Short- and long-term outcomes of intraoperative spillage during laparoscopic removal of benign ovarian cysts.

BACKGROUND: To compare the short- and long-term outcomes in patients with and without intraoperative spillage from benign adnexal masses during laparoscopic removal. METHODS: We conducted a retrospective analysis of all cases of laparoscopic removal of ovarian cysts (cystectomy or adnexectomy) in our institution between the years 2013 and 2017, excluding malignant lesions. RESULTS: During the study period, 186 cases of ovarian cyst removal were identified. Intraoperative ovarian cyst spillage (IOCS) occurred in 104 cases (study group), while in the remaining 82 cases no spillage was reported (control group). Baseline clinical characteristics were comparable between groups. Large cyst diameter and intraperitoneal adhesions were significantly associated with the occurrence of IOCS (P  = 0.008 and < 0.001, respectively). The use of an endoscopic retrieval bag was significantly inversely associated with IOCS. Postoperative complications (pain score, hospital stay, febrile illness and recurrence of ovarian cyst) were comparable between groups. CONCLUSIONS: IOCS during laparoscopic cystectomy is associated with larger cyst diameter and intraperitoneal adhesions, but not with adverse short- or long-term outcomes nor with recurrence rates.

Risk factors for early postpartum hemorrhage: A retrospective, population-based, cohort analysis.

OBJECTIVE: To identify risk factors for developing early postpartum hemorrhage (PPH) and to examine whether risk factors vary according to severity and mode of delivery. METHODS: A population-based cohort study was conducted in which all deliveries at a tertiary medical center were included. Risk factors for developing early PPH were compared based on the severity of bleeding as well as the mode of delivery. Multiple logistic regression models were used to control for confounders. RESULTS: Among 322 497 deliveries included in the analysis, early PPH complicated 1811 (0.56%) of all deliveries. Among all cases of early PPH, 505 deliveries (28%) were complicated with severe PPH. Using a logistic regression model, in vitro fertilization (IVF) pregnancy, previous cesarean delivery (CD), pre-eclampsia, placental abruption, and uterine rupture were independently associated only with severe early PPH, while non-progressive second stage of labor, induction of labor, and large for gestational age were independently associated with both severe and mild early PPH. When applying an additional logistic regression model, whereas IVF pregnancy, pre-eclampsia, and large for gestational age were independently associated with early PPH among vaginal deliveries only, placenta previa was independently associated with early PPH among CD only. CONCLUSIONS: Independent risk factors for developing severe PPH solely include IVF pregnancy, previous CD, pre-eclampsia, placental abruption, and uterine rupture. IVF pregnancy, pre-eclampsia, and large for gestational age are independent risk factors for early PPH following vaginal delivery, while placenta previa is independently associated with early PPH after CD only. Due to the recognition of the importance of both the provider and institutional planning and preparation for PPH, the study's results should be viewed within the scope of its retrospective cohort design.

α-1-antitrypsin gene delivery reduces inflammation, increases T-regulatory cell population size and prevents islet allograft rejection.

Antiinflammatory clinical-grade, plasma-derived human α-1 antitrypsin (hAAT) protects islets from allorejection as well as from autoimmune destruction. hAAT also interferes with disease progression in experimental autoimmune encephalomyelitis (EAE) and in collagen-induced arthritis (CIA) mouse models. hAAT increases IL-1 receptor antagonist expression in human mononuclear cells and T-regulatory (Treg) cell population size in animal models. Clinical-grade hAAT contains plasma impurities, multiple hAAT isoforms and various states of inactive hAAT. We thus wished to establish islet-protective activities and effect on Treg cells of plasmid-derived circulating hAAT in whole animals. Islet function was assessed in mice that received allogeneic islet transplants after mice were given hydrodynamic tail-vein injection with pEF-hAAT, a previously described Epstein-Barr virus (EBV) plasmid construct containing the EBV nuclear antigen 1 (EBNA1) and the family of repeat EBNA1 binding site components (designated "EF") alongside the hAAT gene. Sera collected from hAAT-expressing mice were added to lipopolysaccharide (LPS)-stimulated macrophages to assess macrophage responsiveness. Also, maturation of peritoneal cells from hAAT-expressing mice was evaluated. hAAT-expressing mice accepted islet allografts (n = 11), whereas phosphate-buffered saline-injected animals (n = 11), as well as mice treated with truncated-hAAT-plasmid (n = 6) and untreated animals (n = 20) rapidly rejected islet allografts. In hAAT-expressing animals, local Treg cells were abundant at graft sites, and the IL-1 receptor antagonist was elevated in grafts and circulation. Sera from hAAT-expressing mice, but not control mice, inhibited macrophage responses. Finally, peritoneal cells from hAAT-expressing mice exhibited a semimature phenotype. We conclude that plasmid-derived circulating hAAT protects islet allografts from acute rejection, and human plasma impurities are unrelated to islet protection. Future studies may use this in vivo approach to examine the structure-function characteristics of the protective activities of AAT by manipulation of the hAAT plasmid.

Perinatal Outcome and Long-Term Gastrointestinal Morbidity of Offspring of Women with Celiac Disease.

The aim of this study was to evaluate perinatal outcome and long-term offspring gastrointestinal morbidity of women with celiac disease. Perinatal outcomes, as well as long-term gastrointestinal morbidity of offspring of mothers with and without celiac disease were assessed. The study groups were followed until 18 years of age for gastrointestinal-related morbidity. For perinatal outcomes, generalized estimation equation (GEE) models were used. A Kaplan-Meier survival curve was used to compare cumulative incidence of long-term gastrointestinal morbidity, and Cox proportional hazards models were constructed to control for confounders. During the study period, 243,682 deliveries met the inclusion criteria, of which 212 (0.08%) were to mothers with celiac disease. Using GEE models, maternal celiac disease was noted as an independent risk factor for low birth weight and cesarean delivery. Offspring born to mothers with celiac disease had higher rates of gastrointestinal related morbidity (Kaplan-Meier log rank test P < 0.001). Using a Cox proportional hazards model, being born to a mother with celiac disease was found to be an independent risk factor for long-term gastrointestinal morbidity of the offspring. Pregnancy of women with celiac disease is independently associated with adverse perinatal outcome as well as higher risk for long-term gastrointestinal morbidity of offspring.

α1-antitrypsin increases interleukin-1 receptor antagonist production during pancreatic islet graft transplantation.

Although islet transplantation for individuals with type 1 diabetes has been shown to yield superior blood glucose control, it remains inadequate for long-term control. This is partly due to islet injuries and stresses that can lead to beta cell loss. Inhibition of excess IL-1ß activity might minimize islet injuries, thus preserving function. The IL-1 receptor antagonist (IL-1Ra), an endogenous inhibitor of IL-1ß, protects islets from cytokine-induced necrosis and apoptosis. Therefore, an imbalance between IL-1ß and IL-1Ra might influence the courses of allogeneic and autoimmune responses to islets. Our group previously demonstrated that the circulating serine-protease inhibitor human alpha-1-antitrypsin (hAAT), the levels of which increase in circulation during acute-phase immune responses, exhibits anti-inflammatory and islet-protective properties, as well as immunomodulatory activity. In the present study, we sought to determine whether the pancreatic islet allograft-protective activity of hAAT was mediated by IL-1Ra induction. Our results demonstrated that hAAT led to a 2.04-fold increase in IL-1Ra expression in stimulated macrophages and that hAAT-pre-treated islet grafts exhibited a 4.851-fold increase in IL-1Ra transcript levels, which were associated with a moderate inflammatory profile. Unexpectedly, islets that were isolated from IL-1Ra-knockout mice and pre-treated with hAAT before grafting into wild-type mice yielded an increase in intragraft IL-1Ra expression that was presumably derived from infiltrating host cells, albeit in the absence of hAAT treatment of the host. Indeed, hAAT-pre-treated islets generated hAAT-free conditioned medium that could induce IL-1Ra production in cultured macrophages. Finally, we demonstrated that hAAT promoted a distinct phosphorylation and nuclear translocation pattern for p65, a key transcription factor required for IL-1Ra expression.

α1-antitrypsin insufficiency is a possible contributor to preterm premature rupture of membranes.

OBJECTIVE: α1-antitrypsin (AAT) is protective of tissue damage induced by enzymes of inflammatory cell source. Inflammatory cells are involved in preterm labor, preterm premature rupture of membrane (PPROM) and term premature rupture of membrane (PROM). The purpose of this research was to examine whether plasma concentration and activity of AAT differ between these manifestations. METHODS: In a prospective case control study, blood samples were assayed for AAT concentration and activity in 71 individuals. AAT concentration and activity were measured by standard methods. RESULTS: No significant differences were found between AAT levels (p = 0.497) and activity (p = 0.879) in preterm and term labor. AAT levels and activity in PPROM and PROM were not significantly different as well (p = 0.748 and p = 0.880, respectively). While 69 out of 71 patients displayed normal circulating levels of AAT, 2 PPROM patients out of 15 had abnormally low, previously undiagnosed,AAT concentrations, and had subsequently developed complications that were absent in the other groups. CONCLUSIONS: No statistically significant differences were demonstrated in the levels of AAT between patients with preterm and term labor, nor between preterm and term PROM. Yet, unexpectedly, patients that had marked AAT deficiency belonged exclusively to the PPROM group.