Screening criteria for interstitial lung disease associated to rheumatoid arthritis: Expert proposal based on Delphi methodology.

OBJECTIVE: To develop a joint proposal for screening criteria of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and vice versa, which serves as a guidelines in patient referral between the Rheumatology and Pneumology departments to early detection of these patients. METHODS: A systematic literature review was carried out on the risk factors for the development of ILD in RA patients, and for the referral criteria to Rheumatology for suspected early RA. Based on the available evidence, screening criteria were agreed using the Delphi method by a panel of pneumologists and rheumatologists with expertise in these pathologies. RESULTS: Screening criteria for ILD in patients with RA and for the early detection of RA in cases with ILD of unknown etiology have been developed. In both cases, a detection strategy was based on clinical risk factors. Recommendations also included the complementary tests to be carried out in the different clinical scenarios and on the periodicity that screening should be repeated. CONCLUSION: A selective screening strategy is recommended for the first time in the early diagnosis of patients with ILD-RA. This multidisciplinary proposal aims to solve some common clinical questions and help decision-making, although its usefulness to identify these patients with good sensitivity must be confirmed in a validation study.

Human Milk Antioxidative Modifications in Mastitis: Further Beneficial Effects of Cranberry Supplementation.

Mastitis is the inflammation of one or several mammal lobes which can be accompanied by a mammary gland infection, and is the leading cause of undesired early weaning in humans. However, little information exists regarding the changes that this disease may induce in the biochemical composition of human milk, especially in terms of oxidative status. Given that newborns are subject to a significant increase in total ROS burden in their transition to neonatal life and that their antioxidant defense system is not completely developed, the aim of this study was to evaluate antioxidant defense (glutathione peroxidase (GPx), reduced glutathione (GSH), total polyphenol content (TPP), and total antioxidant capacity (TAC)) in milk samples from mothers suffering from mastitis and controls. We also measured the oxidative damage to lipids (malondyaldehyde (MDA)) and proteins (carbonyl group content (CGC)) in these samples. Finally, we tested whether dietary supplementation with cranberries (a product rich in antioxidants) in these breastfeeding mothers during 21 days could improve the oxidative status of milk. GPx activity, TPP, and TAC were increased in milk samples from mastitis-affected women, providing a protective mechanism to the newborn drinking mastitis milk. MDA concentrations were diminished in the mastitis group, confirming this proposal. Some oxidative damage might occur in the mammary gland since the CGC was increased in mastitis milk. Cranberries supplementation seems to strengthen the antioxidant system, further improving the antioxidative state of milk.

How to Restart the Interventional Activity in the COVID-19 Era: The Experience of a Private Pain Unit in Spain.

INTRODUCTION: The situation generated in the health system by the COVID-19 pandemic has provoked a crisis involving the necessity to cancel non-urgent and oncologic activity in the operating room and in day-to-day practice. As the situation continues, the need to reinstate attention for patients with chronic pain grows. The restoration of this activity has to begin with on-site appointments and possible surgical procedures. On-site clinical activity has to guarantee the safety of patients and health workers. OBJECTIVES: The objective of this review was to evaluate how to manage activity in pain units, considering the scenario generated by the pandemic and the implications of chronic pain on the immune system and proposed pharmacological and interventional therapies. METHODS: Besides the established general recommendations (physical distance, surgical masks, gloves, etc.), we established specific recommendations that will allow patient treatment and relieve the disruption of the immune response. It is important to highlight the use of opioids with the least influence in the immune system. Further, individualized corticoid use, risk assessment, reduced immune suppression, and dose adjustment should take patient needs into account. In this scenario, we highlight the use of radiofrequency and neuromodulation therapies, techniques that do not interfere with the immune response. CONCLUSIONS: We describe procedures to implement these recommendations for individual clinical situations, the therapeutic possibilities and safety guidelines for each center, and government recommendations during the COVID-19 pandemic.

Implementation of a Computerized Decision Support System for Computed Tomography Scan Requests for Nontraumatic Headache in the Emergency Department.

BACKGROUND: Nontraumatic headache is a frequent complaint in the emergency department (ED). Cranial computed tomography (CT) is a widely available test for the diagnostic work-up, despite the risk of exposure to ionizing radiation. OBJECTIVES: We sought to develop and evaluate a cranial CT request computerized decision support system (CDSS) for adults with their first presentation of unusual severe nontraumatic headache in the ED. METHODS: Electronic database searches identified clinical decision and prediction rules and studies delineating risk factors in nontraumatic headache. A long list of risk factors extracted from these articles was reduced by a 30-member multidisciplinary expert panel (radiologists, emergency physicians, methodologists), using a 90% agreement threshold. This shortlist was used to develop the algorithm for the cranial CT request CDSS, which was implemented in March 2016. Impact evaluation compared CT scan frequency and diagnostic yield of pathologic findings before (March-August 2015) and after (March-August 2016) implementation. RESULTS: From the 10 selected studies, 10 risk factors were shortlisted to activate a request for cranial CT. Before implementation, 377 cranial CTs were ordered (15.3% of 2469 CT scans) compared with 244 after (9.5% of 2561 CT scans; pre-post difference 5.74%; 95% confidence interval [CI] 3.92-7.56%; p < 0.001), corresponding to a 37.6% relative reduction in the test ordering rate (95% CI 25.7-49.5%; p < 0.001). Despite the reduction in cranial CT scans, we did not observe an increase in pathological findings after introducing the decision support system (70 cases before [18.5%] vs. 35 cases after [14.3%]; pre-post difference -4.0% [95% CI -10.0 to 1.6%]; p = 0.170). CONCLUSION: In nontraumatic headache among adults seen in the ED, CDSS decreased the cranial CT request rate but the diagnostic yield did not improve.

Nódulos necrobióticos pulmonares: una manifestación excepcional de la enfermedad de Crohn / Pulmonary Necrobiotic Nodules: A Rare Manifestation of Crohn's Disease

No disponible

Pulmonary cysts in smoking-related interstitial fibrosis: a form of pseudocyst secondary to pulmonary interstitial emphysema / Quistes pulmonares en el contexto de la fibrosis intersticial pulmonar relacionada con el tabaco: una forma de seudoquiste secundario a enfisema intersticial pulmonar

Smoking-related interstitial fibrosis is a distinct form of fibrosis, found in smokers, which has striking histopathological features. We present a case of pulmonary interstitial fibrosis with cysts in a 58-year-old woman who was a significant active smoker, presenting with a 7 month history of progressive dyspnea. TAC revealed thin-walled pulmonary cysts. An open lung biopsy was performed and the histopathological study showed hyaline fibrous thickening of the alveolar septa, respiratory bronchiolitis and cysts in the thickness of the interlobar septa. Immunohistochemically, the absence of an epithelial, vascular or lymphatic endothelial lining of the cysts would suggest that the cysts had been caused by pulmonary interstitial emphysema. Immunohistochemistry is essential in the differential diagnosis that includes, in this case, true cysts, pseudocysts and pulmonary lymphangiectasia

La fibrosis intersticial relacionada con el tabaco es una forma especial de fibrosis con histología característica que ocurre en fumadores. Presentamos un caso de fibrosis intersticial pulmonar con quistes en una mujer de 58 años con historia de tabaquismo importante, que refería disnea progresiva en los últimos 7 meses. La TAC reveló quistes pulmonares de paredes delgadas. Se realizó una biopsia pulmonar abierta y el estudio histopatológico mostró engrosamiento fibroso hialino de los septos alveolares, bronquiolitis respiratoria y quistes en el espesor de los septos interlobares. Inmunohistoquímicamente, la ausencia de revestimiento epitelial, endotelial vascular y linfático de los quistes, apoya que estos son causados por enfisema intersticial pulmonar. La inmunohistoquímica es esencial en el diagnóstico diferencial que incluye en este caso, quistes verdaderos, seudoquistes y linfangiectasia pulmonar

Pulmonary cysts in smoking-related interstitial fibrosis: a form of pseudocyst secondary to pulmonary interstitial emphysema.

Smoking-related interstitial fibrosis is a distinct form of fibrosis, found in smokers, which has striking histopathological features. We present a case of pulmonary interstitial fibrosis with cysts in a 58-year-old woman who was a significant active smoker, presenting with a 7 month history of progressive dyspnea. TAC revealed thin-walled pulmonary cysts. An open lung biopsy was performed and the histopathological study showed hyaline fibrous thickening of the alveolar septa, respiratory bronchiolitis and cysts in the thickness of the interlobar septa. Immunohistochemically, the absence of an epithelial, vascular or lymphatic endothelial lining of the cysts would suggest that the cysts had been caused by pulmonary interstitial emphysema. Immunohistochemistry is essential in the differential diagnosis that includes, in this case, true cysts, pseudocysts and pulmonary lymphangiectasia.

Prognosis and Follow-Up of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF), a devastating progressive interstitial lung disease (ILD) with no known cause, is the most common and deadly of the idiopathic interstitial pneumonias. With a median survival of 3⁻5 years following diagnosis, IPF is characterized by a progressive decline in lung function and quality of life in most patients. Prognostic factors recognized classically that influence mortality include functional, clinical and radiological parameters. However, in recent years, there has also been progress in the knowledge of genetic factors and biomarkers that may be useful in the prognostic evaluation of these patients. On the other hand, the monitoring of the disease throughout its evolution is key to improving the prognosis of the patients, as it allows for taking therapeutic measures based on this evolution, even early remission for lung transplantation. This article reviews the main prognostic factors of the disease, as well as the most useful way to monitor the disease follow-up.

Síndrome platipnea-ortodeoxia cardiaco: una causa «misteriosa» de hipoxemia / Cardiac platypnea-orthodeoxia syndrome: A «mysterious» cause of hypoxemia

No disponible

Loxoscelismo cutáneo visceral: actualización en el manejo a propósito de un caso / Viscerocutaneous loxoscelism: case report and update on management

Loxoscelism is a condition produced by the bite of Loxosceles laeta. It can present as cutaneous loxoscelism with only vascular dermal manifestations or as viscerocutaneus loxoscelism with systemic compromise and a mortality rate of 1 to 3%. We report the case of an adult patient presenting viscerocutaneus loxoscelism, who was evolving with macrohematuria, edema, and progressive blisters, requiring treatment in the intensive care unit. He was treated according to the actual scientific evidence with antihistamines, corticosteroids, and dual antibiotic therapy covering Streptococcus spp., Staphylococcus spp., and anaerobes, particularly penicillin and tetracycline resistant C. perfringens. The use of dapsone and antiloxosceles-serum was avoided. The patient showed a favorable clinical evolution.

El loxoscelismo es producido por la mordedura de la araña Loxosceles laeta. Puede ser cutáneo, con alteraciones vasculares o cutáneo-visceral, con manifestaciones sistémicas y una mortalidad de 1 a 3%. Se presenta el caso de un paciente adulto con loxoscelismo cutáneo-visceral, que evolucionó con hematuria macroscópica, edema y aparición de flictenas en forma progresiva en antebrazo, requiriendo ser trasladado a la Unidad de Tratamiento Intermedio. Fue manejado según la evidencia científica actual que recomienda el uso de antihistamínicos, corticoesteroides y terapia antibacteriana asociada para la cobertura de Streptococcus spp., Staphylococcus spp. y bacterias anaerobias, especialmente C. perfringens resistente a penicilina y tetracilina, evitando el uso de dapsona y de suero anti-loxosceles. Evolucionó de manera favorable.

Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling.

Splenic marginal zone lymphoma is a small B-cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B-cell lymphomas is hampered by the lack of specific markers. We have analyzed the gene expression and miRNA profiles of 31 splenic marginal zone lymphoma cases. For comparison, 7 spleens with reactive lymphoid hyperplasia, 10 spleens infiltrated by chronic lymphocytic leukemia, 12 spleens with follicular lymphoma, 6 spleens infiltrated by mantle cell lymphoma and 15 lymph nodes infiltrated by nodal marginal zone lymphoma were included. The results were validated by qRT-PCR in an independent series including 77 paraffin-embedded splenic marginal zone lymphomas. The splenic marginal zone lymphoma miRNA signature had deregulated expression of 51 miRNAs. The most highly overexpressed miRNAs were miR-155, miR-21, miR-34a, miR-193b and miR-100, while the most repressed miRNAs were miR-377, miR-27b, miR-145, miR-376a and miR-424. MiRNAs located in 14q32-31 were underexpressed in splenic marginal zone lymphoma compared with reactive lymphoid tissues and other B-cell lymphomas. Finally, the gene expression data were integrated with the miRNA profile to identify functional relationships between genes and deregulated miRNAs. Our study reveals miRNAs that are deregulated in splenic marginal zone lymphoma and identifies new candidate diagnostic molecules for splenic marginal zone lymphoma.

Effect of teledermatology on the prognosis of patients with cutaneous melanoma.

OBJECTIVE: To evaluate differences in the initial prognosis of patients with cutaneous melanoma managed by teledermatology (TD) vs other non-TD referral systems. DESIGN: Descriptive and longitudinal study of a store-and-forward TD system aimed at the triage of patients with suspicious pigmented lesions. SETTING: In 2003, a store-and-forward TD triage system aimed at the selection of patients with skin growths suggestive of cancer was implemented at a skin cancer clinic. This system has been shown to be accurate and reliable and able to significantly shorten waiting periods for consultation with a dermatologist. PARTICIPANTS: Patients with primary cutaneous melanoma referred to the Melanoma Clinic of the Dermatology Unit, Hospital Universitario Virgen Macarena, Seville, Spain, by TD or non-TD tracks were included in the study. MAIN OUTCOME MEASURES: Decisions on the referral of patients with suspicious skin lesions by store-and-forward TD vs by a conventional referral system. Breslow thickness and tumor stage were recorded in each study group (TD and non-TD) and were compared. RESULTS: Two hundred one patients with primary cutaneous melanoma were enrolled in the study. In total, 33.3% were managed at their primary care center by teleconsultation, whereas 66.7% were managed by a conventional referral system. The mean Breslow thickness was significantly lower among patients in the TD group than among patients in the non-TD group (1.06 vs 1.64 mm, P = .03). The frequency of melanoma with a favorable initial prognosis (tumor stages Tis and T1a) was significantly higher in the TD group (70.1% vs 56.9%, P = .03). The odds ratio of having a cutaneous melanoma with a favorable initial prognosis in the TD group was 1.96 (95% CI, 1.14-3.50; P = .04). CONCLUSION: Teledermatology as a screening system for cutaneous melanoma has a favorable effect on the initial prognosis of patients with melanoma.

Nodal marginal zone lymphoma: gene expression and miRNA profiling identify diagnostic markers and potential therapeutic targets.

Nodal marginal zone lymphoma (NMZL) is a small B-cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B-cell lymphomas is hampered by the lack of specific markers. We have analyzed gene expression, miRNA profile, and copy number data from 15 NMZL cases. For comparison, 16 follicular lymphomas (FLs), 9 extranodal marginal zone lymphomas, and 8 reactive lymph nodes and B-cell subtypes were included. The results were validated by quantitative RT-PCR in an independent series, including 61 paraffin-embedded NMZLs. NMZL signature showed an enriched expression of gene sets identifying interleukins, integrins, CD40, PI3K, NF-κB, and TGF-ß, and included genes expressed by normal marginal zone cells and memory B cells. The most highly overexpressed genes were SYK, TACI, CD74, CD82, and CDC42EP5. Genes linked to G(2)/M and germinal center were down-regulated. Comparison of the gene expression profiles of NMZL and FL showed enriched expression of CHIT1, TGFB1, and TACI in NMZL, and BCL6, LMO2, and CD10 in FL. NMZL displayed increased expression of miR-221, miR-223, and let-7f, whereas FL strongly expressed miR-494. Our study identifies new candidate diagnostic molecules for NMZL and reveals survival pathways activated in NMZL.

PIM2 inhibition as a rational therapeutic approach in B-cell lymphoma.

PIM serine/threonine kinases are overexpressed, translocated, or amplified in multiple B-cell lymphoma types. We have explored the frequency and relevance of PIM expression in different B-cell lymphoma types and investigated whether PIM inhibition could be a rational therapeutic approach. Increased expression of PIM2 was detected in subsets of mantle cell lymphoma, diffuse large B-cell lymphoma (DLBLC), follicular lymphoma, marginal zone lymphoma-mucosa-associated lymphoid tissue type, chronic lymphocytic leukemia, and nodal marginal zone lymphoma cases. Increased PIM2 protein expression was associated with an aggressive clinical course in activated B-like-DLBCL patients. Pharmacologic and genetic inhibition of PIM2 revealed p4E-BP1(Thr37/46) and p4E-BP1(Ser65) as molecular biomarkers characteristic of PIM2 activity and indicated the involvement of PIM2 kinase in regulating mammalian target of rapamycin complex 1. The simultaneous genetic inhibition of all 3 PIM kinases induced changes in apoptosis and cell cycle. In conclusion, we show that PIM2 kinase inhibition is a rational approach in DLBCL treatment, identify appropriate biomarkers for pharmacodynamic studies, and provide a new marker for patient stratification.

Identification of HAVCR1 gene haplotypes associated with mRNA expression levels and susceptibility to autoimmune diseases.

Human HAVCR1 gene maps on 5q33.2, a region linked with susceptibility to allergic and autoimmune diseases. The aims of the present study were to define the haplotypes of HAVCR1 gene taking into account both HapMap Project SNP haplotypes and exon 4 variants, to investigate a possible relationship between these haplotypes and mRNA expression levels, and to assess whether HAVCR1 gene is involved in susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Genotyping of three ins/del variants in the exon 4 was performed by fragment length analysis. Five tag SNPs genotypes and mRNA levels were determined using TaqMan assays. We defined four major haplotypes in our population: the two major haplotypes (named haplotypes A and B) bear both the 5383_5397del variant and the two most common SNP sets found in the CEU population. Quantification analysis revealed that genotype B/B had the highest median of mRNA expression levels (vs. BX + XX, p < 0.0001). Additionally, frequency of the genotype BB was significantly higher in RA patients than in controls (12.3 vs. 5.9% in controls, p = 0.0046, p (c) = 0.014, OR = 2.23, 95% CI 1.23-4.10). Our results support a relationship between HAVCR1 haplotypes and mRNA expression levels, and suggest an association of this gene with autoimmune diseases.