Capillaroscopy in 2016 : new perspectives in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disorder of unknown etiology characterized by early impairment of the microvascular system. Nailfold microangiopathy and decreased peripheral blood perfusion are typical clinical aspects of SSc. The best method to evaluate vascular injury is nailfold videocapillaroscopy, which detects peripheral capillary morphology, and classifies and scores the abnormalities into different patterns of microangiopathy. Microangiopathy appears to be the best evaluable predictor of the disease development and has been observed to precede the other symptoms by many years. Peripheral blood perfusion is also impaired in SSc, and there are different methods to assess it: laser Doppler and laser speckle techniques, thermography and other emerging techniques

Coexistence of osteopoikilosis with seronegative spondyloarthritis and Raynaud's phenomenon: first case report with evaluation of the nailfold capillary bed and literature review.

Osteopoikilosis (OPK) is a rare autosomal dominant bone disorder characterized by numerous hyperostotic areas that tend to localize in periarticular osseous regions. It is usually asymptomatic and is often diagnosed incidentally during X-rays. OPK may be an isolated finding or associated with other pathologies, e.g. skin manifestations, rheumatic and/or skeletal disorders. We report a literature review and, for the first time, the coexistence of OPK with seronegative spondyloarthritis and Raynaud's phenomenon in a 48-year old female. To the best of our knowledge, this is the first case of OPK studied by videocapillaroscopy, demonstrating the absence of specific microvascular abnormalities of nailfold capillaries

Subclinical dermal involvement is detectable by high frequency ultrasound even in patients with limited cutaneous systemic sclerosis.

Background: The aim of the study was to detect by skin high-frequency ultrasound (US) possible subclinical skin involvement in patients affected by limited cutaneous systemic sclerosis (lcSSc), in those skin areas apparently not affected by the disease on the basis of a normal modified Rodnan skin score (mRSS). Differences in dermal thickness (DT) in comparison with healthy subjects were investigated. Methods: Fifty patients with lcSSc (age 62 \ub1 13 years (mean \ub1 SD), disease duration 5 \ub1 5 years) and 50 sex-matched and age-matched healthy subjects (age 62 \ub1 11 years) were enrolled. DT was evaluated by both mRSS and US at the usual 17 skin areas (zygoma, fingers, dorsum of the hands, forearms, upper arms, chest, abdomen, thighs, lower legs and feet). Non-parametric tests were used for the statistical analysis. Results: Subclinical dermal involvement was detected by US even in the skin areas in patients with lcSSc, who had a normal local mRSS. In addition, statistically significantly higher mean DT was found in almost all skin areas, when compared to healthy subjects (p < 0.0001 for all areas). In particular, DT was significantly greater in patients with lcSSc than in healthy subjects in four out of six skin areas with a normal mRSS (score = 0) (upper arm, chest and abdomen), despite the clinical classification of lcSSc. Conclusions: This study strongly suggests that subclinical dermal involvement may be detectable by US even in skin areas with a normal mRSS in patients classified as having lcSSc. This should be taken into account during SSc subset classification in clinical studies/trial

Microvascular damage evaluation in systemic sclerosis : the role of nailfold videocapillaroscopy and laser techniques

Microvascular damage and a decrease in peripheral blood perfusion are typical features of systemic sclerosis (SSc) with serious clinical implications, not only for a very early diagnosis, but also for disease progression. Nailfold videocapillaroscopy is a validated and safe imaging technique able to detect peripheral capillary morphology, as well as to classify and to score any nailfold abnormalities into different microangiopathy patterns. Capillaroscopic analysis is now included in the ACR/EULAR classification criteria for SSc. The decrease in peripheral blood perfusion is usually associated with microvascular damage in SSc, which may be studied by different methods. Several of these make use of safe laser technologies. This paper focuses on these new clinical aspects to assess SSc microvascular impairment

Podridão vermelha da raiz da soja em cultivos com diferentes sistemas de manejo e coberturas do solo.

O objetivo deste trabalho foi avaliar o efeito dos sistemas de manejo do solo e de coberturas de inverno sobre o número de propágulos de Fusarium spp. no solo, a incidência da podridão?vermelha?da?raiz (PVR) e a produtividade das cultivares de soja CD 206 e FT Fênix. Foram realizados dois experimentos nos anos agrícolas de 2006/2007 e 2007/2008. Utilizou-se o delineamento experimental de blocos ao acaso, em parcelas subsubdivididas, com três repetições. Foram avaliados dois sistemas de preparo do solo: plantio direto e revolvimento do solo na profundidade de 25 cm. As coberturas de inverno utilizadas foram: aveia?preta, com duas densidades de plantio; aveia?preta + ervilhaca; azevém; e pousio. A incidência da doença, na safra de 2006/2007, na cultivar FT Fênix, foi menor que na CD 206. Na safra 2007/2008, não houve diferença significativa. Houve incremento na produtividade, de 125 kg ha?1, com o solo revolvido, em comparação ao plantio direto. A cobertura com aveia?preta + ervilhaca apresentou maior número de propágulos de Fusarium spp. no solo, na safra de 2006/2007. No entanto, no segundo ano, essa diferença não foi observada. Os sistemas de preparo do solo e as coberturas de inverno utilizadas não influenciam a incidência da PVR em cultivares de soja ou o número de propágulos de Fusarium spp. no solo. O sistema com solo revolvido proporciona aumento de produtividade da soja, no segundo ano de manejo

Low Arousal Threshold Estimation Predicts Failure of Mandibular Advancement Devices in Obstructive Sleep Apnea Syndrome

Introduction: The treatment of choice for obstructive sleep apnea syndrome (OSAS) is continuous positive airway pressure (CPAP). However, CPAP is usually poorly tolerated and mandibular advancement devices (MADs) are an alternative innovative therapeutic approach. Uncertainty still remains as to the most suitable candidates for MAD. Herein, it is hypothesized that the presence of low arousal threshold (low ArTH) could be predictive of MAD treatment failure. Methods: A total of 32 consecutive patients, with OSAS of any severity, who preferred an alternate therapy to CPAP, were treated with a tailored MAD aimed at obtaining 50% of their maximal mandibular advancement. Treatment response after 6 months of therapy was defined as AHI 58.3%. Results: There were 25 (78.1%) responders (p-value < 0.01) at 6 months. Thirteen patients (40.6%) in the non-severe group reached AHI lower than 5 events per hour. MAD treatment significantly reduced the median AHI in all patients from a median value of 22.5 to 6.5 (74.7% of reduction, p-value < 0.001). The mandibular advancement device reduced AHI, whatever the disease severity. A significant higher reduction of Delta AHI, after 6 months of treatment, was found for patients without low ArTH. Conclusions: Low ArTH at baseline was associated with a poorer response to MAD treatment and a lower AHI reduction at 6 months. A non-invasive assessment of Low ArTH can be performed through the Edwards' score, which could help to identify an endotype with a lower predicted response to oral appliances in a clinical setting

Don't forget the jumper's knee in the young sportsman: evaluation of patellar tendinopathy with a high frequency ultrasound probe.

8Patellar tendinopathy, or Jumper's knee, is a painful knee condition caused by inflammation of the patella tendon. This condition is most frequently observed in subjects who play sports that require repetitive regular jumping. Jumper's knee is frequently misdiagnosed as a minor injury and many athletes, like our patient, keep on training and competing and either tend to ignore the injury or attempt to treat it themselves. However, jumper's knee is a serious condition that requires a correct and timely diagnosis, which often necessitates ultrasound investigation in order to start the most appropriate treatment.openopenRuaro B; Cutolo M; Alessandri E; Zaottini F; Picasso R; Pistoia F; Ferrari G; Martinoli C.Ruaro, B; Cutolo, M; Alessandri, E; Zaottini, F; Picasso, R; Pistoia, F; Ferrari, G; Martinoli, C

Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages.

Background Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing profibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its profibrotic effects through the interaction with its receptors (ETA and ETB). The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells. Methods Cultured human monocytes (THP-1 cell line) were activated into macrophages (M0 macrophages) with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls) or treated with either ET-1 (100nM) or interleukin-4 (IL-4, 10ng/mL, M2 inducer) for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM)-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells) or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M) for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Gene expression of interleukin(IL)-10 and macrophage derived chemokine (CCL-22) was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography. Results ET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBMderived macrophages compared to M0-controls and untreated cells. In cultured PBMderived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1-mediated effects were contrasted by ETA/BRA treatment in both cultured cell types. Conclusion ET-1 seems to induce the M2 phenotype in cultured human macrophages, a process apparently contrasted by the action of the ETA/BRA, suggesting possible clinical implications in those fibrotic diseases characterized by increased ET-1 concentrations, such as systemic sclerosis but also type 2 diabetes

A circulating cell population showing both M1 and M2 monocyte/macrophage surface markers characterizes systemic sclerosis patients with lung involvement.

Background: Systemic sclerosis (SSc) is a disorder characterized by immune system alterations, vasculopathy and fibrosis. SSc-related interstitial lung disease (ILD) represents a common and early complication, being the leading cause of mortality. Monocytes/macrophages seem to have a key role in SSc-related ILD. Interestingly, the classically (M1) and alternatively (M2) activated monocyte/macrophage phenotype categorization is currently under revision. Our aim was to evaluate if circulating monocyte/macrophage phenotype could be used as biomarker for lung involvement in SSc. To this purpose we developed a wide phenotype characterization of circulating monocyte/macrophage subsets in SSc patients and we evaluated possible relations with lung involvement parameter values. Methods: A single centre cross-sectional study was performed in fifty-five consecutive SSc patients, during the year 2017. All clinical and instrumental tests requested for SSc follow up and in particular, lung computed tomography (CT) scan, pulmonary function tests (PFTs), Doppler echocardiography with systolic pulmonary artery pressure (sPAP) measurement, blood pro-hormone of brain natriuretic peptide (pro-BNP) evaluation, were performed in each patient in a maximum one-month period. Flow cytometry characterization of circulating cells belonging to the monocyte/macrophage lineage was performed using specific M1 (CD80, CD86, TLR2 and TLR4) and M2 surface markers (CD204, CD163 and CD206). Non-parametric tests were used for statistical analysis. Results: A higher percentage of circulating CD204 + CD163 + CD206 + TLR4 + CD80 + CD86 + and CD14 + CD206 + CD163 + CD204 + TLR4 + CD80 + CD86 + mixed M1/M2 monocyte/macrophage subsets, was identified to characterize patients affected by SSc-related ILD and higher systolic pulmonary artery pressure. Mixed M1/M2 monocyte/macrophage subset showed higher percentages in patients positive for anti-topoisomerase antibody, a known lung involvement predictor. Conclusions: The present study shows for the first time, through a wide flow cytometry surface marker analysis, that higher circulating mixed M1/M2 monocyte/macrophage cell percentages are associated with ILD, sPAP and anti-topoisomerase antibody positivity in SSc, opening the path for research on their possible role as pathogenic or biomarker elements for SSc lung involvement