Changes in chronic idiopathic ulcerative colitis epidemiological pattern in Mexico in a tertiary care hospital.

BACKGROUND: Chronic idiopathic ulcerative colitis (CIUC) is a disease with multifactorial chronic inflammation of the colonic mucosa. Its prevalence ranges from 37.5-250/100,000 in North America to 10-500/100,000 in Europe. In Mexico, there are studies that show an increase in the frequency of new cases. The purpose of this work was to identify possible changes in CIUC behavior in a referral hospital. METHODS: New ulcerative colitis (UC) cases confirmed by histopathology from January 2007 to December 2014 were included. Clinical and demographic data were collected through the review of medical records and direct interview in order to compare them with a previous study conducted at the same institution from January 1986 to December 2006. RESULTS: A total of 189 patients were included. Mean number of UC annual new cases was 23.6. The study included 95 male patients (50 %) and 94 female patients (50 %), with an average age of 44.6 years at diagnosis. The frequency of pancolitis was 77 %, in comparison with 59 % in the previous period. Extra-intestinal manifestations (EIM) were present in 55.8 % and colectomies in 5.2 %. CONCLUSION: There is a lower mean of annual new cases; however, some characteristics of the disease have changed over time: there is an increased frequency of pancolitis and EIM, as well as a decrease in the rate of colectomies.

ANTECEDENTES: La colitis ulcerosa crónica idiopática (CUCI) es una enfermedad con inflamación crónica de la mucosa del colon de origen multifactorial. El objetivo de este trabajo es identificar posibles cambios en el comportamiento de la CUCI en un hospital de referencia. MÉTODOS: Se incluyeron nuevos casos de CUCI confirmados por histopatología de enero del 2007 a diciembre del 2014. RESULTADOS: Se incluyeron un total de 189 pacientes. La media de nuevos casos anuales de CUCI fue de 23.6. Este estudio incorpora 95 pacientes de sexo masculino (50 %) y 94 de sexo femenino (50 %), con una edad promedio al diagnóstico de 44.6 años. La frecuencia de pancolitis fue del 77 %, en comparación con el 59 % en el periodo anterior. Las manifestaciones extraintestinales (MEI) estuvieron presentes en el 55.8 % y las colectomías en el 5.2 %. CONCLUSIÓN: Algunas características de la enfermedad han cambiado con el tiempo: aumento de la frecuencia de pancolitis y MEI, así como disminución de la tasa de colectomías.

Phenotypic and genotypic characterization of vancomycin-resistant Enterococcus faecium clinical isolates from two hospitals in Mexico: First detection of VanB phenotype-vanA genotype.

INTRODUCTION: Enterococcus faecium has emerged as a multidrug-resistant nosocomial pathogen involved in outbreaks worldwide. Our aim was to determine the antimicrobial susceptibility, biofilm production, and clonal relatedness of vancomycin-resistant E. faecium (VREF) clinical isolates from two hospitals in Mexico. METHODS: Consecutive clinical isolates (n=56) were collected in two tertiary care hospitals in Mexico from 2011 to 2014. VREF isolates were characterized by phenotypic and molecular methods including pulsed-field gel electrophoresis (PFGE). RESULTS: VREF isolates were highly resistant to vancomycin, erythromycin, norfloxacin, high-level streptomycin, and teicoplanin, and showed lower resistance to tetracycline, nitrofurantoin and quinupristin-dalfopristin. None of the isolates were resistant to linezolid. The vanA gene was detected in all isolates. Two VanB phenotype-vanA genotype isolates, highly resistant to vancomycin and susceptible to teicoplanin, were detected. Furthermore, 17.9% of the isolates were classified as biofilm producers, and the espfm gene was found in 98.2% of the isolates. A total of 37 distinct PFGE patterns and 6 clones (25% of the isolates as clone A, 5.4% as clone B, and 3.6% each as clone C, D, E, and F) were detected. Clone A was detected in 5 different wards of the same hospital during 14 months of surveillance. CONCLUSION: The high resistance to most antimicrobial agents and the moderate cross-transmission of VREF detected accentuates the need for continuous surveillance of E. faecium in the hospital setting. This is also the first reported incidence of the E. faecium VanB phenotype-vanA genotype in the Americas.

Triple-negative breast carcinoma: heterogeneity in immunophenotypes and pharmacokinetic behavior.

OBJECTIVES: To evaluate the morphokinetic, pharmacokinetic, and diffusion characteristics of triple-negative breast cancers on magnetic resonance (MR) imaging and to analyze whether there is a relation between these parameters and the time to progression. MATERIAL AND METHODS: This was a retrospective observational study of a consecutive series of 100 patients with histologically confirmed triple-negative breast cancer studied at our center between January 2005 and December 2010. We reviewed the findings on MR locoregional extension studies, the histological findings, and the follow-up of patients until August 2014. RESULTS: The most common MR findings for these tumors were a rounded mass (47.3%), well-defined borders (53.7%), ring enhancement (46.2%), type 3 curves (50.5%), hyperintensity within the tumor on T2-weighted sequences, high ADC values (1.04 × 10(-3) mm2/s), and increased capillary permeability (Kep) (0.94 min(-1)). No significant association was observed between the morphokinetic or pharmacokinetic characteristics and the time to progression. The in situ component in the surgical specimens was high, although its expression was low. During follow-up, 25% of patients had metastases, with a predilection for the visceral organs, and survival was low. CONCLUSION: Tumors with the triple-negative phenotype mostly presented in MR as rounded tumors with well-defined borders and ring enhancement. We found no significant association between the morphokinetic or pharmacokinetic characteristics and the time to progression.

[Antibiotic resistance and virulence factors in clinical Salmonella enterica isolates]. / Resistencia a antibióticos y factores de virulencia en aislados clínicos de Salmonella enterica.

INTRODUCTION: The increase of Salmonella enterica isolates multi-resistant to different antibiotics, including ß-lactams and fluoroquinolones, is a problem of clinical importance. The dissemination of Salmonella Typhimurium resistant to ampicillin (AMP)-chloramphenicol (CHL)-streptomycin (STR)-sulphonamides and (SUL)-tetracycline (TET), that harbour the Salmonella Genomic Island type 1 (SGI1), and the acquisition of transferable genetic material have favoured the multi-resistance in this genus. METHODS: A total of 114 clinical S.enterica isolates were studied (period 2009-2010). The susceptibility to 20 antibiotics was determined by disc diffusion and microdilution. The antimicrobial resistance mechanisms and the integrons were analysed by PCR, and sequencing in the AMP(R) isolates. In all the blaPSE-1-positive isolates, the clonal relationship was determined by PFGE, as well as the presence of SGI1 and 29 virulence genes by PCR. RESULTS: Eighteen different serotypes were found among the 114 isolates studied, Typhimurium (61%) and Enteritidis (16%) being the most prevalent. High percentages of resistance to SUL (68%), TET (58%), AMP (55%) and STR (46%) were observed. The great majority (92%) of 63 AMP(R) isolates were multi-resistant, with the AMP-STR-TET-SUL phenotype (19 isolates) being the most frequent one and associated with the blaTEM-1b+strA-strB+tet(B)+sul2 genotype. Class 1 integrons (7 different structures) were observed in 48% AMP(R) isolates, highlighting the blaOXA-1+aadA1 structure (8 isolates), one empty integron and non-classical integrons (5 isolates). The blaPSE-1 gene was detected inside the classical SGI1 structure in 13 clonally-related isolates that showed the same virulence profile. CONCLUSIONS: The high percentage of multi-resistant S.enterica isolates, especially associated to S.Typhimurium, to the AMP, STR, TET and SUL phenotype, and to the blaTEM-1b+strA-strB+tet(B)+sul2 genotype, shows an important risk of possible failures in the treatment of serious infections caused by this serotype.

Phenotype characteristics of patients with colonic serrated polyposis syndrome: a study of 23 cases.

INTRODUCTION: Serrated polyposis syndrome (SPS) is a rare entity characterized by the presence of multiple hyperplastic polyps in the colon and an increased risk of presentation and development of colorectal cancer (CRC). OBJECTIVE: To evaluate the clinical and phenotypical characteristics of patients that present one of the 3 WHO criteria for the diagnosis of SPS diagnosed and treated a tour hospital. PATIENTS AND METHODS: Patients with the diagnosis of SPS during 2005-2012 were revised; 24.208 colonoscopies were performed during this period. Age, sex, family history of CRC (APC/MYH), proximal/mixed/distal phenotype, indication for colonoscopy, number, size, location of the hyperplastic polyps, presence of mixed/adenomatous polyps, CRCI, follow-up and endoscopio/surgical treatment. RESULTS: A total of 23 cases were included (19 male). The median age was 51. A total of 34% had a prior family history of CRC or polpyps. Distal phenotype was more frequent (48%). Another 73% presented synchronous adenomatous polyps, and 26% a CRC. A total of 57% were asymptomatic. Surgery was performed in 9 cases (6 for cancer and 3 for polyposis), and 14 were treated by polypectomy and observation. Eleven patients (47%) presented recurrent/persistent lesions after initial surgical/endoscopic treatment. CONCLUSION: SPS is an heterogeneous syndrome that is variable in the type, size, distribution and number of polyps, and is more common in male smokers with a distal phenotype. The majority of patients also present synchronous adenomatous polyps. These patients require an organized multidisciplinary evaluation.

[Advanced Parkinson's disease: clinical characteristics and treatment (part 1)]. / Enfermedad de Parkinson avanzada. Características clínicas y tratamiento (parte I).

INTRODUCTION: A large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced Parkinson's disease. OBJECTIVE: To define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease. DEVELOPMENT: This consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL). CONCLUSIONS: Severe motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD.

Phenotypic and genotypic characterization of Colombian clinical isolates of Sporothrix spp. / Caracterización fenotípica y genotípica de aislamientos clínicos colombianos de Sporothrix spp.

INTRODUCTION: For over a century, Sporothrix schenckii was considered the sole species responsible for sporotrichosis. In 2007, scientific community confirmed the disease could be caused by various Sporothrix species. These species differed in their virulence factors and their antifungal sensitivity. OBJECTIVE: This study aims to characterize 42 Colombian clinical isolates of Sporothrix spp. phenotypically and genotypically. MATERIAL AND METHODS: Forty-two clinical isolates were characterized using phenotypic methods. It involved various culture media to determine their growth range at different temperatures and to assess the type and distribution of pigment and colony texture. Microscopic morphology was evaluated through microcultures, as well as the conidia diameter, type of sporulation, and morphology. Additionally, the assimilation of carbohydrates was selected as a physiological trait for species identification. Genotyping of 40 isolates was performed through partial amplification of the calmodulin gene, followed by sequence analysis. RESULTS: Molecular studies enabled the identification of 32 isolates of S. schenckii and 8 isolates of S. globosa. The combination of phenotypic and genotypic methods eased these species characterizations and the recognition keys development based on parameters such as growth diameter at 25 and 30 ºC, colony texture (membranous or velvety) on potato dextrose agar, and microscopic morphology with predominance of pigmented triangular, elongated oval globose, or subglobose conidia. CONCLUSIONS: Confirmation of the phenotypic characteristics and molecular analysis is crucial for identifying Sporothrix species and determining adequate treatment. This study represents the first phenotypical and genotypical characterization of clinical isolates of Sporothrix spp. reported in Colombia.

Introducción: Por más de un siglo se creyó que Sporothrix schenckii era la única especie responsable de la esporotricosis. Sin embargo, en el 2007, se consideró que podría ser causada por diferentes especies de Sporothrix, que difieren en sus factores de virulencia y su sensibilidad a los antifúngicos. Objetivo: Caracterizar fenotípica y genotípicamente 42 aislamientos clínicos colombianos de Sporothrix spp. Materiales y métodos: Se caracterizaron 42 aislamientos clínicos mediante métodos fenotípicos. Se usaron varios medios de cultivo para determinar el rango de crecimiento a diferentes temperaturas, el tipo y la distribución del pigmento, y la textura de las colonias. Se evaluó la morfología microscópica por microcultivos mediante la determinación del diámetro, el tipo de esporulación y la morfología de las conidias. La asimilación de carbohidratos se usó como una característica fisiológica para identificar las especies. La genotipificación de los 40 aislamientos se llevó a cabo mediante la amplificación parcial del gen que codifica para la calmodulina y se confirmó por secuenciación. Resultados: Mediante estudios moleculares, se identificaron 32 aislamientos de S. schenckii y ocho de S. globosa. La combinación de métodos fenotípicos y genotípicos permitió caracterizar las especies y construir claves para su reconocimiento, con base en parámetros como el diámetro de crecimiento a 25 y 30 ºC, la textura de las colonias (membranosa, aterciopelada) en agar papa dextrosa y la morfología microscópica con predominio de conidias (triangulares pigmentadas, ovales globosas elongadas, subglobosas). Conclusiones: La caracterización fenotípica y los análisis moleculares son necesarios para identificar las especies de Sporothrix y, de esta forma, elegir el tratamiento indicado. Esta es la primera caracterización fenotípica y genotípica reportada de aislamientos clínicos colombianos de Sporothrix spp.

Lack of association between metabolic phenotype and food consumption by degree of food processing: results from the Study of Workers' Health (ESAT).

Introduction: Introduction: an increase in the consumption of processed and ultra-processed foods may predispose to metabolic abnormalities. Objective: to verify the association of food consumption with metabolic phenotype in workers from a quaternary hospital in Rio de Janeiro, Brazil. Methods: workers of both sexes aged > 18 years were eligible. A food frequency questionnaire and the NOVA classification were used in the food consumption analysis. Metabolic phenotype considered the presence of at least one metabolic alteration (blood glucose, serum lipids, and blood pressure) combined with BMI (eutrophic or excess weight) as follows: 1) metabolically healthy eutrophic (MHE); 2) metabolically unhealthy eutrophic (MUE); 3) metabolically healthy excess weight (MHEW); 4) metabolically unhealthy excess weight (MUEW). Results: from the included 160 participants (mean age, 45.2 ± 1.1 years; 59.4 %, women), 21.9 % self-reported arterial hypertension and 4.4 % diabetes. Most presented excess weight (74.6 %), with approximately 40 % being obese. The MUEW phenotype had higher body fat percentage and central adiposity represented by higher WC and VFA in comparison to the other phenotypes. The lean body mass was similar between the groups. The median of ultra-processed foods was 32.4 % for eutrophic, 32.7 % for overweight, and 34.3 % for obese subjects. No significant associations were observed between ultra-processed food consumption and metabolically unhealthy eutrophic (OR: 1.01; 95 % CI: 0.96-1.06), metabolically healthy excess weight (OR: 1.03; 95 % CI: 0.98-1.08), and metabolically unhealthy excess weight (OR: 1.00; 95 % CI: 0.96-1.05) in comparison to metabolically healthy eutrophic. Conclusion: consumption of ultra-processed food was high. In this cross-sectional analysis, no association of metabolic phenotypes with consumption of food groups according to degree of food processing were observed.

Introducción: Introducción: el incremento del consumo de alimentos procesados y ultraprocesados puede predisponer a alteraciones metabólicas. Objetivo: verificar la asociación del consumo de alimentos con el fenotipo metabólico en trabajadores de un hospital cuaternario de Rio de Janeiro, Brasil. Métodos: fueron elegibles trabajadores de ambos sexos de edad > 18 años. El cuestionario de frecuencia de alimentos y la clasificación NOVA se utilizaron en el análisis del consumo de alimentos. El fenotipo metabólico consideró la presencia de al menos una alteración metabólica (glucemia, lípidos séricos y presión arterial) combinada con el IMC (eutrófico o exceso de peso) de la siguiente manera: 1) eutrófico metabólicamente saludable (EHM); 2) eutróficos metabólicamente no saludables (MUE); 3) exceso de peso metabólicamente saludable (MHEW); 4) exceso de peso metabólicamente no saludable (MUEW). Resultados: de los 160 participantes incluidos (edad media: 45,2 ± 1,1 años, 59,5 % de mujeres), el 21,9 % refirieron hipertensión arterial y el 4,4 % diabetes. La mayoría presentaron exceso de peso (74,6 %), siendo aproximadamente un 40 % obesos. El fenotipo MUEW presentó mayor porcentaje de grasa corporal y adiposidad central representada por mayor CC y VFA en comparación con los otros fenotipos. La masa corporal magra fue similar entre los grupos. La mediana de alimentos ultraprocesados fue de 32,4 % para los eutróficos, 32,7 % para el sobrepeso y 34,3 % para los obesos. No se observaron asociaciones significativas entre el consumo de ultraprocesados y el fenotipo eutrófico metabólicamente no saludable (OR: 1,01; IC 95 %: 0,96-1,06), exceso de peso metabólicamente saludable (OR: 1,03; IC 95 %: 0,98-1,08) y exceso de peso metabólicamente no saludable (OR: 1,00; IC 95 %: 0,96-1,05) en comparación con los eutróficos metabólicamente sanos. Conclusión: el consumo de alimentos ultraprocesados fue elevado. En este análisis transversal, no se observó asociación de fenotipos metabólicos y consumo de grupos de alimentos según el grado de procesamiento de los alimentos.

Frailty phenotype in heart failure: A condition that transcends age.

INTRODUCTION AND OBJECTIVES: Studies on younger frail and pre-frail subjects suffering from heart failure (HF) are scarce, except for those focusing on the critically ill. This work aims to describe differences between younger (<65 years) and older (≥65 years) pre-frail and frail HF outpatients regarding their nutritional, functional and clinical statuses. METHODS: In this cross-sectional study, a sample of 99 HF frail and pre-frail patients (aged 24-81 years, 38.4% women, 21.2% frail, 59.6% <65 years) was recruited from an HF outpatients' clinic in northern Portugal. Muscle mass was estimated from mid-upper arm muscle circumference. Weight status was assessed using body mass index. Hand grip strength and gait speed were measured. Medical records were reviewed. Associations between participants' characteristics and age were calculated using binary logistic regression. RESULTS: Age was associated with hand grip strength (OR=0.90), gait speed (OR=0.01) and diabetes (OR=4.95). Obesity, muscle mass or heart failure functional classes were not associated with age categories. CONCLUSION: There is an overall lack of differentiation between younger and older HF patients with the frailty phenotype. Therefore, frailty phenotype should be assessed in all patients, regardless of age. Hand grip strength seems to be a good predictor for older age and more studies are needed to define age-specific hand grip strength cut-offs for HF populations.

Derivation and validation of new prehospital phenotypes for adults with COVID-19. / Derivación y validación de nuevos fenotipos prehospitalarios en pacientes adultos con enfermedad por COVID-19.

OBJECTIVES: To characterize phenotypes of prehospital patients with COVID-19 to facilitate early identification of at-risk groups. MATERIAL AND METHODS: Multicenter observational noninterventional study of a retrospective cohort of 3789 patients, analyzing 52 prehospital variables. The main outcomes were 4 clusters of prehospital variables describing the phenotypes. Secondary outcomes were hospitalization, mechanical ventilation, admission to an intensive care unit, and cumulative mortality inside or outside the hospital on days 1, 2, 3, 7, 14, 21, and 28 after hospitalization and after start of prehospital care. RESULTS: We used a principal components multiple correspondence analysis (factor analysis) followed by decomposition into 4 clusters as follows: cluster 1, 1090 patients (28.7%); cluster 2, 1420 (37.4%); cluster 3, 250 (6.6%), and cluster 4, 1029 (27.1%). Cluster 4 was comprised of the oldest patients and had the highest frequencies of residence in group facilities and low arterial oxygen saturation. This group also had the highest mortality (44.8% at 28 days). Cluster 1 was comprised of the youngest patients and had the highest frequencies of smoking, fever, and requirement for mechanical ventilation. This group had the most favorable prognosis and the lowest mortality. CONCLUSION: Patients with COVID-19 evaluated by emergency medical responders and transferred to hospital emergency departments can be classified into 4 phenotypes with different clinical, therapeutic, and prognostic characteristics. The phenotypes can help health care professionals to quickly assess a patient's future risk, thus informing clinical decisions.

OBJETIVO: Desarrollar un fenotipado prehospitalario de pacientes con COVID-19 que permita una identificación temprana de los grupos de riesgo. METODO: Estudio observacional de cohorte retrospectivo multicéntrico, sin intervención con 3.789 pacientes y 52 variables prehospitalarias. Las variables de resultado principal fueron las cuatro agrupaciones prehospitalarios obtenidos, #1, #2, #3 y #4. Los resultados secundarios fueron: ingreso hospitalario, ventilación mecánica, ingreso en unidad de cuidados intensivos y mortalidad acumulada a los 1, 2, 3, 7, 14, 21 y 28 días desde el ingreso hospitalario (hospitalaria y extrahospitalaria). RESULTADOS: Por medio de una descomposición en componentes principales/correspondencia múltiple de datos mixtos (continuos y categóricos), seguido de una descomposición en agrupaciones, se obtuvo cuatro agrupaciones/fenotipos #1, #2, #3 y #4 de 1.090 (28,7%), 1.420 (37,4%), 250 (6,6%) y 1.029 (27,1%) pacientes, respectivamente. El grupo #4, compuesto por los pacientes de mayor edad, baja saturación de oxígeno e institucionalización es el que presenta la mayor mortalidad (44,8% de mortalidad a 28 días). El grupo #1, compuesto de pacientes de menor edad, con mayor porcentaje de tabaquismo, fiebre y necesidades de ventilación mecánica, es el de pronóstico más favorable con la menor tasa de mortalidad. CONCLUSIONES: Los pacientes con COVID-19 valorados por los servicios médicos de emergencias y transferidos al servicio de urgencias hospitalario se pueden clasificar en 4 fenotipos con diferentes consideraciones clínicas, terapéuticas y de pronóstico, y permite a los profesionales sanitarios discriminar rápidamente el nivel de riesgo futuro del paciente y ayuda por lo tanto en el proceso de toma de decisiones.

Correlation between genetic polymorphisms in apolipoprotein E and atrial fibrillation.

This work explores correlations between genetic polymorphisms in apolipoprotein E (ApoE) and atrial fibrillation (AF). We detected polymorphisms in the APOE gene in 64 patients with AF and 49 non-AF volunteers at the Department of Cardiology of Lianyungang Second People's Hospital between July 2017 and July 2019. We found significant differences in age, body mass index, left atrial diameter, and left ventricular ejection fraction between the two groups. Six APOE genotypes were observed: ɛ2/ɛ2; ɛ2/ɛ3; ɛ2/ɛ4; ɛ3/ɛ3; ɛ3/ɛ4; and ɛ4/ɛ4. The ɛ3/ɛ3 genotype was significantly less frequent in the AF group than in the control group, while the ɛ3/ɛ4 and ɛ4/ɛ4 genotypes were significantly more frequent in the AF group than in the control group (p<0.05). ApoE3 penetrance was significantly lower in the AF group than in the control group (p<0.05), while ApoE4 penetrance was significantly higher in the AF group than in the control group (p<0.05). ApoE3 penetrance was significantly lower in the AF group than in the control group (p<0.05). Binary logistic regression analysis showed that age, body mass index, left atrial diameter, left ventricular ejection fraction, and ApoE4 were risk factors for AF. Finally, we found that ApoE polymorphisms impacted the occurrence of AF and that ApoE4 is an AF-sensitive phenotype.

[Outcome of selective mating in the Entlebucher Mountain Dog for reduction of ureteral ectopia]. / Ergebnis der selektiven Verpaarung beim Entlebucher Sennenhund zur Reduktion der ureteralen Ektopie.

INTRODUCTION: The Entlebucher Mountain Dog is predisposed to ureteral ectopia and associated diseases of the urinary tract as well as the kidneys, which can have severe to lethal consequences. Due to the clustered occurrence of clinical signs in 11 % of Entlebucher Mountain dogs in the absence of a genetic test for ureteral ectopia, screening was introduced in 2008 to allow phenotype-based breeding selection. The ureteral orifices of the dogs are visualized by ultrasound and existing urinary retention or urinary incontinence is documented. The diagnostic findings were evaluated centrally with assignment to one of five phenotypes depending on the localization of the ureteral orifices and the renal and ureteral shape. Breeding approval and mating restrictions are the responsibility of the respective breeding associations and predominantly Entlebucher Mountain Dogs with extravesical ectopic ureters and/or clinical signs were excluded from breeding. The effect of phenotype-based selective mating on the incidence of ureteral ectopia and its clinical signs, as well as possible factors influencing the expression of the phenotype, were determined in the birth cohorts after the introduction of screening. Analysis of the data set of 1456 phenotyped Entlebucher Mountain Dogs showed, that at 11 % versus 5 %, males were more frequently assigned to the extravesical phenotype than females. The effect of phenotype-based breeding selection was examined in a subpopulation consisting of phenotyped parents and their offspring (n = 876). The prevalence of the extravesical phenotype decreased from 24 % in the 2005 to 2007 birth cohorts to 1,4 % in the 2015 to 2017 birth cohorts. Since 2015 almost no Entlebucher Mountain Dogs with incontinence, hydroureter or hydronephrosis have been recorded. It was feared that the additional selection measures to control ureteral ectopia in the small Entlebucher Mountain Dog population would intensify the inbreeding increase. However, this has so far remained absent. Therefore, as long as no genetic test is available, it is recommended to continue phenotype-based breeding selection with exclusion of dogs with extravesical ureteral ectopia and/or hydroureter/hydronephrosis/urinary incontinence, while keeping an eye on the development of the inbreeding coefficient.

INTRODUCTION: Le Bouvier de l'Entlebuch est prédisposé à l'ectopie urétérale et aux maladies associées des voies urinaires ainsi que des reins, ce qui peut entraîner des conséquences fatales. En raison de l'apparition de signes cliniques chez 11 % des chiens et en l'absence d'un test génétique pour l'ectopie urétérale, un dépistage a été introduit en 2008 pour permettre une sélection d'élevage basée sur le phénotype. Les orifices urétraux des chiens ont été visualisés par échographie et la rétention ou l'incontinence urinaire existante documentée. Les résultats du diagnostic ont été évalués de manière centralisée avec attribution à l'un des cinq phénotypes en fonction de la localisation des orifices urétéraux ainsi que de la forme des reins et des uretères. L'approbation pour la reproduction et les restrictions d'accouplement relèvent de la responsabilité des associations d'élevage respectives et les bouviers de l'Entlebuch présentant des uretères ectopiques extravésicaux et/ou des signes cliniques ont majoritairement été exclus de la reproduction. L'effet de cet accouplement sélectif basé sur le phénotype sur l'incidence de l'ectopie urétérale et de ses signes cliniques ainsi que les facteurs possibles influençant l'expression du phénotype ont été déterminés dans les cohortes de naissance après l'introduction du dépistage. L'analyse de l'ensemble des données de 1456 Bouviers de l'Entlebuch phénotypés a montré que, à 11 % contre 5 %, les mâles étaient plus fréquemment affectés au phénotype extravésical que les femelles. L'effet de la sélection d'élevage basée sur le phénotype a été examiné dans une sous-population composée de parents phénotypés et de leur progéniture (n = 876). La prévalence du phénotype extravésical est passée de 24 % dans les cohortes de naissance de 2005 à 2007 à 1,4 % dans les cohortes de naissance de 2015 à 2017. Depuis 2015, presque aucun bouvier d'Entlebuch présentant une incontinence, un hydrouretère ou une hydronéphrose n'a été enregistré. Une possible augmentation de la consanguinité due aux mesures de sélection supplémentaires visant à contrôler l'ectopie urétérale ne s'est pas produite. Par conséquent, tant qu'aucun test génétique n'est disponible, il est recommandé de poursuivre la sélection d'élevage basée sur le phénotype avec exclusion des chiens présentant une ectopie urétérale extravésicale et/ou une hydrouretère/hydronéphrose/incontinence urinaire, tout en surveillant l'évolution du coefficient de consanguinité.

Genotype-phenotype correlations in hypertrophic cardiomyopathy: a multicenter study in Portugal and Spain of the TPM1 p.Arg21Leu variant.

INTRODUCTION AND OBJECTIVES: TPM1 is one of the main hypertrophic cardiomyopathy (HCM) genes. Clinical information on carriers is relatively scarce, limiting the interpretation of genetic findings in individual patients. Our aim was to establish genotype-phenotype correlations of the TPM1 p.Arg21Leu variant in a serie of pedigrees. METHODS: TPM1 was evaluated by next-generation sequencing in 10 561 unrelated probands with inherited heart diseases. Familial genetic screening was performed by the Sanger method. We analyzed TPM1 p.Arg21Leu pedigrees for cosegregation, clinical characteristics, and outcomes. We also estimated the geographical distribution of the carrier families in Portugal and Spain. RESULTS: The TPM1 p.Arg21Leu variant was identified in 25/4099 (0.61%) HCM-cases, and was absent in 6462 control individuals with other inherited cardiac phenotypes (P<.0001). In total, 83 carriers (31 probands) were identified. The combined LOD score for familial cosegregation was 3.95. The cumulative probability of diagnosis in carriers was 50% at the age of 50 years for males, and was 25% in female carriers. At the age of 70 years, 17% of males and 46% of female carriers were unaffected. Mean maximal left ventricular wall thickness was 21.4 ±7.65mm. Calculated HCM sudden death risk was low in 34 carriers (77.5%), intermediated in 8 (18%), and high in only 2 (4.5%). Survival free of cardiovascular death or heart transplant was 87.5% at 50 years. Six percent of carriers were homozygous and 18% had an additional variant. Family origin was concentrated in Galicia, Extremadura, and northern Portugal, suggesting a founder effect. CONCLUSIONS: TPM1 p.Arg21Leu is a pathogenic HCM variant associated with late-onset/incomplete penetrance and a generally favorable prognosis.

Clinical and neurophysiological findings in patients with hereditary neuropathy with liability to pressure palsy and chromosome 17p11.2 deletion.

INTRODUCTION: Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disorder, typically presenting with recurrent episodes of mononeuropathy in nerves susceptible to compression, with similar neurophysiological characteristics. However, other clinical and neurophysiological presentations have been reported. METHODS: We retrospectively analysed the clinical and neurophysiological characteristics of 20 patients with genetically confirmed HNPP. Sixteen patients were studied in our department between 1996 and 2016. RESULTS: In addition to the typical characteristics of HNPP, we found atypical forms including recurrent positional sensory symptoms in 3 patients, chronic sensorimotor polyneuropathy in one, and non-progressive mononeuropathy in one. Onset was early in 2 patients: one at the age of 7 years, with common peroneal nerve injury, and another at birth, with brachial plexus involvement. By frequency, the main pathological findings in the nerve conduction study were: decreased sensory nerve conduction velocity in the sural (84%) and the median and superficial peroneal nerves (94%); decreased motor nerve conduction velocity in the ulnar nerve through the elbow (97%), and increased motor distal latency of the median and deep peroneal nerves (74%). CONCLUSION: Our results confirm the clinical variability of HNPP, with the most frequent nerve conduction study findings being the generalised decrease in sensory nerve conduction velocity, in addition to motor involvement, mainly in locations susceptible to nerve compression. The nerve conduction study can detect typical, atypical, and asymptomatic cases of HNPP.

Behçet's disease phenotypes and clinical outcomes: A cohort study in egyptian patients.

INTRODUCTION: Behçet's disease (BD) is a systemic inflammatory disease with various presentations. The data on the course of BD in Egyptian patients are limited. OBJECTIVES: The objective of the study was to describe the evolution and association of the different phenotypes of BD. MATERIAL AND METHODS: This chronological cohort study included adult Egyptian patients suffering from BD. Demographic data and the chronological order of the disease's manifestations were collected. RESULTS: The study included 233 patients. Their mean age at the onset of the disease was 26.3±6.9 years. The mean duration from onset of the disease to meeting the criteria was 11.2±30.3 months. The mean duration of the disease was 96.8±72.2 months. On onset of the disease, the most common phenotypes were mucocutaneous (84.5%), musculoskeletal (15.9%), ocular (14.6%) and peripheral venous disease (PVD) (7.3%); on the other hand, pulmonary, peripheral arterial and great vessel phenotypes evolved several years after onset of the disease. The mean time from meeting the criteria to the evolution of a new phenotype was 53.8±58.7 months. Associations between the different phenotypes were observed: PVD and superficial thrombophlebitis, peripheral arterial disease and PVD; another association was also observed between aortic involvement and cerebrovascular disease. CONCLUSION: BD could continue to evolve several years after onset of the disease, making the previous belief about BD yield questionable. BD tends to respect the anatomy of the affected system. Some phenotypes tend to coexist, suggesting a shared aethiopathogeny and that the disease is of a systemic nature.

Presence or Absence of Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease is Associated With Distinct Phenotypes.

INTRODUCTION: Reduced skeletal muscle function and cognitive performance are common extrapulmonary features in Chronic Obstructive Pulmonary Disease (COPD) but their connection remains unclear. Whether presence or absence of skeletal muscle dysfunction in COPD patients is linked to a specific phenotype consisting of reduced cognitive performance, comorbidities and nutritional and metabolic disturbances needs further investigation. METHODS: Thirty-seven patients with COPD (grade II-IV) were divided into two phenotypic cohorts based on the presence (COPD dysfunctional, n=25) or absence (COPD functional, n=12) of muscle dysfunction. These cohorts were compared to 28 healthy, age matched controls. Muscle strength (dynamometry), cognitive performance (Trail Making Test and STROOP Test), body composition (Dual-energy X-Ray Absorptiometry), habitual physical activity, comorbidities and mood status (questionnaires) were measured. Pulse administration of stable amino acid tracers was performed to measure whole body production rates. RESULTS: Presence of muscle dysfunction in COPD was independent of muscle mass or severity of airflow obstruction but associated with impaired STROOP Test performance (p=0.04), reduced resting O2 saturation (p=0.003) and physical inactivity (p=0.01), and specific amino acid metabolic disturbances (enhanced leucine (p=0.02) and arginine (p=0.06) production). In contrast, COPD patients with normal muscle function presented with anxiety, increased fat mass, plasma glucose concentration, and metabolic syndrome related comorbidities (hypertension and dyslipidemia). CONCLUSION: COPD patients with muscle dysfunction show characteristics of a cognitive - metabolic impairment phenotype, influenced by the presence of hypoxia, whereas those with normal muscle function present a phenotype of metabolic syndrome and mood disturbances.

Hereditary distal renal tubular acidosis: Genotypic correlation, evolution to long term, and new therapeutic perspectives.

Distal renal tubular acidosis (DRTA) is a rare disease resulting from a failure in the normal urine acidification process at the distal tubule and collecting duct level. It is characterised by persistent hyperchloremic metabolic acidosis, with a normal anion gap in plasma, in the presence of high urinary pH and low urinary excretion of ammonium. To date, 5 genes whose mutations give rise to primary DRTA have been described. Alterations in the ATP6V1B1 and ATP6V0A4 genes are inherited recessively and are associated with forms of early onset and, in many cases, with neurosensorial deafness. Pathogenic variants in the SLC4A1 gene are habitually inherited dominantly and give rise to milder symptoms, with a later diagnosis and milder electrolytic alterations. Nonetheless, evolution to nephrocalcinosis and lithiasis, and the development of chronic kidney disease in the medium to long term has been described in a similar manner in all 3 groups. Lastly, recessive forms of DTRA associated to mutations in the FOXI1 and WDR72 genes have also been described. The clinical management of DTRA is based on bicarbonate or citrate salts, which do not succeed in correcting all cases of the metabolic alterations described and, thus, the consequences associated with them. Recently, a new treatment based on slow-release bicarbonate and citrate salts has received the designation of orphan drug in Europe for the treatment of DTRA.

Intestinal-type mucinous adenocarcinoma of the Bartholin gland in a perimenopausal woman. A case report and review of the literature.

We report the case of a 46-year-old woman who presented with a tumor on the left labium majus in the region of the Bartholin gland. Surgical excision revealed a mucinous adenocarcinoma of intestinal-type (CK20+, CDX-2+). Magnetic resonance imaging, computed tomography of the chest and abdomen and colonoscopy ruled out the presence of other tumors. A second immunohistochemical study showed negative results for GATA-3, mammaglobin and GCDFP-15. Molecular analysis revealed a mutation in exon 2 of the KRAS gene. We discuss its differential diagnosis and the importance of being aware of this unusual variant of a mucinous adenocarcinoma the Bartholin gland.

[Evaluation of pathological response to neoadjuvant chemotherapy in breast cancer: correlation with molecular phenotype]. / Evaluación de la respuesta patológica a quimioterapia neoadyuvante en cáncer de mama: correlación con el fenotipo molecular.

INTRODUCTION AND OBJECTIVE: Breast cancer can be classified into different molecular subtypes with important therapeutic and prognostic implications. Neoadjuvant chemotherapy (NAC) increases the possibility of performing conservative surgery and allows in vivo testing of the sensitivity of the tumor. Our aim was to evaluate the pathological response to NAC in relation to the molecular phenotype and the different definitions of the pathological response. PATIENTS: 228 patients treated with NAC and subsequent surgery between 2012 and 2018 were selected from our breast cancer database. Molecular phenotypes were established based on the criteria of the St Gallen 2013 Conference. Pathological response was evaluated following Miller-Payne (breast) and Sataloff (axilla) classification systems. RESULTS: The most frequent molecular phenotype was luminal B/HER2 negative (30.3%), followed by luminal B/HER2 positive (26.3%), triple negative (24.6%), HER2 positive (13.2%), and luminal A (5.7%). The rate of pathological complete response (pCR) was 35.5% in breast and 15.3% in axilla. The rate of pCR considering breast and axilla together was 26.8%. The molecular phenotype with the highest rate of pCR was HER2 positive (66.7%) followed by triple negative (30.4%), luminal B/HER2 positive (21.7%), luminal B/HER2 negative (14.5%), and luminal A (7.7%) (p < 0.001). The same results were found with the different definitions of pCR we evaluated. CONCLUSIONS: Complete pathological response to NAC in breast cancer depends largely on the molecular phenotype of the tumor, regardless of the definition of pCR, with the highest response rates in the breast and axilla in the HER2 positive and triple negative phenotypes.

Macular involvement in congenital aniridia.

This review updates the knowledge about the morphological assessment of the foveal hypoplasia in congenital aniridia and resumes the reported genotype-phenotype correlations known to date. Congenital aniridia is a pan ocular disease. Although iris absence is considered the hallmark of this entity, foveal hypoplasia is present in 94.7%-84% of patients. A foveal morphology assessed by optical coherence tomography in which external retina structures can be identified, with presence of the lengthening of photoreceptors outer segment and a greater external retinal thickness, is associated with a better visual outcome, regardless a foveal pit is identified or not. This analysis can be performed once the external retina has completed its differentiation, by 6 years old. PAX6 mutations that introduce premature termination codon, C terminal extension or PAX6 involving deletions have been related to lesser foveal differentiation. Better foveal differentiation has been associated to non-coding PAX6 mutations.