Exploring protocol development: Implementing systematic contextual memory to enhance real-time fMRI neurofeedback.

Objective: The goal of this study was to explore the development and implementation of a protocol for real-time fMRI neurofeedback (rtfMRI-nf) and to assess the potential for enhancing the selective brain activation using stimuli from Virtual Reality (VR). In this study we focused on two specific brain regions, supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). Publications by other study groups have suggested impaired function in these specific brain regions in patients with the diagnoses Attention Deficit Hyperactivity Disorder (ADHD) and Tourette's Syndrome (TS). This study explored the development of a protocol to investigate if attention and contextual memory may be used to systematically strengthen the procedure of rtfMRI-nf. Methods: We used open-science software and platforms for rtfMRI-nf and for developing a simulated repetition of the rtfMRI-nf brain training in VR. We conducted seven exploratory tests in which we updated the protocol at each step. During rtfMRI-nf, MRI images are analyzed live while a person is undergoing an MRI scan, and the results are simultaneously shown to the person in the MRI-scanner. By focusing the analysis on specific regions of the brain, this procedure can be used to help the person strengthen conscious control of these regions. The VR simulation of the same experience involved a walk through the hospital toward the MRI scanner where the training sessions were conducted, as well as a subsequent simulated repetition of the MRI training. The VR simulation was a 2D projection of the experience.The seven exploratory tests involved 19 volunteers. Through this exploration, methods for aiming within the brain (e.g. masks/algorithms for coordinate-system control) and calculations for the analyses (e.g. calculations based on connectivity versus activity) were updated by the project team throughout the project. The final procedure involved three initial rounds of rtfMRI-nf for learning brain strategies. Then, the volunteers were provided with VR headsets and given instructions for one week of use. Afterward, a new session with three rounds of rtfMRI-nf was conducted. Results: Through our exploration of the indirect effect parameters - brain region activity (directed oxygenated blood flow), connectivity (degree of correlated activity in different regions), and neurofeedback score - the volunteers tended to increase activity in the reinforced brain regions through our seven tests. Updates of procedures and analyses were always conducted between pilots, and never within. The VR simulated repetition was tested in pilot 7, but the role of the VR contribution in this setting is unclear due to underpowered testing. Conclusion: This proof-of-concept protocol implies how rtfMRI-nf may be used to selectively train two brain regions (SMA and rIFG). The method may likely be adapted to train any given region in the brain, but readers are advised to update and adapt the procedure to experimental needs.

Ascending with ultrasound: telementored eFAST in flight-a feasibility study.

PURPOSE: Teleultrasound uses telecommunication technologies to transmit ultrasound images from a remote location to an expert who guides the acquisition of images and interprets them in real time. Multiple studies have demonstrated the feasibility of teleultrasound. However, its application during helicopter flight using long-term evolution (LTE) for streaming has not been studied. Therefore, we conducted a study to examine the feasibility of teleultrasound in an Airbus H145 helicopter. METHODS: Four anesthesiologists and one military physician were recruited to perform telementored extended Focused Assessment with Sonography in Trauma (eFAST) during nine helicopter flights, each with a unique healthy volunteer. A radiologist was recruited as a remote expert, guiding the physicians in their examinations. The examining physicians reported the user experience of telementored eFAST on a questionnaire, while the remote expert rated the diagnostic quality of the images on a 1-5 Likert scale. In addition, we measured the duration of the examinations and key LTE network parameters including signal strength, quality, and continuity. RESULTS: The images were rated to an average of 4.9 by the remote expert, corresponding to good diagnostic quality. The average duration of telementored eFAST was 05:54 min. LTE coverage was negatively affected by proximity to urban areas and ceased above 2000 ft altitude. Occasional audio problems were addressed by using the Voice over LTE network for communication. The examining physicians unanimously reported on the questionnaire that they would use telementored eFAST on patients. CONCLUSION: Telementored eFAST is feasible in ambulance helicopters and can produce images of good diagnostic quality. However, it relies on stable LTE coverage, which is influenced by many factors, including the helicopter's altitude and flight path. Furthermore, its benefit on patient outcomes remains to be proven.

An investigator-sponsored pragmatic randomized controlled trial of AntiCoagulation vs AcetylSalicylic Acid after Transcatheter Aortic Valve Implantation: Rationale and design of ACASA-TAVI.

BACKGROUND: The optimal antithrombotic therapy after transcatheter aortic valve implantation (TAVI) is unknown. Bioprosthetic valve dysfunction (BVD) is associated with adverse outcomes and may be prevented by anticoagulation therapy. A dedicated randomized trial comparing monotherapy NOAC to single antiplatelet therapy has not been performed previously. We hypothesize that therapy with any anti-factor Xa NOAC will reduce BVD compared to antiplatelet therapy, without compromising safety. METHODS: ACASA-TAVI is a multicenter, prospective, randomized, open-label, blinded endpoint, all-comers trial comparing a monotherapy anti-factor Xa NOAC strategy (intervention arm) with a single antiplatelet therapy strategy (control arm) after successful TAVI. Three-hundred and sixty patients without indication for oral anticoagulation will be randomized in a 1:1 ratio to either apixaban 5 mg twice per day, edoxaban 60 mg daily, or rivaroxaban 20 mg daily for 12 months followed by acetylsalicylic acid 75 mg daily indefinitely, or to acetylsalicylic acid 75 mg daily indefinitely. The 2 co-primary outcomes are (1) incidence of Hypo-Attenuated Leaflet Thickening (HALT) on 4-dimensional cardiac CT at 12 months, and (2) a Safety Composite of VARC-3 bleeding events, thromboembolic events (myocardial infarction and stroke), and death from any cause, at 12 months. RESULTS: The first 100 patients had a mean age of 74 ± 3.6 years, 33% were female, the average body-mass index was 27.9 ± 4.4 kg/m2, and 15% were smokers. A balloon-expanded valve was used in 82% and a self-expandable valve in 18%. CONCLUSIONS: The trial is planned, initiated, funded, and conducted without industry involvement. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05035277.

Systemic symptoms in irritable bowel syndrome: An investigative study on the role of enterocyte disintegrity, endotoxemia and inflammation.

Irritable bowel syndrome (IBS) is often accompanied by extra­intestinal symptoms, including fatigue and musculoskeletal pain. The present study aimed to investigate whether these symptoms were associated with markers of enterocyte disintegrity, endotoxemia and inflammation. Patients with IBS were recruited consecutively from our outpatient clinic (n=94) and compared with a group of healthy controls (n=20). Habitual symptoms were assessed using the IBS Severity Scoring System, the Fatigue Impact Scale and Visual Analogue Scales for measuring musculoskeletal pain. A lactulose challenge test was performed to induce post­prandial symptoms, and blood samples were obtained prior to and 90 min following lactulose ingestion to determine levels of intestinal fatty acid binding protein (iFABP), lipopolysaccharide (LPS), the LPS co­receptor soluble cluster of differentiation (sCD) 14, monocyte chemoattractant protein­1 (MCP­1) and calprotectin. Habitual symptom scores were high among the included patients, and lactulose ingestion induced significantly more symptoms in the patient group compared with the healthy control group (P=0.0001). Serum levels of iFABP were reduced in IBS patients compared with healthy controls, prior to and following lactulose ingestion (P=0.0002 and P=0.0001, respectively). Following lactulose ingestion, iFABP levels decreased in IBS patients (P=0.0001) and in healthy controls (P=0.02). Fasting levels of LPS, sCD14, MCP­1 and calprotectin were not significantly different between IBS patients and healthy controls. However, following lactulose ingestion, LPS levels increased in healthy controls (P=0.03), whereas MCP­1 levels decreased in IBS patients (P=0.008). Intestinal and extra­intestinal symptom severities were not correlated with levels of circulating biomarkers. No assessed biomarker in the present study appeared to be associated with symptom development in IBS patients. However, the implications of the low levels of iFABP observed require further investigation.

Low serum levels of short-chain fatty acids after lactulose ingestion may indicate impaired colonic fermentation in patients with irritable bowel syndrome.

BACKGROUND: Ingestion of low-digestible carbohydrates triggers symptoms in patients with irritable bowel syndrome (IBS). These carbohydrates become substrates for microbial fermentation in the colon, yielding short-chain fatty acids (SCFAs) that are readily absorbed. Aiming to compare colonic fermentation in patients with IBS and healthy controls, we analyzed the concentrations of SCFA in serum at fasting and 90 minutes following ingestion of an unabsorbable, but fermentable carbohydrate, lactulose. METHODS: Patients with IBS according to Rome III criteria (n=22) and healthy controls (n=20) ingested 10 g lactulose dissolved in water. Symptoms were graded by questionnaires and SCFA were analyzed using hollow fiber-supported liquid membrane extraction coupled with gas chromatography. RESULTS: Lactulose induced more symptoms in patients with IBS than in healthy controls (P=0.0001). Fasting serum levels of SCFA did not differ between patients with IBS and controls. However, the postprandial levels of total SCFA (P=0.0002), acetic acid (P=0.005), propionic acid (P=0.0001), and butyric acid (P=0.01) were significantly lower in patients with IBS compared with healthy controls. There was no correlation between the levels of serum SCFA and symptom severity. CONCLUSION: Low-serum levels of SCFA after lactulose ingestion may indicate impaired colonic fermentation in patients with IBS. Conceivably, this disturbance is related to symptom generation, but the mechanism is not clear.

Functional bowel symptoms, fibromyalgia and fatigue: a food-induced triad?

OBJECTIVE: Patients with perceived food hypersensitivity typically present with multiple health complaints. We aimed to assess the severity of their intestinal and extra-intestinal symptoms. MATERIALS AND METHODS: In a prospective study, 84 patients referred to our outpatient clinic for investigation of perceived food hypersensitivity were enrolled consecutively. Irritable bowel syndrome (IBS) was diagnosed according to the Rome III criteria. Severity and impact of bowel symptoms, fatigue and musculoskeletal pain were evaluated by using the following questionnaires: The IBS Severity Scoring System (IBS-SSS), the Fatigue Impact Scale (FIS), the FibroFatigue Scale (FFS), and visual analogue scales (VAS) for scoring of musculoskeletal pain. RESULTS: All but one patient were diagnosed with IBS, 58% with severe symptoms. Extra-intestinal symptoms suggestive of chronic fatigue and fibromyalgia were demonstrated in 85% and 71%, respectively. Neither IgE-mediated food allergy nor organic pathology could explain the patients' symptoms. Nevertheless, malabsorption of fat was demonstrated in 10 of 38 subjects. CONCLUSIONS: Perceived food hypersensitivity may be associated with severe, debilitating illness. The comorbid triad of IBS, chronic fatigue, and musculoskeletal pain is striking and may point to a common underlying cause.

[Treatment of pseudoaneurysms after vascular interventions]. / Behandling av pseudoaneurismer etter karintervensjoner.

BACKGROUND: Increasing numbers of patients undergoing angiographic procedures result in an increase in the total number of complications. False aneurysm may develop in 1-5% after femoral artery puncture. Until recently, ultrasound-guided compression was the preferred method of treatment, in a few cases surgery. A newer method with ultrasound-guided injection of thrombin has been shown to be effective. MATERIAL AND METHODS: Between 2000 and 2003, twenty-seven patients were diagnosed with iatrogenic false aneurysms in our hospital. The diagnosis was obtained by ultrasound when clinically suspected. Twelve patients were treated with compression technique, one with surgery, twelve with ultrasound-guided injection of thrombin, and two received no active treatment. RESULTS AND CONCLUSION: Ultrasound-guided needle injection of thrombin was a good method of treatment with a success rate of 100%, as compared to 83% with compression technique. Days in hospital stay were few and no complications were observed. Based on the good results reported in the literature and our own experience, we suggest that ultrasound-guided injection of thrombin should be the treatment of choice for femoral pseudoaneurysms.