Interferon‐γ Inhibits Metalloproteinase Activity and Cytotrophoblast Cell Migration

Citation Fontana VA, Sanchez M, Cebral E, Calvo JC. Interferon‐γ inhibits metalloproteinase activity and cytotrophoblast cell migration. Am J Reprod Immunol 2010; 64: 20–26 Problem Establishment of a successful pregnancy relies on a complex fetal–mother communication that starts with the embryo adhering and invading the endometrium. This requires remodeling of extracellular matrix, performed by metalloproteinases. Cytokines, such as interferon‐γ (IFN‐γ), play a role in implantation and could affect the success of pregnancy. Method of study Using JEG‐3 cell line as model, we cultured the cells in the presence or absence of IFN‐γ and determined the activities of MMP‐2 and MMP‐9 using zymography and the secretion of leptin using Western blot. Results Interferon‐γ inhibits gelatinase activity from MMP‐2 and MMP‐9 in a dose‐dependent manner, reducing the secretion of leptin (not because of a general inhibition on protein synthesis) and impairs cell migration on Matrigel. Conclusion Our results correlate with previous reports from our laboratory indicating that IFN‐ γ is deleterious for mouse embryo outgrowth, having an effect on metalloproteinases activity as well as leptin secretion.     

The potential for bi-lateral agreements in medical tourism: A qualitative study of stakeholder perspectives from the UK and India

Background  

Globalisation has prompted countries to evaluate their position on trade in health services. However, this is often done from a multi-lateral, rather than a regional or bi-lateral perspective. In a previous review, we concluded that most of the issues raised could be better addressed from a bi-lateral relationship. We report here the results of a qualitative exercise to assess stakeholders' perceptions on the prospects for such a bi-lateral system, and its ability to address concerns associated with medical tourism.     

Which criteria should be used for starting pharmacologic therapy for management of gestational diabetes in pregnancy? Evidence from randomized controlled trials

Introduction: There is inconclusive evidence to support any specific criteria for starting pharmacologic therapy after diet in women with gestational diabetes mellitus (GDM). We aimed to analyze the most used criteria for starting pharmacologic treatment for patients with GDM.

Material and methods: Electronic databases were searched from their inception to September 2017. We included all the randomized controlled trials (RCTs) of GDM managed initially by diet and exercise reporting criteria for starting pharmacologic therapy. RCTs in women with pregestational diabetes were excluded. Data regarding glucose values used for starting pharmacologic therapy were extracted and carefully reviewed.

Results: We included 15 RCTs (4307 women) in the meta-analysis. For fasting glucose target, 8/14 (57%) used a value lower or equal to 90?mg/dL and the remainder used values <99?mg/dL. Of the 10 RCTs targeting 2-h postprandial values, the majority (9/10, 90%) used 120?mg/dL. The majority of RCTs (13/15, 87%) recommended pharmacologic therapy if either 1 or 2 values per 1- or 2-week period were higher than the target values: 7/13 (54%) used 1 value and 6/13 (46%) used 2 values higher than target values. One RCT (7%) used >50% of the values higher than the target values and another one (7%) used >30%.

Conclusion: The majority of RCTs (87%) used very tight criteria of either 1 or 2 values over the target values in the 1 or 2-week period for starting pharmacologic treatment for patients with GDM; more than 50% used 2 values.

• Key Message

• Pharmacologic therapy should be considered in women with gestational diabetes when, despite an adequate diet and exercise, 1 or 2 blood glucose values are over the target values of 90mg/dL fasting or 120mg/dL 2-hour postprandial over 1 or 2 weeks.

     

Complete Genome Analysis of a Rabbit Rotavirus Causing Gastroenteritis in a Human Infant

Group A rotaviruses (RVA) are responsible for causing infantile diarrhea both in humans and animals. The molecular characteristics of lapine RVA strains are only studied to a limited extent and so far G3P[14] and G3P[22] were found to be the most common G/P-genotypes. During the 2012-2013 rotavirus season in Belgium, a G3P[14] RVA strain was isolated from stool collected from a two-year-old boy. We investigated whether RVA/Human-wt/BEL/BE5028/2012/G3P[14] is completely of lapine origin or the result of reassortment event(s). Phylogenetic analyses of all gene segments revealed the following genotype constellation: G3-P[14]-I2-R2-C2-M3-A9-N2-T6-E5-H3 and indicated that BE5028 probably represents a rabbit to human interspecies transmission able to cause disease in a human child. Interestingly, BE5028 showed a close evolutionary relationship to RVA/Human-wt/BEL/B4106/2000/G3P[14], another lapine-like strain isolated in a Belgian child in 2000. The phylogenetic analysis of the NSP3 segment suggests the introduction of a bovine(-like) NSP3 into the lapine RVA population in the past 12 years. Sequence analysis of NSP5 revealed a head-to-tail partial duplication, combined with two short insertions and a deletion, indicative of the continuous circulation of this RVA lineage within the rabbit population.     

Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3

AIM: To evaluate pre-treatment factors associated with sustained virological response(SVR) in patients with hepatitis C virus(HCV) genotype 3 treated with peginterferon and ribavirin(RBV). METHODS: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index,steatosis, INFL3 polymorphism, pre-treatment HCVRNA, type of peginterferon, RBV dose and adherence. RESULTS: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1(± 1.8) wk. Overall, 58%(62/107) of the patients achieved an SVR and 42%(45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/m L(OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis(OR = 0.278, 95%CI: 0.113-0.684,P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥600000 UI/m L and advanced fibrosis, the probability of achieving an SVR was 29%(95%CI: 13.1-45.2).In patients with pre-treatment HCV-RNA 600000UI/m L and mild to moderate fibrosis, the probability of achieving an SVR was 81%(95%CI: 68.8-93.4).CONCLUSION: In patients with HCV genotype 3infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agentsbased regimes.     

Update on the Transmission of Zika Virus Through Breast Milk and Breastfeeding: A Systematic Review of the Evidence

We systematically searched regional and international databases and screened 1658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant to examine the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding-related practices. Fourteen studies met our inclusion criteria and inform this analysis. These studies reported on 97 mother–children pairs who provided breast milk for ZIKV assessment. Seventeen breast milk samples from different women were found positive for ZIKV via RT-PCR, and ZIKV replication was found in cell cultures from five out of seven breast milk samples from different women. Only three out of six infants who had ZIKV infection were breastfed, no evidence of clinical complications was found to be associated with ZIKV RNA in breast milk. This review updates our previous report by including 12 new articles, in which we found no evidence of ZIKV mother-to-child transmission through breast milk intake or breastfeeding. As the certainty of the present evidence is low, additional studies are still warranted to determine if ZIKV can be transmitted through breastfeeding.     

Metabolic acuity score: effect on major complications after bariatric surgery

BackgroundCo-morbid conditions in obese patients contribute to the incidence and severity of major complications after bariatric surgery and significantly increase the cost of the procedure. Previous publications have validated the patient factors that increase the risk of mortality; however, it is currently a rare event. The development of a metabolic acuity score (MAS) to augment the body mass index might allow for accurate preoperative assessment and optimal treatment of patients. The present study has proposed a MAS for decreasing major complications.MethodsProspectively collected outcomes of 2416 patients undergoing Roux-en-Y gastric bypass (n = 1821) or laparoscopic adjustable gastric banding (n = 595) in a community hospital were evaluated for the incidence of major complications, readmissions, and reoperations. Beginning in August of 2006, 1072 patients were divided into MAS groups of 1–4 according to age, body mass index, weight, history of deep vein thrombosis/pulmonary embolism, sleep apnea, diabetes, hypertension, immobility, heart disease, and psychological classification. The acuity groups were compared with each other and with 1344 patients who underwent treatment before the MAS was implemented.ResultsA significant decrease occurred in the readmission rates within 30 days after the MAS was put into practice (8.5% before MAS versus 1.7% after MAS, P <.001) for the Roux-en-Y gastric bypass patients. The postoperative infection rates were lower after implementing the MAS (3.5% before MAS, .7% after MAS, P <.001). After adjusting for random and fixed effects of covariates, the implementation of the MAS significantly reduced the incidence of postoperative internal hernias, infections, deep vein thrombosis, readmissions, and reoperations.ConclusionRecognition of specific patient acuity characteristics through the implementation of MAS and aggressive preoperative and perioperative management led to lower major complication rates and decreased the incidence of readmissions and reoperations after bariatric surgery.     

Psychological classification as a communication and management tool in obese patients undergoing bariatric surgery

BackgroundPsychological evaluations are used to ascertain patient suitability for bariatric surgery and to challenge their ability to comply with therapy. The modern paradigm of obesity includes a neurobiologic component working in parallel with the limbic system of appetite and reward. To achieve the goals of surgery, an evaluation of the psychological fitness of the patient is often included in the clinical pathway. We present a psychological classification system with the goal of integrating the psychological factors into patient treatment.MethodsAll patients (Roux-en-Y gastric bypass, n = 1814; laparoscopic adjustable gastric banding, n = 589) were evaluated using psychological testing/interview and assigned to groups 1–4 before surgery. The group 1 patients (n = 788; 32.8%) did not necessitate intervention, group 2 (n = 1110; 46.2%) were requested to attend the support group, groups 3A (n = 394; 16.4%) and 3B (n = 111; 4.6%) required intervention to continue to surgery, and group 4 patients were not recommended for surgery. The main outcome measures, including complication, readmission, and reoperation rates, were analyzed for differences among the psychological groups.ResultsAfter comparing the outcome measures between each classification, no significant differences were found in the major complication rates, readmissions, reoperations, or length of stay among the groups. Groups 3A and 3B were able to achieve similar rates of success, despite their psychosocial impairment at the initial evaluation.ConclusionThe assignment of a psychological classification can facilitate bariatric team recognition of the unique psychological factors that affect the success of surgery. Assessing the patient's psychological composition and addressing potential psychosocial barriers before surgery can increase the positive long-term outcomes and reduce the incidence of complications after bariatric surgery.