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BACKGROUND: Protection provided by seasonal influenza vaccination (SIV) may be measured against numerous outcomes, and their heterogeneity may hamper decision-making. The aim of this study was to explore outcomes used for estimation of SIV efficacy/effectiveness (VE) and obtain expert consensus on their importance. RESEARCH DESIGN AND METHODS: An umbrella review was first conducted to collect and map outcomes considered in systematic reviews of SIV VE. A Delphi study was then performed to reach expert convergence on the importance of single outcomes, measured on a 9-point Likert scale, in principal target groups, namely children, working-age adults, older adults, subjects with co-morbidities and pregnant women. RESULTS: The literature review identified 489 outcomes. Following data reduction, 20 outcomes were selected for the Delphi process. After two Delphi rounds and a final consensus meeting, convergence was reached. All 20 outcomes were judged to be important or critically important. More severe outcomes, such as influenza-related hospital encounters and mortality with or without laboratory confirmation, were generally top-ranked across all target groups (median scores ≥8 out of 9). CONCLUSIONS: Rather than focusing on laboratory-confirmed infection per se, experimental and observational VE studies should include more severe influenza-related outcomes because they are expected to exercise a greater impact on decision-making.
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Técnica Delphi , Vacunas contra la Influenza , Gripe Humana , Eficacia de las Vacunas , Humanos , Gripe Humana/prevención & control , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Femenino , Embarazo , Vacunación/métodos , Estaciones del Año , Adulto , Toma de Decisiones , NiñoRESUMEN
OBJECTIVE: The R.Evolution project aimed to reach a consensus on the main challenges of conducting clinical research in Italy and possible strategies and approaches to address them and optimize clinical research management. METHODS: A scientific board of experts initially discussed potentially critical areas in clinical research conduct and further explored them through an online national survey. The survey results were further examined by a group of 35 panelists representing different clinical research stakeholders. A Nominal Group Technique and a Delphi approach (two rounds) were used to generate a consensus on critical factors, tools and strategies in clinical research. RESULTS: Four main critical areas were identified: study feasibility, authorization procedures, operational aspects and patient management. The main issues are scarce awareness of the value of clinical research, lack of trained workforce and excessive complexity of protocols and administrative procedures. The Delphi panel identified six intervention areas: culture and patient involvement; procedures; staff, contracts, training and incentives; organization and infrastructure; administrative procedures; and ethics committee. CONCLUSION: According to the R.Evolution project, possible strategies to improve clinical research management in Italy include a deeper understanding of the value of clinical research, the creation of long-term plans for hiring, training, organizing and motivating clinical trial staff, the simplification and harmonization of administrative procedures, as well as protocol design, and the development of stronger networks of centers and stakeholders.
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Consenso , Técnica Delphi , Humanos , ItaliaRESUMEN
BACKGROUND: The COVID-19 pandemic affected healthcare systems worldwide. Predictive models developed by Artificial Intelligence (AI) and based on timely, centralized and standardized real world patient data could improve management of COVID-19 to achieve better clinical outcomes. The objectives of this manuscript are to describe the structure and technologies used to construct a COVID-19 Data Mart architecture and to present how a large hospital has tackled the challenge of supporting daily management of COVID-19 pandemic emergency, by creating a strong retrospective knowledge base, a real time environment and integrated information dashboard for daily practice and early identification of critical condition at patient level. This framework is also used as an informative, continuously enriched data lake, which is a base for several on-going predictive studies. METHODS: The information technology framework for clinical practice and research was described. It was developed using SAS Institute software analytics tool and SAS® Vyia® environment and Open-Source environment R ® and Python ® for fast prototyping and modeling. The included variables and the source extraction procedures were presented. RESULTS: The Data Mart covers a retrospective cohort of 5528 patients with SARS-CoV-2 infection. People who died were older, had more comorbidities, reported more frequently dyspnea at onset, had higher d-dimer, C-reactive protein and urea nitrogen. The dashboard was developed to support the management of COVID-19 patients at three levels: hospital, single ward and individual care level. INTERPRETATION: The COVID-19 Data Mart based on integration of a large collection of clinical data and an AI-based integrated framework has been developed, based on a set of automated procedures for data mining and retrieval, transformation and integration, and has been embedded in the clinical practice to help managing daily care. Benefits from the availability of a Data Mart include the opportunity to build predictive models with a machine learning approach to identify undescribed clinical phenotypes and to foster hospital networks. A real-time updated dashboard built from the Data Mart may represent a valid tool for a better knowledge of epidemiological and clinical features of COVID-19, especially when multiple waves are observed, as well as for epidemic and pandemic events of the same nature (e. g. with critical clinical conditions leading to severe pulmonary inflammation). Therefore, we believe the approach presented in this paper may find several applications in comparable situations even at region or state levels. Finally, models predicting the course of future waves or new pandemics could largely benefit from network of DataMarts.
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COVID-19 , Inteligencia Artificial , COVID-19/epidemiología , Toma de Decisiones Clínicas , Humanos , Pandemias , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic disease that is causing a public health emergency. Characteristics and clinical significance of myocardial injury remain unclear. METHODS: This retrospective single-center study analyzed 189 patients who received a COVID-19 diagnosis out of all 758 subjects with a high sensitive troponin I (Hs-TnI) measurement within the first 24 h of admission at the Policlinico A.Gemelli (Rome, Italy) between February 20th 2020 to April 09th 2020. RESULTS: The prevalence of myocardial injury in our COVID-19 population is of 16%. The patients with cardiac injury were older, had a greater number of cardiovascular comorbidities and higher values of acute phase and inflammatory markers and leucocytes. They required more frequently hospitalization in Intensive Care Unit (10 [32.3%] vs 18 [11.4%]; p = .003) and the mortality rate was significantly higher (17 [54.8%] vs. 15 [9.5%], p < .001). Among patients in ICU, the subjects with myocardial injury showed an increase need of endotracheal intubation (8 out of 9 [88%] vs 7 out of 19[37%], p = .042). Multivariate analyses showed that hs-TnI can significantly predict the degree of COVID-19 disease, the intubation need and in-hospital mortality. CONCLUSIONS: In this study we demonstrate that hs-Tn can significantly predict disease severity, intubation need and in-hospital death. Therefore, it may be reasonable to use Hs-Tn as a clinical tool in COVID-19 patients in order to triage them into different risk groups and can play a pivotal role in the detection of subjects at high risk of cardiac impairment during both the early and recovery stage.
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COVID-19 , Pandemias , Prueba de COVID-19 , Mortalidad Hospitalaria , Humanos , Italia/epidemiología , Prevalencia , Estudios Retrospectivos , Ciudad de Roma , SARS-CoV-2 , TroponinaRESUMEN
Enhanced platelet activation has been reported in patients with essential hypertension and heart failure. The possible contribution of platelet-derived thromboxane (TX)A2 in their pathophysiology remains unclear. We investigated the systemic TXA2 biosynthesis in vivo and gene expression of its receptor TP in 22 essential hypertension patients and a mouse model of salt-sensitive hypertension. The contribution of platelet TXA2 biosynthesis on enhanced blood pressure (BP) and overload-induced cardiac fibrosis was explored in mice by treating with low-dose Aspirin, resulting in selective inhibition of platelet cyclooxygenase (COX)-1-dependent TXA2 generation. In essential hypertensive patients, systemic biosynthesis of TXA2 [assessed by measuring its urinary metabolites (TXM) reflecting predominant platelet source] was enhanced together with higher gene expression of circulating leukocyte TP and TGF-ß, vs. normotensive controls. Similarly, in hypertensive mice with prostacyclin (PGI2) receptor (IP) deletion (IPKO) fed with a high-salt diet, enhanced urinary TXM, and left ventricular TP overexpression were detected vs. normotensive wildtype (WT) mice. Increased cardiac collagen deposition and profibrotic gene expression (including TGF-ß) was found. Low-dose Aspirin administration caused a selective inhibition of platelet TXA2 biosynthesis and mitigated enhanced blood pressure, cardiac fibrosis, and left ventricular profibrotic gene expression in IPKO but not WT mice. Moreover, the number of myofibroblasts and extravasated platelets in the heart was reduced. In cocultures of human platelets and myofibroblasts, platelet TXA2 induced profibrotic gene expression, including TGF-ß1. In conclusion, our results support tailoring low-dose Aspirin treatment in hypertensive patients with unconstrained TXA2/TP pathway to reduce blood pressure and prevent early cardiac fibrosis.
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Antifibróticos/farmacología , Antihipertensivos/farmacología , Aspirina/farmacología , Plaquetas/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Cardiomiopatías/prevención & control , Hipertensión Esencial/tratamiento farmacológico , Miocitos Cardíacos/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Tromboxano A2/sangre , Adulto , Animales , Biomarcadores/sangre , Plaquetas/metabolismo , Cardiomiopatías/sangre , Cardiomiopatías/etiología , Cardiomiopatías/patología , Estudios de Casos y Controles , Células Cultivadas , Modelos Animales de Enfermedad , Hipertensión Esencial/sangre , Hipertensión Esencial/complicaciones , Hipertensión Esencial/fisiopatología , Femenino , Fibrosis , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Miofibroblastos/patología , Receptores de Epoprostenol/genética , Receptores de Epoprostenol/metabolismo , Receptores de Tromboxanos/metabolismoRESUMEN
An 18-year-old man presented to our hospital with muscular pain, diffuse petechiae, spontaneous thigh ecchymosis, edema and pain of the right knee, bilateral pretibial subcutaneous nodules, and gingival hypertrophy and hemorrhage. His history was positive for a mixed anxiety-depressive disorder and a restrictive diet caused by self-diagnosed food allergies. Skin lesions appeared like hyperkeratotic papules with coiled hairs and perifollicular hemorrhages. A diagnosis of scurvy was made upon demonstration of low serum levels of ascorbic acid. An allergy evaluation found cross-reactivity between pollens and food, related to the presence of panallergens. Moreover, we found that our patient was also affected by celiac disease. In conclusion, scurvy should be considered in the differential diagnosis of patients with petechiae and ecchymosis, especially when food restriction, malabsorption, or psychiatric disorders are present.
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Escorbuto , Enfermedades de la Piel , Adolescente , Ácido Ascórbico , Diagnóstico Diferencial , Humanos , Masculino , Escorbuto/complicaciones , Escorbuto/diagnósticoRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease and ranges from simple steatosis to nonalcoholic steatohepatitis. Recently, a platelet role in NAFLD pathogenesis and progression has been reported in mouse models and in patients. We investigated whether platelets are involved in liver and systemic inflammation processes in NAFLD. In this exploratory study we recruited 24 consecutive patients with biopsy-proven diagnosis of NAFLD and 17 healthy volunteers. We measured plasma levels of inflammatory markers by ELISA. We investigated hemostatic and inflammatory transcripts in circulating platelets and leukocytes from NAFLD patients. We analyzed platelet and neutrophil extracellular traps (NET) accumulations in liver sinusoids using CD42 and H3 citrullinated histones immunohistochemical staining on liver biopsies. NAFLD patients had increased inflammation markers and lipolysaccharides plasma levels. We found significant increase of inflammatory transcripts in circulating platelets and not in leukocytes of NAFLD subjects compared with healthy controls. We demonstrated increased intrahepatic platelet accumulation that correlated with NAFLD activity score (NAS) score and intrahepatic neutrophil extracellular traps (NET) formation in liver biopsies of NAFLD patients. NET formation was higher in livers with higher NAS and inflammation scores. The presence of low-grade systemic inflammation and proinflammatory changes of circulating platelets indicate that platelets participate on systemic inflammatory changes associated with NAFLD. Liver platelet accumulation and liver NET formation, together with low-grade endotoxemia, suggest that platelets may act to protect the liver from invading microorganisms by favoring local NET formation.
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Plaquetas/fisiología , Inflamación/patología , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Adulto , Biomarcadores/sangre , Femenino , Regulación de la Expresión Génica , Hemostasis , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
The 2019 novel coronavirus [2019-nCoV], which started to spread from December 2019 onwards, caused a global pandemic. Besides being responsible for the severe acute respiratory syndrome 2 [SARS-CoV-2], the virus can affect other organs causing various symptoms. A close relationship between SARS-CoV-2 and the cardiovascular system has been shown, demonstrating an epidemiological linkage between SARS-CoV-2 and cardiac injury. There are emerging data regarding possible direct myocardial damage by 2019-nCoV. In this review, the most important available evidences will be discussed to clarify the precise mechanisms of cardiovascular injury in SARS-CoV-2 patients, even if further researches are needed.
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Enfermedades Cardiovasculares/etiología , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Animales , Betacoronavirus/inmunología , COVID-19 , Enfermedades Cardiovasculares/epidemiología , Infecciones por Coronavirus/inmunología , Humanos , Pandemias , Neumonía Viral/inmunología , SARS-CoV-2RESUMEN
BACKGROUND: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. METHODS: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. FINDINGS: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100-141.5)].Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%. INTERPRETATION: IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.
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BACKGROUND: Cardiovascular complications represent the major cause of morbidity and mortality of type 2 diabetes mellitus (T2DM) patients. In particular, peripheral artery disease (PAD) represents a frequent T2DM vascular complication and a risk factor for the development of major adverse cardiovascular events (MACE). Among adipokines, omentin-1 serum levels are reduced in T2DM patients with PAD and are inversely related to disease severity. OBJECTIVE: To study the relationship between omentin-1 levels, at baseline, with outcomes after endovascular procedures in T2DM patients with PAD and chronic limb-threatening ischemia (CLTI). RESEARCH DESIGN AND METHODS: We enrolled for our prospective non-randomized study, 207 T2DM patients with PAD and CLTI, requiring revascularization. Omentin-1 serum levels were collected before revascularization and patients incidence outcomes were evaluated at 1, 3, 6 and 12 months. RESULTS: Omentin-1 was reduced in patients with more severe disease (27.24 ± 4.83 vs 30.82 ± 5.48 ng/mL, p < 0.001). Overall, 84 MACE and 96 major adverse limb events (MALE) occurred during the 12-month follow-up. We observed that omentin-1 levels were lower in patients with MACE (26.02 ± 4.05 vs 31.33 ± 5.29 ng/mL, p < 0.001) and MALE (26.67 ± 4.21 vs 31.34 ± 5.54 ng/mL, p < 0.001). The association between omentin-1, MACE and MALE remained significant after adjusting for major risk factors in a multivariate analysis. Receiver operating characteristics (ROC) curve using omentin-1 levels predicted incidence events (area under the curve = 0.80). CONCLUSIONS: We demonstrated that reduced omentin-1 levels, at baseline, are related with worse vascular outcomes in T2DM patients with PAD and CLTI undergoing an endovascular procedure.
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Citocinas/sangre , Diabetes Mellitus Tipo 2/sangre , Procedimientos Endovasculares , Isquemia/terapia , Lectinas/sangre , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/terapia , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedad Crónica , Diabetes Mellitus Tipo 2/diagnóstico , Regulación hacia Abajo , Procedimientos Endovasculares/efectos adversos , Femenino , Proteínas Ligadas a GPI/sangre , Humanos , Isquemia/sangre , Isquemia/diagnóstico , Masculino , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/diagnóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: The primary objective is to demonstrate that COVID-19 convalescent plasma (CCP) prevents progression to severe pneumonia in elderly COVID-19 pneumonia patients with chronic comorbidities. Secondary objectives are to demonstrate that CCP decreases the viral load in nasopharyngeal swabs and increases the anti-SARS-CoV-2 antibody titre in recipients. TRIAL DESIGN: This is a randomized, open-label, parallel group, phase II/III study with a superiority framework. The trial starts with a screening phase II designed with two-tailed alpha=0.2. In case of positive results, the trial will proceed in a formally comparative phase III (alpha=0.05). PARTICIPANTS: Adult patients with confirmed or suspected COVID-19 who are at risk according to CDC definition are eligible. Inclusion criteria are all the following: age ≥ 65; pneumonia at CT scan; PaO2/FiO2 ≥300 mmHg; presence of one or more comorbidities; signed informed consent. Exclusion criteria are one of the following: age < 65; PaO2/FiO2 < 300 mmHg; pending cardiopulmonary arrest; refusal to blood product transfusions; severe IgA deficiency; any life-threatening comorbidity or any other medical condition which, in the opinion of the investigator, makes the patient unsuitable for inclusion. The trial is being conducted at three reference COVID-19 centres in the middle of Italy. INTERVENTION AND COMPARATOR: Intervention: COVID-19 Convalescent Plasma (CCP) in addition to standard therapy. Patients receive three doses (200 ml/day on 3 consecutive days) of ABO matched CCP. Comparator: Standard therapy MAIN OUTCOMES: A. Primary outcome for Phase II: Proportion of patients without progression in severity of pulmonary disease, defined as worsening of 2 points in the ordinal scale of WHO by day 14. B. Primary outcome for Phase III: Proportion of patients without progression in severity of pulmonary disease, defined as worsening of 2 points in the ordinal scale of WHO by day 14. Secondary outcomes for Phase III: Decreased viral load on nasopharyngeal swab at days 6, 9 and 14; Decreased viremia at days 6 and 9; Increased antibody titer against SARS-CoV2 at days 30 and 60; Proportion of patients with negative of SARS-CoV2 nasopharyngeal swab at day 30; Length of hospital stay; Mortality rate at day 28; Total plasma related adverse event (day 60); Total non-plasma related adverse events (day 60); Severe adverse events (SAE) (day 60). RANDOMISATION: Treatment allocation is randomized with a ratio 1:1 in both phase II and phase III. Randomization sequences will be generated at Fondazione Policlinico Gemelli IRCCS through the RedCap web application. Randomized stratification is performed according to age (under/over 80 years), and sex. BLINDING (MASKING): None, this is an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Phase II: 114 patients (57 per arm). Phase III: 182 patients (91 per arm) TRIAL STATUS: The trial recruitment started on May 27, 2020. The anticipated date of recruitment completion is April 30, 2021. The protocol version is 2 (May 10, 2020). TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov (May 5, 2020). The Identifier number is NCT04374526 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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Betacoronavirus/genética , Transfusión Sanguínea/métodos , Infecciones por Coronavirus/terapia , Neumonía Viral/terapia , Anciano , Anciano de 80 o más Años , Betacoronavirus/inmunología , COVID-19 , Comorbilidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Progresión de la Enfermedad , Femenino , Humanos , Inmunización Pasiva/efectos adversos , Inmunización Pasiva/métodos , Consentimiento Informado/ética , Italia/epidemiología , Masculino , Mortalidad/tendencias , Pandemias , Neumonía/diagnóstico por imagen , Neumonía/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/virología , SARS-CoV-2 , Tomografía Computarizada por Rayos X/métodos , Carga Viral/inmunología , Carga Viral/estadística & datos numéricos , Sueroterapia para COVID-19RESUMEN
BACKGROUND: Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients. OBJECTIVE: To evaluate the relationship between baseline serum levels of sortilin, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI). RESEARCH DESIGN AND METHODS: We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin levels were measured before the endovascular intervention and incident outcomes were assessed during a 12 month follow-up. RESULTS: Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using sortilin levels the prediction of MACE incidence improved (area under the curve [AUC] = 0.94) and MALE (AUC = 0.72). CONCLUSIONS: This study demonstrates that sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.
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Proteínas Adaptadoras del Transporte Vesicular/sangre , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/cirugía , Isquemia/epidemiología , Infarto del Miocardio/epidemiología , Enfermedad Arterial Periférica/cirugía , Accidente Cerebrovascular/epidemiología , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica/estadística & datos numéricos , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/etiología , Procedimientos Endovasculares , Femenino , Humanos , Incidencia , Isquemia/cirugía , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/etiología , Pronóstico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Purpose: In heart failure with reduced ejection fraction, catabolic mechanisms have a strong negative impact on mortality and morbidity. The relationship between anabolic hormonal deficiency and heart failure with preserved ejection fraction (HFpEF) has still been poorly investigated. On the other hand, oxidative stress is recognized as a player in the pathogenesis of HFpEF. Therefore, we performed a cohort study in HFpEF aimed to (1) define the multi-hormonal deficiency prevalence in HFpEF patients; (2) investigate the relationships between hormonal deficiencies and echocardiographic indexes; (3) explore the modulatory activity of anabolic hormones on antioxidant systems. Methods: 84 patients with diagnosis of HFpEF were enrolled in the study. Plasma levels of N-terminal pro-brain natriuretic peptide, fasting glucose, insulin, lipid pattern, insulin-like growth factor-1, dehydroepiandrosterone-sulfate (DHEA-S), total testosterone (T, only in male subjects) were evaluated. Hormonal deficiencies were defined according to T.O.S.C.A. multi-centric study, as previously published. An echocardiographic evaluation was performed. Plasma total antioxidant capacity (TAC) was measured using the system metmyoglobin -H2O2 and the chromogen ABTS, whose radical form is spectroscopically revealed; latency time (LAG) in the appearance of ABTS⢠is proportional to antioxidants in sample. Results: Multiple deficiencies were discovered. DHEA-S deficiency in 87% of patients, IGF-1 in 67% of patients, T in 42%. Patients with DHEA-S deficiency showed lower levels of TAC expressed by LAG (mean ± SEM 91.25 ± 9.34 vs. 75.22 ± 4.38 s; p < 0.05). No differences between TAC in patients with or without IGF-1 deficiency were found. A trend toward high level of TAC in patients without hormonal deficiencies compared with patients with one or multiple deficiencies was found. Regarding echocardiographic parameters, Left Atrial and Left Atrial Volume Index were significantly higher in patients with low IGF-1 values (mean ± SD 90.84 ± 3.86 vs. 72.83 ± 3.78 mL; 51.03 ± 2.33 vs. 40.56 ± 2.46 mL/m2, respectively; p < 0.05). Conclusions: Our study showed high prevalence of anabolic deficiencies in HFpEF. DHEA-S seems to influence antioxidant levels; IGF-1 deficiency was associated with alteration in parameters of myocardial structure and dysfunction. These data suggest a role of anabolic hormones in the complex pathophysiological mechanisms of HFpEF and could represent the basis for longitudinal studies and investigations on possible benefits of replacement therapy.
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Antioxidantes/metabolismo , Cardiomiopatías/epidemiología , Insuficiencia Cardíaca/fisiopatología , Factor I del Crecimiento Similar a la Insulina/deficiencia , Volumen Sistólico , Testosterona/deficiencia , Disfunción Ventricular Izquierda/epidemiología , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Disfunción Ventricular Izquierda/metabolismo , Disfunción Ventricular Izquierda/patologíaRESUMEN
Experimental and clinical studies aimed at investigating the mechanism(s) underlying vascular complications of diabetes indicate that a great number of molecules are involved in the pathogenesis of these complications. Most of these molecules are inflammatory mediators or markers generated by immune or adipose tissue. Some of them, i.e. resistin and sortilin, have been shown to be involved in the cross talk between adipocytes and inflammatory cells. This interaction is an attractive area of research, particularly in type 2 diabetes and obesity. Other proteins, such as adiponectin and visfatin, appear to be more promising as possible vascular markers. In addition, some molecules involved in calcium/phosphorus metabolism, such as klotho and FGF23, have an involvement in the pathogenesis of diabetic vasculopathy, which appears to be dependent on the degree of vascular impairment. Inflammatory markers are a promising tool for treatment decisions while measuring plasma levels of adipokines, sortilin, Klotho and FGF23 in adequately sized longitudinal studies is expected to allow a more precise characterization of diabetic vascular disease and the optimal use of personalized treatment strategies.
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Tejido Adiposo/inmunología , Biomarcadores/análisis , Enfermedades Cardiovasculares/diagnóstico , Sistema Inmunológico/inmunología , Transducción de Señal/inmunología , Proteínas Adaptadoras del Transporte Vesicular/análisis , Proteínas Adaptadoras del Transporte Vesicular/sangre , Proteínas Adaptadoras del Transporte Vesicular/inmunología , Adipoquinas/análisis , Adipoquinas/sangre , Adipoquinas/inmunología , Tejido Adiposo/fisiopatología , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Proteína C-Reactiva/inmunología , Enfermedades Cardiovasculares/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Exosomas/inmunología , Factor-23 de Crecimiento de Fibroblastos , Glucuronidasa/análisis , Glucuronidasa/sangre , Glucuronidasa/inmunología , Proteínas HMGB/análisis , Proteínas HMGB/sangre , Proteínas HMGB/inmunología , Humanos , Sistema Inmunológico/fisiopatología , Interleucina-1/análisis , Interleucina-1/sangre , Interleucina-1/inmunología , Proteínas Klotho , Osteoprotegerina/análisis , Osteoprotegerina/sangre , Osteoprotegerina/inmunología , Prevalencia , Componente Amiloide P Sérico/análisis , Componente Amiloide P Sérico/inmunología , Transducción de Señal/fisiología , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/inmunologíaAsunto(s)
Fibrilación Atrial , Estudios de Casos y Controles , Hospitales , Humanos , Medicina Interna , Factores de RiesgoRESUMEN
Diabetes mellitus (DM) is an endemic disease, with growing health and social costs. The complications of diabetes can affect potentially all parts of the human body, from the heart to the kidneys, peripheral and central nervous system, and the vascular bed. Although many mechanisms have been studied, not all players responsible for these complications have been defined yet. High Mobility Group Box-1 (HMGB1) is a non-histone nuclear protein that has been implicated in many pathological processes, from sepsis to ischemia. The purpose of this review is to take stock of all the most recent data available on the role of HMGB1 in the complications of DM.
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Complicaciones de la Diabetes/metabolismo , Proteína HMGB1/metabolismo , Animales , Humanos , Modelos BiológicosAsunto(s)
Albinismo/tratamiento farmacológico , Enfermedades Autoinmunes/tratamiento farmacológico , Trastornos Hemorrágicos/tratamiento farmacológico , Síndrome de Hermanski-Pudlak/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Rituximab/uso terapéutico , Trombastenia/tratamiento farmacológico , Adulto , Anciano , Albinismo/sangre , Enfermedades Autoinmunes/sangre , Femenino , Trastornos Hemorrágicos/sangre , Síndrome de Hermanski-Pudlak/sangre , Humanos , Masculino , Recuento de Plaquetas , Trombastenia/sangreRESUMEN
OBJECTIVE: Peripheral artery disease (PAD) is one of the most relevant complications of diabetes. Although several pharmacological and revascularization approaches are available for treating patients with diabetes and PAD, an endovascular approach is often associated with postprocedural complications that can increase the risk for acute limb ischemia or amputation. However, no definitive molecular associations have been described that could explain the difference in outcomes after endovascular treatment in patients with diabetes, PAD, and chronic limb-threatening ischemia (CLTI). RESEARCH DESIGN AND METHODS: We evaluated the relationship between the levels of the main cytokines associated with diabetic atherosclerosis and the outcomes after endovascular procedures in patients with diabetes, PAD, and CLTI. RESULTS: A total of 299 patients with below-the-knee occlusive disease who were undergoing an angioplasty procedure were enrolled. The levels of key cytokines-osteoprotegerin (OPG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP)-were measured, and major adverse limb events (MALE) and major adverse cardiovascular events (MACE) were assessed 1, 3, 6, and 12 months after the procedure. There was a linear trend from the lowest to the highest quartile for each cytokine at baseline and incident MALE. A linear association was also observed between increasing levels of each cytokine and incident MACE. Receiver operating characteristics models were constructed using clinical and laboratory risk factors, and the inclusion of cytokines significantly improved the prediction of incident events. CONCLUSIONS: We demonstrated that elevated OPG, TNF-α, IL-6, and CRP levels at baseline correlate with worse vascular outcomes in patients with diabetes, PAD, and CLTI undergoing an endovascular procedure.
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Citocinas/sangre , Diabetes Mellitus , Angiopatías Diabéticas/cirugía , Procedimientos Endovasculares , Mediadores de Inflamación/sangre , Extremidad Inferior/cirugía , Enfermedad Arterial Periférica/cirugía , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica/estadística & datos numéricos , Aterosclerosis/etiología , Aterosclerosis/fisiopatología , Aterosclerosis/cirugía , Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología , Diabetes Mellitus/fisiopatología , Diabetes Mellitus/cirugía , Angiopatías Diabéticas/fisiopatología , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Isquemia/sangre , Isquemia/epidemiología , Isquemia/cirugía , Recuperación del Miembro/efectos adversos , Recuperación del Miembro/métodos , Extremidad Inferior/irrigación sanguínea , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/epidemiología , Enfermedad Arterial Periférica/fisiopatología , Estudios Prospectivos , Factores de Riesgo , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
Vascular complications of diabetes mellitus represent a major public health problem. Although many steps forward have been made to define the causes and to find the best possible therapies, the problem remains crucial. In recent years, more and more evidences have defined a link between microbiota and the initiation, promotion, and evolution of atherosclerotic disease, even in the diabetic scenario. There is an urgency to develop the knowledge of modern medicine about the link between gut microbiota and its host's metabolic pathways, and it would be useful to understand and justify the interindividual diversity of clinical disease presentation of diabetic vascular complication even if an optimization of pharmacological treatment has been made or in the case of young patients where hypertension, dyslipidemia, and diabetes are not able to justify a very quick progress of atherosclerotic process. The aim of the present review is to gather all the best available evidence in this regard and to define a new role of the microbiota in this field, from biomarker to possible therapeutic target.