Wilson disease: revision of diagnostic criteria in a clinical series with great genetic homogeneity.

BACKGROUND: Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene. An early diagnosis is crucial to prevent evolution of the disease, as implantation of early therapeutic measures fully prevents its symptoms. As population genetics data predict a higher than initially expected prevalence, it was important to define the basic diagnostic tools to approach population screening. METHODS: A highly genetically homogeneous cohort of 70 patients, belonging to 50 unrelated families, has been selected as a framework to analyze all their clinical, biochemical and genetic characteristics, to define the disease in our population, with an estimated prevalence of 1 in 12,369, and determine the most useful features that reach diagnostic value. RESULTS: Serum ceruloplasmin below 11.5 mg/dL and cupremia below 60 µg/mL, were the best analytical predictors of the disease in asymptomatic individuals, while cupruria or hepatic copper determination were less powerful. Genetic analysis reached a conclusive diagnosis in all 65 patients available for complete testing. Of them, 48 were carriers of at least one p.Leu708Pro mutant allele, with 24 homozygotes. Nine patients carried a promoter deletion mutation, revealing that extended sequencing beyond the ATP7B gene-coding region is essential. All mutations caused hepatic damage since early ages, increasing its severity as diagnosis was delayed, and neurological symptoms appear. CONCLUSION: Serum ceruloplasmin determination followed by genetic screening would reduce costs and favor the prioritization of non-invasive procedures to reach a definitive diagnosis, even for asymptomatic cases.

Genetics of Wilson disease and Wilson-like phenotype in a clinical series from eastern Spain.

Wilson's disease (WD) is an autosomal recessive disorder caused by ATP7B mutations. Subjects with only one mutation may show clinical signs and individuals with biallelic changes may remain asymptomatic. We aimed to achieve a conclusive genetic diagnosis for 34 patients clinically diagnosed of WD. Genetic analysis comprised from analysis of exons to WES (whole exome sequencing), including promoter, introns, UTRs (untranslated regions), besides of study of large deletions/duplications by MLPA (multiplex ligation-dependent probe amplification). Biallelic ATP7B mutations were identified in 30 patients, so that four patients were analyzed using WES. Two affected siblings resulted to be compound heterozygous for mutations in CCDC115, which is involved in a form of congenital disorder of glycosylation. In sum, the majority of patients with a WD phenotype carry ATP7B mutations. However, if genetic diagnosis is not achieved, additional genes should be considered because other disorders may mimic WD.

Reflexiones sobre la COVID 19, desde la perspectiva social / Reflections on the COVID 19, from the social perspective

RESUMEN El año 2020 sorprende al mundo con un nuevo coronavirus que produce la enfermedad COVID-19 altamente contagiosa, de una significativa letalidad. La enfermedad se expande por todos los continentes y se convierte en un desafío para la comunidad científica, los sistemas de salud, los servicios sociales, los gobiernos nacionales y los medios de comunicación social. Ante la emergencia, los saberes sociales contribuyen a la movilización e incorporación social de personas y grupos a la promoción de salud, a la generación, implementación y evaluación de políticas sociales dirigidas a minimizar los efectos de la pandemia. En el presente trabajo se propone como objetivo analizar, desde la perspectiva de la interrelación entre ciencia, tecnología y sociedad, los modelos de desarrollo social que priorizan lo económico sobre otros aspectos de la vida social.

ABSTRACT The year 2020 surprises the world with a new coronavirus that produces the illness COVID-19 highly contagious, of a significant lethality. The illness expands to all the continents and turns into a challenge for the scientific community, the systems of health, the social services, the national governments and the media of social communication. Before the emergency, the social knowledge helps to the mobilization and social incorporation of persons and groups to the health promotion, to the generation, implementation and evaluation of social policies directed to minimize the effects of the pandemic. The present work proposes as objective to analyze, from the perspective of the interrelation between science, technology and society, the models of social development which prioritize the economy instead of other aspects of the social life.

Pertinencia de la promoción de salud en el escenario gerontológico cubano actual

Fundamento: el artículo inicia con el análisis de las propuestas que en promoción de salud se han establecido en conferencias mundiales. A partir de ello se particulariza en la pertinencia de preceptos contenidos en este marco para el contexto gerontológico cubano actual. Objetivo: presentar las ideas principales resultantes de las Conferencias mundiales de promoción de la salud a ser consideradas en contextos demográficamente envejecidos como el cubano. Métodos: se realizó una revisión bibliográfica de documentos emitidos en eventos internacionales desde el año 1978, en áreas de promoción de la salud y de prevención, elaborados por grupos técnicos de alto nivel y especialización de nivel internacional, convocados por la Organización de Naciones Unidas, Organización Mundial de la Salud y Organización Panamericana de la Salud. Se revisaron documentos estatales, del Ministerio de Salud y publicaciones diversas de universidades y entidades relacionadas con el tema del envejecimiento demográfico y la atención al adulto mayor. Resultados: Cuba es un país con reconocimiento internacional en materia de atención y promoción de la salud; posee un sistema gratuito de servicios de salud con resultados comparables a países de alto desarrollo, lo que posibilita el aumento de la esperanza de vida que en la actualidad sitúa a la isla entre los países demográficamente envejecidos. Con lo cual la política de salud necesita ampliar la idea de la salud como un objetivo social, promover el enfoque de las determinantes sociales, así como la mediación de otros sectores sociales además del sanitario en los procesos de salud. Conclusiones: en las condiciones del actual escenario gerontológico cubano las ideas planteadas en las conferencias mundiales de Promoción de la Salud posibilitan validar una interpretación más social y abarcadora del concepto de salud, de la vejez y del envejecimiento en el siglo XXI.

Background: the article begins with the analysis of the proposals that in the matter of health promotion have been established in the world conferences on this topic. From this, the authors particularize in the relevance of precepts contained in the framework of these conferences for the current Cuban gerontological context. Objective: to present the main ideas resulting from the World Health Promotion Conferences to be considered in demographically aged contexts such as the Cuban one. Methods: it was carried out a bibliographic review of documents issued in international events since 1978 to date, in areas of health promotion and prevention, prepared by high-level and specialized technical groups from different countries of the world, convened by the United Nations (UN), World Health Organization (WHO) and Pan American Health Organization (PAHO). At the national level, documents from the State, the Ministry of Health (MINSAP), and various publications from Universities and entities related to the issue of demographic aging and care for the elderly were reviewed. Results: Cuba is a country with international recognition in terms of health care and promotion; through a universal and free system of health services with comparable results to high-development countries. Aspect that greatly facilitated the increase in life expectancy and that currently places the island among the demographically aged countries. With this, health policy needs to broaden the idea of health as a social objective, promote the focus of social determinants, as well as the mediation of other social sectors besides health in health processes. Conclusions: under the conditions of the current Cuban gerontological scenario, the ideas put forward at the World Health Promotion conferences make it possible to validate a more social and comprehensive interpretation of the concept of health, old age and aging in the 21st century.

Blockade of Renin-Angiotensin-Aldosterone System in Elderly Patients with Heart Failure and Chronic Kidney Disease: Results of a Single-Center, Observational Cohort Study.

BACKGROUND: Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEis/ARBs) and mineralocorticoid receptor antagonists (MRAs) have been shown to benefit patients with heart failure with reduced ejection fraction (HFrEF). However, there is a lack of information on the advantages of these drugs for patients with chronic kidney disease (CKD), and this gap is especially pronounced in elderly patients. OBJECTIVE: The objective of this study was to assess the role of treatment consisting of ACEi/ARBs and MRAs in patients ≥ 75 years of age with CKD. METHODS: From January 2008 to July 2014, 390 consecutive patients ≥ 75 years of age with an ejection fraction ≤ 35% and a glomerular filtration rate (GFR) ≤ 60 mL/min/1.73 m2 were included. We analyzed the relationship between treatment with ACEi/ARBs and MRAs and mortality or cardiovascular events. RESULTS: Three hundred and ninety patients were included, with a mean age of 82.6 ± 4.1 years. Mean ejection fraction was 27.9 ± 6.5%. Renal dysfunction was mild (GFR 45-60 mL/min/1.73 m2) in 50.3% of patients, moderate (GFR 30-44 mL/min/1.73 m2) in 37.4%, and severe (GFR < 30 mL/min/1.73 m2) in 12.3%. After 32 ± 23 months, 68.7% of patients were receiving ACEi/ARBs and 40% were receiving MRAs; 65.9% developed a cardiovascular event and 54.4% had died. After multivariate Cox regression analysis, ACEi/ARB treatment was independently associated with a decreased rate of cardiovascular events (hazard ratio 0.71 [95% confidence interval 0.50-0.98]) and MRAs were not associated with a decrease in cardiovascular events or total mortality. CONCLUSIONS: Treatment with ACEi/ARBs in elderly patients with HFrEF and CKD was associated with a lower rate of cardiovascular events, though MRA treatment failed to reduce the risk of morbidity and mortality in our population.

Ultrasound and Histopathologic Correlation of Ovarian Cystadenofibromas: Diagnostic Value of the "Shadow Sign".

OBJECTIVES: Cystadenofibromas (CAFs) are rare benign ovarian tumors without a widely accepted ultrasound (US) pattern. They are usually described by as thin-walled, unilocular or multilocular, and at times septated cysts with scant blood flow and no solid components. We describe a unique US feature, the "shadow sign," seen in prospectively diagnosed benign CAFs. We also provide the histopathologic basis for this typical US appearance. METHODS: Ultrasound (US) examinations were performed in our obstetric and gynecologic US unit. Pathologic examinations were performed by a dedicated gynecologic pathology team. The US and pathology department's database was searched for the diagnosis of a CAF between 2010 and 2017. RESULTS: We identified 20 patients who underwent transvaginal US examinations with a sole US diagnosis of a CAF, and the tumors were surgically removed. The common US feature across the 20 cases was the presence of hyperechoic avascular shadowing nodules. The correlating histologic features were unilocular or multilocular cysts with a smooth internal wall surface lined by a simple epithelium and occasional robust polypoid fibrous stroma. CONCLUSIONS: This US marker helps in differentiating CAFs from borderline ovarian tumors, which do not show this US feature. We hope that recognizing the suggested shadow sign as an additional descriptor of CAFs will lead to minimizing their unnecessary removal and eliminating additional and unnecessary imaging by computed tomography and magnetic resonance imaging.

Cesarean Delivery Changes the Natural Position of the Uterus on Transvaginal Ultrasonography.

OBJECTIVES: To assess whether cesarean delivery changes the natural position of the uterus. METHODS: In this retrospective Institutional Review Board-approved cohort study, we conducted a search of our university gynecologic ultrasonography (US) database. Patients with transvaginal US images before and after either vaginal or cesarean delivery between 2012 and 2015 were included. Women with prior cesarean delivery were excluded. Two readers independently measured antepartum and postpartum flexion angles between the longitudinal axis of the uterine body and the cervix. We calculated intraclass correlation coefficients to measure inter-reader agreement. Antepartum and postpartum uterine flexion angles were compared between patients with vaginal and cesarean delivery. RESULTS: We included 173 patients (107 vaginal and 66 cesarean delivery). The mean interval between scans ± SD was 18 ± 10 months. Inter-reader agreement for flexion angles was almost perfect (intraclass correlation coefficients: antepartum, 0.939; postpartum, 0.969; both P < .001). There was no difference in mean antepartum flexion angles for cesarean delivery (154.8° ± 45.7°) versus vaginal delivery (145.8° ± 43.7°; P = .216). Mean postpartum flexion angles were higher after cesarean delivery (180.4° ± 51.2°) versus vaginal delivery (152.8° ± 47.7°; P = .001. Differences in antepartum and postpartum flexion angles between cesarean and vaginal delivery were statistically significant (25.6° versus 7.0°; P = .027). CONCLUSIONS: Cesarean delivery can change the uterine flexion angle to a more retroflexed position. Therefore, all women with a history of cesarean delivery should undergo a transvaginal US examination before any gynecologic surgery or intrauterine device placement to reduce the possibility of surgical complications.

Tubal Disease and Impersonators/Masqueraders.

Ultrasound is considered the first-line imaging modality in the evaluation of the fallopian tubes. This chapter reviews both the physiologic and pathologic sonographic findings of the fallopian tubes and how to recognize characteristic entities. Specifically, it describes how to use ultrasound techniques to distinguish between pathologic processes including chronic versus acute pelvic inflammatory disease, as well as infertility, torsion, and malignancy. It also describes how to employ modern ultrasound techniques, such as color Doppler, three-dimensional imaging, and salpingocentesis in clinical practice.

El envejecimiento activo: importancia de su promoción para sociedades envejecidas / The active ageing: importance of its promotion for aging societies

Fundamento: el envejecimiento poblacional plantea importantes desafíos: sanitarios, económicos, laborales, una longevidad con más salud y mejor calidad de vida resultan el objetivo primordial a lograr. Objetivo: exponer las determinantes y contribuciones sobre envejecimiento activo implementadas en el área internacional. Métodos: se realizó una revisión bibliográfica en torno al paradigma de envejecimiento activo para conocer sus contribuciones fundamentales y la importancia de su promoción. La recolección de los datos se efectuó mediante el uso de los siguientes recursos: revistas insertadas en base de datos, tales como: PubMed, PsycInfo, Scopus, Proqest, Dialnet y Web of Science. Se consultaron un total de cinco libros en vínculo con el enfoque de envejecimiento activo, manuales de gerontología, además Documentos de la Organización de las Naciones Unidas y de la Organización Mundial de la Salud, relacionados directamente con la temática. Desarrollo: se desarrolla una valoración del paradigma del envejecimiento activo a partir de sus contribuciones y determinantes. El Año Europeo del Envejecimiento Activo y de la Solidaridad In tergeneracional es una de las estrategias desplegadas para la promoción de este enfoque de la vejez. Conclusiones: se precisa un desarrollo en políticas de coordinación institucionales para la protección de la dependencia; que promuevan: la autonomía, la participación y el derecho de los mayores a un envejecimiento activo. Para promover el envejecimiento activo es ineludible la implicación de los sujetos, las políticas sociales y de la sociedad en su conjunto.

Background: population ageing raise important sanitary, economic, and work-related challenges. A healthier longevity and a better quality of life are the prime objectives to accomplish. Objective: to show the determinants and contributions of active ageing implemented at international level. Methods: a bibliographic review related to active ageing was conducted, in order to know its main contributions and the importance of its promotion. Data collection was carried out through the use of the following resources: magazines placed in databases, such as: PubMed, PsycInfo, Scopus, Proqest, Dialnet and Web of Science. Five books on active ageing approach, gerontology handbooks, and documents from the United Nations and World Health Organization directly related to the topic were consulted. Development: an assessment of paradigm of active ageing from its contributions and determinants. The European Year for Active Ageing and Solidarity between Generations is one of the strategies developed for the promotion of this approach to old age. Conclusions: development of institutional coordination policies is required for the protection from dependence. They should promote autonomy, participation and the right of elderly people to an active ageing. For the promotion of an active ageing, the implication of individuals and the whole society, as well as social policies are unavoidable.

Ultrasound diagnosis and management of acquired uterine enhanced myometrial vascularity/arteriovenous malformations.

BACKGROUND: Arteriovenous malformation is a short circuit between an organ's arterial and venous circulation. Arteriovenous malformations are classified as congenital and acquired. In the uterus, they may appear after curettage, cesarean delivery, and myomectomy among others. Their clinical feature is usually vaginal bleeding, which may be severe, if curettage is performed in unrecognized cases. Sonographically on 2-dimensional grayscale ultrasound scanning, the pathologic evidence appears as irregular, anechoic, tortuous, tubular structures that show evidence of increased vascularity when color Doppler is applied. Most of the time they resolve spontaneously; however, if left untreated, they may require involved treatments such as uterine artery embolization or hysterectomy. In the past, uterine artery angiography was the gold standard for the diagnosis; however, ultrasound scanning has diagnosed successfully and helped in the clinical management. Recently, arteriovenous malformations have been referred to as enhanced myometrial vascularities. OBJECTIVES: The purpose of this study was to evaluate the role of transvaginal ultrasound scanning in the diagnosis and treatment of acquired enhanced myometrial vascularity/arteriovenous malformations to outline the natural history of conservatively followed vs treated lesions. METHODS: This was a retrospective study to assess the presentation, treatment, and clinical pictures of patients with uterine Enhanced myometrial vascularity/arteriovenous malformations that were diagnosed with transvaginal ultrasound scanning. We reviewed both (1) ultrasound data (images, measured dimensions, and Doppler blood flow that were defined by its peak systolic velocity and (2) clinical data (age, reproductive status, clinical presentation, inciting event or procedure, surgical history, clinical course, time intervals that included detection to resolution or detection to treatment, and treatment rendered). The diagnostic criteria were "subjective" with a rich vascular network in the myometrium with the use of color Doppler images and "objective" with a high peak systolic velocity of ≥20 cm/sec in the vascular web. Statistical analysis was performed and coded with statistical software where necessary. RESULTS: Twenty-seven patients met the diagnostic criteria of uterine enhanced myometrial vascularity/arteriovenous malformation. Mean age was 31.8 years (range, 18-42 years). Clinical diagnoses of the patients included 10 incomplete abortions, 6 missed abortions, 5 spontaneous complete abortions, 5 cesarean scar pregnancies, and 1 molar pregnancy. Eighty-nine percent of patients had bleeding (n = 24/27), although 1 patient was febrile, and 2 patients were asymptomatic. Recent surgical procedures were performed in 55.5% patients (15/27) that included curettage (n = 10), cesarean deliveries (n = 5), or both (n = 1); 4 patients had a remote history of uterine surgery that included myomectomy. Treatment was varied and included expectant treatment alone in 48% of the patients with serial ultrasound scans and serum human chorionic gonadotropin until resolution (n = 13/27 patients), uterine artery embolization (29.6%; 8/27 patients), methotrexate administration (22.2%; 6/27 patients), hysterectomy (7.4%; 2/27 patients), and curettage (3.7%; 1/27 patients). Three patients required a blood transfusion. Of the 9 patients whose condition required embolization, the conditions of 7 patients resolved after the procedure although 1 patient's condition required operative hysteroscopy and 1 patient's condition required hysterectomy for intractable bleeding. Average peak systolic velocity after embolization in the 9 patients was 85.2 cm/sec (range, 35-170 cm/sec); the average peak systolic velocity of the 16 patients with spontaneous resolution was 58.5 cm/sec (range, 23-90 cm/sec). CONCLUSIONS: Acquired enhanced myometrial vascularity/arteriovenous malformations occurred after unsuccessful pregnancies or treatment procedures that included uterine curettage, cesarean delivery, or cesarean scar pregnancy. Triage of patients for expectant treatment vs intervention with uterine artery embolization based on their clinical status, which was supplemented by objective measurements of blood velocity measurement in the arteriovenous malformation, appears to be a good predictor of outcome. Ultrasound evaluation of patients with early pregnancy failure and persistent bleeding should be considered for evaluation of a possible enhanced myometrial vascularity/arteriovenous malformation.