Comparison of circulating total sFLT-1 to placental-specific sFLT-1 e15a in women with suspected preeclampsia.

INTRODUCTION: Soluble fms-like tyrosine kinase 1 (sFLT-1), a circulating anti-angiogenic factor that binds and antagonizes placental growth factor (PlGF), appears key to preeclamptic pathophysiology. Two main sFLT-1 splice variants exist: sFLT-1 e15a and sFLT-1 i13. Total sFLT-1/PlGF ratios are increasingly used clinically; we explore whether using placental-specific sFLT-1 e15a improves test performance compared with total sFLT-1 in preeclampsia diagnosis. METHODS: Consent was obtained for serum sampling from 96 women with suspected preeclampsia. Total sFLT-1 and PlGF were quantified using the B.R.A.H.M.S Kryptor Compact Plus automated immunoassay platform, and sFLT-1 e15a by custom enzyme-linked immunosorbent assay. Test performance was then assessed by subsequent diagnosis. RESULTS: Of 96 participants, 32 did not develop preeclampsia, 32 had early-onset (<34 weeks') disease and 32 had late-onset (≥34 weeks') disease. In those with preeclampsia, median sFLT-1 and sFLT-1 e15a were significantly increased (7361.0 vs 2463.0 pg/mL, and 946.6 vs 305.4 ng/mL respectively; p < 0.001 for both), and PlGF significantly reduced (43.5 vs 154.4 pg/mL; p < 0.001) compared to those without preeclampsia. Those with early-onset, compared to late-onset, preeclampsia chiefly had lower median PlGF levels (16.0 vs 57.3; p < 0.001), which contributed to higher sFLT-1/PlGF and sFLT-1 e15a/PlGF ratios (830.1 vs 86.7, and 109258.9 vs 12608.7 respectively; p < 0.001 for both). DISCUSSION: sFLT-1 e15a performs comparably to total sFLT-1 in women with suspected preeclampsia, however with higher translational burden. Our results support the expanding clinical use of the sFLT-1/PlGF ratio in suspected preeclampsia, particularly early-onset, to assist with disease diagnosis.

Accounting for the Lombard effect in estimating the probability of detection in passive acoustic surveys: Applications for single sensor mitigation and monitoring.

The detection range of calling animals is commonly described by the passive sonar equations. However, the sonar equations do not account for interactions between source and ambient sound level, i.e., the Lombard effect. This behavior has the potential to introduce non-linearities into the sonar equations and result in incorrectly predicted detection ranges. Here, we investigate the relationship between ambient sound and effective detection ranges for North Atlantic right whales (Eubalaena glacialis) in Cape Cod Bay, MA, USA using a sparse array of acoustic recorders. Generalized estimating equations were used to model the probability that a call was detected as a function of distance between the calling animal and the sensor and the ambient sound level. The model suggests a non-linear relationship between ambient sound levels and the probability of detecting a call. Comparing the non-linear model to the linearized version of the same model resulted in 12 to 25% increases in the effective detection range. We also found evidence of the Lombard effect suggesting that it is the most plausible cause for the non-linearity in the relationship. Finally, we suggest a simple modification to the sonar equation for estimating detection probability for single sensor monitoring applications.

Role of placental, fetal and maternal cardiovascular markers in predicting adverse outcome in women with suspected or confirmed pre-eclampsia.

OBJECTIVE: To assess the performance of placental, fetal and maternal cardiovascular markers in the prediction of adverse perinatal and maternal outcomes in women with suspected or confirmed pre-eclampsia. METHODS: This was a prospective prognostic accuracy study of women with suspected or confirmed pre-eclampsia who underwent a series of investigations to measure maternal hemodynamic indices, mean arterial pressure, augmentation index, ophthalmic artery peak systolic velocity (PSV) ratio, uterine artery pulsatility index (UtA-PI), fetal biometric and Doppler parameters, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). The performance of these markers, individually or in combination, in predicting adverse perinatal and maternal outcomes was then assessed using receiver-operating-characteristics (ROC)-curve analysis. Adverse maternal outcome was defined as one or more of severe hypertension, admission to the intensive care unit, eclampsia, placental abruption, HELLP syndrome, disseminated intravascular coagulation, platelets < 100 × 109 /L, creatinine > 90 µmol/L and alanine aminotransferase > 100 U/L. Adverse perinatal outcome was defined as one or more of preterm birth at or before 34 + 0 weeks, neonatal intensive care unit admission for > 48 h, respiratory distress syndrome, intraventricular hemorrhage, hypoxic ischemic encephalopathy, necrotizing enterocolitis, retinopathy of prematurity and confirmed fetal infection. RESULTS: We recruited 126 women with suspected (n = 31) or confirmed (n = 95) pre-eclampsia at a median gestational age of 33.9 weeks (interquartile range, 30.9-36.3 weeks). Pregnancies with adverse perinatal outcome compared to those without had a higher median UtA-PI (1.3 vs 0.8; P < 0.001), ophthalmic artery PSV ratio (0.8 vs 0.7; P = 0.01) and umbilical artery PI percentile (82.0 vs 68.5; P < 0.01) and lower median estimated fetal weight percentile (4.0 vs 43.0; P < 0.001), abdominal circumference percentile (4.0 vs 63.0; P < 0.001), middle cerebral artery PI percentile (28.0 vs 58.5; P < 0.001) and cerebroplacental ratio percentile (18.0 vs 46.5; P < 0.001). Pregnancies with adverse perinatal outcome also had a higher median sFlt-1 (8208.0 pg/mL vs 4508.0 pg/mL; P < 0.001), lower PlGF (27.2 pg/mL vs 76.3 pg/mL; P < 0.001) and a higher sFlt-1/PlGF ratio (445.4 vs 74.4; P < 0.001). The best performing individual marker for predicting adverse perinatal outcome was the sFlt-1/PlGF ratio (area under the ROC curve (AUC), 0.87 (95% CI, 0.81-0.93)), followed by estimated fetal weight (AUC, 0.81 (95% CI, 0.73-0.89)). Women who experienced adverse maternal outcome had a higher median sFlt-1 level (7471.0 pg/mL vs 5131.0 pg/mL; P < 0.001) and sFlt-1/PlGF ratio (204.3 vs 93.3; P < 0.001) and a lower PlGF level (37.0 pg/mL vs 66.1 pg/mL; P = 0.01) and estimated fetal weight percentile (16.5 vs 37.0; P = 0.04). All markers performed poorly in predicting adverse maternal outcome, with sFlt-1 (AUC, 0.69 (95% CI, 0.60-0.79)) and sFlt-1/PlGF ratio (AUC, 0.69 (95% CI, 0.59-0.78)) demonstrating the best individual performance. The addition of cardiovascular, fetal or other placental indices to the sFlt-1/PlGF ratio did not improve the prediction of adverse maternal or perinatal outcomes. CONCLUSIONS: The sFlt-1/PlGF ratio performs well in predicting adverse perinatal outcomes but is a poor predictor of adverse maternal outcomes in women with suspected or diagnosed pre-eclampsia. The addition of cardiovascular or fetal indices to the model is unlikely to improve the prognostic performance of the sFlt-1/PlGF ratio. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Changes in lifestyle, diet, and body weight during the first COVID 19 'lockdown' in a student sample.

Changes in lifestyle and body weight were examined retrospectively in students at a German university during the first COVID-19 lockdown period (March 12- May 3, 2020) using an online survey. Data from a total of 827 participants was used. Almost half of the students reported perceived body weight changes with about 27% gaining weight and around 22% losing weight. Regression analyses showed that consumption changes in the following food categories: fruits, sweets and cakes, bread and bakery products, pasta, savoury snacks, and meats and sausages were predictive of weight changes. Additionally, changes in the frequency of cooking with fresh ingredients, physical activity, exercise, smoking, and alcohol consumption as well as pre-lockdown BMI were all predictive of weight changes. Given the continuous global pandemic, increased and innovative public health efforts to support this population group are needed.

Impact of COVID-19 pandemic restrictions on pregnancy duration and outcome in Melbourne, Australia.

OBJECTIVE: To investigate the effect of restriction measures implemented to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during the coronavirus disease 2019 (COVID-19) pandemic on pregnancy duration and outcome. METHODS: A before-and-after study was conducted with cohort sampling in three maternity hospitals in Melbourne, Australia, including women who were pregnant when restriction measures were in place during the COVID-19 pandemic (estimated conception date between 1 November 2019 and 29 February 2020) and women who were pregnant before the restrictions (estimated conception date between 1 November 2018 and 28 February 2019). The primary outcome was delivery before 34 weeks' gestation or stillbirth. The main secondary outcome was a composite of adverse perinatal outcomes. Pregnancy outcomes were compared between women exposed to restriction measures and unexposed controls using the χ-square test and modified Poisson regression models, and duration of pregnancy was compared between the groups using survival analysis. RESULTS: In total, 3150 women who were exposed to restriction measures during pregnancy and 3175 unexposed controls were included. Preterm birth before 34 weeks or stillbirth occurred in 95 (3.0%) exposed pregnancies and in 130 (4.1%) controls (risk ratio (RR), 0.74 (95% CI, 0.57-0.96); P = 0.021). Preterm birth before 34 weeks occurred in 2.4% of women in the exposed group and in 3.4% of women in the control group (RR, 0.71 (95% CI, 0.53-0.95); P = 0.022), without evidence of an increase in the rate of stillbirth in the exposed group (0.7% vs 0.9%; RR, 0.83 (95% CI, 0.48-1.44); P = 0.515). Competing-risks regression analysis showed that the effect of the restriction measures on spontaneous preterm birth was stronger and started earlier (subdistribution hazard ratio (HR), 0.81 (95% CI, 0.64-1.03); P = 0.087) than the effect on medically indicated preterm birth (subdistribution HR, 0.89 (95% CI, 0.70-1.12); P = 0.305). The effect was stronger in women with a previous preterm birth (RR, 0.42 (95% CI, 0.21-0.82); P = 0.008) than in parous women without a previous preterm birth (RR, 0.93 (95% CI, 0.63-1.38); P = 0.714) (P for interaction = 0.044). Composite adverse perinatal outcome was less frequent in the exposed group than in controls (all women: 2.1% vs 2.9%; RR, 0.73 (95% CI, 0.54-0.99); P = 0.042); women with a previous preterm birth: 4.5% vs 8.4%; RR, 0.54 (95% CI, 0.25-1.18); P = 0.116). CONCLUSIONS: Restriction measures implemented to mitigate SARS-CoV-2 transmission during the COVID-19 pandemic were associated with a reduced rate of preterm birth before 34 weeks. This reduction was mainly due to a lower rate of spontaneous prematurity. The effect was more substantial in women with a previous preterm birth and was not associated with an increased stillbirth rate. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Sulforaphane Bioavailability and Effects on Blood Pressure in Women with Pregnancy Hypertension.

Sulforaphane, an isothiocyanate found in cruciferous vegetables such as broccoli, shows promise as an adjuvant therapy for preeclampsia. To inform future clinical trials, we set out to determine the bioavailability of sulforaphane in non-pregnant and preeclamptic women. In six healthy female volunteers, we performed a crossover trial to compare the bioavailability of sulforaphane and metabolites afforded by an activated and non-activated broccoli extract preparation. We then undertook a dose escalation study of the activated broccoli extract in 12 women with pregnancy hypertension. In non-pregnant women, an equivalent dose of activated broccoli extract gave higher levels of sulforaphane and metabolites than a non-activated extract (p < 0.0001) and greater area under the curve (AUC) (3559 nM vs. 2172 nM, p = 0.03). Compared to non-pregnant women, in women with preeclampsia, the same dose of activated extract gave lower levels of total metabolites (p < 0.000) and AUC (3559 nM vs. 1653 nM, p = 0.007). Doubling the dose of the activated extract in women with preeclampsia doubled levels of sulforaphane and metabolites (p = 0.02) and AUC (1653 nM vs. 3333 nM, p = 0.02). In women with preeclampsia, activated broccoli extract was associated with modest decreases in diastolic blood pressure (p = 0.05) and circulating levels of sFlt-1 (p = 0.0002). A myrosinase-activated sulforaphane formulation affords better sulforaphane bioavailability than a non-activated formulation. Higher doses of sulforaphane are required to achieve likely effective doses in pregnant women than in non-pregnant women. Sulforaphane may improve endothelial function and blood pressure in women with pregnancy hypertension.

The osteoporosis treatment gap in patients at risk of fracture in European primary care: a multi-country cross-sectional observational study.

This study in 8 countries across Europe found that about 75% of elderly women seen in primary care who were at high risk of osteoporosis-related fractures were not receiving appropriate medication. Lack of osteoporosis diagnosis appeared to be an important contributing factor. INTRODUCTION: Treatment rates in osteoporosis are documented to be low. We wished to assess the osteoporosis treatment gap in women ≥ 70 years in routine primary care across Europe. METHODS: This cross-sectional observational study in 8 European countries collected data from women 70 years or older visiting their general practitioner. The primary outcome was treatment gap: the proportion who were not receiving any osteoporosis medication among those at increased risk of fragility fracture (using history of fracture, 10-year probability of fracture above country-specific Fracture Risk Assessment Tool [FRAX] thresholds, T-score ≤ - 2.5). RESULTS: Median 10-year probability of fracture (without bone mineral density [BMD]) for the 3798 enrolled patients was 7.2% (hip) and 16.6% (major osteoporotic). Overall, 2077 women (55%) met one or more definitions for increased risk of fragility fracture: 1200 had a prior fracture, 1814 exceeded the FRAX threshold, and 318 had a T-score ≤ - 2.5 (only 944 received a dual-energy x-ray absorptiometry [DXA] scan). In those at increased fracture risk, the median 10-year probability of hip and major osteoporotic fracture was 11.2% and 22.8%, vs 4.1% and 11.5% in those deemed not at risk. An osteoporosis diagnosis was recorded in 804 patients (21.2%); most (79.7%) of these were at increased fracture risk. The treatment gap was 74.6%, varying from 53% in Ireland to 91% in Germany. Patients with an osteoporosis diagnosis were found to have a lower treatment gap than those without a diagnosis, with an absolute reduction of 63%. CONCLUSIONS: There is a large treatment gap in women aged ≥ 70 years at increased risk of fragility fracture in routine primary care across Europe. The gap appears to be related to a low rate of osteoporosis diagnosis.

Foley catheter vs oral misoprostol for induction of labor: individual participant data meta-analysis.

OBJECTIVE: To compare the effectiveness and safety of Foley catheter and oral misoprostol for induction of labor (IOL). METHODS: The Cochrane Review on Mechanical Methods for Induction of Labour and Ovid MEDLINE, EMBASE via Ovid, Ovid Emcare, CINAHL Plus, ClinicalTrials.gov and Scopus, from inception to April 2019, were searched for randomized controlled trials (RCTs) comparing Foley catheter to oral misoprostol for IOL in viable singleton gestations. Eligible trials for which raw data were obtained were included and individual participant data meta-analysis was performed. Primary outcomes were vaginal birth, a composite of adverse perinatal outcome (including stillbirth, neonatal death, neonatal seizures, admission to the neonatal intensive care unit, severe respiratory compromise or meconium aspiration syndrome) and a composite of adverse maternal outcome (including admission to the intensive care unit, maternal infection, severe postpartum hemorrhage, maternal death or uterine rupture). The quality of the included RCTs was assessed using the Cochrane Risk of Bias 2 tool and the certainty of evidence was evaluated using the GRADE approach. A two-stage random-effects model was used for meta-analysis according to the intention-to-treat principle and interactions between treatment and baseline characteristics were assessed. RESULTS: Of seven eligible trials, four provided individual participant data for a total of 2815 participants undergoing IOL, of whom 1399 were assigned to Foley catheter and 1416 to oral misoprostol. All four trials provided data for each of the primary outcomes in all 2815 women. Compared with those receiving oral misoprostol, Foley catheter recipients had a slightly decreased chance of vaginal birth (risk ratio (RR), 0.95 (95% CI, 0.91-0.99); I2 , 2.0%; moderate-certainty evidence). A trend towards a lower rate of composite adverse perinatal outcome was found in women undergoing IOL using a Foley catheter compared with oral misoprostol (RR, 0.71 (95% CI, 0.48-1.05); I2 , 14.9%; low-certainty evidence). Composite adverse maternal outcome did not differ between the groups (RR, 1.00 (95% CI, 0.97-1.03); I2 , 0%; moderate-certainty evidence). Meta-analyses of effect modifications did not show significant interactions between intervention and parity or gestational age for any of the primary outcomes. CONCLUSIONS: For women undergoing IOL, Foley catheter is less effective than oral misoprostol, as it was associated with fewer vaginal births. However, while we found no significant difference in maternal safety, Foley catheter induction may reduce adverse perinatal outcomes. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Publisher Correction: Deep neural networks for automated detection of marine mammal species.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Sulforaphane improves syncytiotrophoblast mitochondrial function after in vitro hypoxic and superoxide injury.

INTRODUCTION: Placental mitochondrial dysfunction contributes to the oxidative stress that underlies preeclampsia. Here, we assessed whether sulforaphane (SFN) could improve syncytiotrophoblast mitochondrial function after in vitro hypoxic and superoxide injury. METHODS: Placental cytotrophoblasts were isolated from healthy term placentae (n = 12) and incubated for 48 h in 8% O2 ± 1 µM SFN before acute (4hrs) or chronic (24hrs) hypoxic (1% O2), or superoxide (xanthine/xanthine oxidase) injury. Cytotrophoblasts were also isolated from preeclamptic placentae (n = 5) and cultured in 8% O2 ± 1 µM SFN. Mitochondrial respiration was measured using the Seahorse MitoStress XF assay. Cells were stained with mitotracker red to assess mitochondrial membrane health and mitochondrial gene expression assessed using RT-qPCR. RESULTS: SFN prevented significant reductions in syncytiotrophoblast mitochondrial maximal respiration, spare respiratory capacity, basal respiration and ATP production following acute hypoxia. Chronic hypoxia only reduced maximal and spare respiratory capacity. SFN prevented these negative changes and increased respiration overall. Alternatively, acute superoxide injury significantly increased mitochondrial maximal respiration and spare respiratory capacity. SFN treatment further increased basal respiration following superoxide injury and prevented significant decreases in ATP production and coupling efficiency. In preeclamptic placentae, SFN significantly increased mitochondrial maximal respiration, spare respiratory capacity, basal respiration and ATP production, and decreased proton leak. SFN up-regulated mRNA expression of mitochondrial complexes and corrected an up-regulation in fission gene expression observed after hypoxic-superoxide injury. Finally, preliminary results suggest SFN prevented hypoxia-induced impairment of mitochondrial membrane structure. DISCUSSION: SFN mitigated hypoxia and superoxide induced changes to syncytiotrophoblast mitochondrial function in vitro, and improved mitochondrial respiration in trophoblast cells from preeclamptic placentae.

Koori voices: self-harm, suicide attempts, arrests and substance use among Aboriginal and Torres Strait Islander adolescents following residential treatment.

BACKGROUND: Complex interacting social, economic and historical factors influence the availability and uptake of alcohol and drugs, including among Indigenous communities. Self-harm and suicide as well as homelessness and incarceration, can both precede and result from drug and alcohol use. Rates of self-harm, suicide and incarceration among Aboriginal and Torres Strait Islander people in Australia are among the highest in the world and drug and alcohol treatment programs need to address these underlying complexities. This study examines whether an 'holistic' residential drug and alcohol treatment program for adolescents, with over 30% of clients identifying as Aboriginal and Torres Strait Islander, can improve outcomes post-discharge, including reducing self-harm, suicide attempts, arrests and alcohol and drug use. The program addresses substance use, mental health, employment, accommodation, social/community and family life. Program admission and 3 months' post-discharge data from 2007 to 2016 were analysed. RESULTS: From 2007 to 2016, 619 Aboriginal and Torres Strait Islander young people were admitted to the program; 247 stayed in the program for 30 days or more; 89 were successfully followed up three months post-discharge to determine whether there was a significant improvement from baseline using the McNemar's Test and the Wilcoxon Signed Ranks Test. On admission, 18 people (20%) of the study population reported attempting suicide in the last 3 months and 23 people (30%) reported self-harm. Most had been engaged in the criminal justice system, with 67 people (75%) having been to court and 62 people (70%) arrested one or more times in the past 3 months, with 35 people (41%) in unstable housing, reporting having lived in three or more places in the previous 6 months. At 3 months post-treatment, all (n = 18) who reported suicide attempts in the 3 months prior to admission reported no attempts in the prior 3 months at follow-up. There was also a significant reduction in self-harm with 23 young people out of the 27 who reported self-harm at baseline not reporting self-harm at follow up (85%) and in the proportion of adolescents who reported using cannabis, amphetamines and alcohol, as well as a reduction in the proportion who reported being arrested. CONCLUSIONS: The findings provide support for an 'holistic' residential treatment program as an approach to improve health and related outcomes for Aboriginal and Torres Strait Islander young people. In addition to a focus on multiple aspects of a young person's life in treatment, culturally relevant modes of treatment and support should be a future focus to further strengthen programs when Aboriginal and Torres Strait Islander young people are over-represented in the client group.

Context, complexity and process in the implementation of evidence-based innovation: a realist informed review.

BACKGROUND: This review of scholarly work in health care knowledge translation advances understanding of implementation components that support the complete and timely integration of new knowledge. We adopt a realist approach to investigate what is known from the current literature about the impact of, and the potential relationships between, context, complexity and implementation process. METHODS: Informed by two distinct pathways, knowledge utilization and knowledge translation, we utilize Rogers' Diffusion of Innovations theory (DOI) and Harvey and Kitson's integrated- Promoting Action on Research Implementation in Health Service framework (PARIHS) to ground this review. Articles from 5 databases; Medline, Scopus, PsycInfo, Web of Science, and Google Scholar and a search of authors were retrieved. Themes and patterns related to these implementation components were extracted. Literature was selected for inclusion by consensus. Data extraction was iterative and was moderated by the authors. RESULTS: A total of 67 articles were included in the review. Context was a central component to implementation. It was not clear how and to what extent context impacted implementation. Complexity was found to be a characteristic of context, implementation process, innovations and a product of the relationship between these three elements. Social processes in particular were reported as influential however; descriptions of how these social process impact were limited. Multiple theoretical and operational models were found to ground implementation processes. We offer an emerging conceptual model to illustrate the key discoveries. CONCLUSIONS: The review findings indicate there are dynamic relationship between context, complexity and implementation process for enhancing uptake of evidence-based knowledge in hospital settings. These are represented in a conceptual model. Limited empiric evidence was found to explain the nature of the relationships.

Deep neural networks for automated detection of marine mammal species.

Deep neural networks have advanced the field of detection and classification and allowed for effective identification of signals in challenging data sets. Numerous time-critical conservation needs may benefit from these methods. We developed and empirically studied a variety of deep neural networks to detect the vocalizations of endangered North Atlantic right whales (Eubalaena glacialis). We compared the performance of these deep architectures to that of traditional detection algorithms for the primary vocalization produced by this species, the upcall. We show that deep-learning architectures are capable of producing false-positive rates that are orders of magnitude lower than alternative algorithms while substantially increasing the ability to detect calls. We demonstrate that a deep neural network trained with recordings from a single geographic region recorded over a span of days is capable of generalizing well to data from multiple years and across the species' range, and that the low false positives make the output of the algorithm amenable to quality control for verification. The deep neural networks we developed are relatively easy to implement with existing software, and may provide new insights applicable to the conservation of endangered species.

Use of an automated knot fastener shortens operative times in minimally invasive mitral valve repair.

INTRODUCTION: Longer durations of cardiopulmonary bypass and aortic cross clamp are associated with increased morbidity and mortality. Little is known about the effect of automated knot fasteners (Cor-Knot®) in minimally invasive mitral valve repair on operative times and outcomes. The aim of this study was to evaluate whether these devices shortened cardiopulmonary bypass and aortic cross clamp times and whether this impacted on postoperative outcomes. MATERIALS AND METHODS: All patients undergoing isolated minimally invasive mitral valve repair by a single surgeon between March 2011 and March 2016 were included (n = 108). Two cohorts were created based on the use (n = 52) or non-use (n = 56) of an automated knot fastener. Data concerning intraoperative variables and postoperative outcomes were collected and compared. RESULTS: Preoperative demographics were well matched between groups with no significant difference in logistic Euroscore (manual vs automated: median 3.1, interquartile range, IQR, 2.1-5.5, vs 5.4, IQR 2.2-8.3; P = 0.07, respectively). Comparing manually tied knots to an automated fastener, cardiopulmonary bypass and aortic cross clamp times were significantly shorter in the automated group (cardiopulmonary bypass: median 200 minutes, IQR 180-227, vs 165 minutes (IQR 145-189 minutes), P < 0.001; aortic cross clamp 134 minutes (IQR 121-150 minutes) vs 111 minutes (IQR 91-137 minutes), P < 0.001, respectively). There was no mortality and no strokes, nor were there any differences in postoperative outcomes including reoperation for bleeding, renal failure, intensive care or hospital stay. CONCLUSIONS: The use of an automated knot fastener significantly reduces cardiopulmonary bypass and aortic cross clamp times in minimally invasive mitral valve repair but this does not translate into an improved clinical outcome.