Biologics for pityriasis rubra pilaris treatment: a review of the literature

Pityriasis rubra pilaris (PRP) is a rare inflammatory papulosquamous skin disease, often refractory to conventional therapies. The off-label use of biologics, such as anti-TNF, -IL-12/IL-23, -IL-17 agents, has been proven successful, in the last two decades, in PRP treatment.Our aim was to analyse the literature for the use of biologics in PRP treatment. We conducted a review by "Pubmed" and "clinicaltrial.gov" searches. 68 articles met our selection criteria and were herein discussed. Out of 86 PRP patients, the vast majority of which treated with anti-TNF, -IL-12/IL-23, and -IL-17 biologics, either alone or in combination therapy, a marked-to-complete response (50-78%), a partial response (11-25%) or no/poor response (11-25%) was observed.

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Comparison of ethylenediaminetetraacetic acid-treated desmoglein ELISA and conventional desmoglein ELISA in the evaluation of pemphigus vulgaris in remission

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Dual neutralization of both IL-17A and IL-17F with bimekizumab in patients with psoriasis: results from BE ABLE 1, a 12-week randomized, double-blinded placebo-controlled phase 2b trial

Neutralizing interleukin (IL)-17F in addition to IL-17A may provide a more complete and specific approach to inhibiting inflammation.

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Étude de faisabilité de la spirométrie en médecine générale

Publication date: Available online 29 March 2018
Source:Revue des Maladies Respiratoires
Author(s): L. Bunge, D. Baruch, L. Plantier, T. Mazars, N. Roche, A. Izadifar
La bronchopneumopathie chronique obstructive est une maladie fréquente insuffisamment dépistée par les médecins généralistes (MG) alors que la spirométrie leur est accessible. L'objectif de ce travail était d'évaluer la qualité et l'interprétation des spirométries réalisées par des internes de médecine générale après une formation courte. Trois internes ont été formés pendant une demi-journée à la spirométrie. Dans 5 cabinets de médecine générale, une spirométrie était proposée à tous les fumeurs de plus de 35 ans. Les examens ont été relus en aveugle par un pneumologue expert indépendant pour évaluer leur qualité et leur interprétation. Des 184 patients éligibles, 89 % ont accepté de participer et 66 % (107) sont venus au 2^e rendez-vous. Le pneumologue a évalué la qualité des spirométries comme bonne pour 72 %, moyenne pour 20 % et non interprétable pour 8 %. L'interprétation était correcte pour 91 % des tests. Le coefficient Kappa de concordance de l'interprétation entre MG et expert était de 0,93. Ces tests ont permis de dépister des troubles ventilatoires obstructifs dans 17,5 % des cas. Le temps moyen d'une consultation avec spirométrie était de 19minutes. La consultation dédiée de spirométrie est bien acceptée par les patients en MG. Une formation courte reste à structurer pour permettre la réalisation et l'interprétation de spirométries en MG. Cette étude doit être étendue de façon à mieux étudier la reproductibilité en cas de courbe anormale.COPD is common but is under-diagnosed by general practitioners (GP). GP have a major role in the early diagnosis of this disease. GP could have access to spirometry. The aim of this study was to evaluate the quality and interpretation of spirometry performed by primary care residents following a short education session. Three residents were trained in spirometry for half a day. They then performed spirometry on all smokers over the age of 35 visiting five general practices. The results were reviewed blindly by an independent specialist pulmonologist to assess their quality and interpretation. Among 184 eligible patients, 89% agreed to participate and 66% (n=107) came for the second appointment. The pulmonologist evaluated the quality of spirometry as good in 72% of cases, of suboptimal but acceptable quality in 20% and of poor quality in 8%. Interpretation was accurate in 91% of tests. The Kappa concordance coefficient between GPs and the expert was 0.93. Airflow obstruction was detected in 17.5% of the screened subjects. The average time for a consultation with spirometry was 19minutes. The consultation dedicated to spirometry was well accepted by patients. A short training has to be structured to allow GPs to perform and interpret spirometry properly. This work needs to be extended to better assess reproducibility in cases of abnormal spirometry.



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Influence of Class V preparation on in vivo temperature rise in anesthetized human pulp during exposure to a Polywave® LED light curing unit

Publication date: Available online 29 March 2018
Source:Dental Materials
Author(s): Driellen Christine Zarpellon, Patrício Runnacles, Cristiane Maucoski, Dayane Jaqueline Gross, Ulisses Coelho, Frederick Allen Rueggeberg, Cesar Augusto Galvão Arrais
ObjectiveThis in vivo study evaluated pulp temperature (PT) rise in human premolars having deep Class V preparations during exposure to a light curing unit (LCU) using selected exposure modes (EMs).MethodsAfter local Ethics Committee approval, intact first premolars (n=8) requiring extraction for orthodontic reasons, from 8 volunteers, received infiltrative and intraligamental anesthesia and were isolated using rubber dam. A minute pulp exposure was attained and sterile probe from a wireless, NIST-traceable, temperature acquisition system was inserted into the coronal pulp chamber to continuously monitor PT (°C). A deep buccal Class V preparation was prepared using a high speed diamond bur under air-water spray cooling. The surface was exposed to a Polywave^® LED LCU (Bluephase 20i, Ivoclar Vivadent) using selected EMs, allowing 7-min span between each exposure: 10-s in low (10-s/L), 10-s (10-s/H), 30-s (30-s/H), or 60-s (60-s/H) in high mode; and 5-s-Turbo (5-s/T). Peak PT values and PT increases over physiologic baseline levels (ΔT) were subjected to 1-way, repeated measures ANOVAs, and Bonferroni's post-hoc tests (α=0.05). Linear regression analysis was performed to establish the relationship between applied radiant exposure and ΔT.ResultsAll EMs produced higher peak PT than the baseline temperature (p<0.001). Only 60-s/H mode generated an average ΔT of 5.5°C (p<0.001). A significant, positive relationship was noted between applied radiant exposure and ΔT (r²=0.8962; p<0.001).SignificanceIn vivo exposure of deep Class V preparation to Polywave^® LED LCU increases PT to values considered safe for the pulp, for most EMs. Only the longest evaluated EM caused higher PT increase than the critical ΔT, thought to be associated with pulpal necrosis.



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Concomitant BCORL1 and BRAF Mutations in Vemurafenib-Resistant Melanoma Cells

Publication date: May 2018
Source:Neoplasia, Volume 20, Issue 5
Author(s): Luca Mologni, Mariantonia Costanza, Geeta Geeta Sharma, Michela Viltadi, Luca Massimino, Stefania Citterio, Stefania Purgante, Hima Raman, Alessandra Pirola, Massimo Zucchetti, Rocco Piazza, Carlo Gambacorti-Passerini
BRAF is the most frequently mutated gene in melanoma. Constitutive activation of mutant BRAF^V600E leads to aberrant Ras-independent MAPK signaling and cell transformation. Inhibition of mutant BRAF is a current frontline therapy for such cases, with improved survival compared with chemotherapy. Unfortunately, reactivation of MAPK signaling by several mechanisms has been shown to cause drug resistance and disease recurrence. In this work, we describe the co-occurrence of an in-frame deletion within an amplified BRAF^V600E locus and a missense point mutation of the transcriptional repressor BCORL1 in vemurafenib-resistant A375 melanoma cells. Functional data confirmed that truncated p47BRAF^V600E and mutant BCORL1^Q1076H both contribute to resistance. Interestingly, either endogenous BCORL1 silencing or ectopic BCORL1^Q1076H expression mimicked the effects of a CRISPR/Cas9-edited BCORL1^Q1076H locus, suggesting a complex mixture of loss- and gain-of-function effects caused by the mutation. Transcriptomic data confirmed this hypothesis. Finally, we show that the pan-RAF inhibitor sorafenib is not affected by expression of BRAF deletion variant and effectively synergizes with vemurafenib to block resistant cells, suggesting a possible intervention for this class of mutants.



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Combined Inhibition of ATR and WEE1 as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer

Publication date: May 2018
Source:Neoplasia, Volume 20, Issue 5
Author(s): Juan Jin, Hehui Fang, Fang Yang, Wenfei Ji, Nan Guan, Zijia Sun, Yaqin Shi, Guohua Zhou, Xiaoxiang Guan
Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that poses a clinical challenge. Thus, new therapy strategies are urgently needed. The selective WEE1 inhibitor, AZD1775, has shown strong anti-proliferative effects on a variety of tumors. Here, we first demonstrate that inhibition of ATR by selective inhibitor AZD6738 can enhance AZD1775-caused growth inhibition in TNBC. Our results show that the enhanced cell death is attributed to repressed DNA damage repair and excessive replication stress, thereby causing increased DNA damage reflected by accumulation of the DNA double-strand-break marker γH2AX. On the other hand, combined treatment with AZD6738 and AZD1775 forces mitotic entry of cells with DNA damages by activating CDK1 activity, inducing severely aberrant mitosis and mitotic catastrophe, ultimately resulting in cell death. Dual inhibition of WEE1 and ATR also inactivated RAD51-mediated homologous recombination, which sensitized TNBC cells to cisplatin and PARP inhibitor. Here, based on the preclinical results that ATR inhibition synergizes with WEE1 inhibition in TNBC, we propose that this combination therapy alone, or in parallel with chemotherapy, represents an innovative and potent targeted therapy in TNBC.



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