Resistencia a la insulina y niveles circulantes de adiponectina, leptina, resistina y visfatina en pacientes no diabéticos con hidradenitis supurativa

RESUMEN Justificación. La hidradenitis supurativa (HS) es una enfermedad inflamatoria crónica y recurrente que se origina en el infundíbulo folicular. En los últimos años, se ha demostrado una importante asociación entre las enfermedades inflamatorias crónicas y diversos trastornos metabólicos, como el síndrome metabólico y la resistencia a la insulina (RI), así como el desarrollo prematuro de arteriosclerosis subclínica. Objetivos. Los principales objetivos de este estudio fueron determinar si los pacientes no diabéticos con HS presentan una prevalencia incrementada de RI en comparación con los sujetos control, así como analizar los niveles plasmáticos de las principales adipoquinas (adiponectina, leptina, resistina y visfatina) en estos pacientes y comprobar si existen diferencias significativas con respecto a los valores detectados en los controles. Asimismo, otros objetivos fueron investigar si existe asociación entre la gravedad de la HS, la RI y las concentraciones plasmáticas de las adipoquinas estudiadas y evaluar si existe relación entre la RI y los valores séricos de las adipoquinas en este grupo de pacientes. Pacientes y métodos. Se realizó un estudio transversal de casos y controles en el que se incluyeron 76 pacientes no diabéticos con HS y 61 controles sanos emparejados por edad y sexo. El estudio fue realizado en el Hospital Universitario Marqués de Valdecilla (HUMV), en Santander (Cantabria), entre febrero del año 2014 y marzo del año 2017. En todos los participantes se recogieron los datos demográficos y antropométricos. La gravedad de la HS se evaluó mediante la escala de Hurley y el Hidradenitis Suppurativa Physician Global Assessment (HS-PGA). La RI se determinó mediante la valoración del modelo homeostático de resistencia a la insulina (HOMA-IR), considerando como RI un valor de HOMA-IR mayor o igual a 2,5. Asimismo, las concentraciones plasmáticas de la adiponectina, leptina, resistina y visfatina fueron determinadas en todos los participantes. Resultados. Los valores de HOMA-IR en los pacientes con HS fueron significativamente más elevados que los detectados en el grupo control. La prevalencia de RI fue, asimismo, estadísticamente superior en el grupo de pacientes con HS comparado con los controles sanos. El análisis de regresión lineal multivariable demostró que los valores de HOMA-IR permanecían siendo significativamente más elevados en el grupo de pacientes con HS que en los controles incluso después de ajustar por edad, sexo e índice de masa corporal (IMC). El grupo de pacientes con HS presentó niveles plasmáticos significativamente más elevados de leptina, resistina y visfatina, pero significativamente más bajos de adiponectina que el grupo control. Estas diferencias en los niveles de adipoquinas continuaban siendo estadísticamente significativas tras realizar el ajuste por variables demográficas y el IMC, excepto en el caso de la leptina. En el grupo de pacientes con HS, se observó una correlación negativa y estadísticamente significativamente entre los valores de HOMA-IR y los niveles plasmáticos de adiponectina. Por otra parte, observamos una correlación positiva y estadísticamente significativa entre los valores de HOMA-IR y los niveles séricos de la leptina y la resistina. Además, los niveles séricos elevados de resistina y visfatina se relacionaron con un aumento en el riesgo de desarrollar HS. La RI y las alteraciones en los niveles séricos de las adipoquinas no se correlacionaron con la gravedad de la HS en pacientes no diabéticos con esta enfermedad. Conclusiones. Nuestros resultados demuestran que los pacientes no diabéticos con HS tienen una prevalencia significativamente mayor de RI que los sujetos del grupo control independientemente de variables demográficas y antropométricas. Asimismo, en estos pacientes con HS, las concentraciones séricas de resistina y visfatina son significativamente más altas mientras que las de adiponectina son significativamente menores que las detectadas en los sujetos del grupo control. Los niveles circulantes reducidos de adiponectina y elevados de resistina podrían considerarse como biomarcadores de insulino-resistencia en pacientes no diabéticos con HS. Por otra parte, los niveles plasmáticos elevados de resistina y visfatina se asocian con un riesgo incrementado de desarrollar HS, lo que sugiere que estas dos adipoquinas podrían estar implicadas en la patogenia de la HS. Finalmente, no se ha observado relación entre la gravedad de la HS, la RI y los niveles plasmáticos de las adipoquinas.ABSTRACT Background. Hidradenitis suppurativa (HS) is a chronic and recurrent inflammatory disease of the hair follicle. Recently, an important association has been demonstrated between chronic inflammatory diseases and several metabolic disorders, such as metabolic syndrome and insulin resistance (IR), as well as the premature development of subclinical atherosclerosis. Objectives. The main objectives of this study were to determine whether non-diabetic patients with HS have an increased prevalence of IR compared to control subjects, as well as to analyze plasma levels of major adipokines (adiponectin, leptin, resistin and visfatin) and check for significant differences from the values detected in the controls. Moreover, other objectives were to investigate whether there is an association between the severity of HS, IR and the plasma concentrations of the adipokines and to assess whether a relationship exists between IR and serum adipokines levels in this group of patients. Patients and methods. This cross-sectional case-control study included 76 non-diabetic patients with HS and 61 age- and gender-matched controls. The study was carried out at the Marques de Valdecilla University Hospital, in Santander (Cantabria), between February 2014 and March 2017. Demographic and anthropometric data were collected in all participants. The severity of HS was assessed by the Hurley classification and the Hidradenitis Suppurativa Physician Global Assessment (HS-PGA). IR was determined by the evaluation of the homeostatic model assessment for IR (HOMA-IR). Thus, IR was defined as a HOMA-IR value equal or greater than 2.5. In addition, plasma concentrations of adiponectin, leptin, resistin and visfatin were measured in all participants. Results. HOMA-IR value in HS patients was significantly higher than in control group. The prevalence of IR was also statistically higher in HS group compared with controls. The multivariable linear regression analysis showed that HOMA-IR values remained significantly higher in the group of patients with HS than in controls after adjusting for age, sex and body mass index (BMI). Serum concentrations of leptin, resistin and visfatin were found to be significantly higher and adiponectin levels were significantly lower in HS-patients than in controls. These differences remainded significant even after adjusting for age, sex and BMI, except for leptin. In HS patients, a negative and statistically significant correlation was observed between the values of HOMA-IR and the plasma levels of adiponectin. On the other hand, we observed a positive and statistically significant correlation between HOMA-IR values and serum levels of leptin and resistin. Furthermore, increased serum levels of resistin and visfatin were associated to an increased risk for HS development. We did not find any association between IR and serum adipokine concentrations and the severity of HS in non-diabetic patients with this disease. Conclusions. Our results demonstrate that non-diabetic patients with HS have a significantly higher prevalence of IR than control group regardless of demographic and anthropometric variables. In HS patients, serum concentrations of resistin and visfatin are significantly higher while plasma adiponectin levels are significantly lower than those detected in control group. Reduced adiponectin and increased resistin serum levels may be surrogate biomarkers for IR in patients with HS. Moreover, resistin and visfatin might be independent risk factors for the development of HS, suggesting that these two adipokines may be involved in HS pathogenesis. Finally, no relationship has been observed between the severity of HS, IR and dysregulated adipokines

Association of retinol binding protein4 (RBP4) and ghrelin plasma levels with insulin resistance and disease severity in non-diabetic patients with hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with insulin resistance (IR). Retinol binding protein 4 (RBP4) and ghrelin are two bioactive proteins that have been involved in glucose metabolism and IR, but also in the regulation of immune and inflammatory processes. The aim of this study was to determine the serum levels of RBP4 and ghrelin in patients with HS, and to assess the possible relationship between these levels and IR, disease severity and HS risk. A total of 137 subjects (77 HS patients and 60 controls) without diabetes mellitus were enrolled in this cross-sectional study. Patients with HS had significantly higher RBP4 but lower ghrelin plasma levels than controls, independently of body mass index (BMI). Serum RBP4 levels were positively correlated to disease severity and IR in HS patients. However, we found no association between ghrelin levels and any clinical or laboratory parameters. Moreover, high serum RBP4 and low ghrelin levels were associated with an increased risk for HS. Our results suggest that high RBP4 levels may be a surrogate biomarker for IR in patients with HS. Moreover, increased RBP4 and decreased ghrelin levels could also be independent risk factors for the development of HS

Association of Human Leukocyte Antigens Class II Variants with Susceptibility to Hidradenitis Suppurativa in a Caucasian Spanish Population

Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease of the hair follicle typically presenting recurrent, painful, and inflamed lesions on the inverse areas of the body. Although its pathogenesis remains unknown, the immune system appears to play a potential role. To date, two previous studies have not found any association between the Human Leukocyte Antigen system (HLA) and HS. In this study we analyzed the HLA-A, -B, -C; and DRB1, -DQA1, and ?DQB1 allele distribution in 106 HS patients and 262 healthy controls from a Caucasian population in Cantabria (northern Spain). HLA-A*29 and B*50 were significantly more common in HS patients and A*30 and B*37 in controls, but these associations disappeared after statistical correction. DRB1*07, DQA1*02, and DQB1*02 were significantly more common in controls (p 0.026, p 0.0012, and p 0.0005, respectively) and the HLA allele DQB1*03:01 was significantly more common in HS patients (p 0.00007) after the Bonferroni correction. The DRB1*07~DQA1*02~DQB1*02 haplotype was significantly more common in controls (p < 0.0005). This is the first study showing an association between HLA-class II and HS. Our results suggest that HLA-II alleles (DRB1*07, DQA1*02, DQB1*02, and DQB1*03:01) and the DRB1*07~DQA1*02~DQB1*02 haplotype could influence resistance or susceptibility to HS

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

A facility and community-based assessment of scabies in rural Malawi.

Background Scabies is a neglected tropical disease of the skin, causing severe itching, stigmatizing skin lesions and systemic complications. Since 2015, the DerMalawi project provide an integrated skin diseases clinics and Tele-dermatology care in Malawi. Clinic based data suggested a progressive increase in scabies cases observed. To better identify and treat individuals with scabies in the region, we shifted from a clinic-based model to a community based outreach programme. Methodology/principal findings From May 2015, DerMalawi project provide integrated skin diseases and Tele-dermatological care in the Nkhotakota and Salima health districts in Malawi. Demographic and clinical data of all patients personally attended are recorded. Due to a progressive increase in the number of cases of scabies the project shifted to a community-based outreach programme. For the community outreach activities, we conducted three visits between 2018 to 2019 and undertook screening in schools and villages of Alinafe Hospital catchment area. Treatment was offered for all the cases and school or household contacts. Scabies increased from 2.9% to 39.2% of all cases seen by the DerMalawi project at clinics between 2015 to 2018. During the community-based activities approximately 50% of the population was assessed in each of three visits. The prevalence of scabies was similar in the first two rounds, 15.4% (2392) at the first visit and 17.2% at the second visit. The prevalence of scabies appeared to be lower (2.4%) at the third visit. The prevalence of impetigo appeared unchanged and was 6.7% at the first visit and 5.2% at the final visit. Conclusions/significance Prevalence of scabies in our setting was very high suggesting that scabies is a major public health problem in parts of Malawi. Further work is required to more accurately assess the burden of disease and develop appropriate public health strategies for its control

Patients attended: Scabies, Impetigo and demographic data

A dataset that contains information on patients who received a facility or community-based assessment of Scabies . It contains six variables – age, gender, scabies assessment status, impetigo assessment status, site location, and treatment round number. Data was collected by the DerMalawi project through integrated skin diseases clinics and Tele-dermatology care that they established in 2015 in the Nkhotakota and Salima health districts in Malawi

A facility and community-based assessment of scabies in rural malawi

Altres ajuts: CantabriaLabs; Martiderm; Italfarmaco; Fundación CSAI; Ayuntamiento de Villanueva de la Cañada; Spanish Academy of Dermatology (CG); Colegio Oficial de Médicos de Madrid (CG); Fundación Mutua Madrileña (CG); Celia Delgado Matías Association; Universidad de Salamanca.Background Scabies is a neglected tropical disease of the skin, causing severe itching, stigmatizing skin lesions and systemic complications. Since 2015, the DerMalawi project provide an integrated skin diseases clinics and Tele-dermatology care in Malawi. Clinic based data suggested a progressive increase in scabies cases observed. To better identify and treat individuals with scabies in the region, we shifted from a clinic-based model to a community based outreach programme. Methodology/Principal findings From May 2015, DerMalawi project provide integrated skin diseases and Tele-dermatologi-cal care in the Nkhotakota and Salima health districts in Malawi. Demographic and clinical data of all patients personally attended are recorded. Due to a progressive increase in the number of cases of scabies the project shifted to a community-based outreach programme. For the community outreach activities, we conducted three visits between 2018 to 2019 and undertook screening in schools and villages of Alinafe Hospital catchment area. Treatment was offered for all the cases and school or household contacts. Scabies increased from 2.9% to 39.2% of all cases seen by the DerMalawi project at clinics between 2015 to 2018. During the community-based activities approximately 50% of the population was assessed in each of three visits. The prevalence of scabies was similar in the first two rounds, 15.4% (2392) at the first visit and 17.2% at the second visit. The prevalence of scabies appeared to be lower (2.4%) at the third visit. The prevalence of impetigo appeared unchanged and was 6.7% at the first visit and 5.2% at the final visit. Conclusions/Significance Prevalence of scabies in our setting was very high suggesting that scabies is a major public health problem in parts of Malawi. Further work is required to more accurately assess the burden of disease and develop appropriate public health strategies for its control