Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, little is known about the implication of NETs in cutaneous lupus. In this case series of 30 patients, we compared the amounts of neutrophils producing NETs in cutaneous lesions of different subtypes of lupus (5 with discoid lupus or DLE, 5 with subacute cutaneous lupus or SCLE, 11 with acute cutaneous SLE, 7 with lupus panniculitis and 2 with chilblains). Immunofluorescence was performed on formalin-fixed paraffin-embedded skin biopsies using antibodies against neutrophilic granules (elastase, myeloperoxidase, PR-3 proteins and citrullinated histone 3). Dihydroethidium staining was performed to detect reactive oxygen species (ROS), known inducers of NETs. NETs were detected in the different subtypes of cutaneous lupus as well as in cutaneous lesions of SLE. The amounts of neutrophils producing NETs were significantly higher in lupus panniculitis (49%), acute cutaneous SLE (41%) and DLE (32%), in comparison with SCLE (5%) and chilblains (0%). This suggests that NETs might be associated with more tissue damage and scarring. ROS were observed in the different cutaneous subtypes of lupus independent of NETs.
Plasmacytoid dendritic cells (pDCs) are bone marrow-derived DCs with plasma cell morphology. They are lineage negative and express CD4, CD123, HLA-DR, blood-de
definition of publication was publication of results either in peer-reviewed journals or on ClinicalTrials.gov; our secondary definition was publication in peer-reviewed journals. Variables included in our model (Table 1) were determined a priori.Overall, 141 RCTs met our inclusion criteria. Sixteen RCTs (11%), with 4904 participants, were discontinued prematurely. Reasons included business or sponsor decision (n = 7), insufficient patient recruitment (n = 4) and administration or conduct problems (n = 1). Four RCTs did not provide a reason for discontinuation. Unblinded RCTs (vs. RCTs with blinding of any sort) were significantly more likely to be discontinued (OR 16Á7, 95% CI 2Á22-125) (Table 1).In total, 104 RCTs (74%) met our primary definition of publication, including 93 published in peer-reviewed journals. RCTs investigating topical treatments were significantly more likely to result in nonpublication of results in the multivariable analysis using our primary definition of publication (OR 24Á2, 95% CI 1.14-516) (Table 1), as well as our secondary definition of publication (OR 14Á7, 95% CI 1Á17-185). Discontinued RCTs were associated with nonpublication in the univariable analysis, but this association was attenuated when adjusted for additional factors (OR 4Á50, 95% CI 0Á74-27Á4).In this study of phase III RCTs of psoriasis treatments, 11% of the RCTs were discontinued prematurely, a rate lower than reported in other areas of medicine. [2][3][4] Half of the discontinued RCTs did not cite a reason for discontinuation, and for those that did, the lack of semantic standardization for reasons for discontinuation listed on ClinicalTrials.gov leads to ambiguity and predisposes to misinterpretation. Over a quarter of psoriasis RCTs did not publish their results in peer-reviewed journals or on ClinicalTrials.gov, which is consistent with RCTs in other areas of medicine. 2,3 Topical intervention was the only factor significantly associated with increased nonpublication following adjustment for additional variables. A report on ClinicalTrials.gov for Janus kinase inhibitor therapy suggested that the nonpublication of trials for topical interventions may be related to a lack of efficacy, as many were discontinued due to inefficacy or futility. 5 These findings may also be explained by the increased emphasis in the literature on the evolving systemic treatment landscape.Our study limitations include potential inaccuracies or missing data in trial registry entries, although trial data undergo quality control via automated checks and manual review by ClinicalTrials.gov staff. Our statistical analyses were also limited by the small number of events for certain variables, with inadequate statistical power to assess associations thus limiting interpretation of results.The nonpublication of RCTs of psoriasis remains prevalent. Insight into challenges that prevent RCTs from reaching completion is limited by the lack of reporting of reasons for discontinuation on trial registries. Reporting of reasons for discontinuation on t...
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Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebocontrolled and ustekinumab-controlled phase 3 trials.
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