Scalp psoriasis is often associated with poor adherence to topical therapy. A novel formulation of calcipotriol and betamethasone dipropionate based on polyaphron dispersion (CAL/BDP PAD-cream) showed improved outcomes and satisfaction in the PRO-SCALP study, particularly in patients with high adherence. We evaluated how adherence to CAL/BDP PAD-cream influences patients- and clinicians-reported outcomes and treatment preferences in mild-to-moderate scalp psoriasis under real-life conditions in Europe. PRO-SCALP patients reported their adherence level using a visual analogue scale (VAS). Outcomes were compared between low- and high-adherence subgroups. Among 252 patients, 59.9% reported high adherence (VAS 80-100). Older patients and those with moderate disease reported high adherence (both p < 0.05). High-adherent patients reported higher scores in the Treatment Satisfaction Questionnaire for Medication Version 9, for Convenience of use (p = 0.0019) and Global Satisfaction (p = 0.0166) domains, and in the Psychosocial Effects of Scalp Psoriasis Questionnaire (p = 0.0004) at week 8. Both adherence subgroups showed significant reductions in the scalp Worst Itch Numeric Rating Scale (WI-NRS), scalp-modified Psoriasis Area and Severity Index (S-mPASI), and Scalpdex scores (all p < 0.0001 vs. baseline), although high-adherent patients achieved greater improvements in WI-NRS (p < 0.0001), S-mPASI (p = 0.0153), and the Scalpdex Symptoms domain (p = 0.001) than low-adherent. Each 10% increase in adherence corresponded to a 0.10- and 0.35-point reduction in S-mPASI and WI-NRS (both p < 0.05) at week 8. Scalp-Physician Global Assessment success rates were comparable in low- vs. high-adherence subgroups (65.0% vs. 70.5%; p = 0.3633). Sleep quality improved significantly in both subgroups (p < 0.0001). High adherence was associated with higher Patient Preference Questionnaire scores (p = 0.0012), better Cream Usability Scalp Psoriasis Questionnaire ratings (p = 0.0455) and greater product consumption (p < 0.0001), despite similar once-a-day usage. High adherence to CAL/BDP PAD-cream was associated with greater effectiveness, satisfaction, preference, and QoL. While patients with low adherence still benefited, maximizing adherence is key for optimal real-world outcomes in scalp psoriasis. ClinicalTrials.gov identifier NCT05811234. Scalp psoriasis is a long-lasting disease that greatly impairs quality of life. Due to the presence of hair, the scalp is a hard area to treat. Topical medicines are the first treatment choice. However, many patients struggle to follow them because of inconvenience, cosmetic concerns, side effects, or dissatisfaction, which often leads to poor disease control. One of the most recommended topical treatments is the combination of calcipotriol, a vitamin D analog, and betamethasone dipropionate, a corticosteroid, (CAL/BDP). Based on a new polyaphron dispersion (PAD) technology, CAL/BDP PAD-cream is a novel formulation designed to make treatment easier to use, more cosmetically acceptable, and effective, while maintaining similar safety and tolerability than previous formulations. A recent study (PRO-SCALP), evaluating CAL/BDP PAD-cream in patients with mild-to-moderate scalp psoriasis, showed improvements in treatment outcomes and satisfaction, especially in patients with high adherence (patients that followed the treatment as prescribed). Hence, in this subgroup analysis, patients with low and high adherence were compared. Both groups experienced meaningful improvements, but patients with high adherence presented stronger reductions in itch and scalp lesions, higher satisfaction, and greater preference for CAL/BDP PAD-cream. They also reported greater improvements in quality of life and psychosocial well-being, while sleep improved similarly across both groups. Overall, this study further shows that CAL/BDP PAD-cream is an effective, user-friendly treatment for scalp psoriasis and demonstrates that high adherence leads to better outcomes, underlining the key role of following treatment as prescribed by the healthcare professional for the best control of scalp psoriasis.
The treatment of common warts can occasionally be a challenge in recalcitrant cases, either recurrent ones or non-responders to treatment. In the current study, the efficacy and safety of monotherapy with topical 50% urea cream and combination therapy with topical 50% urea cream and carboxytherapy were assessed and compared in the treatment of recalcitrant common wart. Twenty subjects with recalcitrant common warts in the extremities (excluding the plantar surface) were selected. For the lesions of one side of the body, topical 50% urea cream was used 2 times a day (group A), while for the other side, combination of topical 50% urea cream and carboxytherapy was administered (group B). Carboxytherapy was done weekly, and both treatments were continued until complete resolution. The lesion count and size were assessed until 2 weeks after the fifth session of carboxytherapy. Recurrence rate was evaluated 6 months after complete resolution. Regarding the lesion count, no statistically significant difference was seen between the 2 groups. In group B, decrease of lesion size was significantly greater than that in group A. The time for complete resolution was significantly shorter in the group B. No significant adverse event was reported in either treatment group. No recurrence of lesions was reported 6 months after complete resolution in either group. Our findings demonstrated that both monotherapy with topical 50% urea cream and combination therapy with topical 50% urea cream and carboxytherapy were effective in the treatment of recalcitrant recurrent common warts, although the effectiveness of combination therapy was statistically more.
With the surge in use of glucagon-like peptide 1-receptor agonists (GLP-1RAs) for weight management, "Ozempic Face," one of the dermatologic effects describing facial hollowing, sinking cheeks, and skin laxity, has drawn public attention. While substantial media discourse has surrounded certain dermatologic effects, patient-reported data is needed to more accurately characterize them. This study identifies patient-reported changes in skin, hair, and nails associated with weight management treatment with GLP-1RAs, including the frequency of dermatologic effects relative to weight loss. Our study was conducted through an IRB-approved, voluntary, anonymous survey developed via collaboration between obesity medicine physicians and dermatologists. The survey was then distributed to patients of a virtual cardio-kidney-metabolic treatment program. Responses (n = 1226) were sorted by the percent body weight lost and categorized by medication regimen (glucagon-like peptide 1-receptor agonists; GLP-1RA, nonGLP-1RA, or combination therapy). Patients reported dermatologic and overall physical changes. Dermatologic effects were reported more frequently with greater weight loss. Of respondents reporting greater than 20% body weight loss, (n = 325) 233 (72%; 95% CI 67-76) reported skin sagging, (n = 325) 170 (52%; 95% CI 47-58) reported hair loss, (n = 325) 163 (50%; 95% CI 45-55) reported decreased facial volume, and (n = 325) 107 (33%; 95% CI 28-38) reported reduced strength. Of respondents reporting 10-20% weight loss, (n = 395) 172 (44%; 95% CI 39-49) reported skin sagging, (n = 395) 119 (30%; 95% CI 26-35) reported hair loss, (n = 395) 147 (37%; 95% CI 33-42) reported decreased facial volume, and (n = 395) 76 (19%; 95% CI 16-23%) reported reduced strength. In comparison, of respondents reporting less than 10% weight loss, only (n = 380) 57 (15%; 95% CI 12-19) reported skin sagging, (n = 380) 65 (17%; 95% CI 13-21) reported hair loss, (n = 380) 48 (13%; 95% CI 10-16) reported decreased facial volume, and (n = 380) 35 (9%; 95% CI 7-13) reported reduced strength. The frequency of adverse patient-reported outcomes increased significantly with increasing percentage of body weight loss. Cochran-Armitage trend testing identified significant positive trends across the < 10%, 10-20%, and > 20% body weight loss categories for skin sagging (Z = 15.22), hair loss (Z = 9.91), decreased facial volume (Z = 10.70), and reduced strength (Z = 7.85), with P values of < 0.001. Among survey respondents on at least one GLP-1RA medication therapy, improvement was reported in certain preexisting inflammatory and hormonally driven skin conditions, including hidradenitis suppurativa (n = 15), 13 (87%; 95% CI 60-98); acanthosis nigricans (n = 12), 9 (75%; 95% CI 43-93); psoriasis (n = 47), 22 (47%; 95% CI 32-62); acne (n = 41), 17 (41%; 95% CI 27-57); eczema (n = 64), 17 (27%; 95% CI 17-39); hirsutism (n = 14), 4 (29%; 95% CI 10-56); seborrheic dermatitis (n = 16), 4 (25%; 95% CI 8-52); and skin tags (n = 57), 14 (25%; 95% CI 15-37). This large analysis of patient-reported outcomes suggests that greater weight loss, which often occurred with GLP-1RA treatment regimens versus other weight management therapies, was associated with higher reports of negative aesthetic impacts, most notably skin laxity, facial volume loss, and hair shedding, although with improvement in preexisting inflammatory and hormonally driven dermatological conditions. This calls for further studies to determine the potential mechanisms and incidence behind patient-reported outcomes associated with significant weight loss on GLP-1RA medications.
Erythema nodosum leprosum (ENL) is a severe inflammatory complication of lepromatous leprosy characterised by recurrent inflammatory episodes often requiring prolonged immunosuppression. The severity of ENL can be quantified using the validated and reliable ENLIST ENL Severity Scale (EESS). The longitudinal course of ENL and how it is captured using standardised severity measures has not been well described. We prospectively evaluated the changes in ENL severity over time using the EESS in a randomised clinical trial. Ethics statement. The trial was performed according to the Helsinki Declaration as revised in 2024 and ethical approval was obtained from the London School of Hygiene & Tropical Medicine Research Ethics Committee (15762). Approval was obtained from Dr. Soetomo Hospital Ethics Committee, Indonesian Food and Drug Authority, Ethiopian Ministry of Education Ethics Committee, Ethiopian Food and Drug Authority, AHRI/ALERT Ethics Review Committee, Bombay Leprosy Project Committee, the Leprosy Mission Trust India Ethics Committee, Nepal Health Research Council and Department of Drug Administration, Nepal Government. All participants provided written informed consent before enrolment. MaPs in ENL was registered at www.clinicaltrials.gov (NCT03775460) and the Clinical Trials Registry India (CTRI/2020/11/029074). We conducted a prespecified secondary analysis of participants enrolled in the Methotrexate and Prednisolone Study in ENL, an international multicentre randomised controlled trial conducted in Ethiopia, India, Indonesia, and Nepal. Adults with severe ENL (EESS score ≥9) were followed for 60 weeks with repeated EESS assessments. Longitudinal trajectories were analysed using mixed-effects regression models. Item-level analyses characterised the clinical phenotype captured by the scale. Associations between EESS score, prednisolone exposure, and dermatology-specific health-related quality of life measured using the Dermatology Life Quality Index (DLQI) were examined. A total of 135 participants contributed 1,958 EESS assessments. Mean EESS declined rapidly during the first four weeks of treatment (-2.10 points/week; 95% CI -2.36 to -1.84; p < 0.001), increased modestly during reduction in corticosteroid dose (weeks 4-20), and gradually declined thereafter. Severe ENL (EESS score ≥9) occurred in 20.6% of visits and was characterised primarily by pain and cutaneous inflammatory manifestations. Participants who required additional prednisolone had persistently higher EESS scores and showed limited improvement compared with those who did not receive additional prednisolone. Longitudinal EESS scores were strongly correlated with the DLQI score (Spearman's ρ = 0.75; p < 0.001). The EESS captures clinically meaningful changes in ENL severity, aligns with treatment decisions, and reflects patient-reported severity over time. These findings support the use of the EESS as a robust tool for monitoring ENL severity in both clinical research and routine care.
Atopic dermatitis (AD) is a chronic inflammatory skin disease in which gut-skin axis dysregulation is increasingly implicated. We conducted a prospective pilot study to describe the clinical evolution of pediatric AD following individualized, stool-guided microbiota-targeted therapy and to explore whether baseline dysbiosis markers predict outcomes beyond baseline disease severity. Twenty-one children with AD and laboratory-confirmed gut dysbiosis were enrolled consecutively at a tertiary pediatric center in Romania in a single-arm prospective pilot study. Gut microbiota was assessed using targeted culture-based stool analysis, generating a Flora Index and a binary High Putrefaction Flora classification. Individualized treatment consisted of strain-specific probiotics, prebiotics, and antifungals when indicated. Disease severity was assessed using the Patient-Oriented Eczema Measure (POEM) and Scoring Atopic Dermatitis (SCORAD) at baseline, 30 days, and 90 days. Longitudinal changes were evaluated using repeated-measures ANOVA and hierarchical regression models. High Putrefaction Flora was present in 71.4% of participants. Mean POEM decreased from 14.67 ± 5.22 at baseline to 7.10 ± 3.82 at 90 days, while mean SCORAD decreased from 41.66 ± 15.28 to 17.93 ± 11.68 (both p < 0.001). Approximately 76% of participants achieved a ≥50% reduction in POEM, and 71% achieved a ≥50% reduction in SCORAD. Individualized microbiota-targeted therapy was associated with substantial improvements in both clinical and patient-reported disease severity over the 90-day follow-up. Although children with High Putrefaction Flora exhibited higher disease severity scores in unadjusted analyses, baseline disease severity was the only significant predictor of 90-day outcomes. The Flora Index provided no independent explanatory value. In this exploratory single-arm pilot study, individualized microbiota-targeted therapy was associated with substantial and clinically meaningful improvement in AD severity over 90 days. Dysbiosis markers were associated with disease burden but did not independently predict outcomes, suggesting that they may function primarily as indicators of baseline severity rather than prognostic biomarkers. Because of the uncontrolled study design, causal inferences regarding treatment effects cannot be made, and these findings should be considered hypothesis-generating. Adequately powered randomized controlled trials are required to determine the efficacy of individualized microbiota-targeted interventions in pediatric atopic dermatitis.
Chronic and treatment-resistant dermatologic disorders remain difficult to manage with current therapies because of incomplete efficacy, tolerability limitations, and long-term safety concerns. GZ21T is a topical formulation of curcumin, harmine, and isovanillin that has emerged as a potential novel therapy for inflammatory and neoplastic skin disease. To review the preclinical evidence, proposed mechanism of action, safety data, and future clinical potential of GZ21T in atopic dermatitis, mycosis fungoides, and actinic keratoses. A focused literature review was performed using published preclinical and early translational studies evaluating GZ17-6.02 and topical GZ21T in dermatologic disease models, including atopic dermatitis, mycosis fungoides, and actinic keratoses. Studies were included if they reported mechanistic, efficacy, or safety outcomes relevant to dermatologic application; non-dermatologic studies were used selectively to contextualize safety and pharmacology. Across preclinical models, topical GZ21T reduced inflammation, pruritus, lesion burden, and tumor growth while promoting autophagy and suppressing pro-survival signaling pathways including MAPK, PI3K-AKT, mTOR-related pathways, Wnt, and ERBB signaling. In mycosis fungoides models, GZ17-6.02 increased apoptosis and enhanced tumor cell killing, including in combination with standard agents such as bexarotene. Safety data to date suggest favorable local tolerability, minimal systemic absorption in preclinical topical studies, and reversible liver enzyme elevations in oral phase 1 testing of GZ17-6.02. GZ21T represents a promising topical, multimodal therapeutic approach for inflammatory and premalignant or malignant skin disease. Further clinical studies are needed to confirm efficacy, define long-term safety, and establish its role relative to current standard therapies.
Pustular psoriasis (PP), including generalized pustular psoriasis (GPP) and palmoplantar pustulosis (PPP), is a rare and severe inflammatory dermatosis distinct from plaque psoriasis and associated with significant unmet therapeutic needs. Although advances in immunopathogenesis have identified key cytokine and signaling pathways, evidence-based treatment options remain limited. This systematic review evaluates the efficacy and safety of emerging Janus kinase (JAK) and tyrosine kinase (TYK) inhibitors in the management of PP. This systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed/Medline, Ovid-Embase, and Web of Science were searched from inception to November 15th, 2025, to identify all English-language clinical studies evaluating JAK or TYK inhibitors in patients with GPP or PPP. Methodological quality and risk of bias were independently assessed using National Institutes of Health quality assessment tools and the Murad et al. criteria. Of 2,259 records identified, 33 clinical studies (177 patients with GPP or PPP) met the predefined eligibility criteria. TYK inhibitors were evaluated in three studies of deucravacitinib (n = 11), which showed variable efficacy across reports: improvements in PASI/PPPASI, symptoms, and quality of life in some patients, and discontinuation due to insufficient response in others, with no serious adverse events reported. JAK inhibitors were evaluated in 30 studies involving 166 patients and were associated with improvements in disease severity, quality of life, and physician-assessed outcomes. Favorable responses were reported in observational studies, while rapid clinical improvement was frequently described in case-based evidence. Overall, treatment was generally well tolerated, although interpretation is limited by the predominance of uncontrolled studies and heterogeneous data. Available evidence indicates that JAK and TYK inhibitors may provide clinical benefit in GPP and PPP, particularly in refractory cases, with generally acceptable safety profiles. However, conclusions are limited by small, heterogeneous studies, and well-designed randomized controlled trials with longer follow-up are needed to establish long-term efficacy and safety.
Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma for which surgical excision often causes functional/cosmetic impairment. Photodynamic therapy (PDT) offers a noninvasive alternative, but data on its efficacy and influencing factors remain limited. To evaluate efficacy of 5‑aminolevulinic acid (ALA)‑PDT monotherapy for localized EMPD over one year, and identify baseline predictors of response. This retrospective study included 31 patients with histologically confirmed localized EMPD treated with ALA‑PDT alone. Responses were assessed at 3, 6, and 12 months. Objective response rate (ORR), disease control rate (DCR), and associated response factors were analyzed by Fisher's exact test. At 3 months, ORR was 90.3% (28/31) and DCR 100% (31/31), with no complete responses (CR). At 6 months, CR was 19.4% (6/31), ORR 67.7% (21/31), DCR 83.9% (26/31). At 12 months (n = 30), CR remained 19.4% (6/30), ORR declined to 36.7% (11/30), and DCR to 56.7% (17/30). Lesion diameter ≤5 cm and absence of exudation predicted better 6‑month response (p = 0.020 and p = 0.006); diameter ≤5 cm remained significant at 12 months (p = 0.002). ALA-PDT monotherapy achieves high short‑term responses in localized EMPD, but efficacy declines substantially by 12 months. Lesion diameter ≤5 cm and non-exudative morphology predict better responses.
The association between moderate-to-severe psoriasis and cardiovascular (CV) risk is well known. No clear link between disease activity, disease duration, and CV risk has been established thus far to identify high CV risk patients with psoriasis without CV symptoms. We aimed to investigate the relationship between moderate-to-severe psoriasis and cardiovascular disease (CVD) by introducing and determining the cutoff value for a new tool, the cumulative duration of severe psoriasis (CDSP), reflecting the total duration of severe psoriasis skin symptoms. Ninety-eight asymptomatic patients with moderate-to-severe psoriasis were enrolled in this cross-sectional study, without cardiac symptoms. CDSP was recorded using a structured questionnaire. CDSP threshold, defined as Coronary Artery Calcium Score (CACS) > 0, was determined using receiver operating characteristic curve analysis. Ultrasound (intima-media thickness (IMT) and carotid, brachial, and femoral artery plaque burden) and cardiac computed tomography (CACS, segment involvement score (SIS), and coronary artery disease-reporting and data system severity (CAD-RADS™)) were performed. Controls (n = 248) were matched for age, sex, body mass index, and, where possible, comorbidities. CACS was significantly higher in psoriasis (mean 159.02, standard deviation 365.60) compared to controls (73.12, 166.08), P = 0.029. The CDSP threshold was 60.5 months. Patients with long-CDSP (> 60.5 months) had significantly higher CACS (214.63, 430.11) than patients with short-CDSP (57.61, 162.53), P = 0.012. SIS and CAD-RADS were also significantly higher in the long-CDSP group compared to the short-CDSP group (4.50, 3.85 vs. 1.39, 2.06), P = 0.002 and (2.06, 1.63 vs. 0.71, 1.08), P = 0.003, respectively. Patients with long-CDSP showed a non-significant trend towards higher IMT and peripheral plaque burden. Patients with long-CDSP had a greater extent and severity of CVD. This innovative predictor is easily determined by dermatologists and assists in the early identification of asymptomatic high CV risk patients with psoriasis. Graphical abstract available for this article. Psoriasis is a common skin disease characterized by inflammation, resulting in itchy, red, and scaly skin lesions. The inflammation also affects the blood vessels. Therefore, patients with severe psoriasis have a higher risk of cardiovascular disease, which affects the heart and blood vessels. We propose that patients with longer periods of severe psoriasis are exposed to inflammation for longer and, consequently, are at a higher risk of cardiovascular disease than those with shorter durations of severe symptoms. This study, conducted in Hungary, aimed to investigate the relationship between cumulative duration of severe psoriasis and cardiovascular disease by performing highly sensitive heart scans and ultrasound of blood vessels. Ninety-eight patients with psoriasis were included and matched with non-psoriasis controls. Our findings showed that patients with psoriasis had a greater cardiovascular disease burden, as assessed by imaging tests. Furthermore, patients with long cumulative duration of severe psoriasis (> 60.5 months) had a greater extent and severity of cardiovascular disease than patients with short cumulative duration of severe psoriasis. In conclusion, patients with a long cumulative duration of severe psoriasis are at higher risk of cardiovascular disease. Dermatologists play a vital role in the early identification of asymptomatic high cardiovascular risk patients with psoriasis and referring them to cardiology in order to prevent potentially life-threatening complications, such as heart attacks.
Tildrakizumab is an interleukin-23 p19 inhibitor approved for the treatment of adults with moderate-to-severe plaque psoriasis. While clinical trials have demonstrated tildrakizumab efficacy, studies reporting real-world treatment patterns and outcomes for tildrakizumab initiators in North America are needed. This analysis included patients who initiated tildrakizumab (October 2018 to April 2024) at or after enrollment in the PPD™ CorEvitas™ Psoriasis Registry, an independent observational study of patients with psoriasis under dermatologic care. Drug survival was analyzed using Kaplan-Meier analysis. Effectiveness was assessed by changes from baseline to 12 (± 3) months in outcomes, including Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI), and patient-reported skin pain, itch, and fatigue (scales, 0-100). Results were presented overall and by prior experience with biologic treatments. There were 728 tildrakizumab initiators with mean age 58.4, mean PASI 7.7 (standard deviation [SD] 7.3), mean DLQI 7.3 (SD 6.2), and mean patient-reported skin pain, itch, and fatigue scores of 29.7 (SD 32.5), 46.0 (SD 34.4), and 32.3 (SD 29.4), respectively; 47.7% were female, and 383 (52.6%) were biologic-experienced. Restricted mean drug survival for all, biologic-naïve, and biologic-experienced initiators with follow-up was 35.2, 43.3, and 29.5 months, respectively; overall 12-month persistence was 72.8%. Patients with 12 months follow-up (n = 330) had mean improvements from baseline in PASI (4.9, SD 7.0), DLQI (3.9, SD 5.9), and skin pain (mean 13.1, SD 29.9), itch (mean 22.1, SD 34.7), and fatigue (mean 6.7, SD 29.1); 71.3% and 52.9% achieved PASI ≤ 3 and ≤ 1, respectively. Based on clinician- and patient-reported outcomes and a mean drug survival of almost 3 years, tildrakizumab was effective among real-world patients with plaque psoriasis.
Clinical data surrounding treatment patterns and reasons for discontinuation of oral systemics (OS) for the treatment of adult patients with moderate-severe atopic dermatitis (AD) remain limited. AD-REAL descriptively reports the discontinuation rates and treatment responses at week (W) 24 for patients with AD initiating new OS treatments. AD-REAL is a 12-month, multinational, observational cohort study of adult patients with moderate-to-severe AD commencing either conventional systemics (CS) or baricitinib. Other Janus kinase inhibitors (JAKis) were analyzed ad hoc. The primary objective reported the discontinuation rate of patients at W24 from baseline. Secondary objectives reported outcomes for Eczema Area and Severity index (EASI), Itch Numerical Rating Scale (NRS), and pain NRS. At baseline (N = 313), patients initiated CS (N = 113), baricitinib (N = 87), and other JAKi (N = 92), with a mean EASI of 19.8, 15.8, and 16.4, respectively. At W24, the Kaplan-Meier cumulative incidence of initial treatment discontinuation was 50.8% (95% confidence interval [95% CI] 40.9, 59.8) for CS, 29.0% (95% CI 19.8, 38.8) for baricitinib, and 18.8% (95% CI 11.5, 27.5) for other JAKi. The primary reason for discontinuation of baricitinib and other JAKi was primary lack of effectiveness, while CS discontinued owing to the addition of concomitant systemic treatment, adverse events, and patient/physician decisions. Of the baricitinib and other JAKi cohorts, 81.0% and 84.2% achieved an EASI ≤ 7 score, 38.1% and 38.2% improvement in pain, and 42.0% and 38.5% improvement in itch, while 63.1%, 16.7%, and 14.3% achieved these outcomes for CS, respectively. In this descriptive observational cohort study, patients treated with baricitinib and other JAKi reported numerically lower discontinuation rates and numerically improved clinical outcomes than patients treated with CS. Similar to early reports of baricitinib effectiveness in treating an itch-dominant subpopulation of patients with AD, patients receiving baricitinib in clinical practice reported improved outcomes for severe itch.
This study provides a comprehensive nationwide analysis of extensive-stage small cell lung cancer (ES-SCLC) in Hungary, examining incidence rates, demographic trends, treatment patterns, and survival outcomes. We used data from the National Health Insurance Fund (NHIF) covering the period of 2013-2022, and we analyzed 8,104 ES-SCLC patients who received first-line (1L) etoposide-platinum (EP) chemotherapy, all of whom were confirmed to not have received concomitant chemoradiotherapy or curative thoracic surgery and had histology results in line with SCLC. We evaluated epidemiology, regional distribution, radiotherapy use, and subsequent treatment pathways. For the efficacy analysis, we narrowed the cohort to 5,576 patients who initiated EP within 1 year of their first C34-coded lung cancer diagnosis between 2013 and 2019, enabling 3-year follow-up. Key endpoints included overall survival (OS) and progression-free survival (PFS), the latter of which was inferred using time to first subsequent therapy (TFST). Our results revealed a shifting age distribution toward the age group above 70 years, while the male-to-female ratio gradually evened out. Treatment patterns showed the increasing use of carboplatin over cisplatin and frequent short course radiotherapy. Among those who underwent subsequent therapy, EP rechallenge was most widespread. Despite high initial response rates, survival outcomes remained poor: median PFS was 6.5 months (6-month: 52.9%, 1-year: 19%, 3-year: 5.2%), and median OS was 9.3 months (6-month: 69.8%, 1-year: 37.5%, 3-year: 9.2%). These results were in line with international real-world evidence and clinical trial data. Our findings highlight the aggressive nature of ES-SCLC and provide insight to the limited efficacy of chemotherapy-based therapies, underscoring the need to improve existing 1L and subsequent-line treatments and to introduce novel options. As Hungary transitions into the immunotherapy era, future studies with extended follow-up that incorporate staging, radiotherapy intent, comorbidities, and progression data will be essential for optimizing therapeutic strategies.
Psoriasis vulgaris (PsV) is a chronic, immune-mediated skin disorder that significantly impairs quality of life and often necessitates long-term systemic therapy, especially in moderate-to-severe cases. In Japan, biologic agents targeting interleukin-17 (IL-17) have become central to the management of PsV; however, real-world evidence on their long-term persistence and associated factors remains limited. This retrospective study utilized the Medical Data Vision database to evaluate treatment persistence of IL-17 inhibitors (ixekizumab, secukinumab, brodalumab, or bimekizumab) and factors associated with treatment persistence in Japanese patients with PsV. Patients aged ≥ 15 years with a confirmed diagnosis of PsV and at least one claim of an IL-17 inhibitor between February 2015 and October 2023 were included. Persistence rates of IL-17 inhibitors (including ixekizumab) and ixekizumab were analyzed using the Kaplan-Meier method. Cox proportional hazard regression models were also used to calculate hazard ratios for factors associated with the treatment persistence of IL-17 inhibitors and ixekizumab. The persistence rates at 48 months among patients treated with IL-17 inhibitors (n = 2904) and ixekizumab (n = 1105) were 52.4% and 41.2%, respectively. Similar rates were observed for ixekizumab dosing Q2/Q2 (46.9%) and Q2/Q4 (48.1%). Gender was a factor influencing treatment persistence in the IL-17 inhibitor cohort; however, no such association was observed in the ixekizumab cohort. Prior biologic experience was associated with shorter persistence for both IL-17 inhibitors and ixekizumab. No other demographic or clinical factors showed a significant association. Following ixekizumab treatment, use of phototherapy, topical, and systemic therapies declined, suggesting a shift toward biologic monotherapy. These findings provide real-world evidence of the sustained use of IL-17 inhibitors in Japanese patients with PsV. Persistence showed no significant association with patient characteristics such as age, comorbidities, and concomitant medications.
Allergic contact dermatitis (ACD) and atopic dermatitis (AD) are driven by distinct T cell programs, and safe long-term topical therapies remain limited. Dermal fibroblasts (dFBs) have emerged as active immunomodulators, but whether they can be therapeutically targeted remains unexplored. Here we developed MDI1228, a novel topical pan‑JAK inhibitor with nanomolar potency against JAK1/2/3/TYK2 (IC₅₀ 0.11-0.85 nM) and high selectivity. MDI1228 was evaluated in DNFB‑induced ACD and MC903‑induced AD mouse models, as well as in primary mouse and human cell‑based assays. Topical MDI1228 ameliorated both ACD and AD in mice, reducing T cell infiltration and cytokine production. Mechanistically, MDI1228 not only directly inhibited T cell activation and cytokine production but also disrupted fibroblast‑T cell crosstalk by reducing dFB‑derived chemokine expression. Single‑cell transcriptomics identified dFBs as the primary source of CXCL9/10 in ACD and CCL2 in AD. Conditioned medium and neutralization experiments demonstrated that CXCL9/10‑CXCR3 and CCL2‑CCR2 signaling axes contribute to T cell polarization in a context‑dependent manner. Compared with glucocorticoids, prolonged topical application of MDI1228 showed minimal systemic toxicity and preserved tissue homeostasis. These findings identify dFBs as a central therapeutic node and demonstrate that MDI1228, by directly targeting T cells and disrupting dFB‑derived chemokine axes via JAK inhibition, offers a potent and safe topical treatment for both ACD and AD.
Patients with vitiligo reportedly have an increased risk of sensorineural hearing loss (SNHL), driven by the loss of extracutaneous melanocytes in the inner ear. In a phase 2 dose-ranging study, the oral, selective Janus kinase 1 inhibitor povorcitinib demonstrated substantial repigmentation in patients with extensive nonsegmental vitiligo through 52 weeks of treatment. This exploratory post hoc analysis of the phase 2 study evaluated the prevalence of hearing loss among enrolled patients and examined their associated demographic and clinical characteristics, as well as their audiometric response to povorcitinib. SNHL was defined as a bone-conduction threshold of ≥ 25 dB in either ear and was assessed using all-frequencies average (AFA: 250, 500, 1000, 2000, 3000, 4000, 6000, 8000 Hz), pure-tone average (PTA: 500, 1000, 2000, 4000 Hz), and high-frequencies average (HFA: 2000, 3000, 4000, 6000, 8000 Hz). Of 162 patients assessed for hearing loss, SNHL prevalence at baseline was 10.5% (AFA), 11.7% (PTA), and 14.2% (HFA). Patients with versus without SNHL were significantly older and had significantly greater facial involvement. Following up to 52 weeks of povorcitinib treatment, bone-conduction hearing thresholds improved across all frequency ranges, although no definitive conclusions can be drawn. At week 52, mean percentage change from baseline in the left and right ears was as follows: AFA, - 18.7% (P = 0.08) and - 16.1% (P = 0.10); PTA, - 13.9% (P = 0.18) and - 7.2% (P = 0.25); and HFA, - 11.0% (P = 0.21) and - 12.6% (P = 0.18), respectively. SNHL was common in this patient population, suggesting that audiologic evaluation may be appropriate for some patients with vitiligo to support early detection and management of hearing loss. Changes in hearing with povorcitinib treatment require confirmation in larger patient populations. Graphical abstract available for this article. ClinicalTrials.gov identifier, NCT04818346. Vitiligo is a disease that causes patches of skin to lose color. The same cells that give skin its color, called melanocytes, are also found in the inner ear and help with hearing. When these cells are lost, it may lead to a type of hearing loss called sensorineural hearing loss. This means patients with vitiligo may be at higher risk for hearing loss. In a recent study, patients with widespread vitiligo took an oral medicine called povorcitinib and saw a significant return of their skin color, which means that their melanocytes were being restored. The analysis described here looked at data from that same study to see how many patients had hearing loss at the beginning of the study and whether their hearing changed after treatment. It also looked at any patient traits that might be linked to hearing loss, such as age or how much of their skin had lost color from vitiligo. At the start of the study, just over one in ten patients had at least some sensorineural hearing loss. The patients with hearing loss were generally older and had more color loss of the skin on their faces than patients who did not have hearing loss. After up to a year of treatment with povorcitinib, patients showed some improvement in hearing, but this needs to be confirmed in larger studies. These findings suggest that hearing loss is relatively common in patients with vitiligo, so regular hearing checkups could be helpful for them.
Topical treatment of burn wounds remains challenging because eschar formation, inflammation and impaired vascularization can limit drug penetration and tissue repair. Here, we introduce a flexible large-area microneedle patch for sustained local delivery of extracellular matrix-derived peptides to deep partial-thickness burn wounds. The microneedles were composed of cellulose acetate phthalate and hydroxypropyl methylcellulose and included a transparent water-soluble backing layer to aid placement and allow dissolution after application. The patch delivered two peptides with previously reported biological activity: TSN6, associated with angiogenic responses and TSN18, associated with cell proliferation and epithelial repair. The microneedles retained sharp conical geometry after peptide loading, showed sufficient compressive strength for skin insertion and produced consistent microchannels in ex vivo porcine skin. In vitro studies showed peptide-dependent release over 48 h: TSN18 reached approximately 50% release within 12 h and exceeded 80% release by 48 h, whereas TSN6 was released more slowly, reaching 45% when loaded alone and 58% when co-loaded with TSN18. In a porcine deep partial-thickness burn model, TSN18-treated wounds showed lower burn depth than SSD-treated wounds at day 4 (1174 ± 35 vs. 1628 ± 178 μm, p < 0.05). Co-delivery of TSN6 and TSN18 preserved more dermis than the scrambled peptide control (1667 ± 134 vs. 938 ± 194 μm, p < 0.05) and increased neoepidermal thickness at day 20 compared with scrambled peptide and SSD controls (417 ± 45 vs. 237 ± 25 and 265 ± 16 μm, respectively). Although consistent improvements in macroscopic wound closure and re-epithelialization were not observed across peptide-treated groups, these results show that microneedle-mediated peptide delivery can improve selected tissue-level measures of burn injury and epidermal repair.
Antimicrobial resistance (AMR) poses a significant global health threat, with multidrug-resistant organisms (MDROs) increasingly contributing to healthcare-associated infections (HAIs). Understanding local pathogen distribution and resistance trends is essential for guiding empirical therapy and infection control strategies. This study aims to analyze the pathogen distribution and AMR trends of bacteria in a tertiary hospital in South China from 2021 to 2025. A retrospective analysis was conducted on bacterial isolates collected from a tertiary hospital in Guangzhou, China, from 2021 to 2025. Bacterial identification and antimicrobial susceptibility testing were performed using the VITEK 2 automated system and the Kirby-Bauer disk diffusion method, with results interpreted according to CLSI guidelines. Annual data analysis was conducted using WHONET 5.6 software. Antimicrobial consumption was expressed as defined daily doses (DDD) per 1,000 patient-days, and incidence of HAIs caused by MDROs was calculated as cases per 1,000 patient-days. A total of 25,326 non-duplicate bacterial isolates were analyzed. Gram-negative bacteria predominated throughout the study period, with Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii being the most frequently isolated species. Among Gram-positive bacteria, Staphylococcus aureus showed a marked increase from 2023 onward. Escherichia coli exhibited persistently high resistance to fluoroquinolones (>57%) and third-generation cephalosporins (>50%), with an increasing trend in carbapenem resistance. Klebsiella pneumoniae demonstrated declining resistance to carbapenems but a concerning emergence of tigecycline resistance in 2025 (6.2%). Acinetobacter baumannii maintained high carbapenem resistance (>60%) throughout, with colistin and tigecycline remaining the only consistently effective agents (resistance ≤1.9% and ≤1.8%, respectively). Antimicrobial consumption showed a sustained increase in carbapenem use (from 21.78 to 47.06 DDD per 1,000 patient-days), while incidence of HAIs caused by MDROs declined from 0.30 to 0.12 cases per 1,000 patient-days following intensified infection prevention and control measures implemented in 2024. This study reveals a persistently high burden of MDROs in a South China tertiary hospital, particularly among Gram-negative pathogens. Despite increasing antimicrobial consumption, enhanced IPC measures, including active surveillance and improved contact isolation compliance, effectively reduced HAIs-MDROs incidence. These findings underscore the critical importance of integrated antimicrobial stewardship and infection control strategies in combating AMR.
A transmembrane protein that is extensively expressed, CD47 has an important role in the senescence of cancer cells. Therapy-induced senescence (TIS) by chemotherapy and radiotherapy restrains tumor proliferation yet drives immune evasion and treatment resistance, where CD47 acts as a core regulatory molecule linking cellular senescence and tumor immune escape. In this mini-review, we summarize the mechanisms governing CD47 upregulation during TIS, ranging from DNA damage response signaling, metabolic reprogramming and epigenetic modulation to post-transcriptional RNA modification. After addressing how CD47 is upregulated in TIS, we summarized the function of CD47 in both the maintaining the senescent statue and preventing senescent escape. Three major pathways are addressed. TSP-1/CD47 axis functions as both senescence maintenance and preventing escape, while, p16/c-MYC/CD47 axis and CD47/QPCT axis are responsible for senescence maintenance. Moreover, we summarize the therapeutic strategies toward CD47 blockade as s senolytic way, pointing out a novel strategy for oncotherapy. Overall, CD47 is a pivotal molecular bridge between TIS and immune tolerance. Future research on the role CD47 of cancer senescence, especially after chemotherapy or radiotherapy, could provide novel insight for oncotherapy.
Papulopustular rosacea (PPR) is a chronic inflammatory facial dermatosis with a need for well-tolerated and effective topical therapies. Clascoterone cream 1% is an androgen receptor inhibitor and a promising novel treatment for PPR. In this single-center, single-arm, phase 2 pilot study, adults with PPR applied clascoterone cream 1% twice daily to the face. The primary endpoint was biopsy-proven change in mean sebaceous gland number and diameter over 12 weeks. Secondary endpoints included Dermatology Life Quality Index (DLQI), patient-reported outcomes (PROs), and prevalence of adverse events. Twenty participants were enrolled, and 18 completed the study. Mean sebaceous gland count decreased significantly (4.94 ± 1.98 to 3.61 ± 2.33; P=0.012). Mean gland diameter also decreased, although not significantly (P=0.182). Mean DLQI scores significantly improved (7.5 ± 5.8 to 3.3 ± 5.6; P=0.029). PRO scores were favorable for papules/pustules (3.2 ± 1.1), facial redness (2.7 ± 1.0), general skin appearance (2.7 ± 1.1), and overall treatment satisfaction (3.1 ± 0.7). The treatment was well tolerated, with no serious adverse events. Mild, transient dryness (n=1) and eye irritation (n=1) resolved without intervention. Clascoterone cream 1% demonstrated favorable tolerability, safety, and efficacy in PPR, with significant improvements in sebaceous gland count and patient-centered outcomes. These findings support the therapeutic potential of clascoterone cream 1% for the treatment of PPR.  .
Cranial prostheses (CPs) provide indispensable cosmetic and emotional support for individuals with medical hair loss. However, access remains inconsistent due to variable reimbursement policies and unclear classification as medical vs. cosmetic devices. To characterize global CP coverage frameworks and evaluate how each predominant healthcare system model structures CP access, reimbursement, and eligibility. We conducted a narrative review of CP policies across representative countries within the four major healthcare system models: Beveridge, Bismarck, National Health Insurance, and out-of-pocket systems. We synthesized data from peer-reviewed literature, government and insurance policy documents, and nonprofit resources to identify common themes in coverage and access. CP coverage varies widely across healthcare systems. Beveridge systems provide formal inclusion but demonstrate regional and administrative variability. Bismarck systems range from standardized, diagnosis-based reimbursement to insurer-dependent models with variable out-of-pocket costs. National Health Insurance systems often lack explicit CP coverage, relying on supplemental insurance and charitable support. The United States exhibits a highly fragmented coverage model, while out-of-pocket systems largely lack formal reimbursement pathways. Across all models, oncology-related hair loss is more consistently covered than non-oncologic etiologies. Heterogeneity in available policy data and reliance on publicly available sources may have limited the scope and completeness of our search. CP coverage is globally inconsistent and frequently insufficient, highlighting the need for standardized recognition of CPs as medically necessary devices to improve equitable access.