SAT0460 INGESTION OF LEMON JUICE MAY MODULATE BONE METABOLISM.

Background:An association between bone health and consumption of citrus fruits have been previously reported; however, the effect of lemon juice on bone metabolism have not been explored yet.Objectives:To investigate bone metabolic changes in postmenopausal women assuming lemon juice.Methods:Participants were postmenopausal osteoporotic women without history of clinical fractures who agreed to enrich their diet with lemon juice (Acti Lemon, Polenghi) over a 2-month period. The daily juice dose of 30 ml we suggested was equivalent to one Sicilian organic lemon. Surrogate markers of bone formation as procollagen type 1 N-propeptide (P1NP) and of bone resorption as C-terminal telopeptide of type I collagen (CTX), but also some regulators of bone metabolism as RANK-L, OPG, RANK-L/OPG ratio and sclerostin were assessed at baseline and then at 1 and 2 months after lemon juice administration. Controls were represented by a placebo group of age-matched osteoporotic postmenopausal women.Results:47 participants [mean age 60.2 ± 4.1 yr.] completed the study, without reporting any adverse events. Lemon juice was well tolerated. Over the observation period modifications of bone metabolism occurred: we detected a decreased RANK-L/OPG ratio and increased CTX levels at all time points vs. baseline. Particularly, change at month-1 of sclerostin (versus baseline) has been positively associated with change at month-1 and month-2 of CTX (r=0.46, p=0.01 and r=0.43, p=0.01, respectively). Change at month-1 of OPG was positively associated with change at month-1 of P1NP (r=0.49, p=0.006). Change at month-1 of RANKL/OPG has been related with variation at day 30 of P1NP (r=-0.44, p=0.013). Variation of P1NP at month-1 was related with sclerostin variation at day 30 (r=-0.56, p=0.02) and month-2 vs. baseline value (r=0.44, p=0.017) and with sclerostin variation between month-1 and month-2 (r=0.69, p<0.001). Variation of P1NP between month-1 and month-2 was associated with RANKL change at month-1 (r=-0.35, p=0.05), with sclerostin change at month-1 (r=-0.49, p=0.008) and with sclerostin change between month-1 and month-2 (r=0.41, p=0.028). At a multiple regression analysis the change of P1NP between month-1 and month-2 was independently predicted by the change of sclerostin at month-1 (ß=-1.5, SE 0.5, p=0.006), after correcting for age, BMI and change of RANKL and CTX levels at month-1. No significant modifications raised from controls.Conclusion:Drinking lemon juice may boost bone metabolic changes involving both bone resorption and bone formation.Disclosure of Interests:None declare

[Klinefelter syndrome: clinical and auxological features of 14 patients diagnosed in childhood].

Klinefelter syndrome (KS) is the most frequent chromosomal aneuploidy with a prevalence of 1: 500 men but it often remains a largely undiagnosed condition and only 10% of cases are identified in childhood and adolescence. We report the anamnestic, clinical and auxological findings of 14 KS patients diagnosed in paediatric age. 3/14 patients (21%) with KS were diagnosed in prenatal age by amniocentesis, 1 patient was diagnosed at birth due to genital ambiguity and the remaining 10/14 (71.4%) were diagnosed at a chronological age younger than 15 years old for a clinical picture characterized by a peculiar cognitive and behavioral pattern or genital anomalies and abnormalities of pubertal development. The classical karyotype 47 XXY was present in 10/14 subjects (72%), a mosaic form (46 XY/47 XXY) was present in 2/14 (14%) and a complex aneuploidy (48 XXYY and 48 XXXY) was present in the remaining 2/14 (14%) patients. All KS patients diagnosed in childhood and adolescence (10/14 =71.4 %) showed a stature taller than the respective target height and also the predicted final height (calculated from a chronological age older than 7 years old) and the reached final height were significantly taller than target height. Conclusion: according to our retrospective data we can assert that KS in paediatric age is characterized by a stature taller than target height, often associated with a characteristic cognitive and behavioral pattern while the typical clinical signs and symptoms of KS are lacking and manifest only in late adolescence or adulthood

Evans Syndrome: A case report

Evans syndrome, a combined clinical condition of autoimmune haemolytic anaemia (AHA) and idiopathic thrombocytopaenic purpura (ITP) and has non-specific pathogenesis. The clinical cases are extremely rare, since only 4% of AHA or ITP are incorporated with Evans. It is distinguished from differentials, such as lupus, IgA deficiency, and acquired immunodeficiency, by peripheral blood film, bone marrow, Coombs test, and coagulation profile. A case of adult female from Pabna, Bangladesh is documented in this report. She complained of high grade intermittent fever, exertional dyspnea, icteric skin and sclera. Other features included mild splenomegaly, dark urine, and profuse sweating after fever. Investigation reports were consistent with AHA and ITP, with normal coagulation and viral profile. However, the patient was treated with corticosteroids, platelet and blood transfusion. And in follow-up visits, there was a pattern of gradual decline in erythrocyte sedimentation rate (ESR) and reticulocyte count, with normalization of haemoglobin, red cell, and white cell count. No association with other diseases was found in this case. Bangladesh Med J. 2018 Jan; 47 (3): 37-4

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

Prognostic and theranostic applications of positron emission tomography for a personalized approach to metastatic castration‐resistant prostate cancer

Metastatic castration‐resistant prostate cancer (mCRPC) represents a condition of pro-gressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of mani-festations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been profoundly modified by introducing novel therapeutic tools such as antiandrogen drugs (i.e., abiraterone acetate and enzalutamide), immunotherapy through sipuleucel‐T, and targeted alpha therapy (TAT). This variety of approaches calls for unmet need of biomarkers suitable for patients’ pre‐treatment selection and prognostic stratification. In this sce-nario, imaging with positron emission computed tomography (PET/CT) presents great and still unexplored potential to detect specific molecular and metabolic signatures, some of whom, such as the prostate specific membrane antigen (PSMA), can also be exploited as therapeutic targets, thus combining diagnosis and therapy in the so‐called “theranostic” approach. In this review, we per-formed a web‐based and desktop literature research to investigate the prognostic and theranostic potential of several PET imaging probes, such as18F‐FDG,18F‐choline and68Ga‐PSMA‐11, also covering the emerging tracers still in a pre‐clinical phase (e.g., PARP‐inhibitors’ analogs and the radioligands binding to gastrin releasing peptide receptors/GRPR), highlighting their potential for defining personalized care pathways in mCRPC

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

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 &gt; G (p.Met1Val) and heterozygous, missense mutation of TGFBR1, c.1460G &gt; 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

Is Metabolic Syndrome Useful for Identifying Youths with Obesity at Risk for NAFLD?

The definition of metabolic syndrome (MetS) in childhood is controversial. Recently, a modified version of the International Diabetes Federation (IDF) definition was proposed using reference data from an international population for high waist circumference (WC) and blood pressure (BP), while the fixed cutoffs for lipids and glucose were not changed. We analyzed MetS prevalence using this modified definition (MetS-IDFm) and its association with non-alcoholic fatty liver disease (NAFLD) in 1057 youths (age 6–17 years) with overweight/obesity (OW/OB). A comparison with another modified definition of MetS according to the Adult Treatment Panel III (MetS-ATPIIIm) was performed. The prevalence of MetS-IDFm was 27.8% and 28.9% by MetS-ATPIIIm. The Odds (95% Confidence Intervals) of NAFLD was 2.70 (1.30–5.60) (p = 0.008) for high WC, 1.68 (1.25–2.26)(p = 0.001) for MetS, 1.54 (1.12–2.11)(p = 0.007) for low HDL-Cholesterol, 1.49 (1.04–2.13)(p = 0.032) for high triglycerides and 1.37 (1.03–1.82)(p = 0.033) for high BP. No substantial difference was found in the prevalence of MetS-IDFm and frequency of NAFLD compared to Mets-ATPIIIm definition. Our data demonstrate that one third of youths with OW/OB have MetS, whichever was the criterion. Neither definition was superior to some of their components in identifying youths with OW/OB at risk for NAFLD

[A not very essential obesity: the Rohhad syndrome. Description of two cases and review of the literature].

Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare and complex pediatric disorder . Children typically show ROHHAD after the first years of life with rapid weight gain and subsequently autonomic nervous system dysregulation (altered pain perception, pupillary dysfunction, hypothermia and bradycardia); alveolar hypoventilation with risk of cardiorespiratory arrest and hypothalamic dysfunction (central diabetes insipidus, hypothyroidism, growth hormone and corticotrophin deficiency). Tumours of neural crest origin, such as ganglioneuroblastoma and ganglioneuronoma, are reported in 33% of the patients and may be found in the chest or abdomen. Here we describe two girls who presented with rapid weight gain, at the age of 5 and 9 years respectively. The first was admitted due to obesity and central hypothyroidism. After two months she rapidly developed a clinical picture characterized by thermal dysregulation, hypodipsia and severe hypernatriemia, hypertrigliceridemia, alveolar hypoventilation supported by mechanical ventilation. The second presented with rapid-onset obesity and a mild hyperprolactinemia. After three months of follow- up she was admitted due to a clinical picture of hypothermia, seizures and hyponatremia. Subsequentely she developed altered water balance (severe hypernatremia) and severe hypoventilation . Chest CT and MR imaging showed a posterior mediastinal mass. Endocrinological investigation showed corticotrophin deficiency and central hypothyroidism treated with specific replacement therapies. Conclusions: On the basis of our experiences we can infer that it is necessary perform specific further investigations of hypothalamic function in all the children with rapid onset obesity in order to early prevent the catastrophic consequences that may occur in this syndrome

Distinct platelet crosstalk with adaptive and innate immune cells after adenoviral and mRNA vaccination against SARS-CoV-2

Background: Genetic-based COVID-19 vaccines have proved highly effective in reducing the risk of hospitalization and death. As they were first distributed on a large-scale population, adenoviral-based vaccines were linked to a very rare thrombosis with thrombocytopenia syndrome and the interplay between platelets and vaccinations increasingly gained attention. Objective: To study the crosstalk between platelets and the vaccine-induced immune response. Methods: We prospectively enrolled young healthy volunteers who received the mRNA-based vaccine, BNT162b2 (n=15), or the adenovirus-based vaccine, AZD1222 (n=25) and studied their short-term platelet and immune response before and after vaccine injections. In a separate cohort, we retrospectively analysed the effect of aspirin on the antibody response 1 and 5 months after BNT162b2 vaccination. Results: Here we show that a faster antibody response to either vaccine is associated to the formation of platelet aggregates with marginal zone-like B-cells, a subset geared to bridge the temporal gap between innate and adaptive immunity. However, while the mRNA-based vaccine is associated with a more gradual and tolerogenic response that fosters the crosstalk between platelets and adaptive immunity, the adenovirus-based vaccine, the less immunogenic of the two, evokes an antiviral-like response during which platelets are cleared and less likely to cooperate with B-cells. Moreover, subjects taking aspirin (n=56) display lower antibody levels after BNT162b2 vaccination compared to matched individuals. Conclusions: Platelets are a component of the innate immune pathways that promote the B-cell response after vaccination. Future studies on the platelet-immune crosstalk post-immunization will improve safety, efficacy, and strategic administration of next-generation vaccines