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BACKGROUND: Non-medical use of prescription medications has risen to unprecedented levels over the past decade worldwide; however, studies assessing misuse across medical students are sparse. OBJECTIVES: The purpose of this study was to1) estimate the lifetime and the past-year prevalence of non-medical use of prescription medications among medical students in Greece 2) identify the motivation for use. METHODS: 591 medical students completed an anonymous, self-administered, web-based survey assessing lifetime and past-year prevalence of non-medical use of four classes of prescription drugs (opioid painkillers, tranquillizers, sleeping and stimulant medications). According to the motivation to use the responders were classified into three subtypes (selftreatment, recreational, and mixed). RESULTS: The prevalence of lifetime use was 10.7% for at least one of the four prescription drug classes and 9% of the respondents reported lifetime misuse of multiple categories of prescription drugs. The past-year prevalence was approximately 7.7% for at least one of the four prescription drug classes, while the majority misused the drugs "1-2 times per year". Senior students used tranquilizers more than junior students. Self-treatment and mixed subtypes of tranquillizers misuse was more prevalent among women than men while the self-treatment subtype was the most prevalent subtype in all the four drug classes. CONCLUSIONS: This is the first study investigating non-medical use of prescription medications among Greek medical students and indicates a high prevalence of misuse of some categories of prescription drugs, mostly for self-treatment purposes.
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Motivación , Mal Uso de Medicamentos de Venta con Receta/estadística & datos numéricos , Estudiantes de Medicina/psicología , Adolescente , Adulto , Analgésicos Opioides , Estimulantes del Sistema Nervioso Central , Femenino , Grecia , Humanos , Hipnóticos y Sedantes , Masculino , Prevalencia , Tranquilizantes , Adulto JovenRESUMEN
BACKGROUND: Familial Mediterranean fever (FMF) is an IL-1ß-dependent autoinflammatory disease caused by mutations of Mediterranean fever (MEFV) encoding pyrin and characterized by inflammatory attacks induced by physical or psychological stress. OBJECTIVE: We investigated the underlying mechanism that links stress-induced inflammatory attacks with neutrophil activation and release of IL-1ß-bearing neutrophil extracellular traps (NETs) in patients with FMF. METHODS: RNA sequencing was performed in peripheral neutrophils from 3 patients with FMF isolated both during attacks and remission, 8 patients in remission, and 8 healthy subjects. NET formation and proteins were analyzed by using confocal immunofluorescence microscopy, immunoblotting, myeloperoxidase-DNA complex ELISA, and flow cytometry. Samples from patients with Still's disease and bacterial infections were used also. RESULTS: The stress-related protein regulated in development and DNA damage responses 1 (REDD1) is significantly overexpressed during FMF attacks. Neutrophils from patients with FMF during remission are resistant to autophagy-mediated NET release, which can be overcome through REDD1 induction. Stress-related mediators (eg, epinephrine) decrease this threshold, leading to autophagy-driven NET release, whereas the synchronous inflammatory environment of FMF attack leads to intracellular production of IL-1ß and its release through NETs. REDD1 in autolysosomes colocalizes with pyrin and nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing 3. Mutated pyrin prohibits this colocalization, leading to higher IL-1ß levels on NETs. CONCLUSIONS: This study provides a link between stress and initiation of inflammatory attacks in patients with FMF. REDD1 emerges as a regulator of neutrophil function upstream to pyrin, is involved in NET release and regulation of IL-1ß, and might constitute an important piece in the IL-1ß-mediated inflammation puzzle.
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Fiebre Mediterránea Familiar/inmunología , Inflamación/inmunología , Neutrófilos/inmunología , Estrés Psicológico/inmunología , Factores de Transcripción/metabolismo , Adulto , Autofagia , Progresión de la Enfermedad , Trampas Extracelulares/metabolismo , Fiebre Mediterránea Familiar/genética , Femenino , Humanos , Interleucina-1beta/metabolismo , Masculino , Pirina/genética , Remisión Espontánea , Estrés Fisiológico/inmunología , Adulto JovenRESUMEN
OBJECTIVE: Inflammatory attacks of familial Mediterranean fever (FMF) are characterised by circulation and influx of high number of polymorphonuclear neutrophils (PMN) in the affected sites and profound therapeutic effect of IL-1ß inhibitors. We investigated the role of neutrophil extracellular traps (NET) in the pathogenesis of FMF, and their involvement in IL-1ß production. METHODS: Blood samples were obtained from six FMF patients during remissions and from three patients during attacks. NET formation and NET components were studied by fluorescence techniques, immunobloting and MPO-DNA complex ELISA. RESULTS: PMNs from patients released NETs decorated with IL-1ß during disease attacks. On the other hand, PMNs from patients during remission were resistant to inflammatory stimuli that induce NET release in PMNs from control subjects. Lower basal autophagy levels were identified in PMNs during remission, while induction of autophagy facilitated NET release, suggesting that autophagy is involved in the regulation of NET release. During the resolution of attacks, inhibition of NET formation by negative feedback mechanism was also observed. The anti-inflammatory agents, colchicine and DNAse I, inhibited IL-1ß production in PMNs and IL-1ß activity in NETs, respectively. CONCLUSIONS: We suggest two additive events for triggering the FMF attack; the production of IL-1ß by PMNs and its release through NETs. At the same time NETs, homeostatically, downregulate further NETosis, facilitating the resolution of attack. Compensatorly, lower basal autophagy of PMNs may protect from crises by attenuating the release of pro-inflammatory NETs.
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Trampas Extracelulares/inmunología , Fiebre Mediterránea Familiar/inmunología , Interleucina-1beta/inmunología , Neutrófilos/inmunología , Adulto , Antiinflamatorios/farmacología , Autofagia/inmunología , Estudios de Casos y Controles , Colchicina/farmacología , Desoxirribonucleasa I/farmacología , Trampas Extracelulares/efectos de los fármacos , Retroalimentación Fisiológica , Femenino , Humanos , Interleucina-1beta/biosíntesis , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Inducción de Remisión , Adulto JovenRESUMEN
AIMS: The aim of this study was to perform an up-to-date systematic review and meta-analysis on the efficacy and safety of prophylactic administration of levetiracetam in brain tumour patients. METHOD: A systematic review of studies published until April 2015 was conducted using Scopus/Elsevier, EMBASE and MEDLINE. The search was limited to articles reporting results from adult patients, suffering from brain tumour, undergoing supratentorial craniotomy for tumour resection or biopsy and administered levetiracetam in the perioperative period for seizure prophylaxis. Outcomes included the efficacy and safety of levetiracetam, as well as the tolerability of the specific regimen, defined by the discontinuation of the treatment due to side effects. RESULTS: The systematic review included 1148 patients from 12 studies comparing levetiracetam with no treatment, phenytoin and valproate, while only 243 patients from three studies, comparing levetiracetam vs phenytoin efficacy and safety, were included in the meta-analysis. The combined results from the meta-analysis showed that levetiracetam administration was followed by significantly fewer seizures than treatment with phenytoin (OR = 0.12 [0.03-0.42]: χ(2) = 1.76: I(2) = 0%). Analysis also showed significantly fewer side effects in patients receiving levetiracetam, compared to other groups (P < 0.05). The combined results showed fewer side effects in the levetiracetam group compared to the phenytoin group (OR = 0.65 [0.14-2.99]: χ(2) = 8.79: I(2) = 77%). CONCLUSIONS: The efficacy of prophylaxis with levetiracetam seems to be superior to that with phenytoin and valproate administration. Moreover, levetiracetam use demonstrates fewer side effects in brain tumour patients. Nevertheless, high risk of bias and moderate methodological quality must be taken into account when considering these results.
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Anticonvulsivantes/uso terapéutico , Piracetam/análogos & derivados , Convulsiones/prevención & control , Anticonvulsivantes/efectos adversos , Craneotomía/métodos , Humanos , Levetiracetam , Atención Perioperativa , Fenitoína/efectos adversos , Fenitoína/uso terapéutico , Piracetam/efectos adversos , Piracetam/uso terapéutico , Convulsiones/etiología , Neoplasias Supratentoriales/cirugía , Ácido Valproico/efectos adversos , Ácido Valproico/uso terapéuticoRESUMEN
AIMS: Neutrophil extracellular traps (NETs) are chromatin ï¬laments released by activated polymorphonuclear neutrophils (PMNs) and decorated with granule proteins with various properties. Several lines of evidence implicate NETs in thrombosis. The functional significance and the in vivo relevance of NETs during atherothrombosis in humans have not been addressed until now. METHODS AND RESULTS: Selective sampling of thrombotic material and surrounding blood from the infarct-related coronary artery (IRA) and the non-IRA was performed during primary percutaneous revascularization in 18 patients with ST-segment elevation acute myocardial infarction (STEMI). Thrombi isolated from IRA contained PMNs and NETs decorated with tissue factor (TF). Although TF was expressed intracellularly in circulating PMNs of STEMI patients, active TF was specifically exposed by NETs obtained from the site of plaque rupture. Treatment of NET structures with DNase I abolished TF functionality measurement. In vitro treatment of control PMNs with plasma obtained from IRA and non-IRA was further shown to induce intracellular up-regulation of TF but not NET formation. A second step consisting of the interaction between PMNs and thrombin-activated platelets was required for NET generation and subsequent TF exposure. CONCLUSION: The interaction of thrombin-activated platelets with PMNs at the site of plaque rupture during acute STEMI results in local NET formation and delivery of active TF. The notion that NETs represent a mechanism by which PMNs release thrombogenic signals during atherothrombosis may offer novel therapeutic targets.
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Vasos Coronarios/metabolismo , Trampas Extracelulares/metabolismo , Infarto del Miocardio/metabolismo , Neutrófilos/metabolismo , Tromboplastina/metabolismo , Análisis de Varianza , Estudios de Casos y Controles , Trombosis Coronaria/metabolismo , Trombosis Coronaria/cirugía , Femenino , Humanos , Leucocitos Mononucleares/fisiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/cirugía , Revascularización Miocárdica/métodos , Intervención Coronaria Percutánea , Placa Aterosclerótica , Activación Plaquetaria/fisiología , Rotura Espontánea/metabolismo , Trombina/metabolismoRESUMEN
Neutrophil activation by inflammatory stimuli and the release of extracellular chromatin structures (neutrophil extracellular traps - NETs) have been implicated in inflammatory disorders. Herein, we demonstrate that NETs released by neutrophils treated either with fibrosis-related agents, such as cigarette smoke, magnesium silicate, bleomycin, or with generic NET inducers, such as phorbol 12-myristate 13-acetate, induced activation of lung fibroblasts (LFs) and differentiation into myofibroblast (MF) phenotype. Interestingly, the aforementioned agents or IL-17 (a primary initiator of inflammation/fibrosis) had no direct effect on LF activation and differentiation. MFs treated with NETs demonstrated increased connective tissue growth factor expression, collagen production, and proliferation/migration. These fibrotic effects were significantly decreased after degradation of NETs with DNase1, heparin or myeloperoxidase inhibitor, indicating the key role of NET-derived components in LF differentiation and function. Furthermore, IL-17 was expressed in NETs and promoted the fibrotic activity of differentiated LFs but not their differentiation, suggesting that priming by DNA and histones is essential for IL-17-driven fibrosis. Additionally, autophagy was identified as the orchestrator of NET formation, as shown by inhibition studies using bafilomycin A1 or wortmannin. The above findings were further supported by the detection of NETs in close proximity to alpha-smooth muscle actin (α-SMA)-expressing fibroblasts in biopsies from patients with fibrotic interstitial lung disease or from skin scar tissue. Together, these data suggest that both autophagy and NETs are involved not only in inflammation but also in the ensuing fibrosis and thus may represent potential therapeutic targets in human fibrotic diseases.
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Diferenciación Celular , Cromatina/metabolismo , Cicatriz/metabolismo , Pulmón/metabolismo , Miofibroblastos/metabolismo , Neutrófilos/metabolismo , Comunicación Paracrina , Fibrosis Pulmonar/metabolismo , Actinas/metabolismo , Autofagia , Diferenciación Celular/efectos de los fármacos , Movimiento Celular , Proliferación Celular , Células Cultivadas , Cicatriz/inmunología , Cicatriz/patología , Técnicas de Cocultivo , Colágeno/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Inhibidores Enzimáticos/farmacología , Fibrosis , Humanos , Interleucina-17/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Miofibroblastos/efectos de los fármacos , Miofibroblastos/patología , Activación Neutrófila , Infiltración Neutrófila , Neutrófilos/efectos de los fármacos , Comunicación Paracrina/efectos de los fármacos , Peroxidasa/metabolismo , Fenotipo , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/patología , Piel/inmunología , Piel/metabolismo , Piel/patologíaRESUMEN
OBJECTIVES: Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is characterised by neutrophil activation. An elevated prevalence of venous thromboembolic events has been reported in AAV. Because of the critical role of neutrophils in inflammation associated thrombosis, we asked whether neutrophil tissue factor (TF) may be implicated in the thrombotic diathesis in AAV. METHODS: Neutrophils from four patients and sera from 17 patients with ANCA associated vasculitis with active disease and remission were studied. TF expression was assessed by immunoblotting and confocal microscopy. Circulating DNA levels were evaluated. TF expressing microparticles (MPs) were measured by flow cytometry and thrombin-antithrombin complex levels by ELISA. RESULTS: Peripheral blood neutrophils from four patients with active disease expressed elevated TF levels and released TF expressing neutrophil extracellular traps (NETs) and MPs. TF positive NETs were released by neutrophils isolated from the bronchoalveolar lavage and were detected in nasal and renal biopsy specimens. Elevated levels of circulating DNA and TF expressing neutrophil derived MPs were further observed in sera from patients with active disease. Induction of remission attenuated the aforementioned effects. Control neutrophils treated with sera from patients with active disease released TF bearing NETs and MPs which were abolished after IgG depletion. Treatment of control neutrophils with isolated IgG from sera from patients with active disease also resulted in the release of TF bearing NETs. TF implication in MP dependent thrombin generation was demonstrated by antibody neutralisation studies. CONCLUSIONS: Expression of TF in NETs and neutrophil derived MPs proposes a novel mechanism for the induction of thrombosis and inflammation in active AAV.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/sangre , Micropartículas Derivadas de Células/metabolismo , Trampas Extracelulares/metabolismo , Neutrófilos/metabolismo , Trombofilia/etiología , Tromboplastina/fisiología , Adulto , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Líquido del Lavado Bronquioalveolar/citología , Estudios de Casos y Controles , Femenino , Humanos , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Activación Neutrófila , Inducción de Remisión , Trombofilia/metabolismo , Tromboplastina/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
The objectives of this study were (1) to assess the protective role of NMDA antagonists against the ototoxic effects of aminoglycosides, (2) to provide any possible evidence between ototoxicity due to aminoglycosides and excitotoxicity. An animal experiment was conducted. Twenty-eight, 3-month-old female New Zealand rabbits, weighing 1,000-1,500 g, were studied prospectively for 28 days after intramuscular administration of amikacin (15 mg/kg/day divided into two equal doses) for 14 days. Twenty-one rabbits were categorized into three equal treatment groups and seven animals received no medication and served as the control group. The animals of A, B and C groups were injected, intramuscularly, with amikacin 15 mg/kg/day, divided into two equal doses every day for 14 days. Animals of group A received in parallel memantine (per os) and those of group B received p.o. the same volume of placebo solution. The rabbits of the third group (group C) received on the 15th day and every 2 days for the next 2 weeks, until the day 28, memantine of the same quantity as the members of group A. Differences in DPOAE amplitudes, and therefore in cochlear activity, between group A and group B were revealed. DPOAE amplitudes of group B were further reduced compared to the respective amplitudes in rabbits of group A. No improvement was observed in DPOAE measurements performed after the discontinuation of injections. The findings in group C should be examined separately. The measurements showed apparent reversal ototoxic effects in four of the animals. The development of aminoglycoside otoprotective strategies is a primary goal in ototoxicity research. The administration of NMDA antagonists has been shown to prevent, at least to some extent, toxic damage to hair cells in guinea pigs, treated with aminoglycoside antibiotics.
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Amicacina/toxicidad , Aminoglicósidos/toxicidad , Cóclea/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , Pérdida Auditiva/inducido químicamente , Memantina/farmacología , Emisiones Otoacústicas Espontáneas/efectos de los fármacos , Animales , Femenino , Audición/efectos de los fármacos , Pérdida Auditiva/prevención & control , ConejosRESUMEN
Familial Mediterranean fever (FMF) is an autoinflammatory disease, characterized by MEFV gene mutations and self-limited recurrent episodes of fever and localized serositis. Complement system is a key regulator of the inflammatory process. The aim of this study was to investigate the genetic alterations and mRNA expression pattern of C5aR and C5L2 genes in neutrophils from attack-free FMF patients. No mutations were observed in the two receptors' genes, while the genetic alteration observed in the C5aR1 gene was identified as N279 K polymorphic variant. Furthermore, lower mRNA expression of C5L2 gene was observed in neutrophils from FMF patients compared to control subjects. The binding capacity of rhC5a and the ability to produce reactive oxygen species was similar in neutrophils from healthy subjects and FMF patients and independent of the presence of N279 K polymorphism or mRNA expression of C5L2.
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Fiebre Mediterránea Familiar/genética , Fiebre Mediterránea Familiar/patología , Predisposición Genética a la Enfermedad , Neutrófilos/metabolismo , Neutrófilos/patología , Receptores de Quimiocina/genética , Receptores de Complemento/genética , Adolescente , Adulto , Secuencia de Bases , Niño , Preescolar , Proteínas del Citoesqueleto/genética , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación/genética , Polimorfismo de Longitud del Fragmento de Restricción/genética , Polimorfismo de Nucleótido Simple/genética , Pirina , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptor de Anafilatoxina C5aRESUMEN
BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) devices have emerged as alternatives to anticoagulation for embolic stroke prevention in patients with non-valvular atrial fibrillation (NVAF). The left atrial appendage is known to produce vasoactive neuroendocrine hormones involved in cardiovascular homeostasis. The hemodynamic impact of LAA occlusion on cardiac function remains poorly characterized. METHODS: This is a single-center, retrospective study of sixty-seven consecutive patients who received LAAO utilizing the WATCHMAN device from May 2017 to June 2019. All patients received a comprehensive 2D transthoracic echocardiogram (TTE) prior to the procedure and a post-procedural TTE. 2D echocardiographic pre-/post-procedural measurements including left ventricular ejection fraction, tricuspid regurgitation, estimated pulmonary artery pressure, diastolic parameters, and left atrial and right ventricular strain were statistically analyzed using the paired t-test. RESULTS: Seventy percent of study patients were male with an overall mean age of 73.0 ± 9.0 years. Analysis of post-procedural LAAO revealed statistically significant improvement in left ventricular ejection fraction (52.4 ± 12.6 vs. 56.7 ± 12.7, p < 0.001), an increase in mitral E/e' (14.1 ± 6.5 vs. 18.3 ± 10.8, p < 0.001), and a decrease right ventricular global longitudinal strain (RVGLS) (- 17.5 ± 4.6 vs. - 19.6 ± 5.7, p = 0.027) as compared to pre-procedural TTE. Peak left atrial longitudinal strain (PALS) improved post-LAAO (20.6 ± 12.2 to 22.9 ± 12.9, p = 0.040) with adjustment for cardiac arrhythmias. Post-LAAO, heart failure hospitalizations occurred in 23.9% of patients. CONCLUSIONS: Percutaneous LAAO results in real-time atrial and ventricular hemodynamic changes as assessed by echocardiographic evaluation of LV filling pressures (E/e'), PALS, RVGLS, and LVEF.
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Apéndice Atrial , Fibrilación Atrial , Anciano , Anciano de 80 o más Años , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/cirugía , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
Mitral valve prolapse (MVP) affects approximately 170 million people worldwide; however, phenotypically, there is a wide variety of heterogeneity. In particular subsets, the incidence of sudden cardiac death is calculated to be 998 per 100,000 person-years, which is significantly increased when compared with the general population of MVP patients. Individuals with high-risk features have been identified as young females with bileaflet MVP and electrocardiogram findings of frequent complex ectopy, ST-T wave changes, and inferior T wave inversions. Supplemental imaging modalities in this subgroup demonstrate redundant leaflets and chordae on 2-dimensional transthoracic echocardiography along with varying severity of mitral annular disjunction. Detailed morphologic assessment by 3-dimensional echocardiography provides a quantitative assessment of annular disjunction along with left ventricular longitudinal and basal circumferential strain patterns. Late gadolinium enhancement on cardiac magnetic resonance imaging identifies diffuse and isolated left ventricle fibrosis involving the fascicles and papillary muscles, which has been visualized in isolation during autopsy. Findings of this review propose that sudden cardiac death as a result of malignant arrhythmias arises from automaticity, complex ectopy, and reentry at the level of the fascicles and papillary muscles. The repetitive mechanical stress provides a nidus for the development of both micro- and macrofibrosis easily identified by late gadolinium enhancement on cardiac magnetic resonance imaging. Escalation to electrophysiology studies and early intervention could provide new targeted lifesaving therapies.
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Prolapso de la Válvula Mitral , Medios de Contraste , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Femenino , Gadolinio , Humanos , Prolapso de la Válvula Mitral/diagnóstico , Prolapso de la Válvula Mitral/diagnóstico por imagen , Músculos Papilares/diagnóstico por imagenRESUMEN
Patients with heart transplants who present with severe aortic stenosis may be deemed high-risk surgical candidates due to immunosuppression and multiple comorbid conditions. Appropriately selected patients may be successfully treated with transcatheter aortic valve replacement. (Level of Difficulty: Advanced.).
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OBJECTIVES: To examine temporal trends, predictors, and outcomes of red blood cell (RBC) transfusion in patients undergoing transcatheter aortic valve replacement (TAVR) in the United States. METHODS: We used the National Inpatient Sample databases to identify TAVR procedures performed between January 2012 and September 2015 in the United States. Patients were propensity matched (within the strata of overt and no bleeding) on the likelihood of receiving RBC transfusion, and in-hospital outcomes were compared between the 2 groups in the matched cohort. RESULTS: Among 46,710 TAVR procedures performed during the study period, rates of RBC transfusion were 17.3% (95% confidence interval [CI], 16.1%-18.5%). RBC transfusion rates decreased significantly from 29.5% during the first quarter of 2012 to 10.8% during the third quarter of 2015 (P < .001). Older age, female sex, peripheral vascular disease, chronic kidney disease, anemia, coagulopathy, and fluid/electrolyte disorders were associated with increased odds, whereas elective admission, obesity, and endovascular access were associated with decreased odds of RBC transfusion. In the propensity-matched cohort (7995 pairs with and without RBC transfusion), RBC transfusion was associated with increased risk of in-hospital mortality, infection, and transient ischemic attack/stroke in patients without bleeding (odds ratio [OR]Mortality, 2.29; 95% CI, 1.31-4.02; ORInfection, 2.13; 95% CI, 1.03-4.39; ORTransient ischemic attack/Stroke, 3.36; 95% CI, 1.52-7.45), but not in those with overt bleeding (ORMortality, 1.10; 95% CI, 0.68-1.48; ORInfection, 0.80; 95% CI, 0.45-1.45; ORTransient ischemic attack/Stroke, 1.16; 95% CI, 0.74-1.85); Pinteraction < .05 for all. CONCLUSIONS: RBC transfusion is associated with worse clinical outcomes in TAVR patients without bleeding, but not in those with overt bleeding. The utility and optimal threshold for RBC transfusion in TAVR patients, especially among those with overt bleeding, warrants further prospective investigation.
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Background The relationship between local hospital culture and transfusion rates following endovascular and surgical cardiovascular procedures has not been well studied. Methods and Results Patients undergoing coronary revascularization, aortic valve replacement, lower extremity peripheral vascular intervention, or carotid artery revascularization from up to 852 US hospitals in the Nationwide Readmissions Database were identified. Crude and risk-standardized red blood cell transfusion rates were determined for each procedure. Pearson correlation coefficients were calculated between respective procedural transfusion rates. Median odds ratios were estimated to reflect between-hospital variability in red blood cell transfusion rates following the same procedure for a given patient. There was wide variation in red blood cell transfusion rates across different procedures, from 2% following carotid endarterectomy to 29% following surgical aortic valve replacement. For surgical and endovascular modalities, transfusion rates at the same hospital were highly correlated for aortic valve replacement (r=0.67; P<0.001), moderately correlated for coronary revascularization (r=0.56; P<0.001) and peripheral vascular intervention (r=0.51; P<0.001), and weakly correlated for carotid artery revascularization (r=0.19, P<0.001). Median odds ratios were all >2, highest for coronary artery bypass graft surgery and surgical aortic valve replacement, indicating substantial site variation in transfusion rates. Conclusions After adjustment for patient-related factors, wide variation in red blood cell transfusion rates remained across surgical and endovascular procedures employed for the same cardiovascular condition. Transfusion rates following these procedures are highly correlated at individual hospitals and vary widely across hospitals. In aggregate, these findings suggest that local institutional culture significantly influences the decision to transfuse following invasive cardiovascular procedures and highlight the need for randomized data to inform such decisions.
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Procedimientos Quirúrgicos Cardíacos/estadística & datos numéricos , Procedimientos Endovasculares/estadística & datos numéricos , Transfusión de Eritrocitos/estadística & datos numéricos , Toma de Decisiones Clínicas , Femenino , Capacidad de Camas en Hospitales , Humanos , Masculino , Oportunidad Relativa , Readmisión del Paciente , Selección de Paciente , Utilización de Procedimientos y Técnicas , Estados UnidosRESUMEN
PURPOSE OF REVIEW: Cryptogenic stroke describes a subset of ischemic stroke for which no cause can be found despite a structured investigation. There are a number of putative mechanisms of cryptogenic ischemic stroke including a covert structural cardiac lesion, paroxysmal atrial fibrillation, hypercoagulable state or undiagnosed malignancy. Because many of these proposed mechanisms are embolic - and based on studies of thrombus history showing commonalities between thrombus composition between cardioembolic and cryptogenic strokes - the concept of embolic stroke of undetermined source (ESUS) (Hart et al. Lancet Neurol. 13(4):429-38, 2014; Stroke. 48(4):867-72, 2017) has been proposed to describe cryptogenic strokes that may warrant systemic anticoagulation. In this review, we discuss the phenomena of cryptogenic stroke, ESUS and a proposed management pathway. RECENT FINDINGS: 1. The concept of ESUS was proposed in 2014 as a potentially useful therapeutic entity. Two recent trials - NAVIGATE-ESUS (Hart et al. N Engl J Med. 378(23):2191-201, 2018) and RESPECT-ESUS (Diener 2018) were proposed based on this concept. They were negative for their primary endpoint and for the secondary endpoint of ischemic stroke recurrence. Post-hoc analysis of the WARSS trial (Longstreth et al. Stroke. 44(3):714-9, 2013) suggested that people with elevated pro-BNP benefited from systemic anticoagulation whereas those with a normal pro-BNP did not. This led to the hypothesis that a subgroup of patients at higher risk for embolism from the left atrium would benefit from anticoagulation, even if the WARSS trial was negative for the primary endpoint. Thus, the ARCADIA trial (Kamel et al. Int J Stroke. 14(2):207-14, 2019) was proposed - a randomized, active-control, multi-center trial comparing apixaban with aspirin for secondary stroke prevention in patients with ESUS and biomarkers of left atrial cardiopathy. This trial is actively recruiting. 2. Carotid web - an intimal form of fibromuscular dysplasia - has come to increased prominence in the literature as a cause of embolic stroke. It is a non-stenosis, non-atherosclerotic lesion in the posterior wall of the internal carotid artery that leads to pooling with stasis of blood distal to the lesion and, as a consequence, embolic stroke. It is not usually detected by a standard stroke workup as it masquerades as non-calcified atherosclerosis and does not cause hemodynamically significant stenosis. There have been two major recent papers - a meta-analysis in Stroke (Zhang et al. Stroke. 49(12):2872-6, 2018) and narrative review in JAMA Neurology (Kim et al. JAMA Neurol. 2018) - that addressed this topic. Cryptogenic stroke describes a stroke for which no cause has been found. ESUS is a more precisely-defined entity that mandates a specific workup and implicates remote embolism as a cause of stroke. In ESUS, the options for further investigation include long-term cardiac monitoring, transesophageal echocardiography, investigation for occult malignancy or arterial hypercoagulability. Options for management include anti-platelet therapy (the current standard of care), empiric anticoagulation or enrollment in to a clinical trial examining the use of NOACs compared with aspirin for secondary prevention (such as ARCADIA or ATTICUS). In a person less than 60 years old with ESUS and a patent foramen ovale the risk of a recurrent stroke is low but recent trials have suggested that percutaneous device closure reduces this risk further with an acceptable complication rate.
RESUMEN
BACKGROUND: We evaluated the association between postprocedural packed red blood cell transfusion and morbidity and mortality among patients undergoing transcatheter aortic valve replacement. METHODS: We retrospectively analyzed 429 patients with severe aortic stenosis who underwent transcatheter aortic valve replacement. Propensity-score adjusted multivariable logistic and Cox regression models were used to determine the association of packed red blood cell transfusion with the composite endpoint of death, myocardial infarction, and stroke at 30 days and in hospital, and 1-year mortality. RESULTS: Patients receiving transfusions had a higher 30-day and in-hospital incidence of death, myocardial infarction, or stroke when compared with patients who did not receive transfusions (hazard ratio 2.03, 95% confidence interval: 1.02 to 4.07, p = 0.045; and hazard ratio 2.46, 95% confidence interval: 1.12 to 5.41, p = 0.025, respectively). Postprocedural transfusion was independently associated with 1-year mortality (hazard ratio 2.65, 95% confidence interval: 1.21 to 5.80, p = 0.015). CONCLUSIONS: Packed red blood cell transfusion for patients undergoing transcatheter aortic valve replacement is associated with an increased incidence of adverse outcomes during hospitalization and at 30-day and 1-year follow-up.
Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Transfusión de Eritrocitos , Complicaciones Posoperatorias/epidemiología , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background The aim of the present cross-sectional study was to evaluate associations between pocket money, Mediterranean diet (MD) adherence and growth among Greek adolescents. Methods A total of 319 (157 boys and 162 girls) Greek adolescents, aged 10-18 years participated in the study. Pocket money was recorded, MD adherence was assessed with the KIDMED score and growth was evaluated using the World Health Organization (WHO) growth charts. Results Participants receiving pocket money exceeding 6.0 daily demonstrated increased fast-food consumption and breakfast skipping. Overall, a negative relationship was revealed between pocket money and obesity. However, lower allowance receivers were less likely to be obese, consume fruit per day and more likely to consume breakfast and sweets, compared to average pocket money receivers. Increased MD adherence was associated with a lower risk of overweight and as expected, unhealthy eating habits were observed among obese adolescents. Conclusions Interrelationships tend to exist between MD adherence, pocket money and growth among adolescents.
Asunto(s)
Conducta del Adolescente , Dieta Mediterránea , Conducta Alimentaria , Obesidad/epidemiología , Sobrepeso/epidemiología , Factores Socioeconómicos , Adolescente , Niño , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Estilo de Vida , Masculino , Obesidad/economía , Sobrepeso/economía , Pronóstico , Encuestas y CuestionariosRESUMEN
Mitral regurgitation is the second most common valvular disorder requiring surgical intervention worldwide. This review summarizes the current understanding of primary, degenerative mitral regurgitation with respect to etiology, comprehensive assessment, natural history and management. The new concept of staging of the valvular disorders, newer predictors of adverse and controversy of "watchful waiting" versus "early surgical intervention" for severe, asymptomatic, primary mitral regurgitation are addressed.