1,721,042 research outputs found
Parasympathetic activity increases with digital microvascular damage and vascular endothelial growth factor in systemic sclerosis
No full textThe imbalance between angiogenic and angiostatic factors with derangement of the microvasculature are hallmarks of systemic sclerosis (SSc). Raynaud's phenomenon in SSc probably is due to the impaired neuroendothelial control mechanisms between vasoconstriction and vasodilatation. The aim of this study is to evaluate autonomic nervous system function using heart rate variability (HRV) analysis and to correlate with vascular endothelial growth factor (VEGF)
Machine learning approaches as an alternative to traditional statistical methods in cardiovascular risk prediction
Full text linkPhase angle could be a marker of microvascular damage in systemic sclerosis
No full textObjectives: Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction with
fibrosis of skin and internal organs. Integrity of the endothelial cell is important to its physiologic function
such as production of angiogenetic factors. The aim of this study was to assess whether phase angle (PhA) is
altered in patients with SSc and whether its values correlate with vascular endothelial growth factor (VEGF)
and digital microvascular damage.
Methods: Patients with SSc and matched healthy controls underwent VEGF determination and bioimpedentiometry
(BIA) for PhA assessment. Clinical assessment, disease activity index (DAI), disease severity scale, and
nailfold videocapillaroscopy (NCV) were performed in patients with SSc.
Results: Fifty-five patients (46 women) with a mean age of 53.2 § 13.7 y were studied. The mean value of
VEGF was significantly higher in patients with SSc than in the healthy controls (240.3 § 149.5 versus 139 §
87.5; P = 0.035). The mean value of PhA was significantly lower in the patient grouop than in the healthy controls
(4.51 § 0.87 versus 5.22 § 0.55; P < 0.0001). A significant positive correlation was found between VEGF
and PhA (P = 0.009, beta coefficient = 1.48) in SSc patients. A negative correlation between VEGF and DAI
(P = 0.048, b coefficient = 0.48) was found. PhA median value was significantly (P = 0.006) lower in patients
with late pattern SSc (4.2 [2.55.3]). PhA median value was significantly (P < 0,0001) lower in patients with
digital ulcers (DUs; 4.2 [2.55.3]) than in those without DUs (3.80 [2.505] versus 4.75 [2.807.3]). These
data were confirmed in both female and male patients.
Conclusions: The evaluation of VEGF with PhA, NVC, and DUs could be useful to estimate cellular and microvascular
damage in patients with SSc.
Working and safety profiles of JAK/STAT signaling inhibitors. Are these small molecules also smart?
No full textThe Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway is an important intracellular route through which many different extracellular soluble molecules, by reaching membrane receptors, can signal the nucleus. The spectrum of soluble molecules that use the JAK/STAT pathway through their corresponding receptors is quite large (almost 50 different molecules), and includes some cytokines involved in the pathogenesis of many immune-mediated diseases. Such diseases, when left untreated, present an evident hyperactivation of JAK/STAT signaling. Therefore, given the pathogenetic role of JAK/STAT, drugs known as JAK inhibitors (JAKi), that target one or more JAKs, have been developed to counteract JAK/STAT signal hyperactivation. As some hematological malignancies present an intrinsic JAK/STAT hyperactivation due to a JAK mutation, some JAKi have also been successfully used in this context. Regulatory agencies for drug administration in different countries have already approved a few JAKi in the setting of either immune-mediated diseases or hematological malignancies.
Aim of this review is to describe the physiology of intracellular JAK/STAT pathway signaling and the pathological conditions associated to its dysregulation. Then, the rationale for targeting JAK in rheumatic autoimmune diseases is discussed, along with clinical data from registration studies showing the efficacy of these drugs. Finally, the excellent safety profile of JAKi is discussed in the context of the apparent poor specificity of JAK/STAT pathway signal
Could Sars-coronavirus-2 trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects?
No full textSerum resistin is predictive marker of development of new digital ulcers in systemic sclerosis
No full textSystemic sclerosis (SSc) is autoimmune disease characterized by endothelial dysfunction and microvascular damage. Resistin has been implied in microvascular dysfunction. Objective of this study is to evaluate the association between baseline
resistin and development of new digital ulcers (DUs) in SSc patients. At baseline, serum resistin has been assessed in 70
female SSc patients and 26 healthy controls (HC). In SSc patients, clinical assessment was performed at baseline and after a
52-weeks follow-up. Serum resistin level was increased in SSc patients compared to HC [5.89 ng/ml (2.5 ng/ml–8.1 ng/ml)
vs 2.3 ng/ml (0.4 ng/ml–2.4 ng/ml), p=0.0004)]. Resistin was lower (p=0.005) in SSc patients with early capillaroscopic
pattern than patients with active or late capillaroscopic pattern [2.49 ng/ml (0.89 ng/ml–5.81 ng/ml) vs 7.11 ng/ml (3.48 ng/
ml–11.35 ng/ml) and 6.49 ng/ml (3.35 ng/ml–8.87 ng/ml), respectively]. After a 52-weeks follow-up, 34 (48.6%) patients
developed new DUs. Median serum resistin was signifcantly higher in patients with new DUs than in patients without new
DUs [6.54 ng/ml (3.35 ng/ml–11.02 ng/ml) vs 4.78 ng/ml (1.06 ng/ml–7.6 ng/ml), p=0.019]. Kaplan–Meier curves show a
signifcantly reduced free survival from DUs in patients with increased resistin (p=0.002). In multivariate analysis, resistin
is associated with the development of new DUs. Increased serum resistin level is a predictive marker of new DUs in SSc
Prolonged remission is associated with a reduced risk of cardiovascular disease in patients with systemic lupus erythematosus: a GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study
No full textProlonged remission (PR), defined as a 5-year consecutive period of no disease activity based on SLEDAI-2K, has been reported to be associated with a lower damage accrual over time in patients with systemic lupus erythematosus (SLE), as the consequence of a lower activity burden. Since disease activity is considered to play a role in the incidence of cardiovascular disease (CVD), we investigated the relationship, if any, between PR and the occurrence of a subsequent first CV event in patients with SLE. Out of 488 patients consecutively admitted to two tertiary Italian centers from November 1, 2000, to December 31, 2016, the 294 patients, who had been followed at least for 5 years, had not experienced any CV event at admission, and had been visited biannually during follow-up, were considered for the present study. The incidence of a first CV in patients who had achieved PR was compared with that registered in those who had not. Moreover, it was compared among PR patients subdivided into three groups: complete remission, clinical off-corticosteroids (offCR), and clinical on-corticosteroids remission (onCR). Kaplan–Meier curves and the log-rank test were used to analyze differences in event-free survival among groups. Cox regression was used to investigate disease and therapeutic features associated with the development of a first CV event. During 9 years median follow-up time, 24 (8.1%) CV events occurred. Out of the 294 patients, 126 (42.8%) had achieved PR. Kaplan–Meier analysis revealed a greater overall CV event-free rate in these patients as compared to both those with a shorter lasting remission and those who had never remitted (log-rank test χ2 = 14.43; p = 0.0001). In addition, CV outcome did not differ among PR patients, irrespectively the type of remission achieved (p > 0.05). At multivariate analysis, hydroxychloroquine therapy and PR resulted to be protective (HR 0.19; HR 0.18), while arterial hypertension and antiphospholipid positivity increased the risk of a first CV event (HR 2.61; HR 2.47). The PR, whichever the subtype, is associated with a better CV outcome and should be considered as a treat-to-target goal in the CV risk management of the lupus patient
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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