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Currently, there is scant information regarding the features associated to the persistence of post-COVID-19 syndrome, which is the main aim of the present study. A cohort study of 102 COVID-19 patients was conducted. The post-COVID-19 symptoms were assessed by a standardised questionnaire. Lymphocyte immunophenotyping was performed by flow cytometry and chemokines/cytokines, neutrophil extracellular traps, the tripartite motif 63, anti-cellular, and anti-SARS-CoV-2 IgG antibodies were addressed in serum. The primary outcome was the persistence of post-COVID-19 syndrome after six months follow-up. Thirteen patients (12.7%) developed the primary outcome and had a more frequent history of post-COVID-19 syndrome 3 months after infection onset (p = .044), increased levels of IL-1α (p = .011) and IP-10 (p = .037) and increased CD57 expression in CD8+ T cells (p = .003). There was a trend towards higher levels of IFN-γ (p = .051), IL-1β (p = .062) and IL-6 (p = .087). The history of post COVID-19 in the previous 3 months, obesity, baseline serum MIP-1α and IP-10, and CD57 expression in CD8+ T cells were independently associated with the persistence of post-COVID-19 syndrome. Our data suggest an important relationship between a pro-inflammatory state mediated through metabolic pathways related to obesity and increased cellular senescence as a key element in the persistence of post-COVID-19 syndrome at six months of follow-up.

Objectives SSc is a devastating autoimmune disease characterized by fibrosis and obliterative vasculopathy affecting the skin and visceral organs. While the processes mediating excessive extracellular matrix deposition and fibroblast proliferation are clear, the exact link between autoimmunity and fibrosis remains elusive. Th17 cells have been proposed as critical drivers of profibrotic inflammation during SSc, but little is known about the immune components supporting their pathogenic role. Our aim was to determine cytokine responses of stimulated monocyte-derived dendritic cells (Mo-DCs) and to determine how they influence T-cell cytokine production in SSc. Material and methods Dendritic cells (DCs) activate and shape T cell differentiation by producing polarizing cytokines. Hence, we investigated the cytokine responses of monocyte-derived DCs (Mo-DCs) from patients with limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc) and healthy controls (HCs) after stimulation with toll-like receptor (TLR) agonists. Also, using co-culture assays, we analysed T cell subpopulations after contact with autologous TLR-activated Mo-DCs. Results In general, we observed an increased production of Th17-related cytokines like IL-1β, IL-17F, IL-21 and IL-22 by SSc compared with HC Mo-DCs, with variations between lcSSc vs dcSSc and early- vs late-stage subgroups. Noticeably, we found a significant increment in IL-33 production by Mo-DCs in all SSc cases regardless of their clinical phenotype. Strikingly, T cells displayed Th2, Th17 and dual Th2–Th17 phenotypes after exposure to autologous TLR-stimulated Mo-DCs from SSc patients but not HCs. These changes were pronounced in individuals with early-stage dcSSc and less significant in the late-stage lcSSc subgroup. Conclusions Our findings suggest that functional alterations of DCs promote immune mechanisms favouring the aberrant T cell polarization and profibrotic inflammation behind clinical SSc heterogeneity.

[EN]Introduction and objective: The number of patients with micropapillary thyroid carcinoma (mPTC) is increasing. Clinical practice guidelines have endorsed both active surveillance and surgery as treatment options for mPTC. In this review we aim to describe the current options for the management of mPTC. Synthesis: The evidence accumulated in various studies has allowed us to know the natural history and biological behavior of these tumors. Through extensive experience, it has been shown that the vast majority of these tumors often does not present a significant variation in size, or have very slow growth rates, and even some have decreased in size. Most mPTC are low-risk tumors that will not generate morbidity or mortality despite being untreated. In recent years, clinical practice has evolved towards a less aggressive treatment of these mCPT to avoid morbidity derived from active treatment by surgery and/or radioiodine and/or hormonal suppression. Patients with high-risk tumors should be managed following papillary carcinoma protocols. However, active surveillance (AV) of patients with low-risk tumors has shown excellent oncologic outcomes without increasing morbidity and mortality. When surgical treatment is indicated, lobectomy is a valid option for unifocal mPTC Initial selection criteria for the suitability of being managed by VA should take into account many aspects, including tumor and patient characteristics. If there is a high risk of progression, they should undergo immediate surgery instead of VA. Conclusions: VA has emerged as a new therapeutic alternative for these low-risk tumors, with excellent oncological results and lower complication rates. However, despite the encouraging results of the VA, its implementation in practice depends on many aspects among which are the characteristics of the tumor, the clinical characteristics of the patient and psychosocial factors. [ES]Introducción y objetivo: El número de pacientes con microcarcinoma papilar de la tiroides (mPTC) cada vez es más elevado. Las guías de práctica clínica han respaldado tanto la vigilancia activa como la cirugía como opciones de tratamiento para el (mCPT). En esta revisión nos planteamos como objetivo describir las opciones actuales de manejo del mCPT. Síntesis: La evidencia acumulada en los estudios realizados ha permitido conocer la historia natural y el comportamiento biológico de estos tumores. Mediante las extensas experiencias, se ha evidenciado que la gran mayoría de estos tumores muchas veces no presentan una variación significativa de su tamaño, o presentan tasas de crecimiento muy lentas, e incluso algunos presentan disminución de éste. La mayoría de mCPT son tumores de bajo riesgo clínico que no generarán morbilidad o mortalidad a pesar de no ser tratados. En los últimos años, la práctica clínica ha evolucionado hacia un tratamiento menos agresivo de estos mCPT para evitar la morbilidad derivada del tratamiento activo mediante cirugía y/o radioyodo y/o supresión hormonal. Los pacientes con tumores de alto riesgo deben ser manejados siguiendo los protocolos de los carcinomas papilares. Sin embargo, la vigilancia activa (VA) de pacientes con tumores de bajo riesgo ha mostrado excelentes resultados oncológicos sin aumentar la morbilidad y la mortalidad. Cuando se indica un tratamiento quirúrgico, la lobectomía es una opción válida para estos tumores. Los criterios de selección inicial para la idoneidad de ser manejados mediante VA deben tener en cuenta muchos aspectos, incluidas las características de los tumores y pacientes. En caso de alto riesgo de progresión deben ser sometidos a una cirugía inmediata en lugar de VA. Conclusiones: La VA ha surgido como una nueva alternativa terapéutica para estos tumores de bajo riesgo, con excelentes resultados oncológicos y menores tasas de complicaciones. No obstante, a pesar de los alentadores resultados de la VA, su implementación en la práctica depende de muchos aspectos entre los cuales se encuentran las características del tumor, las características clínicas del paciente y factores psicosociales.

BackgroundUntil now, most of the research addressing long-term humoral responses in coronavirus disease 2019 (COVID-19) had only evaluated the serum titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgGs, without the assessment of the baseline antiviral clinical and immune profile, which is the aim of this study and may be the key factor leading to a broad and sustained antibody response.MethodsWe included 103 patients with COVID-19. When the patients sought medical attention (baseline), a blood sample was drawn to perform immunophenotype of lymphocytes by flow cytometry. The patients were assessed 15 days after baseline and then every month until the third month, followed by a last visit 6 months after recruitment. We evaluated the anti-SARS-COV-2 IgG at all time points, and the serum levels of cytokines, chemokines, anti-cellular (AC) antibodies and neutrophil extracellular traps were also assessed during the follow-up. The primary outcome of the study was the presence of a sustained immune humoral response, defined as an anti-SARS-CoV-2 IgG titer >4.99 arbitrary units/mL in at least two consecutive measures. We used generalized lineal models to assess the features associated with this outcome and to assess the effect of the changes in the cytokines and chemokines throughout time on the development of a sustained humoral immune response.ResultsAt baseline the features associated to a sustained immune humoral response were the diagnosis of critical disease, absolute number of lymphocytes, serum IP-10, IL-4, IL-2, regulatory T cells, CD8+ T cells, and positive AC antibodies. Critical illness and the positivity of AC antibodies were associated with a sustained humoral immune response after 3 months, whilst critical illness and serum IL-13 were the explanatory variables after 6 months.ConclusionA sustained immune humoral response is strongly related to critical COVID-19, which is characterized by the presence of AC antibodies, quantitative abnormalities in the T cell compartment, and the serum cytokines and chemokines during acute infection and throughout time.

Rheumatoid arthritis (RA) patients have a higher frequency of infections than the healthy population. The reason has yet to be explained but involves several factors, of which body composition and rheumatoid cachexia are often overlooked. This study aimed to evaluate whether patients with cachexia, measured by bioelectrical impedance vector analysis, are at an increased risk of developing infections compared with patients without cachexia. A secondary analysis of 186 women with RA enrolled in a randomized trial (ClinicalTrials.gov ID: NCT02900898, September 14, 2016) was completed. Medical records and phone calls were used to record infectious events diagnosed and treated during follow-up. Hazard ratios were calculated using Cox proportional hazard regression analysis, and a predictive model of infection was created. After 36 months of follow-up, 62 patients (26.7% non-cachectic and 44.3% cachectic, p 0.01) developed at least one infectious event. The most common site of was the urinary tract, followed by the lungs and respiratory tract. The presence of cachexia (HR 1.90, 95% CI 1.15-3.13) and the use of glucocorticoids (HR 1.77, 95% CI 1.01-3.09) were associated with infection in univariate and multivariate models. Body mass index (BMI), smoking, and methotrexate use were not associated with a higher frequency of infections. The presence of cachexia and the use of glucocorticoids were identified as predictors of infections in a cohort of female RA patients. More extensive measurements of body composition should be performed beyond BMI in RA patients to better understand its impact and to prevent additional comorbidities and complications. Key Points • The presence of cachexia measured by bioelectrical impedance vector analysis was associated with infectious events in women with rheumatoid arthritis, whereas body mass index did not show an association. • Glucocorticoids were the only drug associated with a higher frequency of infection. None of the disease-modifying antirheumatic drugs, including methotrexate, showed an association.

Background Surgical resection or radiotherapy (RT) are standard approaches for early-staged hypopharyngeal squamous cell carcinoma (HPSCC). Transoral laser microsurgery (TOLMS) seems to provide good oncological and functional results with few local complications. The aim of our study was to analyze the outcomes of TOLMS, with or without neck dissection or RT, in the treatment of HPSCC in a tertiary referral center. Methods A retrospective study was conducted in patients with early T-category (T1–T2) HPSCC treated by TOLMS. Results A total of 34 patients were included in the study. The series includes 17 (50%) T1 and 17 (50%) T2 classified tumors. The 5-year overall survival and disease-specific survival rates were 51% and 66%, respectively, with a 5-year local control rate of 92%. All patients reassumed oral diet and none of them had a tracheostomy at the end of the follow-up. Conclusions TOLMS offers an effective treatment option in terms of oncologic control and function preservation in locally circumscribed HPSCC.

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-H&N35, 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.

The biallelic inheritance of an expanded intronic pentamer (AAGGG)A retrospective descriptive study from an ataxia database comprising 500 patients.The study was performed at the Otorhinolaryngology Department of a hospital in the north of Spain.Specific genetic testing for CANVAS was performed in 13 patients with clinical suspicion of complete or incomplete syndrome. The clinical diagnosis was supported by quantitative vestibular hypofunction, cerebellar atrophy, and abnormal sensory nerve conduction testing.Nine of 13 (69%) patients met clinical diagnostic criteria for definite CANVAS disease. The first manifestation of the syndrome was lower limb dysesthesia in 8 of 13 patients and gait imbalance in 5 of 13. Eleven of 13 (85%) patients were carriers of the biallelic (AAGGG)A genetic cause of CANVAS has recently been discovered. We propose genetic screening for biallelic expansions of the AAGGG pentamer of

To characterize cell line CAE606 derived from a squamous cell carcinoma (SCC) of the external auditory canal (EAC) and to show its usefulness as a model for testing candidate therapeutic agents.Preclinical translational research.Biomedical research institute.The cell line was initiated from a moderately differentiated T2N0M0 EAC SCC. We studied its histologic and genetic features as well as growth and invasion parameters. Sensitivity to cell CDK4/6 cell cycle inhibitor palbociclib was analyzed.CAE606 cells expressed heavy molecular weight cytokeratin, p63, and vimentin. The population doubling time was 25.8 hours, and the cells showed fast collective cell migration in a wound-healing assay. Short tandem repeat analysis confirmed it to be derived from the primary tumor of the patient. Next-generation sequencing revealed alterations in cell cycle regulation genes, including inactivating mutations inThis is the first report of a stable EAC SCC cell line. Its genetic features make it a useful tool for preclinical testing of new therapeutic agents for EAC SCC, particularly those targeting cell cycle regulation in combination with radio- and chemotherapy or other specific signaling pathway inhibitors.

Resumen Introduccion La implantacion unilateral en la hipoacusia profunda bilateral deja al paciente en una situacion de audicion monoaural, con los consiguientes problemas audiologicos, en especial por la incapacidad de percepcion de la palabra en ambientes con ruido de fondo, por el efecto sombra de la cabeza. Se puede mejorar su rendimiento auditivo aprovechando los sistemas inalambricos de enrutamiento de la senal (CROS), para dotarlos de una entrada de sonido bilateral. Metodo Se estudiaron 12 usuarios unilaterales de implante coclear adultos, con experiencia con un procesador de sonido Naida C I Q70 que tiene capacidad de comunicacion inalambrica con el CROS. La comprension del habla en cabina en silencio y en ruido se llevo a cabo utilizando como estimulos el test de oraciones grabadas en espanol en 3 condiciones: habla dirigida hacia el oido no implantado con y sin CROS activado y habla de frente con UltraZoom. Tras un mes de uso del dispositivo CROS, se evaluo la satisfaccion del usuario utilizando cuestionarios. Resultados En silencio, la diferencia media entre el implante unilateral solo y el implante unilateral con el dispositivo CROS fue del 27,6%, mientras que en presencia de ruido fue del 32,5%. Si se comparan las puntuaciones entre presentar activada o no la opcion UltraZoom al utilizar CROS, se demuestra un beneficio de un 35% de inteligibilidad. Todos los sujetos puntuaron su experiencia de uso como satisfactoria. Conclusion El dispositivo CROS utilizado con implante coclear unilateral produce un beneficio objetivo y subjetivo en el reconocimiento de la palabra cuando la senal se dirige hacia el mismo. En este estudio no se reprodujo la condicion de presentacion de la senal verbal en el oido implantado con ruido en el adaptado con el CROS por haberse demostrado previamente que la discriminacion verbal se deteriora de forma importante con respecto al implante unilateral sin CROS.

Introdution Single cochlear implantation usually provides substantial speech intelligibility benefits but bilaterally deaf, unilaterally implanted subjects will continue to experience limitations due to the head shadow effect, like single-sided deaf individuals. In the treatment of individuals with single-sided deafness one option is contralateral routing of signal (CROS) devices, which constitute a non-surgical intervention of the second ear in unilaterally implanted individuals. Method Twelve experienced adult cochlear implant (CI) users with Naida Q70 processor and the CROS device used in combination participated in the study. For the study three conditions were provided: CI only, omnidirectional microphone mode (CROS deactivated); CI plus CROS activated, omnidirectional microphone mode and CI plus CROS activated, UltraZoom mode. Speech reception thresholds were determined in quiet and noise. Subjective feedback regarding the practical usability of the CROS device and the perceived benefit were collected. Results There was a 27.6% improvement in speech understanding in quiet and 32.5% improvement in noise when CROS device was activated. Using advanced directional microphones, a statistically significant benefit of 35% was obtained. The responses to the questionnaires revealed that the subjects perceived benefit in their everyday lives when using the CROS device with their CI. Conclusion The investigated CROS device used by unilateral CI recipients in cases where bilateral implantation is not an option provides both subjective and objective speech recognition benefit when the signal is directed to the CROS device. Unfavourable conditions where speech is presented from the CI side and noise from the CROS side or diffusely were not included in this evaluation since the CROS device adds additional noise and performance is expected to decrease as has previously been shown.

Large pharyngocutaneous fistulas or pharyngostomes are difficult complications to solve, which generate high morbidity and mortality, a poor quality of life and an increase in health costs. Its management must be comprehensive according to general, local and regional factors. We review our experience in treating these pharyngostomes with free flaps. Retrospective study analyzing the results of the reconstruction of 50 patients using free flaps during the period 1991–2019. We exclude patients who required free-flap reconstruction due to primary tumor or those who resolved in other ways. The different types of reconstruction were classified into three types. The 86% (43) were men, and the mean age was 57 years (25–76). In 48% (24/50) the flaps performed were anterolateral thigh (ALT), in 24% (12/50) forearm, in 22% (11/50) parascapular, in 4% (2/50) jejunum and in 2% (1/50) ulnar. A salivary by-pass was placed in 74% (37/50) of the cases. Four cases (8%) presented flap necrosis and two patients died due to treatment. In 86% (43/50) there was some type of complication and 34% (17/50) required surgical revision. 94% (45/48) were able to reintroduce oral feeding. According to our experience, we proposed a regardless size classification: type 1 when only a mucous closure (pharynx) are required (6%), type 2 exclusively skin for cutaneous coverage (10%) and mixed type 3 (mucous and skin) (84%). The treatment of large pharyngostomes with free flaps, despite its complexity, is in our experience the best option for its management.

Resumen Introduccion La hipoacusia neurosensorial (HNS) es el deficit sensorial mas prevalente en nuestro medio. La secuenciacion genomica de nueva generacion (NGS) permite obtener un diagnostico etiologico en un alto porcentaje de pacientes. Nuestro estudio piloto muestra los resultados de la aplicacion sistematica de la NGS en una Unidad de Hipoacusia Infantil, asi como sus implicaciones en el manejo clinico de los pacientes y sus familiares. Material y metodo Se incluyo a 27 pacientes diagnosticados de HNS entre 2014 y 2017 en los que se descarto una causa ambiental. El test genetico consistio en un panel de genes analizados mediante NGS (panel OTOgenicsTM). Este panel ha sido disenado para incluir genes asociados con hipoacusia neurosensorial o mixta, de inicio precoz o tardio, sindromica y no sindromica, independientemente de su patron de herencia. Resultados Se obtuvo un diagnostico genetico en el 56% (15/27) de los pacientes (62% en el caso de las HNS bilaterales); 5/27 (19%) presentaron variantes patogenicas en el gen GJB2 y el resto variantes patogenicas o probablemente patogenicas en otros genes asociados con HNS aislada (PR2X2, TECTA y STRC), con HNS sindromicas (CHD7, GATA3, COL4A5, MITF y SOX10) o con HNS sindromicas y no sindromicas (BSND, ACTG1 y CDH23). Discusion El diagnostico etiologico de la HNS supone un desafio en la practica clinica. Nuestra serie demuestra que es posible implementar el diagnostico genetico en la rutina asistencial y que esta informacion tiene implicaciones pronosticas y terapeuticas.

Introduction Sensorineural hearing loss (SNL) is the most prevalent sensory deficit in our environment. The next generation genomic sequencing (NGS) allows to obtain an etiological diagnosis in a high percentage of patients. Our pilot study shows the results of the systematic application of NGS in a Childhood Hearing Loss Unit, as well as its implications in the clinical management of patients and their families. Material and method We included 27 patients diagnosed with SNH between 2014 and 2017, in which an environmental cause was ruled out. The genetic test consisted of a panel of genes analyzed by NGS (OTOgenics™ panel). This panel has been designed to include genes associated with sensorineural or mixed hearing loss, early onset or late, syndromic and non-syndromic, regardless of their inheritance pattern. Results A genetic diagnosis was obtained in 56% (15/27) of the patients (62% in the case of bilateral HNS). 5/27 (19%) presented pathogenic variants in the GJB2 gene and the rest variants pathogenic and/or probably pathogenic in other genes associated with isolated HNS (PR2 × 2, TECTA and STRC), with syndromic HNS (CHD7, GATA3, COL4A5, MITF and SOX10) or with syndromic and non-syndromic HNS (BSND, ACTG1 and CDH23). Discussion The etiological diagnosis of SNL is a challenge in clinical practice. Our series demonstrates that it is possible to implement genetic diagnosis in the daily routine and that this information has prognostic and therapeutic implications.

Mucosal malignant melanoma (MMM) is a rare and aggressive tumor. Despite effective local therapies, tumor recurrence and metastasis remain frequent. The genetics of MMM remain incompletely understood. This study is aimed to identify actionable genetic alterations by next-generation sequencing. Fifteen MMM samples were analyzed by next-generation and Sanger sequencing. Gene copy number alterations were analyzed by MLPA. Mutation status was correlated with pERK, pAKT, and Ki-67 expression and follow-up data. Inactivating mutations and intragenic deletions in neurofibromatosis type-1 (NF1) were identified in 3 and 2 cases, respectively, (in total 5/15, 33%) and activating mutations in NRAS and KRAS (3/15, 20%) cases. Other mutated genes included CDKN2A, APC, ATM, MITF, FGFR1, and FGFR2. BRAF and KIT mutations were not observed. Cases with NF1 alterations tended to have worse overall survival. The mutational status was not associated with pERK, pAKT, or Ki-67 immunostaining. MMM carries frequent gene mutations activating the MAPK pathway, similar to cutaneous melanoma. In contrast, NF1 is the most frequently affected gene. Intragenic NF1 deletions have not been described before and may go undetected by sequencing studies. This finding is clinically relevant as NF1-mutated melanomas have worse survival and could benefit from therapy with immune checkpoint and MEK inhibitors.

BackgroundMost of the explanatory and prognostic models of COVID-19 lack of a comprehensive assessment of the wide COVID-19 spectrum of abnormalities. The aim of this study was to unveil novel biological features to explain COVID-19 severity and prognosis (death and disease progression).MethodsA predictive model for COVID-19 severity in 121 patients was constructed by ordinal logistic regression calculating odds ratio (OR) with 95% confidence intervals (95% CI) for a set of clinical, immunological, metabolomic, and other biological traits. The accuracy and calibration of the model was tested with the area under the curve (AUC), Somer’s D, and calibration plot. Hazard ratios with 95% CI for adverse outcomes were calculated with a Cox proportional-hazards model.ResultsThe explanatory variables for COVID-19 severity were the body mass index (BMI), hemoglobin, albumin, 3-Hydroxyisovaleric acid, CD8+ effector memory T cells, Th1 cells, low-density granulocytes, monocyte chemoattractant protein-1, plasma TRIM63, and circulating neutrophil extracellular traps. The model showed an outstanding performance with an optimism-adjusted AUC of 0.999, and Somer’s D of 0.999. The predictive variables for adverse outcomes in COVID-19 were severe and critical disease diagnosis, BMI, lactate dehydrogenase, Troponin I, neutrophil/lymphocyte ratio, serum levels of IP-10, malic acid, 3, 4 di-hydroxybutanoic acid, citric acid, myoinositol, and cystine.ConclusionsHerein, we unveil novel immunological and metabolomic features associated with COVID-19 severity and prognosis. Our models encompass the interplay among innate and adaptive immunity, inflammation-induced muscle atrophy and hypoxia as the main drivers of COVID-19 severity.

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.

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.

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.

BackgroundSARS-CoV-2 infection represents a global health problem that has affected millions of people. The fine host immune response and its association with the disease course have not yet been fully elucidated. Consequently, we analyze circulating B cell subsets and their possible relationship with COVID-19 features and severity.MethodsUsing a multiparametric flow cytometric approach, we determined B cell subsets frequencies from 52 COVID-19 patients, grouped them by hierarchical cluster analysis, and correlated their values with clinical data.ResultsThe frequency of CD19+ B cells is increased in severe COVID-19 compared to mild cases. Specific subset frequencies such as transitional B cell subsets increase in mild/moderate cases but decrease with the severity of the disease. Memory B compartment decreased in severe and critical cases, and antibody-secreting cells are increased according to the severity of the disease. Other non-typical subsets such as double-negative B cells also showed significant changes according to disease severity. Globally, these differences allow us to identify severity-associated patient clusters with specific altered subsets. Finally, respiratory parameters, biomarkers of inflammation, and clinical scores exhibited correlations with some of these subpopulations.ConclusionsThe severity of COVID-19 is accompanied by changes in the B cell subpopulations, either immature or terminally differentiated. Furthermore, the existing relationship of B cell subset frequencies with clinical and laboratory parameters suggest that these lymphocytes could serve as potential biomarkers and even active participants in the adaptive antiviral response mounted against SARS-CoV-2.

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 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.

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.