bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug-Induced Erythema Annulare Centrifugum after Dupilumab Therapy: A Case Report.
Authors: Kalsi Simran , Vandyke Santana , Barker Julia , Pierson Joseph
Published: March 2024

Introduction: Dupilumab is a fully human monoclonal antibody therapy FDA-approved to treat moderate-to-severe atopic dermatitis (AD) by interrupting the pro-inflammatory signaling pathway of interleukins 4 and 13. Common side effects of dupilumab include injection-site reactions, ophthalmic complications, and upper respiratory infections. We discuss the necessity for early recognition and management of dupilumab-induced EAC which has not been previously reported as a potential adverse effect.

Case Report: A 48-year-old woman began treatment with dupilumab for severe AD and subsequently presented with a 3-month history of erythematous annular plaques with trailing scale on the trunk and extremities. She failed treatment with topical corticosteroids as well as topical and oral antifungals prior to being diagnosed with biopsy-confirmed erythema annulare centrifugum (EAC). The condition worsened after replacing dupilumab with tralokinumab but resolved after discontinuation of the drugs and has remained clear since.

Conclusion: EAC is a reactive erythema that typically presents as expanding annular papules and plaques with central clearing and in some cases, trailing scale at the rim of the lesions. There are currently no reports in the literature describing the development of EAC secondary to dupilumab. Clinicians should be aware that EAC may be a potential adverse effect of dupilumab.
Histopathological Granuloma Formation in a Subacute Cutaneous Lupus Erythematosus Patient
Authors: Chaisrimaneepan Nattanicha
Published: March 2024

Introduction: Subacute cutaneous lupus erythematosus (SCLE) is one of the cutaneous lupus erythematous subtypes. Being an autoimmune condition in nature, its diagnosis requires compatible clinical presentation with histopathological findings.
Objective: To present a subacute cutaneous lupus erythematosus with granuloma formation.
Case Report: A 56- year-old woman presented with longstanding red plaques on her face, trunk, and extremities. Two skin biopsies were performed during two different visits. The results showed tuberculoid leprosy and multiple granuloma annulare. She was treated accordingly for years with no improvement in her condition. Later, the third skin biopsy with CD123 immunohistochemical stain was done. The result was most consistent with cutaneous lupus erythematosus. Together with her clinical findings, she was finally diagnosed with SCLE. Her rashes resolved after being treated with hydroxychloroquine and topical steroid.
Conclusion: The diagnosis of SCLE must be made based on both clinical presentations and histopathological findings.
Galli Galli Disease: A Challenging Diagnosis in a Bahraini Female Patient
Authors: Dirr McKenzie A. , Almedfa Aysha , Khamdan Fatema
Published: March 2024

Dowling-Degos Disease (DDD) is an inherited cutaneous disease which presents with classic and atypical cutaneous findings, including macules of hyperpigmentation and hypopigmentation in the flexural creases. A variant, termed Galli-Galli Disease (GGD), presents similarly, with the distinguishing feature of acantholysis on histology. Reports of GGD in the literature are rare, due to the infrequency of the diagnosis. This may contribute to a lack of available information and delayed diagnosis, which can result in a frustrating clinical course for patients. We present a female patient who presented with complaints of a burning sensation and painful rash for the last three years on a background of hypopigmented and hyperpigmented macules on the trunk, upper extremities and flexural creases. Comprehensive dermatopathological evaluation and clinical correlates led to the diagnosis of GGD.
Human Leukocyte Antigen DQB1 and its Implication in Scleroderma Pathogenesis: A Systematic Review
Authors: Thibaut Dylan , Doan Vincent , Schroeder Kersten
Published: March 2024

This systematic review explores the association between HLA-DQB1 genes and scleroderma, a chronic autoimmune disease characterized by collagen synthesis dysregulation and tissue fibrosis. A thorough investigation was conducted by utilizing Google Scholar and PubMed to search for relevant studies in the English language. Two independent reviewers were involved in the process of screening for appropriate studies. A limitation of the exclusion of non-English studies potentially introduces language bias. Inclusion criteria focused on articles investigating the association between HLA genes and scleroderma, providing data on patient and control groups. Risk of bias was conducted using the NIH Quality Assessment Tool for Case-Control Studies. The analyses focused on odds ratios (OR) as a measure of the strength of the association of HLA genes with disease susceptibility. Subgroup analyses were performed for Caucasian and Asian samples, along with a combined analysis. In Caucasian samples, DQB1*02:02 was associated with lower odds of scleroderma (OR=0.51, 95% CI [0.41, 0.63]), while DQB1*03:01 was associated with higher odds (OR=1.55, 95% CI [1.22, 1.97]). In Asian samples, DQB1*04:02 and DQB1*06:01 were associated with higher odds of scleroderma (OR=1.51, 95% CI [1.01, 2.24] and OR=1.33, 95% CI [1.06, 1.67], respectively), while DQB1*06:04 was associated with lower odds (OR=0.55, 95% CI [0.37, 0.82]). Combined samples showed decreased odds of scleroderma in DQB1*06:03 (OR=0.68, 95% CI [0.48, 0.95]) and DQB1*06:04 (OR=0.56, 95% CI [0.39, 0.81]).  Future research should explore the interaction between HLA genes and environmental factors to enhance early detection and intervention strategies for individuals at risk of developing scleroderma.
Dupilumab-induced Acanthosis Nigricans
Authors: Yaghi Marita , Ju Teresa , Hu Jamie , Jadoo Arvin , Maderal Andrea
Published: March 2024

Dupilumab is a human monoclonal IgG4 antibody to interleukin-4 (IL-4) and IL-13 approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients six months or older. Several cutaneous adverse reactions to dupilumab have been reported, including facial dermatitis and psoriasis. Herein, we present a unique case of dupilumab-induced acanthosis nigricans (AN) in a patient treated for concomitant AD and contact dermatitis, in the absence of other associated conditions or potential culprit medications. The patient had complete resolution of the lesions with discontinuation of medication, and recurrence upon re-initiation of therapy. This case represents a new cutaneous adverse reaction to dupilumab to which dermatologists should be familiar.
Deucravacitinib in Moderate Plaque Psoriasis: Efficacy in the Phase 3 POETYK PSO-1 and PSO-2 Trials
Authors: Blauvelt Andrew , Korman Neil J. , Merola Joseph F. , Gooderham Melinda , Balagula Eugene , Vanlandingham Rebecca , Treitel Michelle , Wittstock Keith , Hoyt Kim , Banerjee Subhashis , Desai Seemal R.
Published: March 2024

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, was efficacious and well tolerated in adults with moderate to severe plaque psoriasis in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials. We report clinical efficacy of deucravacitinib in the patient subgroup from these trials with baseline plaque psoriasis of moderate severity.

Methods: PSO-1 and PSO-2 randomized patients with moderate to severe plaque psoriasis (PASI ≥12, sPGA ≥3, BSA involvement ≥10% at baseline) 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. Placebo patients crossed over to deucravacitinib at Week 16 in both trials. In PSO-1, deucravacitinib-treated patients received continuous deucravacitinib through Week 52. In PSO-2, PASI 75 responders at Week 24 on deucravacitinib were rerandomized to placebo or deucravacitinib (1:1) through Week 52. In patients meeting criteria for plaque psoriasis of moderate severity, defined as sPGA 3 and BSA 10%-15% at baseline, in the pooled PSO-1/PSO-2 trials, PSO-1 alone, and the PSO-1 placebo crossover population, deucravacitinib efficacy vs placebo was evaluated by PASI 75, PASI 90, and sPGA 0/1 (clear/almost clear) responses (nonresponder imputation) and PASI change from baseline (mBOCF). The Clopper-Pearson method was used to calculate 95% CIs.

Results: PSO-1/PSO-2 moderate psoriasis subgroup PASI 75 response rates were higher with deucravacitinib vs placebo at Week 16 (49.1% [95% CI, 42.5%-55.7%] vs 11.7% [95% CI%, 5.9%-17.4%]) and continued to increase through Week 24 (63.8% [95% CI, 57.5%-70.1%]). PSO-1 PASI 75 response rates were higher with deucravacitinib vs placebo at Week 16 (54.1% [95% CI, 42.1%-65.7%] vs 12.0% [95% CI, 4.5%-24.3%]), Week 24, and were sustained until Week 52. Week 52 PASI 75 response rates for deucravacitinib and placebo crossover groups were comparable (74.3% [95% CI, 62.8%-83.8%] and 67.4% [95% CI, 51.5%-80.9%], respectively). PASI 90 and sPGA 0/1 response rates and change from baseline PASI followed similar patterns, with marked improvement vs placebo at Week 16; peak responses were observed at Week 24 and sustained through Week 52. Efficacy results were comparable to those previously reported for moderate to severe psoriasis.

Conclusion: Deucravacitinib efficacy was confirmed in moderate plaque psoriasis and was consistent with published data in the PSO-1 and PSO-2 overall study population with moderate to severe plaque psoriasis.
Deucravacitinib Long-Term Efficacy in Week 16 Placebo Crossovers: 3-year Results from the POETYK PSO Program
Authors: Lebwohl Mark , Warren Richard B. , Imafuku Shinichi , Bagel Jerry , Armstrong April W. , Passeron Thierry , Banerjee Subhashis , Kisa Renata M. , Vritzali Eleni , Colombo Matthew J. , Scharnitz Thomas , Hoyt Kim , Thaçi Diamant , Blauvelt Andrew
Published: March 2024

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious and well-tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials and through 2 additional years in the POETYK long-term extension (LTE) (NCT04036435) trial in patients treated with deucravacitinib from Day 1 of PSO-1/PSO-2. Here, long-term efficacy was assessed through 3 years in patients who crossed over from placebo to deucravacitinib at Week 16 in PSO-1 or PSO-2 and entered the LTE trial.

Methods: PSO-1 and PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At Week 16, patients randomized to placebo crossed over to deucravacitinib. At Week 52, patients could enroll in the LTE and receive open-label deucravacitinib. Efficacy was evaluated in patients who crossed over from placebo to deucravacitinib at Week 16 of the parent trial and received continuous deucravacitinib through 3 years (Week 148; cutoff June 15, 2022). Outcomes included ≥75%/≥90% reduction from baseline in Psoriasis Area and Severity Index (PASI 75/90) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1). Efficacy is reported using modified nonresponder imputation (mNRI) in patients who reached the Week 148 assessment and those who discontinued before Week 148.

Results: Of 421 patients originally randomized to placebo, 348 crossed over to deucravacitinib at Week 16; of these, 298 completed the parent trials and entered the LTE, with 254 meeting mNRI criteria Efficacy response rates improved from Week 16 on placebo (PASI 75, 13.4%; PASI 90, 4.3%; sPGA 0/1, 11.0%) through Week 52 on deucravacitinib (PASI 75, 75.9%; PASI 90, 47.5%; sPGA 0/1, 59.4%), were generally maintained well through Week 112 (PASI 75, 78.4%; PASI 90, 52.0%; sPGA 0/1, 57.8%), with persistent responses overall observed through Week 148 (PASI 75, 74.4%; PASI 90, 48.1%; sPGA 0/1, 51.1%). Conclusion: These findings further confirm earlier results of once-daily oral deucravacitinib as an effective long-term treatment for patients with moderate to severe plaque psoriasis.
Gene Expression Differences Identified in Skin Samples of Mycosis Fungoides, Atopic Dermatitis, and Psoriasis
Authors: Farberg Aaron , Goldberg Matthew , Quick Ann , Bailey Christine , Zolochevska Olga , Wilkinson Jeff , Silverberg Jonathan , Lio Peter , Koo John , Weinberg Jeffrey , Lebwohl Mark
Published: March 2024

Background: Recent advances in the understanding of the molecular mechanisms underlying atopic dermatitis (AD) and psoriasis (PSO) have led to the development of multiple targeted therapies. Yet, molecular heterogeneity contributes to inconsistent clinical presentation and therapeutic response. Further, systemic treatment of presumed AD or PSO can lead to delays in both diagnosis and proper treatment of patients with a true diagnosis of mycosis fungoides (MF) – a potentially dangerous clinical mimic of AD and PSO that requires a rigorous histologic and molecular workup to diagnose. Therefore, a non-invasive method to distinguish molecular profiles of MF from AD and PSO could inform accurate diagnoses and avoid inappropriate treatment of MF. We have previously shown transcriptomic differences in AD and PSO samples obtained by a non-invasive scraping technique.  However, this technique has not been used to assess differences in gene expression profiles of MF samples.
Objectives: To identify gene expression differences based on diagnosis of MF, AD, or PSO and response to targeted systemic AD or PSO therapies.
Methods: Lesional baseline samples were assessed from 76 patients (AD, n=24; PSO, n=48; and MF, n=4) enrolled in one of two IRB-approved studies (IDENTITY or SIGNAL-MF). Lesional samples were collected by epidermal scraping and preserved in RNA buffer. Library preparation and next generation RNA sequencing was performed using the Ion AmpliSeq Transcriptome Human Gene Expression panel on the S5 Prime sequencer (ThermoFisher). Clinical responses for AD and PSO were further assessed over 3 months using the eczema and psoriasis area and severity index (EASI and PASI, respectively). Genes were considered differentially expressed if there was a log2fold change >|1.0| and padj <.05.
Results: Statistically significant differences in gene expression were observed between AD, PSO, and MF lesions. Further, genes were differentially expressed in baseline skin scrapings obtained from super-responders to dupilumab, which blocks both IL-4 and IL-13 signaling, and PSO therapies including the IL-23 inhibitor risankizumab relative to those who did not achieve ≥90% improvement.
Conclusion: A non-invasive molecular test could be developed to distinguish between AD, PSO, and MF, and further identify super-responders to targeted PSO and AD therapies.
Real-World Efficacy of Spesolimab: Reports from Four Patients with Generalized Pustular Psoriasis
Authors: Tung Joe , Dorsal Jacquelyn , Rezac Laura , Selby Thomas
Published: March 2024

Introduction: Generalized pustular psoriasis (GPP) is a rare, chronic, autoinflammatory skin disease characterized by widespread pustular eruptions that may be accompanied by systemic symptoms. GPP is painful, distressing, and adversely affects patient quality of life (QoL). Spesolimab is a first-in-class anti-IL-36 receptor monoclonal antibody approved for the treatment of GPP flares.
Methods: We describe 4 cases from our respective clinical practices, where individuals with GPP were treated successfully with spesolimab.
Results: Four patient cases of GPP were included; an 18-year-old male, a 58-year-old female; a 36-year-old male, and a 40-year-old female. One patient had a history of GPP, and had experienced 3 prior flares in the preceding year. Two patients had a history of plaque psoriasis. Events preceding the current GPP flare included hydroxychloroquine treatment (n=2), and corticosteroid treatment (n=3). All patients presented with sudden onset of worsening pustular rash (affecting lower extremities [n=1]; extremities and trunk [n=1]; whole body [n=2]). Two patients had systemic symptoms at presentation (1 case: fever, chills, malaise, fatigue; 1 case: severe weakness), and required hospitalization. Two patients received an initial mis-diagnosis of acute generalized exanthematous pustulosis (AGEP). Significant impacts on QoL were reported; all 4 patients were unable to perform normal daily activities; the 18-year-old patient was targeted at school because the skin lesions were perceived to be contagious. The 4 patients received multiple therapies prior to, and concomitantly with, spesolimab treatment, including topical agents, antibiotics, corticosteroids, retinoids, immunosuppressants, and biologics. All 4 patients received two 900 mg intravenous infusions of spesolimab with treatment intervals between 7 and 20 days. Treatment was given at an outpatient infusion center (n=3*), or using a home infusion service (n=1); *1 patient received their first infusion as an inpatient. Significant clinician-assessed improvement in pustules occurred within 1 week of the first spesolimab infusion in 3 patients; the remaining patient reported improvement 1-2 weeks after the second infusion. One of the hospitalized patients experienced 75% improvement in itching, pain, and pustules within 24 hours of the first spesolimab infusion, and was discharged the next day. Spesolimab treatment also improved QoL, with patients experiencing rapid improvements in pain, and their ability to resume their normal daily activities.
Conclusions: These cases demonstrate the efficacy of spesolimab in the real-world, highlighting the ability of spesolimab treatment to rapidly improve GPP symptoms and patient QoL. Administration of spesolimab in an inpatient setting allowed for rapid patient improvement and discharge the next day. These cases also highlight the association of certain drugs as triggers for GPP flares, as well as the importance of AGEP in the differential diagnosis of GPP
Association Between Early Clinical Responses and Long-Term Outcomes With Ruxolitinib Cream Treatment in Mild to Moderate Atopic Dermatitis
Authors: Prajapati Vimal H. , Geng Bob , Blauvelt Andrew , Eichenfield Lawrence F. , Grewal Parbeer , Kircik Leon , Lio Peter , Lynde Charles , Simpson Eric L. , Ren Haobo , Sturm Daniel , Wong Grace , Hong Chih-ho
Published: March 2024

In the TRuE-AD1/2 studies, patients aged ≥12 years with atopic dermatitis (Investigator’s Global Assessment [IGA] 2/3; 3%–20% affected body surface area) were randomized (2:2:1) to twice-daily 0.75%/1.5% ruxolitinib cream or vehicle for an 8-week, double-blind period followed by a 44-week long-term safety (LTS) period of as-needed ruxolitinib cream. This analysis examines associations between Week 8 responder status to 1.5% ruxolitinib cream with LTS outcomes. At Week 8, 57.0% (244/428) of LTS-evaluable patients applying 1.5% ruxolitinib cream achieved IGA–Treatment Success (IGA-TS; IGA 0/1 with ≥2-grade improvement from baseline); 66.6% (285/428) achieved ≥75% improvement in Eczema Area and Severity Index from baseline (EASI-75); 45.8% (196/428) achieved Itch numerical rating scale 0/1 (NRS 0/1). For patients with ≥2 visits (every 4 weeks) during LTS, mean percentages of visits with clear/almost clear skin were 83.2% vs 59.7%, 82.2% vs 54.9%, and 77.3% vs 70.1% for Week 8 IGA-TS, EASI-75, and Itch NRS 0/1 responders vs nonresponders, respectively. Mean percentages of visits with clear/almost clear skin were similar regardless of time to achieve IGA-TS (83.4%/77.4%/81.9% for those achieving at Week 2/4/8), EASI-75 (80.7%/78.8%/81.6%), and Itch NRS 0/1 (75.8%/70.7%/72.8%). During LTS, mean (SD) cumulative treatment-free days due to complete clearance were 149.2 (86.43) vs 104.0 (89.10), 146.4 (88.43) vs 95.9 (83.55), and 142.6 (87.58) vs 124.4 (91.47) for Week 8 IGA-TS, EASI-75, and Itch NRS 0/1 responders vs nonresponders, respectively. Percentage of treatment-free days between study visits (between Weeks 8 and 12 vs Weeks 48 and 52) among Week 8 responders and nonresponders increased from 44.1% to 50.2% and from 16.3% to 42.3% for IGA-TS; from 41.2% to 49.9% and from 14.9% to 40.6% for EASI-75; from 39.8% to 49.4% and from 29.9% to 46.0% for itch NRS 0/1. In summary, efficacy responses achieved with 8-week ruxolitinib cream treatment are associated with higher disease control in LTS; however, nonresponders approach similar disease control with continued treatment. As-needed ruxolitinib cream monotherapy demonstrated substantial long-term disease control regardless of time to first response achievement.
Factors Associated with Persistent Efficacy of Abrocitinib without Flare: A Multivariable Analysis of the JADE-REGIMEN Study
Authors: Thyssen Jacob , Silverberg Jonathan , Blauvelt Andrew , Criado Paolo , Gubelin Walter , Ruano Ruiz Juan , Rojo Ricardo , Terry Ketti , Valdez Hernan , Biswas Pinaki , Feeney Claire
Published: March 2024

Introduction: JADE REGIMEN (NCT03627767) was conducted to evaluate the feasibility of continual, reduced dose or withdrawal of abrocitinib after induction of response in patients with moderate-to-severe atopic dermatitis (AD). This post hoc analysis evaluated patient factors associated with a higher probability of persistent clinical response with abrocitinib, without flare, during a 40-week maintenance period.Methods: Data were analyzed from patients who responded to abrocitinib 200 mg induction therapy (12 weeks) and were randomly assigned to receive abrocitinib (200 or 100 mg) or placebo in the maintenance period (40 weeks). A multivariable logistic regression model with fixed and random effects was fit to determine factors associated with not experiencing flare by week 52. Fixed effects (factors) considered were randomly allocated treatment, age (<18 vs ≥18 years), race, weight, prior use of systemic agents, AD duration, onset of response in induction (early vs late), Investigator’s Global Assessment score at randomization, body surface area (BSA, ≤50% vs >50%) at baseline, and percentage change in Eczema Area and Severity Index (EASI) at randomization. Backward elimination and stepwise model selection procedures were applied with entry and exit criteria based on a P value threshold of 5%.Results:1233 patients received abrocitinib 200 mg in the induction period. By week 12, 798 (64.7%) achieved a response and were randomly assigned to receive maintenance treatment for 40 weeks. In total, 356 patients (44.6%) experienced a protocol-defined flare: 16.5% (200 mg), 39.6% (100 mg), and 77.5% (placebo). After model selection, the analysis identified continuation of treatment with abrocitinib 200 mg (odds ratio [OR], 19.51; 95% CI, 11.28-33.75) or reduced-dose abrocitinib 100 mg (5.27; 3.29-8.46) as the greatest predictors of not experiencing flare during maintenance. Not having previously used systemic agents (OR, 1.53; 95% CI, 1.09-2.14), lower baseline BSA (1.55; 1.10-2.17), and greater percentage reduction of EASI during induction (1.35; 1.15-1.59) were also associated with not experiencing flare.Conclusions: Multivariable analysis of JADE REGIMEN indicated that maintenance treatment with abrocitinib in patients with AD reduced the risk for flare in a dose-dependent manner. Other factors associated with maintaining response to treatment without flare included no previous exposure to systemic agents, lower extent of BSA involvement at baseline, and greater percent change in EASI during induction. These findings may assist clinicians with abrocitinib dosing decisions in the future.
Impact of Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, Deucravacitinib, on Psoriasis in Patients with Active Psoriatic Arthritis: Results from a Phase 2 Trial
Authors: Gottlieb Alice B. , Armstrong April W. , Merola Joseph F. , Napoli Andrew , Nowak Miroslawa , Banerjee Subhashis , Lehman Thomas , Mease Philip J.
Published: March 2024

Introduction: Deucravacitinib (DEUC), an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy. DEUC was superior to apremilast and placebo (PBO) in two phase 3 trials in patients with moderate to severe PsO. DEUC was efficacious on multiple measures of arthritis severity vs PBO in a phase 2 trial in patients with active psoriatic arthritis (PsA) who had ≥1 PsO lesion (≥2 cm). In patients with body surface area (BSA) involvement ≥3% at baseline (80% of patients in this trial), a greater proportion achieved PASI 75 with DEUC (6 mg QD: 42.4%, P=0.01; 12 mg QD: 59.6%, P<0.0001) vs PBO (20.4%) at Week 16. This analysis evaluated the impact of DEUC on PsO in patients with PsA in the phase 2 trial (NCT03881059).

Methods: The phase 2 double-blind PsA trial randomized patients (N=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or DEUC 12 mg QD. After Week 16, patients could enroll in an optional, double-blind period until Week 52. DEUC-treated patients achieving minimal disease activity at Week 16 continued DEUC to Week 52. PsO disease activity measurements were assessed.

Results: Baseline PsO characteristics were comparable across groups. At Week 16, significant decreases from baseline in mean PASI were observed with DEUC vs PBO in patients with baseline BSA ≥3%-<10% or PASI ≤12 even with very low baseline PASI scores, and also in those with baseline BSA ≥10% and PASI >12. Significant decreases in PASI from baseline were observed with DEUC vs PBO in patients with background csDMARD use (DEUC 6 mg, -4.0 and 12 mg, -4.9 vs PBO, -2.3; both P<0.05) and those without csDMARD use (-3.7 and -4.0 vs -2.5, respectively; both P<0.001). At Week 16, greater proportions of DEUC vs PBO patients achieved PASI ≤1 with baseline BSA ≥3% (DEUC 6 mg: 32.2%; DEUC 12 mg: 44.2%; PBO: 18.5%) and in patients with baseline BSA ≥10% and PASI >12 (23.1%; 28.6%; 0.0%). In patients with baseline BSA ≥3%, decreases in mean PASI at Week 16 were maintained through Week 52 in patients continuing DEUC 6 mg (absolute PASI score, Week 16: 2.39, Week 52: 1.22) and 12 mg (Week 16: 0.64, Week 52: 0.24).

Conclusion: DEUC significantly improved PsO in patients with PsA, regardless of baseline PsO severity and background csDMARD use. Improvement was comparable to that observed in the phase 3 POETYK PSO-1 trial.
The 40-gene Expression Profile (40-GEP) Test Identifies Cutaneous Squamous Cell Carcinoma (cSCC) Patients at High Risk of Metastasis within Lower-Staged Tumors to Better Guide Treatment Decisions
Authors: Somani Ally-Khan , Ibrahim Sherrif , Fitzgerald Alison , Siegel Jennifer , Prasai Anesh , Goldberg Matthew , Farberg Aaron , Cañueto Javier , Arron Sarah
Published: March 2024

Introduction- The development of metastases has a profound impact on cSCC patient survival. Lower-stage tumors are those that lack factors that portend higher risk for disease progression and therefore not typically considered for increased surveillance or treatment. However, up to one-third of all metastatic events have been reported for patients originally staged as T1. The 40-GEP test is validated to accurately classify risk for regional and/or distant metastasis in patients with primary cSCC with at least one high-risk factor.  The current study investigated whether the 40-GEP test could independently improve identification of lower-staged tumors at increased risk of metastasis. 

Methods- In an IRB-approved, retrospective, multi-center study, primary tumor tissue and associated clinical data from patients with cSCC and one or more clinicopathologic risk factors (n=897) were collected. Within this overall cohort, lower Brigham and Women’s Hospital (BWH) T-staged samples (n=444 T1 and n=335 T2a) were evaluated by Kaplan-Meier survival analysis to determine metastasis-free survival (MFS) according to 40-GEP risk class (Class 1-low metastatic risk; Class 2A-higher risk; Class 2B-highest risk).

Results- There was a total of 118 metastatic events in the overall cohort, of which 25% (29/118) and 38% (45/118) occurred in BWH T1 and T2a, respectively. BWH T1 tumors had an overall event rate of 6.5% (29/444), with T1/Class 2B tumors having a 5.1-fold increased event rate of 33.3%. BWH T2a tumors had an overall event rate of 13.4% (45/335), with T2a/Class 2B tumors having a 2.7-fold increased event rate of 36.4%. Stratification by the 40-GEP test resulted in significantly different metastasis rates across all three 40-GEP classes within both the T1 and T2a subsets (log-rank tests, p<0.0001 each subset). 

Conclusion- Within a cohort of cSCC patients considered lower risk by current staging alone, the 40-GEP identified patients with a substantial increase in metastatic risk.  The observed rates of metastasis over 10% and 20% are clinically actionable for nodal staging or postoperative adjuvant radiation, respectively. Combining clinicopathologic risk assessment with individual biologic risk, as provided by the 40-GEP test, improves the accuracy of risk assessment used clinically as the basis of treatment decisions.
Real-World Evidence Confirms Risk Stratification of the 31-GEP and i31-GEP in Prospectively Tested Patients with Stage I-III Cutaneous Melanoma
Authors: Pariser David , Sussman Jeffrey , Martin Brian , Ackerman Lindsay , Kraffert Craig , Jarell Abel
Published: March 2024

Introduction: Current American Joint Committee on Cancer (AJCC 8th edition) guidelines in patients with cutaneous melanoma (CM) separate them into risk categories based on the pathological tumor data of Breslow thickness, ulceration status, and sentinel lymph node status. The 31-gene expression profile was developed and prospectively validated to identify patients considered high or low risk by AJCC with low or high-risk tumor biology who may be over- or under-treated by current guidelines. To further advance personalized patient care, the 31-GEP result was integrated with clinical and pathological factors (i31-GEP for risk of recurrence, ROR) to provide a personalized, precise risk of tumor recurrence. 

 

Methods: Patients with stage I-III CM enrolled in the CONNECTION study were prospectively tested with the 31-GEP between 2013 and 2017 (n=1,831). Kaplan-Meier analysis with the log-rank test was used to estimate survival differences between low (Class 1A), intermediate (Class 1B/2A), and high (Class 2) risk groups and the i31-GEP risk groups. The i31-GEP ROR combines Breslow thickness, ulceration, SLN status, mitotic rate, tumor location, age, and the 31-GEP result to provide a personalized estimate of recurrence-free survival (RFS). While guidelines have not established a ROR threshold for determining when to escalate or de-escalate care, the NCCN uses stage IIA versus IIB as the cut-point. This cut-point translates to a 5-year RFS rate of 69.8% and was used for the present analysis. Cox multivariable regression analysis was used to identify predictors of recurrence. 

 

Results: Patients with a Class 1A result had higher 5-year RFS than those with a Class 1B/2A or Class 2B result (94.4% vs. 78.6% vs. 65.5%, p<0.001). The following were significant predictors of recurrence in multivariable analysis: Class 1B/2A (HR=2.07, p<0.001), Class 2B (HR=2.40, p<0.001), positive SLN (HR=4.54, p<0.001), Breslow thickness (HR=1.09, p=0.028), presence of ulceration (HR=1.57, p=0.005), mitotic rate >2/mm2 (HR=1.47, p=0.016), and age (HR=1.02, p<0.001). Patients with a low-risk i31-GEP result had significantly higher 5-year RFS than those considered high risk by the i31-GEP (92.4% vs. 49.7%, p<0.001). 

 

Conclusions: The i31-GEP is validated in a real-world group of prospectively tested patients. The independent i31-GEP ROR test result improves identification of patients whose management should be escalated or de-escalated within current guidelines.
Early Acne Improvements With Fixed-Dose Clindamycin Phosphate 1.2%/ Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel: What to Expect in the First 4 Weeks of Treatment
Authors: Harper Julie , Kircik Leon , Gold Michael , Hebert Adelaide , Sugarman Jeffrey , Green Lawrence , Stein Gold Linda , Baldwin Hilary , Del Rosso James , Guenin Eric
Published: March 2024

Background: Treatments with fast and substantial acne clearance are highly desirable. While a three-pronged approach may increase treatment efficacy versus monotherapy or dual-combination therapy, it is unknown if triple-combination provides more rapid improvement. CAB gel—clindamycin phosphate (clin) 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1%—is the first fixed-dose, triple-combination acne topical. Since rapid/substantial acne improvements and fewer side effects can increase adherence, the efficacy and safety of CAB in the first 4 weeks of treatment was evaluated.

Methods: In a phase 2 (N=741; NCT03170388) and two phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, 12-week studies, participants aged ≥9 years with moderate-to-severe acne were randomized to once-daily CAB or vehicle gel; the phase 2 study included 3 additional dyad arms: BPO/adapalene; clin/BPO; and clin/adapalene. Efficacy assessments included least-squares mean percent change from baseline in inflammatory and noninflammatory lesions. Cutaneous safety/ tolerability assessments were graded from 0=none to 3=severe. Post hoc analyses included percentages of participants with one-third and one-half acne lesion reductions.

Results: At week 4, CAB led to ~55% reductions from baseline in inflammatory acne lesions in the ph2 and pooled ph3 studies, significantly greater than vehicle (~40%) and its 3 dyads (ph2 range: 44.2-47.6%; P<0.05, all). The percentages of participants with one-third and one-half reductions of inflammatory lesions were significantly greater with CAB than vehicle and dyads (P<0.05, all). Similar trends were observed for noninflammatory lesions, though reductions were less pronounced. As expected for retinoids, transient increases from baseline to week 2 in scaling, erythema, itching, burning, and stinging were observed for CAB, BPO/adapalene, and clin/adapalene, with mean scores ≤0.6 (1=mild); no trends in dyspigmentation were observed. Mean scores for all cutaneous assessments were highest for BPO/adapalene, indicating that adding a third product in the fixed-dose CAB gel formulation did not worsen tolerability.

Conclusions: Acne lesion reductions were significantly greater with clin 1.2%/ adapalene 0.15%/BPO 3.1% gel versus its dyads and vehicle gel as early as week 4. More rapid efficacy with this first fixed-dose triple-combination acne product—coupled with its optimized formulation, once-daily dosing, and tolerability—may positively impact treatment adherence.

Funding: Ortho Dermatologics.
Clinical Efficacy and Patient Reported Impacts of Roflumilast Foam 0.3% in Seborrheic Dermatitis: An Analysis of STRATUM Data for Patients Unresponsive or Intolerant to Topical Corticosteroids
Authors: Chu David , Stephenson Brett , Lee Jeff , Bannister Breyanne , Hickey Conor , Westley Tracy , Zirwas Matthew
Published: March 2024

Objective. Roflumilast foam 0.3% has demonstrated efficacy and tolerability in a Phase 3 clinical trial of moderate-to-severe seborrheic dermatitis (SD) patients (STRATUM). The aim of this subgroup analysis is to assess the efficacy and patient-reported quality of life (QOL) effects of roflumilast vs vehicle in patients with an inadequate response, intolerance, or contraindication to topical corticosteroids (TCS).

Methods: Patients 9 years or older with at least moderate seborrheic dermatitis (Investigator Global Assessment [IGA] ≥ 3) were randomized 2:1 to roflumilast or vehicle for 8 weeks. Patients reporting a history of inadequate response, intolerance, or contraindication to topical corticosteroids (TCS) were included in this subgroup analysis. The primary efficacy endpoint was IGA success (Clear or Almost Clear with at least a 2-grade improvement) at Week 8. QOL was assessed using the Dermatology Life Quality Index (DLQI) for patients aged ≥17 years. QOL endpoints included percentage change from baseline in DLQI score, achievement of a minimal important difference (MID; defined as at least a 4-point reduction in DLQI score), and patients achieving a DLQI score of 0 or 1 by treatment group at weeks 2, 4, and 8. Differences in change from baseline DLQI scores were assessed using the Kruskal-Wallis rank sum test. The Cochran–Mantel–Haenzel test was used to assess differences in the proportion of patients achieving binary endpoints between treatments.

Results: 189 patients (129 roflumilast, 60 vehicle) were included in the subgroup analysis. At Week 8, 78.8% of roflumilast patients achieved IGA success vs. 48.3% of vehicle patients (odds ratio [OR] 3.45; 95% confidence interval [CI]: 1.62, 7.36; p<0.001). At each time point, percentage change from baseline in DLQI score was significantly larger for roflumilast-treated patients relative to vehicle (p≤0.001).  Treatment with roflumilast significantly increased the odds of achieving an MID in DLQI across all time points (OR: 6.97; 95% confidence interval [CI]: 3.97, 12.24; p<0.001) and achieving a DLQI score of 0 or 1 (OR: 2.46; 95% CI: 1.58, 3.81; p<0.001).

Conclusions: Roflumilast foam 0.3% provided significant and meaningful efficacy with improved QOL in patients with moderate-to-severe SD who had a prior history of an inadequate response, intolerance, or contraindication to TCS. Clinical improvement aligned with patient-reported outcomes at all key assessment periods.
Extra facial esthetic indications of botulinum toxin: A review
Authors: Arora Gulhima , Singh Nidhi , Arora Sandeep
Published: March 2024

Harnessing of the most potent neurotoxin, botulinum toxin (BTX) has been one of the most significant developments in the field of esthetics. Ever since its approval by the Food and Drug Administration in 2002 for the temporary improvement in the appearance of moderate-to-severe glabellar lines, BTX has been used for numerous off-label esthetic indications, the majority being facial indications. In this review, we intend to discuss the extra facial esthetic indications of BTX which include neck rejuvenation, improving shoulder contours, calf slimming, ankle slimming, and androgenetic alopecia. We have included essential tips for each indication.
The Correlation between Grammar Usage and Indonesian – English Translation Ability of English Study Program Students
Authors: Nurdin Andini Putri Surya , Syarfi Muhammad , Erni Erni
Published: March 2024

Grammar is an important component of a language that contains rules on the sentence structure construction and meaning system of the language. The grammar usage has a contribution in the language learning process, one of which is in translation. This research aimed to discover the correlation between grammar usage and Indonesian – English translation ability of the fourth-semester English Study Program students. The instruments of the research were sentence completion and error recognition questions for English grammar test and Indonesia – English translation essay for translation test. The statistical analysis using Pearson product-moment formula was applied to analyze the correlation between grammar usage and Indonesian – English translation ability of the fourth-semester students. The result of data analysis revealed that the Pearson correlation value r-counted of 0.837 was higher than r-table of 0.320 at the level of confidence 0.05 which meant that alternative hypothesis (Ha) was accepted and of null hypothesis (H0) was rejected. The research findings revealed that there existed a significant correlation between English grammar usage and Indonesian – English translation ability the fourth-semester English Study Program students of Universitas Riau. It is implied that the proficient English grammar students displayed commensurate in Indonesian – English translation ability while those who lack of grammar usage ability found difficulty in translation tasks. This research highlighted the critical role of grammar in shaping translation of the fourth-semester students of Universitas Riau English Study Program.
Using Interactive Language Development Tools to Enhance Cognitive and Literacy Skills in K-12 Education
Authors: Maspul Kurniawan Arif
Published: March 2024

The incorporation of interactive language technologies, such as ChatGPT, into K-12 education has sparked interest as a way to improve language acquisition and cognitive development. This qualitative study investigates the perspectives and experiences of educators enrolled in the Advanced Teaching MEd program who have implemented ChatGPT in their language classes. The study investigates the influence of ChatGPT on language competence, cognitive skills, and literacy development using educator interviews, classroom observations, and a comprehensive literature analysis. The findings underscore ChatGPT's dynamic and interactive nature, which encourages active involvement, knowledge production, and tailored support in the zone of proximal growth. Furthermore, the study demonstrates how ChatGPT improves language proficiency by offering authentic language experiences, timely feedback, and exposure to a variety of linguistic structures. ChatGPT integration helps students become confident communicators and teachers construct dynamic classes that adapt to specific learning needs. Future research should look at the long-term impact of interactive language tools, the importance of teacher training, and the cultural and socioeconomic aspects that influence their use and efficacy. This work adds to the continuing efforts to improve language learning outcomes in K-12 education by increasing our understanding of how interactive language tools can boost cognitive development and language competency.
Developing EFL Critical Reading Aids: Project-Based Learning Activities for Electrical Industrial Engineering Students
Authors: Khulaifiyah Khulaifiyah , Milawati Milawati , Suparti Suparti
Published: March 2024

The Independent Learning and Independent Campus (MBKM) curriculum for vocational education provided learning experiences for students. However, the reading material conducted had not reached the curriculum target. Thus, this study aimed to develop critical reading material and worksheets based on the MBKM curriculum. The development procedure was designed in three stages: defining, designing, and developing for 3-D aids. The research resources employed were validation sheets for critical reading aids and semi-observation sheets to provide student activity during PjBL field trial. The results of this study were project-based learning (PjBL) used to construct English language learning aids for the syllabus and coursework units, including worksheets for critical reading. Hence, this learning aid could slightly enhance students' reading competence, which could lead them to have soft and hard skills as well as meet the MBKM curriculum target.
Development of technology for vocal training of Chinese students in Russian music pedagogical universities
Authors: Сянкэ С.
Published: March 2024

В статье проанализирован подход в разработке технологии вокального обучения китайских студентов, обучающихся в российском музыкально-педагогическом вузе, разработанного в опоре на мировой опыт обучения вокальному искусству, а также с учетом особенностей культуры, мировоззрения, склада менталитета и самобытных национальных музыкально-художественных ценностях представленного контингента обучающихся. Методологической базой для разработки технологии вокального обучения явились: базовые методы русской (советской, российской) системы вокального обучения; принципы обучения вокалу в западноевропейской и мировой практике; религиозно-философская основа и художественно-эстетические критерии вокального искусства в Китае; современные исследования уровня вокальной и музыкальной подготовки китайской студенческой молодежи, обучающейся в российских и китайских ВУЗах; принципы вокального обучения в традициях национальной китайской школы пения и педагогической деятельности выдающихся китайских оперных певцов; принципы педагогики вокального обучения, представленные в научных исследованиях современных китайских ученых – аспирантов российских ВУЗов. Технологии моделирования психоэмоционального состояния (взаимодействие физиологического и технического аспектов звукообразования). Данная технология базируется на методических подходах В.И. Юшманова и Чжоу Сяоянь, но с учетом особенностей применения восточных энергетических практик (заземление, центрирование, дыхание).

The article analyzes the approach to the development of technology for vocal training of Chinese students studying at a Russian music pedagogical university, developed based on global experience in teaching vocal art, as well as taking into account the characteristics of the culture, worldview, mentality and original national musical and artistic values of the represented contingent. students. The methodological basis for the development of vocal training technology was: basic methods of the Russian (Soviet, Russian) system of vocal training; principles of vocal training in Western European and world practice; religious and philosophical basis and artistic and aesthetic criteria of vocal art in China; modern research into the level of vocal and musical training of Chinese students studying at Russian and Chinese universities; principles of vocal training in the traditions of the national Chinese school of singing and the pedagogical activities of outstanding Chinese opera singers; principles of pedagogy of vocal training, presented in the scientific research of modern Chinese scientists - graduate students of Russian universities. Technologies for modeling the psycho-emotional state (interaction of physiological and technical aspects of sound production). This technology is based on the methodological approaches of V.I. Yushmanov and Zhou Xiaoyan, but taking into account the peculiarities of the use of eastern energy practices (grounding, centering, breathing).