Nailfold dermoscopy predicts the absence of a capillaroscopy sclerodermic pattern: The multicentre, prospective VASCUL-R trial.

BACKGROUND: Nailfold capillaroscopy is recommended to diagnose primary or secondary Raynaud's phenomenon (RP). Capillaroscopy is normal in primary RP, which is the most frequent. Screening for RP capillary anomalies with nailfold dermoscopy has been promising. OBJECTIVE: To determine whether normal nailfold dermoscopy-based on the absence of five criteria that define a sclerodermic pattern-is able to predict normal capillaroscopy with good positive-predictive value (PPV). METHODS: Prospective, 2-phase (monocentre and multicentre) study on patients at first consultation for RP undergoing nailfold video capillaroscopy (NVC) and nailfold dermoscopy by two different 'blinded' trained observers, respectively, a vascular specialist and a dermatologist, not familiar with capillaroscopy. The five criteria noted were as follows: disorganization, megacapillaries, low capillary density, avascular areas and haemorrhages. RESULTS: Based on 105 patients, the dermoscopy PPV for a normal NVC was 100% (p = 0.015), with 37.9% sensitivity, when no criterion was observed. Excluding haemorrhages, the PPV remained 100% (p < 0.0001), with sensitivity rising to 73.7% and 100% specificity. CONCLUSION: Normal nailfold dermoscopy with the absence of four easy-to-observe criteria predicts normal NVC with an excellent PPV.

Efficacy and Safety of Botulinum Toxin in Adults with Raynaud's Phenomenon Secondary to Systemic Sclerosis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study.

OBJECTIVE: To determine whether a single session of botulinum toxin type A (BTA) injections into both hands more effectively decreases the frequency of systemic sclerosis-associated Raynaud's phenomenon (SSc-RP) episodes than placebo. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III trial in patients with SSc-RP assessed the effect of 50-unit BTA or placebo injections into the palms of both hands around each neurovascular bundle during 1 session in winter. The primary end point was the between-group difference in the median change in the number of RP episodes from baseline (day 0) to 4 weeks postinjection. Values between the groups were compared with the Wilcoxon rank-sum test. RESULTS: The intent-to-treat analysis included 46 BTA-treated patients and 44 placebo recipients. At 4 weeks after assigned treatment injections, the median number of daily RP episodes decreased comparably in the BTA and placebo groups (median change -1 episode/day [interquartile range (IQR) -1.5, 0 episodes/day] and -1 episode/day [IQR -2.5, 0 episodes/day], respectively) (P = 0.77 versus placebo). Moreover, change in Raynaud's Condition Score, quality of life assessed by Health Assessment Questionnaire disability index, and hand function assessed by shortened Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Cochin Hand Function Scale from baseline to follow-up weeks 4, 12, and 24 did not differ significantly between groups. The BTA group experienced transient hand muscle weakness significantly more frequently (P = 0.003). CONCLUSION: Neither the primary nor secondary end points were reached, and our results do not support any beneficial effect of palmar BTA injections to treat SSc-RP.

Correlation of nailfold capillaroscopy findings with history of digital ulcer on same finger: Results of SCLEROCAP study.

Systemic sclerosis may be complicated by digital ulcers. Nailfold capillaroscopy on one finger might reflect an increased risk of digital ulcer (DU). In the present study we studied the correlations between a history of ulcer and capillary findings on the finger. METHOD: This study is part of Sclerocap, a multicenter study aiming at validating prospectively the prognostic value of Maricq's and Cutolo's capillaroscopic classifications during a three-year longitudinal follow-up. A history of past or present digital ulcer was recorded at inclusion and nailfold capillaroscopy was performed. Elementary findings as well as Cutolo and Maricq's classifications were assessed. RESULTS: 387 patients were included in Sclerocap (327 females, 60 males) and 3096 fingers were examined by capillaroscopy at inclusion: 316 fingers (10%) belonging to 113 patients had a history of DU. Late Cutolo's stage was statistically correlated with a history of DU, both by univariate: OR 2.08 [1.09-3.96] and multivariate analysis: OR 1.97 [1.06-3.63]. Among the elemental abnormalities, only edema and decreased capillary density were correlated with a history of DU by multivariate analysis: respectively OR 1.92 [1.17-3.16] and 0.65 [0.49-0.85]. CONCLUSION: This cross-sectional study in a large cohort of patients with systemic sclerosis shows a correlation between a history of digital ulcer and edema, a decrease in capillary density and the late stage in Cutolo's classification. The extent of capillary abnormalities on one finger is associated with a history of local digital ulcer. Capillaroscopy might be used to predict the risk of DU but these results need first to be confirmed by prospective studies.

Finger Systolic Blood Pressure Index Measurement: A Useful Tool for the Evaluation of Arterial Disease in Patients With Systemic Sclerosis.

OBJECTIVE: To evaluate the prevalence and clinical correlates of peripheral arterial disease of the upper limbs in patients with systemic sclerosis (SSc), as detected with finger brachial pressure index (FBPI) measurements. METHODS: This work is based on the baseline data of the SCLEROCAP multicenter cohort of SSc patients. Finger systolic blood pressure was measured with laser Doppler flowmetry, and the FBPI was obtained as its ratio over the ipsilateral brachial systolic blood pressure. An FBPI of <0.70 was used as the diagnostic criterion for occlusive arterial disease of the upper limbs. Thus, the prevalence of defined arterial disease as well as its clinical, biologic, and capillaroscopic correlates were evaluated. RESULTS: Among 326 enrolled patients, 177 (54.3%) met the criterion for arterial disease (FBPI <0.70). No association was found with the type of SSc nor with the type of associated antinuclear antibodies, but a significant association was found with the duration of the disease (P < 0.001), the capillaroscopic pattern (P < 0.001), and most strikingly with the presence of digital ulcers (42.9% versus 13.4%; P < 0.001). A quantitative relationship was found between the FBPI and the prevalence of digital ulcers and was shown to be independent from the capillaroscopic pattern. CONCLUSION: This cross-sectional study shows a high prevalence of arterial disease of the upper limbs in patients with SSc. FBPI appears to be a strong and independent predictor of digital ulcers. This study suggests that both macro- and microangiopathy are contributing to the ischemic damage of the fingertips.

A reappraisal of the presence of small or large fiber neuropathy in patients with erythromelalgia.

OBJECTIVE: To assess the contribution of large and small nerve fiber alteration in erythromelalgia (EM). METHODS: Thirty-three EM patients were included and underwent clinical evaluation based on EM severity score, DN4, and Utah Early Neuropathy Scale (UENS) score. Neurophysiological evaluation consisted in nerve conduction studies (NCS) for large nerve fibers and specific tests for small nerve fibers: electrochemical skin conductance, cold and warm detection thresholds, and laser evoked potentials. Finally, the evaluation of vascular changes was based on the presence of clinical feature of microvascular disorders and the measurement of the Toe Pressure Index (TPI). RESULTS: While 28 patients (85%) had vascular alteration on TPI or clinical features, 23 patients (70%) had small-fiber neuropathy on neurophysiological tests, and only 10 patients (30%) had large fiber neuropathy on NCS. Regarding clinical scores, there was no difference between groups (presence or absence of large- or small-fiber neuropathy or microvascular disorder) except for a higher UENS score in patients with large fiber neuropathy. CONCLUSION: Peripheral neuropathy, mostly involving small nerve fibers, is almost as common as microvascular changes in EM, but remains inconstant and not related to a specific neuropathic pattern or higher clinical severity. SIGNIFICANCE: The association of neuropathic and vascular factors is not systematic in EM, this syndrome being characterized by different pathophysiological mechanisms leading to a common clinical phenotype.

Low admission blood pressure as a marker of poor 1-year survival in patients with revascularized critical limb ischemia.

OBJECTIVE: To contrast the association between blood pressure (BP) level and antihypertensive medications at hospital admission with 1-year mortality in patients undergoing revascularization for critical limb ischemia (CLI). METHODS: From November 2013 to May 2019, 315 consecutive patients were retrospectively included. A median of seven (IQR 3-13) separate readings were recorded for each patient before revascularization procedure and the average represented patient's mean BP. BP-lowering medications, clinical and biological parameters were recorded at baseline. The main outcome was total 1-year mortality. RESULTS: The cohort included 172 men (55%) and 143 women (45%), with a mean age of 77.9 ±â€Š11.9 years. Treated hypertension was present in 245 (78%) patients; 288 (91%) patients had BP-lowering drug prescriptions (2.1 ±â€Š1.3 medications at baseline). Mean SBP, DBP, mean BP (MBP) and pulse pressure (PP) were 132 ±â€Š18, 70 ±â€Š8, 90 ±â€Š10 and 62 ±â€Š16mmHg. During 1-year follow-up, 80 (25.4%) patients died. In single-pressure multivariate analysis, SBP (hazard ratio 0.97; 95% CI 0.96-0.99; P = 0.005), MBP (hazard ratio 0.96; 95% CI 0.92-0.99; P = 0.01), PP (hazard ratio 0.97; 95% CI 0.95-0.99; P = 0.009), but not DBP, were inversely correlated with 1-year mortality, independently of age, coronary heart disease, left ventricular ejection fraction, brain natriuretic peptide, serum albumin, institutionalized status and antihypertensive drugs. Association between SBP, MBP and PP with 1-year mortality had a quite linear reverse pattern. CONCLUSION: Among patients undergoing revascularization for CLI, there is an inverse correlation between admission SBP, MBP and PP with 1-year mortality. BP may represent a modifiable therapeutic target to prevent poor outcome in CLI patients.

Prevalence and characteristics of pulmonary embolism in 1042 COVID-19 patients with respiratory symptoms: A nested case-control study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. Previous studies reported pulmonary embolism (PE) in severe COVID-19 patients. Aim of the study was to estimate the prevalence of symptomatic PE in COVID-19 patients and to identify the clinical, radiological or biological characteristics associated with PE. PATIENTS/METHODS: We conducted a retrospective nested case-control study in 2 French hospitals. Controls were matched in a 1:2 ratio on the basis of age, sex and center. PE patients with COVID-19 were compared to patients in whom PE was ruled out (CTPA controls) and in whom PE has not been investigated (CT controls). RESULTS: PE was suspected in 269 patients among 1042 COVID-19 patients, and confirmed in 59 patients (5.6%). Half of PE was diagnosed at COVID-19 diagnosis. PE patients did not differ from CT and CTPA controls for thrombosis risk factors. PE patients more often required invasive ventilation compared to CTPA controls (odds ratio (OR) 2.79; 95% confidence interval (CI) 1.33-5.84) and to CT controls (OR 8.07; 95% CI 2.70-23.82). PE patients exhibited more extensive parenchymal lesions (>50%) than CT controls (OR 3.90; 95% CI 1.54-9.94). D-dimer levels were 5.1 (95% CI 1.90-13.76) times higher in PE patients than CTPA controls. CONCLUSIONS: Our results suggest a PE prevalence in COVID-19 patients close to 5% in the whole population and to 20% of the clinically suspected population. PE seems to be associated with more extensive lung damage and to require more frequently invasive ventilation.

Anakinra for severe forms of COVID-19: a cohort study.

BACKGROUND: Coronaviruses can induce the production of interleukin (IL)-1ß, IL-6, tumour necrosis factor, and other cytokines implicated in autoinflammatory disorders. It has been postulated that anakinra, a recombinant IL-1 receptor antagonist, might help to neutralise the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hyperinflammatory state, which is considered to be one cause of acute respiratory distress among patients with COVID-19. We aimed to assess the off-label use of anakinra in patients who were admitted to hospital for severe forms of COVID-19 with symptoms indicative of worsening respiratory function. METHODS: The Ana-COVID study included a prospective cohort from Groupe Hospitalier Paris Saint-Joseph (Paris, France) and a historical control cohort retrospectively selected from the Groupe Hospitalier Paris Saint-Joseph COVID cohort, which began on March 18, 2020. Patients were included in the prospective cohort if they were aged 18 years or older and admitted to Groupe Hospitalier Paris Saint-Joseph with severe COVID-19-related bilateral pneumonia on chest x-ray or lung CT scan. The other inclusion criteria were either laboratory-confirmed SARS-CoV-2 or typical lung infiltrates on a lung CT scan, and either an oxygen saturation of 93% or less under oxygen 6 L/min or more, or aggravation (saturation ≤93% under oxygen 3 L/min) with a loss of 3% of oxygen saturation in ambient air over the previous 24 h. The historical control group of patients had the same inclusion criteria. Patients in the anakinra group were treated with subcutaneous anakinra (100 mg twice a day for 72 h, then 100 mg daily for 7 days) as well as the standard treatments at the institution at the time. Patients in the historical group received standard treatments and supportive care. The main outcome was a composite of either admission to the intensive care unit (ICU) for invasive mechanical ventilation or death. The main analysis was done on an intention-to-treat basis (including all patients in the anakinra group who received at least one injection of anakinra). FINDINGS: From March 24 to April 6, 2020, 52 consecutive patients were included in the anakinra group and 44 historical patients were identified in the Groupe Hospitalier Paris Saint-Joseph COVID cohort study. Admission to the ICU for invasive mechanical ventilation or death occurred in 13 (25%) patients in the anakinra group and 32 (73%) patients in the historical group (hazard ratio [HR] 0·22 [95% CI 0·11-0·41; p<0·0001). The treatment effect of anakinra remained significant in the multivariate analysis (HR 0·22 [95% CI 0·10-0·49]; p=0·0002). An increase in liver aminotransferases occurred in seven (13%) patients in the anakinra group and four (9%) patients in the historical group. INTERPRETATION: Anakinra reduced both need for invasive mechanical ventilation in the ICU and mortality among patients with severe forms of COVID-19, without serious side-effects. Confirmation of efficacy will require controlled trials. FUNDING: Groupe Hospitalier Paris Saint-Joseph.

Predictive value of admission blood pressure for 3-month mortality in patients undergoing revascularization for critical limb ischemia.

OBJECTIVE: In patients with critical limb ischemia (CLI), blood pressure (BP) impact on mortality is unknown. We analyzed the predictive value of SBP, DBP and pulse pressure (PP) at hospital admission on 3-month mortality in patients with CLI undergoing revascularization procedure. METHODS: From November 2013 to December 2018, 297 consecutive patients were retrospectively included. Admission BP was recorded using automated brachial sphygmomanometer, before revascularization procedure. A median of seven (IQR3-13) separate readings were recorded for each patient and the average represented patient's mean BP (mBP). Clinical and biological parameters were recorded at baseline. RESULTS: The cohort included 163 men (55%) and 134 women (45%) with a mean age of 77.7 ±â€Š11.9 years. Treated hypertension and diabetes were present in, respectively, 62 and 48% of patients. Mean SBP, DBP and PP were 132 ±â€Š18, 70 ±â€Š8 and 62 ±â€Š16 mmHg. Thirty-four patients (11.4%) died during 3-month follow-up, mostly from cardiovascular causes. In univariate analysis, age, female sex, brain natriuretic peptide and C-reactive protein were positively correlated with mortality. BMI, mSBP, mDBP, mPP, hemoglobin, serum albumin and statin treatment were negatively correlated with mortality. In single-pressure multivariate analyses, mSBP (P = 0.024) and mPP (P = 0.030) were negatively correlated with mortality. Association between mSBP and mortality had an asymptotic curve pattern and SBP level 135 mmHg or less was significantly correlated with mortality. CONCLUSION: In patients undergoing revascularization for CLI, admission SBP is an independent predictor for short-term mortality with a negative relationship. SBP level 135 mmHg or less represents a warning sign to explore and correct associated comorbidities.

Optimizing finger systolic blood pressure measurements with laser Doppler: Validation of the second phalanx site.

OBJECTIVE: Finger systolic blood pressure measurement (FSBP) has been shown helpful in the detection of distal arterial insufficiency in upper limbs. This work assesses the possibility to measure FSBP on the 2nd phalanx instead of the first one in order to improve its sensitivity and to verify this would not alter the repeatability of the measurement. METHODS: In this multicenter study, FSBP was measured twice in all fingers but the thumbs in consecutive systemic sclerosis patients on the first phalanx and the second phalanx in alternate order using laser-Doppler flowmetry. RESULTS: Thirty-seven patients were enrolled. The repeatability of FSBP was excellent and similar on the first and 2nd phalanxes with coefficients of variation respectively of 7.1% and 7.6%. While the correlation between the FSBP at the two sites was fair (Pearson coefficient 0.69; p < 0.001). The agreement was poor, with a mean difference of 14 mm Hg between the two sites. Significantly higher differences were found in fingers with digital ulcers. The ROC curves showed a better prediction of the 2nd phalanx measurements. CONCLUSION: FSBP has an excellent repeatability whatever the site of phalanx. However, measurements performed on the 2nd phalanx have a better sensitivity for the prediction of digital ulcers.

Evaluation of the Unyvero i60 ITI® multiplex PCR for infected chronic leg ulcers diagnosis.

OBJECTIVES: Unyvero i60 ITI multiplex PCR (mPCR) may identify a large panel of bacteria and antibiotic resistance genes. In this study, we compared results obtained by mPCR to standard bacteriology in chronic leg ulcer (CLU) infections. METHODS: A prospective study, part of the interventional-blinded randomized study "ulcerinfecte" (NCT02889926), was conducted at Saint Joseph Hospital in Paris. Fifty patients with a suspicion of infected CLU were included between February 2017 and September 2018. Conventional bacteriology and mPCR were performed simultaneously on deep skin biopsies. RESULTS: Staphylococcus aureus and Pseudomonas aeruginosa were the most detected pathogens. Regarding the global sensitivity, mPCR is not overcome to the standard culture. Anaerobes and slow growing bacteria were detected with a higher sensitivity rate by mPCR than standard culture. CONCLUSION: Unyvero i60 ITI multiplex PCR detected rapidly pathogenic bacteria in infected CLU especially anaerobes and slow growing bacteria and was particularly effective for patients previously treated with antibiotics.

Peripheral arterial disease and systematic detection of circulating tumor cells: rationale and design of the DETECTOR prospective cohort study.

BACKGROUND: Smoking is a strong risk factor for cancer and atherosclerosis. Cancer mortality, especially from lung cancer, overtakes cardiovascular (CV) death rate in patients with peripheral arterial disease (PAD). Only a few patients with lung cancer after PAD management may benefit from surgical excision. Circulating tumor cells (CTC) associated with low-dose chest CT (LDCT) may improve early cancer detection. This study focuses on a screening strategy that can address not only lung cancer but all tobacco-related cancers in this high-risk population. METHODS: DETECTOR Project is a prospective cohort study in two French University hospitals. Participants are smokers or former smokers (≥30 pack-years, quitted ≤15 years), aged ≥55 to 80 years, with atherosclerotic PAD or abdominal aortic aneurysm. After the first screening round combining LDCT and CTC search on a blood sample, two other screening rounds will be performed at one-year interval. Incidental lung nodule volume, volume doubling time and presence of CTC will be taken into consideration for adapted diagnostic management. In case of negative LDCT and presence of CTC, a contrast enhanced whole-body PET/CT will be performed for extra-pulmonary malignancy screening. Psychological impact of this screening strategy will be evaluated in population study using a qualitative methodology. Assuming 10% prevalence of smoking-associated cancer in the studied population, a total of at least 300 participants will be enrolled. DISCUSSION: Epidemiological data underline an increase incidence in cancer and related death in the follow-up of patients with PAD, compared with the general population, particularly for tobacco-related cancers. The clinical benefit of a special workup for neoplasms in patients with PAD and a history of cigarette smoking has never been investigated. By considering CTCs detection in this very high-risk selected PAD population for tobacco-induced cancer, we expect to detect earlier pulmonary and extra-pulmonary malignancies, at a potentially curable stage. TRIAL REGISTRATION: The study was registered in the French National Agency for Medicines and Health Products Safety (No N° EUDRACT_ID RCB: 2016-A00657-44) and was approved by the ethics Committee for Persons Protection (IRB number 1072 and n° initial agreement 2016-08-02; ClinicalTrials.gov identifier NCT02849041).

Correlation between capillaroscopic classifications and severity in systemic sclerosis: results from SCLEROCAP study at inclusion.

OBJECTIVES: We assessed the correlation between severity of systemic sclerosis (SSc) and current staging systems based on nailfold capillaroscopy. METHODS: SCLEROCAP is a multicenter prospective study including consecutive scleroderma patients who have a yearly routine follow-up with capillaroscopy and digital blood pressure measurement. Capillaroscopy images were read by two observers blinded from each other, then by a third one in the case of discordance. A follow-up of 3 years is planned. The present study assessed the correlation between severity of systemic sclerosis (SSc) and current staging systems based on nail fold capillaroscopy at enrollment in the SCLEROCAP study. Univariate and multivariate logistic regression analysis was performed for both the Maricq and Cutolo classifications. RESULTS: SCLEROCAP included 387 patients in one year. Maricq's active and Cutolo's late classifications were very similar. In multivariate analysis, the number of digital ulcers (OR for 2 ulcers or more, respectively 2.023 [1.074-3.81] and 2.596 [1.434-4.699]) and Rodnan's skin score >15 (OR respectively 32.007 [6.457-158.658] and 18.390 [5.380-62.865]) correlated with Maricq's active and Cutolo's late stages. Haemoglobin rate correlated with Cutolo's late stage (hemoglobin<100 vs. >120 g/dl: OR 0.223 [0.051-0.980]), and total lung capacity with Maricq's active one: increase in 10%: OR0.833 [0.717-0.969]. CONCLUSIONS: The correlations found between capillaroscopy and severity of SSc are promising before the ongoing prospective study definitively assesses whether capillaroscopy staging predicts complications of SSc. Only two capillaroscopic patterns seem useful: one involving many giant capillaries and haemorrhages and the other with severe capillary loss.

Reproducibility of capillaroscopic classifications of systemic sclerosis: results from the SCLEROCAP study.

Objectives: Subgroups of capillaroscopic scleroderma landscape have been correlated with stages of SSc: two groups for Maricq's classification (slow and active), and three for Cutolo's classification (early, active and late). We report inter- and intra-observer agreement for these classifications as a preliminary step in the multicentre prospective SCLEROCAP study, which aims to assess the classification and single capillaroscopic items as prognostic tools for SSc. Methods: SCLEROCAP included 385 patients. Agreement was studied in the first 100 patients, who were independently rated twice by two observers, blind to patients' characteristics; 30 of the patients were rated once by six observers. After consensus meetings, these ratings were held again. Kappa and intraclass correlation coefficients were used to assess agreement. Results: Interobserver agreement on 100 patients was moderate for Maricq and Cutolo classifications [κ 0.47 (0.28, 0.66) and 0.49 (0.33, 0.65), respectively], and became substantial after consensus meetings [0.64 (0.50, 0.77) and 0.69 (0.56, 0.81)]. Intra-observer agreement between two observers was moderate to substantial: κ 0.54 (0.33, 0.75) and 0.70 (0.57, 0.83) for Maricq's classification; 0.57 (0.38, 0.77) and 0.76 (0.65, 0.87) for Cutolo's. Thirty patients were rated once by each of six observers, and agreement was moderate to substantial: κ 0.57 ± 0.10 (Maricq) and 0.61 ± 0.12 (Cutolo). Agreement was substantial for bushy, giant capillaries and microhaemorrhages, moderate for capillary density and low for oedema, disorganization and avascular areas. Conclusion: The moderate reproducibility of Maricq and Cutolo classifications might hamper their prognostic value in SSc patients. Consensus meetings improve reliability, a prerequisite for better prognostic performances. A focus on giant capillaries, haemorrhages and capillary density might be more reliable.

Reproducibility of the scleroderma pattern assessed by wide-field capillaroscopy in subjects suffering from Raynaud's phenomenon.

Objectives: The aim of this work was to study inter- and intra-observer agreement for the diagnosis of scleroderma pattern by wide-field capillaroscopy. Methods: Images were taken from 50 patients known to have SSc and 50 controls consulting for RP who did not have SSc. These images were rated simultaneously by 11 experienced vascular medicine physicians as scleroderma pattern or not. Two weeks later, 7 of the 11 observers again rated the same images. Results: Inter-observer agreement was almost perfect between the 11 observers (κ 0.86 ± 0.01), and the proportion of concordant observations was 79% (70-87). When each observer was compared with the reference, agreement was also almost perfect: κ coefficient 0.92 ± 0.03 and proportion of concordant observations 79% (70-87). Intra-observer agreement was also almost perfect: median κ coefficient 0.94 (0.78-0.96) and median proportion of concordant observations 97% (89-98). Conclusion: Excellent inter- and intra-observer agreement was obtained in experienced vascular physicians for the diagnosis of capillaroscopic landscape by wide-field nailfold capillary microscopy.

Master regulators in primary skin fibroblast fate reprogramming in a human ex vivo model of chronic wounds.

Fibroblasts are important players in regulating tissue homeostasis. In the dermis, they are involved in wound healing where they differentiate into contractile myofibroblasts leading to wound closure. In nonhealing chronic wounds, fibroblasts fail to undertake differentiation. We established and used a human ex vivo model of chronic wounds where fibroblasts can undergo normal myofibroblast differentiation, or take on a nondifferentiable pathological state. At the whole genome scale, we identified the genes that are differentially regulated in these two cell fates. By coupling the search of evolutionary conserved regulatory elements with global gene network expression changes, we identified transcription factors (TF) potentially involved in myofibroblast differentiation, and constructed a network of relationship between these key factors. Among these, we found that TCF4, SOX9, EGR2, and FOXS1 are major regulators of fibroblast to myofibroblast differentiation. Conversely, down-regulation of MEOX2, SIX2, and MAF causes reprogramming of fibroblasts to myofibroblasts even in absence of TGF-ß, the natural inducer of myofibroblast differentiation. These results provide insight into the fibroblast differentiation program and reveal a TF network essential for cellular reprogramming. They could lead to the development of new therapeutics to treat fibroblast-related human pathologies.

A randomized, controlled, double-blind prospective trial with a Lipido-Colloid Technology-Nano-OligoSaccharide Factor wound dressing in the local management of venous leg ulcers.

Venous leg ulcers (VLUs) are the most prevalent chronic wounds in western countries with a heavy socioeconomic impact. Compression therapy is the etiologic treatment of VLU but until now no wound dressing has been shown to be more effective than another. The aim of this study was to assess the efficacy of a new dressing in the management of VLU. Adult patients presenting a noninfected VLU and receiving effective compression therapy were enrolled in this randomized, controlled, double-blind trial. The VLUs were assessed every 2 weeks for 8 weeks. The primary study outcome was the relative Wound Area Reduction (WAR, in %), and the secondary objectives were absolute WAR, healing rate, and percentage of wounds with >40% surface area reduction. One hundred eighty-seven patients were randomly allocated to treatment groups. Median WAR was 58.3% in the Lipido-Colloid Technology-Nano-OligoSaccharide Factor (TLC-NOSF) dressing group (test group) and 31.6% in the TLC dressing group (control group) (difference: -26.7%; 95% confidence interval: -38.3 to -15.1%; p = 0.002). All other efficacy outcomes were also significant in favor of the TLC-NOSF dressing group. Clinical outcomes for patients treated with the new dressing are superior to those patients treated with the TLC dressing (without NOSF compound), suggesting a strong promotion of the VLU healing process.