Systematic in-silico evaluation of fibrosis effects on re-entrant wave dynamics in atrial tissue.

Despite the key role of fibrosis in atrial fibrillation (AF), the effects of different spatial distributions and textures of fibrosis on wave propagation mechanisms in AF are not fully understood. To clarify these aspects, we performed a systematic computational study to assess fibrosis effects on the characteristics and stability of re-entrant waves in electrically-remodelled atrial tissues. A stochastic algorithm, which generated fibrotic distributions with controlled overall amount, average size, and orientation of fibrosis elements, was implemented on a monolayer spheric atrial model. 245 simulations were run at changing fibrosis parameters. The emerging propagation patterns were quantified in terms of rate, regularity, and coupling by frequency-domain analysis of correspondent synthetic bipolar electrograms. At the increase of fibrosis amount, the rate of reentrant waves significantly decreased and higher levels of regularity and coupling were observed (p < 0.0001). Higher spatial variability and pattern stochasticity over repetitions was observed for larger amount of fibrosis, especially in the presence of patchy and compact fibrosis. Overall, propagation slowing and organization led to higher stability of re-entrant waves. These results strengthen the evidence that the amount and spatial distribution of fibrosis concur in dictating re-entry dynamics in remodeled tissue and represent key factors in AF maintenance.

Auditory function in humans at high altitude. A scoping review.

PURPOSE: High-altitude (HA) affects sensory organ response, but its effects on the inner ear are not fully understood. The present scoping review aimed to collect the available evidence about HA effects on the inner ear with focus on auditory function. METHODS: The scoping review was conducted following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for scoping reviews. PubMed, Scopus, and Web of Science electronic databases were systematically searched to identify studies conducted in the last 20 years, which quantified in healthy subjects the effects of HA on auditory function. RESULTS: The systematic search identified 17 studies on a total population of 888 subjects (88.7% male, age: 27.8 ± 4.1 years; median sample size of 15 subjects). Nine studies were conducted in a simulated environment and eight during real expeditions at HA. To quantify auditory function, six studies performed pure tone audiometry, four studies measured otoacoustic emissions (OAE) and eight studies measured auditory evoked responses (AER). Study protocols presented heterogeneity in the spatio-temporal patterns of HA exposure, with highly varying maximal altitudes and exposure durations. CONCLUSION: Most studies reported a reduction of auditory function with HA in terms of either elevation of auditory thresholds, lengthening of AER latencies, reduction of distortion-product and transient-evoked OAEs. Future studies in larger populations, using standardized protocols and multi-technique auditory function evaluation, are needed to further characterize the spatio-temporal pattern of HA effects along the auditory pathways and clarify the pathophysiological implications and reversibility of the observed changes.

Personal Protective Equipment Protocols Lead to a Delayed Initiation of Patient Assessment in Mountain Rescue Operations.

van Veelen, Michiel J., Giulia Roveri, Ivo B. Regli, Tomas Dal Cappello, Anna Vögele, Michela Masè, Marika Falla, and Giacomo Strapazzon. Personal protective equipment protocols lead to a delayed initiation of patient assessment in mountain rescue operations. High Alt Med Biol. 24:127-131, 2023. Introduction: Mountain rescue operations can be challenging in austere environmental conditions and remote settings. Airborne infection prevention measures include donning of personal protective equipment (PPE), potentially delaying the approach to a patient. We aimed to investigate the time delay caused by these prevention measures. Methods: This randomized crossover trial consisted of 24 rescue simulation trials intended to be as realistic as possible, performed by mountain rescue teams in difficult terrain. We analyzed the time needed to perform an airborne infection prevention protocol during the approach to a patient. Time delays in scenarios involving patients already wearing versus not wearing face masks and gloves were compared using a linear mixed model Results: The airborne infection prevention measures (i.e., screening questionnaire, hand antisepsis, and donning of PPE) resulted in a time delay of 98 ± 48 (26-214) seconds on initiation of patient assessment. There was a trend to a shorter time to perform infection prevention measures if the simulated patient was already wearing PPE consisting of face mask and gloves (p = 0.052). Conclusion: Airborne infection prevention measures may delay initiation of patient assessment in mountain rescue operations and could impair clinical outcomes in time-sensitive conditions. Trial registration number 0105095-BZ Ethics Committee review board of Bolzano.

Drones reduce the treatment-free interval in search and rescue operations with telemedical support - A randomized controlled trial.

INTRODUCTION: Response to medical incidents in mountainous areas is delayed due to the remote and challenging terrain. Drones could assist in a quicker search for patients and can facilitate earlier treatment through delivery of medical equipment. We aim to assess the effects of using drones in search and rescue (SAR) operations in challenging terrain. We hypothesize that drones can reduce the search time and treatment-free interval of patients by delivering an emergency kit and telemedical support. METHODS: In this randomized controlled trial with a cross-over design two methods of searching for and initiating treatment of a patient were compared. The primary outcome was a comparison of the times for locating a patient through visual contact and starting treatment on-site between the drone-assisted intervention arm and the conventional ground-rescue control arm. A linear mixed model (LMM) was used to evaluate the effect of using a drone on search and start of treatment times. RESULTS: Twenty-four SAR missions, performed by six SAR teams each with four team members, were analyzed. The mean time to locate the patient was 14.6 min (95% CI 11.3-17.9) in the drone-assisted intervention arm and 20.6 min (95% CI 17.3-23.9) in the control arm. The mean time to start treatment was 15.7 min (95% CI 12.4-19.0) in the drone-assisted arm and 22.4 min (95% CI 19.1-25.7) in the control arm (p < 0.01 for both comparisons). CONCLUSION: The successful use of drones in SAR operations leads to a reduction in search time and treatment-free interval of patients in challenging terrain, which could improve outcomes in patients suffering from traumatic injuries, the most commonly occurring incident requiring mountain rescue operations.

Quantitative assessment of transmural fibrosis profile in the human atrium: evidence for a three-dimensional arrhythmic substrate by slice-to-slice histology.

AIMS: Intramural fibrosis represents a crucial factor in the formation of a three-dimensional (3D) substrate for atrial fibrillation (AF). However, the transmural distribution of fibrosis and its relationship with atrial overload remain largely unknown. The aim of this study is to quantify the transmural profile of atrial fibrosis in patients with different degrees of atrial dilatation and arrhythmic profiles by a high-resolution 3D histology method. METHODS AND RESULTS: Serial microtome-cut tissue slices, sampling the entire atrial wall thickness at 5 µm spatial resolution, were obtained from right atrial appendage specimens in 23 cardiac surgery patients. Atrial slices were picrosirius red stained, imaged by polarized light microscopy, and analysed by a custom-made segmentation algorithm. In all patients, the intramural fibrosis content displayed a progressive decrease alongside tissue depth, passing from 68.6 ± 11.6% in the subepicardium to 10-13% in the subendocardium. Distinct transmural fibrotic profiles were observed in patients with atrial dilatation with respect to control patients, where the first showed a slower decrease of fibrosis along tissue depth (exponential decay constant: 171.2 ± 54.5 vs. 80.9 ± 24.4 µm, P < 0.005). Similar slow fibrotic profiles were observed in patients with AF (142.8 ± 41.7 µm). Subepicardial and midwall levels of fibrosis correlated with the degree of atrial dilatation (ρ = 0.72, P < 0.001), while no correlation was found in subendocardial layers. CONCLUSIONS: Quantification of fibrosis transmural profile at high resolution is feasible by slice-to-slice histology. Deeper penetration of fibrosis in subepicardial and midwall layers in dilated atria may concur to the formation of a 3D arrhythmic substrate.

Low Ambient Temperature Exposition Impairs the Accuracy of a Non-invasive Heat-Flux Thermometer.

Background: Indirect core body temperature (CBT) monitoring from skin sensors is gaining attention for in-field applications thanks to non-invasivity, portability, and easy probe positioning. Among skin sensors, heat-flux devices, such as the so-called Double Sensor (DS), have demonstrated reliability under various experimental and clinical conditions. Still, their accuracy at low ambient temperatures is unknown. In this randomized cross-over trial, we tested the effects of cold temperature exposition on DS performance in tracking CBT. Methods: Twenty-one participants were exposed to a warm (23.2 ± 0.4°C) and cold (-18.7 ± 1.0°C) room condition for 10 min, following a randomized cross-over design. The accuracy of the DS to estimate CBT in both settings was assessed by quantitative comparison with esophageal (reference) and tympanic (comparator) thermometers, using Bland-Altman and correlation analyses (Pearson's correlation coefficient, r, and Lin's concordance correlation coefficient, CCC). Results: In the warm room setting, the DS showed a moderate agreement with the esophageal sensor [bias = 0.09 (-1.51; 1.69) °C, r = 0.40 (p = 0.069), CCC = 0.22 (-0.006; 0.43)] and tympanic sensor [bias = 2.74 (1.13; 4.35) °C, r = 0.54 (p < 0.05), CCC = 0.09 (0.008; 0.16)]. DS accuracy significantly deteriorated in the cold room setting, where DS temperature overestimated esophageal temperature [bias = 2.16 (-0.89; 5.22) °C, r = 0.02 (0.94), CCC = 0.002 (-0.05; 0.06)]. Previous exposition to the cold influenced temperature values measured by the DS in the warm room setting, where significant differences (p < 0.00001) in DS temperature were observed between randomization groups. Conclusion: DS accuracy is influenced by environmental conditions and previous exposure to cold settings. These results suggest the present inadequacy of the DS device for in-field applications in low-temperature environments and advocate further technological advancements and proper sensor insulation to improve performance in these conditions.

Insight into the use of tympanic temperature during target temperature management in emergency and critical care: a scoping review.

BACKGROUND: Target temperature management (TTM) is suggested to reduce brain damage in the presence of global or local ischemia. Prompt TTM application may help to improve outcomes, but it is often hindered by technical problems, mainly related to the portability of cooling devices and temperature monitoring systems. Tympanic temperature (TTy) measurement may represent a practical, non-invasive approach for core temperature monitoring in emergency settings, but its accuracy under different TTM protocols is poorly characterized. The present scoping review aimed to collect the available evidence about TTy monitoring in TTM to describe the technique diffusion in various TTM contexts and its accuracy in comparison with other body sites under different cooling protocols and clinical conditions. METHODS: The scoping review was conducted following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for scoping reviews (PRISMA-ScR). PubMed, Scopus, and Web of Science electronic databases were systematically searched to identify studies conducted in the last 20 years, where TTy was measured in TTM context with specific focus on pre-hospital or in-hospital emergency settings. RESULTS: The systematic search identified 35 studies, 12 performing TTy measurements during TTM in healthy subjects, 17 in patients with acute cardiovascular events, and 6 in patients with acute neurological diseases. The studies showed that TTy was able to track temperature changes induced by either local or whole-body cooling approaches in both pre-hospital and in-hospital settings. Direct comparisons to other core temperature measurements from other body sites were available in 22 studies, which showed a faster and larger change of TTy upon TTM compared to other core temperature measurements. Direct brain temperature measurements were available only in 3 studies and showed a good correlation between TTy and brain temperature, although TTy displayed a tendency to overestimate cooling effects compared to brain temperature. CONCLUSIONS: TTy was capable to track temperature changes under a variety of TTM protocols and clinical conditions in both pre-hospital and in-hospital settings. Due to the heterogeneity and paucity of comparative temperature data, future studies are needed to fully elucidate the advantages of TTy in emergency settings and its capability to track brain temperature.

A Divergence-Based Approach for the Identification of Atrial Fibrillation Focal Drivers From Multipolar Mapping: A Computational Study.

The expanding role of catheter ablation of atrial fibrillation (AF) has stimulated the development of novel mapping strategies to guide the procedure. We introduce a novel approach to characterize wave propagation and identify AF focal drivers from multipolar mapping data. The method reconstructs continuous activation patterns in the mapping area by a radial basis function (RBF) interpolation of multisite activation time series. Velocity vector fields are analytically determined, and the vector field divergence is used as a marker of focal drivers. The method was validated in a tissue patch cellular automaton model and in an anatomically realistic left atrial (LA) model with Courtemanche-Ramirez-Nattel ionic dynamics. Divergence analysis was effective in identifying focal drivers in a complex simulated AF pattern. Localization was reliable even with consistent reduction (47%) in the number of mapping points and in the presence of activation time misdetections (noise <10% of the cycle length). Proof-of-concept application of the method to human AF mapping data showed that divergence analysis consistently detected focal activation in the pulmonary veins and LA appendage area. These results suggest the potential of divergence analysis in combination with multipolar mapping to identify AF critical sites. Further studies on large clinical datasets may help to assess the clinical feasibility and benefit of divergence analysis for the optimization of ablation treatment.

MicroRNAs: New contributors to mechano-electric coupling and atrial fibrillation.

Atrial fibrillation (AF) is a multifactorial disease, which often occurs in the presence of underlying cardiac abnormalities and is supported by electrophysiological and structural alterations, generally referred to as atrial remodeling. Abnormal substrates are commonly encountered in various conditions that predispose to AF, such as hypertension, heart failure, obesity, and sleep apnea, in which atrial stretch plays a key mechanistic role. Emerging evidence suggests a role for microRNAs (small non-coding RNAs) in the pathogenesis of AF, where they can act as post-transcriptional regulators of the genes involved in atrial remodeling. This review summarizes the experimental and clinical evidence that supports the role of microRNAs in the modulation of atrial electrical and structural remodeling with a focus on overload-induced atrial alterations, and discusses the potential contribution of microRNAs to mechano-electrical coupling and AF.

Unsupervised Classification of Atrial Electrograms for Electroanatomic Mapping of Human Persistent Atrial Fibrillation.

OBJECTIVE: Ablation treatment for persistent atrial fibrillation (persAF) remains challenging due to the absence of a 'ground truth' for atrial substrate characterization and the presence of multiple mechanisms driving the arrhythmia. We implemented an unsupervised classification to identify clusters of atrial electrograms (AEGs) with similar patterns, which were then validated by AEG-derived markers. METHODS: 956 bipolar AEGs were collected from 11 persAF patients. CARTO variables (Biosense Webster; ICL, ACI and SCI) were used to create a 3D space, and subsequently used to perform an unsupervised classification with k-means. The characteristics of the identified groups were investigated using nine AEG-derived markers: sample entropy (SampEn), dominant frequency, organization index (OI), determinism, laminarity, recurrence rate (RR), peak-to-peak (PP) amplitude, cycle length (CL), and wave similarity (WS). RESULTS: Five AEG classes with distinct characteristics were identified (F = 582, P<0.0001). The presence of fractionation increased from class 1 to 5, as reflected by the nine markers. Class 1 (25%) included organized AEGs with high WS, determinism, laminarity, and RR, and low SampEn. Class 5 (20%) comprised fractionated AEGs with in low WS, OI, determinism, laminarity, and RR, and in high SampEn. Classes 2 (12%), 3 (13%) and 4 (30%) suggested different degrees of AEG organization. CONCLUSIONS: Our results expand and reinterpret the criteria used for automated AEG classification. The nine markers highlighted electrophysiological differences among the five classes found by the k-means, which could provide a more complete characterization of persAF substrate during ablation target identification in future clinical studies.

Hearables: New Perspectives and Pitfalls of In-Ear Devices for Physiological Monitoring. A Scoping Review.

Technological advancements are opening the possibility of prolonged monitoring of physiological parameters under daily-life conditions, with potential applications in sport science and medicine, and in extreme environments. Among emerging wearable technologies, in-ear devices or hearables possess technical advantages for long-term monitoring, such as non-invasivity, unobtrusivity, good fixing, and reduced motion artifacts, as well as physiological advantages related to the proximity of the ear to the body trunk and the shared vasculature between the ear and the brain. The present scoping review was aimed at identifying and synthesizing the available evidence on the use and performance of in-ear monitoring of physiological parameters, with focus on applications in sport science, sport medicine, occupational medicine, and extreme environment settings. Pubmed, Scopus, and Web of Science electronic databases were systematically searched to identify studies conducted in the last 10 years and addressing the measurement of three main physiological parameters (temperature, heart rate, and oxygen saturation) in healthy subjects. Thirty-nine studies were identified, 24 performing temperature measurement, 12 studies on heart/pulse rate, and three studies on oxygen saturation. The collected evidence supports the premise of in-ear sensors as an innovative and unobtrusive way for physiological monitoring during daily-life and physical activity, but further research and technological advancement are necessary to ameliorate measurement accuracy especially in more challenging scenarios.

Morphological MRI of knee cartilage: repeatability and reproducibility of damage evaluation and correlation with gross pathology examination.

OBJECTIVE: To assess the performance of a morphological evaluation, based on a clinically relevant magnetic resonance imaging (MRI) protocol, in scoring the severity of knee cartilage damage. Specifically, to evaluate the reproducibility, repeatability, and agreement of MRI evaluation with the gross pathology examination (GPE) of the tissue. METHODS: MRI of the knee was performed the day before surgery in 23 patients undergoing total knee arthroplasty. Osteochondral tissue resections were collected and chondral defects were scored by GPE according to a semi-quantitative scale. MR images were independently scored by four radiologists, who assessed the severity of chondral damage according to equivalent criteria. Inter- and intra-rater agreements of MRI evaluations were assessed. Correlation, precision, and accuracy metrics between MRI and GPE scores were calculated. RESULTS: Moderate to substantial inter-rater agreement in scoring cartilage damage by MRI was found among radiologists. Intra-rater agreement was higher than 96%. A significant positive monotonic correlation between GPE and MRI scores was observed for all radiologists, although higher correlation values were obtained by radiologists with expertise in musculoskeletal radiology and/or longer experience. The accuracy of MRI scores displayed a spatial pattern, characterized by lesion overestimation in the lateral condyle and underestimation in the medial condyle with respect to GPE. CONCLUSIONS: Evaluation of knee cartilage morphology by MRI is a reproducible and repeatable technique, which positively correlates with GPE. Clinical expertise in musculoskeletal radiology positively impacts the evaluation reliability. These findings may help to address limitations in MRI evaluation of knee chondral lesions, thus improving MRI assessment of knee cartilage. KEY POINTS: • MRI evaluation of knee cartilage shows moderate to strong correlation with gross pathology examination. • MRI evaluation overestimates cartilage damage in the lateral condyle and underestimates it in the medial condyle. • Education and experience of the radiologist play a role in MRI evaluation of knee chondral lesions.

Monitoring Steam Penetration in Channeled Instruments: An Evidence-Based Worst-Case for Practical Situations.

Steam sterilization of channeled medical devices requires steam penetration into narrow channels. However, a quantitative characterization of this phenomenon in practical situations is lacking. This study evaluates the effect of load, loading pattern, and wrapping system on steam penetration into channels. We tested the hypothesis that a 70 cm tube with one closed end could be representative of the worst case for steam penetration in wrapped channeled instruments in practical conditions. A validated sterilization process was run in a sterilizer equipped with infrared sensors for the measurement of water vapor fraction (WVF). WVF values collected at the closed end of an unwrapped 70 cm reference tube were compared to those obtained at the closed end of wrapped 50 cm test tubes, representative for channeled devices in the clinical practice. The open ends of the test tubes were placed inside packs, testing the effects of different combinations of wrappings, load amounts, and pack positions. The worst case for steam penetration was experimentally defined as the condition showing the lowest WVF value during the exposure phase. WVF values at the closed end of 50 cm long tubes were affected by load amount, wrapping, and pack position. Steam penetration was higher for heavier loads in rigid containers, but lower for heavier loads in soft wrappings (pouch, non-woven fabric, and crepe). In all the tested combinations of load/wrappings related to the clinical practice the 70 cm reference tube displayed lower WVF values than the wrapped 50 cm test tubes, indicating worse steam penetration in the reference than test tubes. Our findings provide experimental evidence that a 70 cm is the worst case in all practical combinations of load and wrapping encountered in the field. The 70 cm tube is a representative for a wrapped 50 cm channel with one end closed and for a wrapped 100 cm channel with both ends open. A measuring system integrating the WVF sensor on a 70 cm tube may provide a physics-based, quantitative steam penetration test for real-time monitoring of the steam sterilization process of channeled instruments.