Ionic liquid-based electroactive materials: a novel approach for cardiac tissue engineering strategies.

Cardiac tissue regeneration strategies are increasingly taking advantage of electroactive scaffolds to actively recreate the tissue microenvironment. In this context, this work reports on advanced materials based on two different ionic liquids (ILs), 2-hydroxyethyl-trimethylammonium dihydrogen phosphate ([Ch][DHP]) and choline bis(trifluoromethylsulfonyl)imide ([Ch][TFSI]), combined with poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) for the development of ionic electroactive IL/polymer hybrid materials for cardiac tissue engineering (TE). The morphological, physico-chemical, thermal and electrical properties of the hybrid materials, as well as their potential use as scaffolds for cardiac TE applications, were evaluated. Besides inducing changes in surface topography, roughness and wettability of the composites, the incorporation of [Ch][DHP] and [Ch][TFSI] leads to the increase in surface (σsurface) and volume (σvolume) electrical conductivities. Furthermore, washing the hybrid samples with phosphate-buffered saline solution strongly decreases the σsurface, whereas σsurface and σvolume of the composites remain almost unaltered after exposure to ultraviolet sterilization treatment. Additionally, it is verified that the incorporation of IL influences the P(VDF-TrFE) microstructure and crystallization process, acting as a defect during its crystallization. Cytotoxicity assays revealed that hybrid films based on [Ch][DHP] alone are not cytotoxic. These films also support H9c2 myoblast cell adhesion and proliferation, demonstrating their suitability for cardiac TE strategies based on electroactive microenvironments.

Liver Injury in Psoriasis Patients Receiving Ustekinumab: A Retrospective Study of 44 Patients Treated in the Clinical Practice Setting.

INTRODUCTION: The therapy of patients with psoriasis and liver disease can be a challenge due to the increased risk of adverse effects from traditional systemic treatments; in addition, although the anti-tumor necrosis factor agents are considered safer, they have also been associated with drug-induced liver injury and reactivation of viral hepatitis. Ustekinumab has a different mechanism of action and the little that is known of its effects on the liver comes from pivotal studies. The objectives of this study were to estimate the incidence of drug-induced liver injury in patients treated with ustekinumab in daily clinical practice and to analyze liver alterations in those patients with pre-existing liver disease. METHOD: All patients treated with the standard regimen of ustekinumab were included in the study. Variables gathered included age, sex, type of psoriasis, nail involvement, arthritis, previous treatments, history of liver disease, viral serology, Psoriasis Area Severity Index (at baseline and at 12, 16, and 52 weeks), transaminase levels, manifestations of liver disease, liver ultrasound, and factors such as body mass index, alcohol consumption, and ferritin levels. RESULTS: Grade 1 elevation of the transaminases was only observed in 6 patients; no cases of severe hypertransaminasemia were observed. None of the patients with elevation of the transaminases at baseline developed problems during treatment. CONCLUSIONS: Ustekinumab-related liver injury is uncommon and mild. From a hepatic point of view, the drug appears safe, even in patients with pre-existing liver disease and those who have developed altered liver function previously with other drugs.

Development of an autoimmune syndrome affecting the skin and internal organs in P-selectin glycoprotein ligand 1 leukocyte receptor-deficient mice.

OBJECTIVE: To define and characterize the progression of the spontaneous autoimmune disease that develops in mice in the absence of the leukocyte adhesion receptor P-selectin glycoprotein ligand 1 (PSGL-1). METHODS: Skin-resident immune cells from PSGL-1-deficient mice and C57BL/6 control mice of different ages were isolated and analyzed by flow cytometry. Biochemical parameters were analyzed in mouse serum and urine, and the presence of serum autoantibodies was investigated. Skin and internal organs were extracted, and their structure was analyzed histologically. RESULTS: Skin-resident innate and adaptive immune cells from PSGL-1(-/-) mice had a proinflammatory phenotype with an imbalanced T effector cell:Treg cell ratio. Sera from PSGL-1(-/-) mice had circulating autoantibodies commonly detected in connective tissue-related human autoimmune diseases. Biochemical and histologic analysis of skin and internal organs revealed skin fibrosis and structural and functional abnormalities in the lungs and kidneys. Furthermore, PSGL-1(-/-) mice exhibited vascular alterations, showing loss of dermal vessels, small vessel medial layer remodeling in the lungs and kidneys, and ischemic processes in the kidney that promote renal infarcts. CONCLUSION: Our study demonstrates that immune system overactivation due to PSGL-1 deficiency triggers an autoimmune syndrome with characteristics similar to systemic sclerosis, including skin fibrosis, vascular alterations, and systemic organ involvement. These results suggest that PSGL-1 expression contributes to the maintenance of the homeostasis of the immune system and could act as a barrier for autoimmunity in mice.

Spanish adaptation of the European guidelines for the evaluation and treatment of actinic keratosis.

Current trends in our setting indicate that the prevalence of actinic keratosis and similar diseases will increase in coming years and impose a greater burden on health care resources. A long list of clinical features must be taken into account when approaching the treatment of actinic keratosis. Until recently, therapeutic approaches focused solely on ablative procedures and the treatment of individual lesions and did not take into account areas of field cancerization. Now that the therapeutic arsenal has grown, standardized criteria are needed to guide the optimal choice of treatment for each patient. The elaboration of evidence-based consensus recommendations for the diagnosis and treatment of actinic keratosis generates knowledge that will help clinicians to deliver the highest level of care possible, standardizing decision-making processes and enhancing awareness among all the health professionals involved in the care pathway.

Paraneoplastic pemphigus with eosinophilic spongiosis and autoantibodies against desmocollins 2 and 3.

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease associated with neoplasms, typically lymphoproliferative disorders. PNP is characterized clinically by painful erosive stomatitis and polymorphous skin lesions. Histopathological findings are also very varied, and include lichen planus-like and pemphigus-like changes. These polymorphic clinicopathological findings are probably due to the complex pathogenic mechanism, in which both cellular and humoral immunity are implicated. Eosinophilic spongiosis, although infrequent, can be found with pemphigus herpetiformis and bullous pemphigoid, although this association has not been established in PNP. The presence of autoantibodies against envoplakin and periplakin in PNP has been reported, but autoantibodies against desmocollins (Dscs) have been found in only a very few cases of PNP, probably due to the lack of studies on such associations. We report the first case, to our knowledge, of PNP with eosinophilic spongiosis as the initial histopathological finding, and presence of autoantibodies to Dsc2 and Dsc3.

Study of idiopathic, exogenous photodermatoses, part II: photobiologic testing.

The second of this series describes the characteristics of 3 types of photobiologic studies: the light test, the photochallenge test, and the photopatch test. We explain how the tests are carried out, the expected results, and their clinical usefulness in various photodermatoses. These tests are needed before attempting to induce adaptation (skin hardening or light tolerance) in the most debilitating cases.

Study of idiopathic, exogenous photodermatoses. Part 1: pathophysiology and technical aspects of photobiologic studies.

Photodermatoses are skin conditions that are induced or exacerbated by electromagnetic radiation (including visible light, UV light, and infrared radiation) from the sun or artificial light sources. In Part 1 of this series we review current understanding of the pathophysiology of these processes and their classification. We also discuss technical aspects and the basic physics of photobiology and describe the equipment required for photobiologic testing and calibration (light sources and measurement instruments).

The relationship between tumour necrosis factor (TNF)-α promoter and IL12B/IL-23R genes polymorphisms and the efficacy of anti-TNF-α therapy in psoriasis: a case-control study.

BACKGROUND: Antitumour necrosis factor (anti-TNF)-α agents can be used successfully to treat patients with psoriasis and other inflammatory diseases. However, very few studies have examined the relationship between TNF-α polymorphisms and the response to anti-TNF-α agents. OBJECTIVES: To study the association of single nucleotide polymorphisms (SNPs) of the TNF-α promoter and IL12B/IL23R genes with the response to anti-TNF-α in patients with psoriasis. METHODS: SNPs for the TNF-α promoter and IL12B/IL23R genes, and the presence of the HLA-Cw6 haplotype were genotyped for 109 patients. We studied the association between these SNPs and the efficacy of treatment at 3 and 6 months [Psoriasis Area and Severity Index (PASI) and body surface area (BSA)]. RESULTS: Patients with the TNF-α-238GG genotype more frequently achieved a PASI75 at 6 months (82·5% vs. 58·8%, P = 0·049). At 6 months, patients with the TNF-α-857CT/TT genotypes showed greater improvements in PASI score and BSA (83·1% vs. 92·7%, P = 0·004; 82·7% vs. 92·6%, P = 0·009) and more frequently achieved PASI75 (71·4% vs. 96·3%, P = 0·006). More patients with the TNF-α-1031TT genotype achieved PASI75 at 3 months (90·8 vs. 75·7, P = 0·047) and 6 months (85·5% vs. 65·7%, P = 0·038) and demonstrated superior improvements in PASI at 6 months (89·9% vs. 78·7%, P = 0·041). Patients with the IL23R-GG genotype (rs11209026) achieved PASI90 at 6 months more frequently (66·3% vs. 0, P = 0·006) and the improvement of the PASI score was also greater (86·8% vs. 67·8%, P = 0·013). Patients with the HLA-Cw6 haplotype showed poorer response than those without this haplotype. CONCLUSION: This study identified a relationship between certain TNF-α and IL12B/IL23R polymorphisms and the short-term response to anti-TNF-α drugs. If these results are confirmed, this information will allow for stratified consent with more accurate prediction of response/personalized choice of treatment hierarchy for the patient.

Coexistence of marginal zone cutaneous B-cell lymphoma and classic Hodgkin disease: does a biological relationship exist?

The coexistence of non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) in the same patient, although previously reported, is very unusual. This situation is extremely rare when the first diagnosis is a cutaneous B NHL, and exceptional if there is no personal background of cytostatic treatment. We report a 44-year-old man who developed cutaneous nodules over a period of two years. A marginal zone cutaneous B-cell lymphoma was diagnosed. On staging investigation a mass in the lingual tonsil was found and excision biopsy showed a classical Hodgkin lymphoma.

Macular lymphocytic arteritis: first clinical presentation with ulcers.

Macular lymphocytic arteritis describes a recently reported entity, clinically characterized by asymptomatic hyperpigmented macules on the lower limbs, without association of systemic diseases. Histopathologically it is characterized by a lymphocytic arteritis with a hyalinized fibrin ring. We report a new case presenting with ulceration, a finding not previously described. A 25-year-old Hispanic woman was evaluated for a 1-year history of a gradually progressive, asymptomatic eruption that begins at level of both knees and progressively affects both legs and feet. She also referred recently appeared ulcers on inner right ankle without previous traumatism. Physical examination revealed multiple fairly well-defined light brown and faint pink patches with petechiae on as well as retiform crusts and livedoid lesions on inner right ankle. Both types of lesions were biopsied showing lymphocytic arteritis with fibrinoid necrosis and thrombus. There were no relevant laboratory alterations. The clinical peculiarity of our case is the clinical image of the lesions mimicking a pigmented purpuric dermatosis and the presence of a non-traumatic ulcer which could be explained because chronic lymphocytic damage may cause ischemic damage. Ulceration in our case supports consideration of macular arteritis as a latent form of cutaneous polyarteritis nodosa.

Prevalence of antiphospholipid antibodies in patients with subacute and chronic cutaneous lupus erythematosus.

BACKGROUND AND OBJECTIVES: The prevalence of antiphospholipid antibodies (APLAs) has been extensively studied in patients with systemic lupus erythematosus (SLE) but not in those with cutaneous lupus erythematosus (CLE). We determined the prevalence of APLAs among our patients with CLE, and analyzed their clinical and serologic characteristics. MATERIALS AND METHODS: This retrospective study analyzed 182 patients with subacute or chronic CLE who had been in follow-up for 5 years. We selected those positive for 1 or more of the following APLAs in 2 measurements at least 12 weeks apart: lupus anticoagulant (LA), anticardiolipin antibodies (ACAs), and anti-ß2-glycoprotein i (anti-ß2-GPI) antibodies. In the case of ACAs and anti-ß2-GPI antibodies, only patients with titers greater than or equal to 40 U/mL were selected. RESULTS: We obtained a series of 13 patients (4 with subacute disease and 9 with chronic disease). Seven met the diagnostic criteria for SLE and only 1 met the diagnostic criteria for antiphospholipid syndrome (APS). The prevalence of APLAs was 38% among patients with SLE and 3.65% among those without SLE. The most prevalent APLA was LA, present in 10 patients. Antinuclear antibodies (ANAs) were detected in 12 patients and anti-double-stranded DNA antibodies in 11. CONCLUSIONS: The prevalence of APLAs among our patients with CLE who did not meet the diagnostic criteria for SLE was similar to that reported in the general population. This, along with the strong assocation between the presence of ANAs and the presence of APLAs, would bring into question the value of determining APLAs in patients with CLE who are negative for ANAs. We also note that there was a high prevalence of discoid lesions but a low prevalence of APS among our patients with CLE who were positive for APLAs.

Safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and chronic viral hepatitis B or C: a retrospective, multicentre study in a clinical setting.

BACKGROUND: Both the safety and efficacy of biologic therapy may be affected in the presence of highly prevalent chronic viral hepatitis. OBJECTIVE: To evaluate the safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and concomitant chronic viral hepatitis. METHODS: This was a retrospective, multicentre study. Twenty-five patients with psoriasis and concurrent hepatitis C virus (HCV) (20 patients) or hepatitis B virus (HBV) (five patients) infection who had received at least one biologic agent (etanercept, 21 treatments; adalimumab, four; ustekinumab, four; infliximab, two) were included. Clinical, imaging and laboratory data were recorded. RESULTS: In the case of HCV infection, the majority of the patients did not exhibit increases in their viral load or serum liver tests. Aspartate aminotransferase, alanine aminotransferase and gamma glutamyl transpeptidase were doubled from the baseline measurement in only one patient treated with etanercept. Two other cases exhibited viral load increases during the follow-up period. In total, 18 of the 26 treatments achieved a 75% improvement in their Psoriasis Area and Severity Index (PASI 75) score during the follow-up period. Two patients treated with etanercept were diagnosed with hepatocellular carcinoma. In the case of HBV infection, all of the patients were being treated with antiviral therapy, and none presented significant variations in viral load or serum liver enzymes. All patients achieved a PASI 75 during follow-up. CONCLUSIONS: Biologic therapy was effective and safe for the majority of our patients with HCV and HBV infection, although there may be a risk of reactivation or aggravation. We describe the first cases to receive ustekinumab. The use of biologics should be limited to those cases in which the risk-benefit ratio is justified.

[Neutrophilic urticaria or urticaria with predominantly neutrophilic inflammatory infiltrate: study of its clinical and histopathologic characteristics and its possible association with rheumatic disease]. / Urticaria con infiltrado inflamatorio de predominio neutrofílico o urticaria neutrofílica. Estudio de sus características clínicas e histopatológicas y de su posible asociación con enfermedad reumatológica.

INTRODUCTION: Neutrophilic urticaria, described by Winkelmann in 1985, has yet to be completely defined and its clinical significance is poorly understood. Nevertheless, recent publications suggest that it could be a marker for rheumatic disease. The primary objective of this study was to compare the prevalence of rheumatic disease in 2 groups of patients with urticaria: those with conventional urticaria (non-neutrophilic inflammatory infiltrate) and those with neutrophilic urticaria. MATERIAL AND METHODS: We retrospectively reviewed all biopsy samples taken from urticarial lesions in our hospital between January 1, 1999 and June 28, 2009. Urticaria was classified according to predefined morphologic and histopathologic patterns. We compared the clinical and histologic characteristics of neutrophilic urticaria with those of conventional urticarias in the 84 patients included. RESULTS: Of the 84 patients, 57.1% had neutrophilic urticaria. We did not find significant differences between the percentages of patients with rheumatic disease between the neutrophilic and nonneutrophilic urticaria groups. In patients with acute urticaria, we found a significantly higher proportion of samples with histopathologic signs of neutrophilic urticaria as opposed to conventional histopathology. Patients with neutrophilic urticaria also had higher white blood cell counts. CONCLUSIONS: The percentage of samples with neutrophilic urticaria in this series (57.1%) is higher than the percentages reported in the literature, possibly because we tended to biopsy recent lesions. We highlight that the presence of neutrophils in the biopsies of urticaria is a common finding and does not appear to be associated with other diseases.