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Abstract Background Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease. HS is difficult‐to‐treat, and a multifaceted treatment approach is recommended to achieve adequate clinical response. A greater understanding of HS treatment could help identify unmet clinical needs. Objectives To evaluate disease characteristics and treatment patterns in a real‐world population of patients with HS in Spain. Methods This retrospective analysis utilised data collected from the Adelphi HS Disease Specific Programme between November 2020 and April 2021. Dermatologists completed patient record forms (PRFs) for consulting HS patients. Outcomes included disease severity, HS clinical signs, quality of life measures, medical treatments and previous surgeries. Results Overall, 53 dermatologists completed 332 PRFs, each representing one patient with HS. Based on physician‐judged disease severity at sampling, 73.8%, 22.9% and 3.3% of patients were classified as mild, moderate or severe, respectively. Overall, patients presented with 2.8±2.7 (mean±SD) HS symptoms, which increased with worsening disease severity. The most frequently reported symptoms were ‘inflammation/redness of HS lesions/abscess’ (45.9%), general pain/discomfort (39.9%) and pain on sitting (32.3%). Overall, patients reported a mean±SD Dermatology Life Quality Index score of 4.7±4.8, which increased with worsening disease severity (mild, 3.9±4.3; moderate, 8.7±5.1; moderate to severe, 9.0±5.1). When asked what effect HS had on everyday activities, a large proportion of patients reported that HS sometimes or greatly affected personal appearance/self‐confidence (66.0%), mood (60.2%), close personal relationships (60.4%), motivation (38.3%), leisure activities (43.0%) and feelings about the future (33.6%). At the time of HS diagnosis, the most frequently prescribed treatment regimens were topicals (70.7%), antibiotics (57.6%) and antiseptics (32.2%). At the time of sampling, the most common treatment regimens were biologics (43.8%), topicals (34.9%) and antibiotics (32.2%). The mean±SD number of surgical interventions was 0.6±0.8; incision and drainage (31.3%), local or limited excision (13.0%), and wide surgical excision of all hair‐bearing skin (9.9%) were the most common surgeries. Conclusions These real‐world data suggest a high disease burden in patients with HS in Spain. Patients received multiple treatments, and a notable proportion underwent surgery. More data are needed to define optimal HS management strategies.

Abstract Background The oral anti‐janus kinase 1 inhibitor upadacitinib has shown a good efficacy–safety profile in the treatment of moderate‐to‐severe atopic dermatitis (AD) in clinical trials; however, few data from real clinical practice have been published so far. Objectives To evaluate the efficacy and safety of upadactinib in clinical practice. Methods An observational and multicentric study was conducted. Inclusion criteria consisted of patients who had previously received upadacitinib in the clinical trial M19‐850 and continued treatment with upadacitinib (15 mg or 30 mg) under daily clinical practice conditions for 12 months. Demographic data, characteristics of AD, treatment response and adverse events were recorded. Preliminary results at 24‐week follow‐up are herein presented. Results A total of 26 patients (61.54% males, mean age: 35.58 years) were included in the study; of these, 92.31% received upadacitinib 30 mg at baseline. At 24 weeks, mean values of Eczema Area and Severity Index and body surface area were 2.26 and 2.37%, respectively, 82.35% of the patients reached the Investigator's Global Assessment 0/1 and the mean value of peak pruritus numerical rating scale was 1.74. Adverse events were present in 19.23% of the cases, causing one definitive treatment interruption (due to herpes zoster) and two temporary treatment discontinuations (due to temporary elevation of creatine kinase). Conclusions These data support the maintenance of the efficacy of upadacitinib at 24‐week posttrial follow‐up, with no unexpected safety concerns. More real‐world data are needed to confirm these results.

BackgroundPsoriasis is a chronic immune-mediated inflammatory systemic disease with skin manifestations characterized by erythematous, scaly, itchy and/or painful plaques resulting from hyperproliferation of keratinocytes. Certolizumab pegol [CZP], a PEGylated antigen binding fragment of a humanized monoclonal antibody against TNF-alpha, is approved for the treatment of moderate-to-severe plaque psoriasis. Patients with psoriasis present clinical and molecular variability, affecting response to treatment. Herein, we utilized an in silico approach to model the effects of CZP in a virtual population (vPop) with moderate-to-severe psoriasis. Our proof-of-concept study aims to assess the performance of our model in generating a vPop and defining CZP response variability based on patient profiles.MethodsWe built a quantitative systems pharmacology (QSP) model of a clinical trial-like vPop with moderate-to-severe psoriasis treated with two dosing schemes of CZP (200 mg and 400 mg, both every two weeks for 16 weeks, starting with a loading dose of CZP 400 mg at weeks 0, 2, and 4). We applied different modelling approaches: (i) an algorithm to generate vPop according to reference population values and comorbidity frequencies in real-world populations; (ii) physiologically based pharmacokinetic (PBPK) models of CZP dosing schemes in each virtual patient; and (iii) systems biology-based models of the mechanism of action (MoA) of the drug.ResultsThe combination of our different modelling approaches yielded a vPop distribution and a PBPK model that aligned with existing literature. Our systems biology and QSP models reproduced known biological and clinical activity, presenting outcomes correlating with clinical efficacy measures. We identified distinct clusters of virtual patients based on their psoriasis-related protein predicted activity when treated with CZP, which could help unravel differences in drug efficacy in diverse subpopulations. Moreover, our models revealed clusters of MoA solutions irrespective of the dosing regimen employed.ConclusionOur study provided patient specific QSP models that reproduced clinical and molecular efficacy features, supporting the use of computational methods as modelling strategy to explore drug response variability. This might shed light on the differences in drug efficacy in diverse subpopulations, especially useful in complex diseases such as psoriasis, through the generation of mechanistically based hypotheses.

Resumen: Introducción: La alergia a las proteínas de la leche de vaca (APLV) es la alergia alimentaria más frecuente en el primer año de vida. No existe un consenso claro respecto a su prevención. Recientemente se ha publicado la recomendación de evitar estas proteínas en la primera semana de vida como medida de prevención en todos los niños, con independencia de su riesgo atópico. El objetivo de este documento es emitir una recomendación sobre el uso de fórmulas extensamente hidrolizadas de PLV en la primera semana de vida para la prevención primaria de la APLV. Métodos: Se constituyó un grupo de expertos propuestos por la Asociación Española de Pediatría (AEP), la Sociedad Española de Inmunología Clínica y Alergología y Asma Pediátrica (SEICAAP), la Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP) y la Sociedad Española de Neonatología (SENEO). Se realizó una revisión crítica de la evidencia publicada en los últimos 10 años sobre el tema. Resultados: Se seleccionaron 72 estudios, de los cuales 66 fueron rechazados por no cumplir los criterios de inclusión. Se incluyeron en la revisión 6 documentos: 3 ensayos clínicos y 3 revisiones sistemáticas, 2 de ellas con metaanálisis. No se observó una reducción estadísticamente significativa en la incidencia de APLV en los grupos de lactantes que recibieron fórmulas hipoalergénicas ni lactancia materna exclusiva. Conclusión: Con base en las evidencias existentes en la actualidad, no se pueden establecer conclusiones claras acerca del efecto de evitar las PLV durante la primera semana de vida en la prevención de la APLV. A pesar de existir datos que pudieran orientar a un cierto efecto beneficioso de su evitación en niños con riesgo atópico, estos resultados no son concluyentes ni generalizables a lactantes sin dicho riesgo. Abstract: Introduction: Cow's milk protein allergy (CMPA) is the most frequent food allergy in the first year of life. There is no clear consensus regarding its prevention. A recommendation to avoid CMP in the first week of life as a preventive measure in all infants, regardless of their atopic risk, has recently been published. The purpose of this document is to issue a recommendation on the use of extensively hydrolyzed CMP formulas in the first week of life for the primary prevention of CMPA. Methods: A group of experts was formed with members proposed by the Spanish Association of Pediatrics (AEP), the Spanish Society of Clinical Immunology and Allergology and Pediatric Asthma (SEICAAP), the Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP) and the Spanish Society of Neonatology (SENEO). The group conducted a critical review of the evidence on the subject published in the last 10 years. Results: The search yielded 72 studies, of which 66 were rejected for not meeting the inclusion criteria. The final review included 6 documents: 3 clinical trials and 3 systematic reviews, 2 of them with meta-analysis. There was no evidence of a statistically significant reduction in the incidence of CMPA in the infants who received hypoallergenic formulae or exclusive breastfeeding. Conclusion: Based on the current evidence, it is not possible to draw clear conclusions about the effect of avoiding CMP in the first week of life for prevention of CMPA. Although there are data that suggest a certain beneficial effect of avoiding CMPA in atopic risk infants, these results are not conclusive enough to extend the recommendation to the general population.

Introduction: Cow’s milk protein allergy (CMPA) is the most frequent food allergy in the first year of life. There is no clear consensus regarding its prevention. A recommendation to avoid CMP in the first week of life as a preventive measure in all infants, regardless of their atopic risk, has recently been published. The purpose of this document is to issue a recommendation on the use of extensively hydrolyzed CMP formulas in the first week of life for the primary prevention of CMPA. Methods: A group of experts was formed with members proposed by the Spanish Association of Pediatrics (AEP), the Spanish Society of Clinical Immunology and Allergology and Pediatric Asthma (SEICAAP), the Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP) and the Spanish Society of Neonatology (SENEO). The group conducted a critical review of the evidence on the subject published in the last 10 years. Results: The search yielded 72 studies, of which 66 were rejected for not meeting the inclusion criteria. The final review included 6 documents: 3 clinical trials and 3 systematic reviews, 2 of them with meta-analysis. There was no evidence of a statistically significant reduction in the incidence of CMPA in the infants who received hypoallergenic formulae or exclusive breastfeeding. Conclusion: Based on the current evidence, it is not possible to draw clear conclusions about the effect of avoiding CMP in the first week of life for prevention of CMPA. Although there are data that suggest a certain beneficial effect of avoiding CMPA in atopic risk infants, these results are not conclusive enough to extend the recommendation to the general population. Resumen: Introducción: La alergia a las proteínas de la leche de vaca (APLV) es la alergia alimentaria más frecuente en el primer año de vida. No existe un consenso claro respecto a su prevención. Recientemente se ha publicado la recomendación de evitar estas proteínas en la primera semana de vida como medida de prevención en todos los niños, con independencia de su riesgo atópico. El objetivo de este documento es emitir una recomendación sobre el uso de fórmulas extensamente hidrolizadas de PLV en la primera semana de vida para la prevención primaria de la APLV. Métodos: Se constituyó un grupo de expertos propuestos por la Asociación Española de Pediatría (AEP), la Sociedad Española de Inmunología Clínica y Alergología y Asma Pediátrica (SEICAAP), la Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP) y la Sociedad Española de Neonatología (SENEO). Se realizó una revisión crítica de la evidencia publicada en los últimos 10 años sobre el tema. Resultados: Se seleccionaron 72 estudios, de los cuales 66 fueron rechazados por no cumplir los criterios de inclusión. Se incluyeron en la revisión 6 documentos: 3 ensayos clínicos y 3 revisiones sistemáticas, 2 de ellas con metaanálisis. No se observó una reducción estadísticamente significativa en la incidencia de APLV en los grupos de lactantes que recibieron fórmulas hipoalergénicas ni lactancia materna exclusiva. Conclusión: Con base en las evidencias existentes en la actualidad, no se pueden establecer conclusiones claras acerca del efecto de evitar las PLV durante la primera semana de vida en la prevención de la APLV. A pesar de existir datos que pudieran orientar a un cierto efecto beneficioso de su evitación en niños con riesgo atópico, estos resultados no son concluyentes ni generalizables a lactantes sin dicho riesgo.

Abstract Introduction Keratinocyte tumors (KT) are frequently observed. Surgery is the treatment gold standard. In some cases, a surgical approach might not be the best option. Radiotherapy (RT) and systemic treatments can frequently cause side effects or be contraindicated. Intralesional methotrexate (MTX) can be a conservative yet effective alternative. We decided to evaluate the effectiveness and safety of intralesional chemotherapy with MTX for the treatment of squamous cell carcinoma (SCC), keratoacanthoma (KA), and basal cell carcinoma (BCC). Methods All patients had a histologically confirmed diagnosis of BCC, SCC, or KA and no indication to surgery or RT. MTX was injected subcutaneously proceeding from the periphery of the lesion toward the center. Different protocols in terms of dose, frequency, and length of treatment were used to compare them. Treatment efficacy was evaluated in terms of tumor size reduction. Patients were divided into three groups: responders (improvement of more than 50%), partial responders (< 50%), and non-responders (no improvement or worsening). All data were analyzed using the chi-squared test (χ 2). Results Thirty-five patients were included. Twenty-one patients suffered from SCC, 12 from KA, and 2 from BCC. KA showed a higher response rate than SCC and BCC. For AK, 92% of patients had a complete resolution; 8% were partial responders. For SCC, 47.6% of cases were responders and 14.3% partial responders, while 38% non-responders. All BCCs showed no improvement. A treatment protocol of weekly injections, performed for 4 to 6 weeks, was the most efficient. Doses of 25 mg/ml per session seemed to be most effective. About one third of our patients developed side effects with mild anemia being the most frequent. Conclusions For selected cases, intralesional MTX can be a safe and effective option for the treatment of KT, especially in case of KA and, to a lesser extent, SCC.

Randomized studies to assess the efficacy of Mohs micrographic surgery in basal cell and squamous cell carcinomas are limited by methodological and ethical issues and a lack of long follow-up periods. This study presents the “real-life” results of a nationwide 7-years cohort on basal cell carcinoma and squamous cell carcinoma treated with Mohs micrographic surgery. A prospective cohort was conducted in 22 Spanish centres (from July 2013 to February 2020) and a multivariate analysis, including characteristics of patients, tumours, surgeries and follow-up, was performed. A total of 4,402 patients followed up for 12,111 patient-years for basal cell carcinoma, and 371 patients with 915 patient-years of follow-up for squamous cell carcinoma were recruited. Risk factors for recurrence included age, non-primary tumours and more stages or unfinished surgeries for both tumours, and immunosuppression for squamous cell carcinoma. Incidence rates of recurrence were 1.3 per 100 person-years for basal cell carcinoma (95% confidence interval 1.1–1.5) and 4.5 for squamous cell carcinoma (95% confidence interval 3.3–6.1), being constant over time (0–5 years). In conclusion, follow-up strategies should be equally intense for at least the first 5 years, with special attention paid to squamous cell carcinoma (especially in immunosuppressed patients), elderly patients, non-primary tumours, and those procedures requiring more stages, or unfinished surgeries.

The treatment of psoriasis has been revolutionized by the emergence of biological therapies. Monoclonal antibodies (mAb) generally have complex pharmacokinetic (PK) properties with nonlinear distribution and elimination. In recent years, several population pharmacokinetic/pharmacodynamic (PK/PD) models capable of describing different types of mAb have been published. This study aims to summarize the findings of a literature search about population PK/PD modeling and therapeutic drug monitoring (TDM) of mAb in psoriasis. A total of 22 articles corresponding to population PK/PD models of tumor necrosis factor (TNF)-α inhibitors (adalimumab and golimumab), interleukin (IL)-23 inhibitors (guselkumab, tildrakizumab, and risankizumab), IL-23/IL-12 inhibitor (ustekinumab), and IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) were collected. A summary of the clinical trials conducted so far in psoriasis was included, together with the current structural population PK and PD models. The most significant and clinical covariates were body weight (BW) and the presence of immunogenicity on clearance (CL). The lack of consensus on PK/PD relationships has prevented establishing an adequate dosage and, therefore, accentuates the need for TDM in psoriasis.

Epidemiological associations linking between obstructive sleep apnea and poorer solid malignant tumor outcomes have recently emerged. Putative pathways proposed to explain that these associations have included enhanced hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) cell expression in the tumor and altered immune functions via intermittent hypoxia (IH). Here, we examined relationships between HIF-1α and VEGF expression and nocturnal IH in cutaneous melanoma (CM) tumor samples. Prospectively recruited patients with CM tumor samples were included and underwent overnight polygraphy. General clinical features, apnea–hypopnea index (AHI), desaturation index (DI4%), and CM characteristics were recorded. Histochemical assessments of VEGF and HIF-1α were performed, and the percentage of positive cells (0, 75%) was blindly tabulated for VEGF expression, and as 0, 0–5.9, 6.0–10.0, >10.0% for HIF-1α expression, respectively. Cases with HIF-1α expression >6% (high expression) were compared with those 75% of cells was compared with those with