OBJECTIVE: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. METHODS: The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients. RESULTS: When attention was directed to heartbeat signals versus exteroception or rest tasks, FND patients showed decreased neural activations (and reduced coactivations) in the right anterior insula and bilateral dorsal anterior cingulate cortices (among other areas), compared with HCs. For FND patients, heartbeat-counting accuracy was positively correlated with right anterior insula and ventromedial prefrontal activations during interoception versus rest. Cardiac interoceptive accuracy was also correlated with bilateral dorsal anterior cingulate activations in the interoception-versus-exteroception contrast, and neural activations were correlated with ITPE scores, showing inverse relationships to those observed for heartbeat-counting accuracy. CONCLUSIONS: This study identified state and trait interoceptive disruptions in FND patients. Convergent between- and within-group findings contextualize the pathophysiological role of cingulo-insular (salience network) areas across the spectrum of functional seizures and functional movement disorder. These findings provide a starting point for the future development of comprehensive neurophysiological assessments of interoception for FND patients, features that also warrant research as potential prognostic and monitoring biomarkers.
- MeSH
- Adult MeSH
- Interoception * physiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Brain Mapping MeSH
- Young Adult MeSH
- Brain * physiopathology diagnostic imaging MeSH
- Nervous System Diseases * physiopathology diagnostic imaging MeSH
- Attention physiology MeSH
- Heart Rate physiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: The histopathological classification for antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (ANCA-GN) is a well-established tool to reflect the variety of patterns and severity of lesions that can occur in kidney biopsies. It was demonstrated previously that deep learning (DL) approaches can aid in identifying histopathological classes of kidney diseases; for example, of diabetic kidney disease. These models can potentially be used as decision support tools for kidney pathologists. Although they reach high prediction accuracies, their "black box" structure makes them nontransparent. Explainable (X) artificial intelligence (AI) techniques can be used to make the AI model decisions accessible for human experts. We have developed a DL-based model, which detects and classifies the glomerular lesions according to the Berden classification. METHODS: Kidney biopsy slides of 80 patients with ANCA-GN from 3 European centers, who underwent a diagnostic kidney biopsy between 1991 and 2011, were included. We also investigated the explainability of our model using Gradient-weighted Class Activation Mapping (Grad-CAM) heatmaps. These maps were analyzed by pathologists to compare the decision-making criteria of humans and the DL model and assess the impact of different training settings. RESULTS: The DL model shows a prediction accuracy of 93% for classifying lesions. The heatmaps from our trained DL models showed that the most predictive areas in the image correlated well with the areas deemed to be important by the pathologist. CONCLUSION: We present the first DL-based computational pipeline for classifying ANCA-GN kidney biopsies as per the Berden classification. XAI techniques helped us to make the decision-making criteria of the DL accessible for renal pathologists, potentially improving clinical decision-making.
- Publication type
- Journal Article MeSH
BACKGROUND: Since the Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II (STAR-AF II), there has been a trend toward pulmonary vein isolation (PVI)-only ablation strategies for persistent atrial fibrillation (PeAF). Electrographic flow (EGF) mapping can identify active sources of atrial fibrillation (AF) and estimate the electrographic flow consistency (EGFC) of wavefront propagation through substrate, revealing functional AF mechanisms. OBJECTIVE: We sought to examine the success of a PVI-only ablation strategy for a redo PeAF/longstanding PeAF population. METHODS: Electrographic Flow-Guided Ablation in Redo Patients With Persistent Atrial Fibrillation (FLOW-AF [NCT04473963]) prospectively enrolled patients with nonparoxysmal AF undergoing redo ablation at 4 centers. One-minute EGF recordings using 64-pole basket catheters were obtained both pre-PVI and post-PVI following a 20-minute wait and confirmation of electrical isolation of veins. Patients with EGF-identified sources were randomized 1:1 to EGF-guided source ablation vs PVI-only. Patients with no sources were not randomized and mostly received PVI only. RESULTS: Study of 85 patients enrolled 24 with EGF-identified sources randomized to PVI only and 23 with no sources receiving PVI only. Of these 47 patients, those with sources (Group 2) had different clinical characteristics including older age and higher CHA2DS2-VASc scores compared with those with no sources (Group 1). After PVI only, Group 1 had 70% (16 of 23) freedom from recurrent AF (FFAF) within 1 year vs Group 2 with 35% (8 of 23), P = .018. In addition, patients with high electrographic flow consistency (EGFC) indicative of healthy or normal substrate had 67% (10 of 15) FFAF vs 45% (14 of 31) in those with low EGFC suggestive of abnormal substrate, P = .011. CONCLUSION: Success rates in no-sources patients receiving PVI only are better than in those with sources randomized to PVI only. For the clinically heterogenous population of patients with PeAF, the presence of EGF-identified sources matters clinically, and PVI only will not be enough for all patients.
- MeSH
- Atrial Fibrillation * surgery physiopathology diagnosis MeSH
- Catheter Ablation * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Heart Conduction System * physiopathology surgery MeSH
- Prospective Studies MeSH
- Aged MeSH
- Pulmonary Veins * surgery physiopathology MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
This study was aimed to analyse the lower limb kinematics during the change of direction (COD) performance with the dominant (DL) and non-dominant (NDL) leg using linear (traditional kinematics) and nonlinear (Self Organising Map-based cluster analysis) approaches. Three 5-0-5 COD performances with the DL and three with the NDL were performed by 23 (aged 21.6 ± 2.3 years) collegiate athletes. No significant difference was observed between the COD duration, and approach speed of DL and NDL. Significantly greater ankle abductions, knee and hip external rotations were identified in COD with DL, compared to NDL (p < .001, d > 0.8). Self Organising Maps portrayed a completely different coordination pattern profile during change of direction performance with the DL and NDL. The cluster analysis illustrated similar inter-individual coordination patterning when participants turned with their DL or NDL. No visible relationship was observed in the cluster analysis of the lower limb joint angles and angular velocities. Outcomes of this study portrayed that coordination patterning (combination of joint angles and the rate of change of angles) could portray the movement patterning differences in different tasks, while a sole investigation on the joint angles or angular velocities may not reveal the underlying mechanisms of movement patterning.
- MeSH
- Leg * physiology MeSH
- Biomechanical Phenomena MeSH
- Lower Extremity * physiology MeSH
- Functional Laterality * physiology MeSH
- Ankle physiology MeSH
- Humans MeSH
- Young Adult MeSH
- Motor Skills * physiology MeSH
- Nonlinear Dynamics MeSH
- Movement physiology MeSH
- Cluster Analysis MeSH
- Athletic Performance * physiology MeSH
- Check Tag
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Ice hockey is a dynamic game. We can observe collisions between the players that bring a risk of injury. There are many hockey clubs in the Czech Republic. These clubs raise great hockey players and many competing players in various levels of national leagues. The aim of this study was to map injuries in Czech hockey players and outline the situation of injury prevention and body care in ice hockey players. METHODS: We used a questionnaire survey method to obtain data. We received answers from 100 male active Czech ice hockey players, playing in the top three highest men's competitions (Extraleague - 2nd league). Individual injuries were analyzed according to specific body parts, injury type, playing position, level of competition using basic statistical characteristics and relative frequency analyses, including the recovery time, injury reason and the injury statistics per 1000 sporting performances in ice hockey. RESULTS: We found that 81% of participants suffered injuries with the overall incidence of injuries was 17.1 per 1000 sports performances and mainly happened during the match compared to training. The most common injuries were in the head and neck area (25%), often caused by a collision with another player, a stick or puck hit, or a collision with a board. Other frequently injured parts were the knees (21%), where internal ligament injuries predominate, and the shoulders (20%), where we recorded mainly ligament injuries. CONCLUSIONS: There is a high risk of various injury types of ice hockey players, that are developed accidentally in all body parts mostly in the match (mostly upper part of the body and knee) or by overloading (hip/groin area). We recommend strategies to avoid or minimize the injury risk of players. The hockey clubs, coaches, and players should extensively and regularly cooperate with physiotherapists, starting from the younger age of hockey groups, to prevent injuries and use regular strengthening of crucial muscle parts, regeneration, and compensatory exercises. We endorse adequately evaluating dangerous foul actions for referees and disciplinary officials also in minor competitions.
- MeSH
- Adult MeSH
- Hockey * injuries MeSH
- Incidence MeSH
- Humans MeSH
- Young Adult MeSH
- Surveys and Questionnaires MeSH
- Athletic Injuries * epidemiology prevention & control MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
AIMS: Among patients with cardiogenic shock, immediate initiation of extracorporeal membrane oxygenation (ECMO) did not demonstrate any benefit at 30 days. The present study evaluated 1-year clinical outcomes of the Extracorporeal Membrane Oxygenation in the therapy of Cardiogenic Shock (ECMO-CS) trial. METHODS AND RESULTS: The ECMO-CS trial randomized 117 patients with severe or rapidly progressing cardiogenic shock to immediate initiation of ECMO or early conservative strategy. The primary endpoint for this analysis was 1-year all-cause mortality. Secondary endpoints included a composite of death, resuscitated cardiac arrest or implantation of another mechanical circulatory support device, duration of mechanical ventilation, and the length of intensive care unit (ICU) and hospital stays. In addition, an unplanned post-hoc subgroup analysis was performed. At 1 year, all-cause death occurred in 40 of 58 (69.0%) patients in the ECMO arm and in 40 of 59 (67.8%) in the early conservative arm (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.66-1.58; p = 0.93). The composite endpoint occurred in 43 (74.1%) patients in the ECMO group and in 47 (79.7%) patients in the early conservative group (HR 0.83, 95% CI 0.55-1.25; p = 0.29). The durations of mechanical ventilation, ICU stay and hospital stay were comparable between groups. Significant interaction with treatment strategy and 1-year mortality was observed in subgroups according to baseline mean arterial pressure (MAP) indicating lower mortality in the subgroup with low baseline MAP (<63 mmHg: HR 0.58, 95% CI 0.29-1.16; pinteraction = 0.017). CONCLUSIONS: Among patients with severe or rapidly progressing cardiogenic shock, immediate initiation of ECMO did not improve clinical outcomes at 1 year compared to the early conservative strategy. However, immediate ECMO initiation might be beneficial in patients with advanced haemodynamic compromise.
- MeSH
- Time Factors MeSH
- Intensive Care Units MeSH
- Shock, Cardiogenic * therapy mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Extracorporeal Membrane Oxygenation * methods MeSH
- Survival Rate trends MeSH
- Aged MeSH
- Respiration, Artificial methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
BACKGROUND AND PURPOSE: Cognitive impairment (CI) in multiple sclerosis (MS) is associated with bidirectional changes in resting-state centrality measures. However, practicable functional magnetic resonance imaging (fMRI) biomarkers of CI are still lacking. The aim of this study was to assess the graph-theory-based degree rank order disruption index (kD) and its association with cognitive processing speed as a marker of CI in patients with MS (PwMS) in a secondary cross-sectional fMRI analysis. METHODS: Differentiation between PwMS and healthy controls (HCs) using kD and its correlation with CI (Symbol Digit Modalities Test) was compared to established imaging biomarkers (regional degree, volumetry, diffusion-weighted imaging, lesion mapping). Additional associations were assessed for fatigue (Fatigue Scale for Motor and Cognitive Functions), gait and global disability. RESULTS: Analysis in 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years) showed lower kD in PwMS than in HCs (median -0.30/-0.06, interquartile range 0.55/0.54; p = 0.009, Mann-Whitney U test), yielding acceptable yet non-superior differentiation (area under curve 0.64). kD and degree in medial prefrontal cortex (MPFC) correlated with CI (kD/MPFC Spearman's ρ = 0.32/-0.45, p = 0.019/0.001, n = 55). kD also explained fatigue (ρ = -0.34, p = 0.010, n = 56) but neither gait nor disability. CONCLUSIONS: kD is a potential biomarker of CI and fatigue warranting further validation.
- MeSH
- Adult MeSH
- Cognitive Dysfunction etiology physiopathology diagnostic imaging MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Cross-Sectional Studies MeSH
- Multiple Sclerosis * complications diagnostic imaging physiopathology MeSH
- Processing Speed MeSH
- Fatigue * physiopathology etiology diagnostic imaging MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: In patients resuscitated after cardiac arrest, a higher mean arterial pressure (MAP) may increase cerebral perfusion and attenuate hypoxic brain injury. Here we present the protocol of the mean arterial pressure after cardiac arrest and resuscitation (MAP-CARE) trial aiming to investigate the influence of MAP targets on patient outcomes. METHODS: MAP-CARE is one component of the Sedation, Temperature and Pressure after Cardiac Arrest and Resuscitation (STEPCARE) 2 x 2 x 2 factorial randomized trial. The MAP-CARE trial is an international, multicenter, parallel-group, investigator-initiated, superiority trial designed to test the hypothesis that targeting a higher (>85 mmHg) (intervention) versus a lower (>65 mmHg) (comparator) MAP after resuscitation from cardiac arrest reduces 6-month mortality (primary outcome). Trial participants are adults with sustained return of spontaneous circulation who are comatose following resuscitation from out-of-hospital cardiac arrest. The two other components of the STEPCARE trial evaluate sedation and temperature control strategies. Apart from the STEPCARE trial interventions, all other aspects of general intensive care will be according to the local practices of the participating site. Neurological prognostication will be performed according to European Resuscitation Council and European Society of Intensive Care Medicine guidelines by a physician blinded to allocation group. The sample size of 3500 participants provides 90% power with an alpha of 0.05 to detect a 5.6 absolute risk reduction in 6-month mortality, assuming a mortality of 60% in the control group. Secondary outcomes will be poor functional outcome 6 months after randomization, patient-reported overall health 6 months after randomization, and the proportion of participants with predefined severe adverse events. CONCLUSION: The MAP-CARE trial will investigate if targeting a higher MAP compared to a lower MAP during intensive care of adults who are comatose following resuscitation from out-of-hospital cardiac arrest reduces 6-month mortality.
- MeSH
- Arterial Pressure * physiology MeSH
- Adult MeSH
- Equivalence Trials as Topic MeSH
- Cardiopulmonary Resuscitation * methods MeSH
- Coma etiology MeSH
- Humans MeSH
- Multicenter Studies as Topic MeSH
- Randomized Controlled Trials as Topic MeSH
- Resuscitation * MeSH
- Heart Arrest * therapy physiopathology mortality MeSH
- Treatment Outcome MeSH
- Out-of-Hospital Cardiac Arrest * therapy physiopathology mortality MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial Protocol MeSH
One of the main challenges in analyzing chemical messengers in the brain is the optimization of tissue sampling and preparation protocols. Limiting postmortem time and terminating enzyme activity is critical to identify low-abundance neurotransmitters and neuropeptides. Here, we used a rapid and uniform conductive heat transfer stabilization method that was compared with a conventional fresh freezing protocol. Together with a selective chemical derivatization method and an optimized quantitation approach using deuterated internal standards, we spatially mapped neurotransmitters and their related metabolites by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in rat brain tissue sections. Although the heat stabilization did not show differences in the levels of dopamine, norepinephrine, and serotonin, their related metabolites 3,4-dihydroxyphenylacetaldehyde, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylacetaldehyde, dihydroxyphenylethyleneglycol, and 5-hydroxyindoleacetic acid were all significantly lower, indicating reduced neurotransmitter postmortem turnover ratios. Heat stabilization enabled detection of an increased number and higher levels of prodynorphin, proenkephalin, and tachykinin-derived bioactive neuropeptides. The low-abundant C-terminal flanking peptide, neuropeptide-γ, and nociceptin remained intact and were exclusively imaged in heat-stabilized brains. Without heat stabilization, degradation fragments of full-length peptides occurred in the fresh frozen tissues. The sample preparation protocols were furthermore tested on rat brains affected by acute anesthesia induced by isoflurane and medetomidine, showing comparable results to non-anesthetized animals on the neurotransmitters level without significant changes. Our data provide evidence for the potential use of heat stabilization prior to MALDI-MSI analyses to improve the examination of the in vivo state of neuronal chemical messengers in brain tissues not impacted by prior acute anesthesia.
- MeSH
- Rats MeSH
- Brain Chemistry * physiology MeSH
- Brain * metabolism MeSH
- Neurons * metabolism chemistry MeSH
- Neurotransmitter Agents * metabolism analysis MeSH
- Rats, Sprague-Dawley MeSH
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization * methods MeSH
- Hot Temperature * MeSH
- Freezing MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The study evaluates the efficacy of RETROICOR (Retrospective Image Correction) in mitigating physiological artifacts within multi-echo (ME) fMRI data. Two RETROICOR implementations were compared: applying corrections to individual echoes (RTC_ind) versus composite multi-echo data (RTC_comp). Data from 50 healthy participants were collected using diverse acquisition parameters, including multiband acceleration factors and varying flip angles, on a Siemens Prisma 3T scanner. Key metrics such as temporal signal-to-noise ratio (tSNR), signal fluctuation sensitivity (SFS), and variance of residuals demonstrated improved data quality in both RETROICOR models, particularly in moderately accelerated runs (multiband factors 4 and 6) with lower flip angles (45°). Differences between RTC_ind and RTC_comp were minimal, suggesting both methods are viable for practical applications. While the highest acceleration (multiband factor 8) degraded data quality, RETROICOR's compatibility with faster acquisition sequences was confirmed. These findings underscore the importance of optimizing acquisition parameters and noise correction techniques for reliable fMRI investigations.
- MeSH
- Artifacts * MeSH
- Adult MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Brain Mapping * methods MeSH
- Young Adult MeSH
- Brain * diagnostic imaging physiology MeSH
- Image Processing, Computer-Assisted * methods MeSH
- Signal-To-Noise Ratio MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH