Effect of systemic vascular resistance on the agreement between stroke volume by non-invasive pulse wave analysis and Doppler ultrasound in healthy volunteers.

BACKGROUND: Stroke volume can be estimated beat-to-beat and non-invasively by pulse wave analysis (PWA). However, its reliability has been questioned during marked alterations in systemic vascular resistance (SVR). We studied the effect of SVR on the agreement between stroke volume by PWA and Doppler ultrasound during reductions in stroke volume in healthy volunteers. METHODS: In a previous study we simultaneously measured stroke volume by PWA (SVPWA) and suprasternal Doppler ultrasound (SVUS). We exposed 16 healthy volunteers to lower body negative pressure (LBNP) to reduce stroke volume in combination with isometric hand grip to elevate SVR. LBNP was increased by 20 mmHg every 6 minutes from 0 to 80 mmHg, or until hemodynamic decompensation. The agreement between SVPWA and SVUS was examined using Bland-Altman analysis with mixed regression. Within-subject limits of agreement (LOA) was calculated from the residual standard deviation. SVRUS was calculated from SVUS. We allowed for a sloped bias line by introducing the mean of the methods and SVRUS as explanatory variables to examine whether the agreement was dependent on the magnitude of stroke volume and SVRUS. RESULTS: Bias ± limits of agreement (LOA) was 27.0 ± 30.1 mL. The within-subject LOA was ±11.1 mL. The within-subject percentage error was 14.6%. The difference between methods decreased with higher means of the methods (-0.15 mL/mL, confidence interval (CI): -0.19 to -0.11, P<0.001). The difference between methods increased with higher SVRUS (0.60 mL/mmHg × min × L-1, 95% CI: 0.48 to 0.72, P<0.001). CONCLUSION: PWA overestimated stroke volume compared to Doppler ultrasound during reductions in stroke volume and elevated SVR in healthy volunteers. The agreement between SVPWA and SVUS decreased during increases in SVR. This is relevant in settings where a high level of reliability is required.

Effect of high-intensity interval training in physiotherapy primary care for patients with inflammatory arthritis: the ExeHeart randomised controlled trial.

OBJECTIVES: To assess the effect of high-intensity interval training (HIIT) delivered in physiotherapy primary care on the primary outcome of cardiorespiratory fitness (CRF) in patients with inflammatory arthritis (IA). Additionally, to explore the effects of HIIT on secondary outcomes, including cardiovascular disease (CVD) risk factors and disease activity. METHODS: Single-blinded randomised controlled trial with 60 patients randomly assigned to either a control group receiving usual care or an exercise group receiving usual care and 12 weeks of individualised HIIT at 90%-95% peak heart rate. Outcomes were assessed at baseline, 3 months and 6 months post baseline and included CRF measured as peak oxygen uptake (VO2peak), classic CVD risk factors, disease activity, anthropometry and patient-reported physical activity, pain, fatigue, disease impact and exercise beliefs and self-efficacy. RESULTS: Intention-to-treat analysis demonstrated a significant between-group difference in VO2peak at 3 months (2.5 mL/kg/min, 95% CI 0.9 to 4.0) and 6 months (2.6 mL/kg/min, 95% CI 0.8 to 4.3) in favour of the exercise group. A beneficial change in self-reported physical activity in favour of the exercise group was observed at 3 and 6 months. The HIIT intervention was well-tolerated with minimal adverse events and no apparent impact on disease activity. Differences in secondary outcomes related to CVD risk factors, disease impact, pain, fatigue and exercise beliefs and self-efficacy were generally small and non-significant. CONCLUSION: After 12 weeks of supervised HIIT delivered in physiotherapy primary care, patients with IA demonstrated a favourable improvement in CRF, with sustained effects at 6-month follow-up. TRIAL REGISTRATION NUMBER: NCT04922840.

Hemodynamic effects of supplemental oxygen versus air in simulated blood loss in healthy volunteers: a randomized, controlled, double-blind, crossover trial.

BACKGROUND: Trauma patients frequently receive supplemental oxygen, but its hemodynamic effects in blood loss are poorly understood. We studied the effects of oxygen on the hemodynamic response and tolerance to simulated blood loss in healthy volunteers. METHODS: Fifteen healthy volunteers were exposed to simulated blood loss by lower body negative pressure (LBNP) on two separate visits at least 24 h apart. They were randomized to inhale 100% oxygen or medical air on visit 1, while inhaling the other on visit 2. To simulate progressive blood loss LBNP was increased every 3 min in levels of 10 mmHg from 0 to 80 mmHg or until hemodynamic decompensation. Oxygen and air were delivered on a reservoired face mask at 15 L/min. The effect of oxygen compared to air on the changes in cardiac output, stroke volume and middle cerebral artery blood velocity (MCAV) was examined with mixed regression to account for repeated measurements within subjects. The effect of oxygen compared to air on the tolerance to blood loss was measured as the time to hemodynamic decompensation in a shared frailty model. Cardiac output was the primary outcome variable. RESULTS: Oxygen had no statistically significant effect on the changes in cardiac output (0.031 L/min/LBNP level, 95% confidence interval (CI): - 0.015 to 0.077, P = 0.188), stroke volume (0.39 mL/LBNP level, 95% CI: - 0.39 to 1.2, P = 0.383), or MCAV (0.25 cm/s/LBNP level, 95% CI: - 0.11 to 0.61, P = 0.176). Four subjects exhibited hemodynamic decompensation when inhaling oxygen compared to 10 when inhaling air (proportional hazard ratio 0.24, 95% CI: 0.065 to 0.85, P = 0.027). CONCLUSIONS: We found no effect of oxygen compared to air on the changes in cardiac output, stroke volume or MCAV during simulated blood loss in healthy volunteers. However, oxygen had a favorable effect on the tolerance to simulated blood loss with fewer hemodynamic decompensations. Our findings suggest that supplemental oxygen does not adversely affect the hemodynamic response to simulated blood loss. Trial registration This trial was registered in ClinicalTrials.gov (NCT05150418) December 9, 2021.

Criterion Validity and Responsiveness of Estimated Cardiorespiratory Fitness Models in Patients with Inflammatory Joint Disease.

Cardiorespiratory fitness (CRF) is an excellent marker of overall health. This study aimed to assess criterion validity and responsiveness of estimated CRF models (eCRF) in patients with inflammatory joint disease (IJD). CRF was measured directly as peak oxygen uptake (VO2peak) by a Cardiopulmonary Exercise Test (CPET), while one generic eCRF model (eCRFGEN) and two disease-specific eCRF models (eCRFALT and eCRFPGA) were used to estimate CRF at baseline and after 3 months in 55 Norwegian patients with IJD. Moderate correlations were observed between eCRFGEN, eCRFALT, eCRFPGA, and VO2peak at baseline (ICC 0.60, 0.64 and 0.62, respectively) and 3 months (ICC 0.62, 0.65 and 0.57, respectively). All eCRF models overestimated measured VO2peak, and there was large variability in agreement of individual measurements at baseline and at 3 months. Weak correlations were observed for responsiveness of eCRFGEN (ICC 0.39), eCRFALT (ICC 0.40) and eCRFPGA (ICC 0.39). Mean differences between change in eCRF models and change in VO2peak were small, but the wide limits of agreement exceeded the pre-defined clinically acceptable margins. The eCRF models possessed adequate ability to detect ≥3.5 mL/kg/min improvement in VO2peak. eCRF may suffice for group-level assessment, but caution is advised when applying eCRF to individual patients with IJD.

Haemodynamic effects of methoxyflurane versus fentanyl and placebo in hypovolaemia: a randomised, double-blind crossover study in healthy volunteers.

Background: Methoxyflurane is approved for relief of moderate to severe pain in conscious adult trauma patients: it may be self-administrated and is well suited for use in austere environments. Trauma patients may sustain injuries causing occult haemorrhage compromising haemodynamic stability, and it is therefore important to elucidate whether methoxyflurane may adversely affect the haemodynamic response to hypovolaemia. Methods: In this randomised, double-blinded, placebo-controlled, three-period crossover study, inhaled methoxyflurane 3 ml, i.v. fentanyl 25 µg, and placebo were administered to 15 healthy volunteers exposed to experimental hypovolaemia in the lower body negative pressure model. The primary endpoint was the effect of treatment on changes in cardiac output, while secondary endpoints were changes in stroke volume and mean arterial pressure and time to haemodynamic decompensation during lower body negative pressure. Results: There were no statistically significant effects of treatment on the changes in cardiac output, stroke volume, or mean arterial pressure during lower body negative pressure. The time to decompensation was longer for methoxyflurane compared with fentanyl (hazard ratio 1.9; 95% confidence interval 0.4-3.4; P=0.010), whereas there was no significant difference to placebo (hazard ratio -1.3; 95% confidence interval -2.8 to 0.23; P=0.117). Conclusions: The present study does not indicate that methoxyflurane has significant adverse haemodynamic effects in conscious adults experiencing hypovolaemia. Clinical trial registration: ClinicalTrials.gov (NCT04641949) and EudraCT (2019-004144-29) https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004144-29/NO.

Eleven-Year Outcomes of a Screening Project for Abdominal Aortic Aneurysm (AAA) in 65-Year-Old Men.

Objective: Since 2011, the Department of Vascular Surgery at Oslo University Hospital has offered screening for abdominal aortic aneurysm (AAA) to 65-year-old men living in Oslo, Norway. The aim of this study was to evaluate the effect of the screening project on AAA-related mortality and rupture and repair rates in the screened population. Methods: This cohort study included men that participated in AAA screening at the Department of Vascular Surgery at Oslo University Hospital in the period May 2011 to September 2019. All men with screen-detected AAA (aortic diameter ≥30 mm) and subaneurysmal aortic dilatation (aortic diameter 25-29 mm) were included. A stratified (1:1 with the subaneurysm group), randomized selection of men with normal aortic diameter (<25 mm) upon screening was also included. The follow-up data on events (ruptures, repairs, and deaths) after screening were collected retrospectively from patient electronic medical records at Oslo University Hospital, the National Population Register and the Norwegian Cause of Death Registry (CoDR). Results: In total, 2048 men were included, with a median follow-up time of 7.1 years (IQR 3.8). Among men with screen-detected AAA, 0.6% died of AAA-related causes (0.9 AAA-related deaths per 1000 person-years). The rupture rate was 0.3% among men with screen-detected AAA or subaneurysmal aortic dilatation, giving an incidence of 0.5 ruptures per 1000 person-years. The overall repair rate in the AAA group was 20.6% (36.1 repairs per 1000 person-years) and 0.6% (0.9 repairs per 1000 person-years) in the subaneurysm group. Conclusion: In a population screened for AAA, the incidence of rupture and the AAA-related mortality was very low. Almost one-fifth of the participants with screen-detected AAA underwent elective repair, representing a group that might have presented with rupture if untreated. These results indicate that screening is valuable in preventing AAA rupture and AAA-related mortality.

The effect of progressive and individualised sport-specific training on the prevalence of injury in football and handball student athletes: a randomised controlled trial.

Objective: To evaluate the effectiveness of communication and coordination combined with designing a progressive and individualised sport-specific training program for reducing injury prevalence in youth female and male football and handball players transitioning to a sports academy high school. An additional aim was to investigate the characteristics of the reported injuries. Methods: Forty-two Norwegian athletes were randomised into an intervention or control group. Mean age, height, weight and BMI was 15.5 ± 0.5 years, 178.6 cm ± 6.3 cm, 71.3 ± 9.8 kg, 22.3 ± 2.7 BMI for the intervention group (IG) (n = 23), and 15.4 ± 0.5 years, 175.6 cm ± 6.6 cm, 67.1 ± 9.8 kg, 21.7 ± 2.4 BMI for the control group (CG) (n = 19). During the summer holiday, the intervention group received weekly progressive, individualised sport-specific training programs and weekly follow-up telephone calls from the researchers. All athletes completed a baseline questionnaire and a physical test battery. Training data and injuries were recorded prospectively for 22 weeks using the Oslo Sports Trauma Research Center Questionnaire on Health Problems (OSTRC-H2). A two-way chi-square (χ2) test of independence was conducted to examine the relationship between groups and injury. Results: Average weekly prevalence of all injuries was 11% (95% CI: 8%-14%) in IG and 19% (95% CI: 13%-26%) in CG. Average weekly prevalence of substantial injuries was 7% (95% CI: 3%-10%) in IG and 10% (95% CI: 6%-13%) in CG. The between-group difference in injuries was significant: χ2 (1, N = 375) = 4.865, p = .031, φ = .114, with 1.8 times higher injury risk in CG vs. IG during the first 12 weeks after enrolment. Conclusions: For student athletes transitioning to a sports academy high school, progressive individualised, sport-specific training programs reduced the prevalence of all-complaint injuries following enrolment. Clubs and schools should prioritise time and resources to implement similar interventions in periods where student athletes have less supervision, such as the summer holidays, to facilitate an optimal transition to a sports academy high school.

Associations between cardiovascular risk factors, disease activity and cardiorespiratory fitness in patients with inflammatory joint disease: a cross-sectional analysis.

BACKGROUND: Inflammatory joint diseases (IJD) are accompanied by an increased risk of cardiovascular disease (CVD). Cardiorespiratory fitness (CRF) is a modifiable CVD risk factor and low levels of CRF associate with an elevated CVD risk. This study aimed to investigate the associations between CVD risk factors, disease activity and CRF in patients with IJD and to explore differences between patients with normal versus low levels of CRF. METHODS: CRF was measured as peak oxygen uptake (VO2peak) with a cardiopulmonary exercise test. Participants were also evaluated for: Body composition, blood pressure, blood lipids, inflammatory markers and disease activity. Patient-reported use of cigarettes/snuff, medication, disease duration, pain, fatigue, CVD history, habitual physical activity and exercise beliefs and self-efficacy were collected by questionnaire. Cross-sectional associations between CVD risk factors, disease-related factors and CRF were analyzed by multiple linear regression. CRF was categorized to normal CRF (VO2peak ≥ 80%) or low CRF (VO2peak < 80%) according to age- and gender-stratified reference data. Differences in demographic, CVD and disease-related factors between patients with normal versus low CRF were explored. RESULTS: In 60 Norwegian patients with IJD [34 females, age 59 years (IQR: 52-63)], mean VO2peak was 30.2 (± 6.9) mL/kg/min, corresponding to 83% (± 18) of normative reference values. Age (coefficient: - 0.18 years, p = 0.01) and fat mass (coefficient: - 0.67 %, p < 0.001) were inversely associated with CRF, while physical activity index (coefficient: 0.13 points, p = 0.05) was positively associated with CRF (R2 = 0.66). There were no significant associations between CRF, classical CVD risk factors and disease-related variables. Compared to patients with low CRF (n = 30), patients with normal CRF (n = 30) had higher peak oxygen uptake (+ 9.4 mL/kg/min, p < 0.001), high-density lipoprotein cholesterol (+ 0.5 mmol L-1, p < 0.001), and exercise self-efficacy (+ 6.9, p < 0.01) as well as lower fat mass (- 8.7%, p < 0.001), resting heart rate (- 8.0 beats/min, p < 0.01) and triglycerides (- 0.5 mmol L-1, p < 0.01). CONCLUSIONS: In this sample of IJD-patients, age, fatmass and physical activity level were associated with CRF. CRF was lower than reference values and patients with normal CRF presented with a more favorable health profile. There is a continued need for exercise interventions to improve CRF in patients with IJD. TRIAL REGISTRATION: NCT04922840.

Bone health in Norwegian female elite runners: a cross-sectional, controlled study.

Objective: The primary objective was to compare bone mineral density (BMD) in Norwegian female elite long-distance runners with a control group of inactive females. Secondary objectives were to identify cases of low BMD, to compare the concentration of bone turnover markers, vitamin D and symptoms of low energy availability (LEA) between the groups, and to identify possible associations between BMD and selected variables. Methods: Fifteen runners and fifteen controls were included. Assessments included dual-energy X-ray absorptiometry measurement of BMD in the total body, lumbar spine and dual proximal femur. Blood samples included endocrine analyses and circulating bone turnover markers. The risk of LEA was assessed through a questionnaire. Results: Runners had higher Z-scores in the dual proximal femur (1.30 (0.20 to 1.80) vs 0.20 (-0.20 to 0.80), p<0.021) and total body (1.70 (1.20 to 2.30) vs 0.90 (0.80 to 1.00), p<0.001). The lumbar spine Z-score was similar between groups (0.10 (-0.70 to 0.60) vs -0.10(-0.50 to 0.50), p=0.983). Three runners had low BMD (Z-score <-1) in the lumbar spine. Vitamin D and bone turnover markers showed no differences between the groups. Forty-seven per cent of the runners were at risk of LEA. Dual proximal femur BMD showed a positive correlation to estradiol and a negative correlation to LEA symptoms in runners. Conclusion: Norwegian female elite runners had higher BMD Z-score in the dual proximal femur and total body compared with controls, while no difference was observed in the lumbar spine. The advantages of long-distance running on bone health seem to be site specific, and there is still a need for the prevention of LEA and menstrual disorders in this group.

Development of a prototype toe sensor for detection of diabetic peripheral small fiber neuropathy.

Diabetic peripheral neuropathy (DPN) affects a large proportion of people with diabetes, and early detection is essential to prevent further progression. Widespread clinical testing relies on simplicity and cost-effectiveness of examination. Early signs of DPN may be detected by assessing the sudomotor nerves, and sudomotor activity can be measured by bioimpedance. We present a prototype toe probe for DPN detection including sensors for measuring skin AC conductance, skin temperature and humidity. The prototype was tested on five participants with DPN and five healthy age-matched controls in a pilot study. Sudomotor sensor responses to a simple deep breathing test were very weak or absent in the DPN group, with all controls having larger responses than the DPN group. Evaporation was lower for the DPN group, and skin temperature was higher on average. For the same foot, the results for sudomotor responses were in agreement with sensory neurography amplitudes from the sural nerve whereas the monofilament test gave normal results for two of the DPN participants. If sufficient detection accuracy is confirmed in larger studies, the method may provide a simple and cost-effective tool to support clinical examination. Clinical Relevance- We present the early realization and testing of a simple device to support early detection of diabetic peripheral neuropathy.

Plasma α-Glutathione S-Transferase in Patients with Chronic Mesenteric Ischemia and Median Arcuate Ligament Syndrome.

Background: Chronic mesenteric ischemia (CMI) due to either atherosclerosis of the mesenteric arteries or median arcuate ligament syndrome (MALS) is an underdiagnosed entity. The etiology of MALS and its existence have been debated and questioned. We aimed to identify plasma biomarkers indicating mesenteric ischemia in patients with CMI and MALS. Methods: Plasma α-glutathione S-transferase (α-GST), intestinal fatty acid-binding protein (I-FABP), citrulline, and ischemia modified albumin (IMA) were analyzed in fifty-eight patients with CMI (Group A, n=44) and MALS (Group B, n=14) before and after revascularization. The plasma levels of these potential biomarkers were compared with those of healthy individuals (Group C, n=16). Group comparison was performed with the Mann-Whitney U-test. Cross-tabulation and its derivatives were obtained. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were calculated. Results: Plasma levels of α-GST were significantly raised in the patients with CMI (7.8 ng/mL, p<0.001) and MALS (8.4 ng/mL, p<0.001), as compared with the control Group C (3.3 ng/mL). The threshold for normal median plasma α-GST levels of 4 ng/mL yielded a sensitivity of 93% and 86%, specificity of 86% and 88%, respectively, for the diagnosis of CMI due to atherosclerosis and MALS. AUC of ROC curves was 0.96 (p<0.0001) for CMI and 0.85 (p<0.002) for MALS. The patient groups did not differ from the healthy controls in any other biomarkers. Conclusion: Plasma α-GST levels are elevated in CMI and MALS patients. Elevated plasma levels of α-GST suggest ischemia as the etiology of MALS.

Effects of experimental hypovolemia and pain on pre-ejection period and pulse transit time in healthy volunteers.

Trauma patients may suffer significant blood loss, and noninvasive methods to diagnose hypovolemia in these patients are needed. Physiologic effects of hypovolemia, aiming to maintain blood pressure, are largely mediated by increased sympathetic nervous activity. Trauma patients may however experience pain, which also increases sympathetic nervous activity, potentially confounding measures of hypovolemia. Elucidating the common and separate effects of the two stimuli on diagnostic methods is therefore important. Lower body negative pressure (LBNP) and cold pressor test (CPT) are experimental models of central hypovolemia and pain, respectively. In the present analysis, we explored the effects of LBNP and CPT on pre-ejection period and pulse transit time, aiming to further elucidate the potential use of these variables in diagnosing hypovolemia in trauma patients. We exposed healthy volunteers to four experimental sequences with hypovolemia (LBNP 60 mmHg) or normovolemia (LBNP 0 mmHg) and pain (CPT) or no pain (sham) in a 2 × 2 fashion. We calculated pre-ejection period and pulse transit time from ECG and ascending aortic blood velocity (suprasternal Doppler) and continuous noninvasive arterial pressure waveform (volume-clamp method). Fourteen subjects were available for the current analyses. This experimental study found that pre-ejection period increased with hypovolemia and remained unaltered with pain. Pulse transit time was reduced by pain and increased with hypovolemia. Thus, the direction of change in pulse transit time has the potential to distinguish hypovolemia and pain.

Effects of supplemental oxygen on systemic and cerebral hemodynamics in experimental hypovolemia: Protocol for a randomized, double blinded crossover study.

Supplemental oxygen is widely administered in trauma patients, often leading to hyperoxia. However, the clinical evidence for providing supplemental oxygen in all trauma patients is scarce, and hyperoxia has been found to increase mortality in some patient populations. Hypovolemia is a common finding in trauma patients, which affects many hemodynamic parameters, but little is known about how supplemental oxygen affects systemic and cerebral hemodynamics during hypovolemia. We therefore plan to conduct an experimental, randomized, double blinded crossover study to investigate the effect of 100% oxygen compared to room air delivered by a face mask with reservoir on systemic and cerebral hemodynamics during simulated hypovolemia in the lower body negative pressure model in 15 healthy volunteers. We will measure cardiac output, stroke volume, blood pressure, middle cerebral artery velocity and tolerance to hypovolemia continuously in all subjects at two visits to investigate whether oxygen affects the cardiovascular response to simulated hypovolemia. The effect of oxygen on the outcome variables will be analyzed with mixed linear regression. Trial registration: The study is registered in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT, registration number 2021-003238-35).

Early Identification of Chronic Mesenteric Ischemia with Endoscopic Duplex Ultrasound.

Introduction: Due to diagnostic delay, chronic mesenteric ischemia (CMI) is underdiagnosed. We assumed that the patients suspected of CMI of the atherosclerotic origin or median arcuate ligament syndrome (MALS) could be identified earlier with endoscopic duplex ultrasound (E-DUS). Patients and Methods: Fifty CMI patients with CTA-verified stenosis of either ≥50% and ≥70% of celiac artery (CA) and superior mesenteric artery (SMA) were examined with E-DUS and transabdominal duplex ultrasound (TA-DUS). Peak systolic velocities (PSV) of ≥200cm/s and ≥275cm/s for CA and SMA, respectively, were compared with CTA. Subgroup analysis was performed for the patients with (n=21) and without (n=29) prior revascularization treatment of CMI. The diagnostic ability of E-DUS and TA-DUS was tested with crosstabulation analysis. Receiver operating characteristics (ROC) curve analysis was performed, and the area under the curve (AUC) was calculated to investigate the test accuracy. Results: In the patients with ≥70% stenosis, E-DUS had higher sensitivity than TA-DUS (91% vs 81% for CA and 100% vs 92% for SMA). AUC for SMA ≥70% in E-DUS was 0.75 and with TA-DUS 0.68. The sensitivity of E-DUS for CTA-verified stenosis ≥70% for CA was 100% in the patients without prior treatment. E-DUS demonstrated higher sensitivity than TA-DUS for both arteries with stenosis ≥50% and ≥70% in the treatment-naive patients. Conclusion: E-DUS is equally valid as TA-DUS for the investigation of CMI patients and should be used as an initial diagnostic tool for patients suspected of CMI.

The Effect of 12-Week Treatment with Intermittent Negative Pressure on Blood Flow Velocity and Flowmotion, Measured with a Novel Doppler Device (Earlybird). Secondary Outcomes from a Randomized Sham-Controlled Trial in Patients with Peripheral Arterial Disease.

BACKGROUND: Treatment with intermittent negative pressure (INP) is proposed as an adjunct to standard care in patients with peripheral arterial disease (PAD). The aims of this study were to evaluate the applicability of a novel ultrasound Dopplerdevice (earlybird) to assess blood flow characteristics in patients with PAD during a treatment session with INP, and whether certain flowproperties could determine who could benefit from INP treatment. METHODS: Secondary outcomes of data from a randomized sham-controlled trial were explored. Patients were randomized to 12 weeks of treatment with 40 mm Hg or 10 mm Hg INP, for one hour twice daily. Earlybird blood flow velocity recordings were made before and after the 12-week treatmentperiod and consists of a 5-min recording in rest, 3-min during INP treatment and 5-min recording after ended INP test-treatment. Mean blood flow velocity (vmean), relative changes in flow and frequency spectrum by Fourier-transform of the respective bandwidths of endothelial, sympathetic, and myogenic functions, were analyzed for the different series of blood flow measurements. RESULTS: In total, 62 patients were eligible for analysis, where 32 patients were treated with 40 mm Hg INP. The acquired recordings were of good quality and were used for descriptive analyses of flow characteristics. An immediate increase in vmean during the negative pressure periods of the INP test-treatment was observed in the 40 mm Hg INP treatment group at both pre- and post-test. There was a significant difference between the treatment groups, with a difference between the medians of 13.7 (P < 0.001) at pre-test and 10.7 (P < 0.001) at posttest. This finding was confirmed with spectrum analysis by Fourier-transform of the bandwidth corresponding to INP treatment. The change in amplitude corresponding to myogenic function after 12-weeks of treatment, was significantly different in favor of the 40 mm Hg INP treatment group. We were not able to detect the specific flow characteristics indicating who would benefit INP-treatment. CONCLUSIONS: Earlybird is an applicable tool for assessing blood flow velocity in patients with PAD. Analysis of the flow velocity recordings shows that INP induces an immediate increase in blood flow velocities during INP. The positive effects of INP may be attributed to recruitment of arterioles, and thereby, increasing blood flow. In these analyses, no flow characteristics were determined which could predict who would benefit INP treatment.

Gut Leakage and Cardiac Biomarkers after Prolonged Strenuous Exercise.

PURPOSE: Transient increase in the cardiac biomarkers troponin T (cTnT) and NT-proBNP are observed during strenuous exercise, even in healthy athletes. Gut leakage, the translocation of bacterial lipopolysaccharide (LPS) into the circulation, is associated with atherosclerosis and cardiovascular disease but has also been reported after prolonged endurance exercise. We aimed to explore the link between exercise-induced gut leakage and cardiac biomarker release. METHODS: Participants in Norseman Xtreme Triathlon (Norseman) were included ( n = 44, age 43 ± 9 yr, 9 [21%] women). Blood samples were taken before and immediately after the race for the determination of biomarkers. cTnT and NT-proBNP were measured by conventional methods. Gut leakage marker LPS was measured by the kinetic, chromogenic limulus amebocyte lysate assay method, whereas LPS-binding protein (LBP), soluble cluster of differentiation 14 (sCD14), and intestinal injury marker intestinal fatty acid-binding protein (I-FABP) were measured by enzyme-linked immunosorbent assay. RESULTS: Median (25, 75 percentiles) finish time was 14 h 33 min (13 h 42 min, 15 h 29 min). TnT and NT-proBNP increased significantly to 38 ng·L -1 (27, 56) and 495 ng·L -1 (310, 828) after the race ( P < 0.001, both). LBP and sCD14 also increased significantly ( P < 0.001, both), as did I-FABP ( P = 0.003), whereas LPS remained unchanged ( P = 0.13). No significant correlations between changes in gut leakage markers and changes in cardiac biomarkers were observed after adjusting for multiple testing. CONCLUSIONS: Cardiac and gut leakage biomarkers increased after Norseman Xtreme triathlon. However, changes in these biomarkers were not intercorrelated, suggesting that the exercise-induced increase in cardiac and gut leakage biomarkers occurs independently of each other.

Vascular Function in Norwegian Female Elite Runners: A Cross-Sectional, Controlled Study.

In general, aerobic exercise has a positive impact on the vascular system, but the syndrome of relative energy-deficiency in sports (RED-S) makes this impact less clear for the athlete. The present cross-sectional controlled study aimed to investigate the vascular function in female elite long-distance runners, compared to inactive women. Sixteen female elite long-distance runners and seventeen healthy controls were recruited. Assessments of vascular function and morphology included endothelial function, evaluated by flow-mediated dilatation (FMD), vascular stiffness, evaluated with pulse wave velocity (PWV), carotid artery reactivity (CAR %), and carotid intima-media thickness (cIMT). Blood samples included hormone analyses, metabolic parameters, lipids, and biomarkers reflecting endothelial activation. RED-S risk was assessed through the low energy availability in female questionnaire (LEAF-Q), and body composition was measured by dual-energy X-ray absorptiometry (DXA). We found no significant differences in brachial FMD, PWV, CAR %, cIMT, or biomarkers reflecting endothelial activation between the two groups. Forty-four percent of the runners had a LEAF-Q score consistent with being at risk of RED-S. Runners showed significantly higher HDL-cholesterol and insulin sensitivity compared to controls. In conclusion, Norwegian female elite runners had an as good vascular function and morphology as inactive women of the same age.

Laparoscopic Surgery for Median Arcuate Ligament Syndrome (MALS): A Prospective Cohort of 52 Patients.

Background: The selection of patients with MALS for surgical treatment depends upon the reliability of the symptom interpretation and the diagnostic work-up. We aimed to follow up the results of the laparoscopic decompression of the patients with MALS. Patients and Methods: In a single-center, 52 consecutive MALS patients were followed-up, prospectively, after transperitoneal laparoscopic decompression. MALS was diagnosed with a computed tomography angiography (CTA) verified stenosis, ≥50% of the celiac artery (CA), and with duplex ultrasound, a peak systolic velocity (PSV) ≥2.0 m/s. Postoperative, CTA, and duplex ultrasound were performed, and the patients were followed-up at 3, 6, 12 months, and yearly after that. Results: Mean age of the patients was 47 ±21 years, and 65% were females. The patients had a mean weight loss of 8.4 ±7.2 kg. Fifty-one patients had the laparoscopic operation with a mean operation time of 102 ± 28 minutes. Forty-seven patients (90%) achieved relief from the symptoms either completely (67%) or partially (23%) at 3-6 months of follow-up. Significant improvement in postoperative PSV was found compared to the preoperative values, p<0.001. Five patients (10%) with no immediate effect of the operation, but two of them became free from symptoms during the mean study follow-up of 2.4 ± 2 years. Five patients (10%) had operative complications, including one trocar injury to the liver, one pneumothorax, and three cases of bleeding from the branches of CA. Two patients died of cancer disease during the study period. Only two patients (4%) had symptoms relapse, both later treated successfully. Conclusion: Laparoscopic transperitoneal decompression provides most of the patients a persistent relief from MALS symptoms.

Effect of high-intensity exercise on cardiorespiratory fitness, cardiovascular disease risk and disease activity in patients with inflammatory joint disease: protocol for the ExeHeart randomised controlled trial.

INTRODUCTION: Inflammatory joint disease (IJD) is associated with increased risk of cardiovascular disease (CVD) fostered by systemic inflammation and a high prevalence of CVD risk factors. Cardiorespiratory fitness (CRF) is an important health parameter and CRF-measures are advocated in routine health evaluations. CRF associates with CVD risk, and exercise modalities such as high intensity interval training (HIIT) can increase CRF and mitigate CVD risk factors. In IJD, exercise is rarely used in CVD risk management and the cardioprotective effect of HIIT is unclear. Furthermore, the clinical applicability of HIIT to primary care settings is largely unknown and warrants investigation. The primary aim is to assess the effect of a HIIT programme on CRF in patients with IJD. Second, we will evaluate the effect of HIIT on CVD risk and disease activity in patients with IJD, feasibility of HIIT in primary care and validity of non-exercise algorithms to detect change in CRF. METHODS AND ANALYSIS: ExeHeart is a single-blinded, randomised controlled trial. Sixty patients with IJD will be recruited from the Preventive Cardio-Rheuma clinic at Diakonhjemmet Hospital, Norway. Patients will be assigned to receive standard care (relevant lifestyle advice and cardio-preventive medication) or standard care plus a 12-week HIIT intervention by physiotherapists in primary care. HIIT sessions will be prescribed at 90%-95% of peak heart rate. Outcomes include CRF (primary outcome), CVD risk factors, anthropometric measures, disease activity and patient-reported outcomes related to pain, fatigue, disease, physical activity and exercise and will be assessed at baseline, 3 months (primary endpoint) and 6 months postbaseline. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Regional Committee for Medical and Health Research Ethics (201227). Participants are required to sign a written informed consent form. Results will be discussed with patient representatives, submitted to peer-reviewed journals and presented at relevant platforms. TRIAL REGISTRATION NUMBER: NCT04922840.