Consequences of gene editing of PRLR on thermotolerance, growth, and male reproduction in cattle.

Global warming is a major challenge to the sustainable and humane production of food because of the increased risk of livestock to heat stress. Here, the example of the prolactin receptor (PRLR) gene is used to demonstrate how gene editing can increase the resistance of cattle to heat stress by the introduction of mutations conferring thermotolerance. Several cattle populations in South and Central America possess natural mutations in PRLR that result in affected animals having short hair and being thermotolerant. CRISPR/Cas9 technology was used to introduce variants of PRLR in two thermosensitive breeds of cattle - Angus and Jersey. Gene-edited animals exhibited superior ability to regulate vaginal temperature (heifers) and rectal temperature (bulls) compared to animals that were not gene-edited. Moreover, gene-edited animals exhibited superior growth characteristics and had larger scrotal circumference. There was no evidence for deleterious effects of the mutation on carcass characteristics or male reproductive function. These results indicate the potential for reducing heat stress in relevant environments to enhance cattle productivity.

Development of a formula for scoring competence of bovine embryos to sustain pregnancy.

Embryo transfer in cattle and other species is a key reproductive technology to improve genetic merit. However, pregnancy loss after embryo transfer is still a major barrier to optimal utilization of the technology. Furthermore, the lack of a method to objectively quantify embryonic competence hinders investigations aimed at improving the competence of an embryo. Based on the knowledge that bovine embryos have an inherent molecular signature that determines their ability for pregnancy establishment which can result in distinct gene expression profiles, we have previously integrated transcriptomic data from independent experiments to identify eight genes capable of predicting embryo competence for survival with high accuracy. In this study, we developed a function for the R software containing a mathematical formula based on the model coefficients to yield an embryonic competence index (ECI) according to the expression of those eight critical genes. Application of the function to a gene expression dataset generates a quantitative ECI value for each embryo that can be employed in statistical analyses when performing an experiment. The folder with the R project and required datasets can be found in https://zenodo.org/records/12515587.

Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study.

Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for ~1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.

Inter hospital transfers in rotor wing aircraft. Patterns and challenges. Protocol for a scoping review.

BACKGROUND: Inter-hospital transfer is necessary for the transport of patients to specialized treatment. Rotor-wing aircraft may be used in lieu of ambulances in time-critical conditions over long distances and when specialist team skills are called for. The purpose of the review is to assess the current scientific literature that describes the scenario to develop a national guideline for inter-hospital transfers using rotor-wing aircraft. The aim is to describe the patterns and challenges. METHODS AND ANALYSIS: The authors will conduct a scoping review as per Joanna Briggs Institute guideline. The protocol for the scoping review will adhere to the Open Science Framework guideline for scoping reviews and we will report the findings of the scoping review as per PRISMA-ScR guideline. We have developed the search strategy with the help of a research librarian and will conduct search in relevant electronic databases and include gray literature as well, using the PRESS and PRISMA-S guidelines. Two authors will independently screen titles and abstracts for inclusion as per eligibility criteria and conflicts will be resolved by a third reviewer. Full text retrieval will be conducted accordingly. We will analyze the extracted data using validated statistical methods. ETHICS AND DISSEMINATION: According to Danish law, scoping reviews are exempt from ethics committee approval. The findings of this scoping review will provide the scientific foundation for a national guideline on rotor-wing aircraft conveyed inter-hospital transfers in Denmark. Furthermore, we will publish the results of the scoping review in a relevant scientific journal.

Cytokine responses of CD4+ T cells and NKT cells to periodontitis-associated bacteria in individuals with or without periodontitis.

AIM: Periodontitis is an inflammatory disease driven by opportunistic bacteria including Porphyromonas gingivalis and Fusobacterium nucleatum, where T-cell and NKT-cell responses to these bacteria in patients with periodontitis grade B or C are not fully elucidated. The objective is to determine if exaggerated proinflammatory Th-cell responses to periodontitis-associated bacteria, but not commensal bacteria, is a characteristic of increased periodontitis grade. METHODS: Mononuclear cells from patients with periodontitis grade C (n = 26) or grade B (n = 33) and healthy controls (HCs; n = 26) were stimulated with P. gingivalis, F. nucleatum or the commensal bacteria, Staphylococcus epidermidis and Cutibacterium acnes. Cytokine production by different T-cell populations and FOXP3-expression by regulatory T cells were assessed by flow cytometry. RESULTS: Compared to HCs, grade C patients had decreased frequencies of interleukin (IL)-10-producing CD4+ T cells before stimulation (p = .02) and increased frequencies of IFN-y-producing CD4+ T cells after stimulation with P. gingivalis (p = .0019). Grade B patients had decreased frequencies of FOXP3+ CD4+ T cells before (p = .030) before and after stimulation with anti-CD2/anti-CD3/anti-CD28-loaded beads (p = .047), P. gingivalis (p = .013) and S. epidermidis (p = .018). Clinical attachment loss correlated with the frequencies of IFN-y-producing Th1 cells in P. gingivalis- and F. nucleatum-stimulated cultures in grade B patients (p = .023 and p = .048, respectively) and with the frequencies of Th17 cells in P. gingivalis-stimulated cultures (p = .0062) in grade C patients. Patients with periodontitis grade C or grade B showed lower frequencies of IL-10-producing NKT cells than HCs in unstimulated cultures (p = .0043 and p = .027 respectively). CONCLUSIONS: Both periodontitis groups showed decreased frequencies of immunoregulatory T-cell and NKT cell subsets at baseline. Clinical attachment loss correlated with P. gingivalis-induced Th17-responses in grade C patients and with Th1-responses in grade B patients when cells were stimulated with P. gingivalis, supporting that dysregulated pro-inflammatory T-cell responses to periodontitis-associated bacteria contribute to the pathogenesis of periodontitis.

Ovarian hyperplasia linked to a mutation in MAN1A2 in a cow with excessive follicular growth and functional oocytes.

Here we report the case of a cow with two ovaries that each exhibited hyperplasia but that otherwise had normal gross morphology. Both ovaries had a large number of tertiary follicles on the ovarian surface. Oocytes from one ovary were studied in more detail. The transcriptome was largely similar to other oocytes. Oocytes could undergo cleavage at a rate consistent with other oocytes and result in blastocyst-stage embryo formation after in vitro maturation and fertilization. Review of the literature from cattle and other species did not reveal reports of a similar type of spontaneous ovarian abnormality. Whole genome sequencing revealed many single nucleotide polymorphisms with predicted large effects on protein structure that could potentially be causative for the phenotype. The variant considered most likely to cause the observed alteration in ovarian function was a mutation in the glycoprotein-modifying enzyme MAN1A2.

Lung cancer patients with anaplastic lymphoma kinase rearrangement lose affiliation with labor market at diagnosis.

Aim: The main purpose of the present study was to investigate the labor market affiliation of ALK+ NSCLC patients in long-term treatment as well as overall survival and incidence/prevalence. Materials & methods: Nationwide retrospective study of all patients with ALK+ NSCLC in Denmark diagnosed between 2012 and 2018. Results: During the study period ALK+ NSCLC patients had a median overall survival of 44.0 months and a 7.8-fold increase in disease prevalence. Six months prior to diagnosis, 81% of ALK+ NSCLC patients ≤60 years of age were employed. At the end of the 18-month follow-up period, 36% were employed. Conclusion: ALK+ NSCLC patients have prolonged survival following diagnosis, but a large fraction of patients lose affiliation with the labor market.

The purpose of this study was to examine the employment status and survival of patients with ALK+ NSCLC who are undergoing long-term treatment. The researchers conducted a study analyzing data from all such patients diagnosed between 2012 and 2018 in Denmark. The results showed that ALK+ NSCLC patients had a median overall survival of 44.0 months and a that the number of patients increased almost eightfold during the study period. Prior to diagnosis, 81% of ALK+ NSCLC patients who were 60 years of age or younger were employed. However, at the end of the 18-month follow-up period, only 36% of these patients were still employed. In conclusion, ALK+ NSCLC patients tend to have prolonged survival after diagnosis. However, a considerable proportion of these patients lose their affiliation with the labor market, indicating the impact of the disease on employment status.

ALK+ NSCLC patients have prolonged survival following diagnosis, but a large fraction of patients lose affiliation with the labor market following diagnosis. #alkpositive #lcsm.

Machine learning to identify endometrial biomarkers predictive of pregnancy success following artificial insemination in dairy cows†.

The objective was to identify a set of genes whose transcript abundance is predictive of a cow's ability to become pregnant following artificial insemination. Endometrial epithelial cells from the uterine body were collected for RNA sequencing using the cytobrush method from 193 first-service Holstein cows at estrus prior to artificial insemination (day 0). A group of 253 first-service cows not used for cytobrush collection were controls. There was no effect of cytobrush collection on pregnancy outcomes at day 30 or 70 or on pregnancy loss between days 30 and 70. There were 2 upregulated and 214 downregulated genes (false discovery rate < 0.05, absolute fold change >2-fold) for cows pregnant at day 30 versus those that were not pregnant. Functional terms overrepresented in the downregulated genes included those related to immune and inflammatory responses. Machine learning for fertility biomarkers with the R package BORUTA resulted in identification of 57 biomarkers that predicted pregnancy outcome at day 30 with an average accuracy of 77%. Thus, machine learning can identify predictive biomarkers of pregnancy in endometrium with high accuracy. Moreover, sampling of endometrial epithelium using the cytobrush can help understand functional characteristics of the endometrium at artificial insemination without compromising cow fertility. Functional characteristics of the genes comprising the set of biomarkers is indicative that a major determinant of cow fertility, at least for first insemination after calving, is immune status of the uterus, which, in turn, is likely to reflect the previous history of uterine disease.

A Systematic Review of Delayed High-Grade Atrioventricular Block After Transcatheter Aortic Valve Implantation.

Background: High-grade atrioventricular block (HGAVB) is common after transcatheter aortic valve implantation (TAVI), often necessitating permanent pacemaker (PPM) implantation. Delayed HGAVB has varying definitions but typically refers to onset 48 hours after TAVI or following discharge and may cause syncope and sudden cardiac death. This review estimates the incidence of delayed HGAVB and identifies limitations of current literature. Methods: A systematic review was performed of the following online databases: Medline, Cochrane, Web of Science, and Scopus. Studies that labelled the outcome of "delayed" or "late" atrioventricular block after TAVI were included; patients with previous PPM or aortic valve surgery were excluded. Initial search yielded 775 studies, which, after screening, was narrowed to 19 studies. Results: Nineteen studies with 14,898 patients were included. Mean age was 81.7 years, and 46.3% were male. Mean Society of Thoracic Surgeons (STS) score was 5.6%, and 31.3% of patients had known atrial fibrillation. The most common access site was transfemoral (84.8%), whereas balloon-expandable valves were used in 62.1%, self-expanding valves in 34.0%, and mechanically expanding valves in 3.9% of cases. The incidence of delayed HGAVB ranged from 1.7% to 14.6%, with significant methodologic heterogeneity noted among the included studies. Conclusions: Delayed HGAVB is a common and potentially serious complication of TAVI, with similar risk factors to acute HGAVB. With a move toward an early discharge strategy post-TAVI, further prospective study of delayed HGAVB is warranted to improve understanding of predisposing factors, incidence, timing, and implications.

Contexte: L'apparition d'un bloc atrioventriculaire de haut degré (BAVHD) est fréquente après l'implantation valvulaire aortique par cathéter (IVAC), ce qui nécessite souvent l'implantation d'un stimulateur cardiaque permanent. Les définitions d'un BAVHD tardif varient, mais elles font habituellement référence à l'apparition du bloc 48 heures après l'IVAC ou après le congé de l'hôpital. Le bloc peut alors provoquer une syncope et une mort subite d'origine cardiaque. Cette analyse vise à estimer l'incidence de la formation d'un BAVHD tardif et à définir les lacunes dans les publications actuelles. Méthodologie: Une analyse des études publiées dans les bases de données en ligne suivantes a été menée : Medline, Cochrane, Web of Science et Scopus. Les études dont le libellé comprenait l'issue du bloc atrioventriculaire tardif ou éloigné (« delayed ¼ ou « late ¼) ont été retenues. Les patients qui avaient antérieurement reçu un stimulateur cardiaque permanent ou subi une intervention chirurgicale de la valve aortique ont été exclus. La recherche initiale a permis de recenser 775 études, nombre qui a été réduit à 19 après l'application des critères de sélection. Résultats: Dix-neuf études totalisant 14 898 patients ont été retenues. L'âge moyen était 81,7 ans, et 46,3 % des patients étaient des hommes. Le score STS (Society of Thoracic Surgeons) moyen était de 5,6 %, et 31,3 % des patients avaient une fibrillation auriculaire. Le point d'accès le plus fréquent était par l'artère fémorale (84,8 %). Des valves expansibles par ballonnet ont été utilisées dans 62,1 % des cas, des valves auto-expansibles dans 34,0 % des cas et des valves expansibles mécaniquement dans 3,9 % des cas. L'incidence du BAVHD tardif variait de 1,7 % à 14,6 %, mais la méthodologie était très hétérogène d'une étude à l'autre. Conclusions: Le BAVHD tardif est une complication fréquente et potentiellement grave de l'IVAC, et ses facteurs de risque sont comparables à ceux du BAVHD aigu. Étant donné la volonté d'adopter une stratégie de congé précoce après une IVAC, une autre étude prospective sur le BAVHD tardif s'impose pour mieux comprendre les facteurs prédisposants, l'incidence, la chronologie et les implications.

Node-degree aware edge sampling mitigates inflated classification performance in biomedical random walk-based graph representation learning.

Motivation: Graph representation learning is a family of related approaches that learn low-dimensional vector representations of nodes and other graph elements called embeddings. Embeddings approximate characteristics of the graph and can be used for a variety of machine-learning tasks such as novel edge prediction. For many biomedical applications, partial knowledge exists about positive edges that represent relationships between pairs of entities, but little to no knowledge is available about negative edges that represent the explicit lack of a relationship between two nodes. For this reason, classification procedures are forced to assume that the vast majority of unlabeled edges are negative. Existing approaches to sampling negative edges for training and evaluating classifiers do so by uniformly sampling pairs of nodes. Results: We show here that this sampling strategy typically leads to sets of positive and negative examples with imbalanced node degree distributions. Using representative heterogeneous biomedical knowledge graph and random walk-based graph machine learning, we show that this strategy substantially impacts classification performance. If users of graph machine-learning models apply the models to prioritize examples that are drawn from approximately the same distribution as the positive examples are, then performance of models as estimated in the validation phase may be artificially inflated. We present a degree-aware node sampling approach that mitigates this effect and is simple to implement. Availability and implementation: Our code and data are publicly available at https://github.com/monarch-initiative/negativeExampleSelection.

Meta-analysis to determine efficacy of colony-stimulating factor 2 for improving pregnancy success after embryo transfer in cattle.

Results have been inconsistent as to whether addition of colony stimulating factor 2 (CSF2) to culture medium improves embryo competence for establishment of pregnancy in cattle and humans. The purpose of the current study was to use all available experiments in cattle concerning effects of CSF2 on pregnancy success after transfer into recipient cattle. The approach was to perform a meta-analysis of all published data sets as well as data from an unpublished experiment described for the first time here. Meta-analysis failed to support the hypothesis that addition of CSF2 to embryo culture medium improves competence of bovine blastocysts to increase pregnancy or calving rates after transfer into recipient females. Thus, its general use as a culture medium additive to increase pregnancy success after embryo transfer is not recommended.

NPSV-deep: a deep learning method for genotyping structural variants in short read genome sequencing data.

MOTIVATION: Structural variants (SVs) play a causal role in numerous diseases but can be difficult to detect and accurately genotype (determine zygosity) with short-read genome sequencing data (SRS). Improving SV genotyping accuracy in SRS data, particularly for the many SVs first detected with long-read sequencing, will improve our understanding of genetic variation. RESULTS: NPSV-deep is a deep learning-based approach for genotyping previously reported insertion and deletion SVs that recasts this task as an image similarity problem. NPSV-deep predicts the SV genotype based on the similarity between pileup images generated from the actual SRS data and matching SRS simulations. We show that NPSV-deep consistently matches or improves upon the state-of-the-art for SV genotyping accuracy across different SV call sets, samples and variant types, including a 25% reduction in genotyping errors for the Genome-in-a-Bottle (GIAB) high-confidence SVs. NPSV-deep is not limited to the SVs as described; it improves deletion genotyping concordance a further 1.5 percentage points for GIAB SVs (92%) by automatically correcting imprecise/incorrectly described SVs. AVAILABILITY AND IMPLEMENTATION: Python/C++ source code and pre-trained models freely available at https://github.com/mlinderm/npsv2.

The ability of contemporary cardiologists to judge the ischemic impact of a coronary lesion visually

BACKGROUND: Landmark trials showed that invasive pressure measurement (Fractional Flow Reserve, FFR) was a better guide to coronary stenting than visual assessment. However, present-day interventionists have benefited from extensive research and personal experience of mapping anatomy to hemodynamics. AIMS: To determine if visual assessment of the angiogram performs as well as invasive measurement of coronary physiology. METHODS: 25 interventional cardiologists independently visually assessed the single vessel coronary disease of 200 randomized participants in The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial (ORBITA). They gave a visual prediction of the FFR and Instantaneous Wave-free Ratio (iFR), denoted vFFR and viFR respectively. Each judged each lesion on 2 occasions, so that every lesion had 50 vFFR, and 50 viFR assessments. The group consensus visual estimates (vFFR-group and viFR-group) and individual cardiologists' visual estimates (vFFR-individual and viFR-individual) were tested alongside invasively measured FFR and iFR for their ability to predict the placebo-controlled reduction in stress echo ischemia with stenting. RESULTS: Placebo-controlled ischemia improvement with stenting was predicted by vFFR-group (p < 0.0001) and viFR-group (p < 0.0001), vFFR-individual (p < 0.0001) and viFR-individual (p < 0.0001). There were no significant differences between the predictive performance of the group visual estimates and their invasive counterparts: p = 0.53 for vFFR vs FFR and p = 0.56 for viFR vs iFR. CONCLUSION: Visual assessment of the angiogram by contemporary experts, provides significant additional information on the amount of ischaemia which can be relieved by placebo-controlled stenting in single vessel coronary artery disease.

The importance of nonobstructive plaque characteristics in symptomatic and asymptomatic coronary artery disease.

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

Anesthesiologists' skills in emergency cricothyroidotomy mandate a brush-up training after 3 months-A randomized controlled trial.

BACKGROUND: In the Difficult Airway Society's 2015 "cannot intubate, cannot oxygenate" guideline, the emergency cricothyroidotomy is the final option when managing an unanticipated difficult airway. How often training for maintenance of this skill is required for anesthesiologists remains unknown. We aimed to assess if specialist-trained anesthesiologists' skills improved from a brush-up intervention and if skills were retained after 3 months. METHODS: In this multicenter, randomized, controlled trial, participants were randomized to either a simulation-based brush-up or no brush-up. Both groups performed a mannequin-based technical skills emergency cricothyroidotomy test twice and were assessed by a blinded rater using a structured assessment tool that included time, positioning, palpation, appropriate employment of instruments, and stepwise progression. After 3 months of non-training, participants completed identical tests of retention. RESULTS: A total of 54 anesthesiologists were included from three hospitals in the Region of Southern Denmark. Thirty-seven percent of the participants had received skills training in emergency cricothyroidotomy in the prior 12 months. The intervention group (N = 27) performed better in the initial tests, with a mean time of 51.5 s (SD = 10.82), a total score per minute of 15.9 points (SD = 4.91), and 93% passing both initial tests compared to the control group (N = 27) with a mean time of 76.8 s (SD = 35.82), a total score per minute of 6.6 (SD = 4.68) and only 15% passing both initial tests. The intervention group managed to retain overall performance in retention tests in terms of performance time (48.9 s, p = .26), total score per minute (13.6 points, p = .094), and passing the tests (75%, p = .059). CONCLUSION: Exposure to simulation-based brush-up training in emergency cricothyroidotomy improved anesthesiologists' technical performance and was overall retained after 3 months. Some loss of skill concerning specific items was observed, highlighting the need for regular training in emergency cricothyroidotomy. Simulation-based training should be prioritized to improve and maintain technical skills in infrequent high-stakes procedures.

Ambulance and helicopter response time. Association with patient outcome and illness severity: Protocol of a systematic literature review and meta-analysis.

BACKGROUND: Response time for emergency medical service units is a key performance indicator. Studies have shown reduced response time association with improved outcome for specific critical conditions. To achieve short response time, emergency vehicles utilize lights and sirens, and crews are allowed to be non-compliant with traffic rules, posing a risk for accident. The purpose of the systematic review and meta-analysis is to provide an overview of the current body of evidence regarding the association, if any, between ambulance and helicopter response time and major complications and mortality in patients conveyed by ambulance and/or helicopter. Our secondary aim will be to enhance knowledge in the field of criteria-based dispatch to provide decision makers with evidence to optimize dispatch of limited resources. RESEARCH QUESTIONS: What is the association between overall emergency medical services unit response time and patient outcomes, major complications, and time-critical conditions? What is the internal and external validity of the included literature? METHODS: We plan the systematic review and meta-analysis to be in accordance with the Cochrane Handbook and Joanna Briggs Institute Manual for Systematic Reviews. The methodology will include formulating the review questions using a Population, Exposure, and Outcome framework. Every study design is eligible, including qualitative, quantitative, and mixed-methods designs. We will include all articles in English, Scandinavian, German, French and Portuguese in this systematic review. RESULTS: We will publish results from the systematic review and meta-analysis in a peer-reviewed journal and we will present the results at scientific conferences and meetings. Results will also be available at www.ahrtemis.dk. CONCLUSION: We will base our conclusions on the findings of the review and meta-analysis.

The ability of contemporary cardiologists to judge the ischemic impact of a coronary lesion visually.

BACKGROUND: Landmark trials showed that invasive pressure measurement (Fractional Flow Reserve, FFR) was a better guide to coronary stenting than visual assessment. However, present-day interventionists have benefited from extensive research and personal experience of mapping anatomy to hemodynamics. AIMS: To determine if visual assessment of the angiogram performs as well as invasive measurement of coronary physiology. METHODS: 25 interventional cardiologists independently visually assessed the single vessel coronary disease of 200 randomized participants in The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial (ORBITA). They gave a visual prediction of the FFR and Instantaneous Wave-free Ratio (iFR), denoted vFFR and viFR respectively. Each judged each lesion on 2 occasions, so that every lesion had 50 vFFR, and 50 viFR assessments. The group consensus visual estimates (vFFR-group and viFR-group) and individual cardiologists' visual estimates (vFFR-individual and viFR-individual) were tested alongside invasively measured FFR and iFR for their ability to predict the placebo-controlled reduction in stress echo ischemia with stenting. RESULTS: Placebo-controlled ischemia improvement with stenting was predicted by vFFR-group (p < 0.0001) and viFR-group (p < 0.0001), vFFR-individual (p < 0.0001) and viFR-individual (p < 0.0001). There were no significant differences between the predictive performance of the group visual estimates and their invasive counterparts: p = 0.53 for vFFR vs FFR and p = 0.56 for viFR vs iFR. CONCLUSION: Visual assessment of the angiogram by contemporary experts, provides significant additional information on the amount of ischaemia which can be relieved by placebo-controlled stenting in single vessel coronary artery disease.