Influence of epidemiological and clinical factors in the reactogenicity to Comirnaty® vaccine in health care workers of a Spanish university teaching hospital (COVIVAC study).

OBJECTIVE: Comirnaty® is an mRNA vaccine against COVID-19 which has been administered to millions of people since the end of 2020. Our aim was to study epidemiological and clinical factors influencing reactogenicity and functional limitation after the first two doses of the vaccine in health care workers (HCWs). METHODS: Prospective post-authorization cohort study to monitor safety and effectiveness of the vaccine. RESULTS: Local side effects were mild and presented both with first and second dose of Comirnaty. Systemic side effects were more frequent after 2nd dose. Nevertheless, previous SARS-CoV-2 infection was associated with systemic effects after the first dose of the vaccine (OR ranging from 2 to 6). No severe adverse effects were reported. According to multivariate analysis, the degree of self-reported functional limitation after the first dose increased with age, female sex, previous COVID-19 contact, previous SARS-CoV-2 infection, and Charlson Comorbidity Index (CCI). After the second dose, the degree of functional limitation observed was lower in those with previous SARS-CoV-2 infection, and it was positively associated to the degree of functional limitation after the first dose. CONCLUSIONS: Systemic adverse effects were more frequent after the second dose of Comirnaty. Previous SARS-CoV-2 infection was associated with systemic effects after the first dose. Age, female sex, previous COVID-19, previous isolation due to COVID-19 contact, and CCI showed to be independent predictors of the degree of functional limitation after the 1st dose of Comirnaty®. After the 2nd dose, the degree of functional limitation was lower in those who previously had SARS-CoV-2 infection.

Propuesta de un índice que resume las medidas preventivas no farmacológicas adoptadas frente al SARS-CoV-2 en las empresas: el caso del Parc de Salut Mar (Barcelona) / A proposal for a summary index of nonpharmacological preventive measures adopted against SARS-CoV-2 in companies: the case of Parc de Salut Mar (Barcelona)

Introducción: Proponer la construcción de un índice numérico con las medidas preventivas no farmacológicas frente a SARS-CoV-2 a partir de la experiencia de una institución sanita-ria en Barcelona, el Parc de Salut Mar (PSMar).Método: La construcción del índice se ha realizado en tres fases. La identificación y selec-ción de las variables a incluir a partir de entrevistas semiestructuradas a informantes clave y la revisión documental. La definición de las dimensiones (constituidas a partir de una o más variables) y, finalmente la operatividad del índice a partir de dichas dimensiones. Se ha estimado el índice en el PSMar, y en sus dos principales centros, el Hospital del Mar y el Hospital de la Esperanza.Resultados: Se identificaron y categorizaron 21 variables, clasificadas en 5 dimensiones: equipos de protección individual, medidas organizativas individuales, medidas organizati-vas colectivas, medidas de vigilancia epidemiológica y actividades formativas. Además, De forma complementaria se añadió si existía un protocolo de actuación. Durante la primera ola, el índice en el Hospital del Mar se mantuvo por encima del valor obtenido en el Hos-pital de la Esperanza, mientras que en la segunda ola ambos índices presentaron valores similares hasta la semana 36, cuando el del hospital del Mar comenzó a presentar valores superiores. Estas oscilaciones se debieron principalmente a las dimensiones equipos de protección individual y actividades formativas.Conclusiones: El índice propuesto pone de manifiesto las dificultades para aplicar las diver-sas medidas preventivas no farmacológicas en las primeras semanas de la pandemia. Esta herramienta puede ser útil para evaluar las actividades desarrolladas frente a la pandemia por parte de los Servicios de Prevención de Riesgos Laborales, con las oportunas adapta-ciones a la realidad de cada empresa (AU)

Introduction: We propose the construction of a numerical index of nonpharmacological preventive measures against SARS-CoV-2 based on the experience of Parc de Salut Mar (PSMar), a healthcare institution in Barcelona.Method: The construction of the index was carried out in three phases. First, we identified and selected the variables to be included based on semi-structured interviews with key in-formants and a review of relevant documents. Second, we defined the dimensions (consist-ing of one or more variables) and, as a final step, operationalised the index based on these dimensions. The index was then applied to generate estimates for the PSMar, and in its two main centres, the Hospital del Mar and the Hospital de la Esperanza.Results: Twenty-one variables were identified and categorised into five dimensions: person-al protective equipment, individual organisational measures, collective organisational mea-sures, epidemiological surveillance measures, and training activities. We also developed an action protocol. During the first SARS-CoV-2 wave, the index at the Hospital del Mar re-mained above that estimated for the Hospital de la Esperanza, whereas in the second wave both indices showed similar values until week 36, when the Hospital del Mar index began o show higher values. These oscillations were mainly due to the dimensions of personal protective equipment and training activities.Conclusions: The proposed index identified the difficulties in implementing the various non-pharmacological preventive measures during the first weeks of the pandemic. This tool can be useful for evaluating the activities carried out by the occupational risk prevention services during the pandemic, followed by appropriate adaptations to the realities of each individual company (AU)

El problema de la multi-resistencia en bacilos gram-negativos en las unidades de cuidados intensivos: estrategias de tratamiento y prevención / The problem of multi-resistance in gram-negative bacilli in intensive care units: Treatment and prevention strategies

El aumento global de infecciones causadas por bacilos gram-negativos multi-resistentes (BGN-MR), lo cual incluye a los carbapenemes, supone uno de los grandes retos actuales en materia de sanidad. Esto incluye Enterobacterales productores de β-lactamasas de espectro extendido, productoras de AmpC desreprimida o Enterobacterales productores de carbapenemasas, así como BGN-MR no fermentadores como Pseudomonas aeruginosa o Acinetobacter baumannii. En Pseudomonas aeruginosa predominan otros mecanismos de resistencias diferentes a las β-lactamasas tales como bombas de expulsión o pérdida de porinas. A. baumannii presenta con frecuencia varios de estos mecanismos de resistencia. La mortalidad es elevada especialmente si el tratamiento empírico es inadecuado. En este capítulo se revisan las estrategias de tratamiento haciendo hincapié en las herramientas para identificar los pacientes en los que estaría justificado tratamiento antibiótico empírico para cubrir BGN-MR, la importancia de la optimización de la administración de estos antibióticos, así como las estrategias de prevención para evitar su diseminación desde pacientes colonizados o infectados por un BGN-MR (AU)

The rise of infections caused by multi-resistant gram-negative bacilli (MR-GNB), which includes carbapenems, represents one of the major current challenges worldwide. These MR-GNB include extended spectrum β-lactamase-producing Enterobacterales, derepressed AmpC-producing or carbapenemase-producing Enterobacterales as well as non-fermenting Gram-negative bacilli such as Pseudomonas aeruginosa or Acinetobacter baumannii. P. aeruginosa predominantly exhibits other resistance mechanisms different to β-lactamases such as expulsion pumps or loss of porins. A. baumannii frequently presents several of these resistance mechanisms. Mortality is high especially if empirical treatment is inadequate. In this review, treatment strategies are revised, describing the tools available to identify patients in whom empirical antibiotic treatment would be justified to cover MR-GNB, the importance of optimizing the administration of these antibiotics, as well as prevention strategies to avoid its spread from patients colonized or infected by a MR-GNB (AU)

The problem of multi-resistance in gram-negative bacilli in intensive care units: Treatment and prevention strategies.

The rise of infections caused by multi-resistant gram-negative bacilli (MR-GNB), which includes carbapenems, represents one of the major current challenges worldwide. These MR-GNB include extended spectrum ß-lactamase-producing Enterobacterales, derepressed AmpC-producing or carbapenemase-producing Enterobacterales as well as non-fermenting Gram-negative bacilli such as Pseudomonas aeruginosa or Acinetobacter baumannii. P. aeruginosa predominantly exhibits other resistance mechanisms different to ß-lactamases such as expulsion pumps or loss of porins. A. baumannii frequently presents several of these resistance mechanisms. Mortality is high especially if empirical treatment is inadequate. In this review, treatment strategies are revised, describing the tools available to identify patients in whom empirical antibiotic treatment would be justified to cover MR-GNB, the importance of optimizing the administration of these antibiotics, as well as prevention strategies to avoid its spread from patients colonized or infected by a MR-GNB.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

OBJECTIVE: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DESIGN: Prospective descriptive multicenter cohort study. SETTING: 26 Intensive care units (ICU) from Andalusian region in Spain. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. RESULTS: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. CONCLUSION: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study / Factores predictivos de la mortalidad a las seis semanas en pacientes críticos con SARS-CoV-2: estudio multicéntrico prospectivo

Objective: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. Design: Prospective descriptive multicenter cohort study. Setting: 26 Intensive care units (ICU) from Andalusian region in Spain. Patients or participants: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. Interventions: None. Variables: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. Results: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. Conclusion: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor (AU)

Objetivo: Identificar los factores de riesgo asociados con la mortalidad a las seis semanas. Diseño: Estudio prospectivo multicéntrico. Ámbito: Se incluyeron a 26 pacientes de la Unidad de Cuidados Intensivos (UCI) de Andalucía. Pacientes o participantes: Pacientes ingresados en UCI por neumonía grave por SARS-CoV-2 del 8 de marzo al 30 de mayo de 2020. Intervenciones: Ninguna. Variables de interés principales: Características demográficas, clínicas y escalas de gravedad. Se analizaron tratamientos de soporte, fármacos y la mortalidad. Resultados: Se incluyeron 495 pacientes, 73 fueron excluidos por incompletos y 422 pacientes se incorporaron en el análisis final. La mediana de edad fue de 63 años, 305 (72,3%) eran hombres. La mortalidad en la UCI fue: 144/422 34%; mortalidad a los 14 días: 81/422 (19,2%); mortalidad a los 28 días: 121/422 (28,7%); mortalidad a las seis semanas 152/422 36,5%. Los factores asociados con la mortalidad a los 42 días fueron la edad, APACHE II, SOFA > 6 y LDH al ingreso > 470 U/L, uso de vasopresores, necesidad de técnicas de reemplazo de la función renal, porcentaje de linfocitos a las 72 horas del ingreso en UCI < 6,5%, y trombocitopenia, mientras que el uso de lopinavir/ritonavir fue identificado como un factor protector. Conclusiones: La edad, gravedad y fracaso orgánico junto con la necesidad de terapias de soporte fueron identificadas como factores predictores de mortalidad a las seis semanas. La administración de corticoesteroides a dosis altas no mostró beneficios en la mortalidad, al igual que el tratamiento con tocilizumab, lopinavir/ritonavir se identificaron como un factor protector (AU)

Destino de los artículos rechazados en Medicina Intensiva en el período 2015-2017 / Fate of rejected manuscripts in the journal Medicina Intensiva during 2015-2017 period

Objetivo Conocer el destino de los trabajos rechazados en Medicina Intensiva (MI) en el período del 2015 al 2017 con seguimiento hasta el 2019. Diseño Estudio retrospectivo observacional. Ámbito Publicaciones en revistas biomédicas. Participantes Manuscritos rechazados en la revista Medicina Intensiva. Intervenciones Ninguna Variables de interés Tiempo de publicación, factor de impacto (FI), citas generadas y variables asociadas con la publicación. Resultados De 344 originales y 263 cartas científicas, se rechazaron 420 (69,2%). Se publicaron después 205 (48,8%) y 66 de ellos generaron 180 citas. El FI de las revistas fue menor en 173 casos (84,4%). En 21, el número de citas válidas para FI fue mayor que el FI de MI. El origen del manuscrito odds ratio (OR) 2,11 (IC 95% 1,29 a 3,46), la mujer como autora OR 1,58 (IC 95% 1,03 a 2,44), que estuviera en lengua inglesa OR 2,38 (IC 95% 1,41 a 4,0) y que el artículo hubiera pasado a revisores OR 1,71 (IC 95% 1,10 a 2,66) se asociaron con mayor tasa de publicación en revistas indexadas en PubMed. Conclusiones Los artículos rechazados en MI tienen una tasa media de publicación en otras revistas, principalmente con menos FI y generando menor número de citas que el FI de MI. (AU)

Objective To know the fate of the rejected manuscripts in Medicina Intensiva journal (MI) from 2015 to 2017 with surveillance until 2019. Design Retrospective observational study. Setting Biomedical journals publication. Participants Rejected manuscripts in MI journal. Interventions None. Main variables of interest Time of publication, impact factor (IF), generated citations and variables associated to publication. Results The 69% (420) of analyzed articles (344 originals and 263 scientific letters) were rejected, and 205 (48.8%) were subsequently published, with 180 citations of 66 articles. Journal IF was lower in 173 (84.4%) articles. The number of FI-valid citations was higher than the FI of MI in 21 articles. Origin of manuscript OR 2,11 (IC 95% 1.29 – 3.46), female author OR 1.58 (IC 95% 1.03-2.44), english language OR 2,38 (IC 95% 1.41-4.0) and reviewed papers OR 1.71 (IC 95% 1.10-2.66) were associated to publication in PubMed database. Conclusions The rejected articles in MI have a mean publication rate in other journals. Most of these articles are published in journals with less IF and fewer citations than the IF of MI. (AU)

Fate of rejected manuscripts in the journal Medicina Intensiva during 2015-2017 period.

OBJECTIVE: To know the fate of the rejected manuscripts in Medicina Intensiva journal (MI) from 2015 to 2017 with surveillance until 2019. DESIGN: Retrospective observational study. SETTING: Biomedical journals publication. PARTICIPANTS: Rejected manuscripts in MI journal. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Time of publication, impact factor (IF), generated citations and variables associated to publication. RESULTS: The 69% (420) of analyzed articles (344 originals and 263 scientific letters) were rejected, and 205 (48.8%) were subsequently published, with 180 citations of 66 articles. Journal IF was lower in 173 (84.4%) articles. The number of FI-valid citations was higher than the FI of MI in 21 articles. Origin of manuscript OR 2,11 (IC 95% 1.29-3.46), female author OR 1.58 (IC 95% 1.03-2.44), english language OR 2,38 (IC 95% 1.41-4.0) and reviewed papers OR 1.71 (IC 95% 1.10-2.66) were associated to publication in PubMed database. CONCLUSIONS: The rejected articles in MI have a mean publication rate in other journals. Most of these articles are published in journals with less IF and fewer citations than the IF of MI.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

OBJECTIVE: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DESIGN: Prospective descriptive multicenter cohort study. SETTING: 26 Intensive care units (ICU) from Andalusian region in Spain. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. RESULTS: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. CONCLUSION: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

Fate of rejected manuscripts in the journal Medicina Intensiva during 2015-2017 period. / Destino de los artículos rechazados en Medicina Intensiva en el período 2015-2017.

OBJECTIVE: To know the fate of the rejected manuscripts in Medicina Intensiva journal (MI) from 2015 to 2017 with surveillance until 2019. DESIGN: Retrospective observational study. SETTING: Biomedical journals publication. PARTICIPANTS: Rejected manuscripts in MI journal. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Time of publication, impact factor (IF), generated citations and variables associated to publication. RESULTS: The 69% (420) of analyzed articles (344 originals and 263 scientific letters) were rejected, and 205 (48.8%) were subsequently published, with 180 citations of 66 articles. Journal IF was lower in 173 (84.4%) articles. The number of FI-valid citations was higher than the FI of MI in 21 articles. Origin of manuscript OR 2,11 (IC 95% 1.29 - 3.46), female author OR 1.58 (IC 95% 1.03-2.44), english language OR 2,38 (IC 95% 1.41-4.0) and reviewed papers OR 1.71 (IC 95% 1.10-2.66) were associated to publication in PubMed database. CONCLUSIONS: The rejected articles in MI have a mean publication rate in other journals. Most of these articles are published in journals with less IF and fewer citations than the IF of MI.

The Practice of Paediatric Radiation Oncology in Low- and Middle-income Countries: Outcomes of an International Atomic Energy Agency Study.

AIMS: Childhood cancer survival is suboptimal in most low- and middle-income countries (LMICs). Radiotherapy plays a significant role in the standard care of many patients. To assess the current status of paediatric radiotherapy, the International Atomic Energy Agency (IAEA) undertook a global survey and a review of practice in eight leading treatment centres in middle-income countries (MICs) under Coordinated Research Project E3.30.31; 'Paediatric radiation oncology practice in low and middle income countries: a patterns-of-care study by the International Atomic Energy Agency.' MATERIALS AND METHODS: A survey of paediatric radiotherapy practices was distributed to 189 centres worldwide. Eight leading radiotherapy centres in MICs treating a significant number of children were selected and developed a database of individual patients treated in their centres comprising 46 variables related to radiotherapy technique. RESULTS: Data were received from 134 radiotherapy centres in 42 countries. The percentage of children treated with curative intent fell sequentially from high-income countries (HICs; 82%) to low-income countries (53%). Increasing deficiencies were identified in diagnostic imaging, radiation staff numbers, radiotherapy technology and supportive care. More than 92.3% of centres in HICs practice multidisciplinary tumour board decision making, whereas only 65.5% of centres in LMICs use this process. Clinical guidelines were used in most centres. Practice in the eight specialist centres in MICs approximated more closely to that in HICs, but only 52% of patients were treated according to national/international protocols whereas institution-based protocols were used in 41%. CONCLUSIONS: Quality levels in paediatric radiotherapy differ among countries but also between centres within countries. In many LMICs, resources are scarce, coordination with paediatric oncology is poor or non-existent and access to supportive care is limited. Multidisciplinary treatment planning enhances care and development may represent an area where external partners can help. Commitment to the use of protocols is evident, but current international guidelines may lack relevance; the development of resources that reflect the capacity and needs of LMICs is required. In some LMICs, there are already leading centres experienced in paediatric radiotherapy where patient care approximates to that in HICs. These centres have the potential to drive improvements in service, training, mentorship and research in their regions and ultimately to improve the care and outcomes for paediatric cancer patients.

Adequate antibiotic monitoring to improve what needs to be improved / Monitorización adecuada de antibióticos para mejorar lo que necesita mejorarse

No disponible

Impact of the mechanical hyperkeratotic lesions and its association with quality of life: An observational case-control study.

BACKGROUND: Mechanical hyperkeratotic lesions (MHL) are common condition amongst population of all ages. Such problems may be associated with pain, reduction in mobility, changes of gait and risk of falls and is believed to affect the quality of life (QoL), general health and optimal foot health. OBJECTIVE: The main aim of this study was to describe and compare both foot and general health-related QoL in two groups of participants: (i) with MHL and (ii) healthy controls. METHOD: A total sample of 150 patients, mean age 49.50 ± 36.50 years, was recruited from an outpatient clinic. Demographic data, medical history and clinical characteristics of overall health were determined, and the obtained values were compared by the Foot Health Status Questionnaire (FHSQ). RESULTS: The FHSQ scores of the sample with MHL showed lower scores than control subjects in sections one and two for footwear, general and foot health, foot pain, foot function and physical activity (P < 0.01), but not for social capacity and vigour (P > 0.01). CONCLUSIONS: People with MHL showed a decrease in QoL, based on FHSQ scores, regardless of gender.

Pneumonia in mechanically ventilated patients: no diagnostic and prognostic value of different quantitative tracheal aspirates thresholds.

BACKGROUND: Diagnosis of pneumonia in ventilated patients is challenging due to the lack of specific and definitive clinical symptoms, laboratory data or radiological abnormalities. METHODS: Based on quantitative tracheal aspirate (QTA) results, three groups of patients were compared: <105 cfu/ml, ≥105 cfu/ml and <106 cfu/ml, and ≥106 cfu/ml. We recorded demographic variables, underlying diseases and severity of illness at ICU admission. On the day of pneumonia diagnosis, we registered temperature, leukocyte count, C-reactive protein, Sequential Organ Failure Assessment (SOFA) score, clinical pulmonary infection score (CPIS) and adequacy of empirical antimicrobial therapy. RESULTS: In 231 episodes, clinical presentation, laboratory data, severity of illness, CPIS, the presence of bacteremia and radiological score did not differ among the three groups. ICU and hospital mortalities were also similar in the three groups. Factors independently associated with in-hospital mortality were age, SOFA score and inappropriate antimicrobial therapy. The bacterial burden in the QTA was not included in the model. CONCLUSIONS: Quantification of tracheal aspirate samples may not be necessary in ventilated patients clinically suspected of having nosocomial pneumonia.

Corticoids synergize with IL-1 in the induction of LCN2.

OBJECTIVE: Lipocalin-2 (LCN2) is an adipokine that was first identified in neutrophil granules. In the last years it was recognized as a factor that could impair chondrocyte phenotype, cartilage homeostasis as well as growth plate development. Both pro-inflammatory cytokines and glucocorticoids (GCs) modulate LCN2 expression. Actually, GCs were found to be LCN2 inducers, suggesting that part of the negative actions exerted by these anti-inflammatory drugs at cartilage level could be mediated by this adipokine. So, in this study we wanted to investigate whether corticoids were able to act in synergy with IL-1 in the induction of LCN2 and the signaling pathway involved in this process. MATERIALS AND METHODS: For the realization of this work, ATDC5 mouse chondrogenic cell line was used. We determined the mRNA and protein expression of LCN2 by real-time reverse transcription-polymerase chain reaction (RT-qPCR) and western blot respectively, after GC or mineralcorticoid treatment. Different signaling pathways inhibitors were also used. RESULTS: GC and mineralcorticoid were able to induce the expression of LCN2 in ATDC5 cells. Interestingly, both corticoids synergized with IL-1 in the induction of LCN2. The effect of these corticoids on the expression of LCN2 occurred through GC or mineralcorticoid receptors and the kinases PI3K, ERK1/2 and JAK2. CONCLUSIONS: Prolonged use of corticoids may have detrimental effects on cartilage homeostasis. Based on our results, we conclude that corticoids could increase the negative actions exerted by IL-1 by increasing the expression of LCN2.