2q37 deletions in patients with an albright hereditary osteodystrophy phenotype and PTH resistance

Pseudohypoparathyroidism (PHP) is a rare endocrine disorder derived from the defective activation of the cAMP pathway by the parathyroid hormone secondary to GNAS molecular defects. PHP subtypes are defined by the presence/absence of specific clinical/biochemical features. PHP1A is characterized by resistance to multiple hormones with features of Albright hereditary osteodystrophy (AHO), while pseudopseudohypoparathyroidism (PPHP) is characterized by AHO in the absence of PTH resistance. Small subsets of PHP and PPHP patients without known molecular defects have been re-diagnosed as being affected by the brachydactyly-mental retardation syndrome (BDMR), also known as the AHO-like syndrome. This study aimed to analyse 24 PHP1A and 51 PPHP patients without a molecular diagnosis for the presence of BDMR-associated 2q37 deletions to improve the differential diagnosis and to identify features that might help to avoid a misdiagnosis. Molecular investigations identified 4 deletions in 4 unrelated patients. The affected patients showed a combination of the most pathognomonic AHO features. Of note, 3 of the patients also displayed mild PTH resistance, and none of the patients developed ectopic ossifications. Our work confirmed the rarity of the misdiagnosis of BDMR in PHP patients through the identification of 4 patients bearing a 2q37 deletion in a cohort of 73 PHP patients (5.3%). Three patients with the deletion presented a PHP1A phenotype in the absence of any BDMR-specific findings. Further studies on larger case series are needed to elucidate the overlap between these clinical entities and to allow the early identification of patients

Improved Molecular Diagnosis of McCune-Albright Syndrome and Bone Fibrous Dysplasia by Digital PCR

McCune-Albright syndrome (MAS) is a rare congenital disorder characterized by the association of endocrine and nonendocrine anomalies caused by somatic activating variants of GNAS. The mosaic state of variants makes the clinical presentation extremely heterogeneous depending on involved tissues. Biological samples bearing a low level of mosaicism frequently lead to false-negative results with an underestimation of causative molecular alterations, and the analysis of biopsies is often needed to obtain a molecular diagnosis. To date, no reliable analytical method for the noninvasive testing of blood is available. This study was aimed at validating a novel and highly sensitive technique, the digital PCR (dPCR), to increase the detection rate of GNAS alterations in patients with a clinical suspicion of MAS and, in particular, in blood. We screened different tissues (blood, bone, cutis, ovary, and ovarian cyst) collected from 54 MAS patients by different technical approaches. Considering blood, Sanger was unable to detect mutations, the allele-specific PCR and the co-amplification at lower denaturation temperature had a 9.1% and 18.1% detection rate, respectively, whereas the dPCR reached a 37.8% detection rate. In conclusion, the dPCR resulted in a cost-effective, reliable, and rapid method allowing the selective amplification of low-frequency variants and able to improve GNAS mutant allele detection, especially in the blood

AGRICOLTURA CONSERVATIVA IN FRIULI VENEZIA GIULIA: UNA OPPORTUNITA' PER I SEMINATIVI

Principles and analysis of the perspectives for diffusion of conservation agriculture with reference to practical applications

Circulating cardiovascular biomarkers in recurrent atrial fibrillation: data from the GISSI-atrial fibrillation trial.

Objective. We evaluated the prognostic role of circulating cardiovascular biomarkers in patients with a history of recent atrial fibrillation (AF).Background. Predicting long-term maintenance of sinus rhythm in patients with AF is difficult.Methods. Plasma concentrations of three specific cardiac markers [high-sensitivity troponin T (hsTnT), N-terminal probrain natriuretic peptide (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP)] and three stable fragments of vasoactive peptides [mid-regional proadrenomedullin (MR-proADM), copeptin (CT-proAVP) and CT-proendothelin-1 (CT-proET-1)] were measured at baseline and after 6 and 12 months in 382 patients enrolled in the GISSI-AF study, a prospective randomized trial to determine the effect of valsartan to reduce the recurrence of AF. The association between these markers, clinical characteristics and recurrence of AF was tested by univariate and multivariate Cox models.Results. Mean patient age was 68 \ub1 9 years (37.2% females). A total of 84.8% of patients had a history of hypertension. In total, 59.7% qualified for history of AF because of successful cardioversion, 11.8% because of two or more episodes of AF in the 6 months preceding randomization and 28.5% because of both. Patients in AF at 6 or 12 months (203 (53.1%) with first recurrence) had significantly higher concentrations of most biomarkers. Despite low baseline levels, higher concentrations of hsTnT {adjusted hazard ratio (HR) [95% confidence intervals (CIs) for 1 SD increment] (1.15 [1.04-1.28], P = 0.007), MR-proANP (1.15 [1.01-1.30], P = 0.04), NT-proBNP (1.24 [1.11-1.39], P = 0.0001) and CT-proET-1 (1.16 [1.01-1.33], P = 0.03) independently predicted higher risk of a first recurrence of AF. Changes over time of MR-proANP tended to predict subsequent recurrence (adjusted HR [95%CI]) (1.53 [0.98-2.37], P = 0.06).Conclusion. Circulating markers of cardiomyocyte injury/strain and endothelin are related to recurrence of AF in patients in sinus rhythm with a history of recent AF

EMERGENCY PLANNING IN CASE OF CBRN EVENTS: AN INNOVATIVE METHODOLOGY TO IMPROVE THE SAFETY KNOWLEDGE OF ADVISORS AND FIRST RESPONDERS BY A MULTIDISCIPLINARY TABLE TOP EXERCISE.

ABSTRACT Nowadays Chemical-Biological-Radiological-Nuclear (CRBN) risks are one of the main safety concern. The radiological disasters of Fukushima and Chernobyl, the chemical events of Seveso or the release of Sarin in the Tokio Subway,and the biological emergencies such as the H1N1 flue represent few examples of a dreadful evidence: : CBRNe risks are a real and global threat around us. A CBRNe event can be either of an intentional and un-intentional nature and it is important to have highly specialized advisors that can support decision makers and first responders to face this threat. The University of Rome Tor Vergata, in collaboration with the most important Italian and International Bodies that work in the field of CBRN safety and security and supported by NATO and OPCW, organized two International Master Courses in Protection against CBRN events. In this context, a Table Top Exercise (TTX) was organized, in collaboration with the Ministry of Interior and Ministry of Defence, taking into account that, in each country, the system response to CBRNe events strongly depends also on law and procedures, that enforce the advisors and first responders to rely with different skills and roles in function of the administration of origin. The organized TTX was aimed to test the level preparation of the Master students and experts working in Italy in the field of CBRN events and to test the emergency planning preparation. In particular, a radiological release was simulated in a Harbour facility in Urban Area. The students were divided in multidisciplinary groups with heterogeneous competences. Each group was supported by CBRNì experts and was stressed by the injects from a Command and Operative Centre. Responsiveness to the injects and to the stress together with the ability to organize and manage safety and security operations, but also to interpret each role in the team according to according to national laws, were evaluated for each group. The scenario, the logistic organization, on-going adjustments during the exercise and the outcomes will be presented and analyzed by the authors in this paper. PRELIMINARY INDEX 1. Abstract 2. Introduction 3. Table Top Exercise (TTX) 3.1 What is a TTX 3.2 How the TTX is organized 3.3 Scenario and injects 3.4 Organizational and technical solutions 4. Dat

Frecuencia de prolongación del intervalo QTc en adultos infectados con VIH de Paraguay en 2020

Introduction: the prolonged QTc interval predisposes to serious arrhythmias. Various medications, including antiretrovirals, can prolong it. The objectives were to determine the demographic, clinical characteristics and the frequency of the prolonged QTc interval in patients with HIV. Methods: we conducted a prospective, observational study with a control group. Men and women, over 18 years of age, with HIV infection, who attended the National Hospital (Itauguá, Paraguay) during 2020, were included. Medical students acted as a control group. All subjects who did not give their consent and those with arrhythmias were excluded. Demographic, clinical, laboratory variables and 12-channel electrocardiogram at rest were measured. The study was approved by the Ethics Committee of the Universidad Privada del Este (Paraguay). Results: 39 HIV patients and 39 healthy controls entered the study. The mean age of the cases was 37 ± 11 years, being 59% male. The most frequent comorbidity in the cases was obesity (7.6%). The mean values ​​of urea, creatinine, K, Ca and Mg in the cases were in the normal range. Prolonged QTc was detected in 18% of the cases and in 0% of the controls. The subjects with the electrocardiographic alteration were all on antiretroviral and multiple antibiotic treatment known to be associated with prolonged Qtc. Conclusion: the frequency of prolonged QTc in HIV patients was 18% and in healthy controls it was 0%. Regular monitoring of the electrocardiogram is recommended in HIV patients receiving drugs that prolong the QT interval.Introducción: el intervalo QTc prolongado predispone a arritmias graves. Diversos medicamentos, entre ellos los antirretrovirales, pueden prolongarlo. Los objetivos fueron determinar las características demográficas, clínicas y la frecuencia del intervalo QTc prolongado en pacientes con VIH. Métodos: estudio observacional, prospectivo, con grupo control. Se incluyeron varones y mujeres, mayores de 18 años, portadores de infección por VIH, que acudieron al Hospital Nacional (Itauguá, Paraguay) durante 2020. Actuaron como grupo control los estudiantes de Medicina. Se excluyeron todos los sujetos que no dieron su consentimiento y los portadores de arritmias. Se midieron variables demográficas, clínicas, laboratoriales y electrocardiograma de 12 canales en reposo. El estudio contó con la aprobación del Comité de Ética de la Universidad Privada del Este (Paraguay). Resultados: ingresaron al estudio 39 pacientes con VIH y 39 controles sanos. La edad media de los casos fue 37 ± 11 años, siendo 59% del sexo masculino. La comorbilidad más frecuente en los casos fue la obesidad (7,6%). Los valores medios de urea, creatinina, K, Ca y Mg en los casos se hallaban en rango normal. Se detectó 18% de QTc prolongado en casos y 0% en los controles. Estos sujetos con alteración electrocardiográfica se hallaban todos en tratamiento antirretroviral y antibiótico múltiple de conocida asociación con QTc prolongado. Conclusión: la frecuencia de QTc prolongado en pacientes con VIH fue del 18% y en controles sanos fue del 0%. Se recomienda el control periódico del electrocardiograma en pacientes con VIH en tratamiento con fármacos que prolongan el intervalo QT

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%