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Simple Summary Sinonasal carcinomas are rare tumors with an overall poor prognosis. Due to limitations in local therapeutic approaches, systemic neo-adjuvant or adjuvant therapies are becoming increasingly important in order to improve patient outcome. This study aimed to examine potentially therapeutic targetable molecular alterations in different sinonasal tumors, including deficiency in mismatch repair proteins and microsatellite instability as well as driver mutations. According to our results, immunohistochemical (IHC) analysis of mismatch repair (MMR) proteins and sequencing-based panel analysis should be integrated into the diagnostics of clinically aggressive inverted sinonasal papilloma (ISP) and sinonasal squamous cell carcinoma (SNSCC) in order to enable the therapeutic possibility of a targeted therapy. Abstract Due to limitations in local therapy approaches for sinonasal tumors, improvement in systemic therapies plays a pivotal role for prolongation of the patient’s survival. The aim of this study was to examine potential biomarkers, including deficiency in mismatch repair proteins (dMMR)/microsatellite instability (MSI-H) in sinonasal cancers and their precancerous lesions. A comprehensive analysis of 10 sinonasal cancer cell lines by whole exome sequencing, screening 174 sinonasal tumors by immunohistochemistry (IHC) for mismatch repair deficiency and next generation sequencing (NGS) of 136 tumor samples revealed a dMMR/MSI-H sinonasal squamous cell carcinoma (SNSCC) cell line based on a somatic missense mutation in MLH1 and an overall frequency of dMMR/MSI-H SNSCC of 3.2% (4/125). Targetable EGFR mutations were found in 89.3% (25/28) of inverted sinonasal papilloma (ISP) and in 60% (6/10) of ISP-associated carcinomas. While PIK3CA and EGFR mutations were not mutually exclusive, KRAS mutated tumors were an EGFR-wildtype. The effect of potential driver mutations in FGFR2, FGFR3, BRAF, HRAS, MAP2K1, PTEN, NOTCH1 and CARD11 need further investigation. Our results suggest that biomarker testing, including MMR-IHC and NGS panel analysis, should be integrated into the diagnostics of clinically aggressive ISPs and SNSCC to assess prognosis and facilitate therapeutic decisions.

To evaluate CCL2, CXCL8, and CXCL10 in the tears of patients with Primary Sjögren's syndrome (PSS) and correlate them with ocular symptoms/discomfort and objective ocular tests.We studied 21 patients with PSS. A single ophthalmologist, expert in dry eye, examined the patients and assessed tear film breakup time, Schirmer I test, tear meniscus height, Van Bijsterveld staining score and SICCA Ocular Staining Score. We also assessed the ESSPRI and ocular dryness VAS and the Ocular Surface Disease Index (OSDI), a 12-item scale assessing symptoms associated with dry eye disease and their impact on vision (ocular symptoms/discomfort). Tear samples collected with sterile tear flow strips were frozen at -86 °C until testing. After thawing, tears were extracted from the strips. We tested CCL2, CXCL8, and CXCL10 by luminometry. We also included 21 healthy control subjects without a dry eye.CXCL8 levels were similar in patients and controls. PSS patients had lower levels of CXCL10 (472.8 vs. 1652 pg/μL, p = 0.009) and CCL2 (1.08 vs. 9 pg/μL, p = 0.0001) than controls. Patients with worse ocular sicca symptoms/discomfort had the lowest CXCL10 levels (239.3 vs. 646.2 pg/μL, p = 0.02). CCL2 correlated with tear meniscus height (τ = 0.37, p = 0.02) and with OSS (τ = -0.3, p = 0.05).We found lower levels of CXCL10 and CCL2 in the tears of patients with PSS, associating the former with worse ocular symptoms and the latter with positive ocular target tests.

Carotid blowout syndrome (CBS) is defined as a rupture of common carotid artery or its branches. Endovascular intervention has been advocated as first line of treatment for CBS. This Case Report describes 5 patients with prior history of head and neck cancer who presented with CBS. Two patients presented as acute, 2 as impending, and one as threatened CBS. The lesions found were pseudoaneurysm and focal vascular irregularities involving the common carotid artery, cervical internal carotid artery and lingual artery. Embolization and occlusion with detachable coils of the artery was used in all patients. Technical success and immediate hemostasis were achieved in all patients. One patient presented transient cranial nerve palsy. No recurrent CBS was reported during the follow-up. In our experience, coil embolization, if possible, is a safe and efficient technique in treatment of CBS secondary to head and neck cancers.

Sinonasal squamous cell carcinoma (SNSCC) is an aggressive tumor predominantly arising in the maxillary sinus and nasal cavities. Advances in imaging, surgical and radiotherapeutic techniques have reduced complications and morbidity, however, the prognosis generally remains poor, with an overall 5-year survival rate of 30–50%. As immunotherapy may be a new therapeutic option, we analyzed CD8+ tumor-infiltrating lymphocytes (TILs) and the tumor microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) in a series of 57 SNSCCs. Using immunohistochemistry, tissue samples of 57 SNSCCs were analyzed for expression of CD8 on TILs and of PD-L1 on tumor cells. The results were correlated to the clinical and survival data. In total, 88% (50/57) of the tumors had intratumoral CD8+ TILs, 19% (11/57)—CD8high (&gt, 10%), and 39/57 (68%)—CD8low (1–10%). PD-L1 positivity (&gt, 5%) was observed in 46% (26/57) of the SNSCCs and significantly co-occurred with CD8+ TILs (p = 0.000). Using univariate analysis, high intratumoral CD8+ TILs and TMIT I (CD8high/PD-L1pos) correlated with a worse survival rate. These results indicate that SNSCCs are immunogenic tumors, similar to head and neck squamous cell carcinomas. Nineteen percent of the cases were both CD8high and PD-L1pos and this subgroup may benefit from therapy with immune checkpoint inhibitors.

Resumen Antecedentes y objetivo El riesgo de meningitis bacteriana aumenta en los pacientes con implante coclear. Por ello, se indica la vacunacion antineumococica, antigripal y frente a Haemophilus influenzae tipo b en este grupo. El objetivo del presente estudio es conocer el cumplimiento del calendario vacunal en los pacientes implantados en un hospital de referencia. Materiales y metodos Se incluyeron los pacientes con implante coclear intervenidos entre 2005 y 2015. Se evaluaron las coberturas vacunales frente a gripe estacional, Haemophilus influenzae tipo b, neumococo conjugada de 13 serotipos y neumococo polisacarida de 23 serotipos. Se dividio la muestra en 2 grupos por edad ( Resultados De los 153 pacientes estudiados (28,01% 0-13 anos y 71,9% ≥ 14), solo 2 (5,71%) tuvieron un 100% de adherencia al calendario vacunal, mientras que el 65,71% registro un cumplimiento del 50% o menor. Globalmente, la cobertura de vacunacion frente a la pauta secuencial de neumococo fue del 48,57%. La poblacion pediatrica supero el 90% de cobertura para la vacuna frente a Haemophilus influenzae tipo b y neumococo conjugada de 13 serotipos, mientras que en los mayores de 14 anos apenas supero el 50%. La cobertura frente a gripe estacional fue inferior al 40%. Se obtuvo una correlacion inversa entre la edad y el cumplimiento, aunque no estadisticamente significativa. Conclusiones Las coberturas de vacunacion en los pacientes con implante coclear evaluados son mas bajas de lo esperado. Se propone la colaboracion estrecha entre los servicios de Otorrinolaringologia y las Unidades de Vacunas como principal estrategia para la mejora.

The risk of bacterial meningitis increases in cochlear implant patients. Therefore, pneumococcal, influenza and Haemophilus influenzae type b vaccination is indicated in this group. The aim of this study was to determine compliance with the vaccination calendar in patients implanted in a referral hospital.Patients with cochlear implant operated between 2005 and 2015 were included. Vaccine coverage for seasonal influenza, Haemophilus influenzae type b and pneumococcal conjugate 13-serotypes and pneumococcal polysaccharide 23-serotypes was evaluated. The sample was divided into 2 age groups (14 years and≥14 years). A univariate and bivariate analysis was performed.Of the 153 patients studied (28.01% 0-13 years old and 71.9%≥14), only 2 (5.71%) had 100% adherence to the vaccination schedule, while 65.71% had compliance of 50% or less. Overall, vaccination coverage against the sequential pneumococcal pattern was 48.57%. The paediatric population exceeded 90% coverage for the vaccine against Haemophilus influenzae type b and pneumococcal conjugate 13-serotypes while in those over 14 years of age it barely exceeded 50%. Influenza coverage was less than 40%. An inverse correlation was obtained between age and compliance, although not statistically significant.Vaccination coverage in patients with cochlear implant is lower than expected. Close collaboration between Otolaryngology departments and the Vaccination Units is proposed as the main strategy for improvement.

Resumen Introduccion y objetivos La inadecuada retroalimentacion auditiva en los ninos con hipoacusia prelocutiva altera la articulacion de consonantes y vocales. El proposito de esta investigacion es comparar la produccion de vocales en ninos hipoacusicos hispanohablantes con implante coclear o adaptacion audioprotesica con ninos normooyentes por medio del analisis acustico de las frecuencias formanticas y el espacio vocal. Metodo Un total de 56 ninos con hipoacusia prelocutiva (25 con implante coclear y 31 con audifonos) y 47 ninos normooyentes participaron en el estudio. Los 2 primeros formantes (F1 y F2) de las 5 vocales del idioma espanol se midieron utilizando el programa Praat. Para analizar las diferencias entre los 3 grupos se aplico el metodo ANOVA de analisis de la varianza y el test de Scheffe. Tambien se calculo el area del espacio vocal. Resultados El valor medio del F1 en todas las vocales no mostro diferencias significativas en los 3 grupos de ninos. Para las vocales /i/, /o/ y /u/ el valor medio del F2 fue significativamente diferente entre los 2 grupos de ninos hipoacusicos y el grupo de ninos normooyentes. Conclusion Ambos grupos de ninos con hipoacusia prelocutiva tienden a presentar sutiles desviaciones en la articulacion de las vocales que pueden ser analizadas mediante un programa de analisis acustico.

Resumen Introduccion y objetivos El tratamiento principal de los carcinomas diferenciados de tiroides es la cirugia seguida de radioyodo. El proposito de este estudio es exponer nuestra experiencia en el manejo de estos tumores. Material y metodo Se presenta un estudio retrospectivo de los 55 pacientes intervenidos quirurgicamente de un carcinoma diferenciado de tiroides en nuestro hospital entre los anos 2007 y 2011. Resultados La edad media al diagnostico fue de 49 anos, con un predominio femenino (78% de los casos). El 78% de los pacientes se encontraban en fases iniciales (estadios i y ii ). El diagnostico histopatologico definitivo fue de carcinoma papilar en el 84% y folicular en el 16% restante. A todos, salvo a 2 pacientes (4%), se les realizo una tiroidectomia total, acompanada de linfadenectomia en el 58% de los casos. Un 9% de los pacientes presento hipoparatiroidismo permanente y aunque un 18% sufrio paralisis recurrencial unilateral transitoria, un 40% de ellos se recupero completamente a los 6 meses. Se administro radioyodo en el postoperatorio al 89% de los pacientes. Se produjo un 40% de recidivas, la mayor parte de las cuales (29% de los pacientes) se localizaron a nivel cervical. La supervivencia a los 5 anos fue del 87%, siendo del 95% en el subtipo papilar y descendiendo al 56% en el folicular (p = 0,001). Discusion/conclusiones Los carcinomas diferenciados de tiroides son tumores con un pronostico excelente tras un tratamiento quirurgico adecuado previa valoracion preoperatoria exhaustiva y seguimiento postoperatorio estricto debido a las tasas significativas de recidiva.

Resumen Introduccion y objetivos La fiabilidad de las calificaciones perceptuales de la calidad global de la voz y sus dimensiones especificas es dificil de alcanzar, por cuanto estos juicios dependen de la subjetividad del examinador. De este modo, la busqueda de unas medidas clinicas que sean objetivas, validas y accesibles es una prioridad para incluirlas en los protocolos de evaluacion de la voz. El proposito del presente estudio fue: 1) determinar la exactitud diagnostica de un unico parametro acustico, la prominencia del pico cepstral suavizado (CPPS), para predecir la presencia y severidad de una disfonia en vocales sostenidas y habla conectada utilizando el programa Praat; 2) determinar la relacion entre las medidas del CPPS y las calificaciones perceptuales de la calidad vocal; y 3) describir los valores normativos del CPPS. Metodo Se obtuvo el valor del CPPS de muestras vocales sostenidas y de habla conectada de 72 sujetos hispanohablantes con trastornos vocales y de 52 sujetos hispanohablantes sanos utilizando el programa Praat. Se llevo a cabo un estudio estadistico completo utilizando el programa SPSS de IBM version 23. Resultados Se encontro una sensibilidad de un 70% y una especificidad de un 85%. La severidad estimada de la voz, tanto en vocal sostenida como en habla conectada, se correlaciono de forma importante con las calificaciones perceptuales de severidad global de la disfonia. Conclusiones Un parametro acustico unico, el CPPS calculado mediante el programa Praat, predice de forma importante el estatus de un trastorno vocal. Se considera la incorporacion del CPPS para complementar la valoracion clinica de la voz.

Introduction and objectives Perceptual rating of overall voice quality and other more specific perceptual dimensions is difficult, as such judgments depend on the listener's subjectivity. Thus, finding objective, valid, and accessible clinical measures to include in comprehensive voice evaluation protocols is a priority. The purposes of this study were to (1) determine the diagnostic accuracy of a single acoustic measure, smoothed cepstral peak prominence (CPPS), to predict voice disorder status from sustained vowels and connected speech samples using the software Praat; (2) to determine the relationship between measures of CPPS and perceptual ratings of vocal quality; and (3) describe the normative values of CPPS. Method Measures of CPPS were obtained from connected speech and sustained vowel recordings of 72 Spanish-speaking subjects with voice disorders and 52 nondysphonic Spanish-speaking subjects with no vocal disorders using freely downloadable Praat software. IBM SPSS Statistics software version 23 was used to complete the statistical analyses. Results Results revealed a 70% sensitivity rate, a specificity rate of 85%. Estimated severity for sustained vowels and connected speech were strongly correlated and significantly associated with listener ratings of dysphonia severity. Conclusions A single acoustic measure of CPPS was highly predictive of voice disorder status using Praat software. Clinicians may consider using CPPS to complement clinical voice evaluation and screening protocols.

Objective The objective was to determine the results of the treatment of severe and/or refractory epistaxis requiring hospital admission. In addition, the results of arterial ligation versus embolisation were compared. Material and method Sixty-three patients with severe and/or refractory epistaxis requiring hospital admission between August 2014 and December 2016 were included prospectively. Results Eleven patients (17%) underwent embolisation, 5 (8%) endoscopy ligation and the remaining 47 (75%) underwent conservative treatment with tamponade. The mean age of the patients in which conservative measures were sufficient was 72 years, while the age of those treated with embolisation was 71 years and of those who underwent surgery was 53 years. For the patients who underwent conservative treatment or surgery, the average stay was 6 days, compared to 9 days for those who underwent embolisation. One patient suffered a hemispheric stroke after embolisation. No post-surgical complications were observed. Conclusions Most cases of severe and/or refractory epistaxis are resolved by conventional tamponade. Endoscopy ligation is associated with a decrease in hospital stay, without serious complications. It is advisable to have all the possible therapeutic options available, for which the presence of interventional radiologists and experienced surgeons is essential to avoid complications and decide the treatment to be performed individually for each patient.

Resumen Introduccion y objetivos El objetivo fue determinar los resultados del tratamiento de las epistaxis graves y/o refractarias que requirieron ingreso hospitalario. Ademas se compararon los resultados del tratamiento mediante ligadura arterial o embolizacion. Material y metodo Se incluyeron de forma prospectiva 63 pacientes con epistaxis grave y/o refractaria que requirieron ingreso hospitalario entre agosto de 2014 y diciembre de 2016. Resultados En 11 pacientes (17%) se realizo embolizacion, 5 (8%) fueron intervenidos mediante endoscopia y en los 47 restantes (75%) se realizo tratamiento conservador. La edad media de los pacientes en los que las medidas conservadoras fueron suficientes fue de 72 anos, mientras que la edad de aquellos tratados con embolizacion fue de 71 anos y de los que fueron intervenidos quirurgicamente fue de 53 anos. En los pacientes sometidos a tratamiento conservador o a cirugia la estancia media fue de 6 dias, frente a 9 dias en aquellos en los que se realizo embolizacion. Un paciente sufrio un ictus hemisferico tras la embolizacion. No se observaron complicaciones posquirurgicas. Conclusiones La mayoria de los pacientes con epistaxis graves y/o refractarias se resuelven mediante taponamiento convencional. El tratamiento mediante ligadura arterial esta asociado a una disminucion de la estancia hospitalaria, sin observarse complicaciones graves. Es aconsejable disponer de todas las opciones terapeuticas posibles para lo cual la presencia de radiologos intervencionistas y cirujanos experimentados es fundamental para evitar complicaciones y decidir el tratamiento a realizar de forma individual en cada paciente.

Resumen Antecedentes y objetivos Los angiofibromas juveniles (AJ) son tumores benignos cuyo tratamiento de eleccion es la cirugia. Dada su localizacion y su comportamiento expansivo pueden generar una elevada morbilidad. Tienen gran tendencia al sangrado y su tratamiento es complejo. El manejo de los AJ ha cambiado, pero continua siendo un reto. El objetivo de este estudio fue revisar a una serie de pacientes con AJ tratados mediante un abordaje endonasal endoscopico endonasal. Material y metodos Se revisaron las historias medicas de todos los pacientes con AJ intervenidos mediante un abordaje endoscopico endonasal. Las principales variables estudiadas incluyeron el estadio tumoral, la perdida de sangre intraoperatoria, la tasa de complicaciones y la tasa de persistencia o recidiva. Resultados Se incluyeron un total de 31 pacientes, 30 varones y una mujer. La edad media fue de 17 anos. Segun la clasificacion de Radkowski, un caso pertenecia al estadio I, 5 al estadio IIA, 9 al estadio IIB, 4 al estadio IIC, 10 al estadio IIIA y 2 al estadio IIIB. El 39% de los AJ pertenecian a estadios avanzados (IIIA y IIIB). La perdida media de sangre fue de 1.156 ml. Excepto en un caso, no se observaron complicaciones significativas. La tasa de persistencia/recurrencia al finalizar el seguimiento fue del 6% (2 AJ en estadio avanzado). El seguimiento medio fue de 86 meses. Conclusiones Este estudio retrospectivo respalda que la opcion de los abordajes endoscopicos endonasales para el tratamiento de los AJ es factible y se asocia con buenos resultados a largo plazo.

Introduction Contralateral sensorineural hearing loss (CSNHL) after vestibular schwannoma (VS) is a severe complication, especially in those cases in which hearing preservation in the operated side was not possible. There are several theories that attempt to explain this issue, but there is no established guideline of treatment. Material and methods We report 4 patients treated in our institution who developed a severe CSNHL after surgery. Results Of the 185 cases of VS treated with surgery, 4 patients (2.2%) developed a CSNHL after VS surgery. After medical treatment, partial recovery of hearing occurred in one patient the other 3 patients presented a well-established severe SNHL. Conclusions Established treatment guidelines do not exist, but the use of high doses of corticosteroids has been recommended and cochlear implant in cases with no recovery and complete hearing loss may be useful.

Background and Objectives Juvenile angiofibroma (JA) is a benign tumour, for which the treatment of choice is surgery. It may be associated with significant morbidity because of its anatomical location and its locally destructive growth pattern. Severe haemorrhage constitutes a high risk in JA and its surgical management can be complex. The management of JA remains a challenge. The objective of this study was to review a series of patients with JA treated via the endonasal/endoscopic approach. Material and Methods Medical records of patients operated for JA were reviewed. Main outcome measures: tumour stage, intraoperative blood loss, complications and persistence/recurrence rates. Results A total of 30 male patients and one female were included. The mean age was 17 years. Using the Radkowski classification, one JA was classified as stage I, 5 stage IIA, 9 stage IIB, 4 stage IIC, 10 stage IIIA and 2 stage IIIB. Thirty-nine percent of the JA was classified as advanced stage JA (IIIA and IIIB). The mean blood loss was 1.156 mL except in one case, no significant complications were observed. Tumour persistence/recurrence was observed in 2 JA (6%), at the end of the follow-up. Mean postoperative follow-up time was 86 months. Conclusions This retrospective study supports the notion that endonasal endoscopic approaches for a JA are a feasible option associated with good long-term results.

Resumen Antecedentes y objetivos En estudios previos hemos indicado que EGFR tiene un papel en la carcinogenesis en un subgrupo de carcinomas epidermoides nasosinusales (CENS). Ademas, EGFR activa a 2 de las mas importantes vias de senalizacion intracelular como son la PI3K/pAKT/mTOR/pS6 y la via MAP-cinasas. El objetivo de este estudio fue evaluar la participacion de la ruta de EGFR/PI3K/pAKT/mTOR/pS6 y su relacion con parametros clinico-patologicos y de seguimiento de los CENS. Material y metodos La expresion proteica de PTEN, pAKT, mTOR y pS6 fue analizada mediante inmunohistoquimica en 54 CENS. Los resultados fueron relacionados con diversos parametros clinico-patologicos y la supervivencia. Resultados La perdida de expresion de PTEN se observo en 33/54 casos (61%) y la sobreexpresion de pAKT, mTOR y pS6 se observo en 19/54 casos (35%), 8/54 casos (15%) y 47/54 casos (87%), respectivamente. La perdida de expresion de PTEN se relaciono con la invasion intracraneal y el desarrollo de metastasis regionales (p = 0,005). La ausencia de sobreexpresion de pS6 se relaciono con una supervivencia especifica (p = 0,008) y global (p = 0,007) mas favorables y la ausencia de recidivas locales (p = 0,055). No se observaron relaciones significativas entre la expresion de pAKT y mTOR y los parametros clinico-patologicos estudiados. Conclusiones Las alteraciones en la expresion de los componentes de la via EGFR/PI3K/pAKT/mTOR/pS6 son frecuentes en un subgrupo de CENS. Este estudio revela que la ausencia de sobreexpresion de pS6 se relaciona con mejores resultados clinicos, por lo que la expresion pS6 podria considerarse como un marcador pronostico.

Background: We performed a comparative analysis between an organ-preservation protocol and surgery followed by radiotherapy in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx, Methods: 60 previously untreated patients who were treated with induction chemotherapy followed by chemoradiotherapy in responders were compared with a control group of 60 patients treated with up-front surgery. Both groups were statistically comparable, according to the subsite, TNM (tumor-node-metastasis) stage, age, and sex, Results: Mean age was 58 years and 92% were male. No significant statistical difference was observed for overall survival (OS) (HR 0.75, 95% CI 0.48–1,18, P = 0.22) and disease-specific survival (DSS) (HR 0.98, 95% CI 0.52–1.83, P = 0.96). Also, there was no significant difference for recurrence-free survival (HR 0.931, 95% CI 0.57–1.71, P = 0.81), metastases-free survival (HR 2.23, 95% CI 0.67–7.41, P = 0.19), and the appearance of second primary tumors (HR 1.22, 95% CI 0.51–2.88, P = 0.64), Conclusions: The results of the organ-preservation approach did not appear inferior to those of surgery plus (chemo)radiotherapy for patients with T3/T4a larynx and T2–T4a hypopharynx cancer with respect to OS and DSS, locoregional control and metastases-free survival.

Patients with advanced laryngeal and hypopharyngeal cancer are often treated with chemo-radiotherapy to avoid total laryngectomy. Subclinical swallowing disorders could be present in these patients even though patients do not complain of any symptoms. We sought to evaluate the impact of chemoradiation on swallowing and quality of life.We studied 21 patients undergoing chemo-radiotherapy for advanced laryngeal and hypopharyngeal cancer. All patients were tumor-free and none reported symptoms related to dysphagia during follow-up or showed altered routine screening tests (EAT-10) to detect it. Swallowing functions were assessed using volume-viscosity swallow test (V-VST) and fiberoptic endoscopic evaluation of swallowing (FEES). Quality of life was assessed with the EORT-HN35, and SWAL-QOL scales.Frequent alterations in swallowing efficacy (100%) and safety (85.5%) were detected with V-VST and FEES. Quality-of-life scales showed a reduction in their scores between 12 and 17%, mainly in the areas of symptoms.Swallowing disorders are common after chemo-radiotherapy, even in patients who do not clinically manifest these disorders, contributing to a decrease in patients' quality of life. FEES and V-VST are useful procedures to detect asymptomatic swallowing disorders.

Minimally invasive video-assisted parathyroidectomy (MIVAP) has become a standard approach to primary hyperparathyroidism (pHPT) since described. Although intraoperative parathyroid hormone assay (IOPTH) has been generalized as a complementary technique to MIVAP, its actual impact on the surgical success of this technique is not without controversy. The aim of this study was to describe our results in the management of pHPT with successful preoperative localization, by MIVAP technique, without IOPTH determination, confirming in a larger series our preliminary results.A retrospective descriptive study was conducted in pHPT patients treated by MIVAP with no IOPTH determination in a tertiary hospital between 2007 and 2019.A total of 167 patients were included in the study. Biochemical cure was achieved in 96.4%, and 94.1% did not present any surgical complication. The mean duration of surgery was 61 min, and the mean length of hospital stay was 1.8 days CONCLUSIONS: In case of positive preoperative localization studies, MIVAP is a safe and effective technique for the surgical treatment of pHPT due to a parathyroid adenoma, regardless of IOPTH determination, with a success rate 95% and a low complication rate.

Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes. In total, 223 sequence variants were found in 70 genes. Matched tumor/germline comparison in 27 cases revealed that 57% were in fact germline variants. In 20 of these 27 cases, 58 somatic variants in 33 different genes were identified, the most frequent being PIK3CA (5 cases), APC and ATM (4 cases), and KRAS, NF1, LRP1B and BRCA1 (3 cases). Many of the somatic gene variants affected PI3K, MAPK/ERK, WNT and DNA repair signaling pathways, although not in a mutually exclusive manner. None of the alterations were related to histological ITAC subtype, tumor stage or survival. Our data showed that thorough interpretation of somatic mutations requires sequencing analysis of the corresponding germline DNA. Potentially actionable somatic mutations were found in 20 of 27 cases, 8 of which being biomarkers of FDA-approved targeted therapies. Our data implicate new possibilities for personalized treatment of ITAC patients.

The aim of this study was to determine the prevalence of dysphagia in patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), characterizing this condition, both in its objective dimension and in terms of quality of life (QoL). A cross-sectional study was developed in 11 patients diagnosed of CANVAS. In all patients, clinical records were reviewed and the Eating assessment tool 10 (EAT-10) was performed as screening of oropharyngeal dysphagia. To evaluate the QoL impairment secondary to dysphagia, we applied the swallowing quality of life questionnaire (SWAL-QOL) and the MD Anderson Dysphagia Inventory (MDADI). To evaluate the deglutition mechanisms impaired, two objective-instrumental studies were performed: the volume-viscosity swallow test (V-VST) and the fiberoptic endoscopic evaluation of swallowing (FEES). 82% of the patients presented an abnormal EAT-10 score. A correlation was found between the EAT-10 and MDADI and between both QoL questionnaires. After the FEES and V-VST analysis, all 11 patients presented some degree of swallow effectiveness impairment, and most of them safety alterations as well. CANVAS remains an underestimated and underdiagnosed condition and the prevalence of swallowing disorders in those patients is higher than expected. Despite the possibility that EAT-10 works as a useful screening test to predict the results in the QoL questionnaires, the absence of correlation between QoL test and instrumental results suggests that to properly evaluate the patients swallowing status, objective instrumental procedures must be conducted.

We identified the main changes in serum metabolites associated with severe (n=46) and mild (n=19) COVID-19 patients by gas chromatography coupled to mass spectrometry. The modified metabolic profiles were associated to an altered amino acid catabolism in hypoxic conditions. Noteworthy, three 𝛼-hydroxyl acids of amino acid origin increased with disease severity and correlated with altered oxygen saturation levels and clinical markers of lung damage. We hypothesize that the enzymatic conversion of 𝛼-keto-acids to 𝛼- hydroxyl-acids helps to maintain NAD recycling in patients with altered oxygen levels, highlighting the potential relevance of amino acid supplementation during SARS-CoV-2 infection.

Background Cytotoxic chemotherapy can cure advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy. Methods Case-control exploratory study of TCS treated with chemotherapy (≥3 BEP cycles, disease-free ≥3 months) compared with age matched healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. CDKN2A/p16INK4a expression in T cells was measured using qPCR. The percentage of lymphocyte subpopulations and the CDKN2A/p16INK4a expression in TCS were compared with the control group using the Wilcoxon signed-rank test. Results We included 16 cases and 16 controls. The median age was 27 years (minimum 24, maximum 54) and the median time on surveillance was 26.5 months (minimum 3, maximum192). TCS had a lower percentage of total T cells and CD4+ T cells in total lymphocytes. Among the CD4+ T lymphocytes, TCS had less naïve CD4+ and increased memory CD4+ cells. Within the CD8+ T lymphocytes, TCS exhibited a decrease in the percentage of naïve cells and an increase in CD8 + CD45RA + CD57+ cells. TCS also exhibited decreased memory CD19+ B cells compared to the controls. The relative expression of CDKN2A/p16INK4a in T cells was increased in TCS (mean 1.54; 95% CI of the mean: 1.074–2.005; p = 0.048). Conclusion In this exploratory study, TCS showed increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype that has been associated with immunosenescence. Further studies are warranted to define the clinical implications of these alterations in TCS.

BACKGROUND In patients with rheumatoid arthritis (RA) exercise improves muscle strength and decreases fat mass, whereas the consumption of a Mediterranean diet (MD) also has been associated with higher grip strength. Therefore, it is important to explore the combined effects of these interventions on hand grip strength and weight in RA. OBJECTIVE To determine the combined effect of an MD and a dynamic exercise program (DEP) on hand grip strength in women with RA. METHOD In a randomized clinical trial, 106 women with RA were included and assigned to the DEP-MD, DEP and MD groups. Weight, body circumferences, Disease Activity Score-28, Health Assessment Questionnaire Disability Index [HAQ-DI], and hand grip strength were measured at baseline and 24 weeks after the interventions. RESULTS After 24 weeks, hand grip strength showed a significant increase in the DEP group (median 2 kg) compared with DEP-MD (median 0.5 kg) and MD (median -0.5 kg) groups (p = 0.03). In the MD group weight and waist circumference showed a significant decrease (-2.2 kg and -4.3 cm) compared with DEP-MD (0.85 kg and 1.9 cm) and DEP (0.35 kg and 0.5 cm) groups (p

Introduction: Ototoxicity occurs in different percentages in patients after treatment with platinum-based chemotherapy or cranial radiation therapy. The aim of this study was to present our experience in ototoxicity monitoring. Material and methods: A review was made of the registry of paediatric cancer patients referred to the Children’s Hearing Loss Unit from 1999 to 2019. Results: Of the 46 patients referred to this unit, 41 had received platinum as part of their treatment, 17 patients underwent neurosurgery, and 18 patients received cranial radiation therapy. An anamnesis and otoscopy were performed on all of them, and the monitoring was carried out with tone-verbal audiometry and/or distortion products. Hearing loss was observed in eight patients (21.05% of patients referred for audiological follow-up) as a consequence of the treatment. It was impossible to determine the audiological situation in eight patients at the end of treatment. Hearing aid adaption was necessary in two patients. In coordination with Paediatric Oncology, a change from cisplatin to carboplatin due to bilateral grade two ototoxicity was considered appropriate during treatment in one patient. Conclusion: Adequate coordination with Paediatric Oncology is essential to carry out active surveillance for ototoxicity and to modify, if possible, the dosage or type of chemotherapy in case hearing is affected. In our experience, and following current recommendations, a pre-treatment assessment is usually performed, as well as monitoring during treatment, at the end of treatment, and annually thereafter due to the risk of a later development of hearing loss. Resumen: Introducción: La ototoxicidad se presenta en diversos porcentajes según estudios tras el tratamiento con quimioterapia basada en platino y/o radioterapia craneal. El objetivo es mostrar nuestra experiencia en la monitorización de la ototoxicidad. Material y métodos: Se realizó una revisión del 1999 al 2019 en el registro de pacientes oncológicos pediátricos de nuestro hospital y remitidos a la Unidad de Hipoacusia Infantil. Resultados: 46 pacientes fueron remitidos a nuestra unidad. 41 pacientes recibieron platinos como parte de su tratamiento, 17 pacientes fueron sometidos a una intervención neuroquirúrgica y 18 pacientes recibieron radioterapia craneal. A todos se les realizó una anamnesis y otoscopia, y la monitorización se llevó a cabo con una audiometría tono-verbal y/o productos de distorsión. Se objetivó una hipoacusia como secuela del tratamiento en ocho pacientes (21,05% de los pacientes remitidos para seguimiento audiológico). Fue imposible determinar la situación audiológica al finalizar el tratamiento en ocho pacientes. La adaptación audioprotésica fue necesaria en dos pacientes. En la coordinación con Oncología Pediátrica, se consideró oportuno el cambio de cisplatino por carboplatino por ototoxicidad importante durante el tratamiento en un único paciente. Conclusión: Es imprescindible una adecuada coordinación con Oncología Pediátrica para realizar una vigilancia activa de la ototoxicidad y modificar, si es posible, la dosificación o el tipo de quimioterápico en caso de verse afectada la audición. En nuestra experiencia, y siguiendo las recomendaciones actuales, realizamos una valoración pretratamiento, una monitorización durante el tratamiento, al finalizarlo y después de forma anual por el riesgo de desarrollo diferido de una hipoacusia

To describe the clinical and serological characteristics of patients with SLE who reached a state of sustained remission for more than 10 years in the absence of treatment.From a retrospective cohort of 2121 patients, 44 cases with sustained remission (PtRem) were identified and compared with 88 patients whose course has been chronically active (PtAct).The clinical and serological characteristics were analyzed, as well as the treatment of each group at the beginning of the disease and during its evolution.Older age at disease onset was associated with a tendency to reach a state of prolonged remission. These patients also had a higher frequency of thrombocytopenia at the beginning of the disease 34.1% vs 10.2% (p 0.001). PtAct had a significantly higher initial SLEDAI compared with cases (10.4 ± 5.6 vs 14.1 ± 5.8; p 0.001). PtRem had a higher initial frequency of anti-β2 GP1 IgG antibodies. Also, 25% of these patients were serologically active. We did not find differences in the initial treatment between both groups. The accumulated damage measured by SLICC/ACR damage index at the end of the study was significantly less in the patients who remained in prolonged remission.Although patients with SLE who achieve prolonged remission have some different characteristics at baseline compared with PtAct, it is not possible to identify a characteristic phenotype for the former. Achieving a state of prolonged remission should always be the goal in patients with SLE. Key Points • SLE patients can reach a very prolonged state of remission, free of treatment, including antimalarials, for at least 10 years. • Venous thromboembolism and thrombocytopenia are commonly present in patients that achieved remission. • The presence of serological markers of activity, even after 10 years in remission, is a risk factor for relapse.

Background. Intestinal-type adenocarcinoma (ITAC) is a rare tumour occurring in the ethmoid sinus. Recent years have brought advances in endoscopic surgery and precision radiotherapy, however, five-year overall survival has not improved and remains at 35&ndash, 80%, depending on tumour stage and histology. Therefore, there is a need for new therapeutic options. Methods. We evaluated CD8+ tumour-infiltrating lymphocytes (TILs) and tumour microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) as predictive biomarkers for immunotherapy in a series of 133 ITAC. All results were correlated to clinical and follow-up data. Results. The presence of intratumoural CD8+ TILs was low in 57% of cases and high in 8% of cases. Tumoural PD-L1 positivity was observed in 26% of cases. CD8+ TILs and TMIT correlated with the histological subtype of ITAC and with better overall survival. The presence of stromal PD-L1-positive macrophages was related to intratumoural CD8+ TILs. PD-L1 expression on tumour cells or macrophages did not show prognostic value. Conclusions. TMIT classification did not have additional prognostic value over CD8+ TILs alone. The modest percentage of CD8high/PD-L1pos cases indicates that ITAC is a lowly immunogenic tumour type. Nevertheless, a proportion of ITAC, especially the papillary and colonic subtypes, could benefit from therapy with immune checkpoint inhibitors.

Introduction Autoimmune thyroid disease (AITD) is the most common autoimmune disorder worldwide. Remarkably, it is commonly accompanied by other autoimmune diseases, such as rheumatoid arthritis (RA). The immunopathogenic mechanisms behind the coexistence of these disorders are still not completely understood. Immunogenetics influences the physiopathology of these diseases since ethnicity plays an essential role in the inheritance of susceptibility markers. Methods High-resolution HLA class II typing was performed using a sequence-based method. Results The allele frequency of HLA-DRB1∗04:04 and -DRB1∗03:01 were significantly increased in patients with AITD and RA compared to healthy individuals, pC ​= ​0.021, OR ​= ​2.4, 95%CI ​= ​1.19–4.75 and pC ​= ​0.009, OR ​= ​3.4, 95%CI ​= ​1.42–7.93, respectively. Remarkably, these patients have a combined risk given by susceptibility HLA-DRB1 alleles that contain the shared epitope, pC ​= ​0.03, OR ​= ​1.7, IC95% ​= ​1.07–2.76, and a lack of protective alleles carrying aspartic acid70, pC ​= ​0.009, OR ​= ​0.5, IC95% ​= ​0.32–0.84. Discussion The results suggest that patients with AITD and RA have an immunogenetic mechanism that combines the susceptibility alleles associated with both diseases. Importantly, it seems to be linked mainly to the lack of protective alleles with aspartic acid in the position 70, along with the presence of susceptibility alleles that have the sequences QRRAA, QKRAA, and RRRAA at positions 70–74. Conclusion Patients with AITD and RA have a characteristic immunogenetic signature, which could be useful for determining multiple autoimmunities and assessing their relatives’ risk of developing it., Highlights • The HLA-DRB1∗04:04 and -DRB1∗03:01 are the susceptibility alleles in RA and AITD. • The susceptibility in RA and AITD involves HLA-DRB1 shared epitope alleles. • The Mexican mestizo admixture patterns explain the variety of SE alleles in RA and AITD. • The immunopathogenic mechanism involves lack of DRB1 alleles with aspartic acid at 70 position.

Lipid mediators derived from polyunsaturated fatty acids (FA), have been related to inflammation and immune response regulation. Herein we evaluated the intake and serum levels of ω-3 and ω-6 FA among patients with primary Sjögren's syndrome (pSS), and correlated with ocular/oral sicca symptoms, disease activity and a panel of chemokines/cytokines.We included 108 patients and 100 controls. Dietary information was obtained from a food questionnaire of one-day reminder and processed using a nutritional software. Among the SS group, we measured serum ω-3 (α-linolenic acid [α-LN], eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]) and ω-6 (linoleic acid [LA], arachidonic acid [AA]) by gas chromatography flame ionization. We scored the ESSDAI, ESPRI, Schirmer-I test and NSWSF. In a subsample, we assessed the OSDI, ophthalmologic staining scores and measured CXCL8, CXCL10, CCL2, IL-22 and IL-21 in saliva, and CXCL8, CXCL10, CCL2 and CXCL9 in tears by Luminometry.ω-3 and ω-6 intake was lower in SS patients than controls, and did not correlate with serum levels. We found a negative correlation between α-LN and the OSDI and ESSDAI, as well as DHA and ESSDAI. In tears, AA positively correlated with CXCL9, whereas in saliva, α-LN, DHA and the ω3 sum negatively correlated with CCL2. We observed a negative correlation between the ω6 sum and IL-21.pSS patients had deficient omega intake. Lower ocular symptoms, ESSDAI scores and salivary CCL2 correlated with higher ω-3 levels, possible suggesting a role in chronic inflammation. Further studies are warranted to deepen in the knowledge of this association.

Background To evaluate the involvement of EGFR signalling and HPV infection in a cohort of inverted sinonasal papilloma (ISP) and sinonasal squamous cell carcinoma (SNSCC) and their value for prognosis and clinical treatment. Methods We analysed 55 ISP, 14 SNSCC associated with ISP (SNSCC-isp) and and 60 SNSCC not associated with ISP (SNSCC-novo) for EGFR gene mutation and copy number gain, protein expression of EGFR and phosporylated EGFR (pEGFR), and HPV-infection and KRAS mutation. Findings were correlated to clinico-pathological and follow-up data. Results We found EGFR exon 20 mutations in 38% (7/18) ISP, in 50% (6/12) SNSCC-isp and in 5% (1/19) SNSCC-novo. EGFR was expressed in 92% of ISP, while pEGFR was observed in 54% (21/39). SNSCC-isp and SNSCC-novo demonstrated comparable expression of EGFR (57% and 33%) and of pEGFR (44% and 38%). We observed an inverse relation between EGFR exon 20 mutation and pEGFR expression. Four of 39 (10%) ISP carried HPV-16. Oncogenic HPV was detected in 3/12 (25%) SNSSC-isp and in 1/8 (13%) SNSCC-novo. KRAS mutations were not detected in any of the samples. HPV infection was inversely correlated with pEGFR expression but not with EGFR mutation. ISP with EGFR activation by mutation or by phosphorylation had longer ISP-free survival, however, neither EGFR exon 20 mutation, pEGFR expression nor HPV infection demonstrated prognostic value in SNSCC. Conclusions EGFR exon 20 mutation is frequent in ISP and SNSCC-isp, while activation of EGFR through phosphorylation also plays an important role. Our data indicate that a large proportion of SNSCC patients could benefit from therapy with modern EGFR inhibitors.

A large number of tumor types arise from the mucosa of the sinonasal cavities. Although presenting clinically distinct behavior, due to poorly differentiated histologic features, they can be difficult to classify correctly. Our aim was to investigate whether IDH2 and IDH1 mutations may be specific to a subset of undifferentiated and poorly differentiated sinonasal carcinomas. A total of 125 tumor samples of 7 different histologic subtypes were analyzed for IDH mutations by sequencing and mutant-specific immunohistochemistry, and the results were correlated to clinical and follow-up data. The highest incidence of IDH2 mutations occurred in sinonasal undifferentiated carcinoma, with 11/36 (31%) cases affected. However, also, 1/9 neuroendocrine carcinomas, 2/4 high-grade non-intestinal-type adenocarcinomas, and 1/8 poorly differentiated squamous cell carcinomas carried the IDH2 mutation, whereas 1/48 intestinal-type adenocarcinomas harbored an IDH1 mutation. Immunohistochemical analysis of mutant IDH1/2 produced a number of false-negative results, but also 1 false-positive tumor was found. Disease-specific survival was more favorable in IDH2-mutant versus wild-type cases. Our data suggest that IDH-mutant sinonasal cancers, independent of their histologic subtype, may represent a distinct tumor entity with less aggressive clinical behavior. Clinically, patients with these mutations may benefit from specific IDH-guided therapies.

Introduction Autoimmune thyroid disease (AITD) is the most common autoimmune disorder worldwide. Remarkably, it is commonly accompanied by other autoimmune diseases, such as rheumatoid arthritis (RA). The immunopathogenic mechanisms behind the coexistence of these disorders are still not completely understood. Immunogenetics influences the physiopathology of these diseases since ethnicity plays an essential role in the inheritance of susceptibility markers. Methods High-resolution HLA class II typing was performed using a sequence-based method. Results The allele frequency of HLA-DRB1∗04:04 and -DRB1∗03:01 were significantly increased in patients with AITD and RA compared to healthy individuals, pC ​= ​0.021, OR ​= ​2.4, 95%CI ​= ​1.19–4.75 and pC ​= ​0.009, OR ​= ​3.4, 95%CI ​= ​1.42–7.93, respectively. Remarkably, these patients have a combined risk given by susceptibility HLA-DRB1 alleles that contain the shared epitope, pC ​= ​0.03, OR ​= ​1.7, IC95% ​= ​1.07–2.76, and a lack of protective alleles carrying aspartic acid70, pC ​= ​0.009, OR ​= ​0.5, IC95% ​= ​0.32–0.84. Discussion The results suggest that patients with AITD and RA have an immunogenetic mechanism that combines the susceptibility alleles associated with both diseases. Importantly, it seems to be linked mainly to the lack of protective alleles with aspartic acid in the position 70, along with the presence of susceptibility alleles that have the sequences QRRAA, QKRAA, and RRRAA at positions 70–74. Conclusion Patients with AITD and RA have a characteristic immunogenetic signature, which could be useful for determining multiple autoimmunities and assessing their relatives’ risk of developing it.

Resumen Introduccion y objetivos La quimiorradioterapia es el tratamiento de eleccion del carcinoma de nasofaringe. Las recurrencias locales son una de las principales causas de mortalidad en estos pacientes: el rescate quirurgico o la reirradiacion son el tratamiento de eleccion, segun la disponibilidad. El objetivo fue evaluar y comparar los resultados de la cirugia de rescate en el tratamiento de las recidivas locales de los carcinomas nasofaringeos mediante abordajes abiertos vs. endoscopicos. Metodos Veinte pacientes con recidivas locales de carcinomas nasofaringeos fueron intervenidos quirurgicamente: 12 pacientes fueron intervenidos mediante cirugia abierta y 8 mediante un abordaje endoscopico endonasal transpterigoideo. Un paciente fue estadiado como rT1; 3 como rT2; 2 como rT3 y 6 como rT4 en el grupo de abordajes abiertos; en la serie endoscopica, 2 pacientes fueron rT1, 5 fueron rT2 y uno fue rT3. Resultados En 3 de los pacientes (25%) intervenidos mediante cirugia abierta (un rT4, un rT3 y un rT2) no se logro una reseccion macroscopica completa). En el grupo endoscopico la reseccion fue completa en todos los pacientes. La tasa de complicaciones en el grupo intervenido mediante abordajes abiertos fue del 92% (5 complicaciones leves, 5 complicaciones moderadas y una complicacion grave) y en el grupo intervenido mediante endoscopia fue del 100% (7 sufrieron complicaciones leves y un paciente una complicacion grave). La supervivencia a los 3 y 5 anos fue del 53 y del 42% en el abordaje abierto y del 100 y del 75% en el abordaje endoscopico, respectivamente. Conclusiones Los abordajes endoscopicos disminuyen la morbilidad asociada a los abordajes abiertos y permiten obtener un control oncologico favorable.

Background Rheumatoid arthritis (RA) is a complex inflammatory disease that modifies body composition. Although body mass index (BMI) is one of the clinical nutrition tools widely used to assess indirectly nutritional status, it is not able to identify these body alterations. Bioelectrical Vector Analysis (BIVA) is an alternative method to assess hydration and body cell mass of patients with wasting conditions. Objective To investigate the differences in nutrition status according to BMI groups (normal, overweight and obesity) and BIVA classification (cachectic and non-cachectic) in women with RA. Methods Women with confirmed diagnosis of RA were included from January 2015 to June 2016. Whole-body bioelectrical impedance was measured using a tetrapolar and mono-frequency equipment. Patients were classified according to BMI as: low body weight (n = 6, 2.7%), normal (n = 59, 26.3%), overweight (n = 88, 39.3%) and obese (n = 71, 31.7%), and each group was divided into BIVA groups (cachectic 51.8% and non-cachectic 48.2%). Results A total of 224 RA patients were included, with mean age 52.7 years and median disease duration of 12 years. Significant differences were found in weight, arm circumference, waist, hip, resistance/height, reactance/height and erythrocyte sedimentation rate among all BMI groups. However, serum albumin levels were significantly different between cachectic and non-cachectic patients independently of BMI. In all BMI categories, cachectic groups had lower reactance and phase angle than non-cachectic subjects. Conclusion RA patients with normal or even high BMI have a significantly lower muscle component. Evaluation of body composition with BIVA in RA patients could be an option for cachexia detection.

Failure analyses and root cause determination were carried out on the rotor of a high-power generator of gas–diesel dual fuel which presented cracking due to torsional fatigue in its end (region of section change and coupling), after 30,000 h of service. The generator of 307 MW–3000 rpm has a rotor (shaft of 400 mm O) manufactured in a proprietary steel grade equivalent to ASTM A470 type, Class 7 of high hardenability. It was reported that the equipment control system showed, in service, a high level of vibrations, not admissible for continuing the operation. First, and during the equipment shutdown for inspection, the presence of cracks, slant to the rotor shaft, was detected by means of visual inspection and dye penetrant test. The failure region corresponds to the zone of coupling–shaft joint, linked by means of fixation by interference, whereas the cracking spread on two fracture planes at 45° with respect to the rotor shaft. On this zone, where cracking started, a severe fretting corrosion damage was evidenced. The characterization and identification of present damage mechanisms were conducted through macrographic, fractographic, SEM, EDS, chemical analyses, and mechanical tests. It was recognized that from the damage by fretting corrosion, fatigue micro-cracks were produced that spread due to service tensions by a mechanism of fretting fatigue. The fatigue fracture propagation was developed into two orthogonal planes at 45° from the longitudinal shaft, which reveals an inversion in the loading condition, only justifiable by torsional vibrations that were assigned to a torsional resonance typical of the system dynamics. It was considered that the torsional vibrations cause micro-movements between components, promoting fretting corrosion and the subsequent fretting fatigue that finally induced the failure by high-cycle torsional fatigue with low-stress amplitude., Laboratorio de Investigaciones de Metalurgia Física

To evaluate the association of C-reactive protein (CRP) polymorphisms with risk of development SLE in a group of Mexican individuals. Five CRP polymorphisms (rs3093059, rs3093062, rs1800947, rs1130864, and rs1205) were determined by PCR-restriction fragment length polymorphism and SNP rs3093061 by refractory mutation system PCR assay in 126 SLE patients and 131 controls. Four of the polymorphisms showed differences between patients and controls. rs3093061 polymorphism was associated with a lower risk of developing lupus principally in the codominant 2 (OR = 0.219, 95% CI 0.108-0.785, P = 0.015) model. rs1130864 was associated with decreased risk mainly under codominant 1 (OR = 0.288, 95% CI 0.143-0.581, P = 0.001) model. rs1205 was associated under the over-dominant model (OR = 0.504, 95% CI 0.270-0.942, P = 0.032). The rs3091244 polymorphism was associated with decreased risk of SLE mostly under additive (OR = 0.605, 95% CI 0.393-0.931. P = 0.022) model. Our study establishes that rs3093061, rs1130864, rs1205, and rs3091244 polymorphisms are associated with decreased risk of developing SLE.

Contains fulltext : 191237.pdf (Publisher’s version ) (Open Access) The sinonasal cavities harbour a variety of rare tumour types. Many carry a poor prognosis while therapeutic options are limited. Histopathological classification can be difficult, especially for poorly differentiated tumours such as olfactory neuroblastoma (ONB), sinonasal neuroendocrine carcinoma (SNEC) and sinonasal undifferentiated carcinoma (SNUC). We analysed Affymetrix OncoScan genome-wide copy number profiles of these three tumour types, both as originally diagnosed and as regrouped by their cytokeratin (Ck) and neuroendocrine (Ne) expression pattern, aiming to find a relation between phenotype and genotype. According to the original histopathological classification our series consisted of 24 ONB, 11 SNEC and 19 SNUC, while immunohistochemistry indicated 11 Ck-Ne+/ONB, 18 Ck+Ne+/SNEC, 24 Ck+Ne-/SNUC, and 1 Ck-Ne-/unclassified. As originally diagnosed, the three tumour types showed similar copy number profiles. However, when regrouped by Ck/Ne immunostaining we found a distinct set of gains and losses; Ck-Ne+/ONB harboured few and predominantly whole chromosomes abnormalities, Ck+Ne+/SNEC carried both gains and losses in high frequency, and Ck+Ne-/SNUC showed mostly gains. In addition, each tumour carried a number of unique chromosomal deletions. Genome-wide copy number profiling supports the value of immunohistochemical CkNe staining of ONB, SNEC and SNUC for tumour classification, which is important for prognosis and therapeutic decision-making.