First evidence of maternally inherited mosaicism in TGFBR1 and subtle primary myocardial changes in Loeys-Dietz syndrome: a case report

Background: Loeys-Dietz syndrome (LDS) is a rare multisystemic disorder characterized by vascular and skeletal abnormalities, with considerable intra- and interfamilial variability. Case presentation: We report the case of an 8-year-old male with clinical features of two distinct genetic disorders, namely LDS, manifesting in the first months by progressive aortic root dilatation, arterial tortuosity, bifid uvula, and inguinal hernias and oculocutaneous albinism (OCA) manifesting by white hair and skin that does not tan, nystagmus, reduced iris pigment with iris translucency, and reduced retinal pigment). We identified previously reported, homozygous mutations of TYR, c.1A > G (p.Met1Val) and heterozygous, missense mutation of TGFBR1, c.1460G > A (p.Arg487Gln). Family history revealed that his mother underwent multiple surgical repairs for recurrent hemorrhage originating from the buccal artery. Molecular studies confirmed a maternally inherited low grade TGFBR1 mutation somatic mosaicism (18% in peripheral blood leukocytes, 18% in buccal cells and 10% in hair root cells). Maternal cardiac investigations revealed peculiar cardiovascular features: mild tortuosity at the aortic arch, dilatation of the proximal abdominal aorta, multiple deep left ventricular myocardial crypts, and dysplastic mitral valve. TGFBR2 germline mosaicism has been described in three fathers of children carrying TGFBR2 mutations but, to the best of our knowledge, no case of maternally inherited TGFBR1 mutation mosaicism has been reported so far. Conclusions: This case report suggests that individuals with somatic mosaicism might be at risk for mild and unusual forms of LDS but germline mosaicism can lead to full blown picture of the disease in offspring

Minimal clinically important difference in barthel index dyspnea in patients with COPD

Background: The Barthel Index dyspnea (BId) is responsive to physiological changes and pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD). However, the minimum clinically important difference (MCID) has not been established yet. Aim: To identify the MCID of BId in patients with COPD stratified according to the presence of chronic respiratory failure (CRF) or not. Materials and Methods: Using the Medical Research Council (MRC) score as an anchor, receiver operating characteristic curves and quantile regression were retrospectively evaluated before and after pulmonary rehabilitation in 2327 patients with COPD (1151 of them with CRF). Results: The median post-rehabilitation changes in BId for all patients were −10 (interquartile range = −17 to −3, p<0.001), correlating significantly with changes in MRC (r = 0.57, 95% CI = 0.53 to 0.59, p<0.001). Comparing different methods of assessment, the MCID ranged from −6.5 to −9 points for patients without and −7.5 to −12 points for patients with CRF. Conclusion: The most conservative estimate of the MCID is −9 points in patients with COPD, without and −12 in those with CRF. This estimate may be useful in the clinical interpretation of data, particularly in response to intervention studies

Features of Clinical Complexity in European Patients With Atrial Fibrillation: A Report From a European Observational Prospective AF Registry

There is increasing concern regarding impact of clinical complexity in patients with atrial fibrillation (AF). We explored the impact of different clinical complexity features in AF patients. We analyzed patients from a prospective, observational, multicenter Europe-wide AF registry. Features of clinical complexity among patients with CHA2DS2-VASc ≥2 were: (1) history of bleeding; (2) frailty; (3) chronic kidney disease (CKD); (4) ≥2 features. A total of 10,169 patients were analyzed. Of these, 141 (1.4%) had history of bleeding, 954 (9.4%) were frail, 1767 (17.4%) had CKD and 1253 (12.3%) had ≥2 features. All features of clinical complexity were less treated with OAC. History of bleeding (HR 1.94, 95% CI 1.32-2.85), frailty (HR 1.38, 95% CI 1.11-1.71), CKD (HR 1.50, 95% 1.28-1.75) and ≥2 features (HR 2.08, 95% CI 1.73-2.51) were associated with outcomes. Presence of features of clinical complexity is associated with lower use of OAC and higher risk of outcomes

Yield of diagnosis and risk of stroke with screening strategies for atrial fibrillation: a comprehensive review of current evidence

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. The presence of AF is associated with increased risk of systemic thromboembolism, but with the uptake of oral anticoagulant (OAC) and implementation of a holistic and integrated care management, this risk is substantially reduced. The diagnosis of AF requires a 30-s-long electrocardiographic (ECG) trace, irrespective of the presence of symptoms, which may represent the main indication for an ECG tracing. However, almost half patients are asymptomatic at the time of incidental AF diagnosis, with similar risk of stroke of those with clinical AF. This has led to a crucial role of screening for AF, to increase the diagnosis of population at risk of clinical events. The aim of this review is to give a comprehensive overview about the epidemiology of asymptomatic AF, the different screening technologies, the yield of diagnosis in asymptomatic population, and the benefit derived from screening in terms of reduction of clinical adverse events, such as stroke, cardiovascular, and all-cause death. We aim to underline the importance of implementing AF screening programmes and reporting about the debate between scientific societies’ clinical guidelines recommendations and the concerns expressed by the regulatory authorities, which still do not recommend population-wide screening. This review summarizes data on the ongoing trials specifically designed to investigate the benefit of screening in terms of risk of adverse events which will further elucidate the importance of screening in reducing risk of outcomes and influence and inform clinical practice in the next future

Primary mucinous adenocarcinoma in a defunctionalized urinary bladder: a case report

<p>Abstract</p> <p>Introduction</p> <p>Malignancies are rare in defunctionalized bladders and are thought to arise from metaplasia secondary to chronic inflammation. Transitional cell and squamous cell carcinomas are the most common but there are three reported cases of mucinous adenocarcinoma.</p> <p>Case presentation</p> <p>We report a 57-year-old Caucasian man presenting with penile discharge for 30 years following ileal conduit surgery for neurogenic bladder, and who was found to have primary mucinous adenocarcinoma of his defunctionalized bladder.</p> <p>Conclusion</p> <p>Although urinary diversion without cystectomy is less common in current urologic practice, there are many patients with longstanding defunctionalized bladders. While there are no established surveillance protocols, defunctionalized bladder patients with urethral discharge should be evaluated.</p

Estudio sobre las praxeologías que se proponen estudiaren un curso universitario de cálculo

En este trabajo se analizan las organizaciones que se proponen estudiar en un curso de cálculo universitario relativas a las nociones de límite y continuidad funcional. Desde la Teoría Antropológica de lo Didáctico se analizó el material editado por lo profesores destinado a estudiantes universitarios. Los principales resultados indican que se propone el estudio de tareas aisladas, que no conducen a la elaboración y validación de elementos tecnológicos. De esta manera, se evidencia la organización de los saberes en dos niveles: uno teórico y otro práctico, donde este último no tiene incidencia para la conformación del primero. Esto genera una inadecuada interpretación del conocimiento científico, reduciendo su estudio a organizaciones matemáticas desarticuladas

Growth Trajectory and Adult Height in Children with Nonclassical Congenital Adrenal Hyperplasia

Background: Children with nonclassical congenital adrenal hyperplasia (NCCAH) often present increased growth velocity secondary to elevation of adrenal androgens that accelerates bone maturation and might compromise adult height (AH). Objective: The aim of the study was to analyze prognostic factors affecting growth trajectory (GT) and AH in children with NCCAH. Methods: The study was a retrospective, multicentric study. The study population consisted of 192 children with a confirmed molecular diagnosis of NCCAH, followed by pediatric endocrinology centers from diagnosis up to AH. Clinical records were collected and analyzed. AH (standard deviation score; SDS), pubertal growth (PG) (cm), GT from diagnosis to AH (SDS), and AH adjusted to target height (TH) (AH-TH SDS) were evaluated as outcome indicators using stepwise linear regression models. Results: The stepwise linear regression analysis showed that AH and AH-TH were significantly related to chronological age (CA) (p = 0.008 and 0.016), bone age (BA)/CA ratio (p = 0.004 and 0.001), height (H) (p &lt; 0.001 for both parameters) at NCCAH diagnosis, and TH (p = 0.013 and &lt;0.001). PG was higher in males than in females (22.59 ± 5.74 vs. 20.72 ± 17.4 cm, p = 0.002), as physiologically observed, and was positively related to height (p = 0.027), negatively to BMI (p = 0.001) and BA/CA ratio (p = 0.001) at NCCAH diagnosis. Gender, genotype, biochemical data, and hydrocortisone treatment did not significantly impair height outcomes of these NCCAH children. Conclusions: The results of this study suggest that AH and GT of NCCAH patients are mainly affected by the severity of phenotype (CA, BA/CA ratio, and H) at the time of diagnosis. © 2020 S. Karger AG. All rights reserved

Skeptical Look at the Clinical Implication of Metabolic Syndrome in Childhood Obesity

Metabolic syndrome (MetS) is defined by a cluster of several cardio-metabolic risk factors, specifically visceral obesity, hypertension, dyslipidemia, and impaired glucose metabolism, which together increase risks of developing future cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D). This article is a narrative review of the literature and a summary of the main observations, conclusions, and perspectives raised in the literature and the study projects of the Working Group of Childhood Obesity (WGChO) of the Italian Society of Paediatric Endocrinology and Diabetology (ISPED) on MetS in childhood obesity. Although there is an agreement on the distinctive features of MetS, no international diagnostic criteria in a pediatric population exist. Moreover, to date, the prevalence of MetS in childhood is not certain and thus the true value of diagnosis of MetS in youth as well as its clinical implications, is unclear. The aim of this narrative review is to summarize the pathogenesis and current role of MetS in children and adolescents with particular reference to applicability in clinical practice in childhood obesity

Health status in older hospitalized patients with cancer or non-neoplastic chronic diseases

BACKGROUND: Whether cancer is more disabling than other highly prevalent chronic diseases in the elderly is not well understood, and represents the objective of the present study. METHODS: We used data from the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study, a large collaborative observational study based in community and university hospitals located throughout Italy. Our series consisted of three groups of patients with non-neoplastic chronic disease (congestive heart failure, CHF, N = 832; diabetes mellitus, N = 939; chronic obstructive pulmonary disease, COPD, N = 399), and three groups of patients with cancer (solid tumors without metastasis, N = 813; solid tumors with metastasis, N = 259; leukemia/lymphoma, N = 326). Functional capabilities were ascertained using the activities of daily living (ADL) scale, and categorical variables for dependency in at least 1 ADL or dependency in 3 or more ADLs were considered in the analysis. Cognitive status was evaluated by the 10-items Hodgkinson Abbreviated Mental Test (AMT). RESULTS: Cognitive impairment was more prevalent in patients with CHF (28.0%) or COPD (25.8%) than in those with cancer (solid tumors = 22.9%; leukemia/lymphoma = 19.6%; metastatic cancer = 22.8%). Dependency in at least 1 ADL was highly prevalent in patients with metastatic cancer (31.3% vs. 24% for patients with CHF and 22.4% for those with non-metastatic solid tumors, p < 0.001). In people aged 80 years or more, metastatic cancer was not associated with increased prevalence of physical disability. In multivariable analysis, metastatic cancer was associated with a greater prevalence of physical (OR 2.09, 95%CI 1.51–2.90) but not cognitive impairment (OR 1.34, 95%CI 0.94–1.91) with respect to CHF patients. Finally, diabetes was significantly associated with cognitive impairment (OR 1.40, 95%CI 1.11–1.78). CONCLUSION: Cancer should not be considered as an ineluctable cause of severe cognitive and physical impairment, at least not more than other chronic conditions highly prevalent in older people, such as CHF and diabetes mellitus