Clinical and computed tomography findings in cats with nasopharyngeal stenosis.

OBJECTIVES: Concurrent anomalies are often found in nasopharyngeal stenosis and choanal atresia; some seem to be of primary nature, whereas others may be coincidental. This study aimed to report the computed tomography features and related comorbidities of these diseases. MATERIALS AND METHODS: A cross-sectional retrospective study was performed using case and control groups defined according to the presence of signs of upper airway disease and the presence/absence of nasopharyngeal stenosis, respectively. The inclusion criteria were full-head tomography scans and access to clinical records. The exclusion criteria were brachycephalic breed, head trauma and neoplasm. Clinical and computed tomographic findings and relevant comorbidities were recorded. RESULTS: Forty-three cats were included, 23 cases and 20 controls. The case group was significantly younger, had more paranasal sinus anomalies and never had turbinate lysis, also, had significantly more soft palate anomalies, which was significantly shorter. Nasopharyngeal stenosis varied from membrane appearance to partial or complete adhesion of the soft palate to the nasopharynx, was mainly located in the caudal region of the nasopharynx and was imperforated in approximately half of the cases. Imperforated membranes were significantly thicker in the sagittal plane and were significantly associated with nasal obstruction and soft tissue attenuation of the tympanic bulla. Hiatal hernia and ventricular asymmetry were only encountered in three and two cases, respectively, with nasopharyngeal stenosis. CLINICAL SIGNIFICANCE: Computed tomography in cats with nasopharyngeal stenosis can identify concurrent anomalies, can help to differentiate a possible choanal atresia and evaluate the magnitude of its significance.

Hyperglycemia alters N-glycans on colon cancer cells through increased production of activated monosaccharides.

Diabetes Mellitus (DM) is both, correlated and a known risk factor for colorectal cancer (CRC). Besides favoring the incidence of CRC, DM also accelerates its progression, worsening its prognosis. Previously, hyperglycemia, the DM hallmark, has been shown to lead to aberrant glycosylation of CRC cells, heightening their malignancy both in vivo and in vitro. Here we use mass spectrometry to elucidate the composition and putative structures of N-glycans expressed by MC38 cultured in normoglycemic (LG) and hyperglycemic-like conditions (HG). N-glycans, 67, were identified in MC38 cells cultured in LG and HG. The cells grown in HG showed a greater abundance of N-glycans when compared to LNG cells, without changes in the proportion of sialylated, fucosylated and mannosylated N-glycans. Among the identified N-glycans, 16 were differentially expressed, mostly mannosylated and fucosylated, with a minority of them being sialylated. Metabolomics analysis indicates that the alterations observed in the N-glycosylation may be mostly due to increase of the activated monosaccharides pool, through an increased glucose entrance into the cells. The alterations found here corroborate data from the literature regarding the progression of CRC, advocating for development or repositioning of effective treatments against CRC in diabetic patients.

Management of congenital and acquired airway pathologies in newborns by a cross-disciplinary committee at a third level hospital. / Manejo de la patología congénita y adquirida de la vía aérea en el neonato por parte de un comité multidisciplinar en un centro terciario.

INTRODUCTION: Neonatal airway examination through flexible/rigid bronchoscopy has proved to be useful in the presence of persistent stridor and extubation failure, as well as to assess complications following cardiac surgery. At our institution, these examinations are carried out by a pulmonologist, a neonatologist, an otorhinolaryngologist, and a pediatric surgeon from the pediatric airway committee, established in 2014. OBJECTIVE: To analyze the airway examinations performed in neonates during their stay at the neonatology/neonatal intensive care unit since the airway committee was established. MATERIAL AND METHODS: A retrospective study of the airway examinations conducted in neonates from 2015 to 2019 was carried out. Clinical and demographic data, number of examinations, indications, findings, and complications were collected. Results are presented as mean and standard deviation. Statistical significance was established at p < 0.05. RESULTS: 92 airway examinations were analyzed in 51 patients (54.9% of whom were female). 51% of the patients were premature. Extubation failure and persistent respiratory symptoms following successful extubation were the most frequent indications for airway examination (35.3%). Stratification by gestational age or weight at birth was not associated with an increased risk of pathological findings at examination (p > 0.05). The most frequent finding was vocal cord paralysis (n = 14; 27.5%). In 10 patients (19.6%), no pathological findings were observed. CONCLUSION: Airway examination is useful in patients with stridor to identify vocal cord paralysis following extubation failure. It also allows congenital airway pathologies to be diagnosed and treated. The number of examinations with no pathological findings was similar to that reported in international series.

INTRODUCCION: La exploración de vía aérea mediante broncoscopia flexible/rígida en el neonato ha demostrado utilidad en el estridor persistente, extubaciones fallidas o para valorar complicaciones tras cirugía cardiaca. En nuestro hospital estas exploraciones son practicadas por un neumólogo, neonatólogo, otorrinolaringólogo y cirujano pediátrico del Comité de Vía Aérea Pediátrica, formado en 2014. OBJETIVO: Analizar las exploraciones de vía aérea practicadas a neonatos durante su estancia en Neonatología/Unidad de Cuidados Intensivos Neonatales desde la constitución del Comité de Vía Aérea. MATERIAL Y METODOS: Estudio retrospectivo de exploraciones de vía aérea practicadas a neonatos de 2015-2019. Se recogen datos clínicos y demográficos, número de exploraciones, indicación, hallazgos y complicaciones. Se presentan las medias con su desviación estándar. Se consideró un resultado estadísticamente significativo cuando p < 0,05. RESULTADOS: Se analizaron 92 exploraciones de vía aérea en 51 pacientes (género femenino: 54,9%). El 51% de los pacientes fueron prematuros. La extubación fallida y la persistencia de sintomatología respiratoria tras una extubación satisfactoria fueron las indicaciones más frecuentes (35,3%). La estratificación por edad gestacional o por peso al nacimiento no se asociaba a un mayor riesgo de presentar hallazgos patológicos en la exploración. El hallazgo más frecuente fue la parálisis de cuerda vocal (n = 14; 27,5%). En 10 pacientes (19,6%) no se encontraron hallazgos patológicos. CONCLUSION: La exploración de la vía aérea es útil en pacientes con estridor postextubación y para identificar parálisis de cuerda vocal tras extubación fallida. Además, permite el diagnóstico y tratamiento de patologías congénitas de la vía aérea.

Usefulness of digestive biopsy in the diagnosis of graft-versus-host disease. / Utilidad de la biopsia digestiva para el diagnóstico de la enfermedad injerto contra huésped.

INTRODUCTION: Graft-versus-host disease (GVHD) is a frequent complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), with high morbidity and mortality rates. Intestinal clinical signs are unspecific, which means differential diagnosis with infections and drug-related etiology should be carried out. Even though intestinal biopsy is widely considered as the gold standard technique, there is no consensus as to which sampling method is best. OBJECTIVE: To assess the results of the biopsy techniques used in patients with suspected intestinal GVHD. MATERIAL AND METHODS: A retrospective study of patients with suspected intestinal GVHD undergoing allo-HSCT from 2010 to 2019 was carried out. They were assessed through digestive biopsy - esophagogastroduodenal biopsy (upper GI endoscopy - UGIE) or rectal biopsy (colonoscopy or direct biopsy). Quantitative variables, expressed as median and interquartile range, and qualitative variables, expressed as absolute frequency and percentage, were collected. RESULTS: 23 patients were studied, 60.9% of whom were male. Median age at biopsy was 9 years (7-14 years). UGIE was used in 47.8% of patients (n=11), colonoscopy was used in 26.1% of patients (n=6), and direct biopsy was used in 34.8% of patients (n=8), with GVHD positive results in 2 (18.2%), 2 (33.3%), and 4 (50%) patients, respectively. CONCLUSIONS: Samples taken through direct biopsy stand as an effective alternative in GVHD diagnosis.

INTRODUCCION: La enfermedad injerto contra huésped (EICH) es una complicación frecuente de los trasplantes de células precursoras hematopoyéticas alogénicos (alo-TCPH), con gran morbimortalidad. La clínica intestinal es inespecífica, planteando el diagnóstico diferencial con infecciones y etiología medicamentosa. Aunque las biopsias intestinales son el gold standard, no existe consenso sobre la mejor técnica para obtenerlas. OBJETIVO: Evaluar los resultados de las técnicas empleadas para obtener biopsias en pacientes con sospecha de EICH intestinal. MATERIAL Y METODOS: Estudio retrospectivo que incluye pacientes sometidos a alo-TCPH entre 2010 y 2019, con sospecha de EICH intestinal estudiados mediante biopsias digestivas: esofagogastroduodenales (endoscopia digestiva alta - EDA) o rectales (colonoscopia o biopsia directa). Recogimos variables cuantitativas, expresadas como mediana y rango intercuartílico; y cualitativas, expresadas en frecuencia absoluta y porcentaje. RESULTADOS: Estudiamos 23 pacientes (60,9% varones). La mediana de edad en el momento de la biopsia fue 9 años (7-14 años). Empleamos EDA en el 47,8% (n= 11), colonoscopia en 26,1% (n= 6) y biopsia directa en el 34,8% (n= 8); siendo positivas para EICH en 2 (18,2%), 2 (33,3%) y 4 (50%), respectivamente. CONCLUSIONES: Las muestras obtenidas mediante biopsia directa se plantean como una alternativa eficiente en el diagnóstico del EICH.

Avaliação do ponto de congelamento do leite cru por espectroscopia de infravermelho com transformada de Fourier como método de triagem / [Fourier Transform Infrared spectroscopy (FTIR) as a screening method for freezing point in raw milk]

O objetivo deste estudo foi investigar a interferência do teor de gordura do leite no ponto de congelamento (PC) obtido pelo infravermelho com transformada de Fourier (FTIR). Uma fração de leite cru foi desnatada, obtendo-se creme e leite desnatado. O leite integral e o desnatado foram adicionados com água (0%, 2%, 5%, 10%, 15% e 20%). O leite desnatado remanescente foi adicionado com creme (5%, 10%, 15%, 20%) e água (0%, 2%, 5%, 10%, 15% e 20%). As amostras foram analisadas para PC (crioscópio eletrônico e FTIR) e composição (FTIR). O PC medido por FTIR foi altamente correlacionado com o método do crioscópio eletrônico (acima de 98,5%) e, como esperado, a adição de água foi significativa (P≤0,001) ao aumentar o PC do leite em ambos os métodos. No entanto, o alto teor de gordura no leite cru resultou na redução do PC ao se utilizar o FTIR, enquanto o baixo teor de gordura resultou em aumento do PC (P≤0,001). Uma vez que a adição de água causou o efeito inverso do alto teor de gordura no PC medido por FTIR, é importante considerar o teor de gordura do leite para evitar interpretações erradas do PC quando se utiliza o método FTIR.(AU)

The objective of this study was to investigate the interference of milk fat content upon the Freezing Point (FP) obtained by Fourier-transform infrared (FTIR). A fraction of raw milk was skimmed, obtaining cream and skim milk. Whole and skim milk were added with water (0, 2, 5, 10, 15, and 20%). The remaining skim milk was added with cream (5, 10, 15, 20%) and water (0, 2, 5, 10, 15, and 20%). Samples were analyzed for FP (thermistor cryoscope and FTIR) and composition (FTIR). FP measured by FTIR was highly correlated with the thermistor cryoscope method (above 98.5%) and, as expected, water addition was significant (P≤0.001) upon increasing milk FP in both methods. However, high fat content in raw milk resulted in decreasing FP when using FTIR, while low fat content resulted in increased FP (P≤0.001). Since water addition caused the inverse effect of high fat on FP measured by FTIR, it is important to regard the fat content of milk to avoid misinterpretation of FP when using the FTIR method.(AU)

Complete pathological response (pCR) in gastroesophageal cancer: Correlation with metabolic response.

PURPOSE: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery in patients with resectable esophageal or esophagogastric junctional (GEJ) (Siewert I) cancer is associated with long term overall survival benefits. Up to one third of all patients submitted to nCRT present pathological complete response (pCR). 18F-fluorodeoxyglucose positron emission tomography with CT (18F-FDG PET-CT) is an important tool for assessing treatment response. Purpose was to assess retrospectively the power of 18F-FDG PET-CT in predicting pCR to evaluate the feasibility of a "watch and wait" approach. PATIENTS AND METHODS: Retrospective analysis of a prospective database with esophageal or GEJ submitted to pre-operative chemoradiation. Pre and pos treatment 18F-FDG PET-CT were reviewed and classified using visual assessment and PERCIST criteria and the values of maximum standard uptake value were also recorded. Patients were classified as pCR or non-PCR. 18F-FDG PET-CT and pathological findings were compared against each other. RESULTS: Forty-three patients were included. The median age was 67 years and 90.7% were male. All patients underwent preoperative CRT and were evaluated with 18F-FDG PET-CT pre and post treatment. Transthoracic surgery was performed in all patients. Histological type was adenocarcinoma in 37% and squamous cell carcinoma in 58%. pCR was achieved in 56% of cases. Visual assessment of 18F-FDG PET-CT showed overall sensitivity 57.9%, specificity 62.5% and PERCIST criteria had 100% sensibility and 16.7% specificity. CONCLUSIONS: 18F-FDG PET-CT is not an ideal predictor of pCR but if we use the PERCIST criteria we will have a high sensitivity and negative predictive value, avoiding false negative scans.

Fibrin glue treatment associated or not with diathermy for recurrent tracheoesophageal fistula: our results after more than 20 years' experience. / Tratamiento con adhesivo de fibrina asociado o no a diatermia para las fístulas traqueoesofágicas recurrentes: resultados tras más de 20 años de experiencia.

INTRODUCTION: Recurrent tracheoesophageal fistula (RTEF) is a frequent complication (5-10%) in patients with esophageal atresia (EA). Open RTEF surgery has a high morbidity and mortality, so the endoscopic approach represents a promising alternative. We present the long-term results of fibrin glue (FG) bronchoscopic application in patients with RTEF secondary to EA, which was first used by our team in 1994. MATERIAL AND METHODS: A retrospective review of all patients diagnosed with RTEF following EA repair and treated with FG bronchoscopic application from 1993 to 2019 was carried out. In most cases, diathermy was applied prior to FG sealing. The maximum number of endoscopic sessions was 5. In case of persistent RTEF following the fifth session, open surgery was performed. RESULTS: 14 RTEF patients were treated with FG. In all but the first 3 cases (11 patients, 78.6%), diathermy was applied concomitantly. Mean first treatment day was day 85 of life (range: 14-770). Patients received a mean of 2.1 (1-5) endoscopic sessions. Mean follow-up was 12.1 (10-20) years. Overall success rate was 71.4%, without significant differences according to whether diathermy was concomitantly applied or not (72.7% vs. 66.6%). CONCLUSIONS: Fibrin glue bronchoscopic application associated or not associated with diathermy is an excellent option for RTEF treatment in EA patients. The endoscopic approach should be considered as the first-choice treatment for RTEF.

INTRODUCCION: La fístula traqueoesofágica recurrente (FTER) representa una complicación frecuente (5-10%) en los pacientes con atresia de esófago (AE). La cirugía abierta de FTER implica una alta morbimortalidad, por lo que los abordajes endoscópicos suponen una alternativa prometedora. Presentamos los resultados a largo plazo de la aplicación broncoscópica de adhesivo de fibrina (AF) en pacientes con FTER secundaria a AE, técnica utilizada por primera vez en 1994 por nuestro equipo. METODOS: Revisión retrospectiva de 1993 a 2019, incluyendo a todos los pacientes diagnosticados de FTER tras la reparación de AE, y tratados con aplicación broncoscópica de AF. En la mayoría de los casos se aplicó diatermia previamente al sellado con AF. El número máximo de sesiones endoscópicas se estableció en cinco; en caso de persistir FTER tras la quinta sesión, se procedió a cirugía abierta. RESULTADOS: 14 pacientes con FTER fueron tratados con AF; en todos salvo los primeros 3 casos (11 pacientes, 78,6%) se aplicó diatermia concomitante. El día promedio del primer tratamiento fue el día 85 de vida (14 a 770). Los pacientes recibieron una media de 2,1 (1-5) sesiones endoscópicas. El seguimiento medio fue de 12,1 (10-20) años. El éxito global fue del 71,4%, sin apenas variar con la aplicación o no de diatermia concomitante (72,7% vs. 66,6%). CONCLUSIONES: La aplicación broncoscópica de adhesivo de fibrina asociado o no a diatermia representa una excelente opción para el tratamiento de FTER en pacientes con AE. El abordaje endoscópico debe considerarse como tratamiento de primera elección para FTER.

Análise da estrutura populacional de ovinos deslanados do núcleo de conservação / Population structure analysis in sheep without wool in the conservation nucleus

Este estudo analisou a estrutura populacional de ovinos deslanados do núcleo de conservação do estado do Ceará, Brasil. Os parâmetros populacionais foram estimados com base nos dados genealógicos de indivíduos das raças Santa Inês (SI), Somalis (SO) e Morada Nova (MN), nascidos entre os anos de 2001 e 2014. Os parâmetros estimados foram: número de gerações completas equivalentes (GCE), intervalo entre gerações (IEG), número de fundadores (Nf), número efetivo de fundadores (fe), número efetivo de ancestrais (fa), coeficiente de endogamia (F) e índice de contribuição genética (ICG). O GCE médio foi de 1,82, 2,78 e 1,52 para SI, SO e MN, respectivamente. O IEG foi próximo entre as raças, 3,67 anos em média. O Nf para SI, SO e MN foi igual a 225, 194 e 153, respectivamente. As razões fe/fa foram distantes de 1 nas três populações, o que indica ocorrência de gargalo genético, principalmente para SO. Os coeficientes médios de endogamia foram de 1,81%, 0,78% e 0,78% para SI, SO e MN, respectivamente. O ICG foi de 3,32, 5,38 e 2,87 para SI, SO e MN, respectivamente. Os parâmetros populacionais estimados apontam que parte da genética original desses rebanhos foi perdida, principalmente na população da raça Somalis.(AU)

This study evaluated the population structure of sheep without wool from the conservation nucleus in Ceará State, Brazil. Population parameters were estimated on genealogical records of Santa Ines (SI), Somali (SO,) and Morada Nova (MN) breeds, that were born between 2001 and 2014. The following estimates were obtained: number of complete generation equivalents (GCE), generation intervals (IEG), number of founders (Nf), effective number of founders (fe), effective number of ancestors (fa), inbreeding coefficient (F), and genetic contribution index (ICG). Average GCE was 1.82, 2.78, and 1.52 for SI, SO, and MN respectively. Mean IEG was similar between breeds, 3.67 years. The Nf was 225, 194, and 153 for SI, SO, and MN respectively. The fe/fa ratios were different to 1, which is an indication of genetic bottleneck, mainly for SO. The average inbreeding coefficients were 1.81%, 0.78%, and 0.78% for SI, SO, and MN respectively. The ICG was 3.32, 5.38, and 2.87 for SI, SO, and MN respectively. Estimated population parameters indicate that part of the genetics of these breeds was lost, mainly in Somalis.(AU)

The use of Z-scan technique for determination of biochemical parameters in children with solid tumors or leukemias supplemented or not with selenium.

Cancer is a disease that effects cell metabolism causing an imbalance in the health of the patient. On the other hand, malnutrition, presented by oncological patients, is caused by both the disease and its treatment. Some serum biochemical parameters cannot be determined by the traditional method of laboratory blood analysis (spectrophotometry). Among the various techniques that could be used for blood biochemical analysis, we opted for the Z-scan technique, due to its sensitivity to the reading of blood components. Our objective in this work was to compare the data obtained by the Z-scan technique and the spectrophotometry of the serological samples of children with solid tumors and leukemia under treatment, receiving or not selenium supplementation in a randomized, double-blind clinical trial. The biochemical parameters were read based on blood. These blood sampling made at different stages of chemotherapy and selenium supplementation. At each of these stages, the cholesterol, glucose and triglycerides parameters were read using the Z-scan and spectrophotometry techniques. We observed that selenium helps in balancing the health of these patients, and corroborates with our hypothesis that the Z-scan technique may be an alternative for the determination of biochemical parameters.

Estimação de parâmetros genéticos para características de pesos e pesos metabólicos na desmama e pós-desmama em bovinos Brahman / Estimation of genetic parameters for weaning weights and metabolic weights characteristics and post weaning in Brahman cattle

Objetivou-se estimar herdabilidades e correlações de características ponderais com 36.505 animais, da Associação Brasileira de Criadores Zebu. O modelo incluiu efeito genético direto, materno, ambiente permanente, residual - aleatórios e efeitos de grupos contemporâneos - fixos. Os parâmetros foram estimados pelo método de máxima verossimilhança restrita (REML), utilizando-se software Wombat. Os resultados das herdabilidades variaram de 0,20 a 0,25 peso à desmama e ao sobreano; 0,16 a 0,20 peso metabólico não ajustado e ajustado à desmama, 0,21 a 0,25 peso metabólico ajustado à desmama e metabólico ajustado ao sobreano. As correlações genéticas entre peso à desmama e peso metabólico não ajustado à desmama, peso à desmama e peso metabólico ajustado à desmama são, respectivamente 0,76 e 1,00. A correlação genética entre peso ao sobreano e metabólico ao sobreano não ajustado, peso ao sobreano com metabólico sobreano ajustado foram 0,97 e 1,00. Correlação genética entre peso à desmama e ao sobreano foi 0,72, peso metabólico não ajustado à desmama e metabólico não ajustado ao sobreano 0,54, peso metabólico ajustado à desmama e metabólico ajustado ao sobreano foi 0,71. Correlações genéticas entre peso à desmama e metabólico ajustado à desmama e peso ano com metabólico ano ajustado foram 1,00 e 1,00. Portanto, utilização de peso metabólico sem ajuste de idade pode viesar estimativas de parâmetros genéticos.(AU)

The objective of this study was to estimate heritability and correlations of 36,505 animals, belonging to the Brazilian Association of Zebu Breeders. They were estimated by Restricted Maximum Likelihood method (REML) using Wombat software. The model included the direct additive genetic effect, maternal, permanent maternal environment and residual as random and fixed effects of contemporary group. The results of heritability ranged from 0,20 to 0,25 for weaning weight and yearling; 0,16 to 0,20 for real metabolic weaning, 0,21 to 0,25 for metabolic adjusted weight at weaning and yearling metabolic adjusted. The genetic correlations between weaning weight with metabolic real, weaning weight adjusted with metabolic are respectively 0,76 and 1,00. The genetic correlation between yearling weight and metabolic real, yearling weight adjusted metabolic were 0,97 and 1,00. Genetic correlations between weaning weight and yearling was 0,72, real metabolic weight at weaning and yearling real metabolic was 0,54, adjusted metabolic weight at weaning and yearling metabolic adjusted was 0,71. Genetic correlations between weight at weaning and adjusted metabolic and weight-adjusted metabolic year were 1,00 and 1,00. Therefore, the use of metabolic weight without age adjustment can warn the estimates.(AU)

[Multidisciplinary approach on subglottic pathology: a 5-year review]. / Manejo multidisciplinar de la patología subglótica: revisión a 5 años.

INTRODUCTION: Pediatric subglottic pathology still represents a challenge when it comes to choosing the right treatment. We present the management of patients followed in our center for this reason during the last 5 years. MATERIAL AND METHODS: Retrospective study of patients followed by glotosubglottic pathology (stenosis, cysts or granulomas) between 2011 and 2016 in a third level hospital. RESULTS: Twenty-seven patients were included in the review. Treatment options varied according to the nature, location and severity of the subglottic stenosis. Two patients with congenital subglottic stenosis were treated by laryngotracheoplasty. Seventeen patients with acquired subglottic stenosis were included: in one (5.9%) laryngotracheoplasty was performed, one (5.9%) received cricotracheal split, two of them (11.8%) underwent partial cricotracheal resection (PCTR) , seven patients (41.2%) underwent microsurgery, three (17.6%) received tracheal dilatation, and the last three (17.6%) were submitted to observation without needing further treatment. Five patients with post-intubation subglottic cysts received microsurgery. Of three patients diagnosed with post-intubation subglottic granuloma, two (66%) resolved spontaneously and one (33%) required microsurgery. CONCLUSIONS: Management of pediatric subglottic pathology remains a major challenge. Since the creation of the Airway Committee in our center, the improvement in the management of these patients has led to a multidisciplinary management, with the consequent impact on the clinical results.

OBJETIVOS: La patología del espacio subglótico en pacientes pediátricos sigue representando un reto a la hora de elegir el tratamiento idóneo. Presentamos el manejo de los pacientes seguidos en nuestro centro por este motivo durante los últimos 5 años. MATERIAL Y METODOS: Estudio retrospectivo de los pacientes seguidos por patología glotosubglótica (estenosis, quistes o granulomas) entre 2011 y 2016 en un centro de tercer nivel. RESULTADOS: Veintisiete pacientes fueron incluidos en la revisión. Las opciones de tratamiento variaron en función de la naturaleza, la localización y la gravedad de la afectación subglótica. Dos pacientes con estenosis subglótica congénita fueron tratados mediante laringotraqueoplastia. Se incluyeron 17 pacientes con estenosis subglótica adquirida: en uno (5,9%) se realizó laringotraqueoplastia, en uno (5,9%) split cricotiroideo, dos de ellos (11,8%) se intervinieron mediante resección cricotraqueal parcial (PCTR), siete pacientes (41,2%) se sometieron a microcirugía, tres (17,6%) recibieron dilatación traqueal y los tres últimos (17,6%) se sometieron a observación sin necesitar finalmente tratamiento. Cinco pacientes con quistes subglóticos postintubación recibieron microcirugía. De tres pacientes diagnosticados de granuloma subglótico postintubación, dos (66%) se resolvieron espontáneamente y uno (33%) requirió microcirugía. CONCLUSIONES: El manejo de la patología subglótica pediátrica sigue representando un gran desafío. Desde la creación del Comité de Vía Aérea en nuestro centro, la mejoría en la gestión de estos pacientes ha conducido a un manejo multidisciplinar de los mismos, con el consiguiente impacto en los resultados clínicos.

Pomalidomide-dexamethasone in refractory multiple myeloma: long-term follow-up of a multi-cohort phase II clinical trial.

Despite therapeutic advances, multiple myeloma remains incurable, with limited options for patients with refractory disease. We conducted a large, multi-cohort clinical trial testing various doses and treatment schedules of pomalidomide and dexamethasone (Pom/dex) in patients with refractory multiple myeloma. Overall, 345 patients were enrolled to six cohorts based on number and type of prior lines of therapy, pomalidomide dose and schedule. Median prior lines of therapy were three with near universal prior exposure to proteasome inhibitors and/or immunomodulatory drugs. A confirmed response rate of 35% was noted for all cohorts (range 23-65%) with higher responses in cohorts with fewer prior lines of therapy. Median time to confirmed response was ⩽2 months and the longest progression-free survival and overall survival seen in any cohort were 13.1 and 47.9 months, respectively. Observed adverse reactions were as expected, with myelosuppression and fatigue being the most common hematologic and non-hematologic adverse events (AEs), respectively. Longer durations of treatment and response, higher response rates and fewer AEs were noted with the 2 mg pomalidomide dose. This is the longest follow-up data for Pom/dex in refractory multiple myeloma and will help shape the real-world utilization of this regimen.

A soluble inorganic pyrophosphatase from the cattle tick Rhipicephalus microplus capable of hydrolysing polyphosphates.

Polyphosphates have been found in all cell types examined to date and play diverse roles depending on the cell type. In eukaryotic organisms, polyphosphates have been investigated mainly in mammalian cells, and only a few studies have addressed arthropods. Pyrophosphatases have been shown to regulate polyphosphate metabolism. However, these studies were restricted to trypanosomatids. Here we focus on the tick Rhipicephalus microplus, a haematophagous ectoparasite that is highly harmful to cattle. We produced a recombinant R. microplus pyrophosphatase (rRmPPase) with the aim of investigating its kinetic parameters using polyphosphates as substrate. Molecular docking assays of RmPPase with polyphosphates were also carried out. The kinetic and Hill coefficient parameters indicated that rRmPPase has a greater affinity, higher catalytic efficiency and increased cooperativity for sodium phosphate glass type 15 (polyP15 ) than for sodium tripolyphosphate (polyP3 ). Through molecular docking, we found that polyP3 binds close to the Mg2+ atoms in the catalytic region of the protein, participating in their coordination network, whereas polyP15 interactions involve negatively charged phosphate groups and basic amino acid residues, such as Lys56, Arg58 and Lys193; polyP15 has a more favourable theoretical binding affinity than polyP3 , thus supporting the kinetic data. This study shows, for the first time in arthropods, a pyrophosphatase with polyphosphatase activity, suggesting its participation in polyphosphate metabolism.

Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: results of phase IIIb BALLET trial in Spain.

BACKGROUND: Everolimus with exemestane has shown promising activity in patients with hormone-receptor (HR)-positive HER2-negative endocrine-resistant advanced breast cancer. It is necessary, therefore, to characterize the safety profile of this new combination in the real-world clinical setting and in the broadest possible population. PATIENTS AND METHODS: Post-menopausal women with HR-positive HER2-negative advanced breast cancer progressing after prior non-steroidal aromatase inhibitors (NSAIs) were included. The objectives of this analysis were to evaluate the safety profile of this combination in a subset of Spanish patients in the BALLET trial and to characterize grade 3 and 4 adverse events (AEs) in routine clinical practice in Spain. RESULTS: Between September 2012 and July 2013, 429 patients (20% of the overall study population) were included in the BALLET study in 52 hospitals in Spain, of whom 100 (23%) were ≥ 70 years. The median treatment duration was 3.14 and 3.03 months for exemestane and everolimus, respectively. The most common reasons for discontinuation of treatment were local reimbursement of everolimus (43%), followed by disease progression (31%) and the incidence of AEs (15%). The most frequent AEs causing permanent discontinuation were pneumonitis (4%), asthenia (2%) and stomatitis (2%). Overall, 87% of patients experienced at least one AE of any grade, 30% of patients at least one grade 3 AE and 2% of patients a grade 4 AE. CONCLUSION: The safety profile in Spanish patients of the BALLET trial is consistent with the results obtained in the overall population of the trial, as well as in previous clinical trials.

Measurements of femoral angles, femur length, and hip width in cat radiographs / Medidas dos ângulos femorais, comprimento do fêmur e largura do quadril em radiografias de gatos

Femoral angle, femur length, and hip width were measured in radiographs of 92 intact domestic cats, males and females of mixed breed from the Center for Zoonosis Control of the Federal District. The animals showed no trauma, orthopedic diseases or angular deformities and had closed physeal lines. Accordingly, we measured aLPFA (anatomical lateral proximal femoral angle, aLDFA (anatomical lateral distal femoral angle), mLPFA (mechanical lateral proximal femoral angle), mLDFA (mechanical lateral distal femoral angle), IA (femoral inclination angle), FL (femur length) and HW (hip width) using ventrodorsal radiographs, with both hindlimbs in a single exposure to an X-ray beam centered on the hip. The mean values of the variables were: mLPFA: 82.5±3.62°; aLPFA: 80.1±4.29°; mLDFA: 96.1±3.51° (males) and 97.3±2.05° (females); aLDFA: 94,3±3.43°; IA: 136.6±3.86°; FL: 12.9±0.55cm (males) and 13.4±0.66cm (females); and HW: 3.1cm±0.23 (males) and 3.5±0.26cm (females). These values will serve as a reference for the diagnosis of angular deformities and as support for planning corrective osteotomies in domestic cats.(AU)

Foram realizadas mensurações radiográficas dos ângulos femorais e medidas lineares do quadril e do fêmur em 92 gatos domésticos, machos e fêmeas, SRD, oriundos do Centro de Controle de Zoonoses do Distrito Federal, livres de traumas, doenças ortopédicas e deformidades angulares em membros pélvicos, portadores de linhas fiseais fechadas, não castrados. Para tanto, foram obtidos os ângulos aLPFA (ângulo anatômico lateral proximal do fêmur), aLDFA (ângulo anatômico lateral distal do fêmur), mLPFA (ângulo mecânico lateral proximal do fêmur), mLDFA (ângulo mecânico lateral distal do fêmur), AI (ângulo de inclinação do fêmur), CF (comprimento femoral) e LQ (largura de quadril), empregando radiografias em projeções ventrodorsais, com ambos os membros em uma única exposição ao feixe de raios-X, centrada no quadril. Após a apuração dos resultados, os valores médios obtidos foram: mLPFA: 82,5°±3,62, aLPFA: 80,1°±4,29; mLDFA: 96,1°±3.51 (machos) e 97,3°±2,05 (fêmeas), aLDFA: 94,3,6°±3,43; AI: 136,6°±3,86; CF: 136,6°±3,86; 12,9cm±0,55 (machos) e 13,4cm±0,66 (fêmeas) e LQ: 3,1cm±0,23 (machos) e 3,5cm±0,26 (fêmeas), respectivamente. Esses valores servem como referenciais para diagnósticos de deformidades angulares e apoio para planejamento de osteotomias corretivas em felinos domésticos.(AU)

Trends in overall survival and costs of multiple myeloma, 2000-2014.

Little real-world evidence is available to describe the recent trends in treatment costs and outcomes for patients with multiple myeloma (MM). Using the Truven Health MarketScan Research Databases linked with social security administration death records, this study found that the percentage of MM patients using novel therapy continuously increased from 8.7% in 2000 to 61.3% in 2014. Compared with MM patients diagnosed in earlier years, those diagnosed after 2010 had higher rates of novel therapy use and better survival outcomes; patients diagnosed in 2012 were 1.25 times more likely to survive 2 years than those diagnosed in 2006. MM patients showed improved survival over the study period, with the 2-year survival gap between MM patients and matched controls decreasing at a rate of 3% per year. Total costs among MM patients have increased in all healthcare services over the years; however, the relative contribution of drug costs has remained fairly stable since 2009 despite new novel therapies coming to market. Findings from this study corroborate clinical data, suggesting a paradigm shift in MM treatment over the past decade that is associated with substantial survival gains. Future studies should focus on the impact on specific novel agents on patients' outcomes.

Genomic characterization of high-count MBL cases indicates that early detection of driver mutations and subclonal expansion are predictors of adverse clinical outcome.

High-count monoclonal B-cell lymphocytosis (MBL) is an asymptomatic expansion of clonal B cells in the peripheral blood without other manifestations of chronic lymphocytic leukemia (CLL). Yearly, 1% of MBLs evolve to CLL requiring therapy; thus being critical to understand the biological events that determine which MBLs progress to intermediate/advanced CLL. In this study, we performed targeted deep sequencing on 48 high-count MBLs, 47 of them with 2-4 sequential samples analyzed, exploring the mutation status of 21 driver genes and evaluating clonal evolution. We found somatic non-synonymous mutations in 25 MBLs (52%) at the initial time point analyzed, including 12 (25%) with >1 mutated gene. In cases that subsequently progressed to CLL, mutations were detected 41 months (median) prior to progression. Excepting NOTCH1, TP53 and XPO1, which showed a lower incidence in MBL, genes were mutated with a similar prevalence to CLL, indicating the early origin of most driver mutations in the MBL/CLL continuum. MBLs with mutations at the initial time point analyzed were associated with shorter time-to-treatment (TTT). Furthermore, MBLs showing subclonal expansion of driver mutations on sequential evaluation had shorter progression time to CLL and shorter TTT. These findings support that clonal evolution has prognostic implications already at the pre-malignant MBL stage, anticipating which individuals will progress earlier to CLL.

Outcome with lenalidomide plus dexamethasone followed by early autologous stem cell transplantation in patients with newly diagnosed multiple myeloma on the ECOG-ACRIN E4A03 randomized clinical trial: long-term follow-up.

In Eastern Cooperative Oncology Group-ACRIN E4A03, on completion of four cycles of therapy, newly diagnosed multiple myeloma patients had the option of proceeding to autologous peripheral blood stem cell transplant (ASCT) or continuing on their assigned therapy lenalidomide plus low-dose dexamethasone (Ld) or lenalidomide plus high-dose dexamethasone (LD). This landmark analysis compared the outcome of 431 patients surviving their first four cycles of therapy pursuing early ASCT to those continuing on their assigned therapy. Survival distributions were estimated using the Kaplan-Meier method and compared with log-rank test. Ninety patients (21%) opted for early ASCT. The 1-, 2-, 3-, 4- and 5-year survival probability estimates were higher for early ASCT versus no early ASCT at 99, 93, 91, 85 and 80% versus 94, 84, 75, 65 and 57%, respectively. The median overall survival (OS) in the early versus no early ASCT group was not reached (NR) versus 5.78 years. In patients <65 years of age, median OS in the early versus no early ASCT groups was NR in both, hazard ratio 0.79, 95% confidence interval: (0.50, 0.25). In patients ⩾65 years of age, median OS in the early versus no early ASCT was NR versus 5.11 years. ASCT dropped out of statistical significance (P=0.080). Patients opting for ASCT after induction Ld/LD had a higher survival probability and improvement in OS regardless of dexamethasone dose density.