MMP-9 Levels in the Gingival Crevicular Fluid of Chilean Rosacea Patients.

Rosacea is a chronic inflammatory skin disease whose prevalence rates remain unknown in Chile. Laboratory benchmark testing for this disease is not useful, therefore, we aimed to evaluate the gingival crevicular fluid (GCF) levels of extracellular metalloproteinases (MMP)-2 and MMP-9 as novel rosacea biomarkers. We designed a cross-sectional study with a control group. Participants were systemically healthy adults (n = 20) and persons with rosacea (n = 18). We performed a periodontal evaluation and collected gingival crevicular fluid to measure MMP-2 and MMP-9 levels. Analysis showed mean and standard deviation of MMP-9 concentrations in the GCF for patients with rosacea was 764.52 ± 569.83 pg/mL; for healthy patients, it was 260.69 ± 170.43 pg/mL (p < 0.05). The diagnosis of rosacea was responsible for the levels of MMP-9 in the GCF (p < 0.05), as opposed to periodontitis, smoking, and age (p > 0.05). The Area under ROC for MMP-9 was 0.869 (95%, C.I: 0.719−0.956), with a sensitivity of 72.22% and specificity of 81.58% for the diagnosis of rosacea. We conclude that the quantification of MMP-9 in the GCF could be used as a biomarker of rosacea. Also, rosacea was responsible for increasing the levels of MMP-9 in the GCF independent of periodontal status.

Identification of IL-18 and Soluble Cell Adhesion Molecules in the Gingival Crevicular Fluid as Novel Biomarkers of Psoriasis.

Psoriasis is a chronic immunoinflammatory skin disease. Although its diagnosis is clinical, differences in the appearance and severity of lesions pose a challenge for clinicians worldwide. The use of accessible biomarkers for psoriasis could aid in the early diagnosis and treatment of the disease. To date, evidence on the analysis of gingival crevicular fluid (GCF) molecules as novel, accessible, and reliable biomarkers for psoriasis is limited. This cross-sectional study compared the GCF levels of IL-18, soluble (s)ICAM-1, and sE-selectin in psoriatic patients (n = 42) and healthy controls (n = 39). Individuals with psoriasis not undergoing treatment and healthy individuals were included independent of periodontal status. GCF samples were collected, and a multiplex bead immunoassay was performed to quantify the levels of the target molecules. Psoriatic patients presented higher concentrations of IL-18 and lower concentrations of sE-selectin compared to controls (p < 0.05). No differences were found in the levels of sICAM-1 between the two groups (p > 0.05). Psoriasis was associated with IL-18 and E-selectin levels regardless of periodontal status, age, and smoking habit (p < 0.05). The areas under the receiver operating characteristic curve (ROC) for IL-18 and sE-selectin were 0.77 and 0.68, respectively. In conclusion, IL-18 and sE-selectin levels in the GCF could be promising biomarker for psoriasis.

Enfrentamiento de las infecciones de piel en el adulto / Managing adult skin infections

En la actualidad, las infecciones de piel y partes blandas forman parte de un alto porcentaje de las consultas en salud. Estas van desde infecciones leves, donde el manejo se realiza con tratamiento tópico, hasta aquellas con severo compromiso sistémico, requiriendo terapia antibiótica sistémica e incluso el desbridaje quirúrgico. En general, son producto de un desbalance entre los mecanismos de defensa de la barrera cutánea y los factores de virulencia y patogenicidad de los microorganismos que la afectan. Se pueden clasificar según distintos criterios, como por ejemplo, profundidad, gravedad, microorganismos involucrados y si estas son purulentas o no. El reconocer estas entidades clínicas es de suma importancia para llevar a cabo un adecuado tratamiento en los pacientes que presentan estas afecciones, ya que los diagnósticos erróneos llevan a las múltiples consultas con el consiguiente aumento de costos asociados en atención en salud.

Currently, skin and soft tissue infections are part of a high percentage of health consultations. These range from mild infections, where management is performed with topical treatment, to those with severe systemic compromise requiring systemic antibiotic therapy and even surgical debridement. In general, they are the product of an imbalance between the defense mechanisms of the skin barrier and the virulence and pathogenicity factors of the microorganisms that affect it, which can vary from bacterial, viral, fungal and parasites agents. Skin and soft tissue infections can be classified according to different criteria, such as depth, severity, microorganisms involved and whether they are purulent or not. Recognizing these clinical entities is of utmost importance to carry out adequate treatment in patients with these conditions, since erroneous diagnoses lead to multiple consultations with the consequent increase in costs associated with health care

Levels of the interleukins 17A, 22, and 23 and the S100 protein family in the gingival crevicular fluid of psoriatic patients with or without periodontitis,

Abstract Background: Psoriasis and periodontitis are immunologically mediated chronic inflammatory diseases. Epidemiologic evidence has linked both; however, the change of markers in gingival crevicular fluid has been poorly evaluated. Objective: To evaluate the levels of IL-17A, IL-22, IL-23, S100A7, S100A8, and S100A9 in gingival crevicular fluid of psoriatic and healthy subjects with and without periodontitis and their relations to psoriasis severity. Methods: Cross-sectional study. Sample comprised the following groups: healthy controls without periodontitis or with mild periodontitis (n = 21), healthy controls with moderate or severe periodontitis (n = 18), individuals with psoriasis without or mild periodontitis (n = 11), and individuals with psoriasis and moderate or severe periodontitis (n = 32). Levels of IL-17A, IL-22, IL-23, S100A8, and S100A9 were determined by multiplex assay and S100A7 was measured by ELISA. Results: No inter-group differences in the levels of IL-17A, IL-22, IL-23, and S100A7 were found. S100A8 levels were higher in psoriatic patients than controls (p < 0.05). S100A8 was positively correlated with psoriasis severity in the group with psoriasis (p < 0.05). S100A9 exceeded the detection limits. Study limitations: This pilot study presents a small sample size. Conclusions: The concentrations of S100A8 were highest in psoriatic patients regardless of periodontal health/status. S100A8 was associated with the severity of psoriasis. The concentrations of interleukins and S100A7 were similar in psoriatic patients with or without periodontitis vs. healthy controls.

Levels of the interleukins 17A, 22, and 23 and the S100 protein family in the gingival crevicular fluid of psoriatic patients with or without periodontitis.

BACKGROUND: Psoriasis and periodontitis are immunologically mediated chronic inflammatory diseases. Epidemiologic evidence has linked both; however, the change of markers in gingival crevicular fluid has been poorly evaluated. OBJECTIVE: To evaluate the levels of IL-17A, IL-22, IL-23, S100A7, S100A8, and S100A9 in gingival crevicular fluid of psoriatic and healthy subjects with and without periodontitis and their relations to psoriasis severity. METHODS: Cross-sectional study. Sample comprised the following groups: healthy controls without periodontitis or with mild periodontitis (n=21), healthy controls with moderate or severe periodontitis (n=18), individuals with psoriasis without or mild periodontitis (n=11), and individuals with psoriasis and moderate or severe periodontitis (n=32). Levels of IL-17A, IL-22, IL-23, S100A8, and S100A9 were determined by multiplex assay and S100A7 was measured by ELISA. RESULTS: No inter-group differences in the levels of IL-17A, IL-22, IL-23, and S100A7 were found. S100A8 levels were higher in psoriatic patients than controls (p<0.05). S100A8 was positively correlated with psoriasis severity in the group with psoriasis (p<0.05). S100A9 exceeded the detection limits. STUDY LIMITATIONS: This pilot study presents a small sample size. CONCLUSIONS: The concentrations of S100A8 were highest in psoriatic patients regardless of periodontal health/status. S100A8 was associated with the severity of psoriasis. The concentrations of interleukins and S100A7 were similar in psoriatic patients with or without periodontitis vs. healthy controls.

Immunogenicity to biological drugs in psoriasis and psoriatic arthritis

Monoclonal antibodies or fusion proteins, defined as biological drugs, have modified the natural history of numerous immune-mediated disorders, allowing the development of therapies aimed at blocking the pathophysiological pathways of the disease, providing greater efficacy and safety than conventional treatment strategies. Virtually all therapeutic proteins elicit an immune response, producing anti-drug antibodies (ADAs) against hypervariable regions of immunoglobulins. Immunogenicity against biological drugs can alter their pharmacokinetic and pharmacodynamic properties, thereby reducing the efficacy of these drugs. In more severe cases, ADAs can neutralize the therapeutic effects of the drug or cause serious adverse effects, mainly hypersensitivity reactions. The prevalence of ADAs varies widely depending on the type of test used, occurrence of false-negative results, and non-specific binding to the drug, making it difficult to accurately assess their clinical impact. Concomitant use of immunosuppressors efficiently reduces the immunogenicity in a dose-dependent manner, either by decreasing the frequency of detectable ADAs or by delaying their appearance, thereby enhancing the effectiveness of biological therapies. Among the new therapeutic strategies for the management of psoriasis, biological agents have gained increasing importance in recent years as they interrupt key inflammation pathways involved in the physiopathology of the disease. Reports regarding ADA in new biologics are still scarce, but the most recent evidence tends to show little impact on the clinical response to the drug, even with prolonged treatment. It is therefore essential to standardize laboratory tests to determine the presence and titles of ADAs to establish their administration and management guidelines that allow the determination of the real clinical impact of these drugs.

Presente y futuro del tratamiento biológico y moléculas pequeñas en la dermatitis atópica / Present and future of biological treatment and small molecules in atopic dermatitis

La dermatitis atópica (DA) es una condición inflamatoria crónica de la piel de etiología multifactorial. Buscando mejorar la respuesta clínica minimizando los efectos adversos y ampliar el arsenal terapéutico disponible, se ha dado pie al desarrollo de nuevos fármacos con resultados prometedores en la calidad de vida. Los inmunomoduladores sistémicos clásicos son considerados el tratamiento estándar en los casos de DA moderada a severa refractaria al tratamiento con corticoides tópicos. Estos se encasillan dentro de las denominadas moléculas pequeñas, junto con los inhibidores de Janus- en un efecto pleiotrópico en las citoquinas y por ende, no selectivo. Los medicamentos biológicos poseen ventajas frente a los inmunomoduladores clásicos, principalmente su mayor especificidad gracias a la similitud con las moléculas endógenas. Dupilumab se mantiene siendo el único fármaco biológico aprobado por la FDA para el tratamiento de la DA, con una seguridad a corto plazo demostrada. Algunas moléculas nuevas, como el tralokinumab y los inhibidores JAK, presentan resultados prometedores. De este grupo, abrocitinib pareciera posicionarse como una alternativa al menos similar que dupilumab. La creciente investigación de nuevas alternativas ha creado una revolución terapéutica para que nuestros pacientes puedan acceder a una mejor calidad de vida. No obstante, es difícil lograr comprender la efectividad y seguridad de cada uno de los tratamientos disponibles, por la falta de estudios comparativos. La siguiente revisión muestra las nuevas terapias biológicas y algunas moléculas pequeñas con evidencia para su uso en DA

Atopic dermatitis (AD) is a chronic inflammatory condition of the skin with a multifactorial etiology. Seeking to improve the clinical response by minimizing adverse effects and expanding the available therapeutic arsenal, the development of new drugs has led to promising results on quality of life. Classic systemic immunomodulators are considered the standard treatment in cases of moderate to severe AD refractory to treatment with topical corticosteroids. These are classified into molecules, along with Janus kinase inhibitors (JAKs). Small molecules act on intracellular targets, with the inconveniency of producing a pleiotropic effect on cytokines and, therefore, non-selective actions. Biologics have advantages over classical immunomodulators, mainly their greater specificity thanks to the similarity between endogenous molecules. Dupilumab remains the only biologic drug approved by the FDA for the treatment of AD, with demonstrated short-term safety. Some new molecules, such as tralokinumab and JAK inhibitors, have shown promising results. Of this group, abrocitinib seems to be positioned as an alternative at least similar to dupilumab. The current investigation of new alternatives has created a therapeutic revolution so that we can offer our patients a better quality of life. However, it is difficult to understand the efficacy and safety of each of the available treatments due to the lack of comparative studies. The following review shows the new biological therapies and small molecules with evidence for their use in DA.

[Panniculitis in association with target therapy in melanoma patient, what the dermatologist should know: A case report]. / Paniculitis secundaria a terapia target en paciente con melanoma, lo que el dermatólogo debe saber: reporte de un caso.

Target therapies are currently a therapeutic option increasingly used for the management of patients with metastatic melanoma. However, there are multiple adverse pharmacological effects associated with their use that have been described. Cutaneous adverse reactions are the most frequent. We report the case of a 55-year-old man with a diagnosis of stage IV BRAFV600E-mutated metastatic cutaneous melanoma undergoing treatment with dabrafenib/trametinib, who consulted due to the development of erythematous nodular lesions in the upper and lower limbs associated with febrile sensation during the course of treatment. Infection was ruled out and a biopsy of the skin lesions was done, which provided the histopathological confirmation of a predominantly septal, granulomatous with leukocytoclastic vasculitis, mixed panniculitis. Panniculitis associated with this therapy has been described in the literature and has been considered an immune-mediated pharmacological adverse effect. It is considered to be related to a better prognosis in the treatment of metastatic melanoma. Consequently, as shown in this case report, target therapy should not be discontinued and symptomatic medication should be given to alleviate patient discomfort. The dermatologist should know and properly interpret this adverse effect and prescribe the most appropriate management for the patient.

Las terapias target constituyen hoy en día una alternativa terapéutica cada vez más utilizada para el manejo de pacientes con melanoma metastásico. Sin embargo, se han descrito múltiples efectos farmacológicos adversos asociados a su uso, siendo los cutáneos los de mayor prevalencia. Se presenta el caso de un hombre de 55 años con diagnóstico de melanoma cutáneo metastásico etapa IV, BRAFV600E mutado, en tratamiento con dabrafenib/trametinib que consultó por desarrollo de lesiones nodulares eritematosas sensibles en extremidades superiores e inferiores, asociadas a sensación febril durante el curso del tratamiento. Se descartó alguna infección sobreagregada. Se realizó una biopsia de las lesiones cutáneas, con confirmación diagnóstica histopatológica de una paniculitis mixta de predominio septal, granulomatosa y con vasculitis leucocitoclástica. La paniculitis asociada a esta terapia ha sido descrita en la literatura y se ha considerado un efecto farmacológico inmunomediado adverso, relacionándose a un mejor pronóstico para el melanoma metastásico en tratamiento. Por lo tanto, así como en el caso presentado, se evita la suspensión del fármaco y se asocia terapia sintomática en caso de mayores molestias del paciente. Es de alta relevancia para el dermatólogo conocer e interpretar adecuadamente este efecto adverso farmacológico, y así indicar el manejo más adecuado para el paciente.

Políticas públicas de promoción de estilos de vida saludable como forma de gobierno por medio de la comunidad / Políticas públicas para promover estilos de vida saudáveis como forma de governo através da comunidade / Public policies to promote healthy lifestyles as a form of government through community

Basado en un estudio de caso, este artículo avanza en la comprensión de los mecanismos concretos que encauzan procesos de subjetivación en el contexto de políticas públicas de promoción de estilos de vida saludable. Analiza el funcionamiento del Programa Vida Sana, implementado por el Gobierno de Chile en el marco del Sistema Elige Vivir Sano, por medio de entrevistas a beneficiarias y a la profesora responsable de las sesiones de actividad física del programa en una localidad de Santiago. Su análisis sugiere la coexistencia de una racionalidad de la elección, que tradicionalmente ha sido identificada con el discurso de la vida activa, con una racionalidad que enfatiza el cuidado mutuo entre los miembros de una comunidad. Se propone que esto tiene implicancias teóricas para la comprensión de las políticas públicas deportivas y de salud como forma de gobierno por medio de la comunidad.

Com base em um estudo de caso, este artigo avança na compreensão dos mecanismos específicos que canalizam os processos de subjetivação no contexto das políticas públicas para promover estilos de vida saudáveis. Analisa a operação do Programa Vida Sana, implementado pelo Governo do Chile, no âmbito do Sistema Escolha Uma Vida Saudável, por meio de entrevistas com beneficiários e a professora responsável pelas sessões de atividade física do programa em um distrito de Santiago. Sua análise sugere a convivência de uma racionalidade de escolha, que tradicionalmente tem sido identificada com o discurso da vida ativa, com uma racionalidade que enfatiza o cuidado mútuo entre os membros de uma comunidade. Propõe-se que isso tenha implicações teóricas para a compreensão das políticas públicas de esportes e saúde como forma de governo através da comunidade.

Based on a case study, this article advances in understanding the concrete mechanisms that channel subjectivation processes in the context of public policies to promote healthy lifestyles. It analyzes the operation of the Vida Sana Program, implemented by the Government of Chile within the framework of the Choose Healthy Living System, through interviews with beneficiaries and the teacher responsible for the program's physical activity sessions in a district of Santiago. Its analysis suggests the coexistence of a rationality of choice, which has traditionally been identified with the discourse of active life, with a rationality that emphasizes mutual care among members of a community. The study proposes that it has theoretical implications for understanding sports and health public policies as a form of governing through community.

Las Lógicas del Trabajo Moral en Telemedicina: Disputas en Torno a la Legitimidad de Políticas de Salud Digital / The Logics of Moral Work in Telemedicine: Disputes on the Legitimacy of Digital Health Policies / A Lógica do Trabalho Moral na Telemedicina: Disputas Sobre a Legitimidade das Políticas de Saúde Digital

Resumen: A partir del estudio de un programa de teleneurología implementado en Biobío, Chile, este artículo analiza las lógicas que articulan el trabajo moral de la medicina a distancia. Desde un enfoque pragmático informado por la semiótica material, la teoría de la subjetivación y la sociología de la moralidad, este artículo analiza tres lógicas que dan sentido a prácticas de valuación del programa de teleneurología. Ellas son desplegadas por actores que desempeñan roles distintos, generando puntos de tensión y encauzando la constante evolución de los entramados sociomateriales en que se realiza el cuidado de salud. Una lógica cívico industrial fundamenta discursos públicos que destacan la reducción de las listas de espera de especialidad como prueba de valor del programa de telemedicina. Desde una lógica de la seguridad, en tanto, personal médico prioriza la adopción de estándares que, orientados a controlar los riesgos implicados en la realización de medicina a distancia, son tenidos como válidos por una comunidad profesional. Por su parte, adoptando una lógica del cuidado, pacientes y médicos generales enfatizan el despliegue de prácticas orientadas a atender la situación particular que experimenta cada paciente. Se propone que reconocer las lógicas que distintos actores puedan adoptar para otorgar valor a las prácticas de cuidado de salud puede favorecer la comprensión, anticipación y resolución de las tensiones que emergen con la implementación de tecnologías de salud digital y telemedicina.

Abstract: Based on the study of a teleneurology program implemented in Biobío, Chile, this article analyses the logics that articulate the moral work of medicine at a distance. From a pragmatic approach informed by material semiotics, the theory of subjectivisation and the sociology of morality, this article analyses three logics that give meaning to practices of valuation of the teleneurology program. These are deployed by actors who play different roles, generating points of tension, and channeling the constant evolution of the socio-material networks in which health care is performed. A civic industrial logic underpins public discourses that highlight the reduction of waiting lists as proof of the value of the telemedicine program. From a safety logic, meanwhile, medical staff prioritizes the adoption of standards that, aimed at controlling the risks involved in the realisation of medicine remotely, are held as valid by a professional community. For their part, adopting logic of care, patients and general practitioners emphasize the deployment of practices aimed at attending the particular situation experienced by each patient. It is proposed that recognizing the logics that different actors may adopt when giving value to health care practices can promote understanding, anticipating and solving the tensions that arise with the implementation of digital health technologies and telemedicine.

Resumo: Com base no estudo de um programa de teleneurologia implementado em Biobío, Chile, este artigo analisa as lógicas que articulam o trabalho moral da medicina à distância. A partir de uma abordagem pragmática informada pela semiótica material, a teoria da subjetivação e a sociologia da moralidade, este artigo analisa três lógicas que dão sentido às práticas de valorização do programa de teleneurologia. Eles são implantados por atores que desempenham diferentes papéis, gerando pontos de estresse e canalizando a constante evolução dos tecidos sociomateriais nos quais os cuidados de saúde são realizados. Uma lógica cívica industrial apoia discursos públicos que destacam o declínio das listas de espera de especialidade como prova de valor do programa de telemedicina. A partir de uma lógica de segurança, entretanto, a equipe médica prioriza a adoção de padrões que, visando controlar os riscos envolvidos na realização da medicina remotamente, são mantidos como válidos por uma comunidade profissional. Por sua vez, adotar uma lógica de cuidado, pacientes e clínicos gerais enfatizam a implantação de práticas voltadas ao atendimento da situação particular vivenciada por cada paciente. Propõe-se que o reconhecimento das lógicas que diferentes atores podem adotar para valorizar as práticas de saúde pode promover a compreensão, antecipação e resolução das tensões que surgem com a implementação das tecnologias de saúde digital e telemedicina.