Clinical risk factors in patients with interstitial lung disease associated with anti-MDA5 autoantibodies / Factores de riesgo clínicos en pacientes con enfermedad pulmonar intersticial con anticuerpos anti-MDA5

Introduction The anti-MDA5-associated autoimmune disease represents a poorly understood entity. The study's objectives were to describe a cohort of interstitial lung disease (ILD) patients who were positive for anti-MDA5 autoantibody and identify clinical risk factors associated with survival. Methods This single-center cohort study included ILD patients positive for anti-MDA5 autoantibody. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. Results Fifty-three ILD-MDA5 positive patients were included; twelve died during follow-up due to rapidly progressive interstitial lung disease (RP-ILD). Dermatological signs of anti-MDA5 (Gottron papules, Gottron sign, palmar papules, V-neck sign, facial dermatomyositis rashes, and skin ulcers) were strongly associated with death secondary to RP-ILD (HR: 3.7, 95% CI: 1.02–13.35). Patients with dermatological signs were younger, had higher anti-MDA5 autoantibodies titers, more frequent inflammatory patterns in HRCT evaluation, and less fibrosis extent in HRCT. Conclusion Dermatological manifestation in ILD patients to anti-MDA5 autoantibodies are associated with RP-ILD and short-term fatal outcomes. Dermatological signs may identify a subgroup of ILD-positive to anti-MDA5 patients with a high risk of RP-ILD (AU)

Introducción La enfermedad autoinmune asociada a los anticuerpos anti-MDA5 es una entidad poco estudiada. Los objetivos de este estudio son describir una cohorte de sujetos con enfermedad pulmonar intersticial (EPI) positivos al anticuerpo anti-MDA5 e identificar los factores clínicos de riesgo asociados con la supervivencia. Métodos Estudio de cohorte de un solo centro de pacientes con EPI y positivos al anticuerpo anti-MDA5. Se registraron las características clínicas basales y se realizó un análisis de supervivencia para identificar los factores de riesgo asociados con la supervivencia. Resultados Se incluyeron 53 pacientes con EPI y positivos a anti-MDA5; 12 pacientes fallecieron por una enfermedad intersticial rápidamente progresiva (EPI-RP). Los signos dermatológicos asociados a anti-MDA5 (pápulas de Gottron, signo de Gottron, pápulas palmares, signo de la V del escote, eritema facial de dermatomiositis y úlceras cutáneas) se asociaron fuertemente con la EPI-RP (HR: 3,7, IC 95%: 1,02-13,35). Los pacientes con manifestaciones dermatológicas eran más jóvenes, tenían mayores títulos de anticuerpos anti-MDA5, tenían mayor frecuencia de patrones inflamatorios en la tomografía de tórax de alta resolución y menor extensión de la fibrosis en la TCAR. Conclusión Las manifestaciones dermatológicas en los pacientes con EPI positivos a anticuerpos anti-MDA5 están asociados a EPI-RP y a desenlaces fatales al corto plazo. Los signos dermatológicos pueden identificar un subgrupo de pacientes positivos a anti-MDA5 con mayor riesgo de EPI-RP (AU)

Timing of umbilical cord occlusion, delayed vs early, in preterm babies: A randomized controlled trial (CODE-P Trial).

INTRODUCTION: Our hypothesis was that delayed cord clamping (DCC) (not earlier than 30 s; at 30-60 s) in premature neonates (born between 26.0 and 32.6 weeks of gestation), as compared with the usual early cord clamping (ECC), significantly reduces the need for blood transfusions and incidence of intraventricular haemorrhage (IVH) without an increased rate of maternal postpartum haemorrhage. MATERIAL AND METHODS: A prospective, open-label, randomized, controlled trial was conducted at Vall d'Hebron Hospital from July 2014 to December 2018. All pregnant women at risk of impending preterm birth (≥26.0-<33.0 weeks of gestation) who were admitted to the obstetrics emergency department were evaluated for eligibility. If they met the eligibility criteria, they were invited to participate in the study and, if they agreed, they signed an informed consent. Patients were randomly assigned to one of two groups: ECC group and DCC group. RESULTS: Our study included a total of 57 patients: 30 in the ECC group and 27 in the DCC group. Due to a lack of funding and low recruitment rates, the study was discontinued in 2018. Maternal characteristics and obstetric outcomes were similar between both groups. The intention-to-treat analysis did not reveal any differences between groups for neonatal red blood cell transfusions, neonatal IVH or maternal postpartum haemorrhage. There were no differences for secondary outcomes. Similarly, no differences were observed in the as-treated analysis. CONCLUSION: The primary and secondary outcomes of our study were not achieved. Therefore, more meta-analysis and trials are needed to evaluate the appropriate timing of cord clamping in preterm birth.

Clinical risk factors in patients with interstitial lung disease associated with anti-MDA5 autoantibodies.

INTRODUCTION: The anti-MDA5-associated autoimmune disease represents a poorly understood entity. The study's objectives were to describe a cohort of interstitial lung disease (ILD) patients who were positive for anti-MDA5 autoantibody and identify clinical risk factors associated with survival. METHODS: This single-center cohort study included ILD patients positive for anti-MDA5 autoantibody. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. RESULTS: Fifty-three ILD-MDA5 positive patients were included; twelve died during follow-up due to rapidly progressive interstitial lung disease (RP-ILD). Dermatological signs of anti-MDA5 (Gottron papules, Gottron sign, palmar papules, V-neck sign, facial dermatomyositis rashes, and skin ulcers) were strongly associated with death secondary to RP-ILD (HR: 3.7, 95% CI: 1.02-13.35). Patients with dermatological signs were younger, had higher anti-MDA5 autoantibodies titers, more frequent inflammatory patterns in HRCT evaluation, and less fibrosis extent in HRCT. CONCLUSION: Dermatological manifestation in ILD patients to anti-MDA5 autoantibodies are associated with RP-ILD and short-term fatal outcomes. Dermatological signs may identify a subgroup of ILD-positive to anti-MDA5 patients with a high risk of RP-ILD.

Interstitial lung disease progression in patients with anti-aminoacyl transfer-RNA-synthetase autoantibodies is characterized by higher levels of sCD163.

BACKGROUND: Patients with anti-tRNA autoantibodies are characterized by arthritis, mechanic´s hands, fever, Raynaud´s phenomenon, and interstitial lung disease (ILD), in at least two clinical scenarios: the antisynthetase syndrome (ASSD) and interstitial pneumonia with autoimmune features (IPAF). The anti-tRNA-ILD treatment is centered on the administration of corticosteroids and a wide variety of immunosuppressive drugs; however, the effectiveness of the treatment depends on factors not fully understood. This research work aimed to quantify the serum levels of two molecules related to pulmonary fibrosis and explore their relationship with the progression of ILD associated with ASSD METHODOLOGY: Serum levels of sCD163 and TGF-ß1 from baseline and after six months of treatment of ILD patients' positives to anti-tRNA were included in the current study. At six months, patients were classified as with or without ILD progression RESULTS: Forty patients were included (anti-Jo1, anti-PL7, anti-PL12, and anti-Ej). Five patients (12.5%) had ILD progression and were characterized by higher levels of sCD163 at baseline. Baseline sCD163 serum levels showed good discriminatory capacity in patients with ILD progression. On the other hand, at follow-up, serum TGF-ß1 levels significantly increased in both patients' groups, with and without progression CONCLUSION: Basal levels of sCD163 were higher in patients who later developed ILD progression and kinetics of both molecules suggests the participation of M2 macrophages in the development of ILD.

Enhanced Activity of NLRP3 Inflammasome in the Lung of Patients with Anti-Synthetase Syndrome.

Anti-synthetase syndrome (ASSD) is an autoimmune disorder characterized by inflammatory interstitial lung disease (ILD). The main objective of this work was to quantify the concentrations of cytokines and molecules associated with inflammasome activation in bronchoalveolar lavage (BAL) of patients with ASSD and a comparison group of systemic sclerosis (SSc) patients. Cytokines and lactate dehydrogenase (LDH) were determined using the concentrated BAL protein. The activity of caspase-1 and concentration of NLRP3 with the protein purified from the cell pellet in each group of patients. We found higher caspase-1 levels in ASSD vs. SSc, 1.25 RFU vs. 0.75 RFU p = 0.003, and LDH levels at 0.15 OD vs. 0.09 OD p < 0.001. A significant difference was observed in molecules associated with inflammasome activation, IL-18: 1.42 pg/mL vs. 0.87 pg/mL p = 0.02 and IFN-γ: 0.9 pg/mL vs. 0.86 pg/mL, p = 0.01. A positive correlation was found between caspase-1 and LDH in the patients with ASSD Rho 0.58 (p = 0.008) but not in the SSc group. In patients with ASSD, greater caspase-1 and higher LDH activity were observed in BAL, suggesting cell death due to pyroptosis and activation of the inflammasome pathway.

MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression.

BACKGROUND: The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. METHODS: Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline. RESULTS: Out of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. CONCLUSION: In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.

Single Nucleotide Polymorphism in the IL17A Gene Is Associated with Interstitial Lung Disease Positive to Anti-Jo1 Antisynthetase Autoantibodies.

Antisynthetase syndrome (ASSD) is a rare multisystemic connective tissue disease affecting the skin, joints, muscles, and lungs, characterized by anti-aminoacyl transfer-RNA-synthetases (anti-tRNA) autoantibodies production, being anti-Jo1 the most frequent. We included one-hundred twenty-one ASSD patients and 340 healthy subjects (HS), and also, we divided the case group into anti-Jo1 and non-anti-Jo1. Two single nucleotide polymorphisms (SNPs) in the IL17A gene were evaluated. Anti-Jo1 was the most common anti-tRNA antibody in our cohort, and the most frequent tomographic pattern was non-specific interstitial pneumonia (NSIP). Anti-Jo1 ASSD patients had higher levels of creatine phosphokinase than the non-anti-Jo1 group. Significant differences in genotype frequencies with rs8193036/CC between anti-Jo1 vs. non-anti-Jo1 ASSD patients (p < 0.001), maintaining the association after Bonferroni correction (p = 0.002). Additionally, in the anti-Jo1 group vs. HS comparison, we found a statistically significant difference with the same SNP (p = 0.018, OR = 2.91, 95% CI = 1.15-7.35), maintaining the association after Bonferroni correction (p = 0.036). The rs8193036/CC genotype in IL17A is associated with ASSD patients with anti-Jo1. Also, anti-Jo1 and non-anti-Jo1 patients display differences in genotype frequencies.

Methotrexate and rheumatoid arthritis associated interstitial lung disease.

QUESTION ADDRESSED BY THE STUDY: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD. METHODS: Through a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. RESULTS: Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001). ANSWER TO THE QUESTION: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.

Genetic Susceptibility to Antisynthetase Syndrome Associated With Single-Nucleotide Variants in the IL1B Gene That Lead Variation in IL-1ß Serum Levels.

The antisynthetase syndrome (ASSD) is an autoimmune disorder characterized by myositis, arthritis, mechanic's hands, fever, Raynaud phenomenon, and interstitial lung disease (ILD). We aimed to evaluate single-nucleotide polymorphisms in the interleukin 1B (IL1B) gene and their association between ILD with antisynthetase autoantibodies, as well as IL-1ß serum levels. The most frequent antisynthetase autoantibody was anti-Jo1. The most frequent tomographic pattern was non-specific interstitial pneumonia, whereas in the anti-Jo1 subjects, it was organized pneumonia. Anti-Jo1 patients tend to have more significant arthritis, and Raynaud phenomenon have higher levels of creatinine phosphokinase. In the IL1B gene, the GG genotype and G allele of rs1143634 [odds ratio (OR) = 2.21 and OR = 2.60, respectively, p < 0.05] are associated with an increased risk, as well as with the dominant and recessive models (p < 0.05). This finding is maintained after logistic regression analysis adjusting for potential confounding variables (p < 0.05). Subjects with the rs16944/AG heterozygous genotype had higher serum levels of IL-1ß compared to homozygous (p < 0.05). In conclusion, rs1143634 is associated with a higher risk of ASSD. Also, the GA genotype is associated with higher levels of IL-1ß in ASSD patients.

Anti-Aminoacyl Transfer-RNA-Synthetases (Anti-tRNA) Autoantibodies Associated with Interstitial Lung Disease: Pulmonary Disease Progression has a Persistent Elevation of the Th17 Cytokine Profile.

Anti-tRNA autoantibodies are associated with interstitial lung disease (ILD), in at least two clinical scenarios: the anti-synthetase syndrome (ASSD) and interstitial pneumonia with autoimmune features (IPAF). Under pathological conditions, cytokines indicate the participating elements and the course of inflammatory phenomena. We aimed to quantify serum concentrations of different inflammatory cytokines profiles in patients with anti-tRNA associated ILD (anti-tRNA-ILD) and estimate the association between these and ILD improvement and progression. Serum levels of 18 cytokines from baseline and after six months of treatment of ILD patients' positives to anti-tRNA were included in the current study. At six months, patients were classified as with or without ILD progression. A total of 39 patients were included (10 anti-Jo1, eight anti-PL7, 11 anti-PL12, and 10 anti-Ej). Three patients (7.6%) had ILD progression (progressors patients, PP) and showed statistically higher levels in IL-4, IL-10, IL-17A, IL-22, GM-CSF, IL-1ß, IL-6, IL-12, IL-18, and TNF-α, compared to patients without disease progression (no progressors patients, NPP). IL-17A, IL-1ß, and IL-6 (T-helper-lymphocyte (Th)17 inflammatory cytokine profile) were elevated and had a high discriminatory capacity in distinguishing ILD PP of those NPP at follow-up. Overall, there is an association between the cytokines of the Th17 inflammatory profile and the ASSD progression.

MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease.

BACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10-17). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10-35) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10-49). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10-5), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10-6). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.).

El mito de Sísifo y la vigilancia de la salud / El mite de Sísif i la vigilància de la salut / No disponible

No disponible

La vigilancia de la salud y la valoración de la aptitud para trabajar: deconstruir, reconceptualizar y consensuar para mejorar / Health surveillance and fitness for duty: deconstruct, reconceptualize and finding consensus on how to improve

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¿Es posible mejorar la utilidad preventiva de la vigilancia de la salud de los trabajadores en el actual marco normativo? / Is it possible to improve the preventive usefulness of workers' health surveillance in the current regulatory framework? / És possible millorar la utilitat preventiva de la vigilància de la salut dels treballadors en l'actual marc normatiu?

Objetivo: Los exámenes de salud indiscriminados e inespecíficos para dar aparente cumplimiento a las obligaciones empresariales mediante un "listado de aptitudes" determinan la baja utilidad preventiva de nuestro sistema de vigilancia de la salud. Este estudio pretende realizar una interpretación técnica de la Ley de Prevención de riesgos laborales y proponer un nuevo marco conceptual que permita mejorar la vigilancia de la salud dentro de la normativa actual. Método: Mediante técnicas cualitativas de análisis del contenido se estudió el texto de la Ley, se identificaron los conceptos que dificultan el cumplimiento de los objetivos preventivos de la vigilancia de la salud, y se hizo una interpretación técnica, pero ajustada a normativa, para proponer un nuevo marco conceptual. Resultados: Este marco conceptual incluiría: diferenciar claramente vigilancia de la salud de examen de salud (uno de sus instrumentos) y de valoración de la aptitud para trabajar (concepto con entidad propia); reservar la obligatoriedad de la vigilancia para cuando sea «imprescindible» realizarla por la existencia de un riesgo sustancial para los trabajadores o terceros, incluyendo potenciales especialmente sensibles; y comunicar sus resultados mediante recomendaciones preventivas a la empresa, reservando los informes de aptitud para la vigilancia obligatoria y siempre en base a criterios de aptitud claros, preestablecidos y justificados en relación al riesgo. Conclusiones: El nuevo marco conceptual propuesto tiene cabida dentro de la Ley de Prevención de riesgos laborales y su puesta en práctica podría contribuir a mejorar la utilidad preventiva de la vigilancia de la salud sin necesidad de reformar la legislación

Objective: In Spain, the limited preventive usefulness of health surveillance is determined by the indiscriminate use of nonspecific «generic» health examinations aimed at producing a «fitness for work list», presumably allowing companies to comply with health and safety regulations. This study aimed to produce a technical interpretation of the Spanish Prevention of Risks at Work Act and propose a new conceptual framework to favour greater preventive usefulness of health surveillance within the current regulatory framework. Methods: Using qualitative techniques of content analysis, the text of the Law was studied, the key concepts that impeded the fulfilment of the preventive objectives of health surveillance were identified, and a technical interpretation adjusted to regulations was made in order to propose a new conceptual framework Results: This conceptual framework would include: clearly differentiating health surveillance from health examinations (one of its instruments) and from fitness for work evaluations (an independent concept in itself); restricting mandatory health surveillance to situations in which it is «imperative» to carry it out because of the existence of a substantial risk to workers or third parties, including potentially vulnerable workers; and communicating the results of health surveillance through preventive recommendations to the company, reserving fitness for duty certificates -always based on clear, pre-established and justified criteria in relation to risk- for mandatory surveillance. Conclusions: The proposed new conceptual framework falls within the scope of the Spanish Prevention of Risks at Work Act, and its implementation could contribute to improving the preventive usefulness of health surveillance without the need to reform the legislation

Objectiu: Els exàmens de salut indiscriminats i inespecífics perdonar aparent compliment a les obligacions empresarials mitjançant un "llistat d’aptituds" deter minen la baixa utilitat preventiva del nostre sistema de vigilància de la salut. Aquest estudi pretén realitzar una interpretació técnica de la Llei de Prevenció de riscos laborals i proposarun nou marc conceptual que permeti millorar la vigilància de la salut dins de la normativa actual. Métode: Mitjançant tècniques qualitatives d’anàlisi del contingut es va estudiar el text de la Llei, es van identificarels conceptes que dificulten el compliment de ls objectius preventius de la vigilància de la salut, i es va fer una interpretación tècnica, per ò ajustada a la normativa, per proposar un nou marc conceptual. Resultats: Aquest marc conceptual inclouria: diferenciar clarament vigilància de la salut d’examen de salut (un dels seus instruments) i de valoració de l’aptitud per a treballar (concepte amb entitat pròpia); reservar l'obligatoriet at de la vigilància per quan sigui "imprescindible" realitzarla per l’existència d’un risc substancial per als treballadorso tercers, incloent potencia ls especialmente sensibles; i comunicar els seus resultats mitjançant recomanacions preventives a l’empresa, reservant els informes d’aptitud per a la vigilància obligatòria i sempre en base a criteris d’aptitud clars , preestablerts i justificats en relació al risc. Conclusions :El nou marc conceptual propos at té cabuda dins de la Llei de Prevenció de riscos laborals, i la seva posada en pràctica podria contribuir a millorar la utilitat preventiva de la vigilància de la salut sense necessitat de reformar la legislación

[Is it possible to improve the preventive usefulness of workers' health surveillance in the current regulatory framework?] / ¿Es posible mejorar la utilidad preventiva de la vigilancia de la salud de los trabajadores en el actual marco normativo?

OBJECTIVE: In Spain, the limited preventive usefulness of health surveillance is determined by the indiscriminate use of nonspecific "generic" health examinations aimed at producing a "fitness for work list", presumably allowing companies to comply with health and safety regulations. This study aimed to produce a technical interpretation of the Spanish Prevention of Risks at Work Act and propose a new conceptual framework to favour greater preventive usefulness of health surveillance within the current regulatory framework. METHODS: Using qualitative techniques of content analysis, the text of the Law was studied, the key concepts that impeded the fulfilment of the preventive objectives of health surveillance were identified, and a technical interpretation adjusted to regulations was made in order to propose a new conceptual framework RESULTS: This conceptual framework would include: clearly differentiating health surveillance from health examinations (one of its instruments) and from fitness for work evaluations (an independent concept in itself); restricting mandatory health surveillance to situations in which it is "imperative" to carry it out because of the existence of a substantial risk to workers or third parties, including potentially vulnerable workers; and communicating the results of health surveillance through preventive recommendations to the company, reserving fitness for duty certificates -always based on clear, pre-established and justified criteria in relation to risk- for mandatory surveillance. CONCLUSIONS: The proposed new conceptual framework falls within the scope of the Spanish Prevention of Risks at Work Act, and its implementation could contribute to improving the preventive usefulness of health surveillance without the need to reform the legislation.

[Revision of carcinomas in paranasal sinuses]. / Revisión de los carcinomas de senos paranasales.

The annual incidence rate for paranasal sinus cancer is quite low in Europe at approximately 1 case a year per 100 000 inhabitants. The most frequent site is the maxillary sinus; in some countries such as Spain, however, carcinomas of the ethmoidal sinus complex are more prevalent. Squamous cell carcinoma is the most frequent histological type and adenocarcinoma is the one with the best prognosis. In general terms, the association of surgery and radiotherapy continues to be the optimal therapeutic option. The inclusion of an endoscopic endonasal approach for the treatment of these lesions must be considered in very selective cases. Most authors currently accept invasion of the fat and muscles of the orbital apex and infiltration of the conjunctiva and/or sclera as an absolute indication for orbital exenteration. Lymph node involvement at diagnosis or in the course of the disease is infrequent, so prophylactic lymph node treatment would therefore not be indicated.

Revisión de los carcinomas de senos paranasales / Revision of carcinomas in paranasal sinuses

Los carcinomas de senos paranasales presentan una incidencia baja, aproximadamente un caso al año cada 100.000 habitantes entre la población europea. La localización más frecuente es el seno maxilar, aunque en algunos países como España los carcinomas de etmoides son el grupo más numeroso. El tipo histológico más frecuente es el carcinoma escamoso, y el adenocarcinoma es la variante histológica con mejor pronóstico. En términos generales, la combinación de cirugía y radioterapia sigue siendo la modalidad terapéutica óptima. La inclusión del abordaje endonasal endoscópico en el tratamiento de estas lesiones debe considerarse en casos muy seleccionados. Actualmente, la mayoría de los autores acepta como indicaciones para llevar a cabo una exenteración orbitaria la invasión de la grasa, la musculatura y el ápex orbitario y la infiltración de la conjuntiva y/o esclerótica. La afección ganglionar en el momento del diagnóstico o durante el curso de la enfermedad es poco frecuente, lo que justificaría no tratar las cadenas ganglionares de manera profiláctica

The annual incidence rate for paranasal sinus cancer is quite low in Europe at approximately 1 case a year per 100 000 inhabitants. The most frequent site is the maxillary sinus; in some countries such as Spain, however, carcinomas of the ethmoidal sinus complex are more prevalent. Squamous cell carcinoma is the most frequent histological type and adenocarcinoma is the one with the best prognosis. In general terms, the association of surgery and radiotherapy continues to be the optimal therapeutic option. The inclusion of an endoscopic endonasal approach for the treatment of these lesions must be considered in very selective cases. Most authors currently accept invasion of the fat and muscles of the orbital apex and infiltration of the conjunctiva and/or sclera as an absolute indication for orbital exenteration. Lymph node involvement at diagnosis or in the course of the disease is infrequent, so prophylactic lymph node treatment would therefore not be indicated

Serum erythropoietin in the diagnosis of polycythemia vera. A follow-up study.

BACKGROUND AND OBJECTIVE: It has been suggested that the determination of serum erythropoietin (sEpo) may be useful in distinguishing between polycythemia vera (PV), relative polycythemia and secondary polycythemia (SP), but no conclusive evidence has yet been provided for this. In the present work, we evaluated the role of sEpo in the differential diagnosis of polycythemia vera and its usefulness in the follow-up of PV patients. METHODS: sEpo was assessed in 190 patients with polycythemia of different etiologies. A follow-up study was carried out in some of these patients (27 with secondary polycythemia and 17 with polycythemia vera). RESULTS: sEpo levels were higher in SP than in PV and relative polycythemia. There were, however, differences with regard to the various etiologies of SP. Polycythemia related to congenital heart disorders showed the highest levels of sEpo of the SP. When a study was conducted, sEpo alone as a diagnostic parameter displayed an efficiency of more than 90% and the most discriminating value was 5 U/L. Using lower levels (below 2 U/L) and higher levels (above 12 U/L), it was possible to distinguish between SP and PV, although an important overlap was detected between these limits (approximately 50% of cases). The follow-up study showed that in half the patients with SP the levels of sEpo were at times < 12 U/L and at other times greater than this value. At least three determinations were necessary to detect an elevated reading. In PV after venesection there was an increase in sEpo in some cases, although most of the time there was no change. INTERPRETATION AND CONCLUSIONS: Using sEpo, it was possible to differentiate between PV and SP, despite an important overlap. A follow-up study demonstrated that the increase in sEpo was intermittent in SP and that in many of these cases more than one determination could be helpful.