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BACKGROUND: New highly effective drugs for moderate-to-severe cutaneous psoriasis are regularly marketed, and the hierarchy of treatments thus requires frequent review. OBJECTIVES: A Delphi method was used to enable a structured expert consensus on the use of systemic treatments and phototherapy among adults with moderate-to-severe psoriasis. METHODS: The Delphi method consists in achieving a convergence of opinions among a panel of experts using several rounds of questionnaires with controlled feedback between rounds. A two-part Delphi questionnaire was administered online to French psoriasis experts. In the first part, 180 items related to the prescription of systemic treatments and phototherapy for adult patients with moderate-to-severe psoriasis were grouped into 21 sections covering different lines of treatment and different forms of cutaneous psoriasis. The experts voted on each proposal using an ordinal 7-point Likert scale. The second part comprised 11 open-ended questions about special indications for each therapeutic class. These were converted into 101 questions for subsequent rounds. Consensus was deemed to have been reached if more than 80% of the experts agreed with a given proposal. RESULTS: Three rounds of questionnaires were sequentially sent to 35 participants between November 2021 and March 2022. Thirty-three (94%) completed all three rounds. For plaque psoriasis, only methotrexate was recommended by the experts as first-line systemic treatment (89% of votes). Cyclosporin was advocated in pustular and erythrodermic psoriasis, and acitretin was suggested for hyperkeratotic and palmoplantar psoriasis. In the event of failure of or intolerance to non-biological systemic treatments, guselkumab, risankizumab, ixekizumab or secukinumab were recommended by more than 80% of the experts. Tumor Necrosis Factor (TNF) inhibitors remain useful for patients with cardiovascular risk factors. Special indications were provided for each therapeutic class (methotrexate/narrowband ultraviolet B phototherapy, psoralen/ultraviolet A phototherapy, cyclosporin, acitretin, apremilast, TNF inhibitors, interleukin (IL)-12/23 inhibitors, IL-17(R)A inhibitors, and IL-23 inhibitors). CONCLUSIONS: This expert consensus statement indicate that newly available IL-17 and IL-23 inhibitors may be favored over TNF and IL-12/23 inhibitors as first-line biologics. The Centre of Evidence of the French Society of Dermatology has drawn up a decision-making algorithm to guide clinicians in the therapeutic management of moderate-to-severe psoriasis.
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BACKGROUND: Few melanoma cases are reported in individuals with intellectual disability (ID), and prognostic factors at diagnosis are unknown in this population. This work was designed to investigate whether prognostic factors at diagnostic are different in patients with ID compared with a general population. METHODS: Melanoma cases retrieved from Hérault's Tumour Registry (HTR) from 1995 to 2015 were cross-referenced against a list of adult patients with ID, living in Hérault. Major prognostic factors were compared with those in non-ID melanoma patients included in HTR and in patients followed by Montpellier University Hospital and included in the Réseau pour la Recherche et l'Investigation Clinique sur le Mélanome (RIC-Mel) database. RESULTS: Ten melanoma cases in individuals with ID were identified and compared with 3804 non-ID melanoma cases in HTR and 1024 non-ID melanoma cases included in RIC-Mel. Mean Breslow thickness at diagnosis was 4.6 mm in melanoma cases among those with ID versus 1.89 mm in HTR (P = 0.109) and 2.36 mm in RIC-Mel (P = 0.156). Stage at diagnosis was superior to stage IIB in 42.9% of ID cases versus 11.4% of non-ID cases in HTR (P < 0.05) and 8.5% in RIC-Mel (P < 0.05). CONCLUSIONS: Melanomas in patients with ID had less favourable prognostic factors at diagnosis, including higher Breslow thickness and more advanced stage, than melanomas in non-ID patients. These adverse prognostic factors indicate a later diagnosis in this population, leading to a poorer prognosis. This work underlines the need to improve melanoma screening among individuals with ID.
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Deficiência Intelectual , Melanoma , Neoplasias Cutâneas , Adulto , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/epidemiologia , Melanoma/diagnóstico , Melanoma/epidemiologia , Melanoma/patologia , Prognóstico , Sistema de Registros , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologiaRESUMO
INTRODUCTION: When a patient treated by immune checkpoint inhibitors for metastatic melanoma presents with pulmonary symptoms, several diagnoses are possible. We report a case of acute granulomatous lung disease secondary to repeated kayexalate inhalations, and probably stimulated by immunotherapy. CASE REPORT: A patient treated with pembrolizumab and then ipilimumab presented with fever and acute shortness of breath. His pulmonary symptoms got progressively worse, leading to an acute respiratory distress syndrome. Chest CT displayed a pattern of non-specific organized pneumonia. Pulmonary infection, tumor progression, specific immune-related lung toxicity and immunotherapy-induced sarcoidosis were discussed. Histopathological examination of a lung biopsy showed a foreign body granulomatous macrophage reaction associated with crystalline, basophilic, purple and laminated elements, evoking kayexalate particles. These elements helped rewrite the diagnosis and confirmed a kayexalate-induced granulomatous lung disease secondary to repeated aspiration. The patient's respiratory condition got better following discontinuation of kayexalate together with systemic corticosteroids. Symptoms relapsed with resumption of the immunotherapy but were controlled with the addition of a new course of prolonged systemic corticosteroid therapy. We can hypothesize that immunotherapy played a role in the recurrence of the granulomatous lung reaction, or that there was an association between an aspiration pneumonia and an immunotherapy-induced lung toxicity. CONCLUSION: Facing respiratory symptoms during immunotherapy, the treatment may be the cause, but lung biopsy should be performed rapidly to arrive to a certain diagnosis.
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Pneumopatias , Melanoma , Humanos , Imunoterapia/efeitos adversos , Pneumopatias/induzido quimicamente , Pneumopatias/diagnóstico , Melanoma/tratamento farmacológico , Recidiva Local de Neoplasia , PoliestirenosRESUMO
INTRODUCTION: Rituximab (RTX), currently recommended as first-line treatment in moderate to severe pemphigus vulgaris (PV) and superficial pemphigus (PS) along with initial systemic steroids, may also be used as second-line or subsequent treatment, and this therapeutic strategy was investigated in a real-life monocentre retrospective survey. MATERIAL AND METHODS: All patients treated between January 2010 and March 2018 with RTX as second-line or subsequent treatment for moderate to severe PV or PS and followed for at least one year were included. The main objective was to evaluate rates and times of complete clinical remission (CCR) after a first course of RTX. The secondary objectives consisted mainly of treatment safety, and frequency and time to relapse after the initial CCR. RESULTS: The 24 patients selected received on average 2 cycles of RTX (i.e. 24 initial cycles and 24 additional cycles in all) over a mean follow-up period of 45 months. 18/24 (75%) patients achieved initial CCR within a mean 7.7 months. Despite at least one relapse in 13/18 initially responding patients regardless of relapse time, 59% (14/24) and 33% (8/24) were either in CCR and off treatment, or in partial remission, whether treated or untreated, according to the latest patient news, with an overall response rate of 92%. Safety was fair in these fragile patients. DISCUSSION AND CONCLUSION: This survey of the practical use of RTX confirms its interest in moderate to severe pemphigus as a second-line or subsequent treatment, a situation that probably remains relevant even if this molecule is increasingly used as first-line therapy.
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Fatores Imunológicos/uso terapêutico , Pênfigo/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Estudos RetrospectivosRESUMO
We present an analytical model for the role of hydrogen bonding on the spin-orbit coupling of a model DNA molecule. Here, we analyze in detail the electric fields due to the polarization of the hydrogen bond on the DNA base pairs and derive, within a tight binding analytical band folding approach, an intrinsic Rashba coupling which should dictate the order of the spin active effects in the chiral-induced spin selectivity effect. The coupling found is ten times larger than the intrinsic coupling estimated previously and points out to the predominant role of hydrogen bonding in addition to chirality in the case of biological molecules. We expect similar dominant effects in oligopeptides, where the chiral structure is supported by hydrogen-bonding and bears on orbital carrying transport electrons.
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DNA/química , Modelos Químicos , Transporte de Elétrons , Ligação de Hidrogênio , Oligopeptídeos/químicaRESUMO
BACKGROUND: Drug addiction causes chronic wounds (CW) responsible for severe complications. Very few studies are available on this topic. The aim of our study was to describe the demographic, clinical and etiological characteristics as well as the course of CW in drug addicts. PATIENTS AND METHODS: This was a retrospective and prospective multicenter study including all drug addicts with CW. RESULTS: We included 58 patients (17 prospectively), 84.5% of whom were male, of median age 43 years, presenting multiple CW as a result of intravenous (78.2%), inhaled (41.1%) and/or snorted (20%) drug abuse. Addiction to opioids (68.4%), cocaine (47.4%) and/or cannabis (40.4%) was ended and/or treated through substitution in 79.3% of patients. CW were fibrinous and necrotic (42.9 to 53.6%), recurrent (54.2%), and in some cases had been present for more than 1 year (61.5%). Intravenous drug addiction was associated with large, fibrinous, ulcers in a setting of venous and lymphatic insufficiency (74%). Only 23% of these wounds involved the upper limbs. Necrotic ulcers associated with clinical arteriopathy were described mainly with inhaled addiction. Abscesses (50%) and erysipelas (29.3%) were the most common cutaneous complications. After 3 months, 50% of CW were improved and 29.2% of patients were lost to follow-up. DISCUSSION: Drug abuse-related CW occurred preferentially in young men with history of intravenous abuse. For the most part, CW were seen on the legs and were associated with venous and lymphatic insufficiency, and the resulting major risk for cutaneous infection increased morbidity and mortality in this population in whom medical follow-up is inherently complicated.
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Abscesso/etiologia , Erisipela/etiologia , Úlcera Cutânea/etiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Insuficiência Venosa/etiologiaAssuntos
Fatores Imunológicos/uso terapêutico , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Rituximab/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
AIM: These guidelines for the treatment of psoriasis have been developed by the Psoriasis Research Group of the French Society of Dermatology with the aim of providing updated decision-making algorithms for the systemic treatment of adult patients with moderate-to-severe psoriasis. METHODS: Our algorithms were generated after rigorous evaluation of existing guidelines on the treatment of psoriasis and of publications concerning new systemic treatments, not yet incorporated into existing guidelines. A total of nine existing guidelines and 53 publications related to new systemic treatments were found to meet our criteria for use in generating the algorithms. RESULTS: We propose two new algorithms to assess therapeutic response, both of which incorporate emerging criteria for evaluating treatment goals. Updated therapeutic strategy algorithms, incorporating both established and new systemic therapies, were also generated for the treatment of plaque psoriasis and psoriatic arthritis, together with recommendations for the treatment of particular forms of psoriasis and treatment of patients with comorbidities.
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Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Algoritmos , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Tomada de Decisão Clínica , Comorbidade , Feminino , França , Humanos , Imunossupressores/uso terapêutico , Masculino , Terapia PUVA , Gravidez , Complicações na Gravidez/tratamento farmacológico , Resultado do TratamentoRESUMO
Improved knowledge of sentinel node procedures coupled with the results of adjuvant clinical trials in stage III melanoma have prompted the French Cutaneous Oncology Group to propose new guidelines for the management of stage III melanoma. These guidelines comply with the principles of the evidence-based medicine.
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The risk of skin cancer induced by photosensiting drugs is well known. An association between hydrochlorothiazide use and skin cancer has been recently published in some epidemiological studies. A systematic review of case-control or prospectives cohorts showed an increased risk of cutaneous squamous cell carcinoma even if some confusing factors such as tobacco smoking was not analysed. Results are more conflicting for basal cell carcinoma or melanoma. These results do not modify the benefit/risk ratio but should lead to propose preventive mesures: identification of high risk population, avoidance of this drug if possible in immunocompromised patients or with previous skin cancer, regular skin examination in case of long term use of hydrochlorothiazide.