RESUMEN
MucR belongs to a large protein family whose members regulate the expression of virulence and symbiosis genes in α-proteobacteria species. This protein and its homologs were initially studied as classical transcriptional regulators mostly involved in repression of target genes by binding their promoters. Very recent studies have led to the classification of MucR as a new type of Histone-like Nucleoid Structuring (H-NS) protein. Thus this review is an effort to put together a complete and unifying story demonstrating how genetic and biochemical findings on MucR suggested that this protein is not a classical transcriptional regulator, but functions as a novel type of H-NS-like protein, which binds AT-rich regions of genomic DNA and regulates gene expression.
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Ribosome inactivating proteins (RIPs) are specific N-ß-glycosylases that are well-characterized in plants. Their enzymatic action is to damage ribosomes, thereby blocking protein translation. Recently, several research groups have been working on the screening for these toxins in edible plants to facilitate the use of RIPs as biotechnological tools and biopesticides and to overcome public prejudice. Here, four novel monomeric (type 1) RIPs have been isolated from the seeds of Atriplex hortensis L. var. rubra, which is commonly known as edible red mountain spinach. These enzymes, named hortensins 1, 2, 4, and 5, are able to release the ß-fragment and, like many other RIPs, adenines from salmon sperm DNA, thus, acting as polynucleotide:adenosine glycosidases. Structurally, hortensins have a different molecular weight and are purified with different yields (hortensin 1, ~29.5 kDa, 0.28 mg per 100 g; hortensin 2, ~29 kDa, 0.29 mg per 100 g; hortensin 4, ~28.5 kDa, 0.71 mg per 100 g; and hortensin 5, ~30 kDa, 0.65 mg per 100 g); only hortensins 2 and 4 are glycosylated. Furthermore, the major isoforms (hortensins 4 and 5) are cytotoxic toward human continuous glioblastoma U87MG cell line. In addition, the morphological change in U87MG cells in the presence of these toxins is indicative of cell death triggered by the apoptotic pathway, as revealed by nuclear DNA fragmentation (TUNEL assay).
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Atriplex , Proteínas Inactivadoras de Ribosomas Tipo 1 , Semillas , Humanos , Glioblastoma , Ribosomas , Proteínas de Plantas , Línea Celular TumoralRESUMEN
Proteins of the MucR/Ros family play a crucial role in bacterial infection or symbiosis with eukaryotic hosts. MucR from Sinorhizobium meliloti plays a regulatory role in establishing symbiosis with the host plant, both dependent and independent of Quorum Sensing. Here, we report the first characterization of MucR isolated from Sinorhizobium meliloti by mass spectrometry and demonstrate that this protein forms higher-order oligomers in its native condition of expression by SEC-MALS. We show that MucR purified from Sinorhizobium meliloti can bind DNA and recognize the region upstream of the ndvA gene in EMSA, revealing that this gene is a direct target of MucR. Although MucR DNA binding activity was already described, a detailed characterization of Sinorhizobium meliloti DNA targets has never been reported. We, thus, analyze sequences recognized by MucR in the rem gene promoter, showing that this protein recognizes AT-rich sequences and does not require a consensus sequence to bind DNA. Furthermore, we investigate the dependence of MucR DNA binding on the length of DNA targets. Taken together, our studies establish MucR from Sinorhizobium meliloti as a member of a new family of Histone-like Nucleoid Structuring (H-NS) proteins, thus explaining the multifaceted role of this protein in many species of alpha-proteobacteria.
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Proteínas Represoras , Sinorhizobium meliloti , Proteínas Represoras/genética , Sinorhizobium meliloti/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Factores de Transcripción/metabolismo , ADN/genética , ADN/metabolismo , Simbiosis , Regulación Bacteriana de la Expresión GénicaRESUMEN
Glioblastoma, the most dangerous and aggressive type of CNS tumor, appears resistant to many chemotherapy drugs. In the patient-derived glioma cell lines NULU and ZAR, which exhibit drug-resistant phenotypes, we investigated the effect of combined AE (Aloe-emodin) and TMZ (temozolomide) and found a significant additive inhibitory effect on cell growth and a promising cytotoxic effect on both cell lines compared to treatment with single agents. We also examined the effect of combined AE and TMZ treatment on the drug-resistance protein MGMT. The results suggest that using AE combined with traditional drugs restores drug resistance in both primary resistant cell lines (NULU and ZAR). Furthermore, migration assays and scratch tests showed that the combined use of AE and TMZ can slow down the colony formation and migration of glioblastoma cells. These convincing results suggest that AE could be a natural adjuvant agent to potentiate the effects of traditional drugs (TMZ) and overcome drug resistance in glioblastoma cells.
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Aloe , Emodina , Glioblastoma , Humanos , Temozolomida/farmacología , Glioblastoma/tratamiento farmacológico , Línea CelularRESUMEN
BACKGROUND: Older patients are at increased risk of drug-drug interactions (DDIs) due to polypharmacy. Cardiovascular and central nervous system (CNS) drugs are commonly implicated in serious DDIs. OBJECTIVES: This study aimed to determine the prevalence and factors associated with potential 'severe' cardiovascular and CNS DDIs among older (≥ 70 years) community-dwellers. METHODS: This was a prospective cohort study using linked data from a national pharmacy claims database and waves 1 and 2 of The Irish LongituDinal study on Ageing (TILDA). 'Severe' cardiovascular and CNS DDIs were identified using the British National Formulary 77 and Stockley's Drug Interactions. The prevalence of 'severe' DDIs (any DDI vs. none) was calculated. Logistic regression was used to examine the association between sociodemographic, functional ability, and medication-related factors and the risk of DDI exposure between waves 1 and 2. RESULTS: A total of 1466 patients were included [mean age (standard deviation) = 78 (5.5) years; female n = 795, 54.2%]. In total, 332 community-dwellers aged ≥ 70 years [22.65%, 95% confidence interval (CI) 20.58-24.86] were potentially exposed to at least one 'severe' cardiovascular or CNS DDI, with more than half (54.82%) of this cohort dispensed the same DDI for a prolonged time (≥ 3 consecutive claims). Aspirin-warfarin was the most frequently dispensed (co-prescribed) DDI (n = 34, 10.24%, 95% CI 7.39-14.00), followed by atorvastatin-clarithromycin (n = 19, 5.72%, 95% CI 3.64-8.81). Polypharmacy [≥ 10 vs. < 5 drugs, odds ratio (OR) 13.40, 95% CI 8.22-21.85] and depression (depressed vs. not, OR 2.12, 95% CI 1.34-3.34) were significantly associated with these DDIs, after multivariable adjustment. CONCLUSION: 'Severe' cardiovascular and CNS DDIs are prevalent in older community-dwellers in Ireland, and those with polypharmacy and depression are at a significantly increased risk.
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Vida Independiente , Polifarmacia , Anciano , Estudios de Cohortes , Interacciones Farmacológicas , Femenino , Humanos , Estudios Longitudinales , Masculino , Prevalencia , Estudios ProspectivosRESUMEN
ZBTB2 is a protein belonging to the BTB/POZ zinc-finger family whose members typically contain a BTB/POZ domain at the N-terminus and several zinc-finger domains at the C-terminus. Studies have been carried out to disclose the role of ZBTB2 in cell proliferation, in human cancers and in regulating DNA methylation. Moreover, ZBTB2 has been also described as an ARF, p53 and p21 gene repressor as well as an activator of genes modulating pluripotency. In this scenario, ZBTB2 seems to play many functions likely associated with other proteins. Here we report a picture of the ZBTB2 protein partners in U87MG cell line, identified by high-resolution mass spectrometry (MS) that highlights the interplay between ZBTB2 and chromatin remodeling multiprotein complexes. In particular, our analysis reveals the presence, as ZBTB2 candidate interactors, of SMARCA5 and BAZ1B components of the chromatin remodeling complex WICH and PBRM1, a subunit of the SWI/SNF complex. Intriguingly, we identified all the subunits of the NuRD complex among the ZBTB2 interactors. By co-immunoprecipitation experiments and ChIP-seq analysis we definitely identify ZBTB2 as a new partner of the NuRD complex.
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Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Adenosina Trifosfatasas/metabolismo , Línea Celular Tumoral , Cromatina/genética , Proteínas Cromosómicas no Histona/metabolismo , ADN/genética , Metilación de ADN , Proteínas de Unión al ADN/metabolismo , Glioblastoma/metabolismo , Humanos , Inmunoprecipitación/métodos , Espectrometría de Masas/métodos , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/genética , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2/fisiología , Proteínas Nucleares/genética , Nucleosomas/genética , Unión Proteica/genética , Proteínas Represoras/fisiología , Factores de Transcripción/metabolismo , Dedos de Zinc/fisiologíaRESUMEN
The transcription factor CCCTC-binding factor (CTCF) modulates pleiotropic functions mostly related to gene expression regulation. The role of CTCF in large scale genome organization is also well established. A unifying model to explain relationships among many CTCF-mediated activities involves direct or indirect interactions with numerous protein cofactors recruited to specific binding sites. The co-association of CTCF with other architectural proteins such as cohesin, chromodomain helicases, and BRG1, further supports the interplay between master regulators of mammalian genome folding. Here, we report a comprehensive LC-MS/MS mapping of the components of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex co-associated with CTCF including subunits belonging to the core, signature, and ATPase modules. We further show that the localization patterns of representative SWI/SNF members significantly overlap with CTCF sites on transcriptionally active chromatin regions. Moreover, we provide evidence of a direct binding of the BRK-BRG1 domain to the zinc finger motifs 4-8 of CTCF, thus, suggesting that these domains mediate the interaction of CTCF with the SWI/SNF complex. These findings provide an updated view of the cooperative nature between CTCF and the SWI/SNF ATP-dependent chromatin remodeling complexes, an important step for understanding how these architectural proteins collaborate to shape the genome.
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Factor de Unión a CCCTC/genética , Ensamble y Desensamble de Cromatina/genética , Proteínas Cromosómicas no Histona/genética , ADN Helicasas/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética , Dedos de Zinc/genética , Adenosina Trifosfatasas/genética , Sitios de Unión/genética , Proteínas de Ciclo Celular/genética , Regulación de la Expresión Génica/genética , Genoma Humano/genética , Humanos , Complejos Multiproteicos/genética , Mapas de Interacción de Proteínas/genética , Espectrometría de Masas en Tándem , CohesinasRESUMEN
BACKGROUND: Studies have emphasized the importance of geographical factors and general practitioner (GP) characteristics in influencing drug prescriptions. OBJECTIVES: To: (i) ascertain the prevalence rate (PR) of use of drugs in six therapeutic categories used for chronic conditions; (ii) assess how geographical characteristics and GP characteristics may influence drug prescribing. METHODS: This study is part of the EDU.RE.DRUG Project, a national collaborative project founded by Italian Medicine Agency (AIFA). Cross-sectional analyses were undertaken employing the pharmacy-claim databases of four local health units (LHUs) located in two Italian regions: Lombardy and Campania. Six drug categories were evaluated: proton-pump inhibitors; antibiotics; respiratory-system drugs; statins; agents acting on the renin-angiotensin system; psychoanaleptic drugs. The PR was estimated according to drug categories at the LHU level. A linear multivariate regression analysis was undertaken to evaluate the association between the PR and geographical area, age and sex of GPs, number of patients, and percentage of patients aged >65 per GP. RESULTS: LHUs in Campania showed a PR that was significantly higher than that in Lombardy. Antibiotics showed the highest PR in all the LHUs assessed, ranging from 32.5% in Lecco (Lombardy) to 59.7% in Naples-2 (Campania). Multivariate linear regression analysis confirmed the association of the PR with geographical area for all drug categories. Being located in Campania increased the possibility of receiving a drug prescription from the categories considered, with estimates more marked for antibiotics, proton-pump-inhibitors, and respiratory-system drugs. CONCLUSIONS: This study provides information about the PR of medications used for treating common and costly conditions in Italy and highlighted a significant geographical variation. These insights could help to develop area-specific strategies to optimize prescribing behavior.
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The protein MucR from Brucella abortus has been described as a transcriptional regulator of many virulence genes. It is a member of the Ros/MucR family comprising proteins that control the expression of genes important for the successful interaction of α-proteobacteria with their eukaryotic hosts. Despite clear evidence of the role of MucR in repressing virulence genes, no study has been carried out so far demonstrating the direct interaction of this protein with the promoter of its target gene babR encoding a LuxR-like regulator repressing virB genes. In this study, we show for the first time the ability of MucR to bind the promoter of babR in electrophoretic mobility shift assays demonstrating a direct role of MucR in repressing this gene. Furthermore, we demonstrate that MucR can bind the virB gene promoter. Analyses by RT-qPCR showed no significant differences in the expression level of virB genes in Brucella abortus CC092 lacking MucR compared to the wild-type Brucella abortus strain, indicating that MucR binding to the virB promoter has little impact on virB gene expression in B. abortus 2308. The MucR modality to bind the two promoters analyzed supports our previous hypothesis that this is a histone-like protein never found before in Brucella.
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Proteínas Bacterianas/genética , Brucella abortus/genética , Regiones Promotoras Genéticas , Factores de Transcripción/genética , Factores de Virulencia/genética , Proteínas Bacterianas/metabolismo , Brucella abortus/metabolismo , Regulación Bacteriana de la Expresión Génica , Unión Proteica , Factores de Transcripción/metabolismo , Factores de Virulencia/metabolismoRESUMEN
PURPOSE: The purpose was to analyze drug prescription and antibiotic use by age and sex in Italy's Campania Region, and to estimate the distribution of prescription rates in children (≤14 years old), adults (between 15 and 65 years old), and older adults (≥65 years old) at a municipality level. METHODS: This was a retrospective analysis of pharmacy records in Campania (Southern Italy), in 2016. Difference in antibiotic prescriptions in different age groups was assessed by prevalence rates. Age-adjusted prevalence rates were categorized into quintiles and mapped by the patient's municipality of residence. Relationship between prevalence rates for the different age groups was estimated using the non-parametric Spearman rank correlation test. RESULTS: There were 2,738,118 were patients with at least one antibiotic prescription. Antibiotics prescription was higher in children aged <5 years and in the older adults aged >70 years. Prevalence rate distribution was different among municipalities in all age groups. A positive correlation between the rank distribution of prevalence rates at municipality level was identified for children and adults (rs=0.56; P<0.01), adults and the older adults (rs=0.79; P<0.01), and children and the older adults (rs=0.46; P<0.01). Among the studied age groups, the most prescribed antibiotic class was penicillin (except the older adults aged ≥85 years) ranging from 45% in children to 27.2% in the older adults. Fluoroquinolones were the least prescribed antibiotic class, ranging from 0.2% in children to 30.2% in the older adults. CONCLUSION: A considerably high use of antibiotic drugs has been detected in Campania Region, with values exceeding the regional and national average. Prescriptions at municipal level differ from one age group to another. Antibiotic use is often unjustified, and to decrease the number of prescriptions and improve their appropriateness, several measures at territorial level are recommended.
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Background: Antihypertensive drugs play a crucial role in reducing cardiovascular morbidity and mortality. Variability in prescribing patterns constitutes a major challenge for current healthcare systems. This study aimed to compare patterns of use of antihypertensives in general practice in two southern European populations. Methods: Observational study. Data on antihypertensive drugs consumption in primary care setting (2016) were obtained from pharmacy refill records in Campania (Italy) and Aragon (Spain). Prescribing rates and the number of defined daily doses [DDD/1,000 inhabitants/day (DID)] were calculated, and the Drug Utilization 90% (DU90%) approach used to reveal differences in prescribing patterns in both regions. Results: Antihypertensive prescribing rates in Campania and Aragon were 250.8 (95%CI: 250.2-251.3) and 201.7 (95%CI: 200.9-202.5) users/1,000 inhabitants/year. Overall consumption was of 310.1 and 256.8 DID, respectively. Spanish users, especially women and the elderly, consumed a greater volume of diuretics. Conversely, other therapeutic subgroups were more consumed in Campania. However, the most prescribed subgroups accounted for comparable proportions of the total consumption in each region. Conclusions: Both prescribing rates and intensity of antihypertensive use were higher in Campania. Pharmacy refill records in cross-country comparisons allow to know the factors influencing variability in prescribing habits with a view to improving prescribing quality.
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Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Atención Primaria de Salud/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/normas , EspañaRESUMEN
PURPOSE: The aim of this study was to analyze the geographic variation in systemic antibiotic prescription at a regional level and to explore the influence of socioeconomic and sociodemographic variables. METHODS: This study was a retrospective analysis of reimbursement pharmacy records in the outpatient settings of Italy's Campania Region in 2016. Standardized antibiotic prescription rates were calculated at municipality and Local Health Unit (LHU) level. Antibiotic consumption was analyzed as defined daily doses (DDD)/1000 inhabitants per day (DID). Logistic regression was performed to evaluate the association between antibiotic prescription and sociodemographic and socioeconomic determinants at a municipality level. RESULTS: The average antibiotic prevalence rate was 46.8%. At LHU level, the age-adjusted prevalence rates ranged from 41.1% in Benevento to 51.0% in Naples2. Significant differences were found among municipalities, from 15.2% in Omignano (Salerno LHU [Sa-LHU]) to 61.9% in Moschiano (Avellino [Av-LHU]). The geographic distribution also showed significant differences in terms of antibiotic consumption, from 6.7 DID in Omignano to 41.6 in San Marcelino (Caserta [Ce-LHU]). Logistic regression showed that both municipality type and average annual income level were the main determinants of antibiotic prescription. Urban municipalities were more than eight times as likely to have antibiotic high prevalence rates compared to rural municipalities (adjusted odds ratio [OR]: 8.62; 95% confidence interval [CI]: 4.06-18.30, P<0.001). Low average annual income level municipalities were more than eight times as likely to have antibiotic high prevalence rates compared to high average annual income level municipalities (adjusted OR: 8.48; 95% CI: 3.45-20.81, P<0.001). CONCLUSION: We provide a snapshot of Campania's antibiotic consumption, evidencing the impact of both socioeconomic and sociodemographic factors on the prevalence of antibiotic prescription. The observed intraregional variability underlines the lack of shared therapeutic protocols and the need for careful monitoring. Our results can be useful for decision makers to plan educational interventions, thus optimizing health resources and improving rational drug use.
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PURPOSE: The aim was to describe the current use of biological therapies among patients affected by psoriasis and to analyze a drug utilization profile in naïve patients in terms of switching and treatment costs in a Local Health Unit (LHU) of Southern Italy. METHODS: We conducted an observational retrospective cohort analysis using the health-related administrative databases of a LHU in Southern Italy covering a population of about one million inhabitants. All subjects with a main or secondary diagnosis of psoriasis who received at least one prescription of biological therapies between January 1, 2010 and December 31, 2014 were analyzed. Switching rate was evaluated in naïve patients within the first year of treatment. Drug cost was calculated for all drugs prescribed and comprised both costs for psoriasis drugs and costs for other treatments. RESULTS: About 20% of patients identified with a diagnosis of psoriasis were under treatment with biological drugs. Among 385 subjects treated with biological therapy, 51.2% were in treatment with etanercept and 33% with adalimumab. Among naïve patients, switching rate to a different biological drug, within the first year of treatment, was 7.3%. The per patient yearly drug cost was 10,536: 96.8% for psoriasis-related drugs and 3.2% for other pharmaceutical treatments. The annual average cost per patient switching from the initial treatment was 13,021, while for those who did not switch from the initial treatment, the annual average cost was 10,342, with a significant difference of about 2,680 per patient per year (p=0.002). CONCLUSION: Our data may be useful in exploring the dynamics that characterize the use of biological therapy within a specific context and to optimize the use of resources for a better management of the disease.
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OBJECTIVES: The objective of this study was to investigate the prognostic role of quantitative reduction of congestion during hospitalization assessed by Bioelectrical Impedance Vector Analysis (BIVA) serial evaluations in patients admitted for acute heart failure (AHF). BACKGROUND: AHF is a frequent reason for patients to be admitted. Exacerbation of chronic heart failure is linked with a progressive worsening of the disease with increased incidence of death. Fluid overload is the main mechanism underlying acute decompensation in these patients. BIVA is a validated technique able to quantify fluid overload. METHODS: a prospective, multicentre, observational study in AHF and no AHF patients in three Emergency Departments centres in Italy. Clinical data and BIVA evaluations were performed at admission (t0) and discharge (tdis). A follow-up phone call was carried out at 90 days. RESULTS: Three hundred and thirty-six patients were enrolled (221 AHF and 115 no AHF patients). We found that clinical signs showed the most powerful prognostic relevance. In particular the presence of rales and lower limb oedema at tdis were linked with events relapse at 90 days. At t0, congestion detected by BIVA was observed only in the AHF group, and significantly decreased at tdis. An increase of resistance variation (dR/H) >11 Ω/m during hospitalization was associated with survival. BIVA showed significant results in predicting total events, both at t0 (area under the curve (AUC) 0.56, p<0.04) and at tdis (AUC 0.57, p<0.03). When combined with clinical signs, BIVA showed a very good predictive value for cardiovascular events at 90 days (AUC 0.97, p<0.0001). CONCLUSIONS: In AHF patients, an accurate physical examination evaluating the presence of rales and lower limbs oedema remains the cornerstone in the management of patients with AHF. A congestion reduction, obtained as a consequence of therapies and detected through BIVA analysis, with an increase of dR/H >11 Ω/m during hospitalization seems to be associated with increased 90 day survival in patients admitted for AHF.
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Impedancia Eléctrica , Insuficiencia Cardíaca/diagnóstico , Hospitalización/estadística & datos numéricos , Alta del Paciente/estadística & datos numéricos , Pronóstico , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Disnea/diagnóstico , Edema Cardíaco/complicaciones , Edema Cardíaco/diagnóstico , Servicio de Urgencia en Hospital , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Italia/epidemiología , Extremidad Inferior/patología , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recurrencia , Ruidos Respiratorios/diagnósticoRESUMEN
During the recent years, immigration in Italy has increased. There are few data on the health status of immigrants and there is a need to improve their healthcare. Cardiovascular disorders account for 7.6% of immigrants' diseases and cause 3.6% of the total deaths. Lack of healthcare services to general medicine support and prescriptions leads immigrants to contact the Emergency Department (ED) to receive medical assistance. Primary endpoints of this study were to assess the use of national healthcare system by immigrants and to determine the incidence of cardiovascular diseases, and the frequency and type of risk factors for cardiovascular diseases in these patients. A no-profit, observational, multicentre study was conducted from April to September 2012. We studied 642 foreign patients referring to the ED for various symptoms/signs. One hundred and fourteen patients referred for suspected cardiovascular disease and 105 had a confirmed final diagnosis of cardiovascular disease. The more represented ethnic origin was Caucasian (59%), whereas the most represented country was Romania (24%). The main symptom recorded at ED arrival was chest pain (37.1%). Final cardiovascular diagnoses were represented by: hypertensive crisis (28.5%), acute coronary syndrome (20%), acute heart failure (12.3%), atrial fibrillation (10.4%) and chest pain (10.4%). Past medical history of cardiovascular disease, hypertension, obesity and male sex showed independent significant predictive value for cardiovascular disease diagnosis.Our study provides support for the development of specific primary prevention of cardiovascular risk factors in immigrants with the important role of culturally competent education of individuals and families. Better outpatient management seems to be needed in order to limit the need for emergency room referral.
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Enfermedades Cardiovasculares/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Emigrantes e Inmigrantes/estadística & datos numéricos , Programas Nacionales de Salud/estadística & datos numéricos , Adulto , Anciano , Femenino , Humanos , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Heart failure is a disease characterized by high prevalence and mortality, and frequent rehospitalizations. The aim of this study is to investigate the prognostic power of combining brain natriuretic peptide (BNP) and congestion status detected by bioelectrical impedance vector analysis (BIVA) in acute heart failure patients. This is an observational, prospective, and a multicentre study. BNP assessment was measured upon hospital arrival, while BIVA analysis was obtained at the time of discharge. Cardiovascular deaths were evaluated at 90 days by a follow up phone call. 292 patients were enrolled. Compared to survivors, BNP was higher in the non-survivors group (mean value 838 vs 515 pg/ml, p < 0.001). At discharge, BIVA shows a statistically significant difference in hydration status between survivors and non-survivors [respectively, hydration index (HI) 85 vs 74, p < 0.001; reactance (Xc) 26.7 vs 37, p < 0.001; resistance (R) 445 vs 503, p < 0.01)]. Discharge BIVA shows a prognostic value in predicting cardiovascular death [HI: area under the curve (AUC) 0.715, 95% confidence interval (95% CI) 0.65-0.76; p < 0.004; Xc: AUC 0.712, 95% CI 0.655-0.76, p < 0.007; R: AUC 0.65, 95% CI 0.29-0.706, p < 0.0247]. The combination of BIVA with BNP gives a greater prognostic power for cardiovascular mortality [combined receiving operating characteristic (ROC): AUC 0.74; 95% CI 0.68-0.79; p < 0.001]. In acute heart failure patients, higher BNP levels upon hospital admission, and congestion detected by BIVA at discharge have a significant predictive value for 90 days cardiovascular mortality. The combined use of admission BNP and BIVA discharge seems to be a useful tool for increasing prognostic power in these patients.
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Impedancia Eléctrica/uso terapéutico , Insuficiencia Cardíaca/mortalidad , Péptido Natriurético Encefálico/análisis , Alta del Paciente/estadística & datos numéricos , Pronóstico , Anciano , Anciano de 80 o más Años , Brasil , Disnea/etiología , Servicio de Urgencia en Hospital/organización & administración , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Péptido Natriurético Encefálico/sangre , Estudios Prospectivos , Ciudad de Roma , Análisis de SupervivenciaRESUMEN
BACKGROUND: High-sensitivity cardiac troponin I (hs-cTnI) and the soluble isoform of suppression of tumorigenicity 2 (sST2) are useful prognostic biomarkers in acute coronary syndrome (ACS). The aim of this study was to test the short term prognostic value of sST2 compared with hs-cTnI in patients with chest pain. METHODS: Assays for hs-cTnI and sST2 were performed in 157 patients admitted to the Emergency Department (ED) for chest pain at arrival. In-hospital and 30-day follow-up mortalities were assessed. RESULTS: The incidence of ACS was 37%; 33 patients were diagnosed with ST elevation myocardial infarction (STEMI), and 25 were diagnosed with non-ST elevation myocardial infarction (NSTEMI). Compared with the no acute coronary syndrome (NO ACS) group, the median level of hs-cTnI was higher in ACS patients: 7.22 (5.24-14) pg/mL vs 68 (15.33-163.50) pg/mL (P<0.0001). In all patients, the sST2 level at arrival showed higher independent predictive power than hs-cTnI (odds ratio [OR] 20.13, P<0.0001 and OR 2.61, P<0.0008, respectively). sST2 at ED arrival showed a greater prognostic value for cardiovascular events in STEMI (area under the curve [AUC] 0.80, P<0.001) than NSTEMI patients (AUC 0.72, P<0.05). Overall, 51% of the STEMI patients with an sST2 value>35 ng/mL at ED arrival died during the 30-day follow-up. CONCLUSIONS: sST2 has a greater prognostic value for 30-day cardiac mortality after discharge in patients presenting to the ED for chest pain compared with hs-cTnI. In STEMI patients, an sST2 value >35 ng/mL at ED arrival showed the highest predictive power for short-term mortality.
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Síndrome Coronario Agudo/mortalidad , Proteína 1 Similar al Receptor de Interleucina-1/análisis , Troponina I/análisis , Síndrome Coronario Agudo/diagnóstico , Anciano , Área Bajo la Curva , Biomarcadores/análisis , Dolor en el Pecho , Servicio de Urgencia en Hospital , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Curva ROCRESUMEN
BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, painful, inflammatory disorder of hair follicles and manifests with several cutaneous findings, including double comedones, papules, cysts, nodules, draining abscesses, and sinus tracts. It is associated with tremendous morbidity and decreased quality of life. Treatment of HS is challenging. Recently, there have been mixed reports regarding the efficacy of anakinra, an interleukin 1 receptor antagonist, in the management of HS.
CASE: A 55-year-old African American male with a several year history of severe HS, recalcitrant to multiple prior treatments, was treated with a 12 week course of anakinra 100 mg subcutaneously daily. After 3 months of therapy, minimal change was observed, and the patient strongly preferred to cease therapy due to lack of improvement and pain associated with daily injections.
CONCLUSION: Our case of severe HS proved refractory to anakinra. Tolerance of this therapy may be a limiting factor for some patients due to necessity for daily injections.
J Drugs Dermatol. 2016;15(6):772-774.