A Dynamic Objective Evaluation of Peripheral Arterial Disease by Near-Infrared Spectroscopy

AbstractObjectivesNear-Infrared Spectroscopy (NIRS), suitable for dynamic measurements, is not routinely used for peripheral arterial disease (PAD). We propose a dynamic NIRS-based measurement to quantify variations in muscle metabolism in PAD.MethodSixty-seven consecutive PAD patients (males=56, age 71.6±8.7 years) and 28 healthy subjects (males=12, age 30.4±11.9 years) were studied. An echo-colour Doppler (ECD) was performed and the ankle–brachial index (ABI) was calculated. Participants performed an incremental treadmill test with NIRS probes on the gastrocnemius. Variations in oxygenated (HbO2), deoxygenated (HHb), total (tHb=HbO2+HHb), and differential (dHb=HbO2−HHb) haemoglobin were recorded and quantified as area-under-curve (AUC) within the range 1.7–3.0kmh−1. Heart rate was recorded, and the number of beats in the same interval was calculated (dHr).ResultsO2HbAUC, HHbAUC and dHbAUC differed between diseased and non-diseased legs (P<0.0001) and exhibited different patterns related to PAD severity according to the ABI value. A compensatory heart rate increase was observed in PAD patients. Compared with the ECD positivity for occlusions/stenoses or multiple plaques, only the receiver-operating characteristic (ROC) analysis of dHbAUC (area=0.932, P<0.0001) showed a sensitivity/specificity of 87.6/93.4 for values ≤−197 (LR+LR−: 13.36/0.13).ConclusionThe dynamic NIRS-based test, quantifying muscle metabolic response according to presence and degree of PAD, allows the evaluation of patients with walking disabilities

Secondary Endoleak Management Following TEVAR and EVAR.

Endovascular abdominal and thoracic aortic aneurysm repair and are widely used to treat increasingly complex aneurysms. Secondary endoleaks, defined as those detected more than 30 days after the procedure and after previous negative imaging, remain a challenge for aortic specialists, conferring a need for long-term surveillance and reintervention. Endoleaks are classified on the basis of their anatomic site and aetiology. Type 1 and type 2 endoleaks (EL1 and EL2) are the most common endoleaks necessitating intervention. The management of these requires an understanding of their mechanics, and the risk of sac enlargement and rupture due to increased sac pressure. Endovascular techniques are the main treatment approach to manage secondary endoleaks. However, surgery should be considered where endovascular treatments fail to arrest aneurysm growth. This chapter reviews the aetiology, significance, management strategy and techniques for different endoleak types

Data monitoring roadmap. The experience of the Italian Multiple Sclerosis and Related Disorders Register

Introduction Over the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked.This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register.MethodsThe Register collects, through a standardized Web-based Application, unique patients.Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated.ResultsThe Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients.The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000-2015) to 60% (enrolment period 2016-2022). In the cohort of patients registered after 2016, there were &gt;= 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2).Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months.ConclusionsData from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

A toe-flexion NIRS-assisted test for rapid assessment of foot perfusion in peripheral arterial disease: feasibility, validity and diagnostic accuracy

Objectives: We assessed feasibility, validity and diagnostic accuracy of a non-invasive dynamic ambulatory test with Near-Infrared Spectroscopy (NIRS) evaluating foot perfusion in Peripheral Arterial Disease (PAD). Design: Prospective observational study. Materials and Methods: Eighty PAD patients (63 males, 71±9 y) including 41 patients with coexisting diabetes), participated. Thirteen healthy subjects (8 males, 26±8 y) were also studied by Echo-Color-Doppler providing 160 diseased and 26 non-diseased limbs. Under clinostatic conditions, participants performed a 10-repetition toe-flexion test with NIRS probes on the dorsum of each foot; the area-under-curve of the oxygenated hemoglobin trace (‘toflex-area’) was calculated and the ankle brachial index (ABI) was measured. Time of execution, rate of wrong tests and adverse reactions were recorded. Within-session reliability was assessed by administering the test twice after five-minute interval. Validity was assessed determining whether the toflex-area was: i) dependent on the oxygen delivery from the lower limb arteries simulating PAD conditions by a progressive blood flow restriction (40‒120% of systolic pressure) in healthy subjects; ii) consistent with the degree of PAD ranked by ABI and correlated with ABI and ankle pressures values in PAD patients. The diagnostic accuracy in detecting PAD was compared to Echo-Color-Doppler examination. Results: All tests were rapidly, satisfactorily (<1% mistakes) and safely performed. Toflex-area values, superimposable in the two sessions (ICC: 0.92), were: comparable to PAD values following blood flow restriction, consistent with PAD severity, correlated to dorsal pedis artery pressure (r=0.21; p=0.007) and ABI (r=0.65; p<0.001) in PAD, but not in the presence of diabetes. Toflex-area was comparable to Echo-Color-Doppler for detection of PAD following receiver-operating characteristic curve analysis (area=0.987, p<0.001; toflex-area values ≤-28a.u., sensitivity/specificity: 95.6/100). Conclusion: Toe-flexion test enables ambulatory assessment of foot perfusion and PAD detection, even in the presence of non-measurable ABI or diseases affecting microcirculation

Uncovering the interactions driving carotenoid binding in light-harvesting complexes

Carotenoids are essential constituents of plant light-harvesting complexes (LHCs), being involved in protein stability, light harvesting, and photoprotection. Unlike chlorophylls, whose binding to LHCs is known to require coordination of the central magnesium, carotenoid binding relies on weaker intermolecular interactions (such as hydrogen bonds and van der Waals forces), whose character is far more elusive. Here we addressed the key interactions responsible for carotenoid binding to LHCs by combining molecular dynamics simulations and polarizable quantum mechanics/molecular mechanics calculations on the major LHC, LHCII. We found that carotenoid binding is mainly stabilized by van der Waals interactions with the surrounding chlorophyll macrocycles rather than by hydrogen bonds to the protein, the latter being more labile than predicted from structural data. Furthermore, the interaction network in the binding pockets is relatively insensitive to the chemical structure of the embedded carotenoid. Our results are consistent with a number of experimental data and challenge the role played by specific interactions in the assembly of pigment-protein complexes

Cyclophosphamide for multiple sclerosis

BACKGROUND:Multiple sclerosis is a presumed cell-mediated autoimmune disease of the central nervous system. Cyclophosphamide (CFX) is a cytotoxic and immunosuppressive agent, used in systemic autoimmune diseases. Controversial results have been reported on its efficacy in MS. We conducted a systematic review of all relevant trials, evaluating the efficacy of CFX in patients with progressive MS.OBJECTIVES:The main objective was to determine whether CFX slows the progression of MS.SEARCH STRATEGY:We searched the Cochrane MS Group Trials Register (searched June 2006), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3 2006), MEDLINE (January 1966 to June 2006), EMBASE (January 1988 to June 2006) and reference lists of articles. We also contacted researchers in the field.SELECTION CRITERIA:Randomised controlled trials (RCTs) evaluating the clinical effect of CFX treatment in patients affected by clinically definite progressive MS.CFX had to be administered alone or in combination with adrenocorticotropic hormone (ACTH) or steroids. The comparison group had to be placebo or no treatment or the same co-intervention (ACTH or steroids)DATA COLLECTION AND ANALYSIS:Two reviewers independently decided the eligibility of the study, assessed the trial quality and extracted data. We also contacted study authors for original data.MAIN RESULTS:Of the 461 identified references, we initially selected 70: only four RCTs were included for the final analysis. Intensive immunosuppression with CFX (alone or associated with ACTH or prednisone) in patients with progressive MS compared to placebo or no treatment (152 participants) did not prevent the long-term (12, 18, 24 months) clinical disability progression as defined as evolution to a next step of Expanded Disability Status Scale (EDSS) score. However, the mean change in disability (final disability subtracted from the baseline) significantly favoured the treated group at 12 (effect size - 0.21, 95% confidence interval - 0.25 to -0.17) and 18 months (- 0.19, 95% confidence interval - 0.24 to - 0.14) but favoured the control group at 24 months (0.14, CI 0.07 to 0.21). We were unable to verify the efficacy of other schedules. Five patients died; sepsis and amenorrhea frequently occurred in treated patients (descriptive analysis).AUTHORS' CONCLUSIONS:We were unable to achieve all of the objectives specified for the review. This review shows that the overall effect of CFX (administered as intensive schedule) in the treatment of progressive MS does not support its use in clinical practice

Reliability of the Vascular Claudication Reporting in Diabetic Patients With Peripheral Arterial Disease: A Study With Near-Infrared Spectroscopy.

We evaluated whether altered reporting of ischemic symptoms occurs in diabetic patients with peripheral arterial disease (PAD) and stable claudication. Patients (n = 152) with claudication were enrolled (120 males; mean age: 71.0 ± 8.6 years): 74 with diabetes (DM-PAD) and 78 without (DMfree-PAD). The degree of muscle oxygenation at symptom onset and maximal speed (Smax) during an incremental treadmill test was recorded at the gastrocnemius by near-infrared spectroscopy (NIRS) and quantified by area under the curve of oxygenated hemoglobin (AUC-Hbo2) and area under the curve of differential hemoglobin (AUC-dHb). The DM-PAD and DMfree-PAD showed similar exercise capacities inversely correlated with the degree of muscle oxygenation but significantly lower values of AUC-Hbo2 and AUC-dHb for DM-PAD at symptom onset and Smax (-356 vs -122 and -1200 vs -359, P < .0001). During a NIRS-assisted test, the report of claudication in the presence of diabetes was delayed, occurring at a lower degree of oxygenation than in patients with PAD only, with potential implications for testing, functional staging, and balance disorders