proliferation/migration in inflammatory environments, with MSC osteogenesis occurring only in the absence of IFN-γ/TNF. These effects of IL-22 on MSC function is a novel pathway for exploring pathological, post-inflammation osteogenesis in human SpA.

Anti-IL-6 receptor monoclonal antibody as a new treatment of endometriosis.

Many pro-inflammatory cytokines especially tumor necrotic factor alpha (TNFα), interleukin (IL)-1ß, and IL-6 have crucial role in the pathogenesis of endometriosis. In this study, we investigated the immune-modulatory role of humanized anti-IL-6 receptor monoclonal antibodies in the treatment of endometriosis. This is a prospective, randomized, controlled, blinded study in which Sprague Dawley rats were used as animal model of endometriosis. Animals were randomly divided into two groups, a test group which received tocilizumab (Actemra; Roche, Switzerland) and a control group which received saline. Afterwards, a comparison was done between the eutopic and ectopic endometrium that was excised from both groups, histopathologically and immune-histochemically. Histopathologic assessment and immune-histochemical staining were performed using antibodies against IL-6. Tocilizumab significantly suppressed the volume of endometriotic lesions compared with non-treated rats (P = 0.006) and atrophied the ectopic endometrial-like epithelium (in 42.8% of treated rats vs 0% in the control group). Tocilizumab also decreased the anti-IL-6 receptor immune-histochemical staining intensity in ectopic endometrium (from non to +++ in the test group vs ++ or more in the control group), with no apparent difference in the eutopic one reflecting the down-regulation of IL-6-producing cells in ectopic endometriotic lesions. In rats with induced endometriosis, anti-IL-6 receptor monoclonal antibodies could offer a new horizon of usage of this immune-modulatory biologic drug, used in other autoimmune diseases, in treatment of endometriosis.

Timing of initiation of low-molecular-weight heparin administration in pregnant women with antiphospholipid syndrome: a randomized clinical trial of efficacy and safety.

OBJECTIVE: We aimed to evaluate the effect of different timing of initiation of low-molecular-weight heparin (LMWH) administration on the pregnancy outcomes in women with antiphospholipid syndrome (APS). MATERIALS AND METHODS: A randomized controlled study was conducted on women with obstetrical APS. All participants were randomly divided at documentation of positive pregnancy test into two groups; early initiation group in which LMWH therapy was started once positive pregnancy test was established (in the fifth week of gestation), and later initiation group in which LMWH therapy was started after sonographic confirmation of fetal cardiac pulsation (in the seventh week of gestation). In both groups, LMWH (enoxaparin) was given at a dose of 40 mg/day subcutaneously and the therapy continued until end of pregnancy. The primary outcome measure was ongoing pregnancy rate and the secondary outcome measures were fetal loss, live birth rate, preterm labor before 34 weeks of gestation, intrauterine growth restriction (IUGR), and congenital fetal malformations. RESULTS: Ninety-four women (48 in the early initiation group and 46 in the later initiation group) were subjected to final analysis. The ongoing pregnancy rate was significantly higher in the early initiation group than in the later initiation group (81.2% vs 60.9%; P=0.040). However, both groups were similar in the incidences of fetal loss, preterm labor before 34 weeks of gestation, and IUGR, and live birth rate. No recorded congenital fetal malformations in both groups. CONCLUSION: Early administration of LMWH for pregnant women with obstetrical APS reduces early pregnancy loss, but does not affect the incidence of late obstetrical complications.