Sidestream Dark Field Imaging of the Microcirculation to Assess Preeclampsia Microvascular Dysfunction.

BackgroundDevelopment of predictive models of preeclampsia has only yielded modest results. We hypothesized that impaired indices of microcirculatory function could be detected using sidestream dark field imaging. The objective of this study was to examine microvascular function in women at high risk for preeclampsia at mid-gestation.MethodsWomen between 16 and 22 weeks of gestation were screened for eligibility. Patients were recruited if they met eligibility criteria indicating high risk for preeclampsia. Investigators performed non-invasive sidestream dark field imaging of the sublingual microcirculation. Images were analyzed to determine microcirculatory parameters (microvascular flow index, perfused vessel density, total vessel density, and proportion of perfused vessels). After delivery, charts were reviewed to determine if they developed gestational hypertension, preeclampsia or severe preeclampsia.ResultsTwelve of 66 participants (18.2%) developed preeclampsia or severe preeclampsia during the course of their pregnancy. Microvascular flow index was not significantly different between participants with normal pregnancies and participants with preeclampsia or severe preeclampsia (2.75 ± 0.38 vs. 2.80 ± 0.34, respectively; P = 0.459). Similarly, there were no significant differences between groups in the remaining microcirculatory parameters.ConclusionsSidestream dark field imaging of the sublingual microcirculation may remain an appropriate tool to identify women at risk for preeclampsia, albeit later in pregnancy

Sidestream Dark Field Imaging of the Microcirculation to Assess Preeclampsia Microvascular Dysfunction.

BackgroundDevelopment of predictive models of preeclampsia has only yielded modest results. We hypothesized that impaired indices of microcirculatory function could be detected using sidestream dark field imaging. The objective of this study was to examine microvascular function in women at high risk for preeclampsia at mid-gestation.MethodsWomen between 16 and 22 weeks of gestation were screened for eligibility. Patients were recruited if they met eligibility criteria indicating high risk for preeclampsia. Investigators performed non-invasive sidestream dark field imaging of the sublingual microcirculation. Images were analyzed to determine microcirculatory parameters (microvascular flow index, perfused vessel density, total vessel density, and proportion of perfused vessels). After delivery, charts were reviewed to determine if they developed gestational hypertension, preeclampsia or severe preeclampsia.ResultsTwelve of 66 participants (18.2%) developed preeclampsia or severe preeclampsia during the course of their pregnancy. Microvascular flow index was not significantly different between participants with normal pregnancies and participants with preeclampsia or severe preeclampsia (2.75 ± 0.38 vs. 2.80 ± 0.34, respectively; P = 0.459). Similarly, there were no significant differences between groups in the remaining microcirculatory parameters.ConclusionsSidestream dark field imaging of the sublingual microcirculation may remain an appropriate tool to identify women at risk for preeclampsia, albeit later in pregnancy

Patient Preferences for Outcomes Associated With Labor Epidural Analgesia.

Purpose Patient preferences for labor epidural analgesia (LEA) have been incompletely evaluated. This study aimed to determine the importance of various LEA outcomes to both antenatal and postpartum patients. Methods This was a cross-sectional study approved by the institutional ethics board. Questionnaires were distributed to two separate and distinct cohorts screened for eligibility: pregnant patients at an antenatal visit and postpartum patients during childbirth admission. A list of common LEA outcomes was compiled using research published in leading anesthesia journals. Participants ranked the outcomes according to perceived importance. They assigned each a number from 1 to 10 (priority ranking; 1 indicated the highest priority outcome and 10 the least). They were also asked to 'spend' 100 towards the outcomes (relative value scale), allocating more money to outcomes more important to them. Results Two hundred twenty questionnaires were completed (105 antenatal, 115 postpartum). 'Achieving desired pain relief' was the most important outcome for both cohorts. It was valued more by the postpartum cohort (Median 50 (25 - 60) vs $30 (18 - 50)). 'Overall satisfaction with the pain management,' 'experiencing a short time to achieve pain relief,' and 'experiencing a short duration of labor' received more money than avoiding various LEA-related side effects. The postpartum cohort ranked 'experiencing a short time to achieve pain relief' as more important than the antenatal cohort (Median 5 (3 - 7) vs 3 (2 - 5)). Conclusions Achieving the desired pain relief was the highest LEA outcome preference for both antenatal and postpartum patients. Avoiding side effects was less important relative to pain-related outcomes

Human immunodeficiency virus 1 (HIV-1) virion infectivity factor (Vif) is part of reverse transcription complexes and acts as an accessory factor for reverse transcription

Virion infectivity factor (Vif) facilitates HIV infection by counteracting APOBEC3G late in replication in virus-producer cells. Here, we show that early after infection of new target cells Vif is part of the HIV reverse transcription machinery and acts as an accessory factor for reverse transcription. Vif protein was present in gradient fractions containing reverse transcription complexes (RTCs), and anti-Vif antibody immunoprecipitated HIV reverse transcription products from these gradient fractions. To investigate a role for Vif in RTCs independent of APOBEC3G, we created an intracellular environment that would restrict reverse transcription by pre-treating permissive target cells with 5-Fluoro 2-deoxyuridine, a thymidylate synthetase inhibitor, prior to infection with virus from permissive cells. Infectivity assays and quantitation of reverse transcription products demonstrated that replication of HIV lacking Vif was inhibited to a greater degree than wild type, without concurrent mutation of reverse transcription products, suggesting compromised reverse transcription in the absence of Vif.Jillian M. Carr, Carl Coolen, Adam J. Davis, Christopher J. Burrell, Peng L

Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial

Background: Although metformin is increasingly being used in women with type 2 diabetes during pregnancy, little data exist on the benefits and harms of metformin use on pregnancy outcomes in these women. We aimed to investigate the effects of the addition of metformin to a standard regimen of insulin on neonatal morbidity and mortality in pregnant women with type 2 diabetes. Methods: In this prospective, multicentre, international, randomised, parallel, double-masked, placebo-controlled trial, women with type 2 diabetes during pregnancy were randomly assigned from 25 centres in Canada and four in Australia to receive either metformin 1000 mg twice daily or placebo, added to insulin. Randomisation was done via a web-based computerised randomisation service and stratified by centre and pre-pregnancy BMI (<30 kg/m2 or ≥30 kg/m2) in a ratio of 1:1 using random block sizes of 4 and 6. Women were eligible if they had type 2 diabetes, were on insulin, had a singleton viable pregnancy, and were between 6 and 22 weeks plus 6 days' gestation. Participants were asked to check their fasting blood glucose level before the first meal of the day, before the last meal of the day, and 2 h after each meal. Insulin doses were adjusted aiming for identical glucose targets (fasting glucose <5·3 mmol/L [95 mg/dL], 2-h postprandial glucose <6·7 mmol/L [120 mg/dL]). Study visits were done monthly and patients were seen every 1–4 weeks as was needed for standard clinical care. At study visits blood pressure and bodyweight were measured; patients were asked about tolerance to their pills, any hospitalisations, insulin doses, and severe hypoglycaemia events; and glucometer readings were downloaded to the central coordinating centre. Participants, caregivers, and outcome assessors were masked to the intervention. The primary outcome was a composite of fetal and neonatal outcomes, for which we calculated the relative risk and 95% CI between groups, stratifying by site and BMI using a log-binomial regression model with an intention-to-treat analysis. Secondary outcomes included several relevant maternal and neonatal outcomes. The trial was registered with ClinicalTrials.gov, NCT01353391. Findings: Between May 25, 2011, and Oct 11, 2018, we randomly assigned 502 women, 253 (50%) to metformin and 249 (50%) to placebo. Complete data were available for 233 (92%) participants in the metformin group and 240 (96%) in the placebo group for the primary outcome. We found no significant difference in the primary composite neonatal outcome between the two groups (40% vs 40%; p=0·86; relative risk [RR] 1·02 [0·83 to 1·26]). Compared with women in the placebo group, metformin-treated women achieved better glycaemic control (HbA1c at 34 weeks' gestation 41·0 mmol/mol [SD 8·5] vs 43·2 mmol/mol [–10]; 5·90% vs 6·10%; p=0·015; mean glucose 6·05 [0·93] vs 6·27 [0·90]; difference −0·2 [–0·4 to 0·0]), required less insulin (1·1 units per kg per day vs 1·5 units per kg per day; difference −0·4 [95% CI −0·5 to −0·2]; p<0·0001), gained less weight (7·2 kg vs 9·0 kg; difference −1·8 [–2·7 to −0·9]; p<0·0001) and had fewer caesarean births (125 [53%] of 234 in the metformin group vs 148 [63%] of 236 in the placebo group; relative risk [RR] 0·85 [95% CI 0·73 to 0·99]; p=0·031). We found no significant difference between the groups in hypertensive disorders (55 [23%] in the metformin group vs 56 [23%] in the placebo group; p=0·93; RR 0·99 [0·72 to 1·35]). Compared with those in the placebo group, metformin-exposed infants weighed less (mean birthweight 3156 g [SD 742] vs 3375 g [742]; difference −218 [–353 to −82]; p=0·002), fewer were above the 97th centile for birthweight (20 [9%] in the metformin group vs 34 [15%] in the placebo group; RR 0·58 [0·34 to 0·97]; p=0·041), fewer weighed 4000 g or more at birth (28 [12%] in the metformin group vs 44 [19%] in the placebo group; RR 0·65 [0·43 to 0·99]; p=0·046), and metformin-exposed infants had reduced adiposity measures (mean sum of skinfolds 16·0 mm [SD 5·0] vs 17·4 [6·2] mm; difference −1·41 [–2·6 to −0·2]; p=0·024; mean neonatal fat mass 13·2 [SD 6·2] vs 14·6 [5·0]; p=0·017). 30 (13%) infants in the metformin group and 15 (7%) in the placebo group were small for gestational age (RR 1·96 [1·10 to 3·64]; p=0·026). We found no significant difference in the cord c-peptide between groups (673 pmol/L [435] in the metformin group vs 758 pmol/L [595] in the placebo group; p=0·10; ratio of means 0·88 [0·72 to 1·02]). The most common adverse event reported was gastrointestinal (38 events in the metformin group and 38 events in the placebo group). Interpretation: We found several maternal glycaemic and neonatal adiposity benefits in the metformin group. Along with reduced maternal weight gain and insulin dosage and improved glycaemic control, the lower adiposity and infant size measurements resulted in fewer large infants but a higher proportion of small-for-gestational-age infants. Understanding the implications of these effects on infants will be important to properly advise patients who are contemplating the use of metformin during pregnancy.The trial was funded by the Canadian Institutes of Health Research, the Lunenfeld-Tanenbaum Research Institute, Toronto, ON, Canada, and the Department of Medicine, University of Toronto, Toronto, ON, Canada