Successful Removal of 17 Tattoos Self-Administered Using Black Eyeliner Ink with Quality-Switched Neodymium-Doped Yttrium Aluminum Garnet 1,064-nm Laser: A Case Report.

Introduction: Tattooing has a rich historical presence in various human civilizations, with the earliest physical evidence dating back to around 3258 BC. While acceptance of tattoos is increasing in the Western world, negative associations remain. Short-pulsed lasers, such as Q-Switched (QS) or picosecond lasers, are the gold standard for tattoo removal. Case Presentation: This case report discusses the successful removal of 17 amateur tattoos, which were self-administered by a 19-year-old female patient using black eyeliner ink and sewing needles. The tattoos, distributed across her body, including the face and hands, were partially or completely removed over 10 sessions using the QS Neodymium-doped Yttrium Aluminum Garnet 1,064-nm laser. Conclusion: The factors that influence the efficacy of tattoo removal are highlighted, including tattoo type, location, and coexisting fibrosis. The psychological and social importance of effective tattoo removal is emphasized, particularly for young people seeking to disassociate from past experiences or affiliations.

Case report: Area of focus of management of severe pityriasis rubra pilaris by dose optimization of adalimumab biosimilar in combination with acitretin and montelukast.

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder characterized by hyperkeratotic follicular papules, orange-red scaling plaques with islands of sparing and palmoplantar keratoderma. While spontaneous resolution occurs in some cases, treatment can be challenging for others. The use of biologics in PRP management has gained attention in recent studies, although their high costs and potential side effects present limitations. We present a case of a 71-year-old patient with treatment-resistant PRP who showed significant improvement through optimized adalimumab treatment. Considering the emerging role of phospholipase A2 in PRP pathogenesis, montelukast was added, further enhancing the therapeutic response. By maintaining montelukast and prolonging the adalimumab interval to 3 and 4 weeks, effective dose optimization was achieved without PRP relapse. This case report highlights the potential for adalimumab dose optimization by shortening the initial treatment interval for increased effectiveness and lengthening the interval during the maintenance phase to conserve medication doses. Montelukast appears to assist in sustaining clinical outcomes during interval prolongation, necessitating further investigation through additional studies.

Dimethyl Fumarate Used as an Effective Treatment for Granuloma Annulare Disseminatum: An Immunohistochemical Case Study.

This investigation demonstrates the use of dimethyl fumarate (DMF) for the treatment of disseminated granuloma annulare (GAD), a rare and chronic inflammatory skin disease. In this case, progressive GAD was treated with DMF, resulting in significant improvement of skin lesions within 5 weeks and complete healing within 7 months. Clinical response was associated with a reduction in inflammatory cells, including both T cell subsets (CD4+ > CD8+), CD183+/CXCR3+ cells, Langerhans cells (CD1a+), myeloid DCs, M1- and M2-like macrophages and the activation marker HLA-DR in immunohistochemical analysis. These findings support the use of DMF as a promising treatment option for this rare skin condition.

HPV Vaccination in Immunosuppressed Patients with Established Skin Warts and Non-Melanoma Skin Cancer: A Single-Institutional Cohort Study.

cSCC (cutaneous squamous cell carcinoma) and its precursors are a major cause of morbidity, especially in immunosuppressed patients, and are frequently associated with human papillomavirus (HPV) infections. The purpose of this study is to investigate the therapeutic potential of alpha-HPV vaccination for immunosuppressed patients with established cSCC and its precursors. In this retrospective study, all patients who received Gardasil-9®, a nonavalent HPV vaccine, as secondary prophylaxis were examined. Dermatologic interventions in both the pre- and post-vaccination periods were analyzed with zero-inflated Poisson regression and a proportional intensity model for repeated events with consideration of the clinically relevant cofactors. The hazard ratio for major dermatologic interventions was 0.27 (CI 0.14-0.51, p < 0.001) between pre- and post-Gardasil-9® intervention. Gardasil-9® vaccination showed good efficacy in reducing major dermatologic interventions even after correction of relevant cofactors and national COVID-19 caseloads during the observational period. Alpha-HPV vaccination may potentially cause a significant decrease in dermatologic interventions and overall mortality as well as healthcare costs in immunosuppressed patients with high skin tumor burden.

Skin hyperpigmentation index in melasma: A complementary method to classic scoring systems.

BACKGROUND: Due to relapsing nature of melasma with significant impact on quality of life, an objective measurement score is warranted, especially to follow-up the patients with melasma and their therapy response in a quantitative and precise manner. AIMS: To prove concordance of skin hyperpigmentation index (SHI) with well-established scores in melasma and demonstrate its superiority regarding inter-rater reliability. Development of SHI mapping for its integration in common scores. METHODS: Calculation of SHI and common melasma scores by five dermatologists. Inter-rater reliability was assessed by intraclass correlation coefficient (ICC) and concordance by Kendall correlation coefficient. RESULTS: Strong concordance of SHI with melasma area and severity index (MASI)-Darkness (0.48; 95% CI: 0.32, 0.63), melasma severity index (MSI)-Pigmentation (0.45; 95% CI: 0.26, 0.61), and melasma severity scale (MSS) (0.6; 95% CI: 0.42, 0.74). Using step function for mapping SHI into pigmentation scores showed an improvement of inter-rater reliability with a difference in (ICC of 0.22 for MASI-Darkness and 0.19 for MSI-Pigmentation), leading to an excellent agreement. CONCLUSION: Skin hyperpigmentation index could be an important additional cost-and time-conserving assessment method, to follow-up the patients with melasma undergoing brightening therapies in clinical studies, as well as in routine clinical practice. It is in strong concordance with well-established scores but superior regarding inter-rater reliability.

Canakinumab leads to rapid reduction of neutrophilic inflammation and long-lasting response in Schnitzler syndrome.

Interleukin-1 (IL-1)-blocking therapies are effective in reducing disease severity and inflammation in Schnitzler syndrome. Here, we present a patient with Schnitzler syndrome treated successfully using canakinumab for over 10 years. Complete clinical response was associated with a decrease in dermal neutrophil number and expression of the pro-inflammatory cytokines IL-1ß, IL-8, and IL-17 as assessed by immunohistochemical studies.

Randomized Open-Label Trial Comparing Teledermatology vs. Face-to-Face Consultation in the Follow-Up of Patients with Mild-to-Moderate Acne.

Background: Acne vulgaris is one of the most common dermatological diseases, especially in adolescents and young adults. Objective: The current study aimed to compare teledermatology versus face-to-face consultation in the follow-up of patients with mild-to-moderate acne. Methods: In this investigator-initiated, parallel arms, open-label, randomized clinical trial, after screening, participants were randomly assigned in a 1:1 ratio to be followed up through teledermatology or standard face-to-face consultations for a period of 6 months. The primary endpoint was the cumulative time spent by physician for consultations or online assessments. Results: Out of 24 patients (21 females and 3 males; mean age 23.0 ± 3.3 years) underwent randomization in the two study groups. In intention-to-treat analysis, the cumulative time spent by physician was higher in the teledermatology group compared to face-to-face consultations with an average difference of 8:24 mm:ss (95% CI: 1:17-15:31). However, the cumulative time spent by the patient was significantly lower in the teledermatology group (mean difference 1:21:39 hh:mm:ss; 95% CI: 41:51-2:01:27). An optimal reduction of acne-severity was observed in both groups, without significant differences between them. The patient's satisfaction did not change significantly over time and between groups, and was generally quite high. AEs were reported by one patient in the teledermatology group and four patients in the consultation group. Conclusion: Acne might be an optimal disease to be followed up using a teledermatology platform, to relieve the burden on patients and medical staff. However, it is necessary to implement more user-friendly platforms in order to achieve the best possible results in the treatment and follow-up of acne patients.

Long-Term Follow-Up of Lentigo Maligna Patients Treated with Imiquimod 5% Cream.

BACKGROUND: The study investigated the long-term efficacy of imiquimod 5% cream for LM, with a focus on disease recurrence and the possible prognostic factors of disease-free survival (DFS) in a cohort, with long-term follow-up. METHODS: Consecutive patients with histologically confirmed LM were included. Imiquimod 5% cream was applied until weeping erosion appeared on the LM-affected skin. The evaluation was performed through clinical examination and dermoscopy. RESULTS: We analyzed 111 patients with LM (median age: 72 years, 61.3% women) with tumor clearance after imiquimod therapy, with a median follow-up of 8 years. The overall patient survival rates were 85.5% (95% confidence interval (CI): 78.5-92.6) and 70.4% (95% CI: 60.3-80.5) at 5 and 10 years, respectively. Among the 23 patients (20.1%) with relapse at follow-up, 17 (73.9%) were treated with surgery, five (21.7%) continued imiquimod therapy, and one (4.3%) underwent both surgery and radiotherapy. After adjustment for age and LM area in multivariable models, localization of LM in the nasal region was identified as a prognostic factor for DFS (HR = 2.66; 95% CI: 1.06-6.64). CONCLUSION: If surgical excision is not possible due to the patients' age/comorbidities or critical cosmetic localization, imiquimod could provide optimal outcomes with an optimal risk of relapse for the management of LM.

Skin hyperpigmentation after sclerotherapy with polidocanol: A systematic review.

Skin hyperpigmentation after sclerotherapy with polidocanol-containing sclerosants is a common local side effect. Sclerotherapists should be familiar with factors that trigger hyperpigmentation after sclerotherapy with polidocanol-containing sclerosants. A systematic literature review of works reporting hyperpigmentation after sclerotherapy for telangiectasias, reticular veins, side branches and truncal varices with polidocanol-containing sclerosants was performed. Reported incidence rates, follow-up periods and potentially triggering factors were assessed and analysed. The search yielded 1687 results; of these, 27 reports met the inclusion criteria. The incidence of hyperpigmentation seemed to increase with higher concentrations of polidocanol and was more evident after sclerotherapy for epifascial veins than for intrafascial truncal veins when the polidocanol concentration was more than 0.25%. Regarding sclerotherapy for telangiectasias and reticular veins, the incidence of hyperpigmentation ranged between 2% and 25% for polidocanol 0.25% (liquid and foam), between 12.5% and 67.9% for polidocanol 0.5% (liquid and foam) and between 13% and 73% for polidocanol 1% (liquid and foam). Regarding truncal veins, the incidence ranged from 7% to 45.8% for polidocanol 1% (liquid and foam), from 16% to 17% for polidocanol 2% (foam) and from 7.4% to 32.5% for polidocanol 3% (liquid and foam). Regarding the treatment of side branches, the incidence of hyperpigmentation ranged from 5.6% to 53% for both foam and liquid sclerotherapy. Regarding the duration of hyperpigmentation, there are few data describing reticular veins and telangiectasias. Hyperpigmentation persisting for more than 6 months has been reported to have an incidence of up to 7.5%. Hyperpigmentation persisting for more than 1 year after foam polidocanol 1%-3% treatment for truncal veins has an incidence ranging from 8.1% to 17.5%. Other factors such as higher volumes and compression therapy after treatment seem to have a minor influence. Data regarding hyperpigmentation after polidocanol-related sclerotherapy are poor and should be improved by higher-quality research.

Subcapsular Sinus Macrophages Promote Melanoma Metastasis to the Sentinel Lymph Nodes via an IL1α-STAT3 Axis.

During melanoma metastasis, tumor cells originating in the skin migrate via lymphatic vessels to the sentinel lymph node (sLN). This process facilitates tumor cell spread across the body. Here, we characterized the innate inflammatory response to melanoma in the metastatic microenvironment of the sLN. We found that macrophages located in the subcapsular sinus (SS) produced protumoral IL1α after recognition of tumoral antigens. Moreover, we confirmed that the elimination of LN macrophages or the administration of an IL1α-specific blocking antibody reduced metastatic spread. To understand the mechanism of action of IL1α in the context of the sLN microenvironment, we applied single-cell RNA sequencing to microdissected metastases obtained from animals treated with the IL1α-specific blocking antibody. Among the different pathways affected, we identified STAT3 as one of the main targets of IL1α signaling in metastatic tumor cells. Moreover, we found that the antitumoral effect of the anti-IL1α was not mediated by lymphocytes because Il1r1 knockout mice did not show significant differences in metastasis growth. Finally, we found a synergistic antimetastatic effect of the combination of IL1α blockade and STAT3 inhibition with stattic, highlighting a new immunotherapy approach to preventing melanoma metastasis.

Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy.

BACKGROUND: The majority of patients with B-cell-depleting therapies show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 immune responses in patients of the RituxiVac study compared with healthy volunteers and investigate the immunogenicity of a third vaccination in previously humoral non-responding patients. METHODS: We investigated the humoral and cell-mediated immune response after SARS-CoV-2 messanger RNA vaccination in patients with a history with anti-CD20 therapies. Coprimary outcomes were antispike and SARS-CoV-2-stimulated interferon-γ concentrations in vaccine responders 4.3 months (median; IQR: 3.6-4.8 months) after first evaluation, and humoral and cell-mediated immunity (CMI) after a third vaccine dose in previous humoral non-responders. Immunity decay rates were compared using analysis of covariance in linear regression. RESULTS: 5.6 months (IQR: 5.1-6.7) after the second vaccination, we detected antispike IgG in 88% (29/33) and CMI in 44% (14/32) of patients with a humoral response after two-dose vaccination compared with 92% (24/26) healthy volunteers with antispike IgG and 69% (11/16) with CMI 6.8 months after the second vaccination (IQR: 6.0-7.1). Decay rates of antibody concentrations were comparable between patients and controls (p=0.70). In two-dose non-responders, a third SARS-CoV-2 vaccine elicited humoral responses in 19% (6/32) and CMI in 32% (10/31) participants. CONCLUSION: This study reveals comparable immunity decay rates between patients with anti-CD20 treatments and healthy volunteers, but inefficient humoral or CMI after a third SARS-CoV-2 vaccine in most two-dose humoral non-responders calling for individually tailored vaccination strategies in this population.Trial registration numberNCT04877496; ClinicalTrials.gov number.

Long-Term Effectiveness and Drug Survival of Apremilast in Treating Psoriasis: A Real-World Experience.

BACKGROUND: Apremilast is an oral phosphodiesterase 4 (PDE4) inhibitor used for the treatment of moderate to severe psoriasis. Long-term data on the effectiveness and drug survival of patients treated with apremilast are limited. OBJECTIVE: The aim of this study was to analyze the characteristics, effectiveness, and drug survival of patients treated with apremilast in a real-world setting. METHODS: We conducted a retrospective cohort study of patients with psoriasis who received at least 1 dose of apremilast between 2015 and 2018. We documented sex; age; type, duration, and severity (using Psoriasis Area Severity Index [PASI] and Dermatology Life Quality Index [DLQI]) of psoriasis; comorbidities; previous treatment modalities; adverse events; and reasons for therapy discontinuation. For drug survival, estimates and efficacy analysis with Kaplan-Meier statistics were used. RESULTS: The drug survival rate of the 93 reviewed patients was 69.5% at 6 months, 34.7% at 12 months, and 25.8% at 24 months after initiating therapy. The median survival duration was 8.0 months. Therapy was discontinued in 66.6 and 27.8% due to loss of efficacy and adverse events, respectively. At 24 months, 35.9% had achieved PASI75 response and 23.7% had achieved PASI90 response. Most observed adverse events were gastrointestinal issues, weight loss, and headache. CONCLUSIONS: Apremilast is an effective and well-tolerated therapy for patients with moderate to severe psoriasis, especially for patients with difficult-to-treat locations and/or contraindications to other biologics. Furthermore, apremilast was used for patients with a history of nonresponse to biologics and was favored for patients with relatively low PASI (<10) and a high DLQI.

Melanoma of the Nail Apparatus: An Analysis of Patients' Survival and Associated Factors.

BACKGROUND: There are no proper management guidelines for nail apparatus melanoma (NAM). OBJECTIVE: This study aimed to describe the clinical features, the presence of locoregional and distant metastases and disease-free and overall survival of NAM treated at our institution. METHODS: A retrospective cohort review of patients with single, primary localized histopathologically confirmed NAM was performed. Collected data consisted of patients' characteristics and tumor features. In addition, local recurrence, locoregional metastases, distant metastases, disease-free survival (DFS) and overall survival (OS) were used as the main outcomes in our analysis. RESULTS: Thirty patients with NAM were included. The overall survival (OS) in our patients at 5 and 10 years was 85.6 and 73.4%, respectively. DFS was significantly higher in patients with primary tumor location in the hand and without tumor-infiltrating lymphocytes (p value = 0.01 and 0.04, respectively). The patients with in situ melanoma or Breslow thickness <1 mm had a significantly higher chance of DFS and OS (90.0 and 94.1% at 5 years, respectively) than those with thicker NAM (58.3 and 55.6% at 5 years, respectively). A total of 53.3% of 30 patients underwent primary excision and covering with a full-thickness skin graft, while 13.3% of our 30 patients underwent digit amputation. The patients who underwent excision and covering with a full-thickness skin graft showed a complete overall survival (100% at 5 years). CONCLUSION: Primary tumor location in the hand and lower tumor thickness might be correlated with better patients' survival. The study results suggest that total amputation might not be necessary in all NAM cases.

Effect of topical application of platelet-rich plasma on chronic venous leg ulcerations.

Wound products that reliably support healing of chronic leg ulcers remain a huge unmet need in clinical practice. Due to the lack of standardized comparable protocols and different systems for platelet-rich plasma (PRP) preparation, there is limited data on healing rates in chronic venous ulcers. In our case series with a total of seven chronic leg ulcers in four patients, we investigated the healing rates based on standardized digital photographs of chronic venous ulcers after application of topical PRP using a digital imaging software. In 5 out of 7 ulcers, the PRP-treated wound half showed faster healing as compared the control half of the wound. In this case series, PRP-treated sides of chronic venous leg ulcers showed a tendency for accelerated healing as compared to nontreated collateral wound side. Our data support the evaluation of topical PRP treatment in the management of chronic venous leg ulcers.

Efficacy Assessment of the High-Frequency High-Intensity Focused Ultrasound as a New Treatment for Actinic Keratosis.

BACKGROUND: Actinic keratosis (AK) is the most common precancerous cutaneous lesion, with risk of progression to cutaneous squamous cell carcinoma. In the current study, we evaluated the efficacy of 20-MHz high-intensity focused ultrasound (HIFU), as a new treatment modality for AK. MATERIALS AND METHODS: Patients with AK lesions (grades I-III) treated with HIFU were included in the study. The clinical assessment was performed 3 months after therapy. RESULTS: Twenty-one patients (14 men, 7 women) with 108 AK lesions (grades I-III) were included in the current study. Ages ranged from 62 to 85 years (mean 72.6 years). Clinically complete resolution of the actinic damage in the treated area was detected in 72.2% of lesions. Furthermore, 28 lesions (26%) showed a reduction of the AK grade, or partial response, after the therapy. Most of the patients experienced annoying but short pain during the procedure. However, late adverse effects of the therapy, such as hypopigmentation, hyperpigmentation and erythema were reported only in a small portion of the lesions. CONCLUSIONS: 20-MHz HIFU could be an effective and safe alternative treatment for AK.

Reliability Assessment and Validation of the Skin Hyperpigmentation Index Compared to the Physician Global Assessment Score.

BACKGROUND: The skin hyperpigmentation index (SHI), a new objective method for measuring skin hyperpigmentation, needs validation. OBJECTIVE: To gain evidence of the reliability and validity of the SHI. METHODS: Fifteen raters were divided into 3 groups (5 dermatologists, 5 nondermatologist physicians, and 5 nonphysician clinicians). Each rated 5 pigmented mole lesions with mild-to-severe hyperpigmentation to determine intra- and interrater reliability. All raters photographed the lesions and rated them using the subjective Physician Global Assessment (PGA) score. The same photographs were then assessed based on automatic computer measurement software using the online SHI tool (https://shi.skinimageanalysis.com). RESULTS: The SHI reliability was excellent for all intra- and interrater assessments, while most PGA assessments showed good intra- and interrater agreement. Between-group reliability was excellent for SHI, while moderate-to-good for PGA evaluations. Concordance between the SHI and PGA assessments was strong across all groups of assessors. CONCLUSION: There is evidence that the SHI is a reliable instrument for measuring skin hyperpigmentation, and can be used by nonexperienced clinicians.

Comparison of teledermatological examinations with conventional office visits in management of acne vulgaris: A review of current literature.

Acne vulgaris is the most common skin disease in the world, particularly affecting adolescents and young adults. Telemedicine has grown rapidly in the past few years and represents a new simplification in modern medicine. The aim of this literature review is to provide an overview of acne vulgaris in teledermatology and to identify the differences between teledermatological examinations and face-to-face consultations. For this purpose, a systematic literature search of the PubMed database was performed, up to the end of 2019. The content of 109 studies matching the keywords acne, acne vulgaris, teledermatology, telehealth, or telemedicine was screened, and 13 studies were systematically reviewed and compared. The analysis of the studies shows that patients living in remote areas benefit greatly from online visits since it is less time consuming and financially favorable, which is also associated with higher patient satisfaction. In addition, the satisfaction of doctors, the main safety concerns of patients, and a brief insight into telemedicine in other specialties are discussed. Taking the results of the different studies into account, the conclusion is that telemedicine is well accepted and often even desired by most patients and will likely become a very important part of modern medicine in the future.

Humoral and cellular responses to mRNA vaccines against SARS-CoV-2 in patients with a history of CD20 B-cell-depleting therapy (RituxiVac): an investigator-initiated, single-centre, open-label study.

BACKGROUND: B-cell-depleting therapies increase the risk of morbidity and mortality due to COVID-19. Evidence-based SARS-CoV-2 vaccination strategies for patients on B-cell-depleting therapies are scarce. We aimed to investigate humoral and cell-mediated immune responses to SARS-CoV-2 mRNA-based vaccines in patients receiving CD20-targeted B-cell-depleting agents for autoimmune disease, malignancy, or transplantation. METHODS: The RituxiVac study was an investigator-initiated, single-centre, open-label study done at the Bern University Hospital (Bern, Switzerland). Patients with a treatment history of anti-CD20-depleting agents (rituximab or ocrelizumab) and with no previous history of SARS-CoV-2 infection were enrolled between April 26 and June 30, 2021, for analysis of humoral and cell-mediated immune responses (by interferon-γ [IFNγ] release assay) at least 4 weeks after completing vaccination against SARS-CoV-2. Healthy controls without a history of SARS-CoV-2 infection were also enrolled at least 4 weeks after completing vaccination against SARS-CoV-2. All study participants received two doses of either the Pfizer-BioNTech BNT162b2 vaccine or the Moderna mRNA-1273 vaccine. The primary outcome was the proportion of patients with a history of anti-CD20 treatment who showed a humoral immune response against the SARS-CoV-2 spike protein in comparison with immunocompetent controls. Prespecified secondary endpoints were the effect of anti-CD20 therapy (including time since last treatment and cumulative dose) on humoral or cell-mediated immune responses to SARS-CoV-2 vaccination, and biomarkers of immunocompetence. This study is registered with ClinicalTrials.gov, NCT04877496. FINDINGS: The final study population comprised 96 patients and 29 immunocompetent controls. The median age of patients was 67 years (IQR 57-72) and of controls was 54 years (45-62), and 51 (53%) of 96 patients and 19 (66%) of 29 controls were female. The median time since last anti-CD20 treatment was 1·07 years (IQR 0·48-2·55) and the median cumulative dose of an anti-CD20 depleting agent was 2·80 g (1·50-5·00). Anti-spike IgG antibodies were detected in 47 (49%) of 96 patients 1·79 months (IQR 1·16-2·48) after the second vaccine dose compared to 29 (100%) of 29 controls 1·81 months (1·17-2·48) after the second vaccine dose (p<0·001). SARS-CoV-2-specific IFNγ release was detected in 13 (20%) of 66 patients and 21 (75%) of 28 of healthy controls (p<0·001). Only nine (14%) of 66 patients were double positive for anti-SARS-CoV-2 spike IgG and cell-mediated responses, compared with 21 (75%) of 28 healthy controls (p<0·001). Time since last anti-CD20 therapy (>7·6 months; positive predictive value 0·78), peripheral CD19+ cell count (>27 cells per µL; positive predictive value 0·70), and CD4+ lymphocyte count (>653 cells per µL; positive predictive value 0·71) were predictive of humoral vaccine response (area under the curve [AUC] 67% [95% CI 56-78] for time since last anti-CD20 therapy, 67% [55-80] for peripheral CD19+ count, and 66% [54-79] for CD4+ count). INTERPRETATION: This study provides further evidence of blunted humoral and cell-mediated immune responses elicited by SARS-CoV-2 mRNA vaccines in patients with a history of CD20 B-cell-depleting treatment. Lymphocyte subpopulation counts were associated with vaccine response in this highly vulnerable population. On validation, these results could help guide both the administration of SARS-CoV-2 vaccines and B-cell-depleting agents in this population. FUNDING: Bern University Hospital.

ATG5 and ATG7 Expression Levels Are Reduced in Cutaneous Melanoma and Regulated by NRF1.

Autophagy is a highly conserved cellular process in which intracellular proteins and organelles are sequestered and degraded after the fusion of double-membrane vesicles known as autophagosomes with lysosomes. The process of autophagy is dependent on autophagy-related (ATG) proteins. The role of autophagy in cancer is very complex and still elusive. We investigated the expression of ATG proteins in benign nevi, primary and metastatic melanoma tissues using customized tissue microarrays (TMA). Results from immunohistochemistry show that the expression of ATG5 and ATG7 is significantly reduced in melanoma tissues compared to benign nevi. This reduction correlated with changes in the expression of autophagic activity markers, suggesting decreased basal levels of autophagy in primary and metastatic melanomas. Furthermore, the analysis of survival data of melanoma patients revealed an association between reduced ATG5 and ATG7 levels with an unfavourable clinical outcome. Currently, the mechanisms regulating ATG expression levels in human melanoma remains unknown. Using bioinformatic predictions of transcription factor (TF) binding motifs in accessible chromatin of primary melanocytes, we identified new TFs involved in the regulation of core ATGs. We then show that nuclear respiratory factor 1 (NRF1) stimulates the production of mRNA and protein as well as the promoter activity of ATG5 and ATG7. Moreover, NRF1 deficiency increased in vitro migration of melanoma cells. Our results support the concept that reduced autophagic activity contributes to melanoma development and progression, and identifies NRF1 as a novel TF involved in the regulation of both ATG5 and ATG7 genes.