Thyroid hormone induces ossification and terminal maturation in a preserved OA cartilage biomimetic model.

OBJECTIVE: To characterize aspects of triiodothyronine (T3) induced chondrocyte terminal maturation within the molecular osteoarthritis pathophysiology using the previously established T3 human ex vivo osteochondral explant model. DESIGNS: RNA-sequencing was performed on explant cartilage obtained from OA patients (n = 8), that was cultured ex vivo with or without T3 (10 ng/ml), and main findings were validated using RT-qPCR in an independent sample set (n = 22). Enrichment analysis was used for functional clustering and comparisons with available OA patient RNA-sequencing and GWAS datasets were used to establish relevance for OA pathophysiology by linking to OA patient genomic profiles. RESULTS: Besides the upregulation of known hypertrophic genes EPAS1 and ANKH, T3 treatment resulted in differential expression of 247 genes with main pathways linked to extracellular matrix and ossification. CCDC80, CDON, ANKH and ATOH8 were among the genes found to consistently mark early, ongoing and terminal maturational OA processes in patients. Furthermore, among the 37 OA risk genes that were significantly affected in cartilage by T3 were COL12A1, TNC, SPARC and PAPPA. CONCLUSIONS: RNA-sequencing results show that metabolic activation and recuperation of growth plate morphology are induced by T3 in OA chondrocytes, indicating terminal maturation is accelerated. The molecular mechanisms involved in hypertrophy were linked to all stages of OA pathophysiology and will be used to validate disease models for drug testing.

WWP2 confers risk to osteoarthritis by affecting cartilage matrix deposition via hypoxia associated genes.

OBJECTIVE: To explore the co-expression network of the osteoarthritis (OA) risk gene WWP2 in articular cartilage and study cartilage characteristics when mimicking the effect of OA risk allele rs1052429-A on WWP2 expression in a human 3D in vitro model of cartilage. METHOD: Co-expression behavior of WWP2 with genes expressed in lesioned OA articular cartilage (N = 35 samples) was explored. By applying lentiviral particle mediated WWP2 upregulation in 3D in vitro pellet cultures of human primary chondrocytes (N = 8 donors) the effects of upregulation on cartilage matrix deposition was evaluated. Finally, we transfected primary chondrocytes with miR-140 mimics to evaluate whether miR-140 and WWP2 are involved in similar pathways. RESULTS: Upon performing Spearman correlations in lesioned OA cartilage, 98 highly correlating genes (|ρ| > 0.7) were identified. Among these genes, we identified GJA1, GDF10, STC2, WDR1, and WNK4. Subsequent upregulation of WWP2 on 3D chondrocyte pellet cultures resulted in a decreased expression of COL2A1 and ACAN and an increase in EPAS1 expression. Additionally, we observed a decreased expression of GDF10, STC2, and GJA1. Proteomics analysis identified 42 proteins being differentially expressed with WWP2 upregulation, which were enriched for ubiquitin conjugating enzyme activity. Finally, upregulation of miR-140 in 2D chondrocytes resulted in significant upregulation of WWP2 and WDR1. CONCLUSIONS: Mimicking the effect of OA risk allele rs1052429-A on WWP2 expression initiates detrimental processes in the cartilage shown by a response in hypoxia associated genes EPAS1, GDF10, and GJA1 and a decrease in anabolic markers, COL2A1 and ACAN.

Manejo de hemorragia posamigdalectomía en Chile / Treatment of post tonsillectomy bleeding in Chile

Resumen Introducción: La amigdalectomía es una de las cirugías más frecuentes en la población pediátrica. Aunque se considera una cirugía sencilla y segura, no está exenta de riesgos, siendo el principal la hemorragia posoperatoria. Objetivo: Evaluar el manejo de la hemorragia posamigdalectomía en otorrinolaringólogos en Chile. Material y Método: Se realizó un estudio transversal descriptivo sobre la experiencia y manejo de hemorragias posamigdalectomía mediante una encuesta difundida a socios activos de la Sociedad Chilena de Otorrinolaringología, Medicina y Cirugía de Cabeza y Cuello (SOCHIORL). Resultados: Se recopilaron respuestas de 102 de los 348 socios. El 97% ha presentado esta complicación. La medida inicial ante una hemorragia tardía fuera de una unidad de otorrinolaringología es derivar al servicio de urgencias en el 88% de los casos. En urgencia, la indicación más frecuente es administrar ácido tranexámico endovenoso en un 80%. En el caso de hemorragia sin estigmas de sangrado actual, un 68% indica alta con control precoz. Si se evidencian coágulos en la fosa amigdalina, el 72% indica hospitalización para observación. Si se evidencia sangrado activo, el 94% indica hospitalización y revisión de hemostasia en pabellón. Conclusión: Los resultados a nivel nacional, según este estudio, son concordantes con la literatura mundial. El manejo en el servicio de urgencia se basa en la experiencia del tratante. Respecto a los distintos escenarios clínicos, se recomienda hospitalización en caso de evidenciar coágulos y manejo en pabellón en la presencia de sangrado activo. El manejo es variable en pacientes sin hallazgos al examen físico.

Abstract Introduction: Tonsillectomy is one of the most frequent surgeries in the pediatric population. Although it is considered a simple and safe surgery, it has associated risks, the main one being postoperative bleeding. Aim: Evaluate the management of post-tonsillectomy hemorrhage in otorhinolaryngologists practicing in Chile. Material and Method: A descriptive cross-sectional study was carried out on the experience and management of post-tonsillectomy hemorrhage through a survey distributed to active members of the Sociedad Chilena de Otorrinolaringología, Medicina y Cirugía de Cabeza y Cuello (SOCHIORL). Results: Responses were collected from 102 out of 348 active members, of which 97% have presented this complication. The initial measure in a late hemorrhage occurring outside of an otolaryngology unit is referral to the emergency department in 88% of cases. In the emergency room, the most frequent management is to administer intravenous tranexamic acid in 80%. In the case of hemorrhage without trace of current bleeding, 68% discharge with early control. If clots are evident in the tonsillar fossa, 72% admit for observation. If there is evidence of active bleeding, 94% admit and perform revision surgery. Conclusion: Results of this study are consistent with international literature. Management in the emergency department is based on the experience of the treating physician and different clinical scenarios. Hospitalization is recommended when clots are observed, revision surgery when evidence of active bleeding and, in patients with no findings at the moment of the evaluation, management is variable.

IsobaricQuant enables cross-platform quantification, visualization, and filtering of isobarically-labeled peptides.

In mass spectrometry (MS)-based quantitative proteomics, labeling with isobaric mass tags such as iTRAQ and TMT can substantially improve sample throughput and reduce peptide missing values. Nonetheless, the quantification of labeled peptides tends to suffer from reduced accuracy due to the co-isolation of co-eluting precursors of similar mass-to-charge. Acquisition approaches such as multistage MS3 or ion mobility separation address this problem, yet are difficult to audit and limited to expensive instrumentation. Here we introduce IsobaricQuant, an open-source software tool for quantification, visualization, and filtering of peptides labeled with isobaric mass tags, with specific focus on precursor interference. IsobaricQuant is compatible with MS2 and MS3 acquisition strategies, has a viewer that allows assessing interference, and provides several scores to aid the filtering of scans with compression. We demonstrate that IsobaricQuant quantifications are accurate by comparing it with commonly used software. We further show that its QC scores can successfully filter out scans with reduced quantitative accuracy at MS2 and MS3 levels, removing inaccurate peptide quantifications and decreasing protein CVs. Finally, we apply IsobaricQuant to a PISA dataset and show that QC scores improve the sensitivity of the identification of protein targets of a kinase inhibitor. IsobaricQuant is available at https://github.com/Villen-Lab/isobaricquant.

Foetal lipoprotein oxidation and preeclampsia.

Preeclampsia (PE) is a multisystemic syndrome specific to pregnancy. Although PE is the leading cause of death from complications associated with pregnancy, its aetiology is still unknown. In PE, lipid metabolism is altered. When lipids are damaged, both the mother and the foetus may be at risk. Lipoproteins contain apolipoproteins, triacylglycerols, free and esterified cholesterol, and phospholipids, all of which are susceptible to oxidative stress when high levels of oxygen and nitrogen free radicals are present. Lipoperoxidation can occur in three stages: mild, moderate, and severe. In severe lipid damage, highly toxic products such as malondialdehyde (MDA) can be generated; under these conditions, low-density lipoprotein (LDL) proteins can be oxidized (oxLDL). oxLDL is a biomolecule that can affect the production of nitric oxide (NO), the main vasodilator derived from the endothelium. oxLDL can interfere with the transduction of the signals responsible for triggering the activation of endothelial nitric oxide synthase (eNOS), causing reduced vasodilation and endothelial dysfunction, which are the main characteristics of preeclampsia. The objective of the review was to analyse the information the current information about exists about the impact generated by the oxidation of LDL and HDL lipoproteins in neonates of women with preeclampsia and how these alterations can predispose the neonate to develop diseases in adulthood.PE can cause foetal loss, intrauterine growth restriction, or developmental complications. Neonates of mothers with PE have a high risk of cardiovascular diseases, stroke, mental retardation, sensory deficiencies and an increased risk of developing metabolic diseases. PE not only affects the foetus, generating complications during pregnancy but also predisposes them to chronic diseases in adulthood.

El buceo recreativo y la otorrinolaringología: ¿qué sabemos y deberíamos saber? / Recreational diving and otolaryngology: what do we know and should we know?

El buceo recreativo es una práctica cada vez más popular en la población mundial, sin embargo, no está exenta de riesgos. A medida que transcurre una inmersión, el buzo es susceptible a una serie de cambios de presión que afectan las distintas cavidades que contienen aire dentro del cuerpo humano, tales como el oído, cavidades paranasales y los pulmones. Existe un gran espectro de patologías asociadas al buceo, explicándose la mayoría de ellas por el barotrauma asociado, cuya gravedad depende de la magnitud del daño asociado, pudiendo presentar desde manifestaciones a nivel local, así como también a nivel sistémico. Las patologías otológicas suelen ser las más frecuentes y el principal motivo de consulta en este tipo de pacientes. Sin embargo, las afecciones otoneurológicas, rinosinusales, de vía aérea y sistémicas pueden ser comunes dependiendo de cada perfil de buceo. Actualmente no existen recomendaciones locales sobre esta práctica, por lo que el conocimiento de la fisiología, fisiopatología y el tratamiento de las patologías otorrinolaringológicas asociadas deben ser conocidas a medida que este deporte se vuelve cada vez más popular. Se realizó una revisión de la literatura sobre las distintas afecciones otorrinolaringológicas con el fin de sistematizarlas y elaborar recomendaciones para establecer una práctica segura.

Recreational diving is an increasingly popular practice in the world; however, it is not without risks. As a dive progresses, the diver is susceptible to a series of pressure changes that affect the air-containing cavities, such as the ear, paranasal cavities, and lungs. There is a large spectrum of pathologies associated with diving, most of them being explained by associated barotrauma, the severity of which depends on the magnitude of the associated damage, could present local manifestations, as well as at systemic level. Otological pathologies are usually the most frequent and the main reason for consultation in this type of patients, however, otoneurological, rhinosinusal, airway and systemic conditions can be common depending on each diving profile. Currently there are no local recommendations on this practice, therefore, knowledge of the physiology, pathophysiology and treatment of associated otorhinolaryngological pathologies should be known as this sport becomes increasingly popular. A review of the literature on the different ear, nose and throat conditions was carried out in order to systematize them and develop recommendations to establish a safe practice.

Uso de profilaxis antibiótica en el taponamiento nasal, una revisión actualizada

Resumen El uso de profilaxis antibiótica en el taponamiento nasal es una práctica ampliamente usada por el eventual riesgo de síndrome de shock tóxico o complicaciones infecciosas locales. En los últimos años, se ha cuestionado su real impacto tomando en cuenta los riesgos asociados al uso de antibióticos y la baja o casi nula incidencia de las complicaciones infecciosas. Se realizó una revisión exhaustiva de la literatura sobre el uso de profilaxis antibiótica en taponamiento nasal. Se observó que no existían diferencias estadísticamente significativas en la incidencia de complicaciones infecciosas y no hubo reportes de síndrome de shock tóxico en ninguno de los grupos con y sin profilaxis antibiótica. No hubo diferencias significativas en los cultivos de los pacientes con o sin antibióticos en taponamiento nasal por epistaxis. El uso de profilaxis antibiótica en taponamiento nasal es una práctica cuestionable y se requieren más estudios al respecto.

Abstract Antibiotic prophylaxis in nasal packing is a widely used practice due to the possible risk of toxic shock syndrome and infectious complications. Lately, its real impact has been questioned due to the associated risks with antibiotic use and low incidence of infectious complications. A comprehensive review of the literature on the use of antibiotic prophylaxis in nasal packing was performed. No statistically significant differences in the incidence of infectious complications and no reports of toxic shock syndrome were reported in any of the groups with and without antibiotic prophylaxis. There were no significant differences in the antibiotic cultures of patients with or without prophylactic antibiotics in nasal packing due to epistaxis. The use of antibiotic prophylaxis in nasal packing is a questionable practice and further studies are required.

Characterization of dynamic changes in Matrix Gla Protein (MGP) gene expression as function of genetic risk alleles, osteoarthritis relevant stimuli, and the vitamin K inhibitor warfarin.

OBJECTIVE: We here aimed to characterize changes of Matrix Gla Protein (MGP) expression in relation to its recently identified OA risk allele rs1800801-T in OA cartilage, subchondral bone and human ex vivo osteochondral explants subjected to OA related stimuli. Given that MGP function depends on vitamin K bioavailability, we studied the effect of frequently prescribed vitamin K antagonist warfarin. METHODS: Differential (allelic) mRNA expression of MGP was analyzed using RNA-sequencing data of human OA cartilage and subchondral bone. Human osteochondral explants were used to study exposures to interleukin one beta (IL-1ß; inflammation), triiodothyronine (T3; Hypertrophy), warfarin, or 65% mechanical stress (65%MS) as function of rs1800801 genotypes. RESULTS: We confirmed that the MGP risk allele rs1800801-T was associated with lower expression and that MGP was significantly upregulated in lesioned as compared to preserved OA tissues, mainly in risk allele carriers, in both cartilage and subchondral bone. Moreover, MGP expression was downregulated in response to OA like triggers in cartilage and subchondral bone and this effect might be reduced in carriers of the rs1800801-T risk allele. Finally, warfarin treatment in cartilage increased COL10A1 and reduced SOX9 and MMP3 expression and in subchondral bone reduced COL1A1 and POSTN expression. DISCUSSION & CONCLUSIONS: Our data highlights that the genetic risk allele lowers MGP expression and upon OA relevant triggers may hamper adequate dynamic changes in MGP expression, mainly in cartilage. The determined direct negative effect of warfarin on human explant cultures functionally underscores the previously found association between vitamin K deficiency and OA.

FAIMS-MS might contribute to phosphopeptides identification in plasma.

FAIMS interface is gaining popularity because of the impressive 100-fold signal to noise enhancement in addition to the recent coupling to the Orbitrap technology, the most important analyzer developed in the last 20 years. The selection of group of ions and effective removal of single-charged ones at particular compensation voltages increases around 50% the proteome coverage at expenses of lower peptides coverage. However, specific setting for phosphoproteome analysis is yet poorly described. Here we have found the maximum transmission for several tryptic phosphopeptides isolated from a single complex mixture and we have set an experimental method based on five compensation voltages partially different to the ones described previously, demonstrating the relevance of voltages higher than 47 V, with an increase of around 20% of unique phosphopeptides. Using this experimental setup two complex phosphoproteomes isolates (SH-SY5Y cell line and plasma) were analyzed and found increments of 50% on phosphopeptides identification with the proposed method with respect to a previous one, for the cell line extract. Meanwhile for plasma 109 of the detected phosphopeptides are found for first time in this body fluid, presumably due to the release of intracellular proteins. With this FAIMS setup, 60% of the proteins identified are classified as very low abundant proteins.

Variants of FOXO3 and RPA3 genes affecting IGF-1 levels alter the risk of development of primary osteoarthritis.

INTRODUCTION: Pathologically high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in patients with acromegaly are associated with arthropathy. Several studies highlight the potential role of the GH/IGF-1 axis in primary osteoarthritis (OA). We aimed to disentangle the role of IGF-1 levels in primary OA pathogenesis. METHODS: Patients from the Genetics osteoARthritis and Progression (GARP) Study with familial, generalized, symptomatic OA (n = 337, mean age: 59.8 ± 7.4 years, 82% female) were compared to Leiden Longevity Study (LLS) controls (n = 456, mean age: 59.8 ± 6.8 years, 51% female). Subjects were clinically and radiographically assessed, serum IGF-1 levels were measured, and 10 quantitative trait loci (QTL) in the FOXO3, IGFBP3/TNS3, RPA3, SPOCK2 genes, previously related to serum IGF-1 levels, were genotyped. Linear or binary logistic generalized estimating equation models were performed. RESULTS: Serum IGF-1 levels were increased in OA patients, with male patients exhibiting the strongest effect (males OR = 1.10 (1.04-1.17), P=0.002 vs females OR = 1.04 (1.01-1.07), P = 0.02). Independent of the increased IGF-1 levels, male carriers of the minor allele of FOXO3 QTL rs4946936 had a lower risk to develop hip OA (OR = 0.41 (0.18-0.90), P = 0.026). Additionally, independent of IGF-1 levels, female carriers of the minor alleles of RPA3 QTL rs11769597 had a higher risk to develop knee OA (OR = 1.90 (1.20-2.99), P = 0.006). CONCLUSION: Patients with primary OA had significantly higher IGF-1 levels compared to controls. Moreover, SNPs in the FOXO3 and RPA3 genes were associated with an altered risk of OA. Therefore, altered IGF-1 levels affect the development of OA, and are potentially the result of the pathophysiological OA process.

Vértigo posicional paroxístico benigno: factores de riesgo asociados y eficacia de las maniobras de reposición / Benign paroxysmal positional vertigo: associated risk factors and efficacy of particle repositioning maneuvers

INTRODUCCIÓN: El vértigo posicional paroxístico benigno (VPPB) es el vértigo periférico más frecuente. El tratamiento depende del compromiso de los canales semicirculares (CSC) y/o cúpulas, y consiste en maniobras de reposición de partículas. OBJETIVO: Evaluar los factores de riesgo asociados al VPPB en pacientes atendidos en el Servicio de Otorrinolaringología de la Red de Salud UC Christus. Evaluar la tasa de éxito de las maniobras de reposición. MATERIAL Y MÉTODO: Estudio retrospectivo. Se revisaron casos de VPPB con indicación de maniobras de reposición durante los años 2016-2017. Se obtuvo información demográfica, antecedentes médicos, la maniobra realizada y su éxito. Se evaluaron comorbilidades y temporada del año. RESULTADOS: Se incluyeron 195 consultas, realizándose 293 maniobras. La mayoría de los pacientes fueron mujeres (74%) con edad promedio de 63 años. Comorbilidades más frecuentes fueron hipertensión, dislipidemia y diabetes mellitus. El 20% presentó una hipofunción vestibular concomitante, 23% presentó antecedentes de VPPB y 8% compromiso bilateral. Canalolitiasis del CSC posterior fue predominante (90%). En el 77,3% se resuelve el caso con una maniobra. Los casos fueron más frecuentes en primavera y otoño. CONCLUSIONES: El VPPB fue más frecuente en mujeres, con una edad promedio de 63 años. La mayoría presentó canalolitiasis unilateral lográndose resolución con una maniobra de reposición.

INTRODUCTION: Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vertigo. The treatment depends on the semicircular canal (SCC) and/or cupula involved and consists of particle repositioning maneuvers. AIM: Analyze risk factors associated with BPPV for patients seen at the otorhinolaryngology department of the UC Christus health center. Evaluate the success rate of the repositioning maneuvers. MATERIAL AND METHODS: Retrospective study. All cases of BPPV for which a repositioning maneuver was prescribed during the years 2016-2017 were reviewed. Data obtained includes demographics, medical history, maneuver performed, and its success rate. Comorbidities and seasonality were evaluated. RESULTS: 195 cases were included; with 293 maneuvers. The majority were women (74%), and the average age was 63 years. Common comorbidities were hypertension, dyslipidemia and diabetes mellitus. Concurrently, 20% had unilateral vestibular hypofunction, 23% had a history of BPPV, and 8% had bilateral involvement. Posterior SCC canalithiasis was most common (90%). In 77.3%, the case was resolved with one maneuver. Cases were most frequent in the spring and autumn season. CONCLUSION: BPPV was more common in women with an average age of 63 years. The majority of patients presented with unilateral canalithiasis obtaining a complete recovery with a single maneuver.

[Gossypibomas in neurosurgery]. / Gossypibomas en neurocirugía.

INTRODUCTION: The term «gossypiboma¼ comes from the Latin gossypium, which refers to a genus of cotton plants, and from the Swahili word boma, which translates as «place of concealment¼. It may be mistaken for tumorous lesions or abscesses due to the way it is encapsulated, as evidenced in imaging examinations, and its variable and non-specific clinical features, which give rise to difficulty in its diagnosis and significant morbidity. AIM: To synthesise the available evidence on the presence of gossypibomas during neurosurgical procedures. DEVELOPMENT: A review was performed that included a search for articles in English and Spanish published in the last 15 years in PubMed, Ebsco Host, Embase, Mediclatina, Cochrane, Lilacs and Scopus, between January and June 2019, using the keywords «gossypiboma¼, «textiloma¼, «neurosurgery¼ and «neurosurgical procedures¼. In all, a total of 630 articles were found in the search, although, after selecting them by title and abstract, 22 case report articles were included for this review process. Altogether 36 individuals were identified, of whom 21 (58.3%) were women, and whose mean age was 56.1 years. Surgical sponges were observed as gossypibomas in 20 cases (55.6%). CONCLUSIONS: Gossypiboma is a complication secondary to surgical procedures that presents fairly unspecific signs and symptoms. The time that elapses before it appears usually ranges from a few days to several years after surgery and is correlated with multiple medical and legal implications.

TITLE: Gossypibomas en neurocirugía.Introducción. El término «gossypiboma¼ proviene del latín gossypium, que hace referencia a un género de plantas de algodón, y de la palabra kiswahili boma, que se traduce como «lugar de escondite¼. Puede confundirse con lesiones tumorales o abscesos debido a la forma de encapsulación evidenciada en los exámenes imaginológicos y su clínica variable e inespecífica, situación que genera dificultad para el diagnóstico y una morbilidad importante. Objetivo. Sintetizar la evidencia disponible sobre la presencia de gossypibomas durante la realización de procedimientos quirúrgicos en neurocirugía. Desarrollo. Se realizó una revisión en la cual se incluyó una búsqueda de artículos en inglés y castellano publicados en los últimos 15 años en PubMed, Ebsco Host, Embase, Mediclatina, Cochrane, Lilacs y Scopus, entre enero y junio de 2019, utilizando las palabras clave «gossypiboma¼, «textiloma¼, «neurosurgery¼ y «neurosurgical procedures¼. El total de artículos encontrados en la búsqueda fue de 630; sin embargo, tras la selección por título y resumen fueron 22 los artículos de informe de caso que se incluyeron. Se identificó a un total de 36 individuos, de los cuales 21 (58,3%) eran mujeres, y cuya edad media era de 56,1 años. En 20 casos (55,6%) se observaron esponjas quirúrgicas como gossypibomas. Conclusiones. El gossypiboma es una complicación secundaria a procedimientos quirúrgicos, con signos y síntomas bastante inespecíficos. Su tiempo de aparición suele oscilar entre unos cuantos días hasta varios años después de realizada la cirugía y se correlaciona con múltiples implicaciones médicas y legales.

Esmirtazapine treatment of postmenopausal vasomotor symptoms: two randomized controlled trials.

OBJECTIVES: Two identical 12-week, randomized, double-blind, placebo-controlled, multi-arm, parallel-group Phase III studies (Study P012, NCT00560833; Study P013, NCT00535288) evaluated the efficacy and safety of esmirtazapine, an investigational medicine, for the treatment of moderate to severe vasomotor symptoms (VMS) in postmenopausal women. METHODS: Participants were randomized to placebo or esmirtazapine (2.25, 4.5, 9.0, or 18.0 mg). Co-primary efficacy endpoints (daily frequency and severity of moderate to severe VMS, both at weeks 4 and 12) were based on participative LogPad daily diaries. Adverse events (AEs) were recorded. RESULTS: In Studies P012 and P013, 942 and 946 participants were randomized, respectively. Compared with placebo, esmirtazapine significantly reduced the mean daily frequency by 1.4-2.2 moderate to severe VMS at weeks 4 and 12 (both ≥4.5 mg) and mean daily severity by 0.06-0.08 symptoms at weeks 4 (≥4.5 mg) and 12 (9.0 mg P012; 18.0 mg P013 only). Esmirtazapine was generally well tolerated with a more favorable safety profile at lower doses. Somnolence and fatigue were the most frequently reported AEs. CONCLUSIONS: Esmirtazapine reduced the frequency and severity of moderate to severe VMS associated with menopause and was generally well tolerated in the study population.

Oxidative Stress in Spinocerebellar Ataxia Type 7 Is Associated with Disease Severity.

Spinocerebellar ataxia type 7 is a neurodegenerative inherited disease caused by a CAG expansion in the coding region of the ATXN7 gene, which results in the synthesis of polyglutamine-containing ataxin-7. Expression of mutant ataxin-7 disturbs different cell processes, including transcriptional regulation, protein conformation and clearance, autophagy, and glutamate transport; however, mechanisms underlying neurodegeneration in SCA7 are still unknown. Implication of oxidative stress in the pathogenesis of various neurodegenerative diseases, including polyglutamine disorders, has recently emerged. We perform a cross-sectional study to determine for the first time pheripheral levels of different oxidative stress markers in 29 SCA7 patients and 28 age- and sex-matched healthy subjects. Patients with SCA7 exhibit oxidative damage to lipids (high levels of lipid hydroperoxides and malondialdehyde) and proteins (elevated levels of advanced oxidation protein products and protein carbonyls). Furthermore, SCA7 patients showed enhanced activity of various anti-oxidant enzymes (glutathione reductase, glutathione peroxidase, and paraoxonase) as well as increased total anti-oxidant capacity, which suggest that activation of the antioxidant defense system might occur to counteract oxidant damage. Strikingly, we found positive correlation between some altered oxidative stress markers and disease severity, as determined by different clinical scales, with early-onset patients showing a more severe disturbance of the redox system than adult-onset patients. In summay, our results suggest that oxidative stress might contribute to SCA7 pathogenesis. Furthermore, oxidative stress biomarkers that were found relevant to SCA7 in this study could be useful to follow disease progression and monitor therapeutic intervention.

Síndrome de Susac: caso clínico y revisión / Susac syndrome: clinical case and literature review

RESUMEN El síndrome de Susac (SS) es una enfermedad autoinmune microangiopática poco frecuente, caracterizada por la tríada clínica: encefalopatía, alteraciones visuales e hipoacusia. Es una entidad de prevalencia desconocida dado su difícil diagnóstico debido a que la mayoría de las veces no se presenta con la tríada clínica clásica, y, dado que presenta múltiples diagnósticos diferenciales. Se reporta un caso de SS presentado en el Hospital del Salvador, con descripción de sus manifestaciones clínicas, estudio y manejo inicial. Además de una revisión en la literatura sobre la variabilidad de los hallazgos clínicos y el manejo de esta patología.

ABSTRACT Susac syndrome (SS) is a rare autoimmune micronagiopathic disease, characterized by the clinical triad of, encephalopathy, visual impairment and hearing loss. It is a difficult entity to diagnose since most of the time it does not present itself with the classical clinical triad, and it may be confused with other differential diagnoses. One clinical case of a patient with SS is described, its clinical manifestations, diagnosis and initial treatment. In addition, a literature review about the multiple clinical findings and management of these disease.

Oxidative modifications of foetal LDL-c and HDL-c lipoproteins in preeclampsia.

BACKGROUND: Oxidative modifications have been observed in lipids and proteins in lipoproteins isolated from women with preeclampsia. Thus, newborns could also be susceptible to this damage directly through their mothers. In this study, we evaluated the oxidative profile of LDL-c and HDL-c lipoproteins isolated from the umbilical cord from newborns born to women with preeclampsia. METHODS: Thirty newborns born to women with preeclampsia and thirty newborns born to women with healthy pregnancies were included. Lipid-damage biomarkers, including conjugated dienes, lipohydroperoxides and malondialdehyde, were measured. The reduction of nitroblue tetrazolium, formation of dityrosines, and carbonylation of proteins were assessed as indicators of protein damage. The protective activity of paraoxonase-I on HDL-c particles was evaluated. The total antioxidant capacity and lipid profiles were quantified in plasma. Data were analysed using Student's t-tests and Pearson correlation coefficients. RESULTS: Compared with the control group, the preeclampsia group had an increase in the percentage of lipid damage in both lipoproteins. There was an increase of 23.3 and 19.9% for conjugated dienes, 82.4 and 21.1% for lipohydroperoxides, and 103.8 and 51.5% for malondialdehyde in LDL-c and HDL-c, respectively. However, these infants did not show evident damage in protein oxidation. The activity of the enzyme paraoxonase-I was decreased by 36.2%; by contrast, the total antioxidant capacity was increased by 40% (protein) and 28.8% (non-protein). CONCLUSIONS: The oxidative modifications that occur in HDL-c and LDL-c isolated from newborns from women with preeclampsia are mainly caused by lipoperoxidation processes related to evident paraoxonase-I inactivation. The absence of protein damage is likely linked to an increase in total antioxidant capacity. Therefore, antioxidant support could be helpful in reducing oxidative stress in mother/newborn dyads.

Timpanoplastía endoscópica: experiencia en el Hospital del Salvador / Endoscopic tympanoplasty: experience in Hospital del Salvador

RESUMEN Introducción: La técnica endoscópica para la cirugía de oído ha presentado un gran avance en los últimos años, debido al avance de las ópticas de alta resolución e instrumental quirúrgico. El uso de endoscopio en timpanoplastías facilita la visualización de zonas de difícil acceso, como es el caso de pacientes con pared anterior del conducto auditivo externo prominente y perforaciones timpánicas anteriores, además permite la revisión de la caja timpánica y de las vías de ventilación del oído medio. Objetivo: Mostrar la timpanoplastía endoscópica (TE) como alternativa en pacientes con otitis media crónica y analizar el éxito anatómico y funcional. Material y método: Revisión de fichas clínicas de pacientes sometidos a TE en el Hospital del Salvador. Resultados: Catorce pacientes fueron operados entre octubre de 2015 y agosto de 2016. La edad promedio fue de 45 años. Todos fueron sometidos a TE unilateral. Once de 14 perforaciones comprometía alguno de los cuadrantes anteriores. De éstas, en el 82% el borde anterior de la perforación no era visible con otomicroscopía. Se realizó otoendoscopía y audiometría 2 meses poscirugía, logrando un éxito anatómico de 92,8%, y mejoría en el PTP posoperatorio en todos los pacientes. Conclusión: Los resultados obtenidos son similares a los descritos utilizando microscopio. La TE permite mejor visualización convirtiendo esta técnica en una alternativa quirúrgica y de docencia atractiva. Es necesario realizar seguimiento a estos pacientes y aumentar el número de pacientes en el futuro.

ABSTRACT Introduction: The endoscopic ear surgery technique has been a great advance in the last years due to the developments in high resolution optics and surgical instruments. The use of an endoscope provides the visualization of difficult access zones in the middle ear, such as patients with prominent anterior wall of the external auditory canal and anterior tympanic perforations. Aim: To describe the endoscopic tympanoplasty (ET) as an alternative treatment for patients who suffer from chronic otitis media, and to analyze the functional and anatomic outcome. Material and method: Clinical record review of patients submitted to a ET in Hospital del Salvador. Results: 14 patients were operated during October 2015 and August 2016. The average age was 45 years. All of them where submitted to a unilateral ET. 11 of 14 perforations compromised some of the anterior quadrants. In 82% of the latter the anterior edge of the perforation was not visible with otomicroscopy. An otomicroscopy and audiometry were performed 2 months after surgery, anatomic outcome success was of 92,8%, and PTA improved after surgery in all patients. Conclusion: The obtained results are similar to those described using microscope. ET allows improved visualization making this technique an attractive surgery and teaching choice. It is necessary to evaluate these results with a higher number of patients.

Cirugía endoscópica de oído para el manejo del colesteatoma atical / Endoscopic ear surgery approach for attic cholesteatoma treatment

RESUMEN El colesteatoma es la presencia de epitelio plano queratinizado en zonas neumatizadas del hueso temporal, cuya ubicación más frecuente es el ático. En la década de los noventa, se inicia el desarrollo de la cirugía endoscópica de oído, ofreciendo una nueva perspectiva en el tratamiento del colesteatoma. Se presentan dos casos clínicos de pacientes con colesteatoma atical. Se realiza abordaje endoscópico transcanal con resección macroscópica completa del colesteatoma. Audiometría posoperatoria evidencia mejoría de hipoacusia de conducción.

ABSTRACT The cholesteatoma is the presence of keratinized squamous epithelium in pneumatized areas of the temporal bone, its most frequent location is the attic. In the 1990s the development of the ear endoscopic surgery begins, offering a new perspective for cholesteatoma treatment. Two clinical cases of patients who present attic cholestatoma are described. A transcanal endoscopic approach with complete macroscopic resection was accomplished. Post-surgical audiometry shows improvement of the conductive hearing loss.

Dehiscencia del canal semicircular superior como causa de tinnitus pulsátil / Superior semicircular canal dehiscence as cause of pulsatile tinnitus

RESUMEN El tinnitus se presenta en forma crónica en alrededor del 10% de los adultos, siendo el 4% de estos casos tinnitus pulsátil (TP). El TP se caracteriza por ser rítmico y sincrónico al latido cardiaco. Existen múltiples causas descritas, pero en un grupo importante de casos, no se logra objetivar su origen. Nuestro objetivo es presentar casos de dehiscencia del canal semicircular superior (DCSS) como causa de tinnitus pulsátil y su estudio. Se presentan dos pacientes evaluadas por tinnitus pulsátil. En ambos casos se descartan causas sistémicas, ECO doppler carotídeo sin alteración, angio TAC y RNM sin hallazgos. En reconstrucción de Pöschl se sospecha DCSS, por lo que se estudia con potenciales miogénicos evocados cVEMP y oVEMP con disminución de umbral y respuesta aumentada en oído afectado. En los casos expuestos el tinnitus aparece como síntoma único asociado a la presencia de DCSS, que fue confirmada con estudio imagenológico y VEMPs. El estudio con angio TAC permite pesquisar diversas causas asociadas. Los VEMPs confirman el diagnóstico, teniendo el oVEMP mayor sensibilidad. Como conclusión la DCSS es una entidad a tener presente como diagnóstico diferencial del tinnitus pulsátil y ante su sospecha se debe explorar con VEMPs.

ABSTRACT Tinnitus occurs chronically in about 10% of adults, being pulsatile tinnitus a 4% of these cases (TP). TP is characterized by being rythmic and sychronous to the heart beat. There are many described causes, but in a significant group of cases it is not possible to determine its origin. Our aim is present clinical cases of superior semicircular canal dehiscence (SSCD) as the cause of pulsatile tinnitus and its study. Clinical cases: Two patients present pulsatile tinnitus in her right ear. System causes were discarded, normal Carotid Doppler ultrasonography, Anglo CT scan and MRI without findings. In Pöschl reconstruction SSCD can be observed. Evoked myogenic potentials (VEMPs) by suspicion of SSCD Syndrome, cVEMP and oVEMP with a elevated amplitudes and lower thresholds ipsilateral response. In the cases exposed, tinnitus appears as a single symptom associated with the presence of SSCD which was confirmed with imaging studies and VEMPs. The AngioTAC allows to investigate several associated causes. The VEMPs confirm the diagnosis, with oVEMP having a greater sensitivity. The SSCD is an entity to have in my mind as a differential diagnosis of pulsatile tinnitus and, if suspected, should be explored with VEMPs.