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Diabetic peripheral neuropathy (DPN) may lead to several changes in the skin, and some of these may influence the skin impedance spectrum. In the present study we have developed a prototype solution for skin impedance spectroscopy at selected skin sites (big toe pulp, heel and toe ball) that was tested in a pilot study on five patients with DPN and five healthy controls. At the big toe, most of the controls had markedly lower impedance than the DPN group, especially in the range of 1-100 kHz. The separation between the groups seems to be weaker at the heel and weakest at the toeball. The results may indicate that monitoring of the skin impedance spectrum may be a method for detection of skin changes associated with DPN, encouraging further studies with the big toe sensor in particular.

Introduction: Non-invasive cuffless blood pressure devices have shown promising results in accurately estimating blood pressure when comparing measurements at rest. However, none of commercially available or prototype cuffless devices have yet been validated according to the appropriate standards. The aim of the present study was to bridge this gap and evaluate the ability of a prototype cuffless device, developed by Aidee Health AS, to track changes in blood pressure compared to a non-invasive, continuous blood pressure monitor (Human NIBP or Nexfin) in a laboratory set up. The performance was evaluated according to the metrics and statistical methodology described in the ISO 81060-3:2022 standard. However, the present study is not a validation study and thus the study was not conducted according to the ISO 81060-3:2022 protocol, e.g., non-invasive reference and distribution of age not fulfilled. Method: Data were sampled continuously, beat-to-beat, from both the cuffless and the reference device. The cuffless device was calibrated once using the reference BP measurement. Three different techniques (isometric exercise, mental stress, and cold pressor test) were used to induce blood pressure changes in 38 healthy adults. Results: The mean difference (standard deviation) was 0.3 (8.7) mmHg for systolic blood pressure, 0.04 (6.6) mmHg for diastolic blood pressure, and 0.8 (7.9) mmHg for mean arterial pressure, meeting the Accuracy requirement of ISO 81060-3:2022 (≤6.0 (10.0) mmHg). The corresponding results for the Stability criteria were 1.9 (9.2) mmHg, 2.9 (8.1) mmHg and 2.5 (9.5) mmHg. The acceptance criteria for the Change requirement were achieved for the 85th percentile of ≤50% error for diastolic blood pressure and mean arterial pressure but were higher than the limit for systolic blood pressure (56% vs. ≤50%) and for all parameters for the 50th percentile (32%–39% vs. ≤25%). Conclusions: The present study demonstrated that the cuffless device could track blood pressure changes in healthy adults across different activities and showed promising results in achieving the acceptance criteria from ISO 81060-3:2022. [ABSTRACT FROM AUTHOR]

Arterial vasodilation is dependent on nitric oxide synthesized from L-arginine by endothelial nitric oxide synthase. Triathletes are reported to display altered serum concentrations of nitric oxide metabolites such as L-arginine, asymmetric dimethyl arginine (ADMA) and symmetric dimethyl arginine (SDMA) shortly after completing long-distance triathlon races. In other populations, similar changes to nitric oxide metabolites are established risk markers of cardiovascular disease. The objective of this study was to assess serum concentrations of metabolites for endothelial nitric oxide synthesis in triathletes one week following a long-distance triathlon race. In this prospective observational study, we used high-performance liquid chromatography to measure circulating concentrations of L-arginine, ADMA, and SDMA in triathletes. Venous blood samples were collected before, immediately after, day one, and one week following the triathlon race. Serum concentrations and L-arginine/ADMA ratio were determined for each time-point and compared to baseline. L-arginine/ADMA ratio was reduced on day one (147 ± 32 vs 163 ± 40, p < 0.02). ADMA was reduced immediately after and increased at day one and remained elevated at one week (0.29 ± 0.05 mM, p < 0.001, 0.44 ± 0.08 mM, p < 0.001 and 0.42 ± 0.07 μM, p = 0.04, respectively vs 0.40 ± 0.05 μM). SDMA was increased at all time-points when compared to baseline (0.48 ± 0.10 μM, p < 0.001, 0.53 ± 0.11 μM, p < 0.001 and 0.42 ± 0.08 μM, p = 0.048 vs 0.38 ± 0.05 μM). L-arginine was only decreased immediately after (46.0 ± 9.3 μM vs. 64.6 ± 16.1 μM, p < 0.001). Long-distance triathlon racing induces altered levels of metabolites for endothelial nitric oxide production that mostly normalizes within one week following racing. The clinical relevance of these transient changes has yet to be elucidated in the athletic population. [ABSTRACT FROM AUTHOR]

Large‐volume therapeutic phlebotomy is the mainstay of hemochromatosis treatment and offers an opportunity to investigate the hemodynamic changes during acute hypovolemia. An otherwise healthy 64‐year‐old male with hemochromatosis participated. On nine separate visits, 1000 mL therapeutic phlebotomy was performed. On one occasion, pre‐ and post‐phlebotomy orthostatic challenge with 27° reverse Trendelenburg position was administered. Mean arterial pressure, heart rate, and stroke volume were measured continuously during the procedures. The patient's tolerance to the interventions was continuously evaluated. The procedures were well tolerated by the patient. Mean arterial pressure was maintained during hemorrhage and following phlebotomy in both supine and reverse Trendelenburg positions, primarily through an increase in heart rate and systemic vascular resistance. The present study found that 1000 mL therapeutic phlebotomy in a patient with hemochromatosis may be acceptably and safely used to model hemorrhage. The approach demonstrates high clinical applicability and ethically robustness in comparison with volunteer studies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In young patients referred for exercise-induced pain in the legs, false positive tests are a potential problem for the post-exercise ankle–brachial index (ABI) test when using the current American Heart Association guidelines for diagnosing peripheral artery disease (PAD). The present study aimed to investigate post-exercise ABI in healthy young people, and to explore whether the current diagnostic criteria for pathological ABI should be revised. Forty-eight volunteers (18–30 years) were included. Resting examinations included ABI and ultrasound of the external iliac artery. Post-exercise examinations after a treadmill load included ABI and ultrasound of the external iliac artery; after 0 min and after 3 min. A total of 60.5% of the participants had a post-exercise decrease in ABI > 20%. A total of 6.5% showed a decrease in ankle systolic blood pressure >30 mmHg. No significant association was observed between a change in blood flow in the external iliac artery and a reduction in ABI post-exercise. Analyses of the ultrasound recordings showed no turbulence in the external iliac artery. According to the results, a 20% decrease in ABI post-exercise seems to be a physiological condition present in young people. We support the need for a reassessment of the criteria for diagnosing PAD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]