The role of heparin and heparin-binding growth factors in pre-eclampsia

The aims of this study tested the hypothesis that expression of heparin-binding growth factors (HBGFs) in normal placental development was altered in a specific pregnancy disorder preeclampsia. HBGFs bind to heparin, a glycosaminoglycan (GAG) affecting activity. I investigated the role of heparin and HBGFs in pathophysiology of pre-eclampsia. Placental tissue from a cohort study of 87 women was performed following uncomplicated pregnancy at term, but not in labour (TNL, n=26), preterm labour (PTL, n=17), following labour onset (TL, n=21), first trimester (FNL, n=4) and pre-eclampsia (PE, n=19). The HBGFs studied were vascular endothelial growth factor (VEGF), placental growth factor (PLGF), fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), heparin-binding epidermal growth factor (HB-EGF), midkine (MK), pleiotrophin (PTN), and cluster differentiation (CD105). The localisation of HBGFs and receptors VEGFR-1, /(sflt-1), PLGFR-1, VEGFR-2 and FGF2R-1 in placenta were detected. The expression of VEGF, PLGF, FGF2, HGF, PDGF, CD105 was confined to villous trophoblast, endothelial cells except for MK, HB-EGF and PTN was specifically to villous trophoblast. The total RNA production in human placentae samples (n=7) from PE and controls were analysed using qRTPCR. Placental expression of mRNA was extracted for primer assays of PLGF, FGF2, MK, PTN, and endogenous housekeeping gene as Succinate dehydrogenase complex subunit A (SDHA). FGF2 and SDHA mRNA expression was significantly different using Mann-Whitney U test. An in vitro villous trophoblast invasion model was performed with human fibrosarcoma HT1080 invasive cells (positive control), mouse embryonic fibroblast NIH/3T3 non-invasive cells (negative control) and immortalised human primary villous trophoblastic cell lines TCL-1.The greatest stimulation was by FGF2, PDGF-BB, HGF, MK and co-incubation with heparin enhanced these responses, except for PTN using the Mann-Whitney U test. Heparin’s role is indicated in mediating the effects of HBGFs. It’s suggests heparin therapeutic use in the treatment of pre-eclampsia

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised