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Abstract: Objective: Both spatial variability and temporal variability of skin blood flow are high. Laser speckle contrast imagers (LSCI) allow non-contact, real-time recording of cutaneous blood flow on large skin surfaces. Thereafter, the observer can define different sizes for the region of interest (ROI) in the images to decrease spatial variability and different durations over which the blood flow values are averaged (time of interest, TOI) to decrease temporal variability. We aimed to evaluate the impact of the choices of ROI and TOI on the analysis of rest blood flow and post occlusive reactive hyperemia (PORH). Methods: Cutaneous blood flow (CBF) was assessed at rest and during PORH. Three different sizes of ROI (1mm2, 10mm2 and 100mm2), and three different TOI (CBF averaged over 1s, 15s, and 30s for rest, and over 1s, 5s and 10s for PORH peak) were evaluated. Inter-subjects and intra-subjects coefficient of variations (inter-CV and intra-CV) were studied. Results: The inter-subject variability of CBF is about 25% at rest and is moderately improved when the size of the ROI increases (inter-CV=31%, for 1s and 1mm2 versus inter-CV=23%, for 15s and 100mm2). However, increasing the TOI does not improve the results. The variability of the PORH peak is lower with an inter-CV varying between 11.4% (10s and 100mm2) and 21.6% (5s and 1mm2). The lowest intra-CV for the CBF at rest was 7.3% (TOI of 15s on a ROI of 100mm2) and was 3.1% for the PORH peak (TOI of 10s on a ROI of 100mm2). Conclusion: We suggest that a size of ROI larger than 10mm2 and a TOI longer than 1s are required to reduce the variability of CBF measurements both at rest and during PORH peak evaluations at the forearm level. Many technical aspects such as comparison of laser speckle contrast imaging and laser Doppler imaging or the effect of skin to head distance on recorded values with LCSI are required to improve future studies using this fascinating clinical tool. [Copyright &y& Elsevier]

Abstract: Cutaneous blood flow (CBF) can be assessed non-invasively with lasers. Unfortunately, movement artefacts in the laser skin signal (LSsk) might sometimes compromise the interpretation of the data. To date, no method is available to remove movement artefacts point-by-point. Using a laser speckle contrast imager, we simultaneously recorded LSsk and the signal backscattered from an adjacent opaque surface (LSos). The completion of a first protocol allowed a definition of a simple equation to calculate the CBF from movement artefact-affected traces of LSsk and LSos. We then recorded LSsk and LSos before, during and for 5min after the tourniquet ischemia, both when subjects (n=8) were immobile or submitted to external passive movements of random intensity throughout the test. The typical post-occlusive reactive hyperemia trace was not identifiable within the LSsk recordings, with LSsk being 2 to 3 times higher during movements than in the immobile situation. After the calculation of CBF, traces in the immobile versus movement conditions were comparable, with the “r” cross-correlation coefficient being 0.930+/−0.010. Our method might facilitate future investigations in microvascular physiology and pathophysiology, specifically in subjects who have frequent or continuous involuntary movements. [Copyright &y& Elsevier]

Abstract: Low-dose aspirin is largely but non-homogeneously used in primary prevention of cardiovascular complication in type-2 diabetic patients. We hypothesised that low-dose aspirin could interfere with the cutaneous neurovascular responses in type-2 diabetic patients. Galvanic current-induced vasodilatation (CIV) is an original non-noxious integrative model of neurovascular interaction and is impaired under low-dose aspirin in healthy subjects. Twenty type-2 diabetic patients (ten not receiving aspirin: D-NA and ten regularly receiving ≤150 mg/day aspirin: D-A), and ten age-, BMI-, and gender-matched non-diabetic control volunteers (MC), underwent macro- and microvascular investigations, including: CIV, acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis, post-occlusive hyperemia (POH), neuropathy symptom (NSS) and disability (NDS) scores, and thermal and vibration sensory thresholds. Results are presented as median [25–75 centile] and microvascular results are expressed in multiple from baseline conductance (%Cb). CIV was 554 [349–769] %Cb in MC, 251 [190–355] %Cb in D-NA and 159 [136–202] %Cb in D-A (p <0.05). No differences were observed between the three groups except for CIV, which is impaired in diabetic patients and further impaired in those regularly receiving low-dose aspirin, while other macrovascular, microvascular and clinical-sensitivity investigations show no significant difference. Potential clinical markers for the impairment of the neurovascular interaction are still required in diabetes. Correlation of the CIV response with the risk of cutaneous complications in diabetic patients remains to be tested. [Copyright &y& Elsevier]

Introduction: Hidradenitis suppurativa (HS) is a common and debilitating disease, in which the only effective treatment involves a wide excision of the affected skin. Secondary wound healing and skin grafting are two well-known options for managing these defects, but perforator flaps provide a new therapeutic alternative by ensuring reconstructions of large defects, reducing donor site morbidity, and enhancing functional recovery. The aim of this study was to achieve a systematic review of perforator flaps use in HS. Patients and Methods: PubMed and Cochrane databases were searched from 1989 to 2021. The PRISMA statement was used in the study selection process and the review was registered on PROSPERO. Furthermore, patient characteristics, operative technique, complications, and recurrences were searched. Results: Thirty-six articles were selected including 286 patients and 387 flaps. Axillary localization was mostly represented (83.2%). Direct donor site closure was achieved in 99.1% of cases. In total, 15.1% of the flaps presented at least one of the following complications: wound dehiscence (5.5%), partial necrosis (2.9%), hematoma or seroma (2.1%), infection (2.1%), venous congestion (1.8%), and nerve injury (0.3%). Two cases of total necrosis were recorded. Recurrence of the disease was observed in 2.7% of the defects. Conclusions: Pedicled perforator flaps are a reliable and reproducible technique in the reconstruction of HS defects. They are associated with a low recurrence rate while ensuring an effective reconstruction with reduced morbidity and faster recovery compared to the techniques classically used in this indication. [ABSTRACT FROM AUTHOR]

Abstract: Background: Laser Speckle contrast imaging (LSCI) allows non-contact, real-time recording of cutaneous blood flow (CBF). Different distances from laser-head to skin (distancesL–S) can be chosen by the operator to perform these recordings. We aimed to evaluate the impact of different DistancesL–S on the analysis of rest blood flow and post-occlusive reactive hyperemia (PORH). Methods: Four distancesL–S (10, 15, 20, and 30cm) were evaluated in a random order in 11 healthy subjects. We analyzed the concordance between each recording at each distanceL–S. We compared CBF results (absolute values and cutaneous vascular conductance (CBF divided by mean arterial pressure)) obtained for each distanceL–S. The intra-subject coefficients of variation due to distancesL–S (intra-CV, in%) were also studied. Results: The mean “r” (standard deviation) cross-correlation coefficient was 0.99 (0.00) between each CBF trace issued from different distanceL–S. Both kinds of CBF results, at rest and for PORH peak, show non-significant differences when the distanceL–S is modified. The intra-CV varies from 5.9% to 8.6% at rest and from 5.6% to 9.1% for the PORH peak. Conclusion: DistanceL–S neither influences SBFR at rest, nor at peak post-occlusive hyperemia in the 10–30cm interval using LSCI. [Copyright &y& Elsevier]

Background and aims The first cause of low-dose acetylsalicylic-acid (ASA) inefficacy is poor adherence to treatment. No non-invasive technique is available to assess ASA intake. Current-induced vasodilation (CIV) was found abolished in healthy volunteers after low-dose ASA intake. We tested clinical characteristics, treatments, and comorbid conditions influencing CIV amplitude in vascular patients. Methods CIV was tested in 400 patients (277 males and 123 females, aged 65.4 ± 13.4 years). We focused on clinical characteristics, treatments, and comorbid conditions as covariates of CIV amplitude. We studied the CIV amplitude to covariate relationships with multivariate linear regression and receiver operating characteristics (ROC). Results The multivariate linear model determined that ASA intake within the last 48 h and the interaction between ASA intake and body mass index (BMI) were the sole covariates associated with CIV amplitude. For the whole population, the area under the ROC curve (AUC) for CIV to predict ASA intake was 0.853 [95% confidence interval (CI): 0.814–0.892]. Considering separately the areas observed for non-obese (BMI ≤30, n = 303) and obese (BMI>30, n = 93) patients, the AUC [95% CI] was 0.873 [0.832–0.915] and 0.776 [0.675–0.878], respectively ( p  = 0.083). Conclusions ASA is the only drug that affects the amplitude of CIV response observed after galvanic current application to the skin of vascular patients. CIV depends on BMI but not age or gender. As such, CIV appears to be a potential objective marker of ASA intake and could facilitate future non-invasive assessments of adherence to ASA treatment. [ABSTRACT FROM AUTHOR]

Purpose: Microcirculatory dysfunction plays a key role in the development of sepsis during which core temperature is often disturbed. Skin microvascular assessment using laser techniques has been suggested to evaluate microvascular dysfunction during sepsis, but skin microcirculation is also a major effector of human thermoregulation. Therefore we aimed to study the effect of skin temperature on endothelial- and non-endothelial microvascular responses. Methods: Fifteen healthy participants were studied at different randomized ambient temperatures leading to low (28.0+/−2.0°C), intermediate (31.6+/−2.1°C), and high (34.1+/−1.3°C) skin temperatures. We measured skin blood flow using laser speckle contrast imaging on the forearm in response to vasodilator microvascular tests: acetylcholine (ACh) iontophoresis, sodium nitroprussiate (SNP) iontophoresis, and post-occlusive reactive hyperemia (PORH). The results are expressed as absolute (laser speckle perfusion units, LSPU) or normalized values (cutaneous vascular conductance, CVC in LSPU/mmHg and multiple of baseline). Results: Maximal vasodilation induced by these tests is modified by skin temperature. A low skin temperature induced a significant lower vasodilation for all microvascular tests when results are expressed either in absolute values or in CVC. For example, ACh peak was 57.6+/−19.6LSPU, 66.8+/−22.2LSPU and 88.5+/−13.0LSPU for low, intermediate and high skin temperature respectively (p<0.05). When results are expressed in multiple of baseline, statistical difference disappeared. Conclusions: These results suggest that skin temperature has to be well controlled when performing microvascular assessments in order to avoid any bias. The effect of skin temperature can be corrected by expressing the results in multiple of baseline. [ABSTRACT FROM AUTHOR]

Background: Endothelial dysfunction precedes atherosclerosis. Vasodilation induced by acetylcholine (ACh) is a specific test of endothelial function. Reproducibility of laser techniques such as laser-Doppler-flowmetry (LDF) and Laser-speckle-contrast-imaging (LSCI) to detect ACh vasodilation is debated and results expressions lack standardization. We aimed to study at a 7-day interval (i) the inter-subject reproducibility, (ii) the intra-subjects reproducibility, and (iii) the effect of the results expressions over variability. Methods and Results: Using LDF and LSCI simultaneously, we performed two different ACh-iontophoresis protocols. The maximal ACh vasodilation (peak-ACh) was expressed as absolute or normalized flow or conductance values. Inter-subject reproducibility was expressed as coefficient of variation (inter-CV,%). Intra-subject reproducibility was expressed as within subject coefficients of variation (intra-CV,%), and intra-class correlation coefficients (ICC). Fifteen healthy subjects were included. The inter-subject reproducibility of peak-ACh depended upon the expression of the results and ranged from 55% to 162% for LDF and from 17% to 83% for LSCI. The intra-subject reproducibility (intra-CV/ICC) of peak-ACh was reduced when assessed with LSCI compared to LDF no matter how the results were expressed and whatever the protocol used. The highest intra-subject reproducibility was found using LSCI. It was 18.7%/0.87 for a single current stimulation (expressed as cutaneous vascular conductance) and 11.4%/0.61 for multiple current stimulations (expressed as absolute value). Conclusion: ACh-iontophoresis coupled with LSCI is a promising test to assess endothelial function because it is reproducible, safe, and non-invasive. N°: NCT01664572. [ABSTRACT FROM AUTHOR]

Healthy skin is protected from pressure-induced ischemic damage because of the presence of pressure-induced vasodilation (PIV). PIV relies on small sensory nerve fibers and endothelial function. Since aging alters both nervous and vascular functions, we hypothesized that PIV is altered with aging. We compared PIV in non-neuropathic and neuropathic older subjects (60–75 years) with that of young subjects (20–35 years). Laser Doppler flowmetry was used to evaluate the cutaneous responses to local pressure application, acetylcholine, and local heating. Quantitative sensory tests were used to evaluate sensory-nerve-fiber function. The non-neuropathic older subjects had an impaired PIV (12±7% increase in blood flow with pressure) compared with young subjects (62±4%, P<0.001). In the presence of peripheral neuropathy, the older subjects were totally deprived of PIV, leading to early pressure-induced cutaneous ischemia (−31±10%, P<0.001). This inability of the skin to adapt to localized pressure in older subjects is related to the severity of the sensory-fiber dysfunction rather than to endothelial dysfunction, which was comparable between the non-neuropathic (141±19% increased blood flow with acetylcholine, P<0.05) and neuropathic older subjects (145±28% increase, P<0.05) compared with young subjects (234±25% increase). [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Endothelial dysfunction has been proposed as a potential mechanism implicated in the pathogenesis of cardiovascular complications of obstructive sleep apnea syndrome (OSAS). This study aimed to evaluate the microvascular endothelial function (MVEV) in OSAS and the impact on MVEF of 2 months of treatment with continuous positive airway pressure (CPAP) and mandibular advancement device (MAD). Methods: Microvascular reactivity was assessed using laser Doppler flowmetry combined with acetylcholine (Ach) and sodium nitroprusside (SNP) iontophoresis in 24 OSAS patients and 9 control patients. In 12 of the 24 OSAS patients, microvascular reactivity was reassessed after 2 months of CPAP and MAD using a randomized cross-over design. Results: Ach-induced vasodilation was significantly lower in OSAS patients than in matched controls and correlated negatively with apnea hypopnea index (r =−0.49, p <0.025) and nocturnal oxygen desaturations (r =−0.63, p <0.002). Ach-induced vasodilation increased significantly with both CPAP and MAD. The increase in Ach-induced vasodilation under OSAS treatment correlated with the decrease in nocturnal oxygen desaturations (r =0.48, p =0.016). Conclusion: Our study shows an impairment of MVEF in OSAS related to OSAS severity. Both CPAP and MAD treatments were associated with an improvement in MVEF that could contribute to improve cardiovascular outcome in OSAS patients. [Copyright &y& Elsevier]

Proton acceleration by high-intensity laser pulses from ultrathin foils for hadron therapy is discussed. With the improvement of the laser intensity contrast ratio to 10-11 achieved on the Hercules laser at the University of Michigan, it became possible to attain laser-solid interactions at intensities up to 1022 W/cm2 that allows an efficient regime of laser-driven ion acceleration from submicron foils. Particle-in-cell (PIC) computer simulations of proton acceleration in the directed Coulomb explosion regime from ultrathin double-layer (heavy ions/light ions) foils of different thicknesses were performed under the anticipated experimental conditions for the Hercules laser with pulse energies from 3 to 15 J, pulse duration of 30 fs at full width half maximum (FWHM), focused to a spot size of 0.8 μm (FWHM). In this regime heavy ions expand predominantly in the direction of laser pulse propagation enhancing the longitudinal charge separation electric field that accelerates light ions. The dependence of the maximum proton energy on the foil thickness has been found and the laser pulse characteristics have been matched with the thickness of the target to ensure the most efficient acceleration. Moreover, the proton spectrum demonstrates a peaked structure at high energies, which is required for radiation therapy. Two-dimensional PIC simulations show that a 150–500 TW laser pulse is able to accelerate protons up to 100–220 MeV energies. [ABSTRACT FROM AUTHOR]

Using signal processing measures we evaluate the effect of aging on the peripheral cardiovascular system. Laser Doppler flowmetry (LDF) signals, reflecting the microvascular perfusion, are recorded on the forearm of 27 healthy subjects between 20–30, 40–50, or 60–70 years old. Wavelet-based representations, Hölder exponents, and sample entropy values are computed for each time series. The results indicate a possible modification of the peripheral cardiovascular system with aging. Thus, the endothelial-related metabolic activity decreases, but not significantly, with aging. Furthermore, LDF signals are more monofractal for elderly subjects than for young people for whom LDF signals are weakly multifractal: the average range of Hölder exponents computed with a parametric generalized quadratic variation based estimation method is 0.13 for subjects between 20 and 30 years old and 0.06 for subjects between 60 and 70 years old. Moreover, the average mean sample entropy value of LDF signals slightly decreases with age: it is 1.34 for subjects between 20 and 30 years old and 1.19 for subjects between 60 and 70 years old. Our results could assist in gaining knowledge on the relationship between microvascular system status and age and could also lead to a more accurate age-related nonlinear modeling. [ABSTRACT FROM AUTHOR]

A relativistic plasma shutter technique is proposed and tested to remove the sub-100 ps pedestal of a high-intensity laser pulse. The shutter is an ultrathin foil placed before the target of interest. As the leading edge of the laser ionizes the shutter material it will expand into a relativistically underdense plasma allowing for the peak pulse to propagate through while rejecting the low intensity pedestal. An increase in the laser temporal contrast is demonstrated by measuring characteristic signatures in the accelerated proton spectra and directionality from the interaction of 30 TW pulses with ultrathin foils along with supporting hydrodynamic and particle-in-cell simulations. [ABSTRACT FROM AUTHOR]