Chronic endometritis and infertility — in vitro fertilization outcomes: systematic review and meta-analysis

Background. The relevance of the problem is related to the high prevalence of chronic endometritis (CE); its role in female infertility, implantation failures during assisted reproductive technology procedures, and recurrent miscarriage; as well as the lack of a unified strategy in the diagnosis and treatment of this pathology. The present systematic review with a meta-analysis focuses on evaluating the impact of CE and its therapy on the outcome of in vitro fertilization. In addition, the effect of CE of various severity on the outcomes of assisted reproductive technologies is analyzed. Objective. To analyze the effect of CE of varying severity and its treatment on the outcomes of in vitro fertilization. Methods. Using PubMed, Medline, Scopus, Embase, ELibrary, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry, and Russian Science Citation Index, a systematic search was conducted for articles published over the past 12 years that met the following criteria: randomized controlled trial examining the effect of CE of varying severity on fertility and ways to treat it. The following indicators were calculated: ongoing pregnancy/live birth, clinical pregnancy, and miscarriage rates. A total of 4145 patients (from ten studies) were included. A meta-analysis was performed using Stata 11.0 software (The Cochrane Collaboration, Oxford, UK). The heterogeneity was considered low at I2 <30%, moderate at 30–50%, and high at >50%. Results. Women with CE exhibited lower ongoing pregnancy/live birth (OR 1.97; p = 0.02) and clinical pregnancy rates (OR 2.28; p = 0.002) as compared to women without it. CE treatment increased the ongoing pregnancy/live birth (OR 5.33; p < 0.0001) and clinical pregnancy rates (OR 3.64; p = 0.0001). In vitro fertilization outcomes were comparable in women treated for CE and women without CE (ongoing pregnancy/live birth rate, clinical pregnancy rate, and miscarriage rate: p = ns). Women with severe CE exhibited lower ongoing pregnancy/live birth (OR 0.43; p = 0.003) and clinical pregnancy rates (OR 0.40; p = 0.0007). Mild CE showed no significant effect on in vitro fertilization outcomes (ongoing pregnancy/ live birth rate, clinical pregnancy rate, and miscarriage rate: p = ns). Conclusion. The conducted meta-analysis showed that CE significantly reduces the ongoing pregnancy/live birth and clinical pregnancy rates in infertile women undergoing in vitro fertilization. Noteworthy is that antimicrobial therapy in such patients improves the results of assisted reproductive technologies, which are comparable to those of patients without CE. The negative impact of this pathology on the implantation capacity of the endometrium is most often observed in the severe form, while its mild form has virtually no effect on the in vitro fertilization outcome

MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis

Naftali Kaminski and colleagues find increased levels of specific proteins in the bloodstream of individuals with idiopathic pulmonary fibrosis, and suggest that these proteins may ultimately provide a biomarker for the disease

Circulating mediators of inflammation and immune activation in AIDS-related non-Hodgkin lymphoma

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods: This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed beadbased immunoassays. Results: A subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions: These findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease. © 2014 Nolen et al

The Influence of Radiographic Phenotype and Smoking Status on Peripheral Blood Biomarker Patterns in Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is characterized by both airway remodeling and parenchymal destruction. The identification of unique biomarker patterns associated with airway dominant versus parenchymal dominant patterns would support the existence of unique phenotypes representing independent biologic processes. A cross-sectional study was performed to examine the association of serum biomarkers with radiographic airway and parenchymal phenotypes of COPD. Methodology/Principal Findings: Serum from 234 subjects enrolled in a CT screening cohort was analyzed for 33 cytokines and growth factors using a multiplex protein array. The association of serum markers with forced expiratory volume in one second percent predicted (FEV1%) and quantitative CT measurements of airway thickening and emphysema was assessed with and without stratification for current smoking status. Significant associations were found with several serum inflammatory proteins and measurements of FEV1%, airway thickening, and parenchymal emphysema independent of smoking status. The association of select analytes with airway thickening and emphysema was independent of FEV1%. Furthermore, the relationship between other inflammatory markers and measurements of physiologic obstruction or airway thickening was dependent on current smoking status. Conclusions/Significance: Airway and parenchymal phenotypes of COPD are associated with unique systemic serum biomarker profiles. Serum biomarker patterns may provide a more precise classification of the COPD syndrome, provide insights into disease pathogenesis and identify targets for novel patient-specific biological therapies. © 2009 Bon et al

Drug-Selected Human Lung Cancer Stem Cells: Cytokine Network, Tumorigenic and Metastatic Properties

Background: Cancer stem cells (CSCs) are thought to be responsible for tumor regeneration after chemotherapy, although direct confirmation of this remains forthcoming. We therefore investigated whether drug treatment could enrich and maintain CSCs and whether the high tumorogenic and metastatic abilities of CSCs were based on their marked ability to produce growth and angiogenic factors and express their cognate receptors to stimulate tumor cell proliferation and stroma formation. Methodology/Findings: Treatment of lung tumor cells with doxorubicin, cisplatin, or etoposide resulted in the selection of drug surviving cells (DSCs). These cells expressed CD133, CD117, SSEA-3, TRA1-81, Oct-4, and nuclear β-catenin and lost expression of the differentiation markers cytokeratins 8/18 (CK 8/18). DSCs were able to grow as tumor spheres, maintain self-renewal capacity, and differentiate. Differentiated progenitors lost expression of CD133, gained CK 8/18 and acquired drug sensitivity. In the presence of drugs, differentiation of DSCs was abrogated allowing propagation of cells with CSC-like characteristics. Lung DSCs demonstrated high tumorogenic and metastatic potential following inoculation into SCID mice, which supported their classification as CSCs. Luminex analysis of human and murine cytokines in sonicated lysates of parental- and CSC-derived tumors revealed that CSC-derived tumors contained two- to three-fold higher levels of human angiogenic and growth factors (VEGF, bFGF, IL-6, IL-8, HGF, PDGF-BB, G-CSF, and SCGF-β). CSCs also showed elevated levels of expression of human VEGFR2, FGFR2, CXCR1, 2 and 4 receptors. Moreover, human CSCs growing in SCID mice stimulated murine stroma to produce elevated levels of angiogenic and growth factors. Conlusions/Significance: These findings suggest that chemotherapy can lead to propagation of CSCs and prevention of their differentiation. The high tumorigenic and metastatic potentials of CSCs are associated with efficient cytokine network production that may represent a target for increased efficacy of cancer therapy. © 2008 Levina et al

Managing Environmental Risk in Presence of Climate Change: The Role of Adaptation in the Nile Basin of Ethiopia

This study investigates the impact of climate change adaptation on farm households' downside risk exposure in the Nile Basin of Ethiopia. The analysis relies on a moment-based specification of the stochastic production function. We use an empirical strategy that accounts for the heterogeneity in the decision on whether to adapt or not, and for unobservable characteristics of farmers and their farm. We find that past adaptation to climate change (i) reduces current downside risk exposure, and so the risk of crop failure; (ii) would have been more beneficial to the non-adapters if they adapted, in terms of reduction in downside risk exposure; and (iii) is a successful risk management strategy that makes the adapters more resilient to climatic conditions