Objective
To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)–associated uveitis.
Methods
We conducted a multicenter study of patients with ...JIA‐associated uveitis that was refractory to conventional immunosuppressive drugs and anti–tumor necrosis factor (anti‐TNF) agents.
Results
We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 range 1–5), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 μm to 259.1 ± 39.5 μm after 6 months of TCZ (P = 0.012). The best‐corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P < 0.01). After a median follow‐up of 12 months, visual improvement persisted, and complete remission of uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral conjunctivitis and bullous impetigo in 1 patient.
Conclusion
TCZ appears to be a useful therapy for severe refractory JIA‐associated uveitis.
Summary
Background
Frontal fibrosing alopecia (FFA) is a chronic cicatricial alopecia with an increasing incidence and unknown aetiology.
Aim
To identify possible environmental and hormonal factors ...related to FFA.
Methods
We conducted a multicentre case–control study paired by sex and age, and recruited 664 women (335 cases and 329 controls) and 106 men (20 cases and 86 controls). Study subjects completed an exhaustive questionnaire enquiring about pharmacological, environmental, hormonal, social, job exposure, lifestyle, drugs and diet factors to which they were exposed at least 5 years prior to the onset of the disease.
Results
For women, there was a statistical association between alopecia and history of pregnancy (OR = 1.6; 95% CI 1.06–2.41), use of facial sunscreen (OR = 1.6; 95% CI 1.06–2.41) and hormone replacement therapy (HRT) (OR = 1.76; 95% CI 1.11–2.8) or raloxifene (no controls exposed therefore OR was not calculated), exposure to alkylphenolic compounds (OR = 1.48; 95% CI 1.05–2.08), and presence of rosacea (OR = 1.91; 95% CI 1.07–3.39), lichen planus pigmentosus (LPP) (OR = 5.14; 95% CI 1.11–23.6) or hypothyroidism (OR = 1.73; 95% CI 1.11–2.69). For men, there was a statistical association between alopecia and use of facial sunscreens (OR = 11.6; 95% CI 1.7–80.9) or antiageing creams (OR = 1.84; 95% CI 1.04–3.23).
Conclusions
FFA seems to be associated with hormonal exposure (pregnancy, HRT and raloxifene), comorbidities (hypothyroidism, LPP and rosacea) and environmental factors (facial sunscreens, antiageing creams and occupational exposure). Further research is required to analyse the exact mechanism in which these environmental factors participate in the development of this alopecia.
The hypothesis of this study is that long-term high-fat diets (HFD) induce perivascular adipose tissue (PVAT) dysfunction characterized by a redox imbalance, which might contribute to aggravate ...endothelial dysfunction in obesity.
C57BL/6J mice were fed either control or HFD (45% kcal from fat) for 32 weeks. Body weight, lumbar and mesenteric adipose tissue weights were significantly higher in HFD animals compared to controls. The anticontractile effect of PVAT in mesenteric arteries (MA) was lost after 32 week HFD and mesenteric endothelial-dependent relaxation was significantly impaired in presence of PVAT in HFD mice (Emax = 71.0±5.1 vs Emax = 58.5±4.2, p<0.001). The inhibitory effect of L-NAME on Ach-induced relaxation was less intense in the HFD group compared with controls suggesting a reduction of endothelial NO availability. Expression of eNOS and NO bioavailability were reduced in MA and almost undetectable in mesenteric PVAT of the HFD group. Superoxide levels and NOX activity were higher in PVAT of HFD mice. Apocynin only reduced contractile responses to NA in HFD animals. Expression of ec-SOD and total SOD activity were significantly reduced in PVAT of HFD mice. No changes were observed in Mn-SOD, Cu/Zn-SOD or catalase. The ratio GSSG/(GSH+GSSG) was 2-fold higher in the mesenteric PVAT from HFD animals compared to controls.
We suggest that the imbalance between pro-oxidant (NOX, superoxide anions, hydrogen peroxide) and anti-oxidant (eNOS, NO, ecSOD, GSSG) mechanisms in PVAT after long-term HFD might contribute to the aggravation of endothelial dysfunction.
Median concentration of total PBDEs in maternal serum, paternal serum, umbilical cord serum, and breast milk samples were 12, 12, 17, and 6.1 ng/g lipid weight (lw) in Vallecas and 9.7, 12, 15, and ...5.5 ng/g lw in Getafe. The median value found in placentas was 1.9 ng/g lw (in Vallecas). BDE 47 was the predominant congener in serum samples (maternal, paternal, and umbilical cord), while BDE 209 was predominant in placenta and breast milk samples. BDEs 196 and 197 were detected in most of the placenta and breast milk samples. The results show that PBDEs, like other POPs, can cross the placenta barrier, although the speed of the process seems to differ for each PBDE congeners. The total PBDE concentrations found in this study are consistent with research reported elsewhere. They are in the same range as those recently reported by other European and Asian studies and lower than those conducted in the U.S.A. No significant differences were found (p > 0.05) between regions, sexes, and ages, while statistically significant differences (p < 0.05) were found between maternal serum, umbilical cord serum, and breast milk samples. The presence of PBDEs in cord blood and placenta samples indicates that there is prenatal exposure of PBDEs, which could continue after birth via breast milk.
Background
Some chronic inflammatory skin diseases, such as psoriasis, have been associated with an increased prevalence of non‐alcoholic fatty liver disease (NAFLD). Nevertheless, this prevalence in ...hidradenitis suppurativa (HS) has not been assessed to date.
Objectives
To determine the prevalence of NAFLD in patients with HS and the risk factors associated with this disorder.
Methods
This case–control study enrolled 70 HS patients and 150 age‐ and gender‐matched controls who were evaluated by hepatic ultrasonography (US) and transient elastography (TE) after excluding other secondary causes of chronic liver disease. The diagnosis of NAFLD was established if US and/or TE were altered.
Results
The prevalence of NAFLD was significantly increased in patients with HS compared to controls (72.9% vs. 24.7%: P < 0.001). In the multivariable regression model adjusted for age, sex and classic metabolic risk factors for NAFLD, HS was significantly and independently associated with the presence of NAFLD OR 7.75 confidence interval (CI) 2.54–23.64; P < 0.001.
Conclusions
Our results show a high prevalence of NAFLD in HS patients independent of classic metabolic risk factors. Therefore, we suggest HS patients to be evaluated for NAFLD and managed accordingly.
In spite of the extensive potential of human mesenchymal stem cells (hMSCs) in cell therapy, little is known about the molecular mechanisms that regulate their therapeutic properties. We aimed to ...identify microRNAs (miRNAs) involved in controlling the transition between the resting and reparative phenotypes of hMSCs, hypothesizing that these miRNAs must be present in the undifferentiated cells and downregulated to allow initiation of distinct activation/differentiation programs. Differential miRNA expression analyses revealed that miR-335 is significantly downregulated upon hMSC differentiation. In addition, hMSCs derived from a variety of tissues express miR-335 at a higher level than human skin fibroblasts, and overexpression of miR-335 in hMSCs inhibited their proliferation and migration, as well as their osteogenic and adipogenic potential. Expression of miR-335 in hMSCs was upregulated by the canonical Wnt signaling pathway, a positive regulator of MSC self-renewal, and downregulated by interferon-γ (IFN-γ), a pro-inflammatory cytokine that has an important role in activating the immunomodulatory properties of hMSCs. Differential gene expression analyses, in combination with computational searches, defined a cluster of 62 putative target genes for miR-335 in hMSCs. Western blot and 3'UTR reporter assays confirmed RUNX2 as a direct target of miR-335 in hMSCs. These results strongly suggest that miR-335 downregulation is critical for the acquisition of reparative MSC phenotypes.
Introduction
Treatment retention and adherence are used as outcomes in numerous randomized clinical trials and observational studies conducted in the addiction field. Although usual criteria are ...3/6 months of treatment retention or number of sessions attended, there is not a methodological support for conclusions using these criteria. This study analyzed the usefulness of retention and adherence to predict therapeutic success.
Methods
Retrospective observational study using real‐world data from electronic health records of 11,907 patients in treatment diagnosed with cocaine, alcohol, cannabis and opiate use disorders or harmful use.
Results
Moderate effect size relations were found between the different type of clinical discharge and months in retention (η2 = 0.12) and proportion of attendance (η2 = 0.10). No relationship was found with the number of sessions attended. Using cut‐off points (i.e., 3 or 6 months in treatment or attending 6 therapy sessions) worsens the ability to predict the type of discharge.
Discussions/Conclusion
Treatment retention and adherence are indicators moderately related to therapeutic success. Research using these indicators to assess the effectiveness of therapies should complement their results with other clinical indicators and quality of life measures.
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