Six-Month Outcomes after Restrictive or Liberal Transfusion for Cardiac Surgery.

BACKGROUND: We reported previously that, in patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive transfusion strategy was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or 28 days after surgery, whichever came first. We now report the clinical outcomes at 6 months after surgery. METHODS: We randomly assigned 5243 adults undergoing cardiac surgery to a restrictive red-cell transfusion strategy (transfusion if the hemoglobin concentration was <7.5 g per deciliter intraoperatively or postoperatively) or a liberal red-cell transfusion strategy (transfusion if the hemoglobin concentration was <9.5 g per deciliter intraoperatively or postoperatively when the patient was in the intensive care unit [ICU] or was <8.5 g per deciliter when the patient was in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis occurring within 6 months after the initial surgery. An expanded secondary composite outcome included all the components of the primary outcome as well as emergency department visit, hospital readmission, or coronary revascularization occurring within 6 months after the index surgery. The secondary outcomes included the individual components of the two composite outcomes. RESULTS: At 6 months after surgery, the primary composite outcome had occurred in 402 of 2317 patients (17.4%) in the restrictive-threshold group and in 402 of 2347 patients (17.1%) in the liberal-threshold group (absolute risk difference before rounding, 0.22 percentage points; 95% confidence interval [CI], -1.95 to 2.39; odds ratio, 1.02; 95% CI, 0.87 to 1.18; P=0.006 for noninferiority). Mortality was 6.2% in the restrictive-threshold group and 6.4% in the liberal-threshold group (odds ratio, 0.95; 95% CI, 0.75 to 1.21). There were no significant between-group differences in the secondary outcomes. CONCLUSIONS: In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy for red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis at 6 months after surgery. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).

Risk prediction models for survival after heart transplantation: A systematic review.

Risk prediction scores have been developed to predict survival following heart transplantation (HT). Our objective was to systematically review the model characteristics and performance for all available scores that predict survival after HT. Ovid Medline and Epub Ahead of Print and In-Process & Other Non-Indexed Citations, Ovid Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Clinical Trials were searched to December 2018. Eligible articles reported a score to predict mortality following HT. Of the 5392 studies screened, 21 studies were included that derived and/or validated 16 scores. Seven (44%) scores were validated in external cohorts and 8 (50%) assessed model performance. Overall model discrimination ranged from poor to moderate (C-statistic/area under the receiver operating characteristics 0.54-0.77). The IMPACT score was the most widely validated, was well calibrated in two large registries, and was best at discriminating 3-month survival (C-statistic 0.76). Most scores did not perform particularly well in any cohort in which they were assessed. This review shows that there are insufficient data to recommend the use of one model over the others for prediction of post-HT outcomes.

Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery.

BACKGROUND: The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. METHODS: In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red-cell transfusion threshold (transfuse if hemoglobin level was <7.5 g per deciliter, starting from induction of anesthesia) or a liberal red-cell transfusion threshold (transfuse if hemoglobin level was <9.5 g per deciliter in the operating room or intensive care unit [ICU] or was <8.5 g per deciliter in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Secondary outcomes included red-cell transfusion and other clinical outcomes. RESULTS: The primary outcome occurred in 11.4% of the patients in the restrictive-threshold group, as compared with 12.5% of those in the liberal-threshold group (absolute risk difference, -1.11 percentage points; 95% confidence interval [CI], -2.93 to 0.72; odds ratio, 0.90; 95% CI, 0.76 to 1.07; P<0.001 for noninferiority). Mortality was 3.0% in the restrictive-threshold group and 3.6% in the liberal-threshold group (odds ratio, 0.85; 95% CI, 0.62 to 1.16). Red-cell transfusion occurred in 52.3% of the patients in the restrictive-threshold group, as compared with 72.6% of those in the liberal-threshold group (odds ratio, 0.41; 95% CI, 0.37 to 0.47). There were no significant between-group differences with regard to the other secondary outcomes. CONCLUSIONS: In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy regarding red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

Combination of Foley and prostaglandins versus Foley and oxytocin for cervical ripening: a network meta-analysis.

BACKGROUND: Trial and meta-analysis data revealed a reduction in time to delivery for Foley and prostaglandins or Foley and oxytocin vs Foley alone. However, there are limited data for the comparison of the 2 combination methods against each other. OBJECTIVE: This study aimed to determine whether Foley and prostaglandins or Foley and oxytocin decrease the time to vaginal delivery using a network meta-analysis. STUDY DESIGN: A network meta-analysis (PROSPERO CRD42018081948) was performed comparing Foley and prostaglandins (prostaglandin E1 or prostaglandin E2) vs Foley and oxytocin for cervical ripening. Foley alone and prostaglandins alone were used as nodes for indirect comparison. Database searches were performed from inception to March 2020 with data abstracted from published manuscripts. Eligibility criteria included randomized trials comparing Foley and oxytocin with Foley and prostaglandins (misoprostol or dinoprostone). Trials that compared Foley catheter or prostaglandins with a combination of Foley and prostaglandins or Foley and concurrent oxytocin were also included. Nulliparous and multiparous women were analyzed together. Foley catheters of any catheter material or size and >24 weeks' gestational age with a live fetus were included. Quasi-randomized, cohorts, and other combination methods for cervical ripening were not included. Prostaglandin E1 and prostaglandin E2 combined methods were analyzed separately in a planned subanalysis. The primary outcome was the mean time from induction to vaginal delivery in hours. Secondary outcomes included time from induction to delivery, delivery within 24 hours, cesarean delivery, chorioamnionitis, endometritis, epidural use, tachysystole, postpartum hemorrhage, meconium, neonatal intensive care unit admission, and 5-minute appearance, pulse, grimace, activity, and respiration score of <7. Data were analyzed as a network meta-analysis using multivariate meta-regression. RESULTS: A total of 30 randomized controlled trials with a total of 6465 women were considered eligible for inclusion in this network meta-analysis. When compared with Foley alone, the use of Foley-oxytocin reduced the time to vaginal delivery by 4.2 hours (mean duration, -4.2 hours; 95% confidence interval, -6.5 to -1.9). Foley-prostaglandins reduced the time to vaginal delivery compared with Foley but did not meet statistical significance (mean duration, -2.9 hours; 95% confidence interval, -5.7 to 0.0; P=.05). When compared head-to-head, there was no difference in the time to vaginal delivery between Foley-prostaglandins and Foley-oxytocin (mean duration, 1.3 hours; 95% confidence interval, -2.0 to 4.7). There was no difference in the rate of cesarean delivery, chorioamnionitis, epidural, tachysystole, postpartum hemorrhage, meconium, neonatal intensive care unit admissions, or 5-minute appearance, pulse, grimace, activity, and respiration score of <7 for Foley-prostaglandins vs Foley-oxytocin, although the rate of endometritis was high for Foley-prostaglandins. In the subanalysis by prostaglandin type, there was no difference in the time to vaginal delivery for Foley-misoprostol vs Foley-dinoprostone vs Foley-oxytocin. However, Foley-dinoprostone had a definite trend toward longer time to all deliveries compared with that of both Foley-misoprostol and Foley-oxytocin (P=.05). CONCLUSION: Time to vaginal delivery was similar when comparing Foley with combined misoprostol, combined dinoprostone, and combined oxytocin. Dinoprostone comparisons are limited by small sample size but suggest longer time to delivery compared with Foley and misoprostol or oxytocin. No significant differences were observed in maternal or neonatal adverse events except for endometritis, but this was limited by the sample size, varied reporting of studies used in the indirect comparisons, and definitions of infectious morbidity use in the studies.

Variation in Cervical Length over Time during a Single Transvaginal Ultrasound Examination.

OBJECTIVE: To quantify the degree of change in cervical length (CL) over a 3-minute transvaginal ultrasound. STUDY DESIGN: We conducted a prospective observational study of nulliparous patients who underwent routine transvaginal CL screening at the time of their second-trimester ultrasound. We recorded CL at four time points (0, 1, 2, 3 minutes) and compared these values to determine the minute-to-minute change within a single patient. RESULTS: A total of 771 patients were included. The mean gestational age was 20.8 weeks (±0.84). We used a linear mixed effect model to assess if each minute during the ultrasound is associated with a change in CL. The intraclass correlation coefficient between minute 0 to minute 3 was 0.82 (95% confidence interval: 0.80, 0.84). This indicates that there is a relatively high within-patient correlation in CL during their ultrasound. Additionally, we stratified patients based on their starting CL; the intraclass correlation coefficient remained high for all groups. We additionally compared CL at each minute. Although there is a statistically significant difference between several time points, the actual difference is small and not clinically meaningful. CONCLUSION: The variation in CL over a 3-minute transvaginal ultrasound examination is not clinically significant. It may be reasonable to conduct this examination over a shorter period.

Cervical Ripening Using Foley Balloon with or without Oxytocin: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess available evidence regarding the use of oxytocin in conjunction with Foley balloon (FB) for cervical ripening. METHODS: Databases from MEDLINE (U.S. National Library of Medicine, 1980-May 12, 2017), MEDLINE (Ovid, 1980-June 30, 2017), the Cochrane Library Controlled Trials Register, ClinicalTrials.gov, and Web of Science were queried for studies on FB cervical ripening with or without oxytocin in pregnant women. Search terms included: "balloon dilatation" OR "mechanical methods" OR "mechanical method" OR "mechanical dilation" OR "mechanical dilatation" OR "mechanical dilations" OR "mechanical dilatations" OR "balloon" OR "Foley" AND "Pitocin" OR "oxytocin." All relevant references were reviewed. Literature for inclusion and methodological quality were reviewed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. RESULTS: Out of 344 citations, six randomized clinical trials (1,133 patients) fulfilled our inclusion criteria. The pooled estimate showed that the cesarean delivery (CD) rate did not differ (relative risk [RR]: 0.91 (95% confidence interval [CI] [0.76-1.10]; p = 0.23) between patients who underwent preinduction cervical ripening with FB alone versus those who received oxytocin in addition to FB. Heterogeneity was not significant among studies (I 2 0.0%; p = 0.64). Furthermore, no differences in other outcomes such as composite and maternal outcomes were detected between these two groups. Compared with simultaneous use of oxytocin with FB, the Foley alone cervical ripening group had a longer induction to delivery time, and lower deliveries within 12 and 24 hours. Subgroup analysis showed that only multiparous women in the Foley alone group had lower rate of vaginal delivery within 24 hours (RR: 0.74, 95% CI [0.61-0.89], p = 0.002) along with a trend toward higher CD rates. CONCLUSION: Adding oxytocin to FB at the time of preinduction cervical ripening does not reduce cesarean rates nor improve maternal or neonatal outcomes. Multiparous women who received FB alone seem to have lower rates of vaginal deliveries within 24 hours, but these results should be interpreted with caution.

A randomized trial of Foley balloon induction of labor trial in nulliparas (FIAT-N).

BACKGROUND: With an increasing rate of induction of labor, it is important to choose induction methods that are safe and efficient in achieving a vaginal delivery. The optimal method for inducing nulliparous women with an unfavorable cervix is not known. OBJECTIVE: We sought to determine if induction of labor with simultaneous use of oxytocin and Foley balloon vs sequential use of Foley balloon followed by oxytocin decreases the time to delivery in nulliparous women. STUDY DESIGN: We conducted a randomized controlled trial of nulliparous women presenting for induction at a single institution from December 2013 through March 2015. After decision for induction was made by their primary provider, women with gestational age ≥24 weeks with a nonanomalous, singleton fetus in vertex presentation with intact membranes were offered participation. Exclusion criteria included history of uterine surgery, unexplained vaginal bleeding, latex allergy, or contraindication to vaginal delivery. Participants were randomized to either simultaneous (oxytocin and Foley balloon) or sequential (oxytocin after expulsion of Foley balloon) induction group. The primary outcome was time from induction to delivery. Secondary outcomes included mode of delivery, estimated blood loss, postpartum hemorrhage, chorioamnionitis, and composite neonatal outcome. Maternal and neonatal outcomes were collected via chart review. Analyses were done on an intention-to-treat basis. RESULTS: A total of 166 patients were enrolled; 82 in the simultaneous and 84 in the sequential group. There were no differences in baseline characteristics in the 2 groups. Patients who received simultaneous oxytocin with insertion of a Foley balloon delivered significantly earlier (15.92 vs 18.87 hours, P = .004) than those in the sequential group. There was no difference in rate of cesarean delivery, estimated blood loss, postpartum hemorrhage, chorioamnionitis, or composite neonatal outcome. CONCLUSION: Simultaneous use of oxytocin and Foley balloon for induction of labor results in a significantly shorter interval to delivery in nulliparas.

Lipoprotein-apheresis reduces circulating microparticles in individuals with familial hypercholesterolemia.

Lipoprotein-apheresis (apheresis) removes LDL-cholesterol in patients with severe dyslipidemia. However, reduction is transient, indicating that the long-term cardiovascular benefits of apheresis may not solely be due to LDL removal. Microparticles (MPs) are submicron vesicles released from the plasma membrane of cells. MPs, particularly platelet-derived MPs, are increasingly being linked to the pathogenesis of many diseases. We aimed to characterize the effect of apheresis on MP size, concentration, cellular origin, and fatty acid concentration in individuals with familial hypercholesterolemia (FH). Plasma and MP samples were collected from 12 individuals with FH undergoing routine apheresis. Tunable resistive pulse sensing (np200) and nanoparticle tracking analysis measured a fall in MP concentration (33 and 15%, respectively; P < 0.05) pre- to post-apheresis. Flow cytometry showed MPs were predominantly annexin V positive and of platelet (CD41) origin both pre- (88.9%) and post-apheresis (88.4%). Fatty acid composition of MPs differed from that of plasma, though apheresis affected a similar profile of fatty acids in both compartments, as measured by GC-flame ionization detection. MP concentration was also shown to positively correlate with thrombin generation potential. In conclusion, we show apheresis nonselectively removes annexin V-positive platelet-derived MPs in individuals with FH. These MPs are potent inducers of coagulation and are elevated in CVD; this reduction in pathological MPs could relate to the long-term benefits of apheresis.

Evaluating the Usability of the Wellness School Assessment Tool Whole School, Whole Community, Whole Child (WellSAT WSCC): A School Wellness Policy Assessment Tool.

BACKGROUND: Adoption of the Whole School, Whole Community, Whole Child (WSCC) model has been slowed by a lack of available tools to support implementation. The Wellness School Assessment Tool (WellSAT) WSCC is an online assessment tool that allows schools to evaluate the alignment of their policies with the WSCC model. This study assesses the usability of the WellSAT WSCC. METHODS: Using a convergent mixed methods design, we collected qualitative and quantitative data from 5 school-based participants with roles in development and evaluation of policy. Participants explored the platform while engaging in a think-aloud procedure and scored a sample policy using the platform. They also completed the System Usability Scale and responded to open-ended questions about the usability of the platform. RESULTS: Participants rated the WellSAT WSCC as an above-average user experience, but data suggested several areas for improvement, including improved instructions, enhanced visual design of the platform, and guidance for subsequent policy changes. CONCLUSION: The WellSAT WSCC provides an above-average user experience but can be improved to increase user experience. These improvements increase the potential for greater use to facilitate integration of the WSCC model into school policy.

The state of coursework on horses in human services at universities and colleges in the United States: a scoping review.

An increasing number of universities and colleges in the United States are offering coursework on adaptive/therapeutic riding and the incorporation of horses in human service areas such as psychotherapy, education, occupational therapy, physical therapy, and speech-language pathology. The first study to identify coursework in these areas was published in 2018. In order to track development over time, we conducted a replication study to determine the prevalence of coursework on horses in human services at higher education institutions. Information gathered for the 2021-2022 academic year included the institution name, geographic location, number of courses and their focus, academic department offering the course, and level of study. We identified 122 courses provided by 48 higher education institutions in 29 states in the following areas: adaptive/therapeutic riding (N = 82, 67.2%), mental health (N = 19, 15.6%), education/learning (N = 2, 1.6%), and equine movement in physical therapy, occupational therapy, and speech-language pathology (hippotherapy) (N = 1, 0.8%). Survey or overview courses (N = 18, 14.8%) were also identified. These courses were offered both at the undergraduate (N = 114, 93.4%) and the graduate level (N = 8, 6.6%) by a total of 48 departments that either focused on animals, such as equine science, animal science, and agriculture (N = 27, 54%) or focused on humans, such as health science or liberal arts (N = 23, 46%). The results inform a discussion on changes over time as well as current challenges and opportunities for academic programs offering coursework about horses in human services.

Mandan, Hidatsa, and Arikara Nation Perspectives on Rez Dogs on the Fort Berthold Reservation in North Dakota, U.S.A.

The research on the relationships between free-roaming dogs, also referred to as reservation dogs or rez dogs, and Indigenous communities is extremely limited. This study aimed to document the cultural significance of rez dogs, challenges related to rez dogs, and community-specific solutions for rez dog issues affecting community health and safety from members of the Mandan, Hidatsa, and Arikara (MHA) Nation, also referred to as the Three Affiliated Tribes (TAT), who live on the Fort Berthold reservation in North Dakota, U.S.A. One hour semi-structured interviews with 14 community members of the MHA Nation were conducted in 2016. The interviews were analyzed via systematic and inductive coding using Gadamer's hermeneutical phenomenology. The primary intervention areas described by the participants included: culturally relevant information sharing, improved animal control policies and practices, and improved access to veterinary care and other animal services.

Animal Control and Field Services Officers' Perspectives on Community Engagement: A Qualitative Phenomenology Study.

Very little is known about the prevalence, scope, and methods of community engagement employed by animal control and field services officers to address the issue of animal cruelty and neglect. This study used a phenomenological approach to understand how officers defined community engagement. The researchers conducted semi-structured interviews with twenty-nine animal control and field services officers. The definitions of community engagement varied greatly across this sample of U.S. officers. However, most officers agreed that strategies such as relationship-building, providing assistance or information, and allowing time for compliance were among the most effective community engagement strategies. In addition, several barriers to incorporating community engagement strategies in the work of animal control professionals were identified. Future research and policymaking should seek to establish a consistent definition of community engagement in animal control and field services that can then be optimized for specific communities through rigorous evaluation.

Role of adipocyte-derived extracellular vesicles in vascular inflammation.

Extracellular vesicles (EVs) are nanometre-sized vesicles released from most cells, including adipocytes. Relatively little is known about adipocyte-derived EVs (ADEVs) in comparison to other EV subtypes, though interest in ADEVs as potential paracrine and endocrine communicators of adipose tissue in obesity is building. Current evidence indicates that ADEVs contribute to the development of adipose tissue dysfunction; a key feature of obese adipose tissue that it is associated with obesity-related comorbidities including cardiovascular disease (CVD). This review summarises our current knowledge of ADEVs in the development of adipose tissue dysfunction and the potential of ADEVs to disrupt redox signalling and exert vascular effects that may exacerbate CVD in obesity.

Establishing a Cardiac Amyloidosis Clinic: A Practical Primer for Cardiologists.

Cardiac amyloidosis is an emerging and important cause of heart failure, arrhythmia, and other cardiovascular disease in Canada. In this context, many centres have expressed interest in the development of effective care pathways for screening, evaluating, and treating this rapidly growing patient population. In October 2019, a group of Canadian stakeholders met, including specialists in cardiac amyloidosis, experts in heart failure and chronic disease management, and academic and community-based cardiologists at various stages of cardiac amyloidosis clinic development. Objectives of the meetings included discussion of existing care pathways, consideration of barriers to program development, and achieving a consensus on essential and desirable components of a best-practice cardiac amyloidosis program. Topics discussed included optimal settings for cardiac amyloidosis clinics and integration with other specialty clinics, funding limitations that act as barriers to program development and potential solutions to these barriers, the roles of the multidisciplinary team and specialist physicians in amyloidosis care, and diagnostic pathways and strategies for the identification of patients with cardiac amyloidosis. In this report, we summarize the discussion points and key recommendations for the development of a cardiac amyloidosis clinic that emerged from this meeting, focused on program integration and care coordination, human resource elements, access to care, and quality improvement and outcome measures in cardiac amyloidosis.

Pain perception during transabdominal chorionic villus sampling: a randomized trial comparing topical ethyl chloride anesthetic spray and lidocaine injection.

Background: Chorionic villus sampling is an important invasive procedure used for early antenatal genetic testing that can be associated with anxiety and fear of pain. Pain analgesia prior to chorionic villus sampling can be offered with subdermal lidocaine; however, lidocaine injection itself is associated with pain. Our objective was to determine whether administration of topical ethyl chloride anesthetic spray is associated with decreased pain perception during transabdominal chorionic villus sampling compared to 1% lidocaine subdermal injection.Study design: Women undergoing transabdominal chorionic villus sampling from 10 to 13 weeks and 6 days in an outpatient setting were randomized with equal allocation to either 1% lidocaine injection or topical ethyl chloride anesthetic spray prior to the procedure. Women were asked about their pain on a scale of 0-100 prior to, during, and after the procedure. The primary outcome was pain perception during time of transabdominal chorionic villus sampling as measured on a 100-mm visual analog scale. The secondary outcome was pain immediately after procedure.Results: From October 2016 to June 2017, a total of 120 women were enrolled (63 in the lidocaine injection group and 57 in the topical ethyl chloride anesthetic spray group). Baseline demographic characteristics were similar between groups. During the procedure, patients in the topical ethyl chloride arm demonstrated significantly higher pain scores compared to the lidocaine injection group (median score of 50 mm (interquartile range [IQR]: 40-65) versus 50 mm (IQR: 30-60); p = .03). There was no significant difference in pain scores before or after the procedure.Conclusion: During transabdominal chorionic villus sampling procedures, topical ethyl chloride anesthetic spray is associated with a higher distribution of pain scores as compared to 1% lidocaine subdermal injection, which suggests higher levels of pain.Clinical trial registration: This trial is registered with clinicaltrials.gov (NCT03140293). https://clinicaltrials.gov/ct2/show/NCT03140293?term=NCT03140293&rank=1.

Inflammatory adipocyte-derived extracellular vesicles promote leukocyte attachment to vascular endothelial cells.

BACKGROUND AND AIMS: Obesity is associated with an increased risk of cardiovascular disease, but the mechanisms involved are not completely understood. In obesity, the adipocyte microenvironment is characterised by both hypoxia and inflammation. Therefore, we sought to determine whether extracellular vesicles (EVs) derived from adipocytes in this setting might be involved in mediating cardiovascular disease, specifically by promoting leukocyte attachment to vascular endothelial cells. METHODS: Mature 3T3-L1 adipocytes were incubated for 24 h under control, TNF-α (30 ng/mL), hypoxia (1% O2), or TNF-α+hypoxia (30 ng/mL, 1% O2) conditions. EVs were isolated by differential ultracentrifugation and analysed by nanoparticle tracking analysis. Primary human umbilical vein endothelial cells (HUVECs) were treated with EVs for 6 h before being lysed for Western blotting to investigate changes in adhesion molecule production, or for use in leukocyte attachment assays. RESULTS: EVs from adipocytes treated with TNF-α and TNF-α+hypoxia increased vascular cell adhesion molecule (VCAM-1) production in HUVECs compared to basal level (4.2 ± 0.6 and 3.8 ± 0.3-fold increase, respectively (p < 0.05)), an effect that was inhibited by an anti-TNF-α neutralising antibody. Production of other adhesion molecules (E-selectin, P-selectin, platelet endothelial cell adhesion molecule and VE-Cadherin) was unchanged. Pre-incubating HUVECs with TNF-α+hypoxia EVs significantly increased leukocyte attachment compared to basal level (3.0 ± 0.4-fold increase (p < 0.05)). CONCLUSIONS: Inflammatory adipocyte EVs induce VCAM-1 production in vascular endothelial cells, accompanied by enhanced leukocyte attachment. Preventing adipocyte derived EV-induced VCAM-1 upregulation may offer a novel therapeutic target in the prevention of obesity-driven cardiovascular disease.