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Micro-anatomical reentry has been identified as a potential driver of atrial fibrillation (AF). In this paper, we introduce a novel computational method which aims to identify which atrial regions are most susceptible to micro-reentry. The approach, which considers the structural basis for micro-reentry only, is based on the premise that the accumulation of electrically insulating interstitial fibrosis can be modelled by simulating percolation-like phenomena on spatial networks. Our results suggest that at high coupling, where micro-reentry is rare, the micro-reentrant substrate is highly clustered in areas where the atrial walls are thin and have convex wall morphology. However, as transverse connections between fibres are removed, mimicking the accumulation of interstitial fibrosis, the substrate becomes less spatially clustered, and the bias to forming in thin, convex regions of the atria is reduced. Comparing our algorithm on image-based models with and without atrial fibre structure, we find that strong longitudinal fibre coupling can suppress the micro-reentrant substrate, whereas regions with disordered fibre orientations have an enhanced risk of micro-reentry. We suggest that with further development, these methods may have future potential for patient-specific risk stratification, taking a longitudinal view of the development of the micro-reentrant substrate. Author summary Atrial fibrillation (AF) is the most common abnormal heart rhythm, yet, despite extensive research, treatment success rates remain poor. In part, this is because there is an incomplete understanding of the mechanistic origin of AF. In this paper, we investigate one proposed mechanism of AF, the formation of “micro-reentrant circuits”, which can be thought of as a “short circuit”, forming when electrically insulating fibrosis (structural repair tissue) infiltrates the space between heart muscle cells. Previously, such circuits have been found in experimental hearts, but identifying these circuits clinically is difficult. Here, we aim to take a small step towards developing computational methods for identifying where in the atria these circuits are most likely to form, drawing on techniques from network science. Our approach indicates that a number of factors are key to determining where circuits form, most notably the thickness of the heart muscle, and the alignment of muscle fibres.

OBJECTIVE: To develop consensus definitions of image-guided surgery, computer-assisted surgery, hybrid operating room, and surgical navigation systems. SUMMARY BACKGROUND DATA: The use of minimally invasive procedures has increased tremendously over the past 2 decades, but terminology related to image-guided minimally invasive procedures has not been standardized, which is a barrier to clear communication. METHODS: Experts in image-guided techniques and specialized engineers were invited to engage in a systematic process to develop consensus definitions of the key terms listed above. The process was designed following review of common consensus-development methodologies and included participation in 4 online surveys and a post-surveys face-to-face panel meeting held in Strasbourg, France. RESULTS: The experts settled on the terms computer-assisted surgery and intervention, image-guided surgery and intervention, hybrid operating room, and guidance systems and agreed-upon definitions of these terms, with rates of consensus of more than 80% for each term. The methodology used proved to be a compelling strategy to overcome the current difficulties related to data growth rates and technological convergence in this field. CONCLUSIONS: Our multidisciplinary collaborative approach resulted in consensus definitions that may improve communication, knowledge transfer, collaboration, and research in the rapidly changing field of image-guided minimally invasive techniques. PMC7771637

BackgroundSeverely injured trauma patients suffering from traumatic cardiac arrest (TCA) and requiring cardiopulmonary resuscitation (CPR) rarely survive. The role of resuscitative endovascular balloon occlusion of the aorta (REBOA) performed early after hospital admission in patients with TCA is not well-defined. As the use of REBOA increases, there is great interest in knowing if there is a survival benefit related to the early use of REBOA after TCA. Using data from the ABOTrauma Registry, we aimed to study the role of REBOA used early after hospital admission in trauma patients who required pre-hospital CPR.MethodsRetrospective and prospective data on the use of REBOA were collected from the ABOTrauma Registry from 11 centers in seven countries globally between 2014 and 2019. In all patients with pre-hospital TCA, the predicted probability of survival, calculated with the Revised Injury Severity Classification II (RISC II), was compared with the observed survival rate.ResultsOf 213 patients in the ABOTrauma Registry, 26 patients (12.2%) who had received pre-hospital CPR were identified. The median (range) Injury Severity Score (ISS) was 45.5 (25–75). Fourteen patients (54%) had been admitted to the hospital with ongoing CPR. Nine patients (35%) died within the first 24 h, while seventeen patients (65%) survived post 24 h. The survival rate to hospital discharge was 27% (n= 7). The predicted mortality using the RISC II was 0.977 (25 out of 26). The observed mortality (19 out of 26) was significantly lower than the predicted mortality (p= 0.049). Patients not responding to REBOA were more likely to die. Only one (10%) out of 10 non-responders survived. The survival rate in the 16 patients responding to REBOA was 37.5% (n= 6). REBOA with a median (range) duration of 45 (8–70) minutes significantly increases blood pressure from the median (range) 56.5 (0–147) to 90 (0–200) mmHg.ConclusionsMortality in patients suffering from TCA and receiving REBOA early after hospital admission is significantly lower than predicted by the RISC II. REBOA may improve survival after TCA. The use of REBOA in these patients should be further investigated.

BackgroundResuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive procedure being increasingly utilized to prevent patients with non-compressible torso hemorrhage from exsanguination. The increased use of REBOA is giving rise to discussion about “Who is and who should be performing it?”MethodsData from the international ABO (aortic balloon occlusion) Trauma Registry from between November 2014 and April 2020 were analyzed concerning the question: By who, how, and where is REBOA being performed? The registry collects retrospective and prospective data concerning use of REBOA in trauma patients.ResultsDuring the study period, 259 patients had been recorded in the registry, 72.5% (n= 188) were males with a median (range) age of 46 (10-96) years. REBOA was performed in the ER in 50.5%, in the OR in 41.5%, and in the angiography suite in 8% of patients. In 54% of the patients REBOA was performed by surgeons (trauma surgeons 28%, vascular surgeons 22%, general surgeons 4%) and in 46% of the patients by non-surgeons (emergency physicians 31%, radiologists 9.5%, anesthetists 5.5%). Common femoral artery (CFA) access was achieved by use of external anatomic landmarks and palpation alone in 119 patients (51%), by cutdown in 57 patients (24%), using ultrasound in 49 patients (21%), and by fluoroscopy in 9 patients (4%). Significant differences between surgeons and non-surgeons were found regarding patient’s age, injury severity, access methods, place where REBOA was performed, location patients were taken to from the emergency room, and mortality.ConclusionA substantial number of both surgical and non-surgical medical disciplines are successfully performing REBOA to an almost equal extent. Surgical cutdown is used less frequently as access to the CFA compared with reports in older literature and puncture by use of external anatomic landmarks and palpation alone is used with a high rate of success. Instead of discussing “Who should be performing REBOA?” future research should focus on “Which patient benefits most from REBOA?”

Atrial fibrillation (AF) is the most common cardiac arrhytmia, characterised by the chaotic motion of electrical wavefronts in the atria. In clinical practice, AF is classified under two primary categories: paroxysmal AF, short intermittent episodes separated by periods of normal electrical activity, and persistent AF, longer uninterrupted episodes of chaotic electrical activity. However, the precise reasons why AF in a given patient is paroxysmal or persistent is poorly understood. Recently, we have introduced the percolation based Christensen-Manani-Peters (CMP) model of AF which naturally exhibits both paroxysmal and persistent AF, but precisely how these differences emerge in the model is unclear. In this paper, we dissect the CMP model to identify the cause of these different AF classifications. Starting from a mean-field model where we describe AF as a simple birth-death process, we add layers of complexity to the model and show that persistent AF arises from the formation of temporally stable structural re-entrant circuits that form from the interaction of wavefront collisions during paroxysmal AF. These results are compatible with recent findings suggesting that the formation of re-entrant drivers in fibrotic border zones perpetuates persistent AF.

Recently, MGME1 was identified as a mitochondrial DNA nuclease with preference for single-stranded DNA (ssDNA) substrates. Loss-of-function mutations in patients lead to mitochondrial disease with DNA depletion, deletions, duplications and rearrangements. Here, we assess the biochemical role of MGME1 in the processing of flap intermediates during mitochondrial DNA replication using reconstituted systems. We show that MGME1 can cleave flaps to enable efficient ligation of newly replicated DNA strands in combination with POLγ. MGME1 generates a pool of imprecisely cut products (short flaps, nicks and gaps) that are converted to ligatable nicks by POLγ through extension or excision of the 3'-end strand. This is dependent on the 3'-5' exonuclease activity of POLγ which limits strand displacement activity and enables POLγ to back up to the nick by 3'-5' degradation. We also demonstrate that POLγ-driven strand displacement is sufficient to generate DNA- but not RNA-flap substrates suitable for MGME1 cleavage and ligation during replication. Our findings have implications for RNA primer removal models, the 5'-end processing of nascent DNA at OriH, and DNA repair.