Photodynamic therapy for actinic keratosis: Is the European consensus protocol for daylight PDT superior to conventional protocol for Aktilite CL 128 PDT?

International audienceBackground: Topical photodynamic therapy (PDT) is an established treatment modality for various dermato-oncologic conditions. In Europe, initially requiring irradiation with red light, PDT of actinic keratosis (AK) can now also be carried out with exposure to daylight that has been clinically proven to be as effective as and less painful than red light. Objectives: In this paper, we propose a comparison between the conventional protocol for Aktilite CL 128 (red light source) PDT and the European consensus protocol for daylight PDT — with the exposure is assumed to be performed during either a clear sunny day or an overcast day — in the treatment of AK with methyl aminolevulinate through a mathematical modeling. Method: This already published modeling that is based on an iterative procedure alternating determination of the local fluence rate and updating of the local optical properties enables to estimate the local damage induced by the therapy. Results: The European consensus protocol for daylight PDT during a sunny day and an overcast day provides, on average, 6.50 and 1.79 times higher PDT local damages at the end 2 of the treatment than those obtained using the conventional protocol for Aktilite CL 128 PDT, respectively. Conclusions: Results analysis shows that, even performed during an overcast day, the European consensus protocol for daylight PDT leads to higher PDT local damages than the efficient conventional protocol for Aktilite CL 128

Comparison of 10 efficient protocols for photodynamic therapy of actinic keratosis: How relevant are effective light dose and local damage in predicting the complete response rate at 3 months?

International audienc

La communication sous forme d’un jeu de plateau pour partager des données et des ressentis d’experts à propos d’un nouveau traitement contre le cancer

La conception de cartes à des fins de communication ou, de manière plus générale, la visualisation de données est un champ de recherches relativement ancien qui a subi de profonds changements au cours de ces dernières années. Si de nombreuses recherches y sont consacrées, très peu d’entre elles s’intéressent à une autre tendance forte du moment : l’emploi ou le détournement du jeu à des fins de communication. Ce papier traite de cette question en abordant le cas d’un support informationnel rappelant un jeu de stratégie sur plateau développé dans un but d’information à propos d’un nouveau procédé de lutte contre le cancer : la thérapie photodynamique.La conception de cartes à des fins de communication ou, de manière plus générale, la visualisation de données est un champ de recherches relativement ancien qui a subi de profonds changements au cours de ces dernières années. Si de nombreuses recherches y sont consacrées, très peu d’entre elles s’intéressent à une autre tendance forte du moment : l’emploi ou le détournement du jeu à des fins de communication. Ce papier traite de cette question en abordant le cas d’un support informationnel rappelant un jeu de stratégie sur plateau développé dans un but d’information à propos d’un nouveau procédé de lutte contre le cancer : la thérapie photodynamique

A Primary Prevention Clinical Risk Score Model for Patients With Brugada Syndrome (BRUGADA-RISK).

OBJECTIVES: The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS). BACKGROUND: Risk stratification in BrS is a significant challenge due to the low event rates and conflicting evidence. METHODS: A multicenter international cohort of patients with BrS and no previous cardiac arrest was used to evaluate the role of 16 proposed clinical or electrocardiogram (ECG) markers in predicting ventricular arrhythmias (VAs)/sudden cardiac death (SCD) during follow-up. Predictive markers were incorporated into a risk score model, and this model was validated by using out-of-sample cross-validation. RESULTS: A total of 1,110 patients with BrS from 16 centers in 8 countries were included (mean age 51.8 ± 13.6 years; 71.8% male). Median follow-up was 5.33 years; 114 patients had VA/SCD (10.3%) with an annual event rate of 1.5%. Of the 16 proposed risk factors, probable arrhythmia-related syncope (hazard ratio [HR]: 3.71; p < 0.001), spontaneous type 1 ECG (HR: 3.80; p < 0.001), early repolarization (HR: 3.42; p < 0.001), and a type 1 Brugada ECG pattern in peripheral leads (HR: 2.33; p < 0.001) were associated with a higher risk of VA/SCD. A risk score model incorporating these factors revealed a sensitivity of 71.2% (95% confidence interval: 61.5% to 84.6%) and a specificity of 80.2% (95% confidence interval: 75.7% to 82.3%) in predicting VA/SCD at 5 years. Calibration plots showed a mean prediction error of 1.2%. The model was effectively validated by using out-of-sample cross-validation according to country. CONCLUSIONS: This multicenter study identified 4 risk factors for VA/SCD in a primary prevention BrS population. A risk score model was generated to quantify risk of VA/SCD in BrS and inform implantable cardioverter-defibrillator prescription

Evaluation of light emitting fabrics to improve efficacy and tolerance of Photodynamic Therapy in dermatology : about actinic keratosis

Contexte : La thérapie photodynamique est un traitement efficace des kératoses actiniques, réparties en champs de cancérisation. Parmi les protocoles approuvés en Europe, le plus largement utilisé nécessite une illumination par lampe à LED. Cependant, la douleur pendant l’illumination et la reproductibilité du traitement sont deux facteurs limitants. Pour améliorer ce traitement, un textile lumineux a été développé. Nous avons évalué ce dispositif avec deux schémas d’illumination : Flexitheraligth à une irradiance de 12,3 mW/cm2 pour obtenir une fluence de 37 J/cm2 et Pho-Istos à une irradiance de 1,3 mW/cm2 pour obtenir une fluence 12J/cm2.Objectifs : Évaluer la non-infériorité, en termes d'efficacité du traitement photodynamique des kératoses actiniques par les dispositifs Flexitheralight et Phos-Istos par rapport au protocole conventionnel utilisant une lampe à LED rouge.Patients, matériels et méthodes : 2 études cliniques de phase II randomisées et contrôlées ont été menées. Nous avons inclus des patients atteints de kératoses actiniques de grade I-II sur le front et le cuir chevelu, traités par thérapie photodynamique au méthylaminolévulinate dans deux zones symétriques. Une zone a été traitée avec le protocole conventionnel, tandis que l'autre zone a été traitée avec le protocole Flexitheralight ou Phos-Istos selon l’étude. Le critère d'évaluation principal était le taux de réponse complète des lésions à trois mois (borne de non-infériorité de -10%). Les critères d'évaluation secondaires comprenaient la douleur signalée par le patient à la fin de l'irradiation évaluée par une échelle visuelle analogique.Résultats : L'étude Flexitheralight a inclus 25 patients traités avec le dispositif Flexitheralight d’un côté (n = 154 kératoses actiniques) et avec la lampe LED sur l’autre côté (n = 156 kératoses actiniques). Le taux de réponse complète avec le protocole Flexitheralight n'était pas inférieur à celui obtenu avec la lampe LED (respectivement 66,0% contre 59,1% ; différence absolue de 6,9% ; intervalle de confiance de 95% de -0,6% à 14,5%). La douleur était significativement moins importante avec le protocole Flexitheralight qu'avec la lampe à LED (moyenne ± écart-type: 0,4 ± 0,6 vs 5,0 ± 2,6; p <0,0001).L'étude Phos-Istos a concerné quarante-six patients traités avec le dispositif Phos-Istos sur une zone (n = 280 lésions) et avec la lampe LED sur la zone controlatérale (n = 280 lésions). Le taux de réponse complète à 3 mois du dispositif Phos-Istos n'était pas inférieur à celui de la lampe LED (79,3% vs 80,7%, respectivement ; différence absolue, -1,6%; intervalle de confiance unilatéral à 95%, - 4,5% à l'infini). Le score de douleur à la fin de l'illumination était significativement plus bas pour le dispositif Phos-Istos que pour la lampe LED (moyenne ± écart type: 0,3 ± 0,6 vs 7,4 ± 2,3; p <0,0001).Conclusions : Les dispositifs d’illumination textiles et les protocoles à faible irradiance ne sont donc pas inférieurs en termes d'efficacité au protocole conventionnel de traitement des kératoses actiniques du front et du cuir chevelu. La tolérance est cependant significativement améliorée.Background: Photodynamic therapy is an effective treatment for actinic keratosis, for patients with large areas of field cancerization. Among the approved protocols in Europe, the most widely used requires illumination with a LED lamp. However, pain during irradiation and the reproductibility are two limiting factors of this protocol. To overcome these limits, a light-emitting fabric-based device was developed. We evaluated these devices and two illumination schemes: Flexitheraligth at a fluence rate of 12.3 mW/cm2 to get a fluence of 37J/cm2 and Pho-Istos at a fluence rate of 1.3 mW/cm2 to get a fluence of 12J/cm2.Objectives: We aim to assess the non-inferiority, in terms of photodynamic therapy efficacy to treat actinic keratosis, of the Flexitheralight and Phos-Istos devices compared with the conventional protocol using the red LED lamp.Methods: Randomized, controlled, phase II clinical studies were performed. We included patients with grade I-II actinic keratosis of the forehead and scalp, treated with methyl aminolevulinate photodynamic therapy in two symmetrical areas. One area was treated with the conventional protocol, whereas the other area was treated with the Flexitheralight or the Phos-Istos protocol, depending on the study. The primary endpoint was the lesion complete response rate at three months (an absolute non-inferiority margin of -10% was used). The secondary endpoints included patient-reported pain at the end of the irradiation.Results: The Flexitheralight study included twenty-five patients treated with the Flexitheralight device on one area (n=154 actinic keratosis) and with the LED lamp on the contralateral area (n=156 actinic keratosis). The lesion complete response rate with the Flexitheralight protocol was non-inferior to that obtained with the LED lamp (66.0% vs. 59.1%, respectively; absolute difference, 6.9%; 95% confidence interval, -0.6% to 14.5%). Patient-reported pain was significantly lower with the Flexitheralight protocol than with the LED lamp (mean ± standard deviation: 0.4 ± 0.6 vs. 5.0 ± 2.6; p<0.0001).The Phos-Istos study included forty-six patients treated with the Phos-Istos device on one area (n=280 lesions) and with the LED lamp on the contralateral area (n=280 lesions). Three months following treatment, the lesion complete response rate of the Phos-Istos device was non-inferior to the LED lamp (79.3% vs. 80.7%, respectively; absolute difference, -1.6%; one-sided 95% confidence interval, -4.5% to infinity). The pain score at the end of illumination was significantly lower for the Phos-Istos device than for the LED lamp (mean±standard deviation: 0.3±0.6 vs. 7.4±2.3; p<0.0001).Conclusions: The light emitting fabrics and the low-irradiance protocols are non-inferior in terms of efficacy and superior in terms of tolerability to the conventional protocol for treating actinic keratoses of the forehead and scalp

Évaluation de dispositifs d’illumination textiles permettant d’améliorer l’efficacité et la tolérance de la Thérapie Photodynamique en Dermatologie : modèle des kératoses actiniques

Background: Photodynamic therapy is an effective treatment for actinic keratosis, for patients with large areas of field cancerization. Among the approved protocols in Europe, the most widely used requires illumination with a LED lamp. However, pain during irradiation and the reproductibility are two limiting factors of this protocol. To overcome these limits, a light-emitting fabric-based device was developed. We evaluated these devices and two illumination schemes: Flexitheraligth at a fluence rate of 12.3 mW/cm2 to get a fluence of 37J/cm2 and Pho-Istos at a fluence rate of 1.3 mW/cm2 to get a fluence of 12J/cm2.Objectives: We aim to assess the non-inferiority, in terms of photodynamic therapy efficacy to treat actinic keratosis, of the Flexitheralight and Phos-Istos devices compared with the conventional protocol using the red LED lamp.Methods: Randomized, controlled, phase II clinical studies were performed. We included patients with grade I-II actinic keratosis of the forehead and scalp, treated with methyl aminolevulinate photodynamic therapy in two symmetrical areas. One area was treated with the conventional protocol, whereas the other area was treated with the Flexitheralight or the Phos-Istos protocol, depending on the study. The primary endpoint was the lesion complete response rate at three months (an absolute non-inferiority margin of -10% was used). The secondary endpoints included patient-reported pain at the end of the irradiation.Results: The Flexitheralight study included twenty-five patients treated with the Flexitheralight device on one area (n=154 actinic keratosis) and with the LED lamp on the contralateral area (n=156 actinic keratosis). The lesion complete response rate with the Flexitheralight protocol was non-inferior to that obtained with the LED lamp (66.0% vs. 59.1%, respectively; absolute difference, 6.9%; 95% confidence interval, -0.6% to 14.5%). Patient-reported pain was significantly lower with the Flexitheralight protocol than with the LED lamp (mean ± standard deviation: 0.4 ± 0.6 vs. 5.0 ± 2.6; p<0.0001).The Phos-Istos study included forty-six patients treated with the Phos-Istos device on one area (n=280 lesions) and with the LED lamp on the contralateral area (n=280 lesions). Three months following treatment, the lesion complete response rate of the Phos-Istos device was non-inferior to the LED lamp (79.3% vs. 80.7%, respectively; absolute difference, -1.6%; one-sided 95% confidence interval, -4.5% to infinity). The pain score at the end of illumination was significantly lower for the Phos-Istos device than for the LED lamp (mean±standard deviation: 0.3±0.6 vs. 7.4±2.3; p<0.0001).Conclusions: The light emitting fabrics and the low-irradiance protocols are non-inferior in terms of efficacy and superior in terms of tolerability to the conventional protocol for treating actinic keratoses of the forehead and scalp.Contexte : La thérapie photodynamique est un traitement efficace des kératoses actiniques, réparties en champs de cancérisation. Parmi les protocoles approuvés en Europe, le plus largement utilisé nécessite une illumination par lampe à LED. Cependant, la douleur pendant l’illumination et la reproductibilité du traitement sont deux facteurs limitants. Pour améliorer ce traitement, un textile lumineux a été développé. Nous avons évalué ce dispositif avec deux schémas d’illumination : Flexitheraligth à une irradiance de 12,3 mW/cm2 pour obtenir une fluence de 37 J/cm2 et Pho-Istos à une irradiance de 1,3 mW/cm2 pour obtenir une fluence 12J/cm2.Objectifs : Évaluer la non-infériorité, en termes d'efficacité du traitement photodynamique des kératoses actiniques par les dispositifs Flexitheralight et Phos-Istos par rapport au protocole conventionnel utilisant une lampe à LED rouge.Patients, matériels et méthodes : 2 études cliniques de phase II randomisées et contrôlées ont été menées. Nous avons inclus des patients atteints de kératoses actiniques de grade I-II sur le front et le cuir chevelu, traités par thérapie photodynamique au méthylaminolévulinate dans deux zones symétriques. Une zone a été traitée avec le protocole conventionnel, tandis que l'autre zone a été traitée avec le protocole Flexitheralight ou Phos-Istos selon l’étude. Le critère d'évaluation principal était le taux de réponse complète des lésions à trois mois (borne de non-infériorité de -10%). Les critères d'évaluation secondaires comprenaient la douleur signalée par le patient à la fin de l'irradiation évaluée par une échelle visuelle analogique.Résultats : L'étude Flexitheralight a inclus 25 patients traités avec le dispositif Flexitheralight d’un côté (n = 154 kératoses actiniques) et avec la lampe LED sur l’autre côté (n = 156 kératoses actiniques). Le taux de réponse complète avec le protocole Flexitheralight n'était pas inférieur à celui obtenu avec la lampe LED (respectivement 66,0% contre 59,1% ; différence absolue de 6,9% ; intervalle de confiance de 95% de -0,6% à 14,5%). La douleur était significativement moins importante avec le protocole Flexitheralight qu'avec la lampe à LED (moyenne ± écart-type: 0,4 ± 0,6 vs 5,0 ± 2,6; p <0,0001).L'étude Phos-Istos a concerné quarante-six patients traités avec le dispositif Phos-Istos sur une zone (n = 280 lésions) et avec la lampe LED sur la zone controlatérale (n = 280 lésions). Le taux de réponse complète à 3 mois du dispositif Phos-Istos n'était pas inférieur à celui de la lampe LED (79,3% vs 80,7%, respectivement ; différence absolue, -1,6%; intervalle de confiance unilatéral à 95%, - 4,5% à l'infini). Le score de douleur à la fin de l'illumination était significativement plus bas pour le dispositif Phos-Istos que pour la lampe LED (moyenne ± écart type: 0,3 ± 0,6 vs 7,4 ± 2,3; p <0,0001).Conclusions : Les dispositifs d’illumination textiles et les protocoles à faible irradiance ne sont donc pas inférieurs en termes d'efficacité au protocole conventionnel de traitement des kératoses actiniques du front et du cuir chevelu. La tolérance est cependant significativement améliorée

Photodynamic therapy for actinic keratosis: a trend towards a decrease in irradiance without loss of efficacy for a better tolerability

International audiencePhotodynamic therapy (PDT) is an established treatment for actinic keratosis (AK). The conventional approved PDT protocol in Europe (C-PDT) involves red-light photoactivation at irradiances higher than 60 mW/cm 2 , making the treatment painful. Several clinical studies have reported similar efficacy and better tolerability when using red-light photoactivation at lower irradiances. The aim of the study was to investigate whether there is a minimum irradiance threshold for red-light photoactivation above which there is no further improvement in efficacy. A photodiode sensor connected to a power meter was used to measure the irradiance delivered to 114 AKs on the scalp and forehead of 19 patients during C-PDT using the Aktilite CL 128 (Galderma SA, Switzerland). The widely ranging measured irradiances, resulting from the heterogeneous photoactivation over the treatment area provided by the Aktilite CL 128, were cross-referenced with the clinically evaluated complete responses (CR) at 3 months. The 66 AKs in CR at 3 months received an average irradiance of 30.9 mW/cm 2 (standard deviation: 16.7 mW/cm 2) compared to 33.3 mW/cm 2 (standard deviation: 17.9 mW/cm 2) for the 48 AKs in incomplete response. No significant effect of the irradiance on the CR at 3 months was found (odds ratio for a 6 mW/cm 2-unit change, 0.96; 95% confidence interval, 0.83 to 1.10; p=0.53). No minimum irradiance threshold could therefore be determined in the considered irradiance range. A red-light device enabling homogeneous irradiation at a lower irradiance than the Aktilite CL 128 may therefore provide similar efficacy and higher treatment tolerability than C-PDT

La communication sous forme d’un jeu de plateau pour partager des données et des ressentis d’experts à propos d’un nouveau traitement contre le cancer

La conception de cartes à des fins de communication ou, de manière plus générale, la visualisation de données est un champ de recherches relativement ancien qui a subi de profonds changements au cours de ces dernières années. Si de nombreuses recherches y sont consacrées, très peu d’entre elles s’intéressent à une autre tendance forte du moment : l’emploi ou le détournement du jeu à des fins de communication. Ce papier traite de cette question en abordant le cas d’un support informationnel rappelant un jeu de stratégie sur plateau développé dans un but d’information à propos d’un nouveau procédé de lutte contre le cancer : la thérapie photodynamique

Weak phylogenetic and habitat effects on root trait variation of 218 Neotropical tree species

International audienceIntroduction: Tropical forests harbor a large diversity of closely related tree species that can thrive across habitats. This biodiversity has been found to correspond to large functional diversity in aboveground traits, and likely also relates to belowground trait variation. Globally, root trait (co-)variation is driven by different belowground resource strategies of species, environmental variation, and phylogeny; however, these patterns mostly reflect observations from temperate biomes and remain unconfirmed in tropical trees. We examine phylogenetic and environmental effects on root trait (co-)variation of trees across habitats in an Amazonian rainforest.Methods: Roots of 218 tree species from ten dominant families were sampled across three major habitats near Manaus, Brazil. We quantified five morphological and architectural root traits to (i) investigate how they reflected different resource strategies across species, (ii) compare them between families and superorders to test phylogenetic effects, and (iii) compare them between habitats to determine environmental effects on root trait expressions and variability.Results: Root traits discriminated species along a tradeoff between root diameter and root branching and, secondly, due to variation in root tissue density. Our results further show weak phylogenetic effects on tropical tree root variation, for example, families from the same superorder showed large divergence in their root traits, while those from different superorders often overlapped in their root morphology and architecture. Root traits differed significantly between habitats but habitat type had only little effect on overall root trait variation.Discussion: Our work suggests that the dimensions and drivers that underlie (co-)variation in tropical root traits may differ from global patterns defined by mostly temperate datasets. Due to (a)biotic environmental differences, different root trait dimensions may underlie the belowground functional diversity in (Neo)tropical forests, and we found little evidence for the strong phylogenetic conservatism observed in root traits in temperate biomes. We highlight important avenues for future research on tropical roots in order to determine the degree of, and shifts in functional diversity belowground as communities and environments change in tropical forests

Weak phylogenetic and habitat effects on root trait variation of 218 Neotropical tree species

Introduction Tropical forests harbor a large diversity of closely related tree species that can thrive across habitats. This biodiversity has been found to correspond to large functional diversity in aboveground traits, and likely also relates to belowground trait variation. Globally, root trait (co-)variation is driven by different belowground resource strategies of species, environmental variation, and phylogeny; however, these patterns mostly reflect observations from temperate biomes and remain unconfirmed in tropical trees. We examine phylogenetic and environmental effects on root trait (co-)variation of trees across habitats in an Amazonian rainforest. Methods Roots of 218 tree species from ten dominant families were sampled across three major habitats near Manaus, Brazil. We quantified five morphological and architectural root traits to (i) investigate how they reflected different resource strategies across species, (ii) compare them between families and superorders to test phylogenetic effects, and (iii) compare them between habitats to determine environmental effects on root trait expressions and variability. Results Root traits discriminated species along a tradeoff between root diameter and root branching and, secondly, due to variation in root tissue density. Our results further show weak phylogenetic effects on tropical tree root variation, for example, families from the same superorder showed large divergence in their root traits, while those from different superorders often overlapped in their root morphology and architecture. Root traits differed significantly between habitats but habitat type had only little effect on overall root trait variation. Discussion Our work suggests that the dimensions and drivers that underlie (co-)variation in tropical root traits may differ from global patterns defined by mostly temperate datasets. Due to (a)biotic environmental differences, different root trait dimensions may underlie the belowground functional diversity in (Neo)tropical forests, and we found little evidence for the strong phylogenetic conservatism observed in root traits in temperate biomes. We highlight important avenues for future research on tropical roots in order to determine the degree of, and shifts in functional diversity belowground as communities and environments change in tropical forests.info:eu-repo/semantics/publishe