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BACKGROUND: Urea cycle disorders (UCDs) are a group of rare inborn diseases caused by a deficiency in one of the six enzymes or one of the two transporters involved in the urea cycle. The most common biochemical feature is elevated blood ammonia levels, which can be toxic at high levels, especially to the brain and may manifest as encephalopathy if left untreated. Glycerol phenylbutyrate (GPB) is currently approved for use in the USA and Europe for patients of all ages with UCD who cannot be managed with protein restriction and/or amino acid supplementation alone. This article presents the author's experience in different exemplary settings and depicts the most efficient management of UCDs with GPB. CASE PRESENTATION: Six patient histories are described. 4 had OCT, one citrullinemia, and one argininosuccinic aciduria. Treatment with GPB was started between 2 days and 14 years of age. Before GPB, one patient had not been treated, 4 had received sodium phenylbutyrate (NaPB), and one Na benzoate. CONCLUSIONS: Overall, treatment with GPB was followed by a relevant metabolic improvement, resulting in better therapeutic compliance, reduced hospitalization, and improved quality of life.
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Calidad de Vida , Trastornos Innatos del Ciclo de la Urea , Humanos , Glutamina/metabolismo , Amoníaco/metabolismo , Amoníaco/uso terapéutico , Trastornos Innatos del Ciclo de la Urea/tratamiento farmacológico , Trastornos Innatos del Ciclo de la Urea/metabolismo , Urea/uso terapéutico , Urea/metabolismoRESUMEN
INTRODUCTION: Due to their rare prevalence and marked heterogeneity, pediatric cardiomyopathies (CMPs) are little known and scarcely reported. We report the etiology, clinical profile and outcome of a consecutive cohort of children diagnosed with CMP and followed at Meyer Children's Hospital over a decade. PATIENTS AND METHODS: We retrospectively reviewed patients consecutively referred from May 2008 to May 2019 for pediatric onset CMP (<18 years). Heart disease caused by arrhythmic disorders, toxic agents, rheumatic conditions and maternal disease were excluded. RESULTS: We enrolled 110 patients (65 males), diagnosed at a median age of 27 [4-134] months; 35% had an infant onset (<1 year of age). A positive family history was more often associated with childhood-onset (38.8%). Hypertrophic cardiomyopathy (HCM; 48 patients) was the most frequent phenotype, followed by dilated cardiomyopathy (DCM; 35 patients). While metabolic and idiopathic etiologies were preponderant in infants, metabolic and sarcomeric diseases were most frequent in the childhood-onset group. Major adverse cardiac events (MACE) occurred in 31.8% of patients, including hospitalization for acute heart failure in 25.5% of patients, most commonly due to DCM. Overall, the most severe outcomes were documented in patients with metabolic diseases. CONCLUSIONS: In a consecutive cohort of pediatric patients with CMP, those with infantile onset and with a metabolic etiology had the worst prognosis. Overall, MACE occurred in 41% of the entire population, most commonly associated with DCM, inborn errors of metabolism and genetic syndromes. Systematic NGS genetic testing was critical for etiological diagnosis and management.
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Cardiomiopatías , Cardiomiopatía Dilatada , Cardiomiopatía Hipertrófica , Humanos , Masculino , Cardiomiopatías/diagnóstico , Cardiomiopatías/epidemiología , Cardiomiopatías/genética , Cardiomiopatía Dilatada/genética , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/epidemiología , Cardiomiopatía Hipertrófica/genética , Estudios RetrospectivosRESUMEN
Background: Zellweger syndrome (ZS) is a congenital autosomal recessive disease within the spectrum of peroxisome biogenesis disorders, characterized by the impairment of peroxisome assembly. The presence of peroxisome enzyme deficiencies leads to complex developmental sequelae, progressive disabilities, and multiorgan damage, due to intracellular accumulation of very-long-chain fatty acids (VLCFAs). Case Presentation: We report the case of an infant affected by ZS in which agammaglobulinemia, detected through neonatal screening of congenital immunodeficiencies, appeared as a peculiar trait standing out among all the other classical characteristics of the syndrome. The exome analysis through next-generation sequencing (NGS), which had previously confirmed the diagnostic suspicion of ZS, was repeated, but no mutations causative of inborn error of immunity (humoral defect) were detected. Conclusion: In this case, no genetic variants accountable for the abovementioned agammaglobulinemia were detected. Given that the scientific literature reports the involvement of peroxisomes in the activation of Nuclear Factor κ-light-chain-enhancer of activated B cells (NF-κB) pathway, which is crucial for B-cell survival, with this work, we hypothesize the existence of a link between ZS and humoral immunodeficiencies. Further studies are required to confirm this hypothesis.
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Mitochondrial diseases (MDs) are a large group of genetically determined multisystem disorders, characterized by extreme phenotypic heterogeneity, attributable in part to the dual genomic control (nuclear and mitochondrial DNA) of the mitochondrial proteome. Advances in next-generation sequencing technologies over the past two decades have presented clinicians with a challenge: to select the candidate disease-causing variants among the huge number of data provided. Unfortunately, the clinical tools available to support genetic interpretations still lack specificity and sensitivity. For this reason, the diagnosis of MDs continues to be difficult, with the new "genotype first" approach still failing to diagnose a large group of patients. With the aim of investigating possible relationships between clinical and/or biochemical phenotypes and definitive molecular diagnoses, we performed a retrospective multicenter study of 111 pediatric patients with clinical suspicion of MD. In this cohort, the strongest predictor of a molecular (in particular an mtDNA-related) diagnosis of MD was neuroimaging evidence of basal ganglia (BG) involvement. Regression analysis confirmed that normal BG imaging predicted negative genetic studies for MD. Psychomotor regression was confirmed as an independent predictor of a definitive diagnosis of MD. The findings of this study corroborate previous data supporting a role for neuroimaging in the diagnostic approach to MDs and reinforce the idea that mtDNA sequencing should be considered for first-line testing, at least in specific groups of children.
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Two patients with a paucisymptomatic hyperckemia underwent a skeletal muscle biopsy and massive gene panel to investigate mutations associated with inherited muscle disorders. In the SGCA gene, sequence analyses revealed a homozygous c.850C > T/p.Arg284Cys in patient 1 and two heterozygous variants (c.739G > A/p.Val247Met and c.850C > T/p.Arg284Cys) in patient 2. Combination of histology and immunofluorence studies showed minimal changes for muscular proteins including the α-sarcoglycan. These two cases highlight the advantages of next-generation sequencing in the differential diagnosis of mild myopathic conditions before considering the more invasive muscle biopsy in sarcoglycanopathies.
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Creatina Quinasa/sangre , Mialgia/etiología , Sarcoglicanopatías/sangre , Sarcoglicanopatías/diagnóstico , Adulto , Femenino , Humanos , Masculino , Mialgia/sangre , Mialgia/patología , Sarcoglicanopatías/complicacionesRESUMEN
Mental health modulates the risk of common chronic conditions. Although inflammation is thought to partly explain this link, its relation with mental health is still unclear and largely unexplored. We investigated three scales assessing psychological resilience (CD-RISC), depression symptoms (PHQ9-6) and mental wellbeing (SF36-MCS) in an Italian adult population cohort (Nmaxâ¯=â¯16,952). This showed a slightly higher frequency of men, more educated and younger participants, compared to samples with incomplete questionnaires. We performed stepwise generalized linear models to test the association between each scale and INFLA-score, a composite blood-based inflammation index. At each step, a class of potential mediators was included in the model, namely health conditions, lifestyle factors, or both (full model). Full model analysis was also conducted on single blood markers involved in the inflammatory process. In the baseline model, we observed significant associations of PHQ9-6 (standardized ß(SE)â¯=â¯0.024(0.009), pâ¯=â¯8.9â¯×â¯10-3) and SF36-MCS (ß(SE)â¯=â¯-0.021(0.008), pâ¯=â¯7â¯×â¯10-3) with INFLA-score. These associations survived adjustment for health conditions but not for lifestyle factors, which explained 81% and 17% of the association with PHQ9-6 and SF36-MCS. Significant associations (pâ¯<â¯4.2â¯×â¯10-3) after mediator adjustment were observed for single low-grade inflammation markers, including platelet distribution width (with PHQ9-6 and CD-RISC), granulocyte- and neutrophil-to-lymphocyte ratios, monocyte and lymphocyte fractions (with SF36-MCS). After imputation of missing data, we observed substantially consistent associations. These findings suggest that the relationship between mental health and low-grade inflammation is largely influenced by lifestyle. However, the associations with specific biomarkers related to inflammation are partly independent and might be explained by biological factors.
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Factores Biológicos , Salud Mental , Adulto , Humanos , Inflamación , Italia , Estilo de Vida , MasculinoRESUMEN
2013/14 saw the start of the introduction of a new live attenuated influenza vaccine (LAIV) programme for children in England. 2018/19 saw co-circulation of both A(H1N1)pdm09 and A(H3N2), when LAIV was offered to all healthy children 2-9â¯years of age. LAIV effectiveness against influenza hospitalisation is not well described. This paper presents the 2018/19 end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza related hospitalisation in children aged 2-17. The test negative case control approach was used to estimate aVE by influenza A subtype and vaccine type. Cases and controls were selected from a sentinel laboratory surveillance system which collates details of individuals tested for influenza with reverse-transcription polymerase chain reaction (RT-PCR) on respiratory samples. Vaccine and clinical history was obtained from general practitioners of study participants. There were 307 hospitalised cases and 679 hospitalised controls. End-of-season influenza aVE was 53.0% (95% CI: 33.3, 66.8) against influenza confirmed hospitalisation; 63.5% (95% CI: 34.4, 79.7) against influenza A(H1N1)pdm09 hospitalisation and 31.1% (95% CI: -53.9, 69.2) against influenza A(H3N2). LAIV aVE was 49.1% (95% CI: 25.9, 65.0) for any influenza and 70.7% (95% CI: 41.8, 85.3) for A(H1N1)pdm09, whereas for those receiving quadrivalent inactivated influenza vaccine (QIV), aVE was 64.4% (95% CI: 29.4, 82.0) and 44.4% (95% CI: -51.9, 79.6) respectively. We provide evidence of overall significant VE for both LAIV and QIV against influenza associated hospitalisation in children 2-17â¯years of age, most notably against influenza A(H1N1)pdm09, with non-significant protection against A(H3N2).
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Hospitalización/estadística & datos numéricos , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Inglaterra , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Gripe Humana/epidemiología , Gripe Humana/virología , Masculino , Vigilancia de Guardia , Vacunación , Vacunas Atenuadas/administración & dosificaciónRESUMEN
OBJECTIVE: Next-generation sequencing (NGS) was applied in molecularly undiagnosed asymptomatic or paucisymptomatic hyperCKemia to investigate whether this technique might allow detection of the genetic basis of the condition. METHODS: Sixty-six patients with undiagnosed asymptomatic or paucisymptomatic hyperCKemia, referred to tertiary neuromuscular centers over an approximately 2-year period, were analyzed using a customized, targeted sequencing panel able to investigate the coding exons and flanking intronic regions of 78 genes associated with limb-girdle muscular dystrophies, rhabdomyolysis, and metabolic and distal myopathies. RESULTS: A molecular diagnosis was reached in 33 cases, corresponding to a positive diagnostic yield of 50%. Variants of unknown significance were found in 17 patients (26%), whereas 16 cases (24%) remained molecularly undefined. The major features of the diagnosed cases were mild proximal muscle weakness (found in 27%) and myalgia (in 24%). Fourteen patients with a molecular diagnosis and mild myopathic features on muscle biopsy remained asymptomatic at a 24-month follow-up. CONCLUSIONS: This study of patients with undiagnosed hyperCKemia, highlighting the advantages of NGS used as a first-tier diagnostic approach in genetically heterogeneous conditions, illustrates the ongoing evolution of molecular diagnosis in the field of clinical neurology. Isolated hyperCKemia can be the sole feature alerting to a progressive muscular disorder requiring careful surveillance.
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England has recently started a new paediatric influenza vaccine programme using a live-attenuated influenza vaccine (LAIV). There is uncertainty over how well the vaccine protects against more severe end-points. A test-negative case-control study was used to estimate vaccine effectiveness (VE) in vaccine-eligible children aged 2-16 years of age in preventing laboratory-confirmed influenza hospitalisation in England in the 2015-2016 season using a national sentinel laboratory surveillance system. Logistic regression was used to estimate the VE with adjustment for sex, risk-group, age group, region, ethnicity, deprivation and month of sample collection. A total of 977 individuals were included in the study (348 cases and 629 controls). The overall adjusted VE for all study ages and vaccine types was 33.4% (95% confidence interval (CI) 2.3-54.6) after adjusting for age group, sex, index of multiple deprivation, ethnicity, region, sample month and risk group. Risk group was shown to be an important confounder. The adjusted VE for all influenza types for the live-attenuated vaccine was 41.9% (95% CI 7.3-63.6) and 28.8% (95% CI -31.1 to 61.3) for the inactivated vaccine. The study provides evidence of the effectiveness of influenza vaccination in preventing hospitalisation due to laboratory-confirmed influenza in children in 2015-2016 and continues to support the rollout of the LAIV childhood programme.
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Hospitalización/estadística & datos numéricos , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Inglaterra , Femenino , Humanos , Masculino , Resultado del Tratamiento , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunologíaRESUMEN
OBJECTIVE: Thymidine kinase 2, encoded by the nuclear gene TK2, is required for mitochondrial DNA maintenance. Autosomal recessive TK2 mutations cause depletion and multiple deletions of mtDNA that manifest predominantly as a myopathy usually beginning in childhood and progressing relentlessly. We investigated the safety and efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies. METHODS: We administered deoxynucleoside monophosphates and deoxynucleoside to 16 TK2-deficient patients under a compassionate use program. RESULTS: In 5 patients with early onset and severe disease, survival and motor functions were better than historically untreated patients. In 11 childhood and adult onset patients, clinical measures stabilized or improved. Three of 8 patients who were nonambulatory at baseline gained the ability to walk on therapy; 4 of 5 patients who required enteric nutrition were able to discontinue feeding tube use; and 1 of 9 patients who required mechanical ventilation became able to breathe independently. In motor functional scales, improvements were observed in the 6-minute walk test performance in 7 of 8 subjects, Egen Klassifikation in 2 of 3, and North Star Ambulatory Assessment in all 5 tested. Baseline elevated serum growth differentiation factor 15 levels decreased with treatment in all 7 patients tested. A side effect observed in 8 of the 16 patients was dose-dependent diarrhea, which did not require withdrawal of treatment. Among 12 other TK2 patients treated with deoxynucleoside, 2 adults developed elevated liver enzymes that normalized following discontinuation of therapy. INTERPRETATION: This open-label study indicates favorable side effect profiles and clinical efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies for TK2 deficiency. ANN NEUROL 2019;86:293-303.
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Ensayos de Uso Compasivo/métodos , Desoxirribonucleósidos/uso terapéutico , Enfermedades Musculares/tratamiento farmacológico , Enfermedades Musculares/enzimología , Timidina Quinasa/deficiencia , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Prueba de Paso/métodosAsunto(s)
Dermatosis Facial/diagnóstico , Adolescente , Adulto , Biopsia , Niño , Dermatosis Facial/patología , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Whole grain (WG) food consumption is associated with lower risk of cardiovascular disease, cancer and neurological diseases. The aim of this study was to assess the consumption of WG food and its major demographic, socioeconomic, psychosocial and behavioral determinants in a general Italian population. METHODS AND RESULTS: Data were from the Italian Nutrition & Health Survey (INHES), a telephone-based survey established in 2010-2013 including 9422 participants aged ≥5 years from all over Italy. WG food intake was assessed by the European Food Propensity Questionnaire and included bread, pasta, breakfast cereals, biscuits and WG soups. WG consumption was categorized as none, occasional (<1 time/week) and regular (≥1 time/week). Overall, 26.9% of the sample reported a regular consumption of WG food (27.2% of adults aged 20-97 y, and 21.9% of children/adolescents aged 5-19 y). In both age-groups, the major food source contributing to total WG intake was WG bread followed by WG pasta. Among adults, greater consumption of WG was associated with healthier lifestyle (e.g. sport activity), and higher educational level. Eating meals outside of the house in adults, and spending >2 h/day watching TV in children/adolescents were inversely associated with WG intake. CONCLUSIONS: The percentage of WG consumers in Italy in 2010-2013 appears to be quite low and still below that recorded in other countries of Europe where consumption is frequently over 50 percent. WG consumption is likely to be influenced by socioeconomic status and is associated with a number of psychosocial factors, meal patterns and eating-related behaviors.
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Dieta Saludable , Conducta Alimentaria , Conductas Relacionadas con la Salud , Comidas , Ingesta Diaria Recomendada , Granos Enteros , Adolescente , Conducta del Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Conducta Infantil , Preescolar , Estudios Transversales , Escolaridad , Ejercicio Físico , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Valor Nutritivo , Tiempo de Pantalla , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: There is poor knowledge on the association between combined lifestyles with mortality risk among individuals at high risk, and little is known on the biological mechanisms that could be on the pathway. METHODS: Longitudinal analysis on 22 839 individuals from the Moli-sani Study (Italy, 2005-2010). Among them, we identified 5200 elderly individuals (≥65 year), 2127 subjects with diabetes and 1180 with cardiovascular disease (CVD) at baseline. A healthy lifestyle score (HLS) was calculated, allocating 1 point for each of the following: abstention from smoking; adherence to Mediterranean diet; physical activity; absence of abdominal obesity. Hazard ratios (HR) with 95% confidence intervals (95%CI) were calculated by multivariable Cox regression and competing risk models. RESULTS: During 8.2 years of follow-up, 1237 deaths occurred. In the general population, adherence to all four healthy lifestyles, compared with none or 1, was associated with lower risk of all-cause (HR = 0.53; 95%CI:0.39-0.72), CVD (HR = 0.54; 0.32-0.91), cancer (HR = 0.62; 0.39-1.00) and mortality from other causes (HR = 0.39; 0.19-0.81). A 1-point increase in HLS was associated with 20%, 22% and 24% lower risk of total mortality among the elderly, in subjects with diabetes or CVD, respectively. Traditional (e.g. blood lipids), inflammatory (e.g. C-reactive protein) and novel biomarkers (e.g. markers of cardiac damage) accounted for up to 24% of the association of HLS with all-cause mortality risk in the general population. CONCLUSIONS: The impact of combined four healthy lifestyles on survival was considerable, both in the general population and among high-risk subgroups. Inflammatory and novel biomarkers of CVD risk explained a substantial proportion of this association.
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Estilo de Vida Saludable , Mortalidad/tendencias , Anciano , Biomarcadores , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus/mortalidad , Dieta Mediterránea , Ejercicio Físico , Femenino , Humanos , Italia , Estudios Longitudinales , Masculino , Obesidad , Estudios Prospectivos , Factores de Riesgo , Cese del Hábito de FumarRESUMEN
Complex I (CI) is the largest component of the mitochondrial respiratory chain (MRC) and it is made up of 7 mitochondrial DNA (mtDNA)-encoded and at least 38 nuclear DNA-encoded subunits. Isolated CI deficiency is the most common single enzyme deficiency in the heterogeneous group of MRC disorders and it is a relatively common etiology of Leigh-like syndrome (LS). With a few exceptions, descriptions of the clinical spectrum of specific mutations in CI are scarce. We here present three unrelated Italian children who harbored the homoplasmic m.10197G>A mutation in MT-ND3 associated with reduced enzyme activity of CI in muscle. Compared with the spectrum of phenotypes seen in 13 previously described families with the same mutation, these children showed some novel clinical features. Two of the boys presented with subacute onset of dystonia, which showed a remitting-relapsing clinical course in one of them. The third boy presented acute symptoms consisting of speech impairment, progressive left-sided hemiparesis, and also vertebral and arterial malformations. In all the children, molecular studies identified a similar mutation load in tissues, and neuroimaging findings were consistent with the features seen in LS. Functional investigations in cultured skin fibroblasts suggested low ATP production in homoplasmic cells. Our results confirm that the m.10197G>A mutation is relevant to these patients' clinical and biochemical phenotypes, which thus expand the array of phenotypes associated with this variant.
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Encéfalo/diagnóstico por imagen , ADN Mitocondrial/genética , Complejo I de Transporte de Electrón/deficiencia , Enfermedades Mitocondriales/genética , Mutación , Fenotipo , Niño , Preescolar , Complejo I de Transporte de Electrón/genética , Humanos , Masculino , Enfermedades Mitocondriales/diagnóstico por imagenRESUMEN
The preoperative computer-assisted resection planning is the basis for every navigation. Thanks to modern algorithms, the prerequisites have been created to carry out a virtual resection planning and a risk analysis. Thus, individual segment resections can be precisely planned in any conceivable combination. The transfer of planning information and resection suggestions to the operating theater is still problematic. The so-called stereotactic liver navigation supports the exact intraoperative implementation of the planned resection strategy and provides the surgeon with real-time three-dimensional information on resection margins and critical structures during the resection. This is made possible by a surgical navigation system that measures the position of surgical instruments and then presents them together with the preoperative surgical planning data. Although surgical navigation systems have been indispensable in neurosurgery and spinal surgery for many years, these procedures have not yet become established as standard in liver surgery. This is mainly due to the technical challenge of navigating a moving organ. As the liver is constantly moving and deforming during surgery due to respiration and surgical manipulation, the surgical navigation system must be able to measure these alterations in order to adapt the preoperative navigation data to the current situation. Despite these advances, further developments are required until navigated liver resection enters clinical routine; however, it is already clear that laparoscopic liver surgery and robotic surgery will benefit most from navigation technology.
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Neoplasias Hepáticas , Cirugía Asistida por Computador , Hepatectomía , Humanos , Imagenología Tridimensional , Neoplasias Hepáticas/cirugíaRESUMEN
BACKGROUND AND AIMS: Evidence indicates that Vitamin D deficiency may be associated with increased risk of cardiovascular disease, although findings on risk of heart failure (HF) are controversial. We investigated the relationship between serum Vitamin D and the incidence of hospitalization for HF in a large prospective cohort of Italian adults. METHODS AND RESULTS: 19,092 (49% men, age range 35-99 years) HF-free individuals from the Moli-sani study, with complete data on serum Vitamin D (25-hydroxyvitamin) levels and incident hospitalized HF, were analysed. The cohort was followed up for a median of 6.2 years. Baseline serum Vitamin D levels were categorized in deficient (<10 ng/mL), insufficient (10-29 ng/mL), and normal (≥30 ng/mL) Incident cases of hospitalization for HF were identified by linkage with the regional hospital discharge registry. Hazard ratios (HRs) were calculated using Cox-proportional hazard models. The prevalence of normal, insufficient or deficient levels of Vitamin D was 12.2%, 79.6% and 8.2%, respectively. During follow-up, 562 admissions to hospital for HF were identified. The incidence of HF was 1.6%, 2.9% and 5.3%, respectively in subjects with normal, insufficient and deficient levels of Vitamin D. After multivariable analysis, individuals with deficiency of Vitamin D had a higher risk of hospitalization for HF (HR: 1.61, 95%CI: 1.06-2.43) than those with normal levels. Further adjustment for subclinical inflammation did not substantially change the association between Vitamin D deficiency and HF. CONCLUSION: Deficiency of Vitamin D was associated, independently of known HF risk factors, with an increased risk of hospitalization for HF in an Italian adult population.
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Insuficiencia Cardíaca/sangre , Hospitalización , Deficiencia de Vitamina D/sangre , Vitamina D/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Humanos , Incidencia , Mediadores de Inflamación/sangre , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Vitamina D/sangre , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiologíaRESUMEN
BACKGROUND/OBJECTIVE: Psychological resilience is a measure of stress coping ability and has been associated with favourable health outcomes. While evidence on the relationship of dietary habits with a number of psychosocial conditions is available, there is lack of studies on their association with psychological resilience in a general adult population. SUBJECTS/METHODS: Cross-sectional analysis on 10 812 subjects recruited within the cohort of the Moli-sani study (2005-2010). Psychological resilience was measured by the 25-item Connor-Davidson Psychological Resilience Scale. Food intake was recorded by the EPIC food frequency questionnaire and adherence to Mediterranean diet was appraised by both a Greek Mediterranean diet score and an Italian Mediterranean Index. Empirically derived dietary patterns were obtained by principal factor analysis. Multivariable linear regression analysis (95%CI) was used to test the association between dietary scores and psychological resilience. RESULTS: Higher adherence to Mediterranean-type diets or consumption of a vegetable-based dietary pattern (obtained from principal factor analysis) were positively associated with psychological resilience (ß=0.43; 95%CI: 0.19-0.66, ß=0.92; 0.69-1.16, and ß=1.18; 0.93-1.44, for Greek Mediterranean diet score, Italian Mediterranean Index and the 'Olive oil and vegetables pattern', respectively). Dietary polyphenol or antioxidant intakes and greater variety in fruit and vegetable consumption were also positively associated with psychological resilience, while the associations with Western-like diets were weak. CONCLUSIONS: In conclusion, Mediterranean diet, vegetable-based dietary patterns and better diet quality were all positively associated with higher psychological resilience, whereas Western-type diets were not.
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Dieta Mediterránea/psicología , Resiliencia Psicológica , Adulto , Estudios de Cohortes , Estudios Transversales , Registros de Dieta , Dieta Saludable , Ingestión de Energía , Conducta Alimentaria , Femenino , Frutas , Humanos , Italia , Masculino , Persona de Mediana Edad , Aceite de Oliva , Estudios Prospectivos , Encuestas y Cuestionarios , VerdurasRESUMEN
BACKGROUND AND AIMS: Fish consumption reportedly reduces the risk of heart disease, but the evidence of cardiovascular advantages associated with fish intake within Mediterranean cohorts is limited. The aim of this study was to test the association between fish intake and risk of composite coronary heart disease (CHD) and stroke in a large population-based cohort adhering to Mediterranean Diet. METHODS AND RESULTS: Prospective analysis on 20,969 subjects free from cardiovascular disease at baseline, enrolled in the Moli-sani study (2005-2010). Food intake was recorded by the Italian version of the EPIC food frequency questionnaire. Hazard ratios were calculated by using multivariable Cox-proportional hazard models. During a median follow-up of 4.3 years, a total of 352 events occurred (n of CHD = 287 and n of stroke = 66). After adjustment for a large panel of covariates, fish intake ≥4 times per week was associated with 40% reduced risk of composite CHD and stroke (HR = 0.60; 95%CI 0.40-0.90), and with 40% lower risk of CHD (HR = 0.60; 95%CI 0.38-0.94) as compared with subjects in the lowest category of intake (<2 times/week). A similar trend of protection was found for stroke risk although results were not significant (HR = 0.62; 95%CI 0.26-1.51). When fish types were considered, protection against the composite outcome and CHD was confined to fatty fish intake. CONCLUSIONS: Fish intake was associated with reduced risk of composite fatal and non-fatal CHD and stroke in a general Mediterranean population. The favourable association was likely to be driven by fatty fish.
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Enfermedad Coronaria/prevención & control , Dieta Saludable , Dieta Mediterránea , Grasas de la Dieta/administración & dosificación , Peces , Alimentos Marinos , Accidente Cerebrovascular/prevención & control , Adulto , Anciano , Animales , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Conducta Alimentaria , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores Protectores , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Factores de TiempoRESUMEN
Neuromedin U (NmU) is a pleiotropic hypothalamic neuropeptide involved in the gut-brain axis. It acts via both a Gαq/11-coupled receptor (NMUR1) and a Gαi-coupled receptor (NMUR2) in different cell types. Expression of both receptors was reported in platelets, but their significance for NmU signaling remains elusive. We studied the potential effects of NmU on human platelet activation. In platelet-rich plasma (PRP), NmU alone (up to 10µM) did not induce any measurable aggregation, but at nanomolar concentrations, it potentiated platelet aggregation by low (mean 0.47µM) ADP concentrations (from 25.9±3.6% to 74.8±2.7% maximal aggregation for ADP vs. ADP+NmU, 100nM, mean±SEM, n=13), accompanied by platelet P-selectin expression and intracellular calcium mobilization. Accordingly, platelet preincubation with NmU for 2min sensitized platelets for subsequent activation by ADP. When P2Y1 was inactivated by 50µM MRS2179, NmU comparably potentiated ADP-induced PRP aggregation, suggestive of cooperative activation with Gαi-coupled P2Y12. Likewise, NmU potentiated platelet aggregation by Gαi-operated epinephrine at subthreshold concentrations (99ng/ml, mean), but not that by Gαq-dependent serotonin (20µM). Platelet aggregation by NmU/epinephrine combination was fully inhibited by the Gαq inhibitor YM-254890 (1µM). qPCR detection and western blot analysis substantiated platelet expression of NMUR1 in different donors, a finding collectively complying with functionally relevant Gαq/11-mediated activation of platelet NMUR1 by NmU. Our findings advocate further studies on platelet sensitization by NmU, released during vascular activation and injury, to define its role as a modifier of platelet responsiveness to the physiological activation signals, operational in cardiovascular health and disease.
Asunto(s)
Neuropéptidos/uso terapéutico , Activación Plaquetaria/efectos de los fármacos , Humanos , Neuropéptidos/farmacología , Transducción de SeñalRESUMEN
Fabry disease (FD) [OMIM 301500] is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in progressive multisystem accumulation of globotriaosylceramide (Gb3). Although the introduction of Enzyme Replacement Therapy (ERT) resulted in a variety of clinical benefits, life-long intravenous (IV) treatment with ERT with an every other week schedule, may interfere with daily life activities and impact on QoL. We report here a multicentric, observational, longitudinal data analysis on a large cohort of 85 Italian FD patients (45 males, 40 females) from 11 out of 20 Italian regions, who received a cumulative number of 4269 home infusions of agalsidase alfa. For the whole cohort, the average duration of home therapy was 1 year and 11 months (range 3 months-4 years and 6 months), and during this period, compliance to treatment (number of infusions performed vs scheduled) reached 100%. The EQ-5 VAS scale was administered to patients to evaluate the self-reported QoL, 58% of patients showing an increase of EQ-5 VAS score at follow up compared to baseline (home treatment start) or remaining stable. A mild increase of average disease severity, measured through Mainz Severity Score Index (MSSI), was found during hospital treatment (p < 0,007), while it remained stable between the first home therapy infusion and last follow up. Interestingly, 4 out of 7 (57%) patients, showing an improvement in FD-related clinical status after starting home therapy, had previously a sub-optimal compliance to treatment during the period of hospital treatment management. Only 4 adverse non serious reactions (0,093%) were reported totally in 2 patients during home treatment. We conclude that home infusions in eligible patients with FD are safe, contribute to improve treatment compliance and therapeutic clinical outcomes, and may have a positive impact on self-perceived QoL.