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Paraneoplastic neurological syndromes (PNSs) are an uncommon complication of cancer, affecting nearby 1/10,000 subjects with a tumour. PNSs can involve all the central and peripheral nervous systems, the muscular system, and the neuromuscular junction, causing extremely variable symptomatology. The diagnosis of the paraneoplastic disease usually precedes the clinical manifestations of cancer, making an immediate recognition of the pathology crucial to obtain a better prognosis. PNSs are autoimmune diseases caused by the expression of common antigens by the tumour and the nervous system. Specific antibodies can help clinicians diagnose them, but unfortunately, they are not always detectable. Immunosuppressive therapy and the treatment of cancer are the cornerstones of therapy for PNSs. This paper reports a case of PNSs associated with breast tumours and focuses on the most common paraneoplastic neurological syndromes. We report a case of a young female with a clinical syndrome of the occurrence of rigidity in the right lower limb with postural instability with walking supported and diplopia, with a final diagnosis of paraneoplastic cerebellar degeneration and seronegative rigid human syndrome associated with infiltrating ductal carcinoma of the breast.
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Streptococcus mitis, a normal inhabitant of the oral cavity, is a member of Viridans Group Streptococci (VGS). Generally recognized as a causative agent of invasive diseases in immunocompromised patients, S. mitis is considered to have low pathogenic potential in immunocompetent individuals. We present a rare case of sinusitis complicated by meningitis and cerebral sino-venous thrombosis (CSVT) caused by S. mitis in a previously healthy 12-year-old boy with poor oral health status. With the aim of understanding the real pathogenic role of this microorganism, an extensive review of the literature about invasive diseases due to S. mitis in pediatric patients was performed. Our data define the critical role of this microorganism in invasive infections, especially in immunocompetent children and in the presence of apparently harmful conditions such as sinusitis and caries. Attention should be paid to the choice of therapy because of VGS's emerging antimicrobial resistance patterns.
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Fabry disease (FD) is a recessive monogenic disease linked to chromosome X due to more than two hundred mutations in the alfa-galactosidase A (GLA) gene. Modifications of the GLA gene may cause the progressive accumulation of globotriaosylceramide (Gb3) and its deacylated form, globotriasylsphingosine (lyso-Gb3), in lysosomes of several types of cells of the heart, kidneys, skin, eyes, peripheral and central nervous system (not clearly and fully demonstrated), and gut with different and pleiotropic clinical symptoms. Among the main symptoms are acroparesthesias and pain crisis (involving the peripheral nervous system), hypohidrosis, abdominal pain, gut motility abnormalities (involving the autonomic system), and finally, cerebrovascular ischemic events due to macrovascular involvement (TIA and stroke) and lacunar strokes and white matter abnormalities due to a small vessel disease (SVS). Gb3 lysosomal accumulation causes cytoplasmatic disruption and subsequent cell death. Additional consequences of Gb3 deposits are inflammatory processes, abnormalities of leukocyte function, and impaired trafficking of some types of immune cells, including lymphocytes, monocytes, CD8+ cells, B cells, and dendritic cells. The involvement of inflammation in AFD pathogenesis conflicts with the reported poor correlation between CRP levels as an inflammation marker and clinical scores such as the Mainz Severity Score Index (MSSI). Also, some authors have suggested an autoimmune reaction is involved in the disease's pathogenetic mechanism after the α-galactosidase A deficiency. Some studies have reported a high degree of neuronal apoptosis inhibiting protein as a critical anti-apoptotic mediator in children with Fabry disease compared to healthy controls. Notably, this apoptotic upregulation did not change after treatment with enzymatic replacement therapy (ERT), with a further upregulation of the apoptosis-inducing factor after ERT started. Gb3-accumulation has been reported to increase the degree of oxidative stress indexes and the production of reactive oxygen species (ROS). Lipids and proteins have been reported as oxidized and not functioning. Thus, neurological complications are linked to different pathogenetic molecular mechanisms. Progressive accumulation of Gb3 represents a possible pathogenetic event of peripheral nerve involvement. In contrast, central nervous system participation in the clinical setting of cerebrovascular ischemic events seems to be due to the epitheliopathy of Anderson-Fabry disease with lacunar lesions and white matter hyperintensities (WMHs). In this review manuscript, we revised molecular mechanisms of peripheral and central neurological complications of Anderson-Fabry Disease. The management of Fabry disease may be improved by the identification of biomarkers that reflect the clinical course, severity, and progression of the disease. Intensive research on biomarkers has been conducted over the years to detect novel markers that may potentially be used in clinical practice as a screening tool, in the context of the diagnostic process and as an indicator of response to treatment. Recent proteomic or metabolomic studies are in progress, investigating plasma proteome profiles in Fabry patients: these assessments may be useful to characterize the molecular pathology of the disease, improve the diagnostic process, and monitor the response to treatment.
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Enfermedad de Fabry , Niño , Humanos , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/genética , Proteómica , Sistema Nervioso Periférico , Biomarcadores , InflamaciónRESUMEN
Background: Different studies have indicated that thiazide diuretics can increase the risk of developing type 2 diabetes (T2D). Therefore, in this study, we investigated whether switching from hydrochlorothiazide (HCTZ) to amlodipine resulted in ameliorating different cardiovascular and metabolic measures in hypertensive patients with or without T2D. Methods: This study [Diuretics and Diabetes Control (DiaDiC)] was a 6-week, single-blind, single-center randomized controlled trial. The first 20 normal glucose-tolerant, 20 prediabetic, and 20 T2D consecutive patients were randomized to continue the previous antihypertensive treatment with HCTZ (12.5-25 mg/day) or to switch from HCTZ to amlodipine (2.5-10 mg/day). The primary endpoints were the absolute change in 7-day continuous subcutaneous glucose monitoring (CSGM) glycemia, serum uric acid concentrations, and endothelial function [measured as flow-mediated dilation (FMD)]. Other secondary endpoints were investigated, including changes in glycated hemoglobin (HbA1c), glycemic variability from 7-day CSGM, and the estimated glomerular filtration rate (eGFR). Results: Amlodipine treatment was associated with a significant reduction in HbA1c (P = 0.03) for both 7-day CSGM glycemia (P = 0.01) and glycemic variability (coefficient of variability %: HCTZ +3%, amlodipine -2.8%), and a reduction in uric acid concentrations (P < 0.001), especially in participants with T2D or prediabetes. Following amlodipine treatment, a significant increase in both eGFR (P = 0.01) and FMD (P = 0.02) was also observed. Conclusions: This study demonstrates that the replacement of HCTZ with amlodipine has several metabolic and cardiovascular beneficial effects. However, further intervention studies are necessary to confirm the clinical effects of thiazides, especially in diabetic people and in those at risk of diabetes.
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Amlodipino/uso terapéutico , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/uso terapéutico , Diabetes Mellitus Tipo 2 , Sustitución de Medicamentos , Metabolismo Energético/efectos de los fármacos , Hidroclorotiazida/uso terapéutico , Hipertensión/tratamiento farmacológico , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Anciano , Amlodipino/efectos adversos , Antihipertensivos/efectos adversos , Biomarcadores/sangre , Bloqueadores de los Canales de Calcio/efectos adversos , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Humanos , Hidroclorotiazida/efectos adversos , Hipertensión/sangre , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Italia , Masculino , Persona de Mediana Edad , Método Simple Ciego , Inhibidores de los Simportadores del Cloruro de Sodio/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Background: It has been reported that changes in cardiac structure and ventricular function associated with obesity have to be attributable to hemodynamic and non-hemodynamic alterations. Accordingly, the aim of this was to evaluate left ventricular hypertrophy (LVH) prevalence and its effect on left ventricular systolic and diastolic function in a cohort of obese patients.Materials and Methods: LV internal diameter (LVID), left ventricular mass (LVM) and LVM/height2.7(LVMI), relative wall thickness (RWT), LV ejection fraction (LVEF), E/A ratio, isovolumic relaxation time, deceleration time of E velocity by echocardiography and pulsed-wave Doppler and total circulating adiponectin (ADPN) by radioimmunoassay were measured in 319 obese subjects with and without LVH.Results: Increased values of BMI, WHR, SBP, DBP, MBP LVID, LVM, LVMI, IVST (p < .001), increased prevalence of subjects with LVEF< 50%,(p < .001), central fat distribution (p < .001), hypertension (p < .001), diabetes (p < .001), metabolic syndrome (p < .02), and reduced value of ADPN (p < .0001) and LVEF (p < .001) were detected in LVH obese subjects than controls without LVH. No significant differences in diastolic parameters were observed between the two groups. LVEF correlated directly with ADPN (p < .0001) and inversely with age (p < .01), BMI (p < .01), WHR (p < .001), MBP (p < .01) MetS (p < .02) and LVMI (p < .001). WHR, MBP, LVMI and ADPN were independently associated with LVEF.Conclusions: In conclusion, our data indicate that obese subjects with LVH might be considered a distinct phenotype of obesity, characterised by LVH, increased prevalence of cardiometabolic comorbidities, central fat distribution, hypoadiponectinemia and early left ventricular systolic dysfunction.
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Adiponectina/sangre , Ventrículos Cardíacos , Hipertrofia Ventricular Izquierda , Obesidad , Disfunción Ventricular Izquierda , Factores de Riesgo Cardiometabólico , Correlación de Datos , Ecocardiografía/métodos , Ecocardiografía Doppler de Pulso/métodos , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Italia/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/diagnóstico , Obesidad/metabolismo , Obesidad/fisiopatología , Tamaño de los Órganos , Fenómica/métodos , Volumen Sistólico , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/etiologíaRESUMEN
Left ventricular ejection fraction (EF) is helpful to differentiate heart failure (HF) phenotype in clinical practice. The aim of the study was to identify simple echocardiographic predictors of post-discharge all-cause mortality in hospitalized HF patients. Patients with acute HF (75 ± 9.8 years), classified in preserved (≥ 50%) and reduced (< 50%) EF (HFpEF and HFrEF, respectively), were enrolled. The mean follow-up period was of 25.4 months. Patients definitively analyzed were 135. At multivariate Cox model, right ventricular diameter (RVd), inferior vena cava diameter (IVCd) and blood urea nitrogen (BUN) resulted to be significantly associated with all-cause mortality in HFpEF (HR 2.4, p = 0.04; HR 1.06, p = 0.02; HR 1.02, p = 0.01), whereas, left atrial volume (LAV) was significantly associated with mortality in HFrEF (HR 1.06, p = 0.006). Excluding LAV from the model, only COPD remained an independent predictor of all-cause mortality (HR 2.15, p = 0.04) in HFrEF. At Kaplan-Meier analysis, no differences of survival between HFrEF and HFpEF were found, however, significantly increased all-cause mortality for higher values of basal-RVd, BUN, and IVCd (log-rank p = 0.0065, 0.0063, 0.0005) in HFpEF, and for COPD and higher LAV (log-rank p = 0.0046, p = 0.033) in HFrEF. These data are indicative that in patients hospitalized with HF, EF is not a suitable predictor of long-term all-cause mortality, whereas, right ventricular volumetric remodeling and IVCd have a prognostic role in HFpEF as well as LAV in HFrEF. Our study suggests that besides EF, other echocardiographic parameters are helpful to optimize the phenotyping and prognostic stratification of HF.
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Insuficiencia Cardíaca/mortalidad , Ventrículos Cardíacos/patología , Pronóstico , Volumen Sistólico/fisiología , Pesos y Medidas/instrumentación , Anciano , Anciano de 80 o más Años , Ecocardiografía/métodos , Ecocardiografía/estadística & datos numéricos , Femenino , Insuficiencia Cardíaca/clasificación , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/anomalías , Humanos , Italia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Pesos y Medidas/normasRESUMEN
The influence of nutrition has the potential to substantially affect physical function and body metabolism. Particular attention has been focused on omega-3 polyunsaturated fatty acids (n-3 PUFAs), which can be found both in terrestrial features and in the marine world. They are responsible for numerous cellular functions, such as signaling, cell membrane fluidity, and structural maintenance. They also regulate the nervous system, blood pressure, hematic clotting, glucose tolerance, and inflammatory processes, which may be useful in all inflammatory conditions. Animal models and cell-based models show that n-3 PUFAs can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that they can influence not only the exercise and the metabolic response of skeletal muscle, but also the functional response for a period of exercise training. In addition, their potential anti-inflammatory and antioxidant activity may provide health benefits and performance improvement especially in those who practice physical activity, due to their increased reactive oxygen production. This review highlights the importance of n-3 PUFAs in our diet, which focuses on their potential healthy effects in sport.
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Ejercicio Físico , Ácidos Grasos Omega-3/administración & dosificación , Ciencias de la Nutrición y del Deporte , HumanosRESUMEN
BACKGROUND: Malnutrition in elderly inpatients hospitalized on medical wards is a significant public health concern. The aim of this study was to investigate nutritional markers as mortality predictors following discharge in hospitalized medical elderly patients. MATERIALS AND METHODS: This is a prospective observational cohort study with follow-up of 48 months. Two hundred and twenty-five individuals aged 60 and older admitted from the hospital emergency room in the past 48 h were investigated at the medical ward in the University hospital in Palermo (Italy). Anthropometric and clinical measurements, Mini-nutritional Assessment (MNA) questionnaire, bioelectrical (BIA) phase angle (PA), grip strength were obtained all within 48 h of admission. Mortality data were verified by means of mortality registry and analysed using Cox-proportional hazard models. RESULTS: Ninety (40%) participants died at the end of follow-up. There were significant relationships between PA, MNA score, age and gender on mortality. Patients in the lowest tertile of PA (< 4·6°) had higher mortality estimates [I vs II tertile: hazard ratio (HR) = 3·40; 95% confidence interval (CI): 2·01-5·77; II vs III tertile: HR = 3·83; 95% CI: 2·21-6·64; log-rank test: χ(2) = 43·6; P < 0·001]. Similarly, the survival curves demonstrated low MNA scores (< 22) were associated with higher mortality estimates (HR = 1·85; 95% CI: 1·22-2·81 χ(2) = 8·2; P = 0·004). CONCLUSIONS: The MNA and BIA-derived phase angle are reasonable tools to identify malnourished patients at high mortality risk and may represent useful markers in intervention trials in this high-risk subgroup.
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Desnutrición/epidemiología , Mortalidad , Evaluación Nutricional , Factores de Edad , Anciano , Anciano de 80 o más Años , Antropometría , Estudios de Cohortes , Comorbilidad , Enfermedad Coronaria/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Impedancia Eléctrica , Femenino , Estudios de Seguimiento , Fuerza de la Mano , Hospitalización , Humanos , Hipertensión/epidemiología , Italia/epidemiología , Fallo Renal Crónico/epidemiología , Masculino , Persona de Mediana Edad , Estado Nutricional , Alta del Paciente , Habitaciones de Pacientes , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de RiesgoRESUMEN
We tested whether nonalcoholic fatty liver disease (NAFLD) and/or its histological severity are associated with vascular white matter lesions (WML) in patients with biopsy-proven NAFLD and in non-NAFLD controls. Data were recorded in 79 consecutive biopsy-proven NAFLD, and in 82 controls with normal ALT and no history of chronic liver diseases, without ultrasonographic evidence of steatosis and liver stiffness value <6âKPa. All subjects underwent magnetic resonance assessment and WML were classified according to the Fazekas score as absent (0/III), or present (mild I/III; moderate II/III, and severe I/III). For the purpose of analyses, all controls were considered without NASH and without F2-F4 liver fibrosis. WML were found in 26.7% of the entire cohort (43/161), of moderate-severe grade in only 6 cases. The prevalence was similar in NAFLD versus no-NAFLD (29.1% vs 24.3%; Pâ=â0.49), but higher in NASH vs no-NASH (37.7% vs 21.2%, Pâ=â0.02) and F2-F4 vs F0-F1 fibrosis (47.3% vs 20.3%, Pâ=â0.001). In both the entire cohort and in NAFLD, only female gender (OR 4.37, 95% CI: 1.79-10.6, Pâ=â0.001; and OR 5.21, 95% CI: 1.39-19.6, Pâ=â0.01), ageâ>â45 years (OR 3.09, 95% CI: 1.06-9.06, Pâ=â0.03; and OR 11.1, 95% CI: 1.14-108.7, Pâ=â0.03), and F2-F4 fibrosis (OR 3.36, 95% CI: 1.29-8.73, Pâ=â0.01; and OR 5.34, 95% CI: 1.40-20.3, Pâ=â0.01) were independently associated with WML (mostly of mild grade) by multivariate analysis. Among NAFLD, the prevalence of WML progressively increased from patients without (1/18; 5.5%), or with 1 (1/17, 5.8%), to those with 2 (9/30; 30%) and further to those with 3 (12/14; 85.7%) risk factors. The presence of WML is not associated with NAFLD, but with metabolic diseases in general, and fibrosis severity of NAFLD. Clinical implications of this issue need to be assessed by longitudinal studies.
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Encefalopatías/etiología , Lóbulo Frontal/patología , Cirrosis Hepática/complicaciones , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Biopsia , Encefalopatías/patología , Diagnóstico Diferencial , Femenino , Humanos , Hígado/diagnóstico por imagen , Cirrosis Hepática/diagnóstico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Factores de Riesgo , Índice de Severidad de la Enfermedad , Ultrasonografía , Sustancia Blanca/patologíaRESUMEN
BACKGROUND: In discharged patients with heart failure (HF), diverse conditions can intervene to worsen outcome. We would investigate whether such factors present on hospital admission can affect long-term mortality in subjects hospitalized for acute HF. METHODS: One hundred twenty-three consecutive patients hospitalized for acute HF (mean age 74.8 years; 57% female) were recruited and followed for 36 months after hospitalization. RESULTS: At multivariate Cox model, only inferior vena cava (IVC) diameter and mean arterial pressure (MAP) registered bed-side on admission, resulted, after correction for all confounders factors, the sole factors significantly associated with a higher risk of all-cause mortality in long-term (HR 1.06, p=0.0057; HR 0.97, p=0.0218; respectively). Study population was subdivided according to median values of IVC diameter (23 mm) and MAP (93.3 mm Hg). The KaplanMeier curve showed that HF patients with both IVC ≥ 23 mm and MAP b93.3 mm Hg on admission had reduced probability of survival free from all-cause death (log rank p = 0.0070 and log rank p = 0.0028, respectively). CONCLUSIONS: In patients hospitalized for acute HF, IVC diameter, measured by hand-carried ultrasound (HCU), and MAP detected on admission are strong predictors of long-term all-cause mortality. The data suggest the need for a careful clinical-therapeutic surveillance on these patients during the post-discharge period. IVC diameter and MAP can be utilized as parameters to stratify prognosis on admission and to be supervised during follow-up.
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Presión Arterial/fisiología , Insuficiencia Cardíaca/mortalidad , Hospitalización , Vena Cava Inferior/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mortalidad , Análisis Multivariante , Tamaño de los Órganos , Pruebas en el Punto de Atención , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Vena Cava Inferior/patologíaRESUMEN
BACKGROUND/AIMS: We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes. METHODS: Consecutive patients (n = 126) with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50), OSA was defined as an apnea/hypopnea index ≥5. A carotid atherosclerotic plaque was defined as a focal thickening >1.3 mm. RESULTS: Prevalence of high OSA risk was similar in patients refusing or accepting PG (76% vs 68%, p = 0.17). Among those accepting PG, overall OSA prevalence was significantly higher in patients with F2-F4 fibrosis compared to those without (72% vs 44%; p = 0.04). Significant fibrosis was independently associated with mean nocturnal oxygen saturation (SaO2)<95% (OR 3.21, 95%C.I. 1.02-7.34; p = 0.04). Prevalence of OSA tended to be higher in patients with, than in those without, carotid plaques (64% vs 40%; p = 0.08). Carotid plaques were independently associated with %time at SaO2<90% >1 (OR 6.30, 95%C.I. 1.02-12.3; p = 0.01). CONCLUSIONS: In NAFLD patients with chronically elevated ALT at low prevalence of morbid obesity, OSA was highly prevalent and indexes of SaO2 resulted independently associated with severity of liver fibrosis and carotid atherosclerosis. These data suggest to consider sleep disordered breathing as a potential additional therapeutic target in severe NAFLD patients.
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Aterosclerosis/epidemiología , Aterosclerosis/etiología , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Apnea Obstructiva del Sueño/complicaciones , Adulto , Anciano , Aterosclerosis/diagnóstico , Biopsia , Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/epidemiología , Enfermedades de las Arterias Carótidas/etiología , Femenino , Humanos , Hipoxia/complicaciones , Cirrosis Hepática/diagnóstico , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Prevalencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Diuretic responsiveness in patients with chronic heart failure (CHF) is better assessed by urine production per unit diuretic dose than by the absolute urine output or diuretic dose. Diuretic resistance arises over time when the plateau rate of sodium and water excretion is reached prior to optimal fluid elimination and may be overcome when hypertonic saline solution (HSS) is added to high doses of furosemide. METHODS: Forty-two consecutively hospitalized patients with refractory CHF were randomized in a 1:1:1 ratio to furosemide doses (125 mg, 250 mg, 500 mg) so that all patients received intravenous furosemide diluted in 150 ml of normal saline (0.9%) in the first step (0-24 h) and the same furosemide dose diluted in 150 ml of HSS (1.4%) in the next step (24-48 h) as to obtain 3 groups as follows: Fourteen patients receiving 125 mg (group 1), fourteen patients receiving 250 mg (group 2), and fourteen patients receiving 500 mg (group 3) of furosemide. Urine samples of all patients were collected at 30, 60, and 90 min, and 3, 4, 5, 6, 8, and 24 h after infusion. Diuresis, sodium excretion, osmolality, and furosemide concentration were evaluated for each urine sample. RESULTS: After randomization, 40 patients completed the study. Two patients, one in group 2 and one in group 3 dropped out. Patients in group 1 (125 mg furosemide) had a mean age of 77 ± 17 years, 43% were male, 6 (43%) had heart failure with a preserved ejection fraction (HFpEF), and 64% were in New York Heart Association (NYHA) class IV; the mean age of patients in group 2 (250 mg furosemide) was 80 ± 8.1 years, 15% were male, 5 (38%) had HFpEF, and 84% were in NYHA class IV; and the mean age of patients in group 3 (500 mg furosemide) was 73 ± 12 years, 54% were male, 6 (46%) had HFpEF, and 69% were in NYHA class IV. HSS added to furosemide increased total urine output, sodium excretion, urinary osmolality, and furosemide urine delivery in all patients and at all time points. The percentage increase was 18,14, and 14% for urine output; 29, 24, and 16% for total sodium excretion; 45, 34, and 20% for urinary osmolarity; and 27, 36, and 32% for total furosemide excretion in groups 1, 2, and 3, respectively. These findings were translated in an improvement in the furosemide dose-response curves in these patients. CONCLUSION: These results may serve as new pathophysiological basis for HSS use in the treatment of refractory CHF.
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Diuréticos/uso terapéutico , Furosemida/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Solución Salina Hipertónica/uso terapéutico , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Diuréticos/administración & dosificación , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Tolerancia a Medicamentos , Femenino , Furosemida/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Concentración Osmolar , Solución Salina Hipertónica/administración & dosificación , Sodio/orinaRESUMEN
Renal dysfunction (RD) and venous congestion are related and common in heart failure (HF). Studies suggest that venous congestion may be the primary driver of RD in HF. In this study, we sought to investigate retrospectively the relationship between common measures of renal function with caval congestion and mortality among outpatients with HF and RD. We reviewed data from 103 HF outpatients (45 males, mean age 74 years, ejection fraction 41.8 ± 11.6 %) with estimated glomerular filtration rate (eGFR) of < 60 ml/min in a single centre. During an ambulatory visit, all patients underwent blood test and ultrasonography of the inferior vena cava (IVC). Caval congestion was defined as IVC with both dilatation and impaired collapsibility. The best values of renal metrics in predicting caval congestion were determined with receiver-operating characteristic analysis. The BUN/Cr ratio is moderately correlated with IVC expiratory maximum diameter (r = 0.31, p < 0.0007). In a multiple logistic regression model, BUN/Cr > 25.5 (adjusted OR 2.98, p 0.015) and eGFR ≤ 45.8 (adjusted OR 5.38, p 0.002) identify patients at risk for caval congestion; a BUN/Cr > 23.7 was the best predictor of impaired collapsibility (adjusted OR 4.41, p 0.001). a BUN/Cr > 25.5 (HR 2.19, 95 % CI 1.21-3.94, p < 0.001) and NYHA class 3 (HR 2.91, 95 % CI 1.60-5.31, p < 0.0005) were independent risk factors associated with all-cause death during a median follow-up of 31 months. In outpatients with HF and RD, a higher BUN/Cr and lower eGFR are reliable renal biomarkers for caval congestion. The BUN/Cr is associated with long-term mortality and may help to stratify HF severity.
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Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Insuficiencia Cardíaca/mortalidad , Hiperemia/diagnóstico por imagen , Insuficiencia Renal/complicaciones , Vena Cava Inferior/diagnóstico por imagen , Anciano , Biomarcadores/sangre , Femenino , Tasa de Filtración Glomerular , Insuficiencia Cardíaca/sangre , Humanos , Italia , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Despite all available therapies, the rates of hospitalization and death from heart failure (HF) remain unacceptably high. The most common reasons for hospital admission are symptoms related to congestion. During hospitalization, most patients respond well to standard therapy and are discharged with significantly improved symptoms. Post-discharge, many patients receive diligent and frequent follow-up. However, rehospitalization rates remain high. One potential explanation is a persistent failure by clinicians to adequately manage congestion in the outpatient setting. The failure to successfully manage these patients post-discharge may represent an unmet need to improve the way congestion is both recognized and treated. A primary aim of future HF management may be to improve clinical surveillance to prevent and manage chronic fluid overload while simultaneously maximizing the use of evidence-based therapies with proven long-term benefit. Improvement in cardiac function is the ultimate goal and maintenance of a "dry" clinical profile is important to prevent hospital admission and improve prognosis. This paper focuses on methods for monitoring congestion, and strategies for water and sodium management in the context of the complex interplay between the cardiac and renal systems. A rationale for improving recognition and treatment of congestion is also proposed.
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Agua Corporal , Insuficiencia Cardíaca/fisiopatología , Riñón/fisiopatología , Sodio en la Dieta/normas , Biomarcadores , Síndrome Cardiorrenal , Diuréticos/uso terapéutico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Hospitalización/estadística & datos numéricos , Humanos , Alta del Paciente , Pronóstico , Sodio en la Dieta/sangre , Evaluación de SíntomasAsunto(s)
Disnea/patología , Hernia Hiatal/patología , Oxígeno/sangre , Páncreas/patología , Estómago/patología , Anciano de 80 o más Años , Disnea/diagnóstico por imagen , Disnea/etiología , Electrocardiografía , Femenino , Hernia Hiatal/sangre , Hernia Hiatal/complicaciones , Hernia Hiatal/diagnóstico por imagen , Humanos , Hipertensión Pulmonar/etiología , Espirometría , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND AND AIM: To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. METHODS: We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT), IMT thickening(IMT≥1 mm) and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery) were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results were validated in a cohort of 267 subjects with clinical or histological diagnosis of NAFLD from Northern Italy, 63 of whom had follow-up examinations. RESULTS: Carotid plaques, IMT thickening and mean maximum IMT were similar in the two cohorts, whereas the prevalence of diabetes, obesity, NASH, and PNPLA3 GG polymorphism(21%vs.13%, pâ=â0.02) were significantly higher in the Sicilian cohort. In this cohort, the prevalence of carotid plaques and IMT thickening was higher in PNPLA3 GG compared to CC/CG genotype(53%vs.32%, pâ=â0.02; 62%vs.28%, p<0.001, respectively). These associations were confirmed at multivariate analyses (OR2.94;95%C.I. 1.12-7.71, pâ=â0.02, and OR4.11;95%C.I. 1.69-9.96, pâ=â0.002, respectively), although have been observed only in patients <50years. Also in the validation cohort, PNPLA3 GG genotype was independently associated with IMT thickening in younger patients only (OR: 6.00,95%C.I. 1.36-29, pâ=â0.01), and to IMT progression (pâ=â0.05) in patients with follow-up examinations. CONCLUSION: PNPLA3 GG genotype is associated with higher severity of carotid atherosclerosis in younger patients with NAFLD. Mechanisms underlying this association, and its clinical relevance need further investigations.
Asunto(s)
Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/genética , Hígado Graso/complicaciones , Hígado Graso/genética , Genotipo , Lipasa/genética , Proteínas de la Membrana/genética , Adulto , Anciano , Alelos , Arterias Carótidas/patología , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CNS). It is a major cause of prosthetic valve endocarditis; mitral valve prolapse (MVP) has emerged as a prominent predisposing structural cardiac abnormality. We describe a case of Staphylococcus lugdunensis endocarditis in an 18-year-old woman with preexisting mitral valve prolapse complaining of fever, a one-month history of continuous-remittent fever (T(max) 38.6°C). The transthoracic echocardiogram revealed large vegetation on the anterior mitral valve leaflet flopping from the atrial side to the ventricular side. Five sets of blood cultures were positive for coagulase-negative staphylococci. During hospitalization, after two weeks of antibiotic therapy, the patient complained of sudden pain in her right leg associated with numbness. Lower limb arterial Doppler ultrasound showed an arterial thrombosis of right common iliac artery. Transfemoral iliac embolectomy was promptly performed and on septic embolus S. lugdunensis with the same antibiotic sensitivity and the same MIC values was again isolated. Our patient underwent cardiac surgery: triangular resection of the A2 with removal of infected tissue including vegetation. Our case is an example of infective endocarditis by S. lugdunensis on native mitral valve in a young woman of 18 with anamnesis valve prolapse.