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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoaV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic. In randomized clinical trials, patients who were treated with the anti-spike monoclonal antibody bamlanivimab had fewer COVID-19-related hospitalizations or emergency department (ED) visits than the control group. Methods: A retrospective cohort was assembled across a multisite healthcare system between November 20, 2020 and March 31, 2021. Ambulatory COVID-19 patients treated with bamlanivimab (n = 209) were propensity score matched without replacement (1:1) to a pool of 1024 eligible control patients who received similar care without bamlanivimab. The primary endpoint was all-cause mortality or admission at 30 days. Secondary endpoints included hospitalization, critical care admission, oxygenation requirements, and infusion-related reactions. Propensity score matching (PSM) analysis was used to assess the effect of bamlanivimab infusion on the composite endpoint and secondary endpoints. Results: A total of n = 209 matched patients were included in each arm of the study. The absolute standardized difference (stddiff) was calculated and indicated a balance between the groups. Almost all variables had a stddiff of less than 0.10, except for respiratory rate (RR) (stddiff = -0.11). For the primary composite endpoint of the matched cohort, 10.1% (n = 21) of patients in the intervention group were hospitalized or deceased within 30-day postbamlanivimab infusion versus 27.8% (n = 58) in the control group (adjusted odds ratio [aOR]: 0.29, 95% confidence interval [CI]: 0.17 to 0.51, P < .001). Conclusion: Patients with ambulatory COVID-19 who received bamlanivimab in the outpatient setting had a statistically significant reduction on the odds of admission postinfusion. Despite bamlanivimab's lack of efficacy on newer SARS-CoV-2 variants, this study demonstrates that neutralizing monoclonal antibodies can be effective against specific variants. If variant identification becomes a more accessible tool in outpatient centers or EDs, more targeted therapeutic options may be considered.
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Anticorpos Monoclonais , COVID-19 , Humanos , Anticorpos Monoclonais/uso terapêutico , SARS-CoV-2 , Estudos RetrospectivosRESUMO
Autophagy, a cellular housekeeping process, is essential to maintain tissue homeostasis, particularly in long-lived cells such as cardiomyocytes. Autophagic activity declines with age and may explain many features of age-related cardiac dysfunction. In this review we summarize the current state of knowledge regarding age-related changes in autophagy in the heart. Recent findings from studies in human hearts are presented, including evidence that the autophagic response is intact in the aged human heart. Impaired autophagic clearance of protein aggregates or deteriorating mitochondria will have multiple consequences including increased arrhythmia risk, decreased contractile function, reduced tolerance to ischemic stress, and increased inflammation; thus autophagy represents a potentially important therapeutic target to mitigate the cardiac consequences of aging. This article is part of a Special Issue entitled CV Aging.
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Envelhecimento/metabolismo , Arritmias Cardíacas/genética , Autofagia/genética , Miocárdio/metabolismo , Envelhecimento/patologia , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patologia , Regulação da Expressão Gênica , Homeostase , Humanos , Longevidade , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: In small children, fluid resuscitation requires rapid administration of a relatively large fluid volume. This is often achieved manually. The optimal syringe size is unknown. OBJECTIVES: The purpose of this study was to determine which syringe delivers fluid in the shortest time. The secondary outcome was to determine which syringe was associated with hand fatigue. METHODS: Participants (n = 20) performed a simulated fluid resuscitation using four syringe sizes: 5 ml, 10 ml, 20 ml, and 60 ml. The 'pull and push' method was used to transfer 250 ml of lactated Ringer's solution from a bag, through IV tubing, into a container. Fluid transfer time (seconds) and hand fatigue were measured. RESULTS: A 'U'-shaped curve was identified between syringe size and transfer time (P < 0.0001). The 10-ml and 20-ml syringes did not differ significantly (231 ± 43 vs 228 ± 45 s, P > 0.2, respectively). The 5-ml and 60-ml syringes did not differ significantly (273 ± 69 s vs 295 ± 64, P = 0.2, respectively). However, the 5-ml syringe required significantly more time than the 10-ml (by 42 s, P = 0.002) or the 20-ml (by 45 s, P = 0.001) syringes. The 60-ml syringe also required significantly more time than the 10-ml (by 64 s, P < 0.0001) or 20-ml (by 67 s, P = 0.0001) syringe. Although all participants transferred the 250 ml, hand fatigue increased as syringe size increased: 5 ml (n = 3), 10 ml (n = 4), 20 ml (n = 7), and 60 ml (n = 15). Most participants preferred using the 10-ml syringe (n = 11/20), followed by 20-ml (n = 6/20), 5-ml (n = 3/20), and 60-ml (n = 0/20) syringes. CONCLUSION: Manual fluid resuscitation using the 'pull and push' method is most rapidly accomplished with the 10-ml or 20-ml syringes. The 60-ml syringe is associated with the most hand fatigue. Participants most preferred the 10-ml or 20-ml syringes.
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Fadiga Muscular , Ressuscitação/métodos , Seringas , Adulto , Criança , Pré-Escolar , Desenho de Equipamento , Hidratação , Mãos , Humanos , Lactente , Soluções Isotônicas , Enfermeiros Anestesistas , Médicos , Lactato de RingerRESUMO
BACKGROUND: Arterial stiffness and low heart rate variability (HRV) have each been associated with increased cardiovascular risk in a variety of patient populations. We explored the relationship between HRV and pulse wave velocity (PWV measure of arterial stiffness) in patients with chronic kidney disease (CKD prior to ESRD) along with examining their association with the outcomes of cardiovascular disease (CVD), death, and progression to end stage renal disease (ESRD). METHODS: The RRI-CKD Study is a 4-center prospective cohort study of CKD stages 3 - 5 (n = 834). A subset underwent both HRV testing by 24-hour Holter and carotid-femoral PWV (n = 240). Multiple linear regression was used to assess predictors of PWV and Cox regression to investigate the association of HRV and PWV with time to first CVD event or death and ESRD. RESULTS: Although several HRV measures were inversely correlated with PWV, this association was attenuated after adjustment for age and/or diabetes and no longer significant after adjustment for C-reactive protein. Low HRV and high PWV were individually associated with increased risk of the composite endpoint of CVD/death in multivariable analysis. The risk of the composite of CVD/death was highest for patients with both low HRV and high PWV. CONCLUSION: Age, diabetes, and inflammation together explained the inverse association between HRV and PWV. Inflammation may play a role in the pathogenesis of both low HRV and high PWV. The combination of low HRV and high PWV showed the strongest association with a composite CVD outcome. Mechanisms underlying abnormalities in PWV and HRV, and the role of these measures as intermediate outcomes in future trials in CKD patients, merit further study.
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Frequência Cardíaca/fisiologia , Análise de Onda de Pulso , Insuficiência Renal Crônica/fisiopatologia , Adulto , Idoso , Proteína C-Reativa/análise , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/complicaçõesRESUMO
Importance There are conflicting data regarding the safety of the use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) medications in hypertensive patients who are susceptible to COVID-19. Objective Our study assesses the association between COVID-19 severity and mortality and the use of ACEIs/ARBs among hospitalized patients with hypertension. Research design, setting, and participants This was a retrospective cohort study. Using the EPIC system of Beaumont Health, Dearborn, Michigan, we identified 5490 patients with COVID-19 who were admitted to the eight Beaumont hospitals. After excluding subjects who have no hypertension and those with missing data, we included 2129 COVID-19 patients who have hypertension. Logistic regression and Cox proportional hazards models were used to analyze the association between history of ACEI/ARB use, intensive care unit (ICU) admission rate, and COVID-19 mortality. Exposure Exposure refers to the use of ACEIs/ARBs as documented in the medical records before admission to the hospitals. Main outcome The main outcome was 30-day COVID-19 mortality and ICU admission rates. Results There were 1281 subjects (60%) with prior ACEI/ARB use and 848 subjects (40%) with no ACEI/ARB use. There was no significant association between ICU admission and the use of ACEIs/ARBs (odds ratio {OR} = 0.95, 95% CI = {0.76, 1.19}, p-value = 0.6). Although the unadjusted logistic regression model demonstrated a statistically significant association between history of ACEI/ARB use and COVID-19 mortality (odds ratio = 1.31, 95% CI = {1.05, 1.66}, p-value = 0.02), the adjusted logistic regression model failed to show this statistically significant association (odds ratio = 1.20, 95% CI = {0.93, 1.54}, p-value = 0.14). Moreover, we were not able to reveal a statistically significant association between 30-day COVID-19 survival and prior use of ACEI/ARB in the adjusted Cox proportional hazards model (hazard ratio {HR} = 1.11, 95% CI = {0.91, 1.40}, p-value = 0.14). Conclusion In this large retrospective study, we conclude that there was no statistically significant association between prior history of ACEI/ARB use and COVID-19 ICU admission rates or mortality in hypertensive patients hospitalized with COVID-19.
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Heart failure is accompanied by adverse cardiac remodeling involving extracellular matrix (ECM). Cardiac ECM acts as a major reservoir for many proteins including growth factors, cytokines, collagens, and proteoglycans. Activated fibroblasts during cardiac injury can alter the composition and activity of these ECM proteins. Through unbiased analysis of a microarray dataset of human heart tissue comparing normal hearts (n = 135) to hearts with ischemic cardiomyopathy (n = 94), we identified Asporin (ASPN) as the top differentially regulated gene (DEG) in ischemic cardiomyopathy; its gene-ontology terms relate closely to fibrosis and cell death. ASPN is a Class I small leucine repeat protein member implicated in cancer, osteoarthritis, and periodontal ligament mineralization. However, its role in cardiac remodeling is still unknown. Here, we initially confirmed our big dataset analysis through cells, mice, and clinical atrial biopsy samples to demonstrate increased Aspn expression after pressure overload or cardiac ischemia/reperfusion injury. We tested the hypothesis that Aspn, being a TGFß1 inhibitor, can attenuate fibrosis in mouse models of cardiac injury. We found that Aspn is released by cardiac fibroblasts and attenuates TGFß signaling. Moreover, Aspn-/- mice displayed increased fibrosis and decreased cardiac function after pressure overload by transverse aortic constriction (TAC) in mice. In addition, Aspn protected cardiomyocytes from hypoxia/reoxygenation-induced cell death and regulated mitochondrial bioenergetics in cardiomyocytes. Increased infarct size after ischemia/reperfusion injury in Aspn-/- mice confirmed Aspn's contribution to cardiomyocyte viability. Echocardiography revealed greater reduction in left ventricular systolic function post-I/R in the Aspn-/- animals compared to wild type. Furthermore, we developed an ASPN-mimic peptide using molecular modeling and docking which when administered to mice prevented TAC-induced fibrosis and preserved heart function. The peptide also reduced infarct size after I/R in mice, demonstrating the translational potential of ASPN-based therapy. Thus, we establish the role of ASPN as a critical ECM molecule that regulates cardiac remodeling to preserve heart function.
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Cardiomiopatias , Insuficiência Cardíaca , Traumatismo por Reperfusão , Animais , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Fibrose , Insuficiência Cardíaca/patologia , Infarto/metabolismo , Infarto/patologia , Isquemia , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Traumatismo por Reperfusão/patologia , Remodelação VentricularRESUMO
BACKGROUND: Markers of collagen turnover have not been well studied in the context of cardiovascular disease in patients with chronic kidney disease (CKD). We investigated the associations between serum markers of collagen turnover [N-terminal procollagen type 3 propeptide (PIIINP) and carboxy-terminal telopeptide (C1TP)] and both pulse wave velocity (PWV) and left ventricular mass index (LVMI) in a CKD cohort. METHODS: The study included 242 patients (mean age 60 ± 15 years, 53% males, 80% Caucasian, CKD Stages 3-5) from the Renal Research Institute (RRI)-CKD Study. Serum PIIINP and C1TP levels were analyzed by radioimmunoassay. PWV was obtained by applanation tonometry from carotid and femoral pressure wave contours. LVMI was measured by echocardiography. Statistical analyses included Pearson's correlations and multiple linear regression. RESULTS: Both PIIINP and C1TP values were significantly higher in more advanced stages of CKD (P < 0.05). A positive correlation was demonstrated between PWV and LVMI (r = 0.25, P = 0.0018), persisting after adjustment for potential confounders (partial r = 0.27, P = 0.0009). PIIINP correlated with PWV (r = 0.16, p = 0.029) and LVMI (r = 0.16, P = 0.0018), while C1TP correlated with LVMI (r = 0.18, P = 0.013) but not with PWV (r = 0.12, P = 0.09). In multivariable analysis adjusting for race, diabetes, estimated glomerular filtration rate (eGFR) and renin-angiotensin-aldosterone system inhibitors, only PWV (ß = 0.45, P = 0.0017) but not LVMI (P = 0.09) remained significantly associated with serum PIIINP. CONCLUSIONS: Our results demonstrate the association of PIIINP (but not C1TP), a circulating biomarker of collagen synthesis with arterial stiffness (but not with LVMI) in a CKD cohort, independent of eGFR. This suggests that altered collagen turnover may play a role in the pathogenesis of arterial stiffness in CKD.
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Artérias/fisiopatologia , Biomarcadores/metabolismo , Colágeno/metabolismo , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/etiologia , Falência Renal Crônica/complicações , Rigidez Vascular , Academias e Institutos , Estudos de Coortes , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Hipertrofia Ventricular Esquerda/metabolismo , Falência Renal Crônica/metabolismo , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Prognóstico , Estudos ProspectivosRESUMO
INTRODUCTION: The optimal approach to screening and risk stratification for non-alcoholic fatty liver disease is challenging given disease burden and variable progression. The aim of this study was to assess primary care physician and referring physician practice patterns regarding non-alcoholic fatty liver disease. METHODS: An anonymous nationwide survey was administered to primary care physicians, endocrinologists, and cardiologists in a: (1) tertiary academic hospital, (2) community hospital, and (3) the American College of Physicians Insider Panel. Survey domains assessed non-alcoholic fatty liver disease knowledge, recommendations for screening, risk stratification, treatment, and referral patterns. RESULTS: A total of 440 providers completed the survey (35.2% completion rate; N = 82 academic hospital, N = 21 community hospital, N = 337 American College of Physicians). Half were male (51.7%), 78% from internal medicine, with 5% subspecialists. Providers were knowledgeable regarding prevalence and risk factors for non-alcoholic fatty liver disease. 58% would support screening for non-alcoholic fatty liver disease and used liver enzymes to do so. Only 22.5% used serum biomarkers and 23% used transient elastography for risk stratification. Primary reason for referral was advanced fibrosis/cirrhosis. 80% reported barriers to treating non-alcoholic fatty liver disease. There was no consistent diet recommended. CONCLUSION: In this nationwide survey, we demonstrated that while overall disease knowledge was good, there was an important disconnect between current guidelines and real-world clinical practice. There is also significant heterogeneity in practice patterns for first-line therapy of non-alcoholic fatty liver disease and the majority of provider's report barriers to treating non-alcoholic fatty liver disease. These findings highlight the potential role for reevaluating screening and risk stratification recommendations in primary care to better align with needs in that setting.
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BACKGROUND: The predictors of arterial stiffness across the spectrum of renal function are unclear. These predictors were investigated across a wide range of estimated glomerular filtration rates (eGFR). METHODS: Carotid-femoral pulse wave velocity (PWV; an index of arterial stiffness) was measured in 264 subjects with chronic kidney disease (CKD) stages 3-5 from three nephrology clinics ('lower GFR group'). PWV was also measured in 149 subjects without previously recognized CKD ('higher GFR group') including n = 26 with eGFR between 30 and 60 ml/min/1.73 m(2) and n = 123 with eGFR between 60 and 100 ml/min/1.73 m(2). The association between PWV and eGFR was investigated using linear regression. RESULTS: The 413 subjects had a mean age of 61.9 years, were 51% male, 28% diabetic and 79% hypertensive. In age-adjusted analyses within the 'lower GFR group', 'higher GFR group' and combined group, PWV correlated with higher systolic blood pressure (SBP), pulse pressure (PP), diabetes mellitus, body mass index (BMI) and resting heart rate (all P < 0.0008). In addition, PWV correlated inversely with eGFR in the 'higher GFR group' (P = 0.03) and combined group (P < 0.0001). In multivariable regression analyses of the combined group (n = 413), PWV was independently predicted by eGFR (P < 0.05). However, eGFR explained at most 4% of the variability in PWV in age-adjusted analyses (compared with 13-15% explained by SBP, PP or diabetes) and <1% of PWV variability in models adjusting for age, SBP, diabetes, heart rate and BMI (P < 0.0001). CONCLUSION: Although eGFR may independently predict PWV, the contribution of GFR per se does not appear to be clinically meaningful when compared with traditional cardiovascular risk factors.
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Aterosclerose/epidemiologia , Pressão Sanguínea/fisiologia , Sistema Cardiovascular/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , Nefropatias/complicações , Rim/fisiopatologia , Idoso , Aterosclerose/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Artérias Carótidas/fisiologia , Doença Crônica , Elasticidade/fisiologia , Feminino , Artéria Femoral/fisiologia , Humanos , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de RiscoRESUMO
INTRODUCTION AND HYPOTHESIS: The objective of this study was to investigate complications, urinary incontinence symptoms, and overall satisfaction in patients undergoing the tension-free vaginal tape-SECUR (TVT-S) for stress urinary incontinence (SUI). METHODS: We reviewed consecutive patients treated with TVT-S between April, 2006 and August, 2007, in a urogynecology practice. Outcomes assessed included complications, voiding function, change in SUI symptoms on the Medical Epidemiological and Social Aspects of Aging (MESA) questionnaire, and overall satisfaction. RESULTS: One hundred forty-one women (age, 54.1 +/- 12 years; BMI, 31.2 +/- 6.6 kg/m(2)) were treated for SUI with the TVT-S; 34 required concomitant procedures. There were no intra-operative complications. Immediate post-operative voiding function returned in all but one patient; none required sling release. Most patients (90%) reported no pain on a verbal pain scale. On follow-up, 117 patients denied SUI symptoms, 16 reported mild symptoms, and eight required additional treatment. The average MESA "stress" subscore decreased by 79% (13.0 +/- 7.8 points, p < 0.0001). Eighty-five percent felt "satisfied" with the procedure. CONCLUSION: TVT-S is a safe and effective treatment for SUI.
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Slings Suburetrais , Incontinência Urinária por Estresse/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Slings Suburetrais/efeitos adversos , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos/métodosRESUMO
Mitophagy occurs during ischemia/reperfusion (I/R) and limits oxidative stress and injury. Mitochondrial turnover was assessed in patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB). Paired biopsies of right atrial appendage before initiation and after weaning from CPB were processed for protein analysis, mitochondrial DNA/nuclear DNA ratio (mtDNA:nucDNA ratio), mtDNA damage, mRNA, and polysome profiling. Mitophagy in the post-CPB samples was evidenced by decreased levels of mitophagy adapters NDP52 and optineurin in whole tissue lysate, decreased Opa1 long form, and translocation of Parkin to the mitochondrial fraction. PCR analysis of mtDNA comparing amplification of short vs. long segments of mtDNA revealed increased damage following cardiac surgery. Surprisingly, a marked increase in several mitochondria-specific protein markers and mtDNA:nucDNA ratio was observed, consistent with increased mitochondrial biogenesis. mRNA analysis suggested that mitochondrial biogenesis was traniscription independent and likely driven by increased translation of existing mRNAs. These findings demonstrate in humans that both mitophagy and mitochondrial biogenesis occur during cardiac surgery involving CPB. We suggest that mitophagy is balanced by mitochondrial biogenesis during I/R stress experienced during surgery. Mitigating mtDNA damage and elucidating mechanisms regulating mitochondrial turnover will lead to interventions to improve outcome after I/R in the setting of heart disease.
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Apêndice Atrial/metabolismo , Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar , DNA Mitocondrial/metabolismo , Mitofagia , Traumatismo por Reperfusão Miocárdica/metabolismo , Biogênese de Organelas , RNA Mensageiro/metabolismo , Idoso , Proteínas de Ciclo Celular , Ponte de Artéria Coronária , DNA/metabolismo , Dano ao DNA , Feminino , GTP Fosfo-Hidrolases/metabolismo , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Proteínas de Membrana Transportadoras , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Polirribossomos , Fator de Transcrição TFIIIA/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Hypertension, diabetes, obesity, and aging are associated with increased arterial stiffness. Both insulin resistance and hyperglycemia may contribute to the development of arterial stiffness. Older nondiabetic hypertensive adults were recruited to test the following hypotheses: (1) insulin resistance is associated with arterial stiffness, and (2) this relationship is independent of glucose tolerance status. Aortic pulse wave velocity (PWV), pulse pressure (PP), insulin sensitivity index (S(I), measured by insulin-assisted frequently sampled iv glucose test), glucose tolerance status, and abdominal fat mass were assessed in 37 older (23 male, 14 female, mean age 69.4 +/- 5.9 yr), nondiabetic, hypertensive adults after a 4-wk antihypertensive medication withdrawal. Both PWV and PP were negatively correlated with S(I) (r = -0.49, P = 0.002, and r = -0.38, P = 0.02, respectively). The mean PWV and PP in those with normal glucose tolerance were not significantly different from those with impaired glucose tolerance (9.8 +/- 2.4 vs. 10.0 +/- 3.1 m/sec, P = 0.79 and 71 +/- 17 vs. 72 +/- 18 mm Hg, P = 0.80, respectively). In multiple regression analysis, PWV and PP remained independently correlated with S(I) (P < 0.05) after adjusting for age, gender, fasting glucose, glucose tolerance status, body mass index, or abdominal fat mass. These results suggest that in hypertensive, nondiabetic, older adults, insulin resistance is associated with arterial stiffness independent of glucose tolerance status.
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Artérias/fisiopatologia , Hipertensão/fisiopatologia , Resistência à Insulina , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
This study tests the hypothesis that increased arterial stiffness is associated with postural hypotension in older adults. Aortic pulse wave velocity and postural blood pressure (BP) response were assessed in 49 nondiabetic community-dwelling normotensive (n=27) and hypertensive (n=22) older adults (mean age+/-SD, 71+/-6.7 years) who were not receiving vasoactive medications. During the 5-minute period of upright posture, 13 subjects had no change or a postural increase in systolic BP (SBP)(+10.6+/-14.6 mm Hg), 27 had a postural decrease of <20 mm Hg (-9.3+/-4.2 mm Hg), and nine had a postural decrease of >20 mm Hg (-29.1+/-8.1 mm Hg). Contrary to the proposed hypothesis, pulse wave velocity was significantly greater in subjects with a postural increase in SBP than in those with a postural decrease in SBP<20 mm Hg (10.2+/-0.68 m/sec vs. 8.3+/-0.37 m/sec; p=0.03) and tended to be greater than in those with a postural decrease in SBP>20 mm Hg (10.2+/-0.68 m/s vs. 8.5+/-0.73 m/sec; p=0.11). Higher pulse wave velocity was associated with a more positive postural SBP response at 1 minute (r=0.42; p=0.024), 3 minutes (r=0.38; p=0.007), and 5 minutes (r=0.45; p=0.001). This study does not support a relationship between arterial stiffness and a postural decrease in BP among healthy older adults; other age-related factors regulating BP homeostasis likely play a greater role.
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Aterosclerose/complicações , Aterosclerose/fisiopatologia , Hipotensão Ortostática/etiologia , Hipotensão Ortostática/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/patologia , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Artéria Carótida Primitiva/patologia , Artéria Carótida Primitiva/fisiopatologia , Feminino , Artéria Femoral/patologia , Artéria Femoral/fisiopatologia , Frequência Cardíaca , Humanos , Hipotensão Ortostática/patologia , Masculino , Pessoa de Meia-Idade , Fluxo Pulsátil , Fatores de RiscoRESUMO
BACKGROUND: The homeostatic intracellular repair response (HIR2) is an endogenous beneficial pathway that eliminates damaged mitochondria and dysfunctional proteins in response to stress. The underlying mechanism is adaptive autophagy. The purpose of this study was to determine whether the HIR2 response is activated in the heart in patients undergoing cardiac surgery and to assess whether it is associated with the duration of ischemic arrest and predicted surgical outcomes. STUDY DESIGN: Autophagy was assessed in 19 patients undergoing coronary artery bypass or valve surgery requiring cardiopulmonary bypass. Biopsies of the right atrial appendage obtained before initiation of cardiopulmonary bypass and after weaning from cardiopulmonary bypass were analyzed for autophagy by immunoblotting for LC3, Beclin-1, autophagy 5-12, and p62. Changes in p62, a marker of autophagic flux, were correlated with duration of ischemia and with the mortality/morbidity risk scores obtained from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (version 2.73). RESULTS: Heart surgery was associated with a robust increase in autophagic flux indicated by depletion of LC3-I, LC3-II, Beclin-1, and autophagy 5-12; the magnitude of change for each of these factors correlated significantly with changes in the flux marker p62. In addition, changes in p62 correlated directly with cross-clamp time and inversely with the mortality and morbidity risk scores. CONCLUSIONS: These findings are consistent with preclinical studies indicating that HIR2 is cardioprotective and reveal that it is activated in patients in response to myocardial ischemic stress. Strategies designed to amplify HIR2 during conditions of cardiac stress might have a therapeutic use and represent an entirely new approach to myocardial protection in patients undergoing heart surgery.
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Autofagia , Procedimentos Cirúrgicos Cardíacos , Homeostase , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Masculino , Pessoa de Meia-Idade , Miocárdio/citologiaRESUMO
The focus for this clinical review is under-prescribing and non-adherence to medication guidelines in older adults after coronary artery bypass grafting (CABG) surgery. Non-adherence occurs in all age groups, but older adults have a unique set of challenges including difficulty hearing, comprehending, and remembering instructions; acquiring and managing multiple medications; and tolerating drug-drug and drug-disease interactions. Still, non-adherence leads to increased morbidity, mortality, and costs to the healthcare system. Factors contributing to non-adherence include failure to initiate therapy before hospital discharge; poor education about the importance of each medication by hospital staff; poor education about medication side effects; polypharmacy; multiple daily dosing; excessive cost; and the physician's lack of knowledge of clinical indicators for use of medications. To improve adherence, healthcare systems must ensure that (i) all patients are prescribed the appropriate medications at discharge; (ii) patients fill and take these medications post-operatively; and (iii) patients continue long-term use of these medications. Interventions must target central administrative policies within healthcare institutions, the difficulties facing providers, as well as the concerns of patients. Corrective efforts need to be started early during the hospitalization and involve practitioners who can follow patients after the date on which surgical care is no longer needed. A solid, ongoing relationship between patients and their primary-care physicians and cardiologists is essential. This review summarizes the post-operative medication guidelines for CABG surgery, describes barriers that limit the adherence to these guidelines, and suggests possible avenues to improve medication adherence in older cardiac surgery patients.
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Ponte de Artéria Coronária , Prescrições de Medicamentos/estatística & dados numéricos , Adesão à Medicação/estatística & dados numéricos , Idoso , Hospitalização/estatística & dados numéricos , Humanos , Preparações Farmacêuticas/provisão & distribuição , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Long-term acute care (LTAC) facilities admit patients with complex, advanced disease states. Study aims were to determine the burden posed on hospitals associated with LTAC exposure and analyze the differences between "present on admission" (POA) multidrug-resistant (MDR), gram-negative organisms (GNO) and POA MDR gram-positive organisms (GPO). METHODS: A multicenter retrospective study was conducted in 13 hospitals from southeast Michigan, from September 1, 2008, to August 31, 2009. Cultures obtained in the first 72 hours of hospitalization (ie, POA) of MDR-GPO and MDR-GNO were reviewed. LTAC exposures in the previous 6 months and direct admission from a LTAC were recorded. RESULTS: Overall, 5,297 patients with 7,147 MDR POA cultures were analyzed: 2,619 (36.6%) were MDR-GNO, and 4,528 (63.4%) were MDR-GPO. LTAC exposure in the past 6 months was present in 251 (5.2%) infectious episodes and was significantly more common among POA MDR-GNO than MDR-GPO (158 [8.6%] and 94 [3.1%], respectively, odds ratio, 2.87; P < .001). Recent LTAC exposure was strongly associated with both carbapenem-resistant Enterobacteriaceae (CRE) (31.6% of all CRE cases, P < .001) and Acinetobacter baumannii (14.9% of all A baumannii cases, P < .001). CONCLUSION: Nearly 10% of MDR-GNO POA had recent LTAC exposure. Hospital efforts to control the spread of MDR-GNO should focus on collaborations and communications with referring LTACs and interventions targeted towards patients with recent LTAC exposure.
Assuntos
Antibacterianos/farmacologia , Infecção Hospitalar/epidemiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/epidemiologia , Humanos , Assistência de Longa Duração , Michigan/epidemiologia , Pessoa de Meia-Idade , Diálise Renal , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto JovemRESUMO
BACKGROUND: Previous studies demonstrated an association between asthma and idiopathic dilated cardiomyopathy (IDCM), raising concerns regarding chronic beta-agonist inhaler use. The purpose of this investigation was to replicate that association. METHODS AND RESULTS: We identified 67 patients with IDCM and 130 controls with predominately ischemic cardiomyopathy. Patients were administered a structured, detailed phone survey by blinded interviewers, and had chart abstractions performed. We had 80% power to detect an odds ratio (OR) > or = 2.6 for the relation of asthma and IDCM. A history of asthma was present in 19.4% v 12.3% for cases and controls respectively, OR, 1.72, (95% confidence interval [CI], 0.72, 4.09), P = .18. The duration of asthma was higher in cases: 32.3 (19.7) years v 13.8 (15.0) years (P = 0.007). With adjustment for confounders, multivariate analyses revealed no significant relations between asthma or beta-agonist use and the later development of IDCM. CONCLUSIONS: It is unlikely that previously occurring asthma or beta-agonist use has a strong relationship to the development of IDCM; however, IDCM and atopic diseases may cluster in families, warranting further work into the genetic relations between atopy and IDCM.