Biofilm of Cutibacterium acnes: a target of different active substances.

BACKGROUND: Acne vulgaris is a chronic inflammatory dermatosis. Cutibacterium acnes plays a crucial role in the acne pathophysiology. Recent works present evidence of C. acnes growing as a biofilm in cutaneous follicles. This development is currently considered one of the leading causes of C. acnes in vivo persistence and resistance to antimicrobials used to treat acne. OBJECTIVE: Our objective was to evaluate the effects of various active compounds (clindamycin, erythromycin, doxycycline, and myrtle extract) on eight distinct, well-characterized strains of C. acnes following their growth in biofilm mode. METHODS/RESULTS: Cutibacterium acnes isolates from phylotypes IA1 and IA2 produce more biofilm than other phylotypes. No antibiotic effect was observed either during the curative test or preventive test. Myrtle extract at 0.01% (w/v) showed significant efficacy on the biofilm for C. acnes strains (curative assays). Furthermore, it appear that myrtle extract and doxycycline together reduce the overall biomass of the biofilm. A significant dose-dependent effect was observed during the preventive test, greater than the one observed under curative conditions, with an important loss of activity of the myrtle extract observed from 0.001% (w/v) concentration onwards. Transmission electron microscopy showed that bacteria treated with myrtle extract grew biofilms much less frequently than untreated bacteria. Additionally, when the quantity of myrtle extract grew, the overall number of bacteria dropped, indicating an additional antibacterial action. CONCLUSION: These findings support the hypothesis that the different C. acnes phylotypes have various aptitudes in forming biofilms. They also suggest that myrtle extract is a promising alternative as an anti-biofilm and antibacterial agent in fighting diseases caused by planktonic and biofilm C. acnes.

Efficacy of Spironolactone Compared with Doxycycline in Moderate Acne in Adult Females: Results of the Multicentre, Controlled, Randomized, Double-blind Prospective and Parallel Female Acne Spironolactone vs doxyCycline Efficacy (FASCE) Study.

Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.

Acne microbiome: From phyla to phylotypes.

Acne vulgaris is a chronic inflammatory skin disease with a complex pathogenesis. Traditionally, the primary pathophysiologic factors in acne have been thought to be: (1) altered sebum production, (2) inflammation, (3) excess keratinization and (4) colonization with the commensal Cutibacterium acnes. However, the role of C. acnes has been unclear, since virtually all adults have C. acnes on their skin yet not all develop acne. In recent years, understanding of the role of C. acnes has expanded. It is still acknowledged to have an important place in acne pathogenesis, but evidence suggests that an imbalance of individual C. acnes phylotypes and an alteration of the skin microbiome trigger acne. In addition, it is now believed that Staphylococcus epidermidis is also an actor in acne development. Together, C. acnes and S. epidermidis maintain and regulate homeostasis of the skin microbiota. Antibiotics, which have long been a staple of acne therapy, induce cutaneous dysbiosis. This finding, together with the long-standing public health edict to spare antibiotic use when possible, highlights the need for a change in acne management strategies. One fertile direction of study for new approaches involves dermocosmetic products that can support epidermal barrier function and have a positive effect on the skin microbiome.

A dermocosmetic regimen is able to mitigate skin sensitivity induced by a retinoid-based fixed combination treatment for acne: Results of a randomized clinical trial.

INTRODUCTION: Topical retinoids cause retinoid-induced skin discomfort (RISD) mainly during the first weeks of use leading to noncompliance and premature treatment discontinuation. A dermocosmetic (DC) may help to reduce treatment-related signs and symptoms and improve adherence. OBJECTIVES: To assess the benefit of a DC regimen compared to a routine skin care regimen (RC) by reducing RISD signs and symptoms induced by a retinoid/benzoyl peroxide fixed-drug combination in subjects with acne. MATERIALS AND METHODS: Double-blind, randomized, comparative study in subjects ≥16 years with mild to moderate acne candidates to a topical adapalene/BPO fixed drug combination (A/BPO). Evaluations took place at Day 0, 7, 14, 28, and 84 and included erythema, desquamation, burning, itching and stinging and RISD (SD, a composite score of local treatment-related signs and symptoms and acne severity. Subjects used daily the DC or RC together with the fixed combination for 84 days. RESULTS: Eighty-eight subjects were included, the mean age was 21 years; 84% were females. At Day 0 the SD score was 0.8 in both groups. A statistically significant difference in terms of skin sensitivity with DC compared to RC (1.6 points, vs. 2.4 points p < 0.05) was observed at Day 14. Clinical sign and symptom scores were more reduced with DC than with RC at all time points. Acne severity improved in both groups. CONCLUSION: DC significantly reduces A/BPO-related RISD compared to RC, especially during the first 14 days of treatment, without interfering with the clinical efficacy of the treatment, thus helping to maintain treatment adherence.

A Salicylic Acid-Based Dermocosmetic is Effective as an Adjunct to Benzoyl Peroxide for Mild to Moderate Acne and as Monotherapy in Maintenance Post Benzoyl Peroxide.

BACKGROUND: A dermocosmetic (DC) containing salicylic acid, niacinamide, and thermal spring water has been developed for the management of mild to moderate acne. AIM: To assess the efficacy of DC as an adjunct to benzoyl peroxide (BPO) every other day compared with BPO over 3 months, and its efficacy as maintenance post-BPO care compared with vehicle for another 3 months. METHODS: Single-center, randomized, double-blind study in 100 patients with mild to moderate facial acne according to the Global Acne Severity (GEA) Scale. During phase 1, subjects received either BPO + vehicle (vehicle group) or BPO + DC (DC group) for 12 weeks. During phase 2, patients were re-randomized to receive either the vehicle or the DC for 12 weeks. Assessments included inflammatory and non-inflammatory lesion count, acne severity using the GEA Scale, local tolerance, quality of life, and quantity of product used. RESULTS: During phase 1, both groups, DC and vehicle, reached the same level of efficacy at month 3, although the quantity of BPO used was significantly reduced in the DC group (P=0.0001). During phase 2, acne continued to significantly improve (all P<0.05) in the DC group, as did clinical signs and symptoms; while patients randomized to vehicle reported relapses of their acne and related symptoms. CONCLUSION: The use of DC significantly reduces the need for BPO with no impact on the efficacy of mild to moderate acne. The use of DC as a maintenance post-BPO allowed a significant reduction of acne relapse compared with vehicle after 3 months of follow-up, with a good tolerance. J Drugs Dermatol. 2023;22(12):1172-1177. doi:10.36849/JDD.7449R1.

Insulin Growth Factor-1 Status in Hidradenitis Suppurativa: A French Institutional Pilot Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the follicles in the apocrine glands and is associated with a deficiency in the innate immunity of the skin. It is characterized by the occurrence of nodules, abscesses, fistulas, scars. OBJECTIVE: Although a relationship has already been demonstrated between HS and innate immunity, IGF-1 status in patients with HS is still unknown. The objective of this pilot study was to determine IGF-1 status in patients with HS as well as its potential relationship with the clinical profile of the disease. METHODS: This monocentric and cross-sectional study involved 39 patients hospitalized at the Dermatology Department of CHU Nantes between November 2014 and January 2018. Clinical data and IGF1 status were collected during the follow-up consultation. RESULTS: Forty-nine percent of the patients had very low levels of IGF-1. At the clinical level, these patients were young and with a short duration of disease. The major difference was that IGF1-deficient patients had a higher BMI than others. The others factors differing between the two patient groups did not reach statistical significance. CONCLUSION: This exploratory pilot study indicates that HS with a low level of IGF-1 could represent a specific phenotype of patients with HS. These preliminary results have to be confirmed with a larger cohort, as they could have practical consequences in the therapeutic care of these patients.

Machine learning algorithm to predict response to immunotherapy in real-life settings for patients with advanced melanoma.

BACKGROUND: Melanoma is one of the most fatal forms of skin cancer. Defining relevant biomarkers to predict treatment outcome based on immune checkpoint inhibitors (ICIs) is needed in order to increase overall survival of metastatic melanoma patients (MM). OBJECTIVES: This study compared different machine learning models in terms of performance to identify biomarkers from clinical diagnosis and follow-up of MM patients, to predict treatment response to ICIs under real-life conditions. MATERIALS & METHODS: Clinical data from melanoma patients with an AJCC status of III C/D or IV, having received ICIs, were extracted from the RIC-MEL database for this pilot study. Light Gradient Boosting Machine, linear regression, Random Forest (RF), Support Vector Machine and Extreme Gradient Boosting were compared in terms of performance. The SHAP (SHapley Additive exPlanations) method was used to assess the link between the different clinical features investigated and the prediction of response to ICIs. RESULTS: RF showed the highest scores for accuracy (0.63) and sensitivity (0.64) and high scores for precision (0.61) and specificity (0.63). AJCC stage (0.076) showed the highest SHAP mean value, thus being the most suitable feature to predict response to treatment. The number of metastatic sites per year (0.049), number of months since first treatment initiation and the Breslow index (both 0.032) were less predictive, but still showed relatively high predictive power. CONCLUSION: This machine learning approach confirms that a certain number of biomarkers may enable prediction of treatment success with ICIs.

Analysis of cost-effectiveness of chemotherapeutic agents and new therapies for the management of unresectable and metastatic melanoma.

BACKGROUND: The advent of targeted therapies and immunotherapies has revolutionized metastatic melanoma (MM) management but their use is associated with high daily costs compared to chemotherapies: €2 for dacarbazine versus €175 for immunotherapies and €413 for targeted therapies. While overall survival (OS) has increased, healthcare expenditures are expected to double by 2030. OBJECTIVES: The aim of this study was to estimate the median OS and costs for MM patients in order to evaluate the effectiveness of new biological or targeted therapies (NT) used since 2013 compared to chemotherapies. MATERIALS & METHODS: This was a retrospective monocentric cost-effectiveness analysis performed in CHU Nantes (Nantes University Hospital). All MM patients treated with conventional chemotherapy as first-line treatment between 2008 and 2012 were included (CHEMO group). The same number of patients treated with NT as first-line between 2013 and 2017 were included (NT group). RESULTS: In total, 161 patients were included in each group. The mean age at diagnosis was 64.7±2.4 years in the CHEMO group and 65.3±2.4 years in the NT group (not significant). The men/women ratio was 1.48 and 1.27, respectively, (not significant). The median OS was 158 days in the CHEMO group and 395 days in the NT group (p<0.001). Treatment cost was €10,280/patient versus €94,676/patient, respectively. The mean incremental cost-effectiveness ratio was €90,184/LY (95% CI: €59,637; €166,395). CONCLUSION: Our study assessed clinical and economic features associated with MM management before and after the advent of NT. Costs and life expectancy have increased. NT appears to be cost-effective.

Panniculitis does not predict clinical response in patients with advanced melanoma under targeted therapy.

BACKGROUND: BRAF and MEK inhibitors have changed the landscape of treatment for advanced melanoma. Among their side effects, panniculitis has been hypothesized to be associated with better survival. OBJECTIVES: In this study, we aimed to explore the association between the occurrence of panniculitis during targeted therapy and outcome of metastatic melanoma. MATERIALS & METHODS: This was a retrospective single-centre comparative study from 2014 to 2019. An English literature review was also conducted to further our understanding of the mechanism(s) involved and identify characteristics of this association, in order to support better management. RESULTS: Ten patients who developed panniculitis during treatment were matched to 26 controls based on potential confounders at treatment introduction. The prevalence of panniculitis was 5.3%. Median progression-free survival (PFS) for all patients was 8.5 months (range: 3.0-94.0). The median PFS for the group with panniculitis was 10.5 months (7.0-undefined) and 7.0 months (6.0-32.0) for controls (p=0.39). According to the scientific literature, panniculitis occurring during targeted therapy affects mainly young people, predominantly women, with variable delay to onset (with half reported cases occurring in the first month). In addition, panniculitis usually only affects the lower limbs or is associated with other clinical signs (fever, arthralgia), without histological specificity. Discontinuation of targeted therapy is not required as spontaneous remission is usually experienced. Symptomatic treatment may be administered but systemic corticosteroids have not been proven to be effective. CONCLUSION: In contrast to the belief that there is a link between panniculitis and clinical response to targeted therapy according to the literature, our results show that there is no significant association between the two.

Efficacy of imiquimod in the management of lentigo maligna.

BACKGROUND: Lentigo maligna (LM) is a melanocytic proliferation occurring on photo-exposed skin that may progress to LM melanoma. Surgery is recommended as first-line treatment. Excision margins of 5-10 mm remain, without international consensus. Several studies have shown that imiquimod, an immunomodulator, induces LM regression. This study investigated the effect of imiquimod versus placebo in neoadjuvant settings. PATIENTS AND METHODS: We performed a prospective, randomized, multicentre, phase III clinical study. Patients were randomly assigned in 1:1 ratio to receive imiquimod or placebo for 4 weeks, followed by LM excision 4 weeks after the last application of imiquimod or placebo. The primary endpoint was extra-lesional excision, with a 5 mm margin from the residual pigmentation after imiquimod or vehicle. Secondary endpoints included the gain on the surface removed between the two groups; number of revision surgeries to obtain extra-lesional excisions; relapse-free time; and number of complete remissions after treatment. RESULTS: A total of 283 patients participated in this study; 247 patients, 121 patients in the placebo group and 126 in the imiquimod group, accounted for the modified ITT population. The first extralesional extirpation was performed in 116 (92%) imiquimod patients and in 102 (84%) placebo patients; the difference was not significant (p = 0.0743). Regarding the surface of LM, imiquimod reduced the LM surface (4.6-3.1 cm2 ) significantly (p < 0.001) more compared to the placebo (3.9-4.1 cm2 ). CONCLUSION: Imiquimod reduces the lentigo maligna surface after 1 month of treatment, without a higher risk of intralesional excision and with a positive aesthetic outcome.

The mechanosensitive TRPV2 calcium channel promotes human melanoma invasiveness and metastatic potential.

Melanoma is a highly aggressive cancer endowed with a unique capacity of rapidly metastasizing, which is fundamentally driven by aberrant cell motility behaviors. Discovering "migrastatics" targets, specifically controlling invasion and dissemination of melanoma cells during metastasis, is therefore of primary importance. Here, we uncover the prominent expression of the plasma membrane TRPV2 calcium channel as a distinctive feature of melanoma tumors, directly related to melanoma metastatic dissemination. In vitro as well as in vivo, TRPV2 activity is sufficient to confer both migratory and invasive potentials, while conversely TRPV2 silencing in highly metastatic melanoma cells prevents aggressive behavior. In invasive melanoma cells, TRPV2 channel localizes at the leading edge, in dynamic nascent adhesions, and regulates calcium-mediated activation of calpain and the ensuing cleavage of the adhesive protein talin, along with F-actin organization. In human melanoma tissues, TRPV2 overexpression correlates with advanced malignancy and poor prognosis, evoking a biomarker potential. Hence, by regulating adhesion and motility, the mechanosensitive TRPV2 channel controls melanoma cell invasiveness, highlighting a new therapeutic option for migrastatics in the treatment of metastatic melanoma.

Predictive factors of response to vismodegib: a French study of 61 patients with multiple or locally advanced basal cell carcinoma

Background: Vismodegib is indicated for the treatment of advanced or metastatic basal cell carcinoma (BCC). The predictive factors of response to vismodegib have so far been poorly described. Objectives: The primary objective was to determine the profile of patients responding to vismodegib and the duration of response. Secondary objectives were to assess whether there is a correlation between the duration of treatment and the risk of relapse, and to define factors associated with relapse. Materials & Methods: We included 61 patients with locally advanced BCC (laBCC) or multiple BCC, treated with vismodegib (150 mg per day), from July 2011 to November 2015, in the Oncodermatology Department of Nantes University Hospital in France. Tumour response was assessed using Response Evaluation Criteria in Solid Tumours version 1.1. Results: Thirty-nine patients had advanced BCC (64%) and 22 patients multiple BCC (36%), including 10 patients with Gorlin syndrome. No factor predicted response to vismodegib. The median progression-free survival (PFS) was 69.5 months for the total population. In multivariate analysis, multiple BCC was the only factor associated with an increased risk of relapse (HR: 13.80 [CI95%, 1.93-98.64, p < 0.01]). Treatment duration decreased the risk of relapse (HR 0.95 [CI95%, 0.90-0.99, p = 0.0467]). Among the 20 patients who experienced relapse during follow-up, 15 (75%) were re-treated with vismodegib, with a response rate of 66%. Conclusion: Although we were unable to establish predictive factors for the response to vismodegib, we demonstrate for the first time that increased treatment duration correlates with a decreased risk of relapse.

Lifestyle habits and impact of the Mediterranean diet on facial acne severity in French women: a case-control study.

Acne is a common benign inflammatory disease, but it has a significant psychosocial impact. The role of the diet in the development of acne is controversial. Some daily foods such as milk and fast-release sugars tend to promote acne. The Mediterranean Diet (MD) is based on virgin olive oil and nuts that are rich in polyphenols with anti-inflammatory properties. The aim of this study was to assess an association between the adherence to the MD and the severity of facial acne in French women. A case-control observational study was conducted in Nantes Hospital (France). Based on a validated PREvención con DIeta MEDiterránean questionnaire, the adherence to the MD was assessed. The Global Evaluation Acne severity score was assessed by a trained dermatologist. Forty women with mild-to-severe acne and 40 control subjects were included. A global linear model identified a significant negative correlation between the severity of acne and the adherence to the MD in acne patients (regression coefficient = -0.17; P = 0.017). This was the first study conducted in France to investigate the relationship between the adherence to the MD and the severity of facial acne in women. This study confirmed the importance of using a holistic approach for acne management. Further studies are needed to confirm our findings.

A Confinement-Driven Nucleation Mechanism of Metal Oxide Nanoparticles Obtained via Thermal Decomposition in Organic Media.

Thermal decomposition is a very efficient synthesis strategy to obtain nanosized metal oxides with controlled structures and properties. For the iron oxide nanoparticle synthesis, it allows an easy tuning of the nanoparticle's size, shape, and composition, which is often explained by the LaMer theory involving a clear separation between nucleation and growth steps. Here, the events before the nucleation of iron oxide nanocrystals are investigated by combining different complementary in situ characterization techniques. These characterizations are carried out not only on powdered iron stearate precursors but also on a preheated liquid reaction mixture. They reveal a new nucleation mechanism for the thermal decomposition method: instead of a homogeneous nucleation, the nucleation occurs within vesicle-like-nanoreactors confining the reactants. The different steps are: 1) the melting and coalescence of iron stearate particles, leading to "droplet-shaped nanostructures" acting as nanoreactors; 2) the formation of a hitherto unobserved iron stearate crystalline phase within the nucleation temperature range, simultaneously with stearate chains loss and Fe(III) to Fe(II) reduction; 3) the formation of iron oxide nuclei inside the nanoreactors, which are then ejected from them. This mechanism paves the way toward a better mastering of the metal oxide nanoparticles synthesis and the control of their properties.

Frequency and Genomic Aspects of Intrinsic Resistance to Vismodegib in Locally Advanced Basal Cell Carcinoma.

PURPOSE: Vismodegib is approved for the treatment of locally advanced basal cell carcinoma (laBCC), but some cases demonstrate intrinsic resistance (IR) to the drug. We sought to assess the frequency of IR to vismodegib in laBCC and its underlying genomic mechanisms. EXPERIMENTAL DESIGN: Response to vismodegib was evaluated in a cohort of 148 laBCC patients. Comprehensive genomic and transcriptomic profiling was performed in a subset of five intrinsically resistant BCC (IR-BCC). RESULTS: We identified that IR-BCC represents 6.1% of laBCC in the studied cohort. Prior treatment with chemotherapy was associated with IR. Genetic events that were previously associated with acquired resistance (AR) in BCC or medulloblastoma were observed in three out of five IR-BCC. However, IR-BCCs were distinct by highly rearranged polyploid genomes. Functional analyses identified hyperactivation of the HIPPO-YAP and WNT pathways at RNA and protein levels in IR-BCC. In vitro assay on the BCC cell line further confirmed that YAP1 overexpression increases the cell proliferation rate. CONCLUSIONS: IR to vismodegib is a rare event in laBCC. IR-BCCs frequently harbor resistance mutations in the Hh pathway, but also are characterized by hyperactivation of the HIPPO-YAP and WNT pathways.

Change in lentigo maligna score assessed by in vivo reflectance confocal microscopy after 1 month of imiquimod treatment for lentigo maligna management.

BACKGROUND: Treatment of lentigo maligna (LM) is challenging because of the potential functional and esthetic surgical sequelae. Imiquimod has been proposed as a treatment for LM. Reflectance confocal microscopy (RCM) is a noninvasive method for the diagnosis of LM and margin assessment. OBJECTIVES: To compare the overall LM score (LMS) assessed by RCM before and 1 month after the start of imiquimod treatment compared to placebo and to define the immunohistochemical (IHC) profile of responders to imiquimod. METHODS: A controlled randomized study was conducted. Forty patients underwent RCM examination with calculation of the LMS at baseline and after 1 month of treatment. An IHC analysis of excised tissues was performed. RESULTS: The 1-month LMS was significantly lower in patients treated with imiquimod compared to those treated with placebo (P < .001). The criteria in the imiquimod-treated patients that demonstrated significant decrease were nonedged papillae; large, round pagetoid cells; atypical cells at the dermoepidermal junction; and follicular location of atypical cells. IHC analysis showed a higher level of interferon gamma in the resected specimens of patients responding to imiquimod (P = .04). LIMITATIONS: Sample size was small. CONCLUSION: Assessing the LMS by RCM was useful to monitor LM response to imiquimod accurately.

Should Targeted Therapy Be Continued in BRAF-Mutant Melanoma Patients after Complete Remission?

BACKGROUND: Targeted therapy is used to treat patients with a BRAF-mutated metastatic melanoma and is continued until disease progression or severe toxicity. No robust data on the management of patients achieving a complete remission (CR) are available. MAIN OBJECTIVE: To determine the relapse rate in the first year after targeted therapy discontinuation in patients in CR. SECONDARY OBJECTIVES: To determine the relapse rates throughout the follow-up and to identify prognostic factors for relapse at 1 year. METHODS: A retrospective, monocentric observational study was conducted in patients with advanced melanoma included in the RIC-Mel database who discontinued targeted therapy after achieving a CR confirmed by CT scan and PET/CT scan. RESULTS: Twenty-nine patients were included. Seventeen (58.6%) patients were treated with BRAF inhibitor (BRAFi) alone and 12 (41.4%) with a BRAFi combined with a MEK inhibitor (BRAFi + MEKi). The median treatment duration was 9.7 months. The relapse rates after discontinuation were 69% at 12 months (BRAFi: 70.6%; BRAFi + MEKi: 66.7%) and 76% at 36 months (BRAFi: 76.5%; BRAFi + MEKi: 75%). A non-significant trend towards a higher risk of relapse was found in women (p = 0.1; RR 3.36; 95% CI 0.77-17.07), in patients with an LDH level greater than the upper limits of normal (p = 0.58; RR 2.43; 95% CI 0.10-56.71), and when more than two metastatic sites were involved (p = 0.19; RR 4.6; 95% CI 0.46-46.51). After relapse, targeted therapy was resumed in 17 patients (7 with BRAFi; 10 with BRAFi + MEKi) with a response rate of 53%. CONCLUSIONS: This real-life study provided long-term data in patients who discontinued targeted therapy after CR. Most patients experienced a relapse in the first year after targeted therapy discontinuation, of whom 50% were in the first 3 months. After targeted therapy resumption, 53% of relapsing patients achieved an objective response. Patients should be followed during the first year after treatment discontinuation. In addition, patients with less than 3 metastatic sites, a baseline LDH level with normal ranges, men, and patients responding rapidly to treatment would be more likely to maintain a CR after treatment discontinuation.

Cutibacterium acnes and Staphylococcus epidermidis: the unmissable modulators of skin inflammatory response.

Acne is a multifactorial inflammatory dermatose that affects all age categories from teenagers to adults, resulting in important psychological impacts. Multiple hypotheses currently attempt to decrypt the physiopathology of this disease, and four main actors were identified as highly implicated in it: hyperkeratinization of the pilosebaceous follicle, hyperseborrheae, host factors (innate immunity) and skin microbiota. In this letter, we present results illustrating the impact of skin microbiota on inflammatory skin response, and how far the proper balance between each bacterial community, especially C. acnes and S. epidermidis, is crucial to maintain an appropriate inflammatory response on the skin. The data presented in this study demonstrate that within the skin microbiota, an imbalance between Cutibacterium acnes and Staphylococcus epidermidis, is able to induce the activation of inflammation-related markers such as IL-1ra, IL-6, IL-8, G-CSF and the molecules C5/C5a, soluble CD14 MIP-3beta, Serpin E1, VCAM-1 and beta-defensin-2. Moreover, S. epidermidis appears to have a more important role than C. acnes on the induction of inflammation-related markers, particularly on IL-6. This work is the basis of future in vitro studies to further understand acne physiopathology, inspiring the development of future innovative therapies based on skin microbiota modulation.