Real-world data on the effectiveness of brodalumab in patients with moderate-to severe plaque psoriasis in the Greek clinical setting (the BrIDGE study).

BACKGROUND: Despite that brodalumab's efficacy and safety have been assessed in randomized clinical trials, real-life data remain scarce. BrIDGE was an observational, prospective, single-cohort, multicentre study that recruited patients with moderate-to severe plaque psoriasis in Greece. OBJECTIVES: The primary objective was to assess the proportion of patients who achieved Psoriasis Area and Severity Index (PASI)100 after 24 weeks. Other endpoints included: the maintenance of PASI90/100 through to 104 weeks, the short-term response [PASI75/90/100 and static Physician's Global Assessment (sPGA) 0/1] to brodalumab at 12-16 weeks and time to complete clearance. Moreover, we explored the change in quality of life [Dermatology Life Quality Index (DLQI) 0/1] and adherence to brodalumab. METHODS: Two hundred patients who were initiating treatment with or switching to brodalumab, were recruited. Analyses were conducted using the as observed data and three imputation approaches were also applied for the missing data (last observation carried forward, 'worst case' and 'best case' scenario). Continuous variables were reported using summary statistics, whereas categorical variables were reported in frequency tables. RESULTS: Based on the 'as observed data', 42.0% of patients achieved PASI100 at Week 24 after 25.9 ± 3.5 weeks and 65% of patients attained PASI100 at Week 104. In total, 70.2%, 47.5% and 32.0% achieved PASI75/90/100, respectively, whereas 72.6% of patients achieved sPGA 0/1, at Weeks 12-16. With respect to sPGA status 82.8%, 89.2% and 92.5% of patients achieved sPGA 0/1 at Weeks 24, 52 and 104, respectively. The time to achieve PASI100 at Weeks 12-16 was 13.7 ± 1.3, 52.1 ± 3.4 weeks at Week 52 and 105.5 ± 4.8 weeks at Week 104. Mean DLQI and Psoriasis Symptom Inventory (PSI) scores decreased by 11.4 ± 7.0 and 15.4 ± 6.5 points from baseline to Week 104, respectively. Adherence to treatment was equal to 98.9%. CONCLUSIONS: Brodalumab confers rapid and durable responses, as well as improvements in the quality of life of moderate-to-severe psoriasis patients.

Disentangling the complexity of psoriasis in the post-genome-wide association era.

In recent years, genome-wide association studies (GWAS) have been instrumental in unraveling the genetic architecture of complex diseases, including psoriasis. The application of large-scale GWA studies in psoriasis has illustrated several associated loci that participate in the cutaneous inflammation, however explaining a fraction of the disease heritability. With the advent of high-throughput sequencing technologies and functional genomics approaches, the post-GWAS era aims to unravel the functional mechanisms underlying the inter-individual variability in psoriasis patients. In this review, we present the key advances of psoriasis GWAS in under-represented populations, rare, non-coding and structural variants and epistatic phenomena that orchestrate the interplay between different cell types. We further review the gene-gene and gene-environment interactions contributing to the disease predisposition and development of comorbidities through Mendelian randomization studies and pleiotropic effects of psoriasis-associated loci. We finally examine the holistic approaches conducted in psoriasis through system genetics and state-of-the-art transcriptomic analyses, discussing their potential implication in the expanding field of precision medicine and characterization of comorbidities.

Protein network and pathway analysis in a pharmacogenetic study of cyclosporine treatment response in Greek patients with psoriasis.

Although cyclosporine comprises a well-established systemic therapy for psoriasis, patients show important heterogeneity in their treatment response. The aim of our study was the pharmacogenetic analysis of 200 Greek patients with psoriasis based on the cyclosporine pathway related protein-protein interaction (PPI) network, reconstructed through the PICKLE meta-database. We genotyped 27 single nucleotide polymorphisms, mapped to 22 key protein nodes of the cyclosporine pathway, via the utilization of the iPLEX®GOLD panel of the MassARRAY® System. Single-SNP analyses showed statistically significant associations between CALM1 rs12885713 (P = 0.0108) and MALT1 rs2874116 (P = 0.0006) polymorphisms with positive response to cyclosporine therapy after correction for multiple comparisons, with the haplotype analyses further enhancing the predictive value of rs12885713 as a pharmacogenetic biomarker for cyclosporine therapy (P = 0.0173). Our findings have the potential to improve our prediction of cyclosporine efficacy and safety in psoriasis patients, as well as provide the framework for the pharmacogenetics of biological therapies in complex diseases.

Sub-population analysis of patients with plaque psoriasis treated with calcipotriol/betamethasone aerosol foam; effectiveness and patient satisfaction, according to baseline disease severity and prior psoriasis treatment experience, in a Greek population.

Fixed combination calcipotriol/betamethasone (Cal/BD) aerosol foam has been shown to be effective in psoriasis treatment in clinical trials, but real-world evidence is currently sparse. The real-world CELSUS study in Greece found that Cal/BD aerosol foam treatment was effective and associated with satisfaction in psoriasis patients. Patients from the CELSUS study (N = 400) were stratified by baseline disease severity according to physician's global assessment (PGA) score (mild vs. moderate vs. severe) and by previous psoriasis treatment (naïve vs. treatment-experienced). Proportions of patients achieving treatment success (clear/almost clear [PGA 0/1]) after 4 weeks' treatment with Cal/BD aerosol foam were reported for each subgroup. Psoriasis area and severity index (PASI) and patient-reported itch, itch-related sleep loss, scaling, dry skin, and erythema numerical rating scores were reported by subgroup. At baseline, 216 (54%) patients were systemic-or-topical psoriasis treatment-naïve and 184 (46%) were treatment experienced. By disease severity, there were 135 versus 89 patients with mild, 69 versus 83 with moderate and 12 versus 12 with severe disease in the treatment-naïve versus treatment-experienced groups, respectively. In the treatment-naïve group, treatment success was achieved by 72.6%, 56.5%, and 66.7% of patients with mild, moderate, and severe disease, respectively, while the proportions in the treatment-experienced group were 60.7%, 42.2%, and 25%, respectively. Reduction from baseline in psoriasis symptoms was observed in all patient groups. The greatest reductions were observed in treatment-naïve patients with severe disease. Clinically relevant benefits were observed with Cal/BD aerosol foam in psoriasis patients, regardless of prior treatment-experience and disease severity at baseline.

Real world experience of brodalumab treatment in patients with moderate-to-severe plaque psoriasis in the Greek population: Results from an interim analysis of the BrIDGE study.

Brodalumab's clinical efficacy and favorable safety profile have been demonstrated during controlled clinical trials, but real-world data remain scarce. BrIDGE, an ongoing 104 week, observational, prospective, multicenter study conducted in Greece, enrolled moderate-to-severe plaque psoriasis patients, with body surface area (BSA) > 10 or psoriasis area severity index score (PASI) > 10 and dermatology life quality index (DLQI) > 10, based on European consensus, initiating brodalumab treatment as per routine clinical practice. This interim analysis includes evaluations 12-16 weeks following treatment initiation. Key efficacy endpoints included proportion of patients achieving static Physician's Global Assessment (sPGA) score of "clear/almost clear" (0/1) and a reduction ≥75%, 90%, 100% from baseline in PASI (PASI75, PASI90, and PASI100) at weeks 12-16. Other endpoints included time to achieve PASI100, changes in self-reported DLQI and psoriasis symptom inventory (PSI) at weeks 12-16. From 200 patients (mean age 51.4 years, 70% male, mean disease duration 13.8 years) enrolled, 72.8% achieved sPGA of 0/1, whereas 70.2%, 47.5%, and 32.0% achieved corresponding PASI75, PASI90, and PASI100 responses following 12-16 weeks of brodalumab treatment, according to the "as-observed" analysis. The mean time to achieve PASI100 was 13.7 ± 1.2 weeks for the 32% who achieved PASI100. Concurrent decreases in mean DLQI and PSI were observed. Furthermore, 90% adherence to brodalumab was noted and nine adverse events were reported. Brodalumab confers substantial clinical improvements short-term as reflected by high levels of skin clearance in moderate-to-severe plaque psoriasis patients within 12-16 weeks of treatment under everyday clinical conditions, followed by improvements in symptoms and quality of life and a favorable safety profile.

Revisiting miRNA Association with Melanoma Recurrence and Metastasis from a Machine Learning Point of View.

The diagnostic and prognostic value of miRNAs in cutaneous melanoma (CM) has been broadly studied and supported by advanced bioinformatics tools. From early studies using miRNA arrays with several limitations, to the recent NGS-derived miRNA expression profiles, an accurate diagnostic panel of a comprehensive pre-specified set of miRNAs that could aid timely identification of specific cancer stages is still elusive, mainly because of the heterogeneity of the approaches and the samples. Herein, we summarize the existing studies that report several miRNAs as important diagnostic and prognostic biomarkers in CM. Using publicly available NGS data, we analyzed the correlation of specific miRNA expression profiles with the expression signatures of known gene targets. Combining network analytics with machine learning, we developed specific non-linear classification models that could successfully predict CM recurrence and metastasis, based on two newly identified miRNA signatures. Subsequent unbiased analyses and independent test sets (i.e., a dataset not used for training, as a validation cohort) using our prediction models resulted in 73.85% and 82.09% accuracy in predicting CM recurrence and metastasis, respectively. Overall, our approach combines detailed analysis of miRNA profiles with heuristic optimization and machine learning, which facilitates dimensionality reduction and optimization of the prediction models. Our approach provides an improved prediction strategy that could serve as an auxiliary tool towards precision treatment.

Nipple candidiasis and painful lactation: an updated overview.

Nipple pain and discomfort during or after breastfeeding remains one of the most common reasons for premature cessation of lactation among the affected women. The belief that yeasts, and especially Candida spp., are responsible for such symptoms is highly supported by many physicians, midwives, or lactation specialists, but is also viewed with scepticism by other health care providers. The aim of this paper is to provide an updated report of the evidence against, as well as in favour of, the "Candida hypothesis". Several studies have documented that lactating women with symptoms such as nipple soreness, with or without radiating breast pain, are more likely to test positive for Candida spp. than non-symptomatic women. However, its role as an undisputable aetiopathogenic factor for infection in these cases cannot always be established. Physicians should evaluate thoroughly such patients, because early and correct recognition of the underlying problem can prevent phenomena of early weaning.

Acremonium nail bed mycetoma masquerading as subungual squamous cell carcinoma.

Acremonium is a large fungal genus that is comprised of approximately 150 species, found ubiquitously in nature. Although the majority are recognized as being saprophytes in soil and pathogens of plants, several species are emerging as causative agents of a variety of human infections, including mycetomas. Herein, we present a young man that was referred to our department with a painful subungual mass that developed following traumatic inoculation of Acremonium spp. In recent years, the role of Acremonium spp. has been increasingly recognized in localized infections, such as mycetoma, in humans. Other locally invasive as well as disseminated infections are also described. Optimal treatment of Acremonium spp. mycetoma is not well defined owing to the rarity of cases, thus posing a therapeutic challenge.

Malacoplakia of the skin: overview of a rare clinical entity.

BACKGROUND: Malacoplakia is a rare acquired, infection-related granulomatous disorder, that may affect many systems, but typically occurs in the urinary tract. Cutaneous involvement is less prevalent, and most commonly presents with a perianal or genital region localization. Cutaneous malacoplakia is believed to be caused by an acquired bactericidal defect of macrophages in the setting of chronic infections and immunocompromised states. A diagnosis of cutaneous malacoplakia should be considered when encountering non-specific granulomatous lesions that are refractory to treatment. Histologic findings are marked by the presence of foamy macrophages containing the pathognomonic Michaelis-Gutman bodies. OBJECTIVES: The aim of this review is to discuss the current perspectives on the pathophysiology, clinical features, diagnosis, and treatment of this disease. We would also like to emphasize that the integration of clinical information, microscopic findings, and exclusion of other cutaneous granulomatous processes is necessary to accurately diagnose this exceedingly rare disease and provide opportunity for therapeutic intervention. PATIENTS/METHODS: Data for this work were collected from the published literature and textbooks. RESULTS: Combined surgical excision and protracted antibiotic courses appear to have the highest success rate. Antibiotics should be culture specific, but drugs that easily permeate the macrophages appear to be the best choice.

Evaluation of T-lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin.

BACKGROUND: Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T-cells (Tregs) in these lesions. METHODS: Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin (NS) were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semiquantitative Klintrup-Mäkinen (K-M) score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification. RESULTS: An increase of all TIL subpolulations from precursor lesions toward inSCC was shown by both scoring systems. Treg counts progressively increased from NS to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes. CONCLUSIONS: T-cells and cytotoxic T-cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K-M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC.

Successful treatment of multifocal pigmented basal cell carcinomas with the application of topical 5% imiquimod cream.

Basal cell carcinoma (BCC) is one of the most frequent skin malignancies, with increasing incidence over the past years. Although the surgical excision is the gold-standard treatment, several other noninvasive therapies have also been developed for the management of these skin tumors, especially in the cases where a surgical intervention does not seem feasible. Imiquimod is an immunomodulatory agent, which has received approval in the topical treatment of superficial BCCs. With this short report, we present the case of a patient with multifocal pigmented BCCs, successfully treated with topical 5% imiquimod cream.