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Simple Summary The majority of patients with sinonasal intestinal-type adenocarcinoma are wood and leather workers. However, the genetic changes that lead to these tumors are not well known. We analyzed 50 tumors for mutations in a set of 120 genes that may be involved in causing this cancer type. We found that 72% of cases carried mutations in genes that are active in Wnt, DNA damage response, MAPK or PI3K signaling pathways. Pathway activation was not related to mutations of genes in these pathways, except for nuclear β-catenin expression to Wnt pathway mutation. No specific gene mutation, mutated pathway, nor pathway activity level was associated with histological subtype, clinical data or survival. Finally, none of the identified mutated genes occurred in such frequency as to be considered a characteristic genetic feature of sinonasal intestinal-type adenocarcinoma. Abstract Sinonasal intestinal-type adenocarcinoma (ITAC) is strongly related to occupational exposure to wood and leather dust, however, little is known on the genetic alterations involved in tumor development and progression. The aim of this study was to identify tumorigenic signaling pathways affected by gene mutations and their relation to clinical features. We applied whole exome sequencing of 120 cancer-related genes in 50 ITACs and analyzed the signaling activity of four specific pathways frequently affected by mutations. Genes involved in DNA damage response showed somatic mutations in 30% of cases, including four tumors that also harbored germline mutations. Genes in Wnt, MAPK and PI3K pathways harbored mutations in 20%, 20% and 24% of cases, respectively. Mutations and copy number gains in receptor tyrosine kinases possibly affecting MAPK and PI3K pathways occurred in 44% of cases. Expression of key pathway proteins showed no correlation to mutations in these pathways, except for nuclear β-catenin and APC/CTNNB1 mutation. No specific gene mutation, mutated pathway, nor pathway activity level showed correlation to clinical data or survival. In addition, a similar mutational profile was observed among histological subtypes. The wide spectrum of gene mutations suggests that ITAC is a genetically heterogeneous without specific characterizing gene mutations.

The coronavirus disease 2019 (COVID-19) is related to enhanced production of NETs, and autoimmune/autoinflammatory phenomena. We evaluated the proportion of low-density granulocytes (LDG) by flow cytometry, and their capacity to produce NETs was compared with that of conventional neutrophils. NETs and their protein cargo were quantified by confocal microscopy and ELISA. Antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and the degradation capacity of NETs were addressed in serum. MILLIPLEX assay was used to assess the cytokine levels in macrophages’ supernatant and serum. We found a higher proportion of LDG in severe and critical COVID-19 which correlated with severity and inflammatory markers. Severe/critical COVID-19 patients had higher plasmatic NE, LL-37 and HMGB1-DNA complexes, whilst ISG-15-DNA complexes were lower in severe patients. Sera from severe/critical COVID-19 patients had lower degradation capacity of NETs, which was reverted after adding hrDNase. Anti-NET antibodies were found in COVID-19, which correlated with ANA and ANCA positivity. NET stimuli enhanced the secretion of cytokines in macrophages. This study unveils the role of COVID-19 NETs as inducers of pro-inflammatory and autoimmune responses. The deficient degradation capacity of NETs may contribute to the accumulation of these structures and anti-NET antibodies are related to the presence of autoantibodies.

Resumen Introduccion y objetivos La laringectomia total (LT), mas eventual radioterapia, ha demostrado ser un tratamiento eficaz en los casos de cancer de hipofaringe localmente avanzado. El objetivo de este trabajo es analizar los resultados oncologicos de este procedimiento en pacientes con cancer de hipofaringe T3 y T4. Metodos Se incluyeron 59 pacientes (33 pacientes con estadio T3 y 26 con estadio T4a) con carcinoma epidermoide primario de hipofaringe tratados mediante LT entre los anos 1998 y 2012. Resultados La edad media fue de 61 anos, con predominio de varones (96,6%). Todos los pacientes excepto uno eran fumadores y el 96% consumia alcohol. Se realizo vaciamiento cervical funcional unilateral en 12 pacientes, radical unilateral en 11 pacientes, funcional bilateral en 20 pacientes y funcional mas radical en 14. El 66% de los pacientes recibieron radioterapia postoperatoria. Un 81% de los pacientes presentaba metastasis ganglionares y de estos un 56% presentaba invasion extracapsular. Un 29% de los pacientes presentaron recidiva locorregional, un 17% desarrollaron metastasis a distancia y un 25% un segundo tumor primario. La supervivencia especifica fue del 46% a los 5 anos. Conclusiones La LT ampliada a faringe (con eventual radioterapia complementaria) ofrece buenos resultados oncologicos en terminos de control locorregional de la enfermedad y supervivencia en el cancer de hipofaringe localmente avanzado, de modo que los protocolos de preservacion de organo deben alcanzar resultados oncologicos similares a los demostrados por la LT.

Introduction and objectives Total laryngectomy (TL), with eventual postoperative radiotherapy, has proven to be effective in treating cases of locally advanced hypopharyngeal cancer. The aim of this study was to analyse the oncological outcomes of this procedure in patients with hypopharyngeal cancer classified T3 and T4. Methods We studied 59 patients (33 T3 and 26 T4a) with primary squamous cell carcinoma of the hypopharynx treated with TL from 1998 to 2012. Results Mean age was 61 years with a male predominance (96.6%). All the patients were smokers and 96% consumed alcohol. Unilateral selective neck dissection (ND) was performed in 12 patients, unilateral radical ND in 11 patients, bilateral selective ND in 20 patients and radical ND plus selective ND in 14 patients. Sixty-six percentage of the patients received postoperative radiotherapy. Lymph node metastases occurred in 81% of the patients and extranodal invasion in 56% of them. Twenty-nine percentage of the patients had loco-regional recurrence, 17% developed distant metastases, and 25% a second primary tumour. The 5-year disease-specific survival was 46%. Conclusions TL extended to pharynx (with eventual postoperative radiotherapy) offers good oncological results in terms of loco-regional control and survival in locally advanced hypopharyngeal cancer, so organ preservation protocols should achieve similar oncological results to those shown by TL.

First bite syndrome is a potential complication of surgery involving the infratemporal fossa, deep lobe of the parotid gland and parapharyngeal space. It is described as an acute and intense pain in the parotid region caused with the first bite of each meal. It is related to damage to sympathetic innervation of the parotid gland. Parasympathetic hyperactivation is believed to stimulate an exaggerated myoepithelial cell contraction causing pain. Usual analgesic treatments have poor results. Botulinum toxin type A causes parasympathetic nerve paralysis of the parotid gland and this fact would minimize salivation and decrease first bite syndrome. The aim of this study is to show the details of the technique and our outcomes in 5 patients treated with botulinum toxin type A.

First bite syndrome is a potential complication of surgery involving the infratemporal fossa, deep lobe of the parotid gland and parapharyngeal space. It is described as an acute and intense pain in the parotid region caused with the first bite of each meal. It is related to damage to sympathetic innervation of the parotid gland. Parasympathetic hyperactivation is believed to stimulate an exaggerated myoepithelial cell contraction causing pain. Usual analgesic treatments have poor results. Botulinum toxin type A causes parasympathetic nerve paralysis of the parotid gland and this fact would minimize salivation and decrease first bite syndrome. The aim of this study is to show the details of the technique and our outcomes in 5 patients treated with botulinum toxin type A.

Introduction Over the past several decades, many acoustic parameters have been studied as sensitive to and to measure dysphonia. However, current acoustic measures might not be sensitive measures of perceived voice quality. A meta-analysis which evaluated the relationship between perceived overall voice quality and several acoustic-phonetic correlates, identified measures that do not rely on the extraction of the fundamental period, such the measures derived from the cepstrum, and that can be used in sustained vowel as well as continuous speech samples. A specific and recently developed method to quantify the severity of overall dysphonia is the acoustic voice quality index (AVQI) that is a multivariate construct that combines multiple acoustic markers to yield a single number that correlates reasonably with overall vocal quality. Methods This research is based on one pool of voice recordings collected in two sets of subjects: 60 vocally normal and 58 voice disordered participants. A sustained vowel and a sample of connected speech were recorded and analyzed to obtain the six parameters included in the AVQI using the program Praat. Statistical analysis was completed using SPSS for Windows, version 12.0. Results Correlation between perception of overall voice quality and AVQI: A significant difference exists ( t (95)=9.5; P Conclusions The findings of this study demonstrate the clinical feasibility of the AVQI as a measure of dysphonia severity.

Resumen Introduccion En las ultimas decadas se han estudiado muchos parametros acusticos con el fin de cuantificar la disfonia, sin embargo las medidas actuales podrian no ser sensibles a la calidad vocal percibida. En un metaanalisis donde se evaluo la relacion entre la calidad global percibida de la voz se identificaron numerosas medidas acusticas que no dependen de la extraccion del periodo fundamental tales como las derivadas del cepstrum y que pueden ser usadas tanto en vocales sostenidas como en habla conectada. Un metodo especifico recientemente disenado para cuantificar la severidad global de la disfonia es el indice acustico de calidad vocal (AVQI) que es un constructo multivariante que combina multiples marcadores acusticos para generar un unico numero que se correlaciona razonablemente con la calidad global vocal. Metodos Esta investigacion se baso en un archivo de voces grabadas procedentes de dos grupos de individuos: 60 personas sanas vocalmente y 58 participantes con trastornos vocales. Se grabaron vocales sostenidas y una muestral de habla conectada para su analisis y asi obtener los seis parametros incluidos en el AVQI utilizando el programa Praat. El analisis estadistico de los resultados se llevo a cabo con el programa SPSS para Windows version 12.0. Resultados Correspondencia entre el valor del AVQI y el grado de severidad global de la disfonia: correlacion r = 0,68 (p Conclusiones Los resultados obtenidos muestran una buena correlacion con la calidad vocal percibida. En conclusion, el AVQI es una medida multivariante, accesible, factible y razonablemente valida para medir clinicamente la severidad global de la severidad de la disfonia.

Introduction and objectives The aim of this study is to present our experience with the diagnostic and therapeutic approaches for parapharyngeal space tumours. Patients and method This study is a retrospective review of 90 patients diagnosed with tumours of the parapharyngeal space and treated surgically between 1984 and 2015. Patients whose tumours were not primary but invaded the parapharyngeal space expanding from another region, tumours originating in the deep lobe of the parotid gland and head and neck metastasis were excluded from this study. Results 74% percent of the parapharyngeal space neoplasms were benign and 26% were malignant. Pleomorphic adenoma was the most common neoplasm (27%), followed by paragangliomas (25%), miscellaneous malignant tumours (16%), neurogenic tumours (12%), miscellaneous benign tumours (10%), and malignant salivary gland tumours (10%). The transcervical approach was used in 56 cases, cervical-transparotid approach in 15 cases, type A infratemporal fossa approach in 13 cases, transmandibular approach in 4 cases and transoral approach in 2 cases. The most common complications were those deriving from nervous injuries. Conclusions Most parapharyngeal space tumours can be removed surgically with a low rate of complications and recurrence. The transcervical approach is the most frequently used.

Resumen Introduccion y objetivos El objetivo de este estudio es presentar nuestra experiencia en el diagnostico y tratamiento de los tumores parafaringeos. Pacientes y metodo Realizamos un estudio retrospectivo de 90 pacientes, diagnosticados y tratados quirurgicamente de una tumoracion parafaringea entre 1984 y 2015. Fueron excluidos los pacientes cuyos tumores no eran primarios, sino que invadian esta region por contiguidad, los tumores originados en el lobulo profundo de la parotida y las metastasis de otros tumores de cabeza y cuello. Resultados El 74% de las neoplasias del espacio parafaringeo fueron de naturaleza benigna y el 26% maligna. Los adenomas pleomorfos fueron los tumores mas frecuentes (27%), seguido por los paragangliomas (25%), un grupo de tumores de origen miscelaneo de naturaleza maligna (16%), los tumores de origen neurogenico (12%), un grupo de tumores de origen miscelaneo de naturaleza benigna (10%) y los tumores malignos de glandulas salivales (10%). El tratamiento fue quirurgico en todos los casos. Se realizo un abordaje transcervical en 56 pacientes, un abordaje cervical-transparotideo en 15 pacientes, un abordaje infratemporal tipo A en 13 pacientes, un abordaje transmandibular en 4 pacientes y en 2 casos un abordaje transoral. Las complicaciones mas frecuentes fueron las derivadas de lesiones de estructuras nerviosas. Conclusiones La mayoria de los tumores localizados en el espacio parafaringeo son subsidiarios de ser tratados de forma quirurgica con una baja tasa de complicaciones y recurrencias. El abordaje transcervical es el mas utilizado.

Several studies suggest an important role of Interleukin-27 in the development of atherosclerosis. The aim of this study was to establish whether the IL-27p28 gene polymorphisms are associated with premature coronary artery disease and/or other cardiovascular risk factors. Four IL-27p28 gene polymorphisms were selected and genotyped in 1162 premature coronary artery disease cases and 1107 controls. rs26528 T and rs40837 A alleles were significantly associated with a lower risk of premature coronary artery disease under different inheritance models (Pdominant = 0.046; Pover-dominant = 0.002; Pco-dominant1 = 0.007 for rs26528T; Pover-dominant = 0.008 and Pco-dominant1 = 0.031 for rs40837). The rs40837 A allele was also associated with a lower risk of insulin resistance, in cases (Pover-dominant = 0.037) and controls (Padditive = 0.008; Pdominant = 0.047; Precessive = 0.014; Pco-dominant2 = 0.006), while the rs26528 T allele was associated with a lower risk of insulin resistance only in the control group (Precessive = 0.016; Pco-dominant2 = 0.021). Interleukin-27 plasma levels were measured in 450 controls and 450 cases, and were significantly higher in cases compared to controls (P = 0.004). However, Interleukin-27 plasma levels were not associated with IL-27p28 polymorphisms. Luciferase assays showed that co-transfection of the rs40837 A allele and miR-379-5p significantly decreased luciferase gene expression. Our study shows for the first time, that IL-27p28 gene polymorphisms are associated with premature coronary artery disease and with some metabolic parameters. The rs40837 A allele in presence of miR-379-5p significantly decreased luciferase gene expression.

Chordomas are rare and low-grade malignant solid tumours, despite their histologically benign appearance, that arise in the bone from embryonic notochordal vestiges of the axial skeleton, a mesoderm-derived structure that is involved in the process of neurulation and embryonic development. Chordomas occurring in the skull base tend to arise in the basiocciput along the clivus. Three major morphological variants have been described (classical, chondroid, and atypical/dedifferentiated). The pathogenesis and molecular mechanisms involved in chordoma development remain uncertain. From a pathological standpoint, the microenvironment of a chordoma is heterogeneous, showing a dual epithelial-mesenchymal differentiation. These tumours are characterised by slow modality of biologic growth, local recurrence, low incidence of metastasis rates, and cancer stem cell (CSC) phenotype. The main molecular findings are connected with brachyury immunoexpression and activation of the downstream Akt and mTOR signalling pathways. The differentiation between typical and atypical chordomas is relevant because the tumoural microenvironment and prognosis are partially different. This review provides an insight into the recent and relevant concepts and histochemical markers expressed in chordomas, with special emphasis on dedifferentiated chordomas and their prognostic implications.

Resumen Introduccion Las translocaciones de la region cromosomica 2p23 causan la sobreexpresion del gen de la quinasa del linfoma anaplasico ( ALK ), un receptor tirosinquinasa involucrado en rutas de senalizacion celular que regulan la proliferacion. Dicha alteracion se identifica en el 5% de los adenocarcinomas de pulmon, representando una diana terapeutica en dicho subgrupo de tumores. Debido a que los adenocarcinomas nasosinusales (ACNS) tienen una histologia similar a los adenocarcinomas de pulmon, el objetivo de este estudio fue evaluar si existen alteraciones en el gen ALK en los ACNS. Metodo La presencia de translocaciones del gen ALK se analizo en 96 muestras de ACNS mediante fluorescence in situ hybridization usando unas sondas «break apart». Ademas se estudio la expresion proteica de ALK por inmunohistoquimica. Resultados En ninguno de los casos se observo la presencia de translocaciones de ALK . Ademas, no se detecto expresion proteica en ninguno de los casos. Conclusiones Los resultados obtenidos sugieren que ALK no desempena un papel relevante en la oncogenesis de los ACNS.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well-identified as risk factors. SLE patients have different phenotypes or clinical presentations, which vary among Mexicans. This variation could be explained by ethnicity and admixture. Since socioeconomic status probably limits and change the patterns of migration, this factor could favor inbreeding and homogamy in some geographic areas. Consequently, it could alter or restrict the possibilities of admixture too. Therefore, the socioeconomic status may also have implications in the susceptibility and the clinical heterogeneity of SLE in Mexican patients.One hundred twenty-three SLE patients and 234 healthy individuals with Mexican admixed ancestry were recruited. HLA alleles were analyzed using the HLA typing method based on Sequence-based typing (SBT).As expected, it was found an increased frequency of the HLA-DRB1*03:01 allele in all socioeconomic groups when compared with healthy individuals. The susceptibility allele found in the low-income SLE patients was HLA-DRB1*04:05 whereas, the susceptibility alleles for the high-income SLE patients were HLA-DRB1*07:01 (pC = 0.03, OR = 2.0) and HLA-DRB1*11:04 (pC = 0.0004, OR = 5.1). Additionally, the frequencies of two protective alleles HLA-DRB1*14:06 (pC = 0.01, OR = 0.28) and HLA-DRB1*16:02 (pC = 0.04, OR = 0.22) were found diminished. These findings correlate with the admixture differences between low-income and high-income SLE patients. The clinical manifestations showed a different distribution between both groups. Arthritis and neurological disorder were prevalent in low-income SLE patients, while the hematological disorder was prevalent in high-income SLE patients.These findings suggest that HLA class II DRB1 genes contribute to the susceptibility and protection to develop SLE differently depending on socioeconomic status. Due to this, the clinical manifestations vary among patients and it could be related to different admixture charge.Key Point• HLA class II DRB1 genes contribute to the susceptibility and protection to develop SLE differently depending on socioeconomic status.

ResumenEl deporte escolar es un tema poco estudiado en la ciudad de Montería, por lo que se desconoce cómo se desarrolla y si este responde a las normas que lo regulan a nivel nacional. El presente estudio tiene como propósito examinar las características del deporte escolar en 15 instituciones educativas del sector público en el área urbana, incluyo revisión documental de los colegios, entrevistas a docentes y valoración de la infraestructura, materiales y equipamientos deportivos. Mediante un estudio de tipo cualitativo con orientación descriptiva y evaluativa se recopilo y se triangulo la información obtenida de las diferentes fuentes. Los resultados muestran que el deporte escolar desarrollado en las instituciones estudiadas se desarrolla al interior de la clase de Educación Física, los espacios, la infraestructura, los equipamientos y materiales con que cuentan las instituciones son insuficientes con relación a la población estudiantil.

The sinonasal cavities harbor a wide variety of histologically distinct cancers, the majority very aggressive with 5-year survival rates between 30–60% and local recurrence as the main cause of death. This is a complex anatomic area, close to structures such the eyes and the brain, which is of special relevance for surgery and postoperative radiotherapy. The low incidence of these rare tumors hampers accumulation of experience with diagnosis and clinical managment as well as knowledge on recurrent genetic aberrations or testing of new treatment strategies. However, recent years have seen a growing number of publications on genetic aberrations providing data that can aid or fine-tune classification and provide molecular targets for treatment with specific inhibitors. In addition, new sinonasal cancer models are created that enable preclinical testing of candidate inhibitor drugs. With more and more novel targeted therapies being developed, options for personalized treatment of sinonasal cancer patients are now opening up.

Background: The lacrimal gland is frequently involved in both IgG4-related disease (IgG4-RD) and Sjogren’s syndrome (SS) and presents with swelling and/or dry eye symptoms. Although a distinct chemokine and cytokine tear profile might distinguish SS from idiopathic dry eye, as of today no study has assessed this issue in IgG4-RD. Objectives: To evaluate and compare a set of chemokine/cytokine in the tears of patients with IgG4-RD and primary SS. Methods: We included 11 patients with IgG4-RD according to the Comprehensive Diagnostic Criteria for IgG4-RD and 17 with primary SS according the AECG criteria, who attended a tertiary referral center in Mexico City. Schirmer-I test were performed using two standardized sterile tear strips, and then immediately frozen at -86°C until assayed. Once defrosted, the tears were extracted from the strips using a buffer containing 0.5 M NaCl and 0.5% Tween-20. Then, the amount (pg/mL) of the following selected chemokines and cytokines were measured by Luminometry: CCL11, G-CSF, IFN-γ, IL-12p40, IL-12p70, IL-13, IL-17A, IL-1α, IL-1β, IL-4, IL-7, CXCL10, CCL2, CCL3, CCL4 and TNF-α. Results: Patients with IgG4-RD were younger (51.3±14.7 vs. 55.7±10.6) and more frequently men (45.5% vs. 5.9%) than SS patients. Regarding the IgG4-RD group, 7 (63.6%) had lacrimal gland involvement, 5 (45.5%) dry eye symptoms and 6 (54.5%) positive Schirmer-I test. We observed multi-organic involvement in 9 patients (81.8%), median number of involved organs of 5, 9 (81.8%) patients had active disease, median IgG4-RD responder index of 6 points, 8 (72.7%) patients had high IgG4 serum levels, and 9 (81.8%) biopsy proven diagnosis. We found higher levels of IL-7 and CCL2, and a trend for G-CSF in the IgG4-RD group. Conversely, primary SS patients had higher levels of IL-12p40, IL-1α, IL-1β, CCL3 and CCL4. At the logistic regression analysis, the variables that remained associated with IgG4-RD were IL-7 (OR 1.43 95% CI 1.06-1.93, p=0.01) and IL12p40 (OR 0.92, 95% CI 0.84-0.99, p=0.01). In a sensitivity analysis, including only 7 IgG4-RD patients with dacryoadenitis, we also observed higher levels of IL-7 and G-CSF in the IgG4-RD group vs primary SS. Conclusion: The chemokine and cytokine profile of tears of patients with IgG4-RD is characterized by a mixed immune response (Th1/Th2/Th17) compare with a predominantly Th1 response in primary SS. Our results also suggest a possible role of IL-7 in the pathogenesis of IgG4-RD. References: [1] Hernandez-Ruiz M, Zlotnik A, Llorente L, Hernandez-Molina G. Markedly high salivary and lacrimal CXCL17 levels in primary Sjogren’s syndrome. Joint Bone Spine. 2018May;85(3):379-380. Disclosure of Interests: None declared

Background: Previous studies have linked the participation of multiple chemokines and cytokines in the physiopathology of primary Sjogren’s syndrome (PSS), however data regarding their presence in tears is scarce Objectives: To evaluate a panel of chemokines/cytokines in the tears of patients with PSS and correlate them with ocular symptoms as well as objective ocular tests. Methods: We included 21 patients with PSS (EULAR/ACR criteria). A single expert ophthalmologist in dry eye evaluated the patients and assessed the tear film break-up time, Schirmer-I test, tear meniscus height, the Van Bijsterveld staining score and the SICCA Ocular Staining Score (OSS). We classified lacrimal dysfunction severity in two categories (1=mild, mild/moderate or moderate, and 2= moderate/severe and severe). We scored the ESSPRI, and ocular dryness VAS as well as the Ocular Surface Disease Index (OSDI), a 12-item scale for the assessment of symptoms related to dry eye disease and their effect on vision. Tear samples were collected using sterile tear flow strips, that were immediately frozen at -86°C until assayed. Once defrosted, the tears were extracted from the strips using a buffer containing 0.5 M NaCl and 0.5% Tween-20. We tested IFN-γ, IL-10, IL-12, IL-17A, IL-1β, IL-2, IL-21, IL-23, IL-5, IL-6, IL-8, TNF-α, BAFF, CXCL10 and CCL2 by Luminometry. We also included 21 healthy controls without dry eye, to test chemokines/cytokines that after our initial screening were meaningful. Results: Most patients were females (90.4%), mean age 59.3±13 years and median disease duration 7.9 years (0.5-27). All of them had ocular and oral symptoms. The median tear film break-up time was 6 seconds (2-9), median Schirmer-I test 6 mm (1-25), median lacrimal meniscus height 1.5 mm (0.5-2), median Van Bijsterveld staining score 10 points (2-18), median OSS 7 points (2-11), median ESPPRI score 6.7 points (2-9.2) and median ocular dryness EVA score 9 points (1-10). We did not detect most of the evaluated chemokines/cytokines with the exception of IL-8, CXCL10, and CCL2. The former was similar in both, patients and controls. PSS patients had lower levels of CXCL10 (472.8 pg/μL vs 1652 pg/μL, p=0.01) and CCL2 (1.08 pg/μL vs 9 pg/μL) than controls. Indeed, patients with worst lacrimal dysfunction severity had the lowest levels of CXCL10 (239.3 pg/μL vs. 646.2 pg/μL, p=0.02). We found correlations among CXCL10 and CCL2 (T=0.30, p=0.02) and lacrimal meniscus height (T=0.55, p=0.005), as well as with CCL2 and lacrimal meniscus height (T=0-57, p=0.01). None of the other variables were correlated. Conclusion: We identified CXCL10 and CCL2 as the main chemokines in tears of patients with PSS. CXCL10 seems to participate in the normal eye homeostasis. Disclosure of Interests: None declared

Objective To assess the effect of a dynamic exercise program (DEP) in combination with a Mediterranean diet (MD) on health-related quality of life in women with rheumatoid arthritis (RA). Method A randomized clinical trial including 144 women with RA diagnosis was performed. Patients were randomized into 4 groups: (1) MD + DEP (n = 36), (2) DEP (n = 37), (3) MD (n = 40), and (4) control (n = 31). All patients received conventional disease-modifying antirheumatic drugs. Health-related quality of life was assessed with 36-item Short Form Health Survey v2 (0-100 score) and disability with Health Assessment Questionnaire Disability Index at enrollment and after 24 weeks. Between-groups comparisons of the change in the quality of life scores from baseline to follow-up were performed using analysis of covariance in which baseline-to-follow-up was the dependent variable, and the intervention group was the independent variable. Results All patients had low disease activity at the time of enrollment, with a mean 28-joint Disease Activity Score of less than 3.2. Patients who were included in the MD + DEP and DEP groups showed 15 points of increase in health-related quality of life global punctuation versus 3.5 in the MD group and -4.6 in the control group (p = 0.01). Also the scores in the physical component after 24 weeks of intervention in the MD + DEP group improved (15.5), in the DEP group (12) and MD group as well (5.1), whereas the control group showed a decrease of the score (-1.7) (p = 0.03 between groups). Conclusions The combination of MD + DEP could improve the quality of life in RA patients with low disease activity receiving conventional disease-modifying antirheumatic drugs.

The quality of anti-virus software relies on simple patterns extracted from binary files. Although these patterns have proven to work on detecting the specifics of software, they are extremely sensitive to concealment strategies, such as polymorphism or metamorphism. These limitations also make anti-virus software predictable, creating a security breach. Any black hat with enough information about the anti-virus behaviour can make its own copy of the software, without any access to the original implementation or database. In this work, we show how this is indeed possible by combining entropy patterns with classification algorithms. Our results, applied to 57 different anti-virus engines, show that we can mimic their behaviour with an accuracy close to 98% in the best case and 75% in the worst, applied on Windows&rsquo, disk resident malware.

Mathematical models of particle size distribution (PSD) are necessary in the modelling and simulation of comminution circuits. In order to evaluate the application of the Swebrec PSD model (SWEF) in the grinding circuit at the Punta Gorda Ni-Co plant, a sampling campaign was carried out with variations in the operating parameters. Subsequently, the fitting of the data to the Gates-Gaudin-Schumann (GGS), Rosin-Rammler (RRS) and SWEF PSD functions was evaluated under statistical criteria. The fitting of the evaluated distribution models showed that these functions are characterized as being sufficiently accurate, as the estimation error does not exceed 3.0% in any of the cases. In the particular case of the Swebrec function, reproducibility for all the products is high. Furthermore, its estimation error does not exceed 2.7% in any of the cases, with a correlation coefficient of the ratio between experimental and simulated data greater than 0.99.

Contains fulltext : 203152.pdf (Publisher’s version ) (Open Access) The International Collaboration on Cancer Reporting was established to internationally unify and standardize the pathologic reporting of cancers based on collected evidence, as well as to allow systematic multi-institutional intercountry data collection to guide cancer care in the future. This data set has been developed by the collaborative efforts of an international multidisciplinary panel of experts involved in the care of patients with carcinomas of the nasal cavity and paranasal sinuses (sinonasal tract). The nasal cavity and paranasal sinuses (including frontal, sphenoid, ethmoid, and maxillary sinuses) comprise a very complex anatomic area of the head and neck, affected by a sometimes bewildering array of neoplasms. Management of malignancies in this anatomic region involves complex surgery because of the anatomic confines and close proximity to many vital structures. Given a multidisciplinary approach, the standardized reporting of the carcinomas that develop in this anatomic region include both required (core) and recommended (noncore) elements in pathology reporting in order to be able to identify critical prognostic factors, often requiring clinical and radiologic correlation. A summary of the International Collaboration on Cancer Reporting guidelines and clinically relevant elements, along with additional explanatory notes, are provided, based on evidentiary support from the literature, set in the context of practical application.

Objective.We aimed to evaluate the usefulness of anti-α-fodrin antibodies (AFA) in combination with rheumatoid factor (RF) and/or antinuclear antibodies (ANA) as an alternative immunological criterion for Sjögren syndrome (SS) among patients with negative anti-Ro/La serology.Methods.The study included 350 patients (100 with rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, and 50 with primary SS) randomly selected and assessed for SS. All patients were tested for ANA, RF, anti-SSA/SSB, and AFA antibodies. SS diagnosis was made on a clinical basis by 2 rheumatologists based on the 6-item screening questionnaire, Schirmer-I test, nonstimulated whole salivary flow rate, fluorescein staining test, autoantibodies, lip biopsy, and medical chart review. Non-SS was defined as lack of clinical diagnosis and not fulfilling the American-European Consensus Group classification criteria and the American College of Rheumatology (ACR) criteria. The ACR criteria were applied substituting the immunological criteria as follows: (1) RF plus ANA > 1:320, (2) RF plus AFA, (3) ANA > 1:320 plus AFA, (4) RF alone, and (5) 2 positive tests out of RF, ANA > 1:320, or AFA. We estimated the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio positivity with 95% CI for each criterion.Results.There were 236 patients (67%) who tested negative for anti-SSA/SSB antibodies, of whom 65 (27.5%) were clinically diagnosed as SS, and 149 (63%) with non-SS. RF + AFA and ANA + AFA performed similarly to RF + ANA > 1:320. The model 2 out of 3 of RF, ANA, or AFA improved the sensitivity from 56.9% to 70.7%, although the specificity decreased.Conclusion.The combination AFA + RF, AFA + ANA > 1:320, or at least 2 out of 3, performed well as a proxy immunological test for patients with SS and negative Ro/La serology.

To identify epigenetic events in intestinal-type sinonasal adenocarcinoma (ITAC) and sinonasal squamous cell carcinoma (SNSCC) and to evaluate their relation to clinicopathologic features and follow-up data.Retrospective study.Academic research hospital.The methylation status of 23 genes in 50 ITACs and 32 SNSCCs was analyzed by methylation-specific multiplex ligation-dependent probe amplification and its relation to clinicopathologic features and follow-up data.Gene methylation was observed in 50% of all tumors. Recurrent methylated genes in SNSCC were RASSF1 and CDH13 (for both, 6 of 32 cases), CHFR (4 of 32 cases), and TIMP3 (2 of 32 cases). None of these genes showed significant correlation to clinicopathologic features or overall survival. In ITAC, recurrent methylated genes were CDH13 (18 of 50 cases), ESR1 (13 of 50 cases), APC (7 of 50 cases), TIMP3 (5 of 50 cases), CASP8 (3 of 50 cases), and HIC1 and RASSF1 (for both, 2 of 50 cases). Papillary and colonic ITAC subtypes carried a mean of 1.26 gene methylations per tumor versus 0.63 in solid and mucinous subtypes. Methylation of TIMP3 was associated with a significantly worse survival in ITAC patients.ITAC carries a higher number and a different profile of gene methylations as compared with SNSCC. Gene methylation plays a greater role in papillary and colonic ITAC subtypes, which may indicate a different tumorigenic pathway for these ITAC subtypes. These findings could be used as prognosticators and may have implications for future individualized therapies based on epigenetic changes.

The 9p21 gene cluster, harboring growth suppressive genes p14 ARF , p15 INK4b , and p16 INK4a , is one of the major aberration hotspots in head and neck cancers. We try to elucidate specific aberrations affecting this region, throughout methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Methylation of the gene was investigated by MS-MLPA in a well-characterized series of 27 laryngeal squamous cell carcinomas and 20 samples of healthy mucosa. Aberrant promoter hypermethylation was confirmed using and methylation-specific. All samples studied except 3 (11 %) presented losses at 9p21 segment. The most common finding was the small deletion (exon 1α) of the p16 INK4a locus (44 %). Deletion of the 9p21 gene cluster was identified in 5 cases (18 %). We only found methylation in 8 samples (30 %) for p15 IK4b -exon 1. Promoter methylation of p14 ARF , p15 IK4b and p16 INK4a was not detected in any tumor sample. Methylation-specific polymerase chain reaction confirmed the results. Our data indicate that there may be a subgroup of patients in which epigenetic regulation of 9p21 segment might have little relevance. Nevertheless, MS-MLPA could not be suitable for the study of methylation at this region and further research is required.

Introduction and objectives Conventional audiometry is the gold standard for quantifying and describing hearing loss. Alternative methods become necessary to assess subjects who are too young to respond reliably. Auditory evoked potentials constitute the most widely used method for determining hearing thresholds objectively; however, this stimulus is not frequency specific. The advent of the auditory steady-state response (ASSR) leads to more specific threshold determination. The current study describes and compares ASSR, auditory brainstem response (ABR) and conventional behavioural tone audiometry thresholds in a group of infants with various degrees of hearing loss. Methods A comparison was made between ASSR, ABR and behavioural hearing thresholds in 35 infants detected in the neonatal hearing screening programme. Results Mean difference scores (±SD) between ABR and high frequency ABR thresholds were 11.2 dB (±13) and 10.2 dB (±11). Pearson correlations between the ASSR and audiometry thresholds were 0.80 and 0.91 (500 Hz); 0.84 and 0.82 (1000 Hz); 0.85 and 0.84 (2000 Hz); and 0.83 and 0.82 (4000 Hz). Conclusion The ASSR technique is a valuable extension of the clinical test battery for hearing-impaired children.

Resumen Introduccion y objetivos La audiometria convencional es el patron de referencia para cuantificar y describir una hipoacusia. Sin embargo, se precisan metodos alternativos para los pacientes muy jovenes que no pueden responder con fiabilidad. Los potenciales evocados auditivos de tronco (PEATC) es el metodo mas extendido para determinar de forma objetiva los umbrales auditivos, sin embargo, no informan especificamente en cada frecuencia. La llegada de los potenciales evocados de estado estable (PEAEE) permite conseguir una determinacion mas especifica en frecuencias. El presente trabajo describe y compara los umbrales obtenidos mediante PEATC, PEAEE y audiometria convencional en un grupo de ninos que presentan varios grados de perdida auditiva. Metodos Se llevo a cabo una comparacion entre los umbrales de PEATC, PEAEE y audiometricos obtenidos de 35 ninos detectados en el programa de cribado auditivo neonatal. Resultados La diferencia media (±DE) entre los umbrales de los PEATC y la banda de 4.000 Hz de los PEAEE fueron 11,2 dB (±13) para el oido derecho y 10,2 dB (±11) para el izquierdo. Las correlaciones de Pearson entre los umbrales de los PEAEE y audiometricos fue 0,80 y 0,91 (500 Hz); 0,84 y 0,82 (1.000 Hz); 0,85 y 0,84 (2.000 Hz); 0,83 y 0,82 (4.000 Hz), respectivamente para oido derecho e izquierdo. Conclusion La tecnica de los PEAEE es una tecnica a tener en cuenta para su inclusion en la bateria de test que se emplea en el diagnostico audiologico de los ninos con hipoacusia.

Varicella infection is one of the most common and contagious infection in children and could course with severe complications. We report the case of a 4-year-old patient derived to our hospital for suspicion of suppurative complication in the context of a varicella infection. A computerized tomographic scanning was performed, showing a large retropharyngeal abscess with mediastinitis. Complications of varicella are up to 2% of patients, but this is the first report of a retropharyngeal and mediastinal abscess in this context. In the face of clinical suspicion, early intervention is important through imaging, intravenous antibiotics and surgical drainage in necessary cases.

Objective To determine the effectiveness and outcomes of SND in the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with clinically positive neck (cN+) at diagnosis. Material and methods We retrospectively reviewed 159 patients with SCCHN with cN+ at diagnosis, who underwent a SND with curative intent at a tertiary care academic teaching hospital in Spain. We registered patient and tumor characteristics, date and site of recurrences, together with the outcomes. Survival rates were calculated by the Kaplan-Meier method. The minimum follow-up was 18 months or till death. Results A total of 28 neck recurrences were found in the whole series but only 10 neck recurrences occurred in absence of local recurrence. The regional control in the neck in absence of local recurrence was observed in 94% of patients. The neck recurrence rates did not correlated with the pN classification (P = 0.49), the administration of postoperative radiotherapy (P = 0.49) or extranodal extension (P = 0.43). The 5-year regional recurrence-free survival rate was 80% and 92% if only isolated neck recurrences are considered. Conclusions SND offers an effective and oncologically safe surgical procedure in selected patients with clinically positive metastatic nodes in the neck. Our findings suggest that in cN1 and cN2 tumors, SND could replace the modified radical neck dissection without compromising oncologic efficacy.

Background and objective Pneumonia remains the main cause of mortality in patients with systemic lupus erythematosus (SLE). The aim of the study was to establish the clinical characteristics, microbiology and risk factors for poor prognosis in patients with SLE and pneumonia. Methods We reviewed medical records of patients with SLE (American College of Rheumatology criteria) and pneumonia who attended the emergency room in a single tertiary care center (January 2010–March 2015). We collected demographics, treatment and disease activity (SLEDAI-2K) data. Severity scales of pneumonia (CURB-65 (acronym for risk factors measured: confusion, urea nitrogen, respiratory rate, blood pressure, 65 years of age and older) and Pneumonia Severity Index (PSI)) were obtained. A negative composite outcome was defined as need for mechanical ventilation, septic shock or death secondary to pneumonia up to 30 days after discharge. We conducted a univariate and multivariable analysis. Results We studied 158 patients (76% women) with 187 episodes of pneumonia. There were no differences in age, SLE duration, SLE activity, treatment or comorbidities between patients with negative composite outcome vs the other group. In 53 episodes, patients presented with a negative composite outcome. Of these, 46 (24.6%) required intubation, 13 (7%) developed shock and 12 (6.4%) died. The most common bacteria isolated was S. aureus, and we observed a high percentage of nonhabitual microorganisms. Fifteen percent of patients who presented with a negative outcome had low values on CURB-65 and PSI scales. Conclusion Patients with SLE and pneumonia have a high risk of complications and present with a high percentage of nonhabitual microorganisms. Severity scales for pneumonia can misclassify as low risk SLE patients with poor prognosis.

Background: Sensorineural hearing loss (SNHL) is the most common sensory impairment. Comprehensive next-generation sequencing (NGS) has become the standard for the etiological diagnosis of early-onset SNHL. However, accurate selection of target genomic regions (gene panel/exome/genome), analytical performance and variant interpretation remain relevant difficulties for its clinical implementation. Methods: We developed a novel NGS panel with 199 genes associated with non-syndromic and/or syndromic SNHL. We evaluated the analytical sensitivity and specificity of the panel on 1624 known single nucleotide variants (SNVs) and indels on a mixture of genomic DNA from 10 previously characterized lymphoblastoid cell lines, and analyzed 50 Spanish patients with presumed hereditary SNHL not caused by GJB2/GJB6, OTOF nor MT-RNR1 mutations. Results: The analytical sensitivity of the test to detect SNVs and indels on the DNA mixture from the cell lines was > 99.5%, with a specificity > 99.9%. The diagnostic yield on the SNHL patients was 42% (21/50): 47.6% (10/21) with autosomal recessive inheritance pattern (BSND, CDH23, MYO15A, STRC [n = 2], USH2A [n = 3], RDX, SLC26A4); 38.1% (8/21) autosomal dominant (ACTG1 [n = 3; 2 de novo], CHD7, GATA3 [de novo], MITF, P2RX2, SOX10), and 14.3% (3/21) X-linked (COL4A5 [de novo], POU3F4, PRPS1). 46.9% of causative variants (15/32) were not in the databases. 28.6% of genetically diagnosed cases (6/21) had previously undetected syndromes (Barakat, Usher type 2A [n = 3] and Waardenburg [n = 2]). 19% of genetic diagnoses (4/21) were attributable to large deletions/duplications (STRC deletion [n = 2]; partial CDH23 duplication; RDX exon 2 deletion). Conclusions: In the era of precision medicine, obtaining an etiologic diagnosis of SNHL is imperative. Here, we contribute to show that, with the right methodology, NGS can be transferred to the clinical practice, boosting the yield of SNHL genetic diagnosis to 50-60% (including GJB2/GJB6 alterations), improving diagnostic/prognostic accuracy, refining genetic and reproductive counseling and revealing clinically relevant undiagnosed syndromes., Work performed at IMOMA for this project was partially supported by a grant from Fundacion Maria Cristina Masaveu Peterson. Work performed at DREAMgenics was partially supported by University of Oviedo Foundation grants (D.C., P.C.P.).

Introduction and objectives Inadequate auditory feedback in prelingually deaf children alters the articulation of consonants and vowels. The purpose of this investigation was to compare vowel production in Spanish-speaking deaf children with cochlear implantation, and with hearing-aids with normal-hearing children by means of acoustic analysis of formant frequencies and vowel space. Methods A total of 56 prelingually deaf children (25 with cochlear implants and 31 wearing hearing-aids) and 47 normal-hearing children participated. The first 2 formants (F1 and F2) of the five Spanish vowels were measured using Praat software. One-way analysis of variance (ANOVA) and post hoc Scheffe test were applied to analyze the differences between the 3 groups. The surface area of the vowel space was also calculated. Results The mean value of F1 in all vowels was not significantly different between the 3 groups. For vowels /i/, /o/ and /u/, the mean value of F2 was significantly different between the 2 groups of deaf children and their normal-hearing peers. Conclusion Both prelingually hearing-impaired groups tended toward subtle deviations in the articulation of vowels that could be analyzed using an objective acoustic analysis program.

Aim To evaluate the stiffness of parotid and submandibular glands using elastography ultrasound and to correlate it with B-mode ultrasonographical, clinical and serological features, salivary profibrotic and inflammatory chemokines, and salivary gland fibrosis. Methods We performed B-mode and elastography ultrasound of major salivary glands of 26 patients with primary Sjogren's syndrome. We registered the shear wave velocity (SWV) and correlated it with the morphologic ultrasonographic changes assessed by the Hocevar scale. We assessed the European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI), non-stimulated whole salivary flow rate (NSWSF), C3 and C4 levels, anti-Ro/La antibodies, salivary inflammatory (C-X-C motif ligand 13 [CXCL13], CXCL10, CXCL8, C-C motif ligand 2 [CCL2], interleukin 10 [IL-10] and IL-6) and pro-fibrotic (CXCL14, CCL28, tumor necrosis factor-related apoptosis-inducing ligand and transforming growth factor β) chemokines and cytokines and evaluated the presence of fibrosis in the minor salivary gland. Results Ninety-two percent of patients were women; mean age was 51.1 ± 11 years; median disease duration was 6.1 years; 92.3% had oral symptoms and 26.9% fibrosis. The median B-mode score was 22.2 points and the median SWV 2.5 m/s (τ = 0.53, P = 0.001). The SWV correlated with the NSWSF (τ = -0.53, P = 0.001), ESSDAI (τ = 0.31, P = 0.03), glandular ESDDAI domain (τ = 0.36, P = 0.02), C4 levels (τ = -0.32, P = 0.04), salivary CXCL13 (τ = 0.29, P = 0.03) and CXCL10 (τ = 0.30, P = 0.003), but not with age and fibrosis. Conclusion WV correlated with the B-mode ultrasound score, systemic and glandular activity and in a large degree with CXCL10, an inflammatory chemokine, but not with fibrosis. An increased SWV might represent chronic glandular inflammation rather than fibrotic changes in these patients.

Transoral laser microsurgery (TLM) has become the standard approach for treatment of early-stage laryngeal carcinoma in most institutions due to their good oncological and functional results with few local complications. The purpose of this study was to analyze the oncological and functional results of TLM in the treatment of laryngeal tumors at our Hospital. Patients with laryngeal squamous cell carcinoma (LSCC) treated from 1998 to 2013 with TLM with curative intention, and with a minimum follow-up of 24 months, were reviewed. 203 patients with LSCC were included. 195 patients were men (96%) and 8 women (4%), with a mean age of 63 years. The series includes 134 (66%) T1, 40 (20%) T2, and 29 (14%) T3-classified tumors. 116 tumors (57%) were in the glottis, 79 (39%) in the supraglottis and 8 (4%) in the anterior commissure. 16 patients (8%) received adjuvant radiotherapy. Initial local control was obtained in 75.5% of patients. The 5-year overall survival rate was 84% and the 5-year disease-specific survival was 90%. The presence of nodal metastasis (p

Introduction and objectives Radioiodine is the principal treatment for differentiated thyroid carcinomas. The aim of this study is to present our experience in the management of these tumours. Material and method We present a retrospective study of 55 patients operated for differentiated thyroid carcinoma in our hospital between 2007 and 2011. Results The mean age at time of diagnosis was 49 years, and females predominated (78% of cases). Seventy eight percent of the patients were in the initial stages (stages I and II). The definitive histopathological diagnosis was papillary carcinoma in 84% and follicular carcinoma in the remaining 16%. All of the patients, with the exception of 2 (4%), underwent total thyroidectomy, with lymphadenectomy in 58% of cases. Nine percent of the patients had permanent hypoparathyroidism and although 18% suffered transitory unilateral paralysis, 40% of these female patients had completely recovered after 6 months. Eighty-nine percent of the patients were given radioiodine postoperatively. There was a recurrence rate of 40% most of which was at cervical level (29% of the patients). Survival at 5 years was 87%, 95% of the papillary subtype, falling to 56% of the follicular subtype (P=.001). Discussion/conclusions The prognosis for differentiated thyroid carcinomas is excellent after appropriate surgical treatment, thorough preoperative assessment, and strict postoperative follow-up due to the significant recurrence rates.

We investigated the proportion of Vβ T cell receptor (TCR) gene expression in peripheral CD3+ lymphocytes in familial and non-familial systemic lupus erythematosus (SLE) patients.The Vβ TCR repertoire was studied in 14 families in which several members had SLE. The Vβ TCR usage in SLE patients (n = 27) was compared with that in healthy members of these multiplex families (n = 47), in 37 sporadic SLE patients who had no relatives with SLE, and in 15 healthy unrelated controls. Vβ TCR repertoire expression was studied by multiparameter flow cytometry with the use of an array of 24 different Vβ TCR gene family-specific monoclonal antibodies.We found the same Vβ TCR expression profile in the comparisons between sporadic SLE and familial SLE cases and healthy relatives, which included increased expression of Vβ 5.2, Vβ 11 and Vβ 16, and lower expression of Vβ 3, Vβ 4, Vβ 7.1 and Vβ 17. Interestingly, solely Vβ 17 was differentially expressed among sporadic and familial SLE. Also, increased expression of Vβ 9 was the hallmark among familial SLE (casesand h ealthy relatives) in comparison to controls.These results highlight the notion that the final profile of the Vβ TCR repertoire seen in familial and non-familial SLE seems to arise from the interaction of genetic, environmental, and immunoregulatory factors. Furthermore, it may contribute to the immunologic abnormalities affecting relatives of SLE patients.Se investigó la proporción de la expresión génica del receptor variable beta de células T (Vβ TCR) en linfocitos periféricos CD3+ en pacientes con lupus eritematoso generalizado (LEG) familiar y no familiar.El repertorio de Vβ TCR se estudió en 14 familias que presentaban más de un miembro con LEG. El uso de Vβ TCR en pacientes con LEG (n = 27) se comparó con el de los miembros sanos de estas familias (n = 47), con 37 pacientes con LEG esporádico y con 15 controles sanos. La expresión del repertorio de Vβ TCR se estudió por citometría de flujo multiparamétrica utilizando un arreglo de 24 diferentes anticuerpos monoclonales específicos de genes familiares para Vβ TCR.Se encontró el mismo perfil de expresión en las comparaciones entre los casos de LEG esporádico y familiar, así como en los consanguíneos sanos de las familias multicasos, que incluía una expresión incrementada de Vβ 5.2, Vβ 11 y Vβ 16, y una menor expresión de Vβ 3, Vβ4, Vβ 7.1 y Vβ 7. De manera interesante, solo Vβ 17 se expresó de modo diferente entre casos familiares y esporádicos de LEG. Igualmente, la expresión incrementada de Vβ 9 fue el distintivo entre los casos de LEG familiar (casos y consanguíneos sanos) y los controles sanos.Estos resultados refuerzan la noción de que el perfil final del repertorio Vβ TCR observado en LEG familiar y no familiar parece surgir de la interacción de factores genéticos, ambientales e inmunorreguladores, además de que pueden explicar las alteraciones inmunitarias que se observan en los consanguíneos sanos de pacientes con LEG.

espanolObjetivo: Se investigo la proporcion de la expresion genica del receptor variable beta de celulas T (Vβ TCR) en linfocitos perifericos CD3+ en pacientes con lupus eritematoso generalizado (LEG) familiar y no familiar. Metodo: El repertorio de Vβ TCR se estudio en 14 familias que presentaban mas de un miembro con LEG. El uso de Vβ TCR en pacientes con LEG (n = 27) se comparo con el de los miembros sanos de estas familias (n = 47), con 37 pacientes con LEG esporadico y con 15 controles sanos. La expresion del repertorio de Vβ TCR se estudio por citometria de flujo multiparametrica utilizando un arreglo de 24 diferentes anticuerpos monoclonales especificos de genes familiares para Vβ TCR. Resultados: Se encontro el mismo perfil de expresion en las comparaciones entre los casos de LEG esporadico y familiar, asi como en los consanguineos sanos de las familias multicasos, que incluia una expresion incrementada de Vβ 5.2, Vβ 11 y Vβ 16, y una menor expresion de Vβ 3, Vβ4, Vβ 7.1 y Vβ 7. De manera interesante, solo Vβ 17 se expreso de modo diferente entre casos familiares y esporadicos de LEG. Igualmente, la expresion incrementada de Vβ 9 fue el distintivo entre los casos de LEG familiar (casos y consanguineos sanos) y los controles sanos. Conclusiones: Estos resultados refuerzan la nocion de que el perfil final del repertorio Vβ TCR observado en LEG familiar y no familiar parece surgir de la interaccion de factores geneticos, ambientales e inmunorreguladores, ademas de que pueden explicar las alteraciones inmunitarias que se observan en los consanguineos sanos de pacientes con LEG. EnglishObjective: We investigated the proportion of Vβ T cell receptor (TCR) gene expression in peripheral CD3+ lymphocytes in familial and non-familial systemic lupus erythematosus (SLE) patients. Method: The Vβ TCR repertoire was studied in 14 families in which several members had SLE. The Vβ TCR usage in SLE patients (n = 27) was compared with that in healthy members of these multiplex families (n = 47), in 37 sporadic SLE patients who had no relatives with SLE, and in 15 healthy unrelated controls. Vβ TCR repertoire expression was studied by multiparameter flow cytometry with the use of an array of 24 different Vβ TCR gene family-specific monoclonal antibodies. Results: We found the same Vβ TCR expression profile in the comparisons between sporadic SLE and familial SLE cases and healthy relatives, which included increased expression of Vβ 5.2, Vβ 11 and Vβ 16, and lower expression of Vβ 3, Vβ 4, Vβ 7.1 and Vβ 17. Interestingly, solely Vβ 17 was differentially expressed among sporadic and familial SLE. Also, increased expression of Vβ 9 was the hallmark among familial SLE (cases and healthy relatives) in comparison to controls. Conclusion: These results highlight the notion that the final profile of the Vβ TCR repertoire seen in familial and non-familial SLE seems to arise from the interaction of genetic, environmental, and immunoregulatory factors. Furthermore, it may contribute to the immunologic abnormalities affecting relatives of SLE patients.

The aim of this study is to compare the association and the predictive capacity of DSA MFI, complement fixing capacity (C3d assay) and IgG subclasses determination in the prediction of FCxM result.We used cryopreserved (70C) sera from potential renal transplant recipients, containing DSA against their respective potential donors. All patients showed negative AHG-CDC CxM and either positive or negative FCxM. Class I and Class II HLA-DSA were determined by Luminex SAB. C3d were detected by Luminex (Lifecodes®Immucor), DSA IgG 1-4 subclasses were evaluated using monoclonal antibodies specific for IgG subclasses (Luminex).93 donor/recipient tests were evaluated; 32 (35.9%) patients presented at least one C3d + Ab, of which only 11 (11.8%) were donor specific. At least one IgG subclass was identified in 45 samples (48.3%). Twenty-seven FCxM tests (29%) were positive. On multivariate analysis HLA mismatches, the IgG subclass detection, DSA MFI and class II PRA remain associated to FCxM whereas C3d + Ab was not associated. For the FCxM prediction, the IgG subclass detection in combination with the DSA-MFI 2800, had the best negative predictive value 93.9 (CI 95%, 84.2-100).Neither the C3d assay nor the IgG subclasses detection alone had an adequate predictive capacity for the FCxM. In the absence of IgG subclass detection and DSA-MFI 2000, the probability of a negative FCxM was near 94%.

El titanio es ampliamente utilizado como implante dental dado que es bioinerte y osteointegrable. Sin embargo, dado que este material no puede inducir el crecimiento de hueso desde su superficie, es usual que se le realicen distintos tratamientos superficiales para desarrollar recubrimientos bioactivos. El tratamiento alcalino tiene por objetivo formar un gel de titanato de sodio amorfo, el cual se puede estabilizar, por medio de un tratamiento térmico posterior. Durante este último, el hidrogel se deshidrata y se densifica para formar una capa de titanato de sodio estable y parcialmente cristalizado. En el presente trabajo se analizaron los efectos producidos por diferentes tratamientos térmicos posteriores al alcalino, sobre superficies de titanio cp con tratamiento superficial de blastinizado y APQ (anodizado por plasma químico). Para cada caso se caracterizó la superficie con el fin de optimizar la condición de aplicación. Las temperaturas de los tratamientos térmicos fueron 400, 600 y 800 ºC, dado que en este rango el titanato varía su proporción de fase amorfa y cristalina y por ende sus propiedades. La evaluación de los resultados se realizó mediante ensayos de adhesión Rockwell C, medición del ángulo de contacto inicial por goniometría, difracción de rayos x, SBF y microscopia electrónica de barrido. Caracterizadas las probetas post tratamiento térmico se pudo observar que, las muestras tratadas a 800 ºC presentaron una estructura superficial cristalina, mala adhesión y no indujeron crecimiento de apatita sobre su superficie. No obstante presentaron una superficie hidrofilica. Por otro lado, las muestras tratadas a 400 y 600 ºC presentaron superficialmente una fase parcialmente cristalizada, con buena adherencia y buena hidrofilicidad. Mediante SEM-EDS, se observó sobre sus superficies la formación de una capa de apatita homogénea., Titanium is widely used as dental implant since it is bio-inert and osseointegratable. However, provided that this material cannot induce bone growth from its surface, it is usual to carry out different surface treatments in order to develop bioactive coatings that increase both the initial rate of bone development and the biological anchorage of implant attachment to the host bone. The aim of the alkaline treatment is to form an amorphous gel of sodium titanate, which can be stabilized by means of a subsequent thermal treatment. During this, the hydro gel is dehydrated and thickened to form a layer of stable and partially crystallized sodium titanate. In the present work it was analyzed the effects produced by different thermal treatments after the alkaline one, on surfaces of cp titanium with surface treatment of blasting and MAO (micro-arc oxidation pro-cess). For each case the surface was characterized in order to enhance the application condition. The temper-ature of the thermal treatments was 400, 600 and 800 ºC, since titanate varies its ratio of amorphous and crys-talline phase in this range and therefore its properties. The assessment of results was carried out by means of Rockwell-C adhesion standard test, measurement of the initial contact angle by goniometry, X-ray diffraction and analytic scanning electronic microscopy. Characterized post thermal treatment samples, it was observed that the samples treated to 800 ºC presented a crystalline superficial structure, bad adherence and did not develop apatite growth on its surface. Neverthe-less, they presented sufficiently surface hydrophilic. On the contrary, the samples treated at 400 and 600 ° C presented superficially a partially crystallized phase, with good adhesion and good hydrophilicity. Through SEM-EDS, the formation of a homogeneous apatite layer was observed on their surfaces., Facultad de Ingeniería, Comisión de Investigaciones Científicas de la provincia de Buenos Aires

The objective of this study was to determine the relationship between citrullinated proteins in synovial tissue with peripheral anti-citrullinated peptides autoantibodies (ACPA) and peptidylarginine deiminase (PADI) PADI2, PADI3, and PADI4 messenger RNA (mRNA) expressions in synovial tissue and fibroblast-like synoviocytes in rheumatoid arthritis (RA) patients. Eleven RA and 12 osteoarthritis (OA) patients who underwent knee replacement surgery were studied. We detected citrullinated proteins in synovial tissue homogenates by western blot and serum ACPA by ELISA to anti-cyclic citrullinated peptide (anti-CCP) antibodies, and PADI2, PADI3, and PADI4 mRNA expressions in synovial tissue and in fibroblast-like synoviocytes. Patients with high amount of citrullinated proteins in synovial tissue (3 out of 7) have high levels of anti-CCP in serum. However, in the remaining 4 patients, the amount of synovial citrullinated proteins was minimal and their sera showed low levels of anti-CCP antibodies. Furthermore, we observed an increase in PADI2 mRNA expression in RA synovial tissue compared with OA patients (p = 0.02). We detected PADI3 mRNA in the synovial tissue of RA patients, but not in the tissue of OA patients. Even though fibroblast-type synoviocytes in RA are not the main source of PADs in the synovial tissue, they express PADI2 mRNA moderately, PADI4 mRNA weakly, while there is no detectable expression of PADI3 mRNA. In conclusion, we found a variety of citrullinated proteins in the synovial tissue of RA patients and the amount of such proteins is related to serum concentration of anti-CCP antibodies. We identified the presence of PADI3 mRNA expression in synovial tissue and PADI2 and PADI4 mRNA expressions in fibroblast-like synoviocytes from patients with RA.

Total laryngectomy (TL) and postoperative radiotherapy (RT), when indicated, have proven to be effective in treating cases of locally advanced laryngeal cancer. The aim of this study was to analyse the oncological outcomes of this procedure in patients with laryngeal cancer classified T3 and T4a.We studied 80 patients (51 T3 and 29 T4a) with primary squamous cell carcinoma of the larynx who underwent TL between 1998 and 2006. Bilateral neck dissection was performed in 54 patients, unilateral in 11, and central in 4. Twenty patients (25%) received postoperative radiotherapy.Mean age was 64 years with a male predominance (97%). As for habits, 96% were smokers and 89% consumed alcohol. Lymph node metastases occurred in 44% of patients and extracapsular invasion in 37% of them. All cases had tumour-free margins. In all, 25% of patients had loco-regional recurrence and 5% developed distant metastases. The 5-year disease-specific survival was 72% and 5-year overall survival was 55%. Variables associated with decreased disease-specific survival were T4 classification (P=.068), N2-N3 classifications (P=.005), extracapsular invasion (P=.018) and stage iv disease (P=.009). On multivariate analysis, the only variable associated with decreased disease-specific survival was the presence of N2-N3 nodal metastases (P=.008).TL is an effective treatment for the management of patients with locally advanced laryngeal cancer. Organ preservation protocols should achieve similar oncological results to those obtained with TL.

Resumen Introduccion y objetivos La laringectomia total (LT), mas eventual radioterapia (RT), ha demostrado ser un tratamiento eficaz en los casos de cancer de laringe localmente avanzado. El objetivo de este trabajo es analizar los resultados oncologicos de este procedimiento en pacientes con cancer de laringe T3 y T4a. Metodos Se incluyeron 80 pacientes (51 T3 y 29 T4a) con carcinoma epidermoide primario de laringe tratados mediante LT entre los anos 1998 y 2006. Se realizo vaciamiento cervical bilateral en 54 pacientes, unilateral en 11 y central en 4. Veinte pacientes (25%) recibieron RT postoperatoria. Resultados La edad media fue de 64 anos, con predominio de varones (97%). El 96% eran fumadores y el 89% consumia alcohol. Un 44% de los pacientes presentaba metastasis ganglionares, y de estos un 37% mostro invasion extracapsular. En todos los casos se obtuvieron bordes libres de tumor. Un 25% de los pacientes presentaron recidiva locorregional y 5% desarrollaron metastasis a distancia. La supervivencia especifica a 5 anos fue de un 72% y la global del 55%. Las variables asociadas a menor supervivencia especifica fueron la clasificacion T4 (p = 0,068), la clasificacion N2-N3 (p = 0,005), la invasion extracapsular (p = 0,018) y el estadio iv (p = 0,009). En el analisis multivariante la unica variable significativa para la supervivencia especifica fue la clasificacion N2-N3 (p = 0,008). Conclusiones La LT es un tratamiento eficaz para el manejo de los pacientes con cancer de laringe localmente avanzado. Los protocolos de preservacion de organo deberian alcanzar resultados oncologicos similares a los demostrados por la LT.

Resumen Introduccion y objetivos Los carcinomas de orofaringe son neoplasias agresivas habitualmente diagnosticadas en estadios avanzados. El objetivo de este estudio es exponer los resultados oncologicos y funcionales del tratamiento de estos tumores mediante reseccion quirurgica transoral (RTO). Metodos Se realizo un estudio retrospectivo en 43 pacientes con carcinoma epidermoide de orofaringe tratados mediante RTO. En el 52% de los casos el tumor se originaba en la region amigdalina, en el 23% en el paladar blando, en el 21% en la base de la lengua y en el 4% en la pared posterior. Ocho casos se clasificaron como estadio I , 9 como estadio II , 7 como estadio III , 16 como estadio IV A y 3 como estadio IV B. Dieciocho pacientes recibieron radioterapia postoperatoria. Se revisaron las historias de estos pacientes para obtener informacion en cuanto a control local y regional, supervivencia total y especifica de la enfermedad, y funcion fonatoria y deglutoria. Resultados La tasa global de recidivas fue del 44%, siendo la tasa de recidivas locales del 18%. La supervivencia global y especifica a los 5 anos fue del 55% y 66%, respectivamente. Las tasas de supervivencia especifica a los 5 anos segun la localizacion tumoral fueron del 100%, 85%, 44%, y 30% para la pared posterior, amigdala, paladar blando y base de la lengua. El control local a los 5 anos fue del 100%, 90%, y 0% para el paladar, amigdala y base de la lengua, respectivamente. En todos los casos se preservo la laringe, y los pacientes no requirieron traqueotomia definitiva y reanudaron la alimentacion oral. Conclusiones La RTO es una alternativa terapeutica eficaz para el tratamiento primario de los carcinomas de orofaringe, en la era de la quimio-radioterapia, obteniendo unos buenos resultados oncologicos y funcionales.