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1.
Clin Exp Dermatol ; 47(10): 1873-1875, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35699684

RESUMO

We found that the systematic use of Delphi consensus diagnostic criteria resulted in substantial changes in management patterns in cases of suspected pyoderma gangrenosum (PG), including a reduction in systemic corticosteroid use, and significantly improved clinical outcomes. This improvement may have resulted from a combination of reduced misdiagnosis, optimized management and reduced iatrogenic harm. Increased utilization of validated diagnostic criteria for PG could optimize provider heuristics, increase diagnostic accuracy, and optimize management and clinical outcomes.


Assuntos
Pioderma Gangrenoso , Corticosteroides/uso terapêutico , Técnica Delphi , Humanos , Pioderma Gangrenoso/diagnóstico
2.
Am J Ther ; 28(5): e525-e530, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33491968

RESUMO

BACKGROUND: The thrombopoietin (TPO) agonists, eltrombopag and romiplostim, stimulate the production of platelets and offer an effective treatment option in relapsed/refractory immune thrombocytopenia (ITP). Recently published 2019 ITP guidelines recommend the TPO agonists as second-line therapy following corticosteroids; however, little data offer insights into comparative efficacy and tolerability. STUDY QUESTION: Is there a difference in the efficacy between romiplostim and eltrombopag in relapsed/refractory ITP? STUDY DESIGN: We conducted a single-center, retrospective chart review of patients with ITP treated with romiplostim or eltrombopag. MEASURES AND OUTCOMES: The primary objective was a sustained platelet response, defined as platelets greater than 50,000/µL in more than 66% of clinic visits over a 6-month period. Secondary objectives sought to evaluate response to and tolerability of TPO agonists. RESULTS: The study included 107 consecutive patients, 67 (63%) on romiplostim and 40 (37%) on eltrombopag. Previous corticosteroids and rituximab were used in 95% and 50% of patients, respectively. There was no difference identified in platelet responses between the TPO-RAs, 72% romiplostim versus 65% eltrombopag (P = 0.520). In addition, no differences were identified in secondary measures of response. CONCLUSIONS: In our experience with romiplostim and eltrombopag for ITP, we did not identify a difference in the efficacy of these agents. Further larger and prospective evaluations should be considered.


Assuntos
Púrpura Trombocitopênica Idiopática , Receptores de Trombopoetina , Plaquetas , Humanos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Proteínas Recombinantes de Fusão , Estudos Retrospectivos , Rituximab
8.
J Anim Ecol ; 82(6): 1254-64, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23895187

RESUMO

1. In mammals, nutrient allocation during lactation is a critical component of maternal care as milk intake promotes juvenile growth and survival, and hence maternal and offspring fitness. 2. Milk composition varies widely across mammals and is hypothesized to have arisen via selection pressures associated with environment, diet and life history. These hypotheses have been proposed based on observations and/or cross-species comparisons that did not standardize for stage of lactation and did not consider evolutionary history of the species in analyses. 3. We conducted the largest comparative analysis of milk composition to date accounting for phylogenetic relationships among species in order to understand the selective advantage of producing milk with specific nutritional profiles. We examined four milk constituents in association with species ecology while incorporating phylogeny in analyses. 4. Phylogenetic signal was apparent for all milk constituents examined. After controlling for phylogeny, diet and relative lactation length explained the greatest amount of variation in milk composition. Several aspects of species' ecologies, including adaptation to arid environments, reproductive output and maternal body mass were not associated with milk composition after accounting for phylogeny. 5. Our results suggest that milk composition is largely a function of evolutionary history, maternal nutrient intake and duration of milk production. Arriving at these conclusions was made possible by including the evolutionary relationships among species.


Assuntos
Evolução Biológica , Mamíferos/fisiologia , Leite/química , Fenômenos Fisiológicos da Nutrição , Animais , Dieta , Ingestão de Energia , Feminino , Lactação , Mamíferos/classificação , Filogenia
9.
Indian J Dermatol Venereol Leprol ; 89(6): 799-806, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37436019

RESUMO

The Janus kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathway has been identified as a key player in the pathophysiology of alopecia areata and a potential target for therapy. Here, we give a narrative review of what is known about Janus kinase inhibitors in alopecia areata. Several clinical trials as well as smaller studies have demonstrated hair regrowth and remission with oral Janus kinase inhibitors therapy, even in patients who failed conventional treatment. Baricitinib is the only US FDA-approved treatment for alopecia areata but data for other oral Janus kinase inhibitors such as tofacitinib, ruxolitinib and ritlecitinib are also promising. Fewer clinical trials have investigated topical Janus kinase inhibitors for alopecia areata, with many of them terminated early due to unfavourable results. Overall, Janus kinase inhibitors are an efficacious addition to the therapeutic arsenal for treatment-refractory alopecia areata. Further work is needed to examine the effects of long-term usage of Janus kinase inhibitors, the efficacy of topical Janus kinase inhibitors, as well as to identify biomarkers that could predict differential therapeutic responses to the various Janus kinase inhibitors.


Assuntos
Alopecia em Áreas , Inibidores de Janus Quinases , Humanos , Alopecia em Áreas/tratamento farmacológico , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , Alopecia/tratamento farmacológico , Cabelo , Janus Quinases
10.
J Invest Dermatol ; 143(7): 1157-1167.e10, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36716917

RESUMO

ERAP1, ERAP2, and LNPEP are aminopeptidases implicated in autoimmune pathophysiology. In this study, we show that ERAP2 is upregulated and ERAP1 is downregulated in patients with psoriasis who are homozygous for autoimmune-linked variants of ERAP. We also demonstrate that aminopeptidase expression is not uniform in the skin. Specifically, the intracellular antigen-processing aminopeptidases ERAP1 and ERAP2 are strongly expressed in basal and early spinous layer keratinocytes, whereas granular layer keratinocytes expressed predominantly LNPEP, an aminopeptidase specialized in the processing of extracellular antigens for presentation to T cells. In psoriasis, basal keratinocytes also expressed the T-cell- and monocyte-attracting chemokine, CCL2, and the T-cell-supporting cytokine, IL-15. In contrast, TGF-ß1 was the major cytokine expressed by healthy control basal keratinocytes. SFRP2-high dermal fibroblasts were also noted to have an ERAP2-high expression phenotype and elevated HLA-C. In psoriasis, the SFRP2-high fibroblast subpopulation also expressed elevated CXCL14. From these results, we postulate that (i) an increased ERAP2/ERAP1 ratio results in altered antigen processing, a potential mechanism by which ERAP risk alleles predispose individuals to autoimmunity; (ii) ERAP2-high expressing cells display a unique major histocompatibility complex-bound peptidome generated from intracellular antigens; and (iii) the granular layer peptidome is skewed toward extracellular antigens.


Assuntos
Predisposição Genética para Doença , Psoríase , Humanos , Aminopeptidases/genética , Psoríase/genética , Fenótipo , Citocinas/genética , Antígenos de Histocompatibilidade Menor/genética , Polimorfismo de Nucleotídeo Único
11.
J Pharm Pract ; : 8971900221125827, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36113085

RESUMO

Objective: To review the pharmacology, pharmacokinetics, clinical efficacy, safety, dosing and administration, and place in therapy of avatrombopag for the treatment of immune thrombocytopenia and chronic liver disease-associated thrombocytopenia. Summary: Avatrombopag is an orally administered thrombopoietin receptor agonist approved for the treatment of immune thrombocytopenia and is the first oral thrombopoietin receptor agonist approved for the treatment of perioperative thrombocytopenia associated with chronic liver disease in adults. The efficacy and safety of avatrombopag has been demonstrated in a multicenter, randomized, double blind, placebo-controlled phase III study in the setting of immune thrombocytopenia and in 2 identically designed, multicenter, randomized, double blind, placebo-controlled phase III trials in the setting of thrombocytopenia associated with chronic liver disease. The most common adverse events reported in the clinical trials were headache, fatigue, and gastrointestinal toxicities. The incidence of bleeding events was comparable between the avatrombopag and placebo treatment groups in each study. Avatrombopag has not been shown to be associated with hepatoxicity and does not require food restriction like the other oral thrombopoietin receptor agonist for immune thrombocytopenia, eltrombopag. Also, unlike eltrombopag for immune thrombocytopenia, it can be dosed less frequently than once daily. Conclusion: Avatrombopag offers another safe and effective oral option for the treatment of immune thrombocytopenia without food restrictions and an alternative, transfusion-sparing option for thrombocytopenia associated with chronic liver disease patients undergoing surgery.

12.
Front Med (Lausanne) ; 9: 1087382, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36703899

RESUMO

Pemphigus vulgaris (PV) is a rare immunobullous disease. Although it classically presents as generalized flaccid blisters affecting the skin and mucosae, atypical cases of PV can be diagnostically challenging. Herein, we report an underrecognized non-blistering manifestation of pemphigus vulgaris, which we call mounded and refractory keratoses (MARK). MARK presents as exuberant scaling plaques on the scalp, often in the skin of color. When MARK features are present, pemphigus vulgaris is prone to misdiagnosis, clinically and histopathologically, leading to delays in appropriate treatment. Specifically, biopsies from these patients may resemble acantholytic dyskeratosis, resulting in initial misdiagnosis. Thus, recognizing this presentation may aid physicians in diagnosing and monitoring the recurrence of pemphigus vulgaris.

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