PROBLEM Women with antiphospholipid antibodies (aPL) are at risk of miscarriage and pre-eclampsia, obstetrical disorders associated with reduced trophoblast invasion and spiral artery transformation. aPL target the placenta by binding beta(2) -glycoprotein I (β(2) GPI) on the trophoblast. In this study, we determined whether aPL alter the trophoblast secretion of angiogenic factors and evaluated the effect of low molecular weight heparin (LMWH) on this response. METHOD OF STUDY First-trimester trophoblast was treated with anti-β(2) GPI antibodies with or without LMWH. Angiogenic factor secretion was measured by enzyme-linked immunosorbent assay. RESULTS Trophoblast cells produced more vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), and soluble endoglin following exposure to anti-β(2) GPI Abs, and this occurred in both a MyD88-dependent and MyD88-independent manner. LMWH was unable to reverse the effects of the anti-β(2) GPI Abs on trophoblast VEGF secretion, but enhanced PlGF. Strikingly, LMWH upregulated soluble fms-like tyrosine kinase receptor-1 (sFlt-1) secretion independently of aPL. CONCLUSION This study demonstrates that aPL perturb the secretion of trophoblast angiogenic factors. LMWH does not reverse this effect but exacerbates sFlt-1 secretion, a potent anti-angiogenic factor. These findings may help to explain why women with antiphospholipid syndrome, who are treated with heparin to prevent early pregnancy loss, remain at increased risk of developing late obstetrical complications, such as pre-eclampsia.
Background
Tracheal diverticula (TD) are rare anomalies that may harbor infected secretions, posing potential risk to patients with lung disease. In an end-stage cystic fibrosis (CF) cohort, we describe the characteristics and associated post-lung transplant (LTx) outcomes of TD.
Methods
Pre-transplant computed tomography (CT)’s were reviewed in CF patients undergoing LTx. TD were characterized radiographically and on autopsy when available. Pre-transplant clinical variables and post-transplant outcomes were compared by TD status.
Results
Of 93 patients, 35 (37.6%) had TD. 58% of TD had fat-stranding, and post-mortem TD examinations revealed histology carrying intense submucosal inflammation, and purulent contents that cultured identical species to sputum. There was no difference in post-LTx survival [HR 1.77 (0.82–3.82), p=0.147], bacterial re-colonization, or rejection in patients with TD compared to those without. Patients with TD were more likely to die from infection, but the result was not statistically significant [HR 2.02 (0.62–6.63), p=0.245].
Conclusions
We found a high prevalence of TD in end-stage CF, where diverticula may represent a large-airway bacterial reservoir. TD were not associated with differences in post-LTx outcomes, but given the infectious concerns further investigation is necessary.
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